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Research Collection Doctoral Thesis Homoallylic π-complexes and related cyclopropyl conjugation Author(s): Rowe, John Westel Publication Date: 1957 Permanent Link: https://doi.org/10.3929/ethz-a-000091233 Rights / License: In Copyright - Non-Commercial Use Permitted This page was generated automatically upon download from the ETH Zurich Research Collection . For more information please consult the Terms of use . ETH Library
Transcript of In Copyright - Non-Commercial Use Permitted Rights ...32932/et… · 0CH2-CHC1=C1©, one chlorine...
Research Collection
Doctoral Thesis
Homoallylic π-complexes and related cyclopropyl conjugation
Author(s): Rowe, John Westel
Publication Date: 1957
Permanent Link: https://doi.org/10.3929/ethz-a-000091233
Rights / License: In Copyright - Non-Commercial Use Permitted
This page was generated automatically upon download from the ETH Zurich Research Collection. For moreinformation please consult the Terms of use.
ETH Library
Prom. Nr. 2657
Homoallylic ff-Complexes
and Related Cyclopropyl Conjugation
Thesis
presented to
the Swiss Federal Institute of Technology Zurich
for the degree of Doctor of Technical Sciences
by
JOHN WESTEL ROWE
B. Sc, M. Sc.
Citizen of the United States of America
Accepted on the recommendation of Prof. Dr. V. Prelog
and Prof. Dr. 0. Jeger
Juris-Verlag Zurich
1957
Dedicated to my wife, Marieli, without whom nothing would
be worthwhile, and to my colleagues who made my stay in
Zurich as enjoyable as it was educational.
ACKNOWLEDGEMENTS
To Herrn Prof. Dr. I. Ruzicka I wish to express my sincere
appreciation for his interest in and support of my
work.
To Herrn Prof. Dr. 0. Jeger, under whose direction this
work was carried out, my deepest gratitude for his
continued encouragement and valuable advice, as well
as my highest respect for his constant inspiration.
To Herrn Prof. Dr. Hs. H. Gunthard for his valuable help in
interpreting my infrared spectras, and to Herrn A. Hub-
scher and Frl. E. Aeberli who recorded them.
To Herrn W. Manser of the Analytical Division of the Organic
Chemistry Laboratory of the E.T.H. for carrying out
scores of microanalyses.
TABLE OP CONTENTS
Preface. 1
Chapter I: Cyclopropane
A. Introduction 4
B. Properties of the Cyclopropyl Ring 4
C. Coulson Bent Bond" Cyclopropane 8
D. Walsh TT-Complex* Cyclopropane 10
E. Conclusions
1. Formation of Cyclopropyl Rings 13
2. Conjugation with the Cyclopropyl Ring 16
Chapter II: TT-Complexes.
A. Allyl-Cyclopropyl Systems 18
B. Homoallyl-Cyclopropylcarbinyl-Cyclobutyl Systems1. Theoretical 22
2. Observed Results - Simple Systems 27
3. Cyclosteroids 324. Dehydronorbornyl-Nortricyclyl Systems 375. 10-Hydroxymethyl-&L(9)-octalin Systems 426. Other Homoallylic Systems 47
C. Valence Tautomerism 53
D. Higher Systems of 7T-Complexes 58
Chapter III: Conjugation with the Cyclopropyl Ring,
A. Introduction 63
B. Olefins 69
C. Carbonyls 77
D. Aromatic Rings 86
E. Crossed Conjugation 89
P. Transmission of Conjugation 94
G. Cyclic Systems - Norcaradiene and Umbellulone 98
Chapter IV: Synthesis of Tricyclo(4:4:l:0)undecane and
lO-Methyl-^SJ-octalin 101
Sxperimental 108
Chapter V: Homoallylic Solvolysis in the OleanolicAcid Series 123
Experimental 126
Appendix:
I. Cyclopropyl Bands in the Infrared 132
II. Discussion Illustrating Uncertainty of
Cyclopropyl Character 134
Bibliography 137
Summary 146
LIST OF ILLUSTRATIONS
I: Conversion of Quinovic Acid into Phyllantholand a-Amyrin 3
II: Bent Bond Cyclopropane 9
III: XT-Complex Cyclopropane 12
IV: Homoallylic TT-Complex 23
V: Potential Energy Relationships 25
VI: SN Competing Mechanisms 29
VII: Homobenzyl TT-Complexes 32
VIII: Cyclosteroid TT-Complexes 35
IX: Bicycloheptene TT-Complexes 38
X: Direct TT-p Interaction 41
XI: 10-Hydroxymethyloctalins 42
XII: 10-Hydroxymethyloctalin TT-Complex 43
XIII: Products from 10-Hydroxymethyloctalin TC-
Complexes 44
XIV: Other Homoallylic TT-Complexes 48
XV: A Non-7T-Complexed Cyclopropylcarbinyl System 51
XVI: Valence Tautomerism - Cyclohexadiene-1,4 54
XVII: Valence Tautomerism - Cycloheptatriene 54
XVIII: Valence Tautomerism - Cyclooctatetraene 56
XIX: Valence Tautomerism - Eucarvone 57
XX: Higher TT-Complexes 59
XXI: Norbornyl Tf-Complex 62
XXII: Cyclopropyl Conjugation 67
XXIII: Dicyclopropyls 68
XXIV: Vinylcyclopropanes 73
XXV: Cyclopropyl Ketones 82
XXVI: Cross-Conjugation 91
XXVII: Transmission of Conjugation 97
XXVIII: Umbellulone 99
XXIX: Synthesis of Tricyclo(4:4:l:0)undecane 103
XXX: Synthesis of 10-Methyl-A1^9 -octalin 107
XXXI: Homoallylic Solvolysis to 18,28-Cyclo-oleanane Derivatives 124
PREFACE
In the course of the conversion of 3B-hydroxy-^ -
27,28-ursenedioic acid (quinovic acid) into 3B-hydroxy-^ -
ursene (ot-amyrin) as shown in Pig. I, an unexpected rear¬
rangement was observed to occur in which a 10-hydroxymethyl-
1(9)^ -octalin system was converted by methylsulfonyl
chloride in pyridine after two hours at 20° directly into
1 t 7 ft ^the corresponding tricyclo(4:4:l:0)undecene-2. ' The
reaction undoubtedly represents a remarkably facile SN
ionization of the mesyl ester anchimerically assisted by
the formation of a strong ff-complex between the p orbitals
of the double bond and the vacant p orbital of the resulting
carbonium ion. In order to more accurately assess the re¬
lative importance of the steric and electronic effects in¬
volved in the formation of this TT-complex, it was considered
desirable to duplicate this reaction with the model sub-
.1(9)stance, 10-hydroxymethyl-£fv -octalin itself.
This has now been carried out as shown in Fig.XXIX-
Chapter IV. The expected rearrangement does indeed occur,
although only at higher temperatures, so that both effects
are indeed of importance. An analogous homoallylic cycli-
zation in the oleanolic acid series was also carried out -
Chapter V.
- 2 -
It was of interest, therefore, to examine the
exact nature of this TT-complex. It was concluded that it
must have an analogous electronic configuration to that of
cyclopropane itself - even when no eyclopropyl ring-con¬
taining products were involved. We therefore first studied
the electronic configuration of the eyclopropyl ring -
Chapter I. These conclusions were then applied to a wide
variety of TT-complex reactions - Chapter II. It was then
noted that the electronic configuration of this TT-complex
is identical to that necessary for conjugation of a eyclo¬
propyl ring with the adjacent p orbital of an olefin, car-
bonyl or aromatic ring. Therefore, as a test of our ideas,
the conjugation in eyclopropyl compounds, especially with
regard to their stereochemistry, was investigated - Chapter
III. Especial attention has been given to the spectral
properties of conjugated cyclopropanes.
Throughout the present work an effort has been
made to cover the subject of homoallylic ll-complexes and
eyclopropyl conjugation as thoroughly as possible. New
ideas have been postulated, and suggestions for future re¬
search are included where it is deemed that they would be
worthwhile or especially interesting.
- 3 -
J)[/yXCQOH i) socig
2) LiAlH
AcO'
QUINOVIC ACID ACETATE
AcO
1)H2/Pt2)LiAlH.
CH20H*T)I^4-)OH~
MsO
2) Wolff-Kishner
r
CH2OH
CH3S02C1/Pyridine2 hours at 20°
> |"CH2OMs
PHYLLANTHOL a-AMYEIN
Figure I:
CONVERSION OP QUINOVIC ACID INTO PHYLLANTHOL AND o-AMYRIN
CHAPTER I
CYCLOPROPANE
Introduction. Cyclopropane can be considered as the
smallest member of the saturated alicyclic series, cyclo-
hexane-cyclopropane. It can also be considered as a member
of the unsaturated series, ethylene-oyclopropane-cyclobutane,
in which two-, three- and four-center unsaturation may be
considered to be present. These two approaches lead to dif¬
ferent molecular orbital pictures for cyclopropane. The
» 1)former leads to the Bent Bond* structure of Coulson ' in
which the carbon configuration is 4sp and considerable
ring strain is present; the latter leads to the *7f-Complex*21
structure of Walsh ' in which the carbon configuration is
23sp +p, and which is strainless. Both of these representa¬
tions, and especially the first, require modification in
order to explain all available data. These modifications in
turn bring the two representations close enough together so
that it is highly probable that the true molecular orbital
configuration of cyclopropane may be considered as a hybri¬
dization of both forms.
Two important results come out of this study. The
first is an ability to predict the ease of formation of a
cyclopropyl ring. The second is an ability to predict
qualitatively the degree in which the cyclopropyl ring will
conjugate with adjacent p orbitals. These results lead not
only to a better understanding of the reaction mechanisms
involved, but also to an understanding of the conjugate
properties of cyclopropyl compounds.
Properties of the Cyclopropyl Ring. Any representation for
cyclopropane must conform with the available chemical and
physical data. This data generally gives information either
- 5 -
on the geometry or on the electrical properties of the
cyclopropyl ring.
Since the geometry of the cyclopropyl ring will
also give information on the electrical properties, these
will be considered first. The basic structure of the cyclo¬
propyl ring with the carbon atoms at the apexes of a planar
equilateral triangle has long been proved by both chemical
and physical means. In particular, the selection rules
operating in infrared and Raman spectroscopy show the
complete symmetry of the molecule with the plane of the
cyclopropyl ring perpendicular to that of the methylene
groups and bisecting their H-C-H angles. To be considered,
then, are the bond lengths, which will give an indication
of the type of orbitals bonding them together, and the
H-C-H angle, which will indicate the molecular orbital con¬
figuration of the carbon atom. Of greatest use have been
infrared, Raman and microwave spectroscopy as well as
electron diffraction.
Electron diffraction studies on cyclopropane have
been carried out by Pauling and Brockway and more recently4)
and accurately by Bastiansen and Hassel. The latter re-
o
port a C-C bond distance of 1.54 A, a C-H bond distance of
1.08 A, and an H-C-H angle of 118.2 ± 2°. Skinner5' confirms
these results, but points out that the C-C bond distanceo
should be reduced to 1.52 A in order to agree with the moment
of inertia calculated by Smith ' from spectroscopic data.
7)Lemaire and Livingston report a C-C bond distance of
o
1.52 A in tetramethyleyclopropane. They also, however, re¬
port a bond angle CH,-C-CH., of 114 which has the relatively
large margin of error of - 6°. An angle of 120° is reported
in spiropentane.' Heilbronner and Schomaker, from
electron diffraction studies on nortricyclane, conclude that
the cyclopropane ring probably has a C-C bond distance ofo
about 1.50 A, and from calculations of the force constants
- 6 -
that the exterior bond angle is 112 . Spinrad"' concludes
from dipole moment data that the chlorine atom in cyclopro-
pyl chloride makes an angle of only 4-8 with the plane of
the ring. However, Stevens points out that this result
may be questioned, and 0'Gorman and Schomaker show by
electron diffraction studies of various chlorinated cyclo-
propanes that chlorine makes an angle of 56 with the plane+ °
of the ring, and confirms a C-C bond distance of 1.52-0.02 A.
The Cl-C-Cl angle of 112 is still smaller than would be ex¬
pected. However, in 1,1-dichloro-ethylene the bond angle is
only 116 instead of the theoretical 120 . This can be
understood when it is remembered that in the resonance form
0CH2-CHC1=C1©, one chlorine atom should possess its normal
electronegative character while the other would be electro¬
positive due to resonance. Thus the two chlorine atoms
in dichlorocyclopropane should be attracted slightly
towards one another. Prom a purely theoretical treatment121
of cyclopropane, Duffey' calculates an H-C-H angle of
180 according to molecular orbital theory. However,
Kilpatrick and Spitzer show that these calculations are
incorrect and arrive at a more reasonable figure of 122°.
Thus the H-C-H angle in cyclopropane is definitely
much closer to the trigonal sp 120 than to the tetrahedral
sp3 109°. Cole14"' points out that the 3040 cm-1 band in
the infrared spectra of cyclopropyl derivatives can be re-
2lated to the sp character of the methylene C-H bond.
15)Arcus ' also points out the increase in stability of the
2sp state due to the lowered steric repulsion of the
geminal substituents. The slightly shorter C-H distance ofo O If.)
1.08 A instead of the normal distance of 1.11 A ; in
ethane would indicate that the bond has considerably more
171s character, ' but not as much as in an ethylenic C-H bond
0 t>)where the distance is 1.06 A. Likewise the C-C bond
o
distance of 1.52 A is slightly shorter than the normal
- 7 -
o
1.54- A in ethane.
Turning to direct evidence for the electronic con¬
figuration of cyclopropane, the well known ability of the
cyclopropane ring to participate in conjugated systems (see
Chapter III) shows the presence of p electrons, although in
such systems it is always possible that this is the result
of polarization of the cyclopropyl ring. However, the pres¬
ence of p electrons has also been shown by direct physical
measurements on cyclopropane itself. Thus the ultraviolet
spectrum of cyclopropane is continuous below 185 mu as ex-
-i o \
pected for mobile p electrons. The oxidation character¬
istics of cyclopropane are also more similar to those of
19)olefins than of alkanes. The high value of the quenching
cross-section for cadmium resonance also indicates mobile p20)
electrons, although to a lesser extent than with olefins.'
The ability of olefinic and aromatic p bonds to
form 7£-complexes with metal ions, bromonium ions, protons21)
etc., is well known.' Similarly cyclopropane has been
22)shown to form complexes with iodine and platinous chlor-
23)ide ,
and the reaction of cyclopropyl compounds with
Lewis acids and bromine probably also proceed via an inter¬
mediate 7^-complex. For example, cyclopropyl ketimines in
the presence of a trace of hydrochloride are decomposed by
heat to pyrrolines, undoubtedly via an intermediate 7T-com-
plex between the positively charged nitrogen and the cyclo¬
propyl ring. In the absence of hydrochloride, these keti-
232)
mines are considerably more stable.'
Cyclopropane can
also form a ^complex with carbonium ions as is discussed
further in Chapter II. These ^complexes involve the dona¬
ting of electrons to the complexing reagent, and show the
cyclopropyl ring as an electron source. This can explain
the decreased stability of alkylated cyclopropanes wherein
the electrophobia of the alkyl group make the ring more
electronegative, and it can, therefore, more readily form
- 8 -
a metastable TF-complex.' It is worth noting that in
spite of calculations of "strain energy" as high as 25
Kcal./mole, *'the cyclopropyl ring is exceptionally stable
25)against anionic and free radical reagents which cannot
form a TF-complex. For example chlorine, unlike bromine and
iodine, does not easily form TT-complexes, and therefore upon
reaction with cyclopropane produces mainly cyclopropyl
chloride. ' 'In addition cyclopropyl nitriles, ketones,
carboxylic acids and their esters, all are more stable due
to the resulting decrease in ring electronegativity.
Additional evidence for the presence of p electrons
may be found in the dipole moment of cyclopropyl chlor¬
ide 'which is intermediate between that of isopropyl
chloride, where the chlorine has an inductive electrophilic
effect, and that of vinyl chloride, where the chlorine has
a tautomeric electrophobic effect. Thus cyclopropyl chlor-
10 29)ide is relatively inert, as is vinyl chloride. ' ' Other
evidence can be obtained by thermodynamic calculations from
the Raman spectra of cyclopropane,'as well as calculati¬
ons of the force constants of the C-H bonds,' which indi¬
cate considerable electron derealization.
In conclusion, therefore, all available evidence
indicates an electron carbon configuration in the cyclo-2
propane ring that approaches 3sp +p much more closely than
4sp3.
The Ooulson "Bent Bond" Cyclopropane. This is a natural out¬
growth of the normal representation of cyclopropane as I in
Pig. II. In order to explain the conjugative properties as
well as the stability of this ring, resonance forms as in II
are assumed. Although in this assumption the carbon atoms
of I would have 4sp AO's, in II they would have 3sp +p AO's
on the charged atoms, and since there are three such reson¬
ance forms, each carbon atom of the ring would thus have
- 9 -
two-thirds such character. The question remains as to how
much the resonance forms represented by II contribute to I.
In 1941 Copley3 'suggested that the 4sp5 C-C AO's
in cyclopropane, as well as ethylene, might overlap at an
angle to one another as in III. This would allow the AO's
to possess angles closer to tetrahedral thus relieving some
of the strain of 60 cyclopropane ring angles. Thus the
areas of high electron density would not lie between the
carbon atoms. Even as late as 1951, Hall and lennard-
Jones33)
postulated a similar picture with cyclopropane,
ethylene and acetylene all possessing equivalent tetrahed¬
ral 4-sp carbon atoms with the AO's overlapping at an angle.
This picture, although it explains many of the facts,
assumes normal properties for the external bonds, which is
contrary to what is known, as well as a lack of electron
density on the line joining the carbon atoms.
II
g = sp3 orbital overlap
Copley: a=109°, b=131°, c=25°
Coulson: a=106°, b=134°, c=23°
III
Pig. II: "BENT bond" CYCLOPROPANE
1)Coulson and Moffitt,"""' in a quantum mechanical
treatment, have built up a very well thought out theory in
which the known properties of cyclopropane are accounted
for by a molecular orbital picture which lies between that
- 10 -
represented by I, with its implied angle of 60 between the
sp AO's (highly strained), and III (Copley), with its tetra-
hedral angle of 109° between the sp AO's (strain-free).
They arrive at an angle of 106 between the AO's as shown in
III (Coulson). Not only is considerable strain relieved,
but the less than tetrahedral angle allows greater overlap
of the sp AO's. Now the fact that the orbitals are non¬
linear might be taken to mean that the overlap will be less,
and therefore that the bond strength will be less. However,
here a new factor enters the picture. The bond distance in
a compound can be considered as the distance resulting in
greatest overlap of the AO's. The sp linear overlap
actually decreases as the distance becomes less thano
1.54 A. However, with these inclined orbitals, the overlap
wi]] increase if the atoms are moved slightly closer to¬
gether. This can account for the shorter C-C bond distance
in cyclopropane and the greater stability of the ring.
Another result of this less than tetrahedral angle between
the C-C AO 's is that the exterior bond angles should be
correspondingly greater, i.e. 113 ,in good agreement with
the observed data.
Although III (Coulson) fairly accurately explains
the properties of cyclopropyl compounds, there is one point
that should be considered. It is shown why the angle bet¬
ween the sp AO's will be less than tetrahedral. However,
the moment that this angle is less than tetrahedral, the
AO hybridization can no longer be pure sp'. The C-C bonds
MUST therefore assume more of a p character, and the exter¬
ior bonds MUST assume more of an s character<
The Walsh "TP-Complex" Cyclopropane. In 1946 Dewar '
postulated a TP-complex type of dative bond to explain the
addition of bromine to olefins. During the next year a
rash of paper appeared debating a similar type of structure
- 11 -
35)
for cyclopropane as well as for ethylene oxide. Walsh '
proposed that cyclopropane could be best represented by the
resonance hybrid of II in Pig. III. This hybrid explains
the numerous unsaturation properties of cyclopropane, and
predicts 3sp +p carbon AO's.
Sir Robert Robinson '
strongly attacked this rep¬
resentation on the basis, 1) that all the distinctive fea¬
tures of the TP-complex were lost on hybridization so that
its use was misleading, 2) that the corresponding represen¬
tation for ethylene oxide was not in accordance with the
facts, and 3) on aesthetic grounds. McDowell '
agreed and
preferred resonance structures of the form in Pig. II, al¬
though as has been pointed out earlier, these must also
possess considerable 3sp +p character. Dewar and Sugden
both supported Walsh's formulation through calculations by
the non-localized molecular orbital method which showed
that the energy content and properties of the resonating
TP-complex were in good agreement with those observed.
Walsh's final paper'
presenting his theory and supporting
evidence in more detail was relatively unchallenged.
The 77^-complex cyclopropane can be represented by
the resonance hybrid of the TF-complex, II in Pig. Ill, or
better as in I. This is the best molecular orbital repre¬
sentation of the result of bringing three methylene groups
together. In it the orbitals overlap in the plane of the
ring at an angle of 60 . Bonding of the methylenes together
with their p AO's perpendicular to the plane of the ring and
with parallel overlap is sterically impossible. As Walsh
points out, this is neither parallel overlap as in olefins,
nor endwise overlap as in sp bonds. However, insofar as
the overlap is parallel, the bond will have p character;
and insofar as the overlap is endwise, the bond will have
sp character. Dividing the p bonds into their component
vectors shows that two-thirds should be considered as pure
- 12 -
p bond, and the other third as pure sp , which is the same
conclusion as is reached from considerations of the reson¬
ance forms of the bent bond cyclopropane. Insofar as the
p orbitals exist as sp AO*s, localized bonding results and
= p orbital overlap1 § = sp orbital overlap
Pig. III:U7T-C0MPLEX" CYCLOPROPANE
2the central sp overlap is vacated. This can also be pre¬
dicted on theoretical grounds. I in Pig. Ill would place2
three electrons in the central sp overlap. This is un¬
stable as one electron would be unpaired. The stablest
configuration would then have two electrons in the central
2 2sp overlap (again representing 67$ sp ). The other four
electrons would be distributed in the three p orbitals with
two of these electrons being strongly bonding, and the
other two weakly anti-bonding and representing the electrons
used to form cyclopropyl TF-complexes. The lower energy
level Of propylene is due to the conversion of these two
weakly anti-bonding electrons into bonding electrons.
The picture that then best represents cyclopropane may
be considered as a hybrid composed of two parts I (Pig.Ill)
plus one part III (Fig.II), i.e. 3sp + V *«
- 13 -
The same reasoning can also be applied to cyclobutane.
Here, however, not only is the unsaturation distributed
over more carbon atoms, but the amount of unsaturation is
considerably less as the p orbitals overlap at right angles
to one another.
Conclusions; Formation of Cyclopropyl Rings. Figs. II and
III show two different methods of portraying the resonance
in cyclopropane. These also indicate two different possible
approaches to the synthesis of cyclopropyl rings. The first
and more usual is by the union of an electropositive carbon
atom with an electronegative if-carbon atom. This is the
basis for most laboratory syntheses of cyclopropanes
wherein a methylene group, rendered acidic by an adjacent
electron sink, loses a proton to a base, and the earbanion
thus formed reacts with the positive dipole of a ¥-carbon-
halogen bond. Typical examples of this are found in the
synthesis of cyclopropyl nitrile and cyclopropanecarboxylic
acid. ' As Dr. Winstein points out (Appendix II), these
reactions are not a TT^-complex type of reaction, and are rela¬
tively independent of steric effects. Another example
would be the well known reaction of trimethylene halides
with zinc, wherein the initially formed metal-organic com¬
pound has a strong dipole. Also of interest is the facile
reaction of 1,4-dibromobutene-2 with diethyl malonate in
65)the presence of base to yield a vinylcyclopropane.
This undoubtedly involves reaction of the initially formed
monomalonic ester earbanion with the olefin which is
highly polarized due to the allyl halogen atom, i.e.
Br*-CH2-*CH^CH V,C(C00Et)2. Completely equivalent is the
CH„
x2
reaction of a carbonium ion with an electronegative carbon
dipole as in the following example representing formation of
125)a cyclopropyl ring via exhaustive methylation.
- 14. -
C00CoHc f\ C00CoEL
© 1 \/(CHj,NCHoCNHC0CH, V
3 3 2, 3 y\COO © v NHCOCH,
On the other hand, the cyclopropyl ring can also be
formed by the union of a carbonium ion with an olefinic
bond via a Tf-complex type of intermediate. This is then
followed by partial rehybridization of the carbon orbitals
2 \from sp towards sp . In this case the stereochemistry is
very important. If the carbonium ion approaches so that its
p AO is parallel to those of the olefin, no bonding will re¬
sult as the steric hinderance between the substituents on
the carbonium ion and those on the olefin will be at a
maximum, even if they are only hydrogen. If, however, the
carbonium ion approaches so that p AO overlaps end-on with
those of the olefin, easy rehybridization of the resulting
"JF-complex can take place with the formation of a cyclo¬
propyl ring.
Three different types of situations can be visualized
for the formation of this TF-complex. In the first, the
carbonium ion is attached by a relatively long carbon chain
to the olefin. This situation would possess a high entropy
of activation and would, therefore, seldom be observed. In
the second case, the carbonium ion is attached by a
shorter chain to the olefin. If it is connected directly
to the olefin, this is simply the linear Tf-p conjugated
allyl carbonium ion. However, if there is one methylene
group between the olefin and carbonium ion, we arrive at the
interesting case of the homoalDylic IP-complex which is dis¬
cussed thoroughly in the next chapter.
In the third case, the olefin and the carbonium ion are
not connected. We know of no example where a reaction of
this type has been carried out. However, I would like to
- 15 -
-1 oQ ^
suggest that benzyl tosylate' when solvolyzed in the
presence of collidine and cyclohexene might produce appreci¬
able amounts of the unknown trans-1-phenylnorcarane. The
unstable benzyl tosylate is best prepared by reaction of
the sodium salt of benzyl alcohol with tosyl chloride in129)
ether,' and purified by crystallization from ether at
-78 or by precipitation with pentane. Preparation of the
tosylate in pyridine is unsatisfactory as it reacts further
with pyridine hydrochloride, probably to produce benzyl
chloride. Heating with an excess of collidine (pyridine
might form pyridinium salts) and cyclohexene should effect
the condensation. Extraction and distillation would yield
the crude products, which however, would contain a number of
unsaturated byproducts. These could be removed by ozoniza-
tion at -78 . Chromatography on active alumina with pentane
followed by distillation should yield the relatively pure
product, which however, may still contain two byproducts -
hexahydrofluorene and pyrolysis products of the polymer
which are usually formed in decompositions of benzyl
tosylates. The product would be expected to melt somewhere
slightly above 0° and to boil at about 120-130°/l° mm*
Another possibility is to condense benzyl tosylate with
maleic anhydride. In this case the well-known trans-1-
phenylcyclopropane-cis-2-cis-3-dicarboxylic acid would be
1^2)
formed.' This could be purified by hydrolysis of the
reaction mixture, extraction, and crystallization from water.
Although no benzyl polymers will be present in this product,
purification may be quite difficult. The corresponding
hydrindene dicarboxylic acid may also be a byproduct.
There are a couple of reactions, however, that are
somewhat analogous to the reaction of a carbonium ion with
an olefin. Doering'
reports that chloroform or bromoform,
potassium t-butoxide and olefins react to form 1,1-dihalo-
cyclopropanes. This undoubtedly involves reaction of the
- 16 -
olefin with a neutral carbene (equivalent to a carbonium ion
minus a proton). Its orbital configuration probably posses¬
ses two p AO's with one electron in each. This half-empty
p orbital may well react via a similar pseudo 7P-complex.
Analogous would be the photochemical reaction of diazo com¬
pounds with olefins, which insofar as they do not involve
intermediate pyrazolines, undoubtedly form cyclopropanes by
a similar carbene pseudo Tt-complex (compare Chapter III -
Valence Tautomery). An interesting modification of this
method has been reported wherein an olefin is oxidized with
145)nitrous oxide to yield a cyclopropane as follows:
NpO olefinR
R1R2C=CR3R4 R1R2C=0 + R3RACN2 *"^
Rl,ui-2
Conclusions; Conjugation with the Cyclopropyl Ring. The
molecular orbital picture for cyclopropane allows us to de¬
termine the steric requirements for conjugation of a cyclo¬
propyl ring with an adjacent p orbital. Since the p orbit-
als of cyclopropane are in the plane of the ring, an ad-
*)jacent p orbital parallel to the plane of the cyclopropyl
ring will be able to engage in TT-TT conjugation. This is the
identical orientation of the p orbitals as for TE-complex
formation from the cyclopropylcarbinyl system. Such a con¬
jugated system can exhibit all the normal conjugative pro¬
perties, i.e., conjugate addition, exaltation of the molecu¬
lar refraction, a bathochromic shift of the ultraviolet
N—*V maximum, and a lowering of the C=Cor C=0 stretching
frequency in the infrared. Transmission of conjugation
through the cyclopropyl ring is also possible.
*) It can not be coplanar with the cyclopropyl ring since
the bonds from the cyclopropyl ring project out at an
angle. However, the conjugation is not decreased
thereby.
- 17 -
Due to the greater steric requirements of the cyclopropyl
ring as well as the 2/3rds p character of the orbitals, how¬
ever, this conjugation will usually he weaker than normal
TT-1T conjugation. The different cyclopropyl conjugated
systems and their steric requirements are discussed in
Chapter III.
CHAPTER II
7T-C0MPLEXES
The Allyl-Cyolopropyl System. This system includes cyclo-
propyl carbonium ions, carbanions and free radicals as well
as cyclopropene, methylenecyclopropane, cyclopropanone and
spiropentane. These all involve a cyclopropyl carton atom
with a 2sp+2p AO, and are capable of isomerizing into the
2corresponding allylic system with the stabler 3sp +p AO,
which in addition is often further stabilized by a greater
degree of resonance. In none of these systems does Brown's'l*4 3)
strain pertain, since the carbon orbitals, although in a
higher energy level due to less hybridization, are at more
or less the expected angles. A cyclopropyne, on the other
hand, would involve true strain since the s+3p AO's could
not assume their expected angles.
The cyclopropyl carbonium ion is highly unstable and
immediately rearranges into the allyl carbonium ion. The
driving force for this rearrangement is the very great
stability of the allyl carbonium ion due to its linear
TF-p resonance wherein the 2 p electrons can equilibrate
through three p orbitals. However, the formation of the
cyclopropyl carbonium ion is relatively difficult since the
external AO's of cyclopropane have more s character and
thus require a greater energy of activation to convert them
into the corresponding p orbital. In other words, the
hydrogens in cyclopropane are more acidic as in ethylene.
Thus cyclopropyl tosylate solvolyzes only slowly in acetic
acid to give allyl acetate. ; likewise cyclopropylamine
reacts with nitrous acid to yield only allyl alcohol. '
The cyclopropyl free radical is considerably more
47)stable. One of the reasons for this is that in the allyl
free radical, the odd unpaired electron is not as highly
- 19 -
stabilized. Thus treatment of cyclopropyl chloride with
48)lithium yields dicyclopropyl. The large amounts of
cyclopropane evolved in the course of this reaction are
probably formed by disproportionation of the free radical.
The cyclopropyl carbanion is also stable. Here again
the allyl carbanion is stabilized by resonance to a consi¬
derably lesser extent than the corresponding carbonium ion
as all of the p orbitals are full. Thus cyclopropyl25,49) 48)
Grignards and cyclopropyl lithium both react nor¬
mally without destruction of the cyclopropyl ring. Treat¬
ment of cyclopropyl ketones with a strong base plus an
alkyl halide results in alkylation, and basic ketonic
cleavage of cyclopropyl ketones also takes place without45,46)
disturbance of the cyclopropyl ring.'
Similarly, the
cyclopropyl group migrates intact in a Schmidt,
Hoffmann, Curtius'
or Beckmann rearrangement.' '
The ease of formation of a cyclopropyl carbanion is, as
expected, intermediate between that of alkanes and alkenes.
Ethyl cyclopropanecarboxylate, instead of forming a
carbanion, reacts with anhydrous base at the carbonyl re-
45,46)miniscent of esters with no a-hydrogens.
' '
Similarly,126)
nitrocyclopropane has an extremely low acidity. This
illustrates the ability of the cyclopropyl ring to engage in
mesomeric resonance. Thus the following resonance hybrids
not only help to explain the above results, but also
clarify the greater stability of these cyclopropanes:
©lT>=c( J *>=c=Ne <3 ^>=i\]e>The racemization and isomerization of cyclopropanecarboxylic
acids containing an alpha hydrogen probably take place via
a similar structure. The resonance in cyclopropanecarboxy¬
lic acid should make it a weaker acid than cyclohexane-
carboxylic acid. However, as in benzoic and acrylic acids,
the inductive effect is predominant so that it is actually
- 20 -
17 27)a slightly stronger acid.
'
The cyclopropyl ring can also resonate although not as
easily (see Chapter I), to forms where the ring acts as an
electron sink as in cyclopropyl chloride and cyclopropyl¬
amine. One would predict, therefore, that these compounds
should be destabilized due to easier proton complexing, and
cyclopropylamine should be a rather weak base, as is indeed
17 27)observed.
'
Similarly, the hyperconjugation of alkyl
groups will also destabilize the ring.'
e^>=ci © <sf>=% ©[[>;>=ch2hAnomalous, however, are some highly substituted nitrocyclo-
propanes. Several cases are reported where these are
50 51 157)
opened by base.' ' '
However, the mechanism is probab-52)
ly not through a simple anion as postulated, but rather
45) 1through either a concerted process
'or a simple SN ioni¬
zation to the unstable cyclopropyl carbonium ion. The
nitrocyclopropanes in question possess substituents which
would assist this latter mechanism.
A final property of cyclopropyl carbanions is that
they are unable to retain their geometrical configuration
when a nitrile or nitro group is substituted on the same
46 51 5"} 157)
carbon atom.' 'JJ' '
This is understandable since
both groups can easily form linear allenic non-conjugated
resonance forms coplanar with the cyclopropyl ring in which
the p orbital of the substituent group is parallel to that
of the carbanion, i.e., h>=C=N© and £>=N\" *". Since it
^O-Vi.
has been shown that a carbanion formed on a carbon atom in
the trigonal state can retain its geometrical configura-54)
tion,'we would like to postulate that a cyclopropyl
carbanion formed from a ring methylene might also retain
its geometrical configuration. For example, the reaction
of optically active l,l-diphenyl-2-bromocyclopropane with
- 21 -
n-butyl lithium followed by carbonation should yield an
optically active acid.
55)Cyclopropene, whose existence is more or less
4-1)forbidden by strain theory, can be considered as an in¬
ternal allene with its 2sp+2p orbitals at the proper angles.
The compound possesses an inherant source of instability,
for polarization of the double bond produces an excited
state with cyclopropyl carbonium ion character. On the
other hand, isomerization to methylacetylene produces
little extra stabilization. This conforms with the known
facts in which cyclopropene is quite unstable, and decompo¬
ses, even at -78°,to yield only polymeric material.
56)2,3-Diphenylcyclopropene-l,l-dicarboxylic acid is con¬
siderably more stable due to the lower level of electron
density in the ring. Upon pyrolysis at 190 , however, a
very interesting reaction takes place. Decarboxylation is
followed by lactonization of the remaining carboxylic acid
group with the double bond to form the B-lactone of
2.3-diphenyl-2-hydroxycyclopropane-carboxylic acid. An¬
other interesting Cyclopropene is found as a natural pro¬
duct in the kernel oil of Stercula foetida, and has been
therefore named sterculic acid; its formula is
CH (CH2)7^(CH2)7COOH.57^ The acid, naturally, is con¬
siderably less stable than the ester, and polymerizes readi¬
ly even at 0. Its ultraviolet spectrum shows only the
weak end absorption to be expected from an isolated double
bond.
The corresponding external allene is methylenecyclo-58)
propane.' This compound is also quite unstable and poly¬
merizes readily. The molecular refraction shows almost no
extra exaltation confirming the lack of cyclopropane-olefin
interaction. More stable due to substitution with carboxyl59)
groups is the Feist acid. This was originally thought
to be a cyclopropene, but it has since been proved to be
- 22 -
l-methylenecyclopropane-trans-2,3-dicarboxylic acid.
Possessing the same molecular orbitals is cyclopropan-
one. However, the polarization of the carbonyl group would
make this compound even less stable, and it has not yet been
isolated. The existence of bicyclo(3:l:0)hexanone-6 as an
intermediate has, however, been proven by Loftfield who
treated labeled a-chlorocyclohexanones with base. The
hydrate, 1,1-cyclopropanediol, would however, be considerab¬
ly more stable since it possesses the normal cyclopropane62)
orbitals. Preparation of this hydrate has been reported,
and its isomerization into propionic acid and the formation
of a methyl hemiacetal are reminiscent of the properties of
ketene.
The final member of this group, spiropentane,-1' is
well known. The stability of this compound is remarkable
when it is remembered that this is a dialkylated cyclopro¬
pane with a 2sp+2p orbital. As expected, the molecular re¬
fraction shows no additional exaltation over that expected
for the cyclopropyl rings alone.
Homoallyl-Cyclopropylcarbinyl-Cyclobutyl System:
Theoretical. In order to avoid confusion let us first study
the postulated properties and predicted behavior in the for¬
mation and reactions of the 7£-complex associated with the
above system, and then by an examination of the available
data determine how reliably the principles derived therefrom
may be applied.
As shown in Fig. IV, the 7£-complex(D) may be formed by
SN ionization of homoallyl(A), cyclopropylcarbinyl(B) or
cyclobutyl(C) derivatives, although the free carbonium ions
probably exist only in a latent form. In turn, the 7P-complex
may decompose via any of these routes, although again the
completely free carbonium ion is seldom formed, and reaction
would be via an appropriately polarized 7Pcomplex. This
- 23
system may he examined by considering the equlibria between
each of these systems and the TP-complex.
CH>—CH
\CH„
QCH04 ^
i «
CHw=«=»0H
\ ©
\i.0Ho4 £
Da
CH
3
"CH„
-•©CHg—0— CH
or ' »\
/ ,-CH„\
CH.—-«—->->CH.
/,8h2
Kb
CH2B
©CH CH2
CH„ 0Ho
1 24 2
Pig. IV: THE HOMOALLYLIC 7T-C0MPLEX
The formation of theTF-complex(Da) from A is obviously
normally difficult. Free rotation around C2-C3 as well as
C3-C4 mean that the probability of assumption of the correct
configuration will be low, i.e., the entropy of activation
will be high. Coplanarity of C1-C2-C3-C4 is unfavorable to
64)p-7T overlap, as well as the fact that the hydrogens of C4
strongly hinder its approach to the olefin as has already
been pointed out. The correct configuration requires that
the plane of C1-C2-C3 approach a perpendicular position with
respect to the plane of C2-C3-C4, and that the empty p orbi¬
tal of C4 be directed towards CI so that it can overlap the
ends of the p orbitals of the double bond to produce an
electronic configuration similar to that of cyclopropane
itself. If, in addition, the departing anion of A is on the
side of C4 opposite the p orbitals of the olefin, as is usu¬
ally the case, there will be an SN rate acceleration due to
the lower level of the potential energy barrier between the
homoallylic compound and the TF-complex. ' The formation of
the TF-complex will not be apprecialbly affected by bulkier
substituents on CI, C2 and C3 (steric hinderance), although
H1
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- 25 -
value of maximum stabilization energy of about 6.7 kcal.y&ole
which is roughly 4-0$ of the corresponding resonance energy
of the allyl carbonium ion. Additional stabilization can al¬
so result from partial rehybridization of the MO's, especial¬
ly in Db. They also calculated the stabilization energy for
the homobenzyl system and found the smaller value of about
4.7 kcal./mole in line with the known poorer conjugating
ability of the phenyl ring and slower rate of solvolysis. On
the other hand a 3,5-diene carbonium ion system with the
greater possibility for electron derealization gave a calcu¬
lated stabilization energy of about 10.3 kcal./mole as would
be expected.
The decomposition of the ^complex does not necessar¬
ily yield the stablest compound, which would usually be ali-
phatic ', but rather primarily that compound which is sepa¬
rated by the lowest potential energy barrier from the ^com¬
plex. These potential energy curves are shown in Fig. V for
(a)
(!)
P.E.
CH2=CHCH2CH2X
Fig. V: POTENTIAL ENERGY RELATIONSHIPS
*) The potential energy difference between homoallyl and
cyclopropylcarbinyl compounds can be estimated from the
difference in the heat of combustion of cyclopropane and
propylene of 7 kcal./mole.
- 26 -
an idealized case in which (a), (b) and (c) are the polar¬
ized transition states of the fl^-complex. The aliphatic
products from SN solvolysis of homoallylic systems via Da
will always retain their configuration and be unrearranged.
If, however, Db plays an important role, decomposition via
(a) can produce rearranged products, although this is seldom
observed as the symmetry of Db leads to decomposition mainly
towards (b) and (c).
TT-complex formation from cyclopropylcarbinyl systems
can proceed more easily insofar as only the free rotation
around C1-C2 need be considered (lower AS). In unsubstitu-
ted cyclopropylcarbinyls the formation of symmetrical Db
produces additional rate enhancement. However, in the usual
case, the cyclopropylcarbinyl is substituted so that a TP-
complex of the form Da is produced. This will, as stated
before, have a higher tendency to decompose towards alipha¬
tic compounds, and a very much lower tendency towards cyclo-
butyl compounds. The conformation for maximal anchimeric
assistance is that in which the departing group leaves
parallel to the bond C3-C4. This allows backside attack by
the p electrons at C2 with the formation of a p orbital at
CI parallel tc that at C2. Steric effects will tend to
favor this orientation. Roberts 'has claimed that in
order to have rate assistance, the p orbital of the carbon-
ium ion must be in the plane perpendicular to one side of
the cyclopropyl ring so that p-<T overlap may take plaee.
According to our picture, these are very poor conditions
indeed for 7£-complexing, the empty p orbital being twisted
60 from that of maximum p-p overlap, and in addition, the
presence of a <T C-C cyclopropyl ring bond is questionable.
His main experimental evidence was based upon the lack of
accelerated solvolysis of nortricyclyl systems. However,
these have been shown to be indeed highly accelerated as
expected.
V|
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- 28 -
compounds of this system. Thus the reaction of nitrous
acid with either cyclopropylcarbinylamine or cyclobutyl-*)
amine '
produces predominantly cyclopropylcarbinol, slight¬
ly less cyclobutanol and 5$ allylcarbinol via the 77^complex,
Db. The reaction of allylcarbinylamine with nitrous acid,
however, produces only 27$ cyclic products with the remain¬
der being rearranged alkenols. Obviously the non-TP-com-
plexed carbonium ion is in this case an important interme¬
diate as a result of the statistical distribution of con¬
formations, most of which are unsuitable for formation of
the TJ^-complex. Important, however, is the fact that the
cyclopropylcarbinol:cyclobutanol ratio is the same as ob¬
served in the reaction with cyclopropylcarbinylamine and
cyclobutylamine confirming that once the TT-complex is
formed, the products are independent of the starting mate¬
rial. Analogously, cyclopropylcarbinyl chloride and cyclo-
butyl chloride solvolyze to give similar mixtures. Of in¬
terest, however, is the fact that cyclobutyl chloride solv-
olyzes only l/27th as fast as cyclopropylcarbinyl chloride
in confirmation of the expected higher energy of activation,
while allylcarbinyl chloride does not react measureably due
to its very high entropy of activation. It has been noted
that during solvolysis of cyclopropylcarbinyl chloride,
cyclobutyl and allylcarbinyl chlorides can be isolated in¬
dicating rearrangement via a 7£-complex ion pair. Treatment
of cyclopropylcarbinol or cyclobutanol with thionyl chlo¬
ride or phosphorus tribromide yields the identical mixture
containing cyclopropylcarbinyl halide and cyclobutyl halide
in the ratio of about 2:1 with only traces of alkenyl
halide. This ratio of 2:1 is also observed in the reaction
*) Compare also the various cyclopropanes produced by the
action of nitrosyl bromide on the Hofmann degredation
products of the different truxillic acids and truxinic
acids.69)
- 29 -
70)and in theof cyclobutyl halides with silver salts,
29)acetolysis of cyclobutyl tosylates. These ring contrac¬
tions of cyclobutyl derivatives are strong evidence against
the classical strained structure of cyclopropane.
Contradictory at first glance are the reactions of
cyclopropylcarbinol and cyclobutanol, or their chlorides,
with Lucas reagent or hydrobromic acid, in which only
alkenyl halides are produced. Here a completely different
mechanism is at work - complexing between the ring and a
proton, which of course decomposes with rupture of the ring.
However, treatment of the cyclic chlorides for a short time
with Lucas reagent containing radioactive chloride showed
halogen exchange as expected for the TT-complex, Db. Corre¬
spondingly, allylcarbinyl chloride showed relatively little
exchange.
Unexpected is the rapid isomerization of cyclopropyl-
carbinyl benzenesulfonate over solid potassium carbonate at
room temperature to yield predominantly allylcarbinyl71) 1
benzenesulfonate. ' This probably occurs via an SN type
of rearrangement as shown in Pig. Via. Similarly, small
amounts of allylcarbinyl tosylate are formed during solvol-
291
ysis of cyclobutyl tosylate.' Even more unexpected is the
C2H5
CH( CH
,'<*--*
CH„
,->
\y0'
(b)
°6H5
(c)
Pig. VI: SIT COMPETING MECHANISMS
- 30 -
very fast SN reaction of cyclopropylcarbinyl benzenesulfo-
nate with ethanolic sodium ethoxide to yield only cyclo-71)
propylcarbinyl ethyl ether.' This is probably a similar
SN reaction of a solvated molecule as shown in Pig. VIb.
A final example of this internal rearrangement via a six-
membered ring transition state is found in the reaction of
cyclopropylcarbinyl Grignards with carbon dioxide, where-
72)upon only allylacetic acid is formed as shown in Pig.Vic.
Similarly, allylacetanilide is formed from the same Grignard
with phenyl isocyanate.' This is completely analogous to
the formation of o-tolylcarbinol from benzyl magnesium75)
chloride and formaldehyde. Cyclobutyl Grignards, which
can not form such an intermediate, do not rearrange even un-
der drastic conditions. ' These internal rearrangements may
thus be considered as competing reactions to 7T-complex for¬
mation.
An interesting exception to the general rule that re¬
actions of homoallyic compounds proceed only with difficulty
via a 7T-complex is shown below. ( f,)f-Dimethylallyl)-carbinyl
chloride solvolyzes with potassium carbonate to yield 60$ of
the corresponding cyclopropyldimethylcarbinol. In this case
the geminal dimethyl groups not only sterically hinder some
of the unfavorable conformations, but also tend to favorably
polarize the double bond. Even more unusual is the reversal
of the reaction by hydrochloric acid. One would expect that
C1-CH2 HC1__ CH2 OH CH3 CI OH
| .0B—C(CH,)9.< -» | \b. C(CHO„-jA| ^CH-0(CH,)9
CH£i d
K2C03 CH£5 d
CH£b *
the normal decomposition of the cyclopropyl-protonTr-complex
would take place. Following Markovnikovfe rule, this should
yield 3-chloro-l-methylpentanol-2. However, the fact that the
alkohol is tertiary, as well as the anchimeric assistance of
the cyclopropyl ring, lead to preferred proton attack on the
oxygen with formation of the carbonium ion W-complex. The
- 31 -
question then arises as to why the TT-complex reacts to form
a cyclopropylcarbinol with base, while with acid the acyclic
olefin is formed. This can be explained thus: the cyclopro-
pyldimethylcarbinyl chloride, which would be initially
formed at equilibrium, is rapidly reversibly reionized due
to the ease of 7T-complex formation until a point is reached
at which the rate of ionization of the homoallylic chloride
(which has been shown to be generally slow) is equal to
that of the cyclopropylcarbinyl chloride. A similar situa¬
tion occurs when 2,2diphenylcyclopropyldiphenylcarbinol is751
treated with dilute acid. ' Instead of forming a cyclopro¬
pyl ring-proton TT-complex, which would decompose according
to Markovnikov, the carbonium ion If-complex is formed which
is especially stabilized in this case due to the phenyl
groups. This then decomposes to l,l,4-,4—tetraphenylbutadi-
ene, not because it is necessarily the most stable product,
but due to the irreversible loss of a proton to form the
highly conjugated system.f\A 1 £ 11 \
Homobenzyl carbonium ions ' ',like homoallyl
carbonium ions, may or may not involve a TP-complex interme¬
diate. Thus many examples are known in which homobenzyl
derivatives show unimolecular rate acceleration and reaction
with retention of configuration, while in other cases this
is not observed. Thus benzylmethylcarbinyl tosylate solvol-
yzes predominantely without phenyl participation in ethanol
or acetic acid, but with phenyl participation in the more
77)polar formic acid. The 7£-complex corresponding to Da in
Fig. IV can also exist in the more symmetrical form, Db.
However, due to the equivalence of the orbitals in the
phenyl ring, these take the form shown in Fig. VII. The
formation of cyclopropyl or cyclobutyl rings is not observed
due to the greater stability of benzene resonance. However,
the formation of the symmetrical phenyl-bridged TT-complex
can lead to rearrangement. Thus the ability of homoallyl
- 32 -
and homobenzyl if-complexes to yield rearranged non-alicyc-
lic products merges with the Wagner-Meerwein rearrange-77)
ment. '
s»
CH;
2 CT2
Da'
Pig. VII: HOMOBENZYL TPCOMPLEXES
Cyclo-Steroids. The 3>5-cyclosteroids, or i-steroids, are
well known in organic chemistry. The best known example is
78 99)
3,5-cyclocholestan-6i3-ol. ' '
However, many other exam-
79) 22pies such as 3,5-cyclosolanidine, 3,5-cyclo-A -
stigmaster-6e-ol, '3,5-cyclopregnanone,'
3,5-cyclo-
androstanone,'
3,5-cyclo-A-cholestene,' '
3,5-7 ft£^ 7 oo fi£^
cyclo-A-cholestene,'
3,5-cyclo-A' -ergostadiene,'
3,5-cyclo-A6'8(14)-cholestadiene,84'88) 3,5-cyclo-A6'8(14)>22ergostatriene,
' ;and 3,5-cyclo-A' -22a-si?irostadi-QO \
ene attest to the general nature of their formation.
5When a 3S-A-steroid rearranges to a 6-substituted cyclo-
steroid, the configuration at C6 is expected to be beta on
mechanistic grounds, and this has been proved to be the
95)case. However, even as recently as 1952, Wallis
claimed that the 6a configuration is to be preferred.'
Epimeric 6a-substituted cyclosteroids may be obtained, how¬
ever, by reduction of 6-ketocyclosteroids.~>'
Cyclo-
steroids are usually prepared by solvolysis of A -3B-halides
or sulfonates in the presence of weak base, or by the action
of lithium aluminium hydride on the sulfonates. In the
- 33 -
latter case, the hydride acts as both a base and a reducing
agent.' ' ' Thus ergosteryl tosylate when aolvolyzed
in pyridine yields cycloergostatriene, while when treated
with lithium aluminum hydride, the diene is formed. How-c no n oo
ever, instead of A '
, a' -cycloergostadiene is produced.
This unexpected product probably involves high rate assist¬
ance, as observed, from thefi' diene system to produce ther op
7)=-complex of the a' -cycloergostadiene-8-carbonium ion.
7 22This rearranges to the 7F-complex of the a' cycloergosta-
diene-6-carbonium ion which then reacts with a hydride ion.
This rearrangement carries the important connotation that
7the a double bond is more stabilized by the additional
hyperconjugative resonance than is the A double bond by
conjugation with the cyclopropyl ring. As is shown later,
this latter conjugation is only fair.
Cholesteryl tosylate reacts as expected with lithiumRq')
aluminum hydride,'as well as with most weak bases with
the exception of pyridine, in which case a cholesteryl-3B-
pyridinium salt is formed. ' The same salt is formed
when cyclocholestan-6fi(or a)-ol is treated with tosyl102
chloride in pyridine; also when 6B-methoxycyclocholestane
is treated with pyridine. The latter reaction requires
the presence of a trace of pyridinium ion which can, in turn,
attack the ether group to form the fiT-complex. The reaction
appears to be general since cycloandrostanes react similar-
102ly. Apparently the cyclosteroid 7Pcomplex cannot easily
stabilize itself by proton ejection from C7, which is, per¬
haps, another indication of the imperfect conjugation to be
expected in A-cyclosteroids.
The rate acceleration, first order kinetics, and
production of products with either retention of configura¬
tion or possessing a cyclopropyl ring indicate a 7^-complex
intermediate.64'77'91'92'95,101^ However, the steric re¬
quirements for the formation of this TT-complex are only
- 34 -
satisfied if the 3-substituent is in the beta equatorial
configuration. Although it is theoretically possible to
prepare a normal cyclosteroid from a carbonium ion gener¬
ated at C3 from a 3a-substituent, the lack of rate accel¬
eration and competing mechanisms would probably prevent it
being observed. Recent attemps to prepare 3>5-cyclo-6a-qo qi 102)
coprostanol derivatives ' ' 'appear to have been un¬
successful. The 10-methyl group and ring B control the
conformation of ring A so that the 3a group cannot assume
the necessary equatorial conformation. Indeed, the 3a
axial conformation greatly increases the rate of E2 elimi-
3 5nation to form A dienes.
The form of the 7T-comj.lex is definitely of the un-
symmetrical Da type. Therefore, no cyclobutyl or rear¬
ranged homoallyl products are to be expected. The lack of
symmetry also produces a less stable 7f-complex. Thus Hol-
ness has calculated from the relative rates of solvolysis
of cholestanyl, cholesteryl and 7-dehydrocholesteryl tosy-
lates (1:100:3000) that the transition states for the lat¬
ter two are stabilized by about 3 and 5 kcal./mole respect-64)
ively. This is slightly less than half of the calcula¬
ted value for the ideal case (6,7 and 10.3 kcal./mole). In
agreement with this is the rather deep ultraviolet of
3,5-cyclo-A-cholestenefA 204 mu (log e=4.2)l 5'inL HL3.X J
which the p orbitals accupy the same position as in the Tf-
complex. In spite of this, the homoallylic cholesterol
system is highly active due to the low entropy resulting
from the fused rings and the 3B configuration. The energy
barrier for decomposition of the tr-complex is apparently
lower toward the cyclosteroids, although their potential
energy is obviously higher than that of the normal steroids;
thus reactions involving an equilibrium (i.e., acid conditi-
\ 95)ons) lead to the normal steroid.
As expected, the rearrangement of the cyclosteroids
- 35 -
back to the normal steroids is also accelerated due to the
formation of the same ^complex.'
The rate is proportion¬
al to hydrogen ion concentration and the heat of activation
is the same as for the solvolysis of cholesteryl tosylate
indicating a common intermediate. The entropy of activ¬
ation, however, is less. If ring B of the cyclosteroid has
a boat conformation (which may be quite stable), a 6a axial
substituent is ideally situated for backside attack by the
C5 p electrons. If, on the other hand, ring B has a chair
conformation, a 6B axial substituent is ideally situated.
Thus for both the forward and reverse reaction, the TF-61)
complex is as represented below.'
The partial bonding
C3-C6 is so weak that it is omitted.
Pig. VIII: CYCLOSTEROID TT-COMPLEX
A similar situation arises with f-cholesterol, or ££-94)*)
cholesten-7B-ol. ' 'The equatorial configuration of the
hydroxy group makes this homoallylic system almost exactly
analogous to cholesterol itself. Indeed as expected, the
reactions of this compound proceed with retention of con¬
figuration showing XT-complex formation. That no cyclic
products are isolated is a result of the fact that two
rings are fused onto the cyclohexanol. The resulting stiff¬
ness hinders the deformation of C7 necessary for greater p
orbital overlap. As a result the TC-complex is even less
symmetrical (stabilized) than that from cholesterol (i.e.j
high heat of activation), and less cyclic product would be
expected. That the 7Pcomplex is formed at all is solely
*) Unexplained is an ultraviolet maximum at 211 mu
(log e=3.5).
- 36 -
due to the fixed favorable conformation of the system (low
entropy of activation). It is to be expected that rate
measurements of the solvolysis would indicate a position
intermediate between cholestanol and cholesterol.
The reactions of cyclosteroids in acid media are also
often via a carbonium ion TT-complex. Since in this case
equilibrium conditions prevail, the more stable normal
steroid will usually be the product. If a proton-cyclopro¬
pane iT-complex were the intermediate, the C6 group would
be undisturbed and a 3-methyl-A-norsteroid would be the
product as is the case in acid isomerization of cyclo-99 100)
cholestane. Even if the C6 group is in the less
favorable equatorial configuration, a TP-complex can be
formed since the entropy effect in cyclopropylcarbinyl
compounds is considerably less than in the corresponding
homoallyl case. Thus acid also converts cyclocholestan-6a-95 102
ol into cholesterol,'
confirming in addition that the
tF-complex, once formed, reacts independently of its precur¬
sor. The fact that the cyclopropylcarbinol is secondary,
and that the cyclopropane ring is somewhat hindered for
complexing with a proton, both assist carbonium ion 7T-com-
plex formation.
The conjugate addition of acids to cyclo-A-cholestene
to yield cholesterol derivatives is another interesting83 99)
example.-"'-" In this case proton attack on the double
bond yields the same 7T-complex as before. Analogously,
treatment of cyclocholestanone-6 with acid involves ready
proton attack on the electronegative oxygen followed by for¬
mation of the carbonium ion ff-complex to yield 6-ketochol-99)
estanol derivatives. '
A final point of interest on the cyclosteroids is
their hydrogenation. Cyclocholestan-6fi-ol is reduced with
97)platinum in acetic acid to cholestanol. A Tf-complex
equilibrium is probably established leading to the more
- 37 -
stable cholesterol which is subsequently reduced. This is
confirmed by the reduction in acetic acid of cyclocholest-98)
anone-6 to cholestanone-6, ' wherein no IF-complex inter¬
mediate is possible. In addition, reduction of cyclochol-
estanol-6, both a and 6, in neutral dioxane leads to the
95)corresponding cholestanol-6. The reduction of cyclo-
95 97)cholestanol-6 and its acetate to cholestane ' '
must,
however, be via prior TP-complex formation.
Hydrogenation does not necessarily lead to the cor-
1 ft d \
responding cholestane. Reduction of A-cyclocholestene,
and probably also A-cyclocholestene,-"""'
leads to 32-7 22
methyl-A-norcoprostane; A' -cycloergostadiene reduces
analogously, although the cyclopropyl ring is probably re¬
duced before the A double bond." '
Cyclocholestane,^'
prepared by Wolff-Kishner reduction of cyclocholestanone-99 100)
6, ' is also reported to be reduced with platinum in
99)acetic acid to 3fi-methyl-A-norcoprostane, although
later workers found that it was non-reducible under these
conditions. ' In any case, it should be possible to se¬
lectively reduce the double bond of A-cyclocholestene
with Raney nickel in neutral solution as was done in theQ/-i.\ Or \
preparation of A -cycloergostadiene.
Dehydronorbornyl-Nortricyclyl System.' '
Exo-5-
norbornenyl halides or sulfonates represent another system
in which fused rings appreciably reduce the entropy factor
of the homoallylic system, 'in this case even more than
in cholesterol types. The unsymmetrical TT-complex, as
shown in Fig. IX '
yields predominantly nortricyclyl
products with the remainder representing reaction with re¬
tention of configuration. This unsymmetrical 7T-complex
can, however, by further derealization of the C3-C4 bond¬
ing electrons pass over into the symmetrical nortricyclyl
fP-complex. The separate existence of the two TP-complexes
- 38 -
can be shown by the fact that unimolecular reactions of exo-
5-norbornenyl systems yield mixtures of nortricyclyl and
exo-5-norbornenyl products in which is found a lower ratio
of cyclic to olefinic product than from solvolysis of
nortricyclyl systems. In addition, reactions of the exo-
14
5-norbornenyl-2,3-C2 system yield some product with re¬
tention of configuration in which radiocarbon is found at
CI and C7, although less than 50$ as should be the case
if the unsymmetrical Tl^-complex is capable of separate
existence. The formation of exo-5-anti-7-dibromonorbornene
by bromination of bicycloheptadiene must proceed via the
symmetrical exo-5-bromonorbornene-6-carbonium ion TF-com-
plex.' ' The symmetrical and unsymmetrical forms of
the TF-complex separated by a small energy barrier are re¬
miniscent of the similar situation in the homobenzyl "n^-com-
plex. The products from even the symmetrical form, however,
will never possess a cyclobutyl ring due to the fact that
this would involve the formation of a highly strained ring
system. In other words, the partial bonds C2-C5 and C2-C4-
are extremely weak, and as in the cholesterol example, are
omitted in Pig. IX.
5-Dehydronorbornyl Nortricyclyl 7-Dehydronorbornyl
Pig. IXs BICYCIOHEPTENE 7T-C0MPLEXES
Exo-5-norbornenyl systems solvolyse 800 times faster
than cyclohexyl due to formation of the 7£-complex (i.e.,*)
anchimeric homoallylic assistance. Endo-5-norbornenyl
*) Only unimolecular rates are considered.
- 39 -
systems, on the other hand, with fixed unfavorable geometry
solvolyze only l/lO as fast as cyclohexyl due to hindering
polar effects.'
However, the endo-5-norbornenyl systems
still undergo unassisted SIT ionisation, and the carbonium
ion, once formed, immediately forms the same ir-complex and
yields the same products as the corresponding exo compound.
Thus, in the solvolysis of endo-5-norbornenyl systems, the
same nortricyclyl and exo-5-norbornenyl products will he
formed, although the percentage of the latter will he some¬
what greater due to direct SN replacement with inversion. '
Also, endo-5-aminonorbornene when treated with nitrous acid
gives a good yield of nortricyclyl alcohol. '
Endo-5-norbornenyl bromide undergoes two unusual re¬
actions. '
Heating in an iron bomb causes rearrangement to
nortricyclyl bromide. The presence of iron would be expected
to assist ionization so that the ir-complex would be slowly
formed. However, this should be a reversible reaction so
that equilibrium conditions would be established, and the
stabler exo-5-norbomenyl bromide might be the expected prod¬
uct. However, at equilibrium, the rates of ionization of
nortricyclyl and exo-5-norbornenyl bromides will be equal.
Since the latter ionizes four times faster than the for¬
mer,°4->10°>
the product should consist of 80$ nortricyclyl
bromide. This is in contrast to the cyclosteroids where the
cyclic form solvolyses faster. The second unusual reaction
of endo-5-norbornenyl bromide is that it reacts with magnesium
to yield Grignard products with the nortricyclyl structure.
Carbanions should not easily form a rr-complex. Roberts
proposes a free radical mechanism, but this, as has been
shown, should not form a »*-complex. Thus cholesteryl bromide
112)gives no cyclosteroid product in a Grignard reaction. The
endo configuration, however, allows the formation of a cyclic
Grignard complex as in Pig VI which may well explain the ob¬
served results. If this is the case, Grignard products from
- 40 -•
the exo bromides should be unrearranged.
Nortricyclyl halides and sulfonates also show rate ac¬
celeration. Originally they were thought to be unacceler-
ated, and this was explained by lack of p orbital over¬
lap on the side of the cyclopropyl ring (see p.26). However,
more recent work has shown that they are indeed accelerated,q
solvolyzing 200 times faster than cyclohexyl, and 2x10 times
faster than the more comparable 7-norbornyl systems to
yield nortricyclyl products. That this is only l/4-th the
acceleration of exo-5-norbornenyl is due to the lack of hyper-
conjugation with the bridgehead,' "i" strain in going from
a less than tetrahedral 97° to a 120 sp carbonium ion,
the weaker p bond character of the cyclopropyl ring, and a
slight entropy factor due to the rigidity of the fused rings.
The first factor, as is shown later, is very important. In
the homologous 3,5-cyclo-8-bicyclo(2:2:2)octyl system, this
steric inhibition to hyperconjugation with the bridgehead is
no longer present, and as a result it would be expected to
solvolyze even more readily; in fact, since the orientation
of the departing group is still ideal for backside attack by
the cyclopropyl p electrons, this case might represent maxi¬
mum anchimeric acceleration due to a cyclopropyl ring.
Anti-7-norbomenyl halides and sulfonates represent a
unique class of homoallylic compounds.' In this case
the "Tie-complex can easily assume the perfectly symmetrical
Db form as shown in Pig. IX, but in spite of this, no cyclic
products can be formed due to the steric strain involved
in fusing both a three and a four membered ring into a
bicycloheptyl skeleton. Therefore, only one product with
retention of configuration is isolated. This ideal orienta¬
tion of the p orbitals gives this system an anchimeric as¬
sistance greater than any other known homoallylic system.
It solvolyzes 10 times faster than cyclohexyl. However,
in order to really appreciate the extent of the rate accel-
- 41 -
eration, it must be compared with the 7-norbornyl sys¬
tem, which is extremely inactive due to steric inhi¬
bition to hyperconjugation between the cation and the
bridgehead. In this case the difference in the rates of
solvolysis is by a facter of 10 times. Syn-7-norbornenyl
systems cannot be anchimerically assisted and are, there¬
fore, also very unreactive.
a 1> e
Pig. X: DIRECT Tf-v INTERACTION
This unique interaction between the C2-C3 TT orbitals
and the empty p orbital at C7 should be parallelled by a
similar interaction when C7 possesses a full p orbital as
in 7-keto or 7-methylene norbornenes (Pig.Xa). 7-Norbornen-
114)one has been synthesized by Norton and Woodward, and
shows a remarkably high maximum in the ultraviolet at 233 mu
(log £=3.11) in 95$ ethanol. Analogously, it would be ex¬
pected that cyclopentadienone dimers (Pig.Xb) should pos¬
sess a similar band, although perhaps masked by the normal
a,B-unsaturated ketone absorption.' ' The interaction
noted by Zurcherc'
in ff -27-aldehydoursenes is un¬
doubtedly also of a similar nature. An even longer wave¬
length and a greater intensity is displayed by 1-4 inter¬
action in the ketone, Pig. Xc, which has the middle ring109,114)
constrained to the boat form. The strain in the
0 r\
bridge (C1-C7-C4 angle is less than sp 120 ) as well as
the polarization of the carbonyl group due to homoallylic
interaction should make the keto group in 7-norbomenone
very susceptible to attack by anions. In agreement with
this is the rapid attack of base on the dimer of cyclopenta-
- 42 -
115)dienone to produce an acid. The elimination of carbon
monoxide from cyclopentadienone dimers has also been shown
to depend on the presence of interaction with the double
bond, which together with the strain in the carbonyl
bonds probably causes the carbonyl carbon atom to assume a
partial 2sp+2p character closer to that present in carbon
monoxide itself. It is likewise to be expected that
7-methylenenorbornenes should show a corresponding inter¬
action between the double bonds. The ultraviolet spectra
of fulvene dimers (Fig. Xb) being prepared in this labora-115)
tory should therefore be very interesting.'
1(9)IQ-Hydroxymethyl-lT -octalin Systems. The simplest mem¬
ber of this series is hydroxymethyloctalin itself (Fig.XIb).
The geometry of this system is such that the entropy factor
present in most homoallylic systems is considerably re¬
duced. Due to the half-chair conformation of the cyclo-
hexene ring, the hydroxymethyl group may take up one of
two possible conformations, quasi-equatorial or quasi-axial
to the cyclohexene ring (in both cases axial to the cyclo-
hexane ring) as shown in Pig. Xlla and b. '
However, the
latter of these two conformations, which is the only one
which can form a 7T-complex, is favored to allow the cyclo-
hexane ring to be joined on by equatorial/quasi-equatorialbonds. Free rotation around the C10-C11 bond is some-
(a) (b)' ^
(o)
Fig. XI: 10-HYDR0XYLMETHYL0CTAIINS
CHgOH
- 43 -
what limited so that the oxygen atom will take up a position
more or less directly cis or trans to 09, the latter being
almost ideal for backside attack of the p electrons in the
double bond. Thus steric requirements limit the molecule to
four conformations, of which one is almost ideal for anchi-
merically assisted IF-complex formation. However, the fact
that this is a hindered neopentyl system will not affect the
rate of solvolysis since it is known that neopentyl and
ethyl systems solvolyze at approximately the same rate.
The use of pyridine in the solvolysis of the sulfonates
is, in some respects, unfortunate insofar as the only reac¬
tions available to the 77-complex are recombination with the
weakly nucleophilic sulfonate ion, rearrangement, formation
of a pyridinium salt, and ejection of a trans axial proton
(to form the vinylcyclopropane). Thus it is possible that
the latter reactions, and not the SH ionization, will be
rate controlling. One method of avoiding this is by carry¬
ing out the solvolysis in dry acetic acid with the more
nucleophilic acetate ion, which would also make rate compar¬
isons easier. Being a neopentyl system, rearrangements of
(a) (b)2
Pig. XII: 10-HYDR0XYMETHYL0CTALIN 7T-C0MPLEX
the carbonium ion can take place competitively with 7Pcomplex
formation. However, the neopentyl system prevents the usual
competing reaction in homoallylic systems of El or E2 elim¬
ination.
- 44 -
The observed result (Chapter IV) is that the hydroxy-
methyloctalin mesylate (methanesulfonate) is quite stable
at room temperature in pyridine, and that the tosylates and
benzenesulfonates react only very slowly at this temperature.
However, upon refluxing in pyridine, reaction rapidly takes
place to produce about 25$ tricyclo(4:4:l:0)undecene-l
(Fig. XIII) by proton ejection and 25$ rearrangement products
(presumably ring enlargement) with the rest probably lost as
pyridinium salts. 10-Hydroxymethyldecalin tosylate,. on the
other hand, is quite stable to refluxing pyridine.
Although Zurcher has claimed that according to
Markownikoff's rule a cyclobutane ring should be formed,
this is neither expected nor observed. The TP-complex is of
the unsymmetrical Da type so that the bond Cl-Cll is quite
weak, and in addition, the highly unstable cyclobutyl car-
bonlum ion which would be formed is sterically hindered, es¬
pecially in the triterpene systems.
Of interest would be the solvolysis of the benzenesul-
fonate in dry acetic acid plus sodium acetate. As shown in
Fig. XIII, this should produce a high yield of tricyclounde-
1) LIAIHa>
2) CrO„/Py.
Fig. XIII: PRODUCTS FROM 10-HYDROXYMETHYLOCTAlIN TT-COMPLEXES
cyl-1 acetate. This could be easily saponified by lithium
aluminum hydride and oxidized with chromic acid in pyri—121
dine to yield tricyclo-undecanone-1 which should have an
- 45 -
interesting ultraviolet absorption (see page 84) This com¬
pound is also of interest in that non-conjugate cleavage of
the cyclopropyl ring with acid would yield a product with
the methyl group rearranged from the CIO to the C9 position.
This is also true of non-conjugate acid cleavage of tricyclo-
undecene-1. However, in both cases conjugate cleavage with
attack of the proton on the 7T-bond instead of the cyclopropyl
methylene would probably occur leading to the conjugated
bicyclo(5:4)undecadiene. This rearrangement is of interest
in the triterpene field, although the degree of conjugation
and sterio effects must be taken into account.
The first example of a TT-complex reaction of a 10-
n n *7 ft ^
hydroxymethyloctalin was discovered by Zurcher.~
'
3B,27,28-trihydroxy-Zk -ursene (Pig. XIa), derived from
quinovie acid, yielded 3,27-cyclo-3fl,28-dimesyloxy-ZT -
ursene when treated with mesyl chloride and pyridine for two
hours at 20 . This is even more reactive than anti-7-nor-
bornenyl tosylate which is stable for four hours in pyridine
in the refrigerator.' The reaction is many times more
rapid than the corresponding model 10-hydroxymethyloctalin
mesylate which reacts only at higher temperatures. The
reasons for this are twofold. The first is that the hydroxy-
methyl group is held rigidly in the quasi-axial position by
the fused rings. The second, and most important, is that due
to the C7 methylene, the' C19a axial hydrogen and the C19S
equatorial methyl group, the least hindered position of the
oxygen is directly trans tothe p orbital overlap of the
olefin (i.e. trans to approximately 012). The entropy factor
in this case is then practically eliminated, and anchimeric
assistance is excellent. In the product, the steric strains
favoring n"-complex formation are largely relieved, although
the C19 substituents tend to slightly twist the cyclopropyl
ring in such a way as to increase the conjugation. This is
discussed further in Chapter III.
_ 46 -
In 3$,28-dihydroxy-AL5(18)-oleanene 122)(Pig. XIc),
another 10-hydroxymethyloctalin system is present. The
geometry of this system shows that the fused rings will
hold the hydroxymethyl group rigidly in the quasi-axial
position. However, the C28 oxygen may still assume a posi¬
tion either cis or trans to Cl8, as in 10-hydroxymethyl¬octalin itself. That the C28 group is considerably less hin¬
dered than the corresponding C27 group has been often noted
in the greater reactivity at C28. ' 'Thus the entropy of
reaction will be slightly reduced by elimination of the un¬
favorable quasi-equatorial conformations, so that the rate
of solvolysis should be slightly increased. The dimesylate,
dibenzenesulfonate and 3-acetoxy-28-benzenesulfonate have
been prepared (Chapter V), and indeed, they are found to be
relatively stable to pyridine at room temperature. Upon re-
fluxing in pyridine, however, they are rapidly solvolyzed to
yield 18,28-cyclo-A" -3fi-hydroxyoleanene esters.
The final member of this group of hydroxymethyloctalins-i Q
is 3B-acetoxy-fi -oleanenol-28 (Pig. Xld) derived from122)
morolic acid. The geometry of this molecule is almost
identical to that of 10-hydroxymethyloctalin itself. The
main effect of the C20 geminal dimethyl groups is to guaran¬
tee that ring E assumes the stabler half-chair form. Again,the hydroxymethyl group can be either quasi-axial or quasi-
equatorial with respect to ring E, with the former favored.
The C28 oxygen will similarly tend to be oriented either cis
or trans to Cl8. Therefore, it would be predicted that it
should form a 7F-complex at about the same rate as the model
system.
Surprisingly, the tosylate is quite stable to refluxingpyridine. Why is this? The answer may well be that the V-
complex is indeed formed, but can only react to give start¬
ing material. The 7n-complex cannot be stabilized by proton
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p-
d-
PVJ
p-
HP
Pp-
-•
*Hj
Pg
h-i
Ph-
1p
p-
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CD
Sio
CD
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0p
P-
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£0"
p-
p-
<d
tr
tr
3o
CD
oCD
4-P*
Mi
siB
cr
Hh3
•t-1
ch
CD
Po
4et-
Pi
p
Ho
p-
II>d
Pi
op
Xct
"Ho
CD
CD
o
Pp"
Hj
CO
l\3
wp
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|.—-
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tr
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PCD
4*•
ch
pp
pCO
op-
3"
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Pd-
33
p>
OH
03
4tr
h-J
p-
PX
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ch
P4
Wp-
OP
CD
3P
PCD
ch
ro
Pi
Pp
Hj
•sP-
OH
4H
P-
BOH
Vj
p1
tr
Vi
4d-
4p
pV|
et-
CD
OOH
otl
4P-
•Sj
VJl
H
P0
CO
CD
oW
tr
p-
OH
H0
p>d
CD
0CD
O.
cr
0*
PCD
p.
4B
ch
CO
4p
p-
co
op
PB
p
eh
P-
P3
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CD
oP
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CO
tr
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PP-
pP
p-
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>9
g3
PB
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HP
ach
OH
cr
9ch
CO
ch
o
- 48 -
The ultraviolet spectra of the product should be practically-
identical with that of carene-4 as discussed in Chapter III.
Substitution of an additional methyl group at C3 on the ole¬
fin would assist the reaction even more due to the resulting
greater stability of the TP-complex. However, it is still
possible that the competing reaction of ring enlargement
might predominate as it produces the least strained product.
CHgO.SPh
(a)
XI-IT
PhSO.CH„
3|2
(b) E2CH—CH=CH—0—OH,-
CH,
Ro0H—OH—"CH—C—CH-,
2I *
CH,
R2C=CH
(c)
OR
(a)
H OR
V
II
i \I V
!•
YI
III IV
VII VIII
Pig. XIV: OTHER HOMOALLY1IC ^COMPLEXES
Another interesting fl^-complex system is shown in Pig.
XlVb. Here the analogous vinylcyclopropane might be pro¬
duced from the aliphatic 2-hydroxymethyl-2-methylpentene-3
- 49 -
12^)
(R=H) ->'by solvolysis of the t-osylate in pyridine. This
neopentyl alcohol could be easily prepared by lithium alu¬
minum hydride reduction of 2,2-dimethyl-#-pentenoic acid, or
its esters. Although these have been occasionally prepared
by several methods,J_
perhaps the most elegant synthesis
would be by condensation of propionaldehyde with acetone to
yield £-hexenone-2. This could be methylated to 3,3-4
dimethyl-A-hexenone-2, which upon oxidation with hypoiodite
should yield the desired acid. However, the dimethyl deriv¬
ative (R=CH,) would probably give better yields in the sol¬
volysis due to easier proton ejection. This would then re¬
quire the use of isovaleraldehyde as the starting aldehyde.
Another very interesting ^complex system, shown in
Pig. XIVc, has been prepared by Winstein,' In this case,
the middle ring is constrained by cis fusion to the rigid
bicycloheptane nuclei so that the equatorial hydroxy group
of I is in the proper position for homoallylic anchimeric
assistance. Observed is that the bromobenzenesulfonate (I)
solvolyzes 10 times faster than the saturated analogue to
yield 70$ of the acetate (I) with retention of configuration
via the TT-complex (11^ plus 30$ of a rearranged acetate (IV)
which is probably formed through further electron derealiz¬
ation to produce the symmetrical ^complex (III). The bromo¬
benzenesulfonate of IV is a homoallylic system with the
proper fixed orientation, so that it also is accelerated
in solvolysis. No cyclopropyl products are found since these
would be rather strained.
The question arises whether simple A-cyclohexenols
might also undergo a TT-complex type of reaction as in Pig.
XlVd. In the simplest case, V, the hydroxy group will take
the favorable equatorial position so that ^complex formation
should indeed be possible as in the norbornenyl system,
although in this case the somewhat less favorable half-chair
conformation is present, and anchimeric assistance would be
- 50 -
somewhat lessened. Solvolysis of the sulfonate in pyridine
might thus yield some bicyclo(3:l:0)hexene-2 (northujene),
VIII, via the unsymmetrical r-complex, VI. Solvolysis in
dry acetic acid plus acetate ion might correspondingly
yield some reaction with retention of configuration and/or
cis-bicyclo(3:l:0)hexan-2-ol acetate, VII, which should also
be highly active in solvolysis. The analogous system de¬
rived by reduction of 5-dihydroumbellulone (Pig, XXVIII)
should similarly solvolyze readily to yield fl-thujene. If
competing mechanisms predominate, r-complex formation should
still be observed upon treatment of the amine with nitrous
acid. In order to observe the reaction with retention of
configuration, substitution of the ring would be necessary,
although this would have to be done so as not to disturb the
equatorial conformation of the hydroxy group, i.e., a cis
5-methyl or a trans 6-methyl group.
An interesting speculation is that the naturally oc-
curing p-menth-l-en-4-ol may be a biological precursor to
ot-thujene and sabinene via air-complex mechanism. To carry
these transformations out in the laboratory, however, might
be difficult since the hydroxy group is no longer necessa¬
rily favored in the required equatorial conformation. The
reverse reaction, formation of a r-complex from the thujenes
and sabinene, should be definitely possible. Thus thujane
and thujone upon treatment with acid yield products with a
cyclopentane ring corresponding to normal Markownikoff pro-
ton-ir-complex ring opening, a and fl-thujene, sabinene, &-
dihydroumbellulone and sabinaketone, on the other hand, could
either undergo the proton-r-complex ring opening with acid
to yield cyclopentane derivatives, or form a carbonium ion
r-complex which would yield six-membered ring products as
is often observed (conjugate ring opening).
- 51 -
In conclusion, therefore, homoallyl and cyclopropylcar-
binyl carbonium ions can be quite highly stabilized under the
proper steric conditions by the formation of a relatively
stable TT-complex, which may lead to considerable rate accel¬
eration, and the form of which will control the products.
As has been shown, the formation of this If-complex from the
cyclopropylcarbinyl carbonium ion is generally far more prob¬
able than from the corresponding homoallyl carbonium ion.
Although no case has been yet reported wherein a cyclopro¬
pylcarbinyl group did not undergo accelerated reaction
(either due to TF-complex formation or to competing intermole-
cular rearrangements), this is not necessarily the case.
Thus the sulfonate of 4,5-cyclo-cis-decalol, I in Pig. XV,
should undergo SN solvolysis no faster than the correspond¬
ing sulfonate of cis-decalol itself. A product with reten¬
tion of configuration may be formed, but this will be due
solely to hinderance to one side of the non-TT-complexed car¬
bonium ion. The product via El elimination would be the in¬
teresting olefin, 4,5-cyclo-fi" -octalin, n, which should
show absolutely no conjugation. In both the carbonium ion
and in the olefin, the p AO's are at right angles to those of
the cyclopropyl ring.
OH
I II
Fig. XV: A NON-TP-COMPLEXED CYCLOPROPYLCARBINYL SYSTEM
The question then arises as to whether a similar com¬
plex can be formed from homoallyl and cyclopropylcarbinyl
free radicals and carbanions. The corresponding complex
would be indeed expected, but as in the corresponding allyl
free radicals and carbanions, it would be less stabilized.
- 52 -
Unfortunately, these systems have been but little studied.
However, it has been reported that cyclopropylcarbinyl ra-
127)dicals are stabilized. This is attributed to a complex
with resonance structures of the form, MlJ^CHp* contribut¬
ing to the stability. Unfortunately, the products from this
reaction have not been studied.
Although the cyclopropylcarbinyl carbonium ion is
highly stabilized by donation of an electron from the anti-
bonding orbital of the cyclopropyl ring, the cyclopropyl
carbanion should be considerably less stabilized since in
this case resonance adds an electron to this anti-bonding
orbital. This has been confirmed by Eastman who states the
cyclopropyl ring functions preferentially as an electron
96)
source.' Thus the ionic excited state in conjugated
vinylcyclopropanes will preferentially possess a negative
charge on the olefin end and a positive charge on the ring
end. This is important for it predicts that conjugated
cyclopropanes will be relatively stable to proton attack
since the proton will preferentially attack the olefin to
form the stable TT-complex. Conjugated carbonyls are natu¬
rally completely analogous.
This allows us to predict the direction of cyclopropyl
ring opening upon acid isomerization. The product must
either correspond to the TT-complex intermediate (conjugate
ring opening), or in the event of proton attack on a cyclo¬
propyl methylene, Markownikoff's Rule will be followed with
opening of the bond opposite the vinyl group favored (non-
conjugate ring opening). Since conjugate ring opening is
reversible, it is paradoxically usually observed only in
poorly conjugated systems wherein reformation of the TT-com¬
plex is less likely. For example, 2-methyl-l-vinylcyclopro-
pane upon conjugate proton attack will produce the
A-hexene-2-carbonium ion, while non-conjugate proton attack
will produce the 3-methyl-&-pentene-2-carbonium ion (but
- 53 -
not the & -hexene-2-carbonium ion).
Valence Tautomerism. The interaction of the double bonds in
If4—cyclohexadienes is well known, as for example, in 1-
14acetyl-A -cyclohexadiene which has a maximum in the ultra¬
violet at a higher wavelength and with a lower intensity than
expected.' Due to the fact that methylene groups in the
sp state have a bond angle of 109 ,the ring will be in a
slight boat form. This means that the p AO's will be in¬
clined towards one another so that direct interaction bet¬
ween the p orbitals can take place. Thus, as shown in
Pig. XVI, 1,4—cyclohexadiene, I, might exist in equilibrium
with its valence tautomer, IV. This latter, incidentally,
represents extremely good conjugation between two cyclopro-
pyl rings. Thus valence tautomeric interaction would prod¬
uce a more puckered boat form with p orbitals on the methyl¬
enes parallel to the plane of the ring. Hyperconjugative
interaction, on the other hand, would produce a more planar
ring with p orbitals on the methylenes perpendicular to the
ring.
Polarization of one of the double bonds of I produces1^4)
the homoallylic system, II and III. Bartlett suggests
that the Tf-complex of II might account for the observed1^5)
interactions in I. Similarly, van Tamelen J'
attempted to
obtain disubstituted northujanes corresponding to III from
1,4-cyclohexadiene, but only 1-2 additions were observed.
Although disappointing, this is not too surprising. In both
II and III, the resulting TT-complex is definitely unsymmetri-
cal, and any hyperconjugative flattening of the ring would
weaken this overlap even more. Thus hyperconjugative inter¬
action appears-to predominate over TT-complex interaction, as
is confirmed by the extreme ease of aromatization of I which
also requires p bonds on the methylenes perpendicular to the
ring.
There is, however, one case where a compound correspond-
CYCLOHEPTATRIENE
III
TAUTOMERISMVALENCEXVII:
II
-C-O
liesequilibriumtautomerictheAlthoughsalt.aisbromide
cycloheptatrienereasons,sametheFor'ion.enylium
137)cycloheptatri-aromaticfullytheformtoionhydrideaof
losseasytoleadsThismethylene.thethroughconjugation
hyper-toduecharacterpseudoaromaticsomepossessestriene
cyclohepta¬addition,In'
conjugation.greateritsto
duefavoredhighlyisformcycloheptatrienethetherefore,
excluded;definitelyischaracteraromaticanyandplace,
takecanringcyclopropylthewithconjugationpoorlatively
re¬onlythatsodienetheofthosetoskewareringpropyl
cyclo¬theofbondsptheHowever,resonance.pseudoaromatic
atoduenorcaradienetheofsidetheonlietopected
ex¬beglancefirstatmightsystemthisforequilibriumThe
XVII.Fig.inshownisII,norcaradiene,tautomervalenceits
withI,(tropylidene),cycloheptatrienehomologousThe
acids.truxillicandtruxinicproducetodiated
irra¬whenacidcinnamicofdimerizationtheofreminiscent
isreactionThisrings.cyclopropylthebetweenconjugation
indicatescompoundthisofspectrumultravioletthepected,
CYCLOHEXADIENE-1,4-TAUTOMERISMVALENCEXVI:Pig.
viviv
inni
^Nl^OOOH
fTYoom
IV
4*
^
0-ex-AsVI.nortetracyclene,interestingtheproducedV,
bicycloheptadiene,theofirradiationthatfound'Cristol
1,4-cyclohexadiene.afromisolatedbeenhasIVtoing
-54-
- 55 -
far towards the triene, by using a reagent that reacts spe¬
cifically with norcaradiene, the equilibrium can be shifted.
Thus maleic anhydryde reacts slowly with cycloheptatriene to-I ^Q \
yield an adduct, III, formed entirely from norcaradiene. '
Nevertheless, norcaradiene is still of importance as
it represents an intermediate in an important synthesis of
cycloheptatrienes. It is well known that diazo compounds,
especially when irradiated, can react with a double bond to
produce a cyclopropane ring.'
Although this may take
place via the intermediate formation and decomposition of a
pyrazoline, a carbene intermediate is more probable.'
Thus diazomethane reacts with aromatic compounds with the
formation of norcaradienes which usually immediately isomer¬ic0,. 14-1}
ize into the corresponding cycloheptatrienes.' ' The
use of ethyl diazoacetate, however, leads to ethyl norcara*-
dienecarboxylates which can be isolated due to the stabiliz¬
ing effect of a carboxyl group on the cyelopropyl ring.^ -1'
These react with only two moles of hydrogen to form norcar-
anes, rapidly absorb oxygen to form a very stable endo per¬
oxide, and rapidly form an adduct with maleic anhydride.
Upon heating they are converted into the monocyclic form
with a corresponding increase in the wavelength of the ultra¬
violet maximum.
144)The next homologue, cyclooctatetraene, III in Pig.
XVIII, has been shown to exist in the form of a puckered
monocyclic ring. Because of the non-planarity, there is no
aromatic resonance, and in fact, because the double bonds
are twisted from linear, there is little conjugation between
adjacent double bonds. However, in this case there is an
interaction between the opposing 1-4 p orbitals which are
tilted towards each other so that one opposing set of p AO s
overlap under the ring and the other set over the ring. It
has been shown that such 1-4 interactions may be quite
strong,'and indeed, lithium and sodium react 1-4 with III.
- 56 -
If in an excited state one of the double bonds is polarized,
the resulting interaction can take the form of the 3-4-
Decomplex, II. Attack by an electrophilic reagent could
thus produce a product corresponding to I, but substituted
on the cyclohexane ring. That reactions of III often prod-
<^\
v^ \yI II III IV
Fig. XVIII: VALENCE TAUTOMERISM - CYCLOOCTATETRAENE
uce products corresponding to I, but substituted instead on
the cyclobutane ring is an indication that I is a true va¬
lence tautomer, and not just a resonance or induced form.
Thus I has a double bond considerably more reactive than in
III, so that selective reaction at this point would shift
the tautomeric equilibrium. Similarly III reacts with maleic
anhydride to yield an adduct corresponding to I. Since III
is the major component of this tautomeric equilibrium, it is
apparent that the 1-4 interaction in III is stronger than
the diene conjugation in I. However, the question of
whether IV is a valence tautomer of III is not yet completely
clear. IV would in no way be stabilized and its existence
is questionable, although a few oxidations of III yield
terephthalic derivatives. Certainly the geometry of III is
not favorable to 1-3 interaction as has been observed in
cycloheptatriene.
The carenone-eucarvone valence tautomerism, I and II
in Fig. XIX, has been shown by the excellent work of Corey
and Burke ' to be a true tautomerism that exists at least
99$ in the monocyclic form. This is not unexpected since
eucarvone possesses a conjugated dienone system, while
carenone, on the other hand, possesses only an enone system.
- 57 -
Pig. XIX: VALENCE TAUTOMERISM - EUCARVONE
Even if the cyolopropyl ring were in a position to conjugate
efficiently with the ketone, the fact that the cyolopropyl
a-carbon atom has only two-thirds p bond character would in¬
dicate a weaker resonance, and in cross-conjugation, the
stronger chromophore usually predominates. Moreover, in
carenone, the flexibility of the ring system will allow ef¬
ficient p orbital overlap of the carbonyl either with the
double bond or with the cyolopropyl ring, but not both. Since
the former naturally predominantes, the cyolopropyl ring in
this case has almost no effect. Thus the ultraviolet maximum
at 229 mu (log e=4.1) in III is normal for an a,S-unsaturated
ketone, while eucarvone has a maximum at 302 mu (log e=3.8)
indicative of its greater conjugation. Since the energy
barrier to interconversion of the two tautomers via their
enolates is very low, I cannot be isolated pure. Thus car-
vone hydrobromide or cyanodehydrocarone when treated with
P0*
IpCD
11
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3P
<!tr
VJ
CO
Pp
op
P-
RH
OH
Hp-
OH
tr
cy
Vj
PP
HCO
P4
H3
VJ
pCD
PP
Vj
C-J.
ch
PCO
P-
H3*
RM
3X
RP
Pi
tr
tr
ch
BP
O
P1
Rch
P-
RR
Hp
<R
0P1
p-
hj
OH
Pp-
Ptr
H3
|<j
PP-
CO
tr
OP
PP
a*
R4
si*•
OH
CD
0*
3p
XHj
CD
0CD
P3
CD
d-
P1
PP-
HR
sp-
Pj
HjP
0p3
pj
0p
CD
XX,P
0CO
.P
p-
P3*
HM
pCQ
CO
>d
SiP-
*d
•P
•d
ch
p.
P1
eh
CO
BOH
0CD
R
XCO
pp-
Pp-
PCD
PB
P>+>
CD
<X
^J
49
P1
Pp-
3P
Pi
4R
**
dp
Rct
-p
0CD
P4
M0
0*
Pp-
3p-
ch
R•d
M
pd-
CO
P>
po
P-
0Pt
4CD
P•*
r0
3*
Hj
PH
3*
3P
ch
pp-
•
nq.cr
h3
CD
=|4
03
BP
Peh
Hj
Hj
3vj
PR
PCD
4CO
pp-
•d
a*
P-
ch
'O
Vj
Pi
P4
eh
CO
CD
<jKD
CO
CO
CD
34
PP-
Vj
3*
PO
0B
Rct
-R
CD
CD
eh
P'Hj
p
CD
4P-
3p
3ch
Och
pP
>d
OH
0CD
<p
ca
Hj
P3*
0P
4pt
X<J
Str
eh
CD
P-
0*
PX
CO
CO
CD
4CH
P1
4ch
03*
o*
RLJ.
0o*
•R
4Hj
ty
P-
PP-
4CD
OH
HCO
Pi
P4
pP
tr
P-
R
3*
HX
Vj
4p
CO
d-
ch
*J
Vj
3H
PCD
Hp
<s3
CO
R
p-
Rp<
p3*
Pp
Pra
3p-
wSi
•d
BSi
Hj
Pi
Hj
PP-
cr
- 59 -
formed by elimination.
Analogously, JC-terpinyl bromide, IV,' could be sol-
volyzed in dry acetic acid plus acetate ion. No anchimeric
assistance would be expected in this case due to the stabler
X
xIV
n ni
XI XII
Pig. XX: HIGHER 77-COMPLEXES
chair form of the ring. However, once the carbonium ion is
formed, it might yield the corresponding bicyclohexane, V,
via the ne-complex. The yield would undoubtedly be rather
low with elimination predominating. However, ozonolysis of
the solvolysis product might yield V as the only possible
saturated acetate. 4-isopropylidenecyclohexyl tosylate, VT,
would be completely analogous except that although elimina-
2tion would no longer take place so readily,SN displacement
should yield considerable amounts of the 1-acetate.
Considering the well known transannular reactions of
large rings, the question arises as to whether solvolysis of
- 60 -
the unsaturated large ring sulfonates, VIII and X, might
lead to the corresponding bicyclic derivatives. Due to their
multiplicity of conformations, anchimeric assistance is cer¬
tainly not to be expected. However, the carbonium ion, once
formed, may well yield the bicyclic derivatives via their
IF-complexes, although as in the previous cases, elimination
2and SN replacement would probably predominate.
Perhaps the best picture of the behavior of higher
TT-complexes can be obtained by an examination of their inter¬
relationships. Thus they can be divided into series as fol¬
lows:
Group A Group B Group C
Series 1. Homoallyl Cyclopropylcarbinyl CyclobutylSeries 2. A^-Pentenyl Cyclobutylcarbinyl CyclopentylSeries 3. ^-Hexenyl Cyclopentylcarbinyl Cyclohexyl
etc.
Within each series the 7P-coniplex will be identical and pos¬
sess an electronic configuration similar to that in cyclo¬
propane itself. However, the formation of the TTC-complex
from different members of a series will take place with var¬
ious degrees of ease so that competing mechanisms of solvoly-
sis may predominate. Although anchimeric assistance is not
necessary for ^complex formation, it helps to reduce the
competing mechanisms. Insofar as a IJC-complex mechanism is
common to the different members of a series, the ratio of
products corresponding to the three possible precursors will
remain identical and be a function of the geometry of the
tT-complex. We can, moreover, draw some general conclusions
from these series. First, the entropy of activation will
decrease as we go from left to right and from bottom to top.5
Thus A -hexenyl should have the highest entropy of activation
and cyclobutyl the lowest. However, the difference between
and within Groups B and C should be relatively minor. The
second generality is that the heat of activation should in¬
crease as we go from left to right and from top to bottom as
- 61 -
a function of the degree of rehybridization necessary to
2produce the three 3sp +p orbitals in the TP-complex. Thus
cyclohexyl should have the greatest heat of activation
(assuming a planar ring) and homoallyl the least. That these
generalities are an oversimplification need not render them
useless.
However, cyclohexyl is definitely anomalous due to
the fact that the ring is not planar. This reduces both the
heat and entropy of activation, especially when constrained
in the boat form as in bicyclo(2:2:l)heptanes, and brings us
to the field of Wagner-Meerwein rearrangements so important
in terpene chemistry. Although these, as well as the numer¬
ous examples of ring contractions and expansions, may be
classed as TC-complex reactions, and have been so formulated151)
by Dewar, ' there is no advantage to treating them in this
way except to reaffirm that the cyclohexyl/ a-hexenyl TP-com-
plex is indeed a valid entity. In addition, it has been
shown by detailed kinetic investigations and tracer studies
that these rearrangements are indeed more complex than was
hitherto believe-d due to extensive proton migration with
equilibration of a series of HP-complexes,y' ' '
as
109 155)well as internal ion pair return.
Since the Wagner-Meerwein rearrangement and the ex¬
tensive bicyclic monoterpenoid interconversions are now fair¬
ly well understood, a brief example of the application of
TF-complex theory will suffice. In the simple case of nor-
bornyl104'113'153^itself as shown in Pig. XXI, the exo form
is anchimerically assisted solvolyzing 360 times faster than
cyclohexyl to form the stabilized carbonium ion (TT-complex)
as shown. The product, as expected from this Tf-complex, con¬
sists of reaction with retention of configuration plus Wagner-
Meerwein rearrangement which corresponds to production of the
cyclopentylcarbinyl carbonium ion. Similarly, endonorbornyl,
although not anchimerically assisted, reacts largely via the
- 62 -
same 7r-complex to give the same products, although less re-
2arrangement is observed due to competing direct SN replace¬
ment. A similar mechanism is probably present in the halo-
genation of norbornylene.'
Although Roberts has
Pig. XXI: NORBORNYL 7T-COMPLEX
stated that this may be via a free radical mechanism,154)
Cristol has shown that the known free radical addition
of p-thiocresol to norbornylene produces no rearrangement in
agreement with the demonstrated poorer ability of free radi¬
cals to form TT~complex type intermediates.
CHAPTER III
CONJUGATION WITH THE CYCLOPROPYL RING
Introduction. The ability of the cyclopropyl group to con¬
jugate with a carbonyl or double bond has been long known
from its chemical reactions wherein conjugate addition on
acid treatment, Friedel-Crafts reactions, malonic ester
65 159 163)syntheses, etc., have been observed. Some vinyl-
cyclopropanes react with maleic anhydride in a Eiels-Alder
reaction,'
although the failure of vinylcyclopropane it¬
self to undergo condensation ' indicates that prior iso-
merization of the cyclopropyl ring may be necessary. Although
the cyclopropyl ring is thermally stable up to 400,the
presence of catalysts or alkyl substituents can appreciably139)
lower the isomerization temperature. Complete reduction
of vinylcyclopropanes in neutral solution under conditions
where the cyclopropyl ring itself would not be attacked has,
however, been only occasionally observed. Thus diethyl 2-
vinylcyclopropane-l,l-dicarboxylate and ethyl l-acetyl-2-
vinylcyclopropane-1-carboxylate are reduced with platinum in
methanol at one atmosphere of hydrogen to the n-pentane de-65}
rivatives. '
Similarly, it has been reported that vinyl-
cyclopropane and isopropenylcyclopropane upon reduction yield
as byproducts some n-pentane and 2-methylpentane (but no 2,3-
dimethylbutane) respectively. However, it has been shown
that this preparation of vinylcyclopropane was probably con¬
taminated with 1,3-pentadienes.'
Thus the double bond of
most conjugated cyclopropanes can be selectively reduced in
neutral solution. In acid solution with proton-cyclopropane
complex formation possible, complete reduction is naturally
facilitated.
However, of greater interest are the physical ihdica-
- 64 -
tions of conjugation. Non-conjugated olefins normally have
boiling points lower, and conjugated olefins higher, than
their saturated analogs. Vinylcyclopropane and isopropenyl-
cyclopropane boil slightly higher than ethyl- and isopropyl-
cyclopropane, thus indicating conjugation. ' Tetranitro-
methane will also produce a color reaction in vinylcyolo-
propanes intermediate between the canary yellow of olefins
and the chocolate brown of conjugated dienes, i.e. orange to
red. 'However, more widely used as a test of con¬
jugation is the molecular refraction. Conjugation normally
produces an exaltation in the molecular refraction over and
above that produced by the double bonds or cyclopropyl ring
alone. However, the usefulness of molecular refraction is
limited "by two factors. The first is the fact that traces
of diene impurities with their high extra exaltation can
give misleading results. The second is the uncertainty in
the value for the group refraction for the cyclopropyl ring.
This has been variously calculated as +0.67 , +0.71,
+0.4-4 and +0.614. Probably no single value adequa¬
tely expresses the cyclopropyl group refraction due to the-i en \
change in its polarization with different substituents. '
In this discussion the value of +0.45 (+13.36 for C,H,--)will be used together with the atomic and group refractivities
of Vogel. This positive refractivity of the cyclopropyl
ring is interesting. The larger strain-free puckered rings
from cyclohexane on up show not a positive, but rather a
small negative increment. ' This points up the similarity
between the cyclopropyl ring and a double bond which posses¬
ses a refractivity of +1.575.
Perhaps the most valuable method for studying the con¬
jugation of cyclopropyl compounds is ultraviolet spectros-173)
copy,'since this gives qualitative information on the
degree and form of the conjugation. Unfortunately, the maxi¬
ma for these systems lie in the far-ultraviolet. Only in the
- 65 -
last few years have measurements on simple conjugated cyclo-
propanes been made, and most of the well known examples, as
in terpene chemistry, have yet to be recorded. Even today,
the recording of far-ultraviolet spectra is far from routine.
In the following sections, extensive data on the ultraviolet
spectra of conjugated cyclopropanes will be given.
Cyclopropane alone does not start to absorb strongly
in the far-ultraviolet until below 185 mu. Olefins, how¬
ever, have a strong N-+V ionic electronic transition max¬
imum at about .175 mu, plus 5 mu per alkyl substituent,
with an intensity almost equal to 10 .
'
Carbonyls have
an N—+V maximum at below 190 mu with an intensity of less
than 10, plus a very weak N-+T radical transition maximum
171)(R band) at about 280 mu. UponTT-TTconjugation, the
N—»V maximum (K band) is shifted about 4-5 mu towards the red
and the intensity is increased. The expected K band maximum
of the conjugated system can be calculated from Woodward's172)
Rule. The R band in conjugated carbonyls is relatively
unaffected. Aromatic rings possess strong N-+V transitions
at about 180 and 200 mu (E bands) plus a weak N—frA homopolar
transition at about 255 mu (B band). Upon conjugation the
expected bathochromic shift to produce a strong K band is ob¬
served, while the weak B band is displaced towards longer
wavelengths.
If a cyclopropyl ring is conjugated with a double bond,
carbonyl or aromatic group, a similar bathochromic shift will
be observed. With ideal conjugation, the wavelength of the K
band maximum, representing the transition energy,should ap¬
proach that of the corresponding system with the cyclopropyl
ring replaced by a double bond. However, the intensity of
absorption, representing the probability of excitation, would
be expected to be somewhat less due to the fact that the
cyclopropyl ring atoms only possess 2/3rds p bond character.
The effect of alkyl substituents on the cyclopropyl ring- has
- 66 -
not yet "been investigated. They might be expected, however,
to exert a similar bathochromic effect, although probably
weaker than the usual 5 mu. This then brings us to the most
important effect - steric. Steric hinderance to conjugation
will result in a hypsochromic shift of the K band, until at
the point of no conjugation, the spectrum will be that of the
isolated double bond, carbonyl or aromatic group. Thus the
conjugation in cyclopropyl systems may be estimated by noting
the position of the K band relative to that of the corres¬
ponding compounds with the cyclopropyl ring replaced with a
double bond and with an isopropyl group. The presence of
steric inhibition to conjugation can also be reflected in a
lower extinction coefficient.
The question then arises as to the steric require¬
ments for conjugation. Most important is that the p orbital
at CI on the cyclopropyl ring must be parallel to those of
the conjugating group. Thus for full ff-7rconjugation, the
plane of the olefin, carbonyl or phenyl group must be at
right angles to the plane of the cyclopropyl ring. This is
the identical orientation of the p orbitals necessary for
maximum anchimeric assistance in TJt-complex formation from the
139 173)cyclopropylcarbinyl system. The claim that the cyclo¬
propyl ring can only conjugate when coplanar with the conju¬
gating group is fallaceous in that due to the bond angles of
the cyclopropyl ring, coplanarity is impossible. The additi¬
onal claim106»139,173-4,209) that conjUgation with the cyclo¬
propyl group is a hyperconjugative phenomenon is difficult to
reconcile with the known feebleness of hyperconjugation,
which in the ultraviolet, for example, results in a batho¬
chromic shift of only 5 mu. In addition, Tt-T hyperconjugation
requires that the p orbital of the conjugating group overlaps
the side of the cyclopropyl ring. This would twist the conju¬
gating P orbital 60 from the direction of maximum IWTconjuga-
tion.
- 67 -
As in dienes, two orientations of parallel p orbital
overlap are possible leading to cis and trans forms as shown
in Pig. XXII a and b, in which the p AO's at CI, C4 and C5
are perpendicular to the plane of the paper.
Nc=c+
(a) (b) (c)
Pig. XXII: CYCLOPROPYT. CONJUGATION
How should the excited electronic transition state be
written for a conjugated cyclopropane? This is shown in Pig.
XXIIc, and is completely analogous to those shown in the
first part of Chapter II. This must not be confused with
open ring resonance forms of the type shown in Pig. II. At
no time is the cyclopropyl ring opened, and the mobile elec¬
tron is either taken from or added to the weakly anti-bonding
electrons of the ring. Thus, as has been stated before,
transition states with the cyclopropyl ring electropositive
(as it will be in cyclopropyl ketones) are stabilized, while
those with the ring electronegative are destabilized, through
vinylcyclopropanes will be preferentially polarized with the
ring electropositive.
The first type of conjugation to be considered is that
between two cyclopropyl rings. It has been shown that al¬
though butadienes possess free rotation around their central
bond, the preferred conformation is s-trans on the basis of
ultraviolet spectra, electron diffraction and Raman spec-176)
tra. In dicyclopropyls with their weaker p bonds, this
rotation should be even less hindered so that in the ground
- 68 -
state, fewer molecules would be expected to exist in the s-
trans form, and as a result, the conjugation between two
cyclopropyl groups would be expected to be quite weak. Even
when in the s-trans form, the 2/3rds p bond character of both
cyclopropyl p orbitals would provide only weak interaction,
and in addition, conjugation would require one of the rings
to be electronegatively charged in the excited state. The
s-cis form would naturally be quite hindered. Unfortunately,48,157,158)
Di-only a few dicyclopropyl systems are known.4-8)
cyclopropyl itself ' does not appear to be conjugated in
that there is absolutely no additional exaltation of the
molecular refraction over that for two cyclopropyl rings.157)
Similarly, l-cyclopropyl-2-phenylcyclopropane shows very
little additional exaltation of the molecular refraction over
that of phenylcyclopropane,' ' and its K band in the
ultraviolet is only 2 mu higher.
XI <D>tt>) (o)
Fig. XXIII: DICYCLOPROPYLS
^N
(d)
However, the last three compounds in Pig. XXIII are held
so that their p orbitals must overlap. (b) has a molecular
orbital structure similar to that of acetylene, and although
it is an extremely unstable system (see Chapter II, part A),
it should be possible to prepare such a compound, and conju¬
gation should be apparent. A compound containing the system
shown in (c) has actually been prepared by Cristol (Pig-
XVI), and is reported to be active in the ultraviolet, al¬
though no quantitative data is given. Attempts to prepare220)
the analogous tetracyclic camphane have been unsuccessful. '
The system (d) should be relatively highly conjugated, It
would be the three-center-unsaturation homologue of cyclobuta-
- 69 -
diene. The possibility of its existence is, however, simi¬
larly questionable due to the severe deformation of its bond
angles.
Olefins. The simplest member of this group is cyclopropyl-179)
acetylene.' Since there is absolutely no steric hinder-
ance, this compound should exhibit maximal cyclopropyl-
olefin conjugation. Unfortunately, however, no data on this
compound is given. Its ultraviolet spectrum should be es¬
pecially interesting, although as with vinylacetylene, the
extinction may be rather low.
Vinylcyclopropane' ' has been prepared extremely
pure. Although Slabey investigated many of its physical pro¬
perties, he neglected to record its absorbtion in the ultra¬
violet. This compound can theoretically exist in an s-cis
and s-trans form as shown in Pig. XXII. The steric hinder-
ance, as indicated by the arrows, will be quite high in the
s-cis form, and although less in the s-trans form, will prob¬
ably still be enough so that the proportion of molecules in
the s-trans form in the ground state will be less than in
butadiene. This, together with the weaker cyclopropyl p AO's,
means that the conjugation should be less than butadiene.
Nevertheless, in the ultraviolet there should be a definite
sharp K band between 180 mu for propylene and 217 mu for buta¬
diene. Vinylcyclopropane does, however, show an appreciable
additional molecular refraction of +0.49. For comparison, the
additional exaltation in isoprene due to conjugation is
65)+0.96. Diethyl 2-vinylcyclopropane-l,l-dicarboxylate
has a similar additional exaltation of the molecular refrac¬
tion attributable to conjugation between the vinyl group
and the cyclopropyl ring. In the ultraviolet it has an
end absorption at 210 mu, log e=3«7, which is considerably
higher than would be expected for a monosubstituted
olefin. The ester groups should not affect the conjugation
- 70 -
too greatly. In the ultraviolet, acid and ester groups
exert relatively weak effects ' ' due to internal compen¬
sation, and in keeping with the loss of the distinctive cha¬
racteristics of the carbonyl group.
The question then arises as to the effect of substitu-
ents on a vinylcyclopropane, especially as regards a possible
steric inhibition to conjugation. Pig. XXII shows that sub¬
stitution of the central carbon of the vinyl group (G4) will
produce steric interaction. Fortunately, several very pure
compounds of this type are known from the reaction of Grig-
nard reagents with cyclopropyl methyl ketone followed by de¬
hydration. A methyl substituent (i.e. isopropenylcyclopro-
pane) ' ' ;produces a definite lowering of the con-
jugative exaltation of the molecular refraction to +0.15,
less than l/3rd that of vinylcyclopropane. The higher
homologues with ethyl, propyl, isopropyl and butyl substitu-
ents (i.e., 2-cyclopropylbutene-l, 2-cyclopropylpentene-l,
2-cyclopropyl-3-methylbutene-l, 2-cyclopropylhexene-l) '
all show absolutely no conjugative exaltation of the mole¬
cular refraction as predicted. Ultraviolet spectroscopy
should confirm this. Substitution of vinylcyclopropanes on
the end of the vinyl group (C5) should produce no appreci¬
able effect, although they will exist as cis-trans isomers.
Thus in the series of l-cyclopropyl-l-methyl-2-alkylethylenes,
which have been prepared quite pure and separated into their
cis and trans isomers,' the conjugation should be les¬
sened by the 1-methyl group as before, but relatively unaf¬
fected by the size of the 2-alkyl group. Thus in the series
where the substituent is hydrogen, methyl, ethyl and propyl
(i.e., isopropenylcyclopropane, 2-cyolopropylbutene-2, 2-
cyclopropylpentene-2, 2-cyclopropylhexene-2), the average
conjugative exaltation of the molecular refraction is +0.15,
+0.20, +0.36 and +0.36 respectively. Not unexpectedly, the
molecular refraction of the cis and trans isomers is practi-
- 71 -
cally identical. The slight increase in the conjugative ex¬
altation with increase in the size of the alkyl group is
probably a result of the greater tendency of the bulky alkyl
group to be oriented away from the cyclopropyl ring thus
favoring conjugation (i.e.,steric hinderance of some of the
relatively poorly conjugating constellations). As expected,
3-cyclopropylpentene-2 shows no conjugative exaltation
of the molecular refraction due to the. hinderance of the
ethyl group at C4-. Although l,l-dimethyl-2-isobutenylcyclo-
propane'should be conjugated, the additional refraction
of + 1.11 indicates that this preparation is highly con¬
taminated with diene.
In the field of pyrethrin chemistry, several vinylcyclo-
propanes are known. 2,2-Etmethyl-3-propenylcyclopropane-l-
carboxylic acid, prepared by decarboxylation of chrysanthe-
mumdicarboxylic acid, and 2,2-dimethyl-3-(l-butenyl)
cyclopropane-1-carboxylic acid ' should be conjugated.
Their ultraviolet spectra should be identical and shifted
towards the visible by the alkyl substituent on the vinyl
group as well as by the geminal dimethyls and carboxyl on
the cyclopropyl ring. Chrysanthemic acid, 2,2-dimethy1-3-
(l-isobutenyl)cyclopropane-l-carboxylic acid,' '
should
absorb about 5 mu higher in the ultraviolet due to the extra
methyl group on the double bond. Chrysanthemumdicarboxylic
acid (pt-methyl-B-( 2, 2-dimethylcyclopropane-3-carboxylio
acid)-acrylic acid] ' ' is reported to have a K band
maximum at 236 mu (log e=4.2). Since substitution of an
olefin by a carboxyl group causes a bathochromic shift of
about 24 mu (as compared to 44 mu for an acetyl group),
we can predict that the K band maximum of the decarboxylation
product will be at about 212 mu indicating fairly good con¬
jugation. Similarly, chrysanthemic acid would thus be ex¬
pected to possess a strong K band at about 217 mu. The
analogous cis and trans fi-(2-methylcyclopropane-3-carboxylic
acid)acrylic acids have been prepared and exhibit a maximum
- 72 -
|Q/-\at 229 mu (log e=4-3)» This is extremely interesting
for if the methyl group on the acrylic acid has a batho-
chromic effect of about 5 mu as in olefins, the ring methyl
groups then have a bathochromic effect of about half as large
or 2 mu. However, if the bathochromic effect of the acrylic
acid methyl group is about 9 mu as in ct,fl-unsaturated ke¬
tones, then ring substituents exert no bathochromic effect.
A comparison of the ultraviolet spectra of acrylic and
methacrylic acids would determine this.
So far only examples which possess free rotation bet¬
ween the cyclopropyl ring and vinyl group have been consider¬
ed. However, a large group of vinylcyclopropaneg are known in
which the cyclopropyl ring is fused with a cyclopentane or
cyclohexane ring to form thujane £bicyclo(3:l:0)hexane] and
carane [bicyclo{5:l:0)heptane] systems in which this free ro¬
tation is frozen. To consider first the thujane system,
these may be further subdivided according to whether the
vinyl group is endo or exo cyclic. The endocyclic thujenes
possess a planar cyclopentene ring. Thus the double bond is
in line with one side of the cyclopropyl ring so that the p
bonds are twisted 30° from the position of parallel overlap
in the cis conformation. Therefore, it is not surprising
that both a and fi-thujene show absolutely no extra exaltation
of the molecular refraction over that for the cyclopropyl
ring alone, although Ostling'
incorrectly attributed this
to the fact that an alkyl group is substituted in the center
of the vinylcyclopropane system. In spite of this poor con¬
jugation, a-thujene still undergoes conjugate reaction with
acids to yield cyclohexane derivatives (anti-Markovnikov) in
contrast to thujane which yield the expected Markovnikov192)
cyclopentane products.' The K band of the thujenes should
be shifted to shorter wavelengths approaching that of the ole¬
fin group alone. Diethyl northujene-l,l-dicarboxylate (die-
thylA -bicyclo(3:l50)hexene-l,l-dicarboxylate) is reported to
73 -
have a maximum in the ultraviolet at 225 mu (log e=3«l)«65)
However, since diethyl 2-vinyleyclopropane--l,l-dicarboxylate65 )
has only an end absorption at 210 mu,' this may he due
to diene impurities. The claim for a bathochromic hypercon-
jugative effect as in cyclopentadiene is questionable, es-
specially where the thujene system is not highly conjugated.
The structure recently proposed by Okuda for hinokiie
188 191)*)
acid,' J ' '
I in Pig. XXIV, is a similar endocyclic
thujene and should, therefore, not be highly conjugated.
000H
Hinokiic Acid (?)
I
COOH
III
Chamic Acid Ledene
IV V
Pig. XXIV: VINYLCYCLOPROPANES
The exocyclic thujenes are not quite so rigid. The
cyclopentene ring is probably slightly puckered"'
so that
the double bond may assume a position of greater or lesser
conjugation. Thus in sabinene, II, a conjugative exaltation
of the molecular refraction of +0.34 indicates fairly good
conjugation, and it is therefore not surprising that it
readily undergoes conjugate anti-Markovnikov ring openingl°/2l
with acids.'
A special case of an exocyclic thujene is
the as yet unknown isopropylenenortricyclane, III. The fused
*) A methyl group is omitted from the stricture in ref. 188.
- 74 -
rings hold this vinylcyclopropane rigidly in the position of
ideal conjugation, making it, therefore, one of the best pos¬
sible examples of olefin-cyclopropane conjugation.
The A-cyclosteroids are somewhat analogous. In this
case the fused ring system holds the vinylcyclopropane ri¬
gidly in a position of fair conjugation. Thus 3,5-cyclo-^-cholestene has a K band which has been estimated at 210 mu
by Klotz,' and measured by Wallis at 204 mu (log e=4.2).
'
The substituted cyclopropyl ring has thus produced a batho-
chromic shift of about 19 mu. Hafey claims that treatment of
cyclocholestene with N-bromosuccinimide followed by dehydro-
bromination yields 3,5-cyclo-A' -cholestadiene. '
However,
he reports no ultraviolet spectrum, and the compound is
probably rather the £' -diene system which is known in
a number of cyclosteroids and has a } at 260-261 mu
85 88)max
(log e=4.4). This is 16 mu higher than the maximum of
a ^'8^14^-cholestadiene (245 mu).172'The first member of the carene type is the endocyclic
carene-4 itself. This compound deviates from planar so that
two conformations are possible - one with poor and one with
good conjugation. The steric effects in the two forms are
about equal so that it is not too surprising that it pos¬
sesses a rather high conjugative exaltation of the molecular
refraction equal to +0.67 (MR-carene-4 minus MR_carene-3).
Corresponding to the as yet unknown conjugated carene-2 is
chamic acid, IV. 'The 4-carboxyl group controls the
conformation. If it is cis to the cyclopropyl ring, the
conformation will be that for no conjugation. If it is trans
to the cyclopropyl ring, the conformation will be that for
good conjugation. Data is lacking to determine which is the
case, but of interest is the fact that base isomerizes the
double bond to the tf position in conjugation with the carb-
oxyl group indicating that the acrylic acid system is more
highly conjugated than the vinylcyclopropane system.
- 75 -
The tricyclo(3:3:l:0)undecene-2 system, analogous to
carene-4> can exist in a conformation either favorable or
unfavorable to conjugation, with the former preferred. Un¬
fortunately the model compound of this system (Chapter IV)
is highly unstable so that it could not be obtained pure.
However, it absorbs in the ultraviolet at X 212 mumax
(log e=4.l) indicating a conjugation better than cyclo-
cholestene. The bathochromic effect of the substituted
cyclopropyl ring in this case is thus about 27 mu. The
question arises as to the possibility of a hyperconjugative
resonance effect which exerts so great a bathochromic shift
in homoannular dienes. In the thujene type this is elimin¬
ated as a factor on the basis of, l) the poor conjugation
in this vinylcyclopropane system, 2) the weaker character
and poorer orientation of the p orbitals in the cyclopropyl
ring, and 3) the lower bathochromic effect in cyclopentadi-
ene. In the carene type, the conjugation is better and the
bathochromic effect of cyclohexadiene is greater so that it
may contribute, although only slightly. An amazing effect
is produced by fixing this model system in a rigid triterpene
nucleus as in 13»27-cyclo-3B-hydroxy-ZT -ursene derivatives,
which have been prepared by solvolysis of the mesylate of
3B,27,28-trihydroxy-A -ursene,'
as well as by reduc¬
tion and dehydration of 3B-acetoxy-13,27-cyclo-12-ketour-
sane.' In these cases the K band maximum shifts to 224-
22§ mu (log £=3«64-3.66). The corresponding diene, elimin¬
ating homoannular effects, would absorb at only about 5 mu
higher. Since no added substj^ients are present on the
vinylcyclopropane system, this extra bathochromic shift of
12 mu must be a steric effect. The bathochromic shift,
*) Zurcher;reports a Amax of 244 mu for the 313,28-
dimesylate; this is undoubtedly a typographical error.
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- 77 -
ax \nT
269 ma (log e=3-9) plus AmnY 206 ma (log e=3.7).202)TDa+
max1 „^
\
Since^"-cholestenone-3 has a K hand at 230 ma (log e=4.0),'
the bathochromic effect of the substitued cyclopropyl ring
in this case is 39 ma. A large part of this effect is prob¬
ably due to the high hathochromio shift produced by Jfand S
substituents on extended conjugated ketones, since the cyclo¬
propyl ring is oriented for only fair conjugation in this
case. Corresponding to this, the hand at 206 ma is probably
the half-chromophore of the vinylcyclopropane system indicat¬
ing a bathochromic shift by the substituted cyclopropyl ring
of about 21 ma similar to the cyclosteroids. The correspond¬
ing half-chromophore at 230 ma for the a,B-unsaturated ketone
system would not be expected since the N-+V transition will
always produce a positive charge at CI which will immediately
form the 7r-complex, thus extending the conjugation. The
vinylcyclopropane transition, on the other hand, can produce
either a positive or negative charge at C2, of which only the
latter is favorable to extension of the conjugation. The
analogous cyclolaudenol, 9,19-cyclo-24-methyl-A -lanostenol-
3, should be capable of forming a similar system with the
same absorption.
Carbonyls. All cyclopropyl carbonyls are of especial inter¬
est since upon reduction to the alcohol and conversion to a
sulfonic acid ester, T7=-complex formation upon solvolysis
should be observed. In addition, the electrophobia of the
cyclopropyl ring and electrophilia of the carbonyl oxygen
should reinforce one another to aid conjugation.
The simplest cyclopropyl carbonyl is cyclopropanealde-
hyde.°^~^'
Although it should be quite highly conjugated
since there are no steric repulsions, the ultraviolet spec¬
trum has not been recorded, and the reported values of re¬
fractive index and density are taken at different tempera¬
tures so that it is only possible to say that there appears
- 78 -
to be a conjugative exaltation of the molecular refraction
as expected. The only definite indication of conjugation is
the fact that the 2,4—dinitrophenylhydrazone is orange-red
instead of orange-yellow in color.
Cyclopropyl ketones can exist in either an s-cis or
s-trans form. Unlike the vinylcyclopropanes, the s-cis form
is in this case probably the less hindered. Therefore, they
would be expected to show a lesser conjugative exaltation of
the molecular refraction as well as a lower bathochromic
shift and extinction coefficient in the ultraviolet. How¬
ever, an additional method is available to test for conjugat¬
ion in cyclopropyl ketones; unconjugated carbonyl groups pos¬
sess a C=0 stretching frequency at 1706-1725 cm" in the in¬
frared while conjugation lowers this to 1665-1685 cm" in2121
a,B-unsaturated ketones. '
The simplest ketone is cyclopropyl methyl ke-
207-11)tone. ' Its ultraviolet absorption, together with
those of the corresponding saturated and unsaturated analo-
. ,
208-9)
gues, is shown below.'
Ketone. K Band R Band
Methyl isopropyl 193 mu(log e=2.6) 280 mu(log e=1.3)Methyl cyclopropyl <208 mu(log e>2.6) 272 mu(log e=1.4-)Methyl vinyl <219 mu(log e>3.6) 321 mu(log e=1.5)
The K band indicates intermediate conjugation as expected.
In the R band, while vinyl ketones produce a bathochromic
shift and increase in intensity, the cyclopropyl ketones,
although producing an intermediate increase in intensity,
have a hypsochromic effect. This has been observed several
times and its significance is not yet clear. However, it
points out the danger in using the position of the R band as
a test of conjugation. Unfortunately this has often been
done due to the difficulty of measuring the K band in the
far-ultraviolet. However, the end absorption at 200-220 mu
- 79 -
may be used as a valid indication of conjugation since sat¬
urated ketones possess a K band that is weaker and at a low¬
er frequency than those of isolated double bonds [i.e., acet¬
one J^^ 188 mu(log e=2.96)] . Cyclopropyl methyl ketone
shows a conjugative exaltation of the molecular refraction
of +0#13167,208-9,211) ag compared t0 +0<28 for methyl vinyl
ketone. ' This lower conjugative exaltation decreases
the usefulness of molecular refraction as a test for conju¬
gation in ketones. In the infrared, the carbonyl absorption-1 210)
is reduced to 1704- cm . The dipole moment is also
intermediate between that of the corresponding saturated and
, -, -,
208)
vinyl analogues.'
The first question is as to effect of a single subs-
tituent on the methyl group of methyl cyclopropyl ketone.
Since in this case the steric effects in the s-cis form are
absolutely unaltered, no change would be expected in the
conjugation. This is confirmed in that the conjugative ex¬
altation of the molecular refraction remains fairly constant
for methyl, ethyl, n-propyl, n-butyl and n-amyl cyclopropyl2111
ketones. The remarkably high value of +0.79 for benzyl211)
cyclopropyl ketone '
may be due either to lack of purity
or to hyperconjuga4.,ion through the methylene group.
The effect of two substituents on the methyl group of
methyl cyclopropyl ketone should similarly have practically
no effect on the conjugation. Thus the conjugative exaltati¬
on of the molecular refraction of cyclopropyl isopropyl ke-
211)tone is +0.14-. The carbonyl band in the infrared is at
1702 cm",while that for diisopropyl ketone is at 1722
cm
1 21 O 21 1.)
.
' J; In the ultraviolet, a situation completely
analogous to methyl cyclopropyl ketone including the unusual
213)hypsochromic shift of the R band is observed.
- 80 -
Ketone K Band B Band
Diisopropyl <200 mu(log e>3.0) 285 mu(log e=1.4)Oyclopropyl isopropyl <208 mu(log e>3.0) 276 mu(log e=1.5)Isopropenyl isopropyl 215 mu(log e=4.0) 305 mu(log e=1.6)
Thus it appears that oyclopropyl isopropyl ketone is slightly
more conjugated than oyclopropyl methyl ketone.
Three methyl substituents produce oyclopropyl t-butyl ke¬
tone. The conjugative exaltation of the molecular refraction
214)is +0.23, and the carbonyl band in the infrared has
shifted to 1684- cm" . These indicate close to perfect
conjugation, and are easily explainable since conformations
unfavorable to conjugation must have one of these methyl
substituents interacting with the oyclopropyl ring. Thus we
have here another case of steric inhibition to unconjugation.
The next question concerns the effect of alkyl substituents
on the oyclopropyl ring. It can be predicted that cis alkyls
at C2 and C3 will hinder the s-trans form, although the effect
on the s-cis form will be minor. A substituent at CI on the
oyclopropyl ring will, however, hinder the s-cis form making
the s-trans configuration the stabler. In either case conju¬
gation is still possible, and may be even enhanced due to the
additional hyperconjugation.
Unfortunately no studies have been made of such com¬
pounds. There is, however, one unusual example of 01 substi¬
tution. A -Pregnen-20-ones react with diazomethane to form215)
16a,17a-methylenepregnan-20-ones, I in Fig. XXV. 'The
angular methyl makes this system most stable in the s-trans
form, and the product appears to be quite highly conjugated.
In the ultraviolet it has an end absorption at 220 mu
(log e=3.9) even stronger than cyclocholestanone. Likewise
the carbonyl band in the infrared is shifted to 1685-1688 cm" .
This is an even greater shift than in cyclocholestanone, and
approaches that of the A -16-methylpregnen-20-one system at
1658 cm-. Of interest is that the carbonyl group, lying bet-
- 81 -
ween the angular methyl group and C12, is highly hindered.
Thus it has not been possible to prepare ketonic derivatives
of this cyclopropyl ketone. As with most cyclopropyl ketones
it is quite stable, even to hot hydrochloric acid, since the
proton preferentially attacks the keto group instead of the
cyclopropyl ring.
Of the alicyclic cyclopropyl ketones, most known ex¬
amples fall into one of three categories: the thujone type
[bicyclo(3:ls0)hexanone}, carone type [bicyclo(4-:l:0)_
heptanones] and the 6-ketocyclosteroids. The first two will
be constrained to the stronger-conjugating s-trans configura¬
tion. Thujone itself is not a conjugated cyclopropyl ketone.
However, the isomeric S-dihydroumbellulone, II, is.' '
Two conformations are possible due to the slight puckering of
the cyclopentene ring.'
If the methyl group is trans to
the cyclopropyl ring, the conformation will be that for only
fair conjugation due to the quasi-equatorial position of the
methyl group. If cis to the cyclopropyl ring, the conjugation
should be quite good, especially since the system is con¬
strained in the s-trans form. Since this compound is produced
by catalytic reduction of umbellulone, we can predict that
the methyl group should indeed be cis, and that fairly good
conjugation should be observed. Thus the conjugative exalta¬
tion of the molecular refraction has the rather high value of
+0.35 (MR-n 8-dihydroumbellulone - MR-, thujone). In the infra¬
red the carbonyl band has been shifted to 1721 cm- from the
usual 1740-1750 cm- observed for cyclopentanones, and close-
-1 212)ly approaches the value of 1716 cm for cyclopentenones.
Its ultraviolet spectrum, 1„
210 mu (log e=3.40), 1^
280 mumax Tiiax
(log e=1.5), also confirms the high conjugation, the K band
217approaching that of cyclopentenone, 1 218 mu (log e=3.98i
Another thujone type system is sabina ketone, III,
produced by oxidation of sabinene. Again two conformati¬
ons, one with good and one with poorer conjugation, are pos-
- 82 -
sible. Unfortunately, spectral data is lacking. However,
the conjugative exaltation of the molecular refraction is
+0.22. ' Treatment with hot dilute sulfuric acid leads
to conjugate rupture of the cyclopropyl ring to produce the
corresponding cyclohexenone.
vA
III
IV 71
Pig. XXV: CYCLOPROPYL KETONES
The final thujone type, and an example of perfect cyclo¬
propyl-carbonyl conjugation, is nortricyclanone, IV. Al¬
though Roberts has prepared this compound by chromic acid
oxidation of nortricyclanol, he isolated it only as its
2,4-dinitrophenylhydrazone. A valid indication of con¬
jugation is that the ultraviolet maximum of this derivative
is shifted towards the visible. In general, however, the
spectra of cyclopropyl ketone derivatives are not a valid
criterion for conjugation, since introduction of the bulky
substituent can appreciably alter the steric balance and re¬
sulting conformation of the system. The tricyclene terpene
derivatives should be analogously perfectly conjugated as,
2 6for example, 4,7,7-trimethyltricyclo(2:2:l:0 ' )heptan-3-one
cm"1700atinfraredtheinabsorbhowever,2-ketocarone,
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con¬willcaroneingroupmethylC4Thehinderance.greater
generallyproducesringcyclopropyltheongroupsdimethyl
geminalofsubstitutionTheconjugation.tofavorableboat
half-<aconjugationtounfavorablehalf-boat<aconjugation
tounfavorablehalf-chaira~conjugationtofavorablechair
half-ahinderance:stericoforderfollowingthewithtions
conforma¬differentfourinexistcantypecaroneThe
infrared.andultraviolettheinabsorption
itsmeasuretoandnortricyclanonepurepreparetorefore,
the¬interest,ofbewouldItconjugation.perfectthealter
notdoesobserve,todifficultmorebandKthemakewould
italthoughwhichspectrum,ultraviolettheoneffectmic
hypsochro-appreciableanhavemaysystemthisinbridgehead
theathyperconjugationoflackHowever,'
acid.lie221)
nortricyclanone-2,3-dicarboxy-stableextremelytheisgous
analo¬Also'
endomethylenebicyclo(3:l:0)hexanone-5.220)219
4,7,7-trimethyl-l,4-and4,5,5-trimethylnortricyclanone-3
isotricyclenone,fl-pericyclocamphanone,3,5-cyclocamphor,
namedbeenalsohaswhichnomenclature),Abstracts(Chemical
-83-
- 84 -
that these two compounds are prepared by catalytic reduction
of the corresponding & olefins. Due to the hinderance of
the geminal dimethyl groups on the cyclopropyl ring, the
hydrogen-containing catalyst approaches from the oppositeside of the molecule forming the carone derivative with the
methyl group cis to the cyclopropyl ring. Since this methyl
group will take the equatorial position, the conformation of
the ring will be the unfavorable half-chair. However, equi¬
libration of these two compounds with alkali should produce
the stabler configuration with the methyl group trans to the
cyclopropyl ring, and which, like carone itself, would be
highly conjugated.
Another analogous carone type is the as yet unknown
tricyclo(3s3:l:0)undecanone-l, VI. Two examples of this
type are known in the triterpenes. The 13,27-cyclo-12-keto-194)
%ursane system 'absorbs in the ultraviolet at A 214-5 mu
"max
(log G=3.68-3.74) indicating fairly good conjugation. Another
interesting indication of conjugation is that it gives no
color with tetranitromethane, although the corresponding
desoxo system gives a pale yellow color. In this case the
favorable half-chair and unfavorable half-boat conformations
are impossible due to the diequatorial bonds to ring B.
However in the unfavorable half-chair conformation, the keto
group is strongly hindered by the C19 equatorial methyl group.
The result is that ring C is in the favorable half-boat form,
leading to fairly good p orbital overlap.
The 13,27-cyclo-15-keto-oleanane system, however, shows
223)no conjugative K band in the ultraviolet. Of the four
possible conformations of ring D, the unfavorable half-chair
and favorable half-boat can be immediately eliminated due to
the high steric interaction between the cyclopropyl ring and
ring E. Of the remaining two forms in which ring E is
joined on by quasi-axial /equatorial bonds, the favorable
half-chair is the more hindered, mainly due to C27-C19 inter-
- 85 -
action. Thus the conformation of ring D is the unfavorable
half-boat with C16 and C17 oriented away from the cyclo¬
propyl ring. This result is especially interesting since
22^)Spring originally concluded that the series of hexa-
cyclic JB-amyrin derivatives prepared by him contained a
cyclobutyl instead of a cyclopropyl ring on the basis of,
1) lack of conjugation in the ultraviolet in the above com¬
pound as well as in some other crossed-conjugated systems
(considered in part E of this chapter), 2) the lack of a
strong band in the infrared at 1000-1020 cm", and 3) the
acid stability and lack of a positive tetranitromethane re¬
action with cyclopropyl carbonyl derivatives. The first
reason is invalid since conjugation with a cyclopropyl ring,
especially in crossed conjugated systems, does not necessari¬
ly have to take place, The second reason is invalid since
the high molecular weight and abundance of bands in the
fingerprint region of triterpenes often lower the prominence
of this band as has been observed in cyclosteroids. The third
reason is invalid since these are both valid functions of con¬
jugation with the cyclopropyl ring, even when weak. Thus
cyclopropyl methyl ketone is quite stable to acid. In a la¬
ter paper, however, Spring favored the cyclopropyl structures
on the basis of mechanistic grounds as well as by analogy194)
with corresponding reactions in the a-amyrin series.
The final cyclopropyl ketones to be considered are the
cyclosteroids. Since the bonds to ring C must be diequatorial,
and due to the rigid union with ring A, only two conformations
are possible, an unfavorable half-boat with the C=0 overlap¬
ping one side of the cyclopropyl ring, and an unfavorable half-
chair with the C=0 overlapping the other side of the cyclo¬
propyl ring. However, an intermediate conformation with C3-
C5-C6-C7 more or less coplanar would be quite highly conju¬
gated. Although at first glance this might sound rather un¬
likely, the fact that the oxygen atom is also coplanar makes
- 86 -
this system quite unhindered. Of interest is that this
system is oonstrained to s-cis conjugation. The observed
data shows that cyclosteroids are indeed highly conjugated.
3»5-cyclo-6-ketocholestane has an absorption in the ultra¬
violet practically identical to carone, especially in the K
87 ^band end absorption. In the infrared the carbonyl ab¬
sorbs at 1683-1695 cm" .
5' *'This is indeed good oonju-
4.gation for ZT-cholestenone-3 absorbs only a little lower at
1678-1680 cm- as compared to 1719 cm" for saturated 3-
ketosteroids. 3>5-cycloandrostan-6,17-dione appears
to be even slightly more conjugated, absorbing at 1680-1689
cm .
Aromatic Rings. For ideal conjugation between an aromatic
and cyclopropyl ring, the planes of the two rings must be at
right angles to one another. This produces a slight hinder-
ance between the CI hydrogen on the cyclopropyl ring and one
of the ortho hydrogens on the aromatic ring, so that the con¬
jugation should be weaker than in the corresponding vinyl-
cyclopropanes.
Phenylcyclopropane itself has been thoroughly
studied. ' It shows a conjugative exaltation of the
molecular refraction of +0.23 as compared with +1.10 for
styrene. Its ultraviolet spectrum as compared with the cor¬
responding saturated and unsaturated analogues, is shown be-
low:162'208>N V Transition R Band
Ethylbenzene 206 mu (log £=3-51) 259 mu (log e=2.23)Phenylcyclopropane 220 mu (log e=3.93) 274 mu (log e=2.45)Styrene 245 mu (log 6=4.21) 290 mu (log e=2.74)
The bands in the near ultraviolet have been correlated with
TT-bond character to give the following bond orders: benzene=
1.0, alkylbenzenes = 1.17 (TWhyperconjugation), phenylcyclo-162")
propane = 1.67 and styrene = 2.0 (fWTconjugation).
- 87 -
We can predict the effect of substituents on this con¬
jugation. An ortho substituent on the aromatic ring will
seriously disturb the conjugation, since in a conformation
suitable for conjugation, it will interact either with the
hydrogen at CI on the oyclopropyl ring, or with the cis
hydrogens at C2 and C3. Two ortho substituents should
produce a completely non-conjugated system. Likewise
substitution of the oyclopropyl ring at CI or at the cis C2
and C3 positions should also hinder conjugation. This has
been confirmed by an examination of the ultraviolet spectrum
of a series of substituted trans-2-phenylcyclopropanecarbox-
amides. '
Although it was thought that transmission of
conjugation between the oyclopropyl ring and the carboxamide
was being measured, actually the main effect measured was
the phenylcyclopropane conjugation. Thus, although 2-o-
tolylcyclopropanecarboxamide possesses no measurable K band
maximum, the corresponding m-tolyl and p-tolyl compounds
possess K bands at 225 mu (log e=3.96) and 226 mu (log e=4.12).
Similarly, 3-methyl-2-phenylcycloprop£.neoarboxamide has a K
band at 221 mu (log e=4.03) since the methyl and phenyl
groups are trans to the carboxamide group and therefore do
not hinder conjugation. However, this result was mistakenly
interpreted to mean that the unsaturation of the oyclopropyl
ring was isolated at C1-C2. Ethyl trans-2-phenylcyclopropane-
carboxylate is also conjugated and possesses a K band at226^
221 mu (log e=4.01), '
only a little higher than phenyl¬
cyclopropane itself as expected from the weak conjugating
power of carboxyl derivatives.
174.)2-Cyclopropylpyridine is completely analogous. It
shows a conjugative exaltation of the molecular refraction
of +0.4 as compared to +1.1 for 2-vinylcyclopropane. Its
ultraviolet spectrum as compared with the corresponding sat¬
urated and unsaturated analogues is:
- 88 -
N~-»V Transition R Band
2-n-Propylpyridine <220 mu (log e>2.7) 262 mu (log e=3-6)2-Cyclopropyl pyridine <220 mu (log e>3.6) 269 nru (log e=3.6)2-Vinylpyridine ~230 mu (log e=4.1) 278 mu (log =3-7)
The assumption, however, that this resonance is due to cop-
lanarity of the two rings is patently false.
Correspondingly, 3-furylcyclopropane and l-(3-furyl)-227)
1-methylcyclopropane have also been prepared. Unfortu¬
nately no spectral data is reported, since although the
former should he highly conjugated, the latter would he hin¬
dered. In both cases, however, the conjugation should be
better than in the corresponding phenyl compounds due to the
lower hinderance resulting from the smaller heterocyclic ring.
As the conclusion of this survey of conjugated cyclo-
propanes, we might consider cyclopropyl cyanides. As has been
often pointed out, carboxyl derivatives possess only a weak
conjugating power. Nevertheless, cyclopropylcarboxyl deriv¬
atives will be conjugated to an intermediate degree between
that of the corresponding saturated and unsaturated deriv¬
atives. The nitriles are completely analogous, and in addi¬
tion, due to the very low steric requirements of the nitrile
group, the cyclopropyl cyanides will always be as highly con-
jugated as is possible. Thus 2-methylcyclopropyl cyanide
has a conjugative exaltation of the molecular refraction of
+0.33 as compared to +0.37 for acrylonitrile. The ultraviolet
spectrum together with those of the corresponding saturated
and unsaturated analogues is given below:
Acetonitrile 167 mu
?-Methylcyclopropyl cyanide ~210 mu (log e=1.16)Acrylonitrile 214-217 mu (log 6=1.70)
- 89 -
Crossed Conjugation. The cyclopropyl ring can engage in
three types of cross-conjugated systems - cross-conjugated
on a carbonyl which is by far the most important, on an
olefin, or on a cyclopropyl ring. The effect of the cyclo¬
propyl ring in such systems is usually rather unimportant
for two reasons. In order for the cross-conjugated system
to exhibit maximal conjugative effects, the whole chromophore
must be coplanar and at right angles to the plane of the
cyclopropyl ring. This requirement is seldom realized due
to the cyclopropyl ring's greater steric requirements. In
addition, in cross-conjugated systems in which one of the
two component chromophores is weaker than the other, the re¬
sultant system tends to exhibit the characteristics of the
stronger chromophore.
Cross-conjugated carbonyls can exhibit several effects.
The conjugative exaltation of the molecular refraction will
be raised slightly. In the infrared the C=0 band will lie at
lower frequencies. Thus a,B,a',B-dienones as well as diaryl
ketones absorb at 1670-1660 cm". In the ultraviolet the
wavelength of the K band maximum is usually less than that
for the corresponding linearly conjugated system.
The most interesting cross-conjugated carbonyls are the
21 ^)dicyclopropyl ketones. Dicyclopropyl ketone itself is
unusual in that steric effects favor a conjugated double
s-cis form, although hinderance of the Cl-Cl' hydrogens pre¬
vents perfect conjugation. Thus while cyclopropyl isopropyl
ketone (page 80) has a carbonyl band 20 cm~ lower than diiso-
propyl ketone, dicyclopropyl ketone has a carbonyl band 8 cm"
lower still at 1694 cm" . In the ultraviolet the K band has
a slight bathochromic shift as evidenced by a higher end ab¬
sorption, log e=3-l> at 208 mu. The E band has an even more
pronounced hypsochromic shift to 266 mu (log £=1.55).
Another interesting dicyclopropyl ketone is 1,2-methylenedi-
hydroumbellulone (l-methyl-4—isopropyltrieyclo(4:l:0 ' :0 ' )-
- 90 -
96)
heptanone-5), I in Pig. XXVI.;
The two cyclopropyl rings
are trans and identically oriented for fair conjugation.
Thus while conjugation in dihydroumbellulone (page 85) has
lowered the carbonyl hand in the infrared by about 23 cm",
the additional conjugation in I lowers the hand 12 cm" more
to 1709 cm". In the ultraviolet the second cyclopropyl
ring produces higher extinction coefficients, a bathochromic
shift of the K band of 4 mu, and a hypsochromic shift of the
E band of 5 mu: ^max 214 mu (log e=3.48), ^^^75 mu (log
e=1.8).
Cyclopropyl vinyl ketones are well known from the re¬
action of cyclopropyl methyl ketone with aldehydes. They can
exist in four cross-conjugated forms: a highly conjugated but
hindered s-trans-cyclopropyl s-cis-vinyl, a medium conjugated
s-cis-cyclopropyl s-cis-vinyl (most probable conformation),
and two highly hindered forms with an s-trans-vinyl orienta¬
tion. The simplest case, cyclopropyl vinyl ketone, is un¬
known, and if prepared would probably polymerize readily.
However, the phenyl derivative, cyclopropyl styryl ketone, has
been thoroughly characterized and does indeed exhibit cross-
conjugation.156-7,209,228)
Jn thg infrared the c=0 and c=c
stretching frequencies are at I685 and 1662 cm" as compared
to 1692 and 1669 cm for isopropyl styryl ketone.;
In
the ultraviolet, however, styryl vinyl ketone, styryl cyclo¬
propyl ketone and styryl isopropyl ketone have very similar
spectra as is to be expected since the stronger styryl-209)
carbonyl chromophore predominates in each case.' The un¬
usual l,3-dicyclopropyl-2-butenone-l shows a similar shift of
the stretching frequencies in the infrared due to cross-
conjugation, 'vmax1672 and 1592 cm"1.21*'
Of the cyclic cross-conjugated carbonyls, the most
interesting would be A-carenone, II. But this rearranges
immediately upon formation into its valence tautomer,
eucarvone.'
However, two derivatives are known, 2-hydroxy-
- 91
&,-carenone-5 and ^f-carenedione-2,5. These both show a
cross conjugated shift in the infrared with >)___ 1659>-1 '\ -1
1641 cm and v 1670, 1628 cm respectively. Neverthe¬
less, their absorption in the ultraviolet is that of the
stronger chromophore: \ 229 mu (log £=4.05) and }
240 mu (log e=3«92) respectively.2
Anomalous is the A -tricyclo(3:3:l:0)undecenone-l
system, III, found in a and fl-amyrin derivatives. The ultra¬
violet spectrum should be that of the stronger enone chromo¬
phore normally observed at ^ 245-250 mu (log £=4.0-4.1)9(11)
max
* -oleanene systems, however, absorb
223)
,223)13,27-Cyclo-12-keto-A
in the ultraviolet at } 234-6 mu (log e=4.0-4.1)^J' The
corresponding cycloursenone system absorbs at ^_„_ 237 mu
1qa^ max
(log e=4.05). The cross-conjugation thus seems to exert
a considerable hypsochromic effect. A possible explanation
is that the cyclopropyl ring produces a conformation less
favorable to conjugation.
II
H- <<f^ AIII IV
Pig. XXVI: CROSS-CONJUGATION
Aryl cyclopropyl ketones are also cross-conjugated
systems with the s-cis conformation of the cyclopropyl ring.
Although the ortho hydrogens will interact with the CI
hydrogen on the cyclopropyl ring to prevent perfect cross-
conjugation, it should nevertheless be quite good. The
simplest member, cyclopropyl phenyl ketone, has been thor¬
oughly investigated.45'156,209'211^ It shows an additional
conjugative exaltation of the molecular refraction due to
- 92 -
cross-conjugation of +0.5 compared to +1.2 for phenyl propen-20Q 211}
yl ketone. The spectral data compared to the cor¬
responding saturated and unsaturated analogues is shown be¬
low:
I.R.228> U.V. - K Band209)
Phenyl methyl ketone 1692 cm" 242 mu (log £=4.09)Phenyl cyclopropyl ketone 1677 cm" 244 mu (log e=4.15)Phenyl propenyl ketone 1680 cm" 256 mu (log £=4.24)
The lower position of the carbonyl stretching frequency
clearly shows cross-conjugation. That the cyclopropyl ketone
is lower than the propenyl ketone is anomalous, but the dif¬
ference is small. The K bands are as expected. Cyclopropyl
phenyl ketone exhibits the absorbtion of the stronger phenyl-
carbonyl chromophore. However, in phenyl propenyl ketone the
two chromophores are more equal and the expected bathochromic
shift is observed. Carr and Burt in 1918 noted completely
analogous results in a comparison of the ultraviolet absorp¬
tion of dimethyl 2-benzoyl-3-phenylcyclopropane-l,l-dicarboxy-
late with the corresponding saturated and unsaturated
analogues.'
One ortho substituent should produce no hinderance to
cross-conjugation. Thus, for example, o-anisyl cyclopropyl
ketone'
exhibits the expected cross-conjugated carbonyl
stretching frequency in the infrared, I664 cm" . Two ortho
substituents should, however, produce an interaction with the
cyclopropyl ring in which the conjugation of both groups with
the carbonyl should be weakened (compare ortho substituted
acetophenones '. Thus mesityl cyclopropyl ketone
has no cross-conjugative exaltation of the molecular refrac¬
tion (compared to mesityl methyl ketone). In the infrared the
carbonyl band is raised to 1679 cm" compared to 1651 cm" for
mesityl propenyl ketone,'which is considerably less hin¬
dered due to the smaller size of the olefinic group, and thus
possesses a small positive cross-conjugative exaltation of the
- 93 -
molecular refraction of +0.5. It is unfortunate that the
ultraviolet spectra of these two mesityl ketones have not
been measured. Mesityl methyl ketone (2,4-,6-trimethylaceto-
phenone) absorbs at X»=,- 242 mu (log e=3.55) ' ^as ex-
pected for the hindered system. Mesityl cyclopropyl ketone
would be expected to have a slightly lower extinction coef¬
ficient due to the greater hinderance of the cyclopropyl
ring, although the band position would probably be about the
same. Mesityl propenyl ketone should show about the same
ultraviolet maximum as phenyl propenyl ketone (256 mu), and
the extinction coefficient should be reduced, although less
than with mesityl cyclopropyl ketone due to the smaller
hinderance of the olefin group.
Substitution of cyclopropyl phenyl ketones at CI of
the cyclopropyl ring will also appreciably hinder cross-con¬
jugation by twisting either or both of the rings from the
favorable conformation. In the special case of 1-benzoyl-l-
phenyl cyclopropane, which is cross-conjugated on both
the carbonyl and the cyclopropyl ring, the bulky phenyl groups
interact to such an extent that cross-conjugation is complete¬
ly destroyed. This should result in a rather high carbonyl
band in the infrared. The ultraviolet absorption should pos¬
sess normal, although probably weaker, phenyl-carbonyl plus
phenyl-cyclopropyl K bands. Unfortunately, the only ex¬
perimental data available is that the 2,4-dinitrophenyl-
hydrazone is yellow, a characteristic of non-conjugated car-
bonyls.
So far only systems cross-conjugated on the carbonyl
have been considered since they are the commonest. However,
systems cross-conjugated on the olefin are also quite possible,
although in this case the effect of the cyclopropyl ring would
be minimal. An example of such a system is 2-cyclopropylbuta-2^1)
diene-1,3. No data is reported for this compound, but it
would be expected to show conjugative properties practically
- 94 -
identical to butadiene itself. Compounds may also be cross-
conjugated on the cyclopropyl ring. These should be especial¬
ly interesting since the competing Tf-IT conjugation is absent.
Unfortunately, however, as has already been pointed out,
substitution at CI on the cyclopropyl ring sterically hinders
conjugation so that these systems will seldom exhibit any
pronounced conjugative effects. Thus 1-acetyl-l-phenylcyclo-
propane shows no conjugative exaltation of the molecular re¬
fraction, and the carbonyl stretchiigband is at
_i 210)1706 cm "". The geminal diphenylcyclopropanes should be
similarly unconjugated. Even in the simplest possible diene
cross-conjugated on a cyclopropyl ring, 1,1-divinylcyclopro-
pane, the hihderance would probably prevent appreciable conju¬
gation. There is, however, a system in which ring fusion
would hold the chromophores in a position of maximal cross-
conjugation, spiro(4:2)heptadione-3,6 (2,2-dimethylenecyclo-
pentadione-1,3), IV in Fig. XXVI. A derivative of this
system, spiro(4:2)hepta-3»6-dione-4,5-dicarboxylic acid, has
been prepared by condensation of cyclopropane-l,l-dicarboxylie2^3)
ester with succinic ester. ' It would be of interest to
compare the conjugative properties of this compound with
2-methylenecyclopentadione-l,3 and 2,2-dimethylcyclopenta-
dione-1,3. Hydrogen bonding in cyclopropane-l,l-dicarbox-
aldehyde should likewise hold this compound in a conforma¬
tion of maximal cross-conjugation. This may also be true
of 1-acetylcyclopropane-l-carboxaldehyde in which splitting
of the carbonyl spectral bands should be observed.
Transmission of Conjugation. Is the cyclopropyl ring capable
of transmitting conjugation between two chromophores? We
believe so, although probably with less efficiency than a
double bond due to the 2/3rds p bond character of the cyclo¬
propyl ring. The difficulty lies in choosing a system in
- 95 -
which both chroniophores are highly conjugated with the cyclc-96)
propyl ring. Eastman has prepared very pure l-acetyl-2,2-
dimethyl-3-(l-isobutenyl)cyclopropane from trans-chrysanthen-
ic acid chloride via a cadmium Grignard, and from a study of
its properties has concluded that the cyclopropyl ring is in¬
capable of transmitting conjugation. He fails to take into
account, however, the fact that in this compound, the acetyl
group, which is probably in the s-cis form, is hindered by
the geminal dimethyl groups on the cyclopropyl ring. In ad¬
dition, as has been pointed out, the vinylcyclopropane con¬
jugation in trans-chrysanthemic acid is not ideal. There¬
fore, the transmission of conjugation should be weak, and this
is indeed what is observed. The ultraviolet spectrum has a
band at }__„ (210 ^ax (log e)3.9) plus shoulders at about 235
mu (log e=3.7) and 280 mu (log e=2.3). The first of these is
undoubtedly the vinylcyclopropane half-chromophore. Reduction
of the carbonyl produces the corresponding alcohol with an
identical end absorption. The second band is probably the
complete vinylcyclopropyl-carbonyl chromophore representing
transmission of conjugation. The third is undoubtedly the R
band of the carbonyl. No separate half-chromophore for the
cyclopropyl-carbonyl system is to be expected since it is
hindered, and either conjugates with the entire vinylcyclo¬
propane or not at all. In the infrared, the carbonyl stretch¬
ing band is at 1692 cm", 12 cm" lower than in cyclopropyl
methyl ketone. Eastman says, "the small bathochromic shift
in the C=0 frequency ... is attributed to the effect of the
gem-dimethyl substitution, not to coupling through the cyclo¬
propane ring since it has been shown that a Y,o -double bond
produces an inappreciable shift in the C=0 frequency of an a,
B-unsaturated aldehyde." This argument is untenable. The
effect of the geminal dimethyls would be rather to raise the
carbonyl band due to steric hinderance to conjugation, and
the carbonyl band at 1704- cm" in cyclopropyl methyl ketone
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IS)
BP
PP
ch
P-
HP
.CD
Pp
PR
P-
ROH
ch
3*
MCO
Rch
PJ
PR
4ra
p-
CD
Vj
OH
4M
3<!
PSj
CD
4ra
*d
Pp-
*i
P-
3ch
PCD
•W
Hi
a*
Vj
OH
MPJ
p"
4cr
Pp.
Vj
p1
H-
pCD
CD
p-
PHj
CO
ch
P-
0*
3*
ro
P3
PP
Rp
PB
p-
cj.
0ca
ro
<Jd-
PP-
P-
tr
43*
PCO
0R
4ch
pCD
dII
4Pi
PP
CJ.
RM
P1
4P
04f
P-
p1
Pp-
P1
3ch
*d
ch
p-
P-
PP
CO
0*
ro
CO
pi
o*
3o
CO
1R
ch
cr
RP-
<J4
P"
4>d
H-
ch
PH-
0B
4CD
cr
PJ
4cr
s0
4p
CD
VJ
p•d
RPi
•d
VJ
ch
-.
3*
Pt
CD
P"
SjR
CO
Pt
CD
3*
-.
ROH
pP
Pp
OH
Os.
Cj>
RCO
|CD
ch
P<
^-'
t*r
RP
P-
0ch
ch
Hj
OH
Hj
Rp
CD
PM
<o
B0
tr
Rts
0*
P"
CO
P-J
Pp
0Vj
>d
CD
P•*
3P
3•
P"
Si4
CD
pB
Vj
Pi
pch
ch
ch
MP
oP
CO
.P-
RP
CO
4\J\
P-
CD
P-
4*—
*—*
R4
CD
04
00
1B
Vj
Hi
P-
PCD
.eh
MOH
CD
P1
Pp-
ch
1P
34
RP1
CD
0*
Ptr
pR
P-
PP-
h-i
CD
P.
RHi
ch
10*
OJ
P0
Vj
40
CD
CD
RR
p-J
Ptr
*d
ch
ra
<R
!><
CD
RCD
Rco
Mch
II3
P-
Pi
0OH
CO
Po
00*
4P-
HPJ
•B
pj
RCD
3d
Peh
34
CO
(n
Rra
4CD
P-
3P
Rd-
pd-
Vj
OJ
B4
P.
pCD
BB
Pp-
CD
CD
p.
CD
CO
3P-
p-
ch
<P<
P0
Hi
P•d
CO
liO
RR
CD
eg3*
R
P"
CO
P-
3cr
p-
POH
ch
M4
VJ
4CD
PP
OH
PP-
ro
o•
tr
4P-
co
eh
R
CD
R3
PB
4P
PB
vj
PCD
ch
ch
M4
CD
aP
4OJ
p>
i?•d
Pch
CD
3*
CD
Vj
p-
Ncr
Op
>«j
P1
OH
P•d
•d
tr
CD
pj
PP
>d
C_l.
>d
0OH
Pp
4P
<!B
H
ch
C4
tr
Pch
h-1
*—^
Pch
RP
ch
RVj
BP
PP
0P
PR
MB
1B
Hj
PP-
RVj
PP
cr
W•d
CJ.
CO
44
p0
1P
PH
P-
p-
pcr
Hi
P0
P-
OH
4N
P.
P1
VJ
4co
-B
p0
Vj
•d
4p
>x
CD
4R
pch
^-^
ep*
P-
P<
Hj
0CD
CO
MP1
PCD
PUl
BR
CD
Rch
RCD
p>K
P-
OH
V|
PJs-J
W?
3P.
CD
3*
eh
Rtr
Rtr
nCTvX
RP1
PHj
tr
CO
1&
4a
OH
p8*
RP
P-
3Vj
o*
Rp-
4OH
H-
ch
PP
•Jr»
ca
P0
ch
CD
CD
Mch
p1
RP
Bca
M3*
PP1
1P
cr
Rp-
0>d
p.
a\
Hj
p-
VJ
P-
<M
Vj
RCD
C-i.
PVj
HH
ch
P*
Rcr
•*»
CO
p-
P3*
P-•
PJ
4p-
ro
ptr
pCD
3Hj
pa*
3*
34f
"d
3*
3CT\
P"
3Vj
Vj
>d
P4
3*
CD
vj
PCD
pl
ch
PP
PB
H-
ch
P-
ch
ch
Ro
*d
R0
30
B(B
cr
OH
XP"
CD
P1
0*
P-J
0p
Sia*
CD
ra
pCD
Vj
Rro
cr
Rp
Pt
PR
R0
ch
CD
P4
CD
ch
CD
ch
VJl
R0
3*
ch
4CD
BVj
B\-
>3*
CD
4cr
cr
R4
p-
CD
4p
3*
4R
pro
p-
p-
d-
0w
3R
1H
P-
P"
d-
Hj
X4
P4
4CO
•d
p>
Vj
CD
Bch
BR
p-
1CO
PCD
VJ
>d
J^-
PP>
Pp-
oP
RR
PP
•vXI
CO
30
P"R
3*
&P1
P1
ra
P1
3P-
OH
BP>
ch
PSi
g3*
RR
P.
ON
P-
-•
R
d-
RP
tr
0P-
PJ
Vj
VJ1
p-
Vj
Pch
3P
M4
3P
H>P
3>>
•d
P<
CD
H3*
CD
•d
PN
3O
P-
Hj
RX
CO
03
>d
PR
Pp
H-
hP
PCO
RR
CD
P'
M<J
ch
3CO
3P
Pp-
BR
CO
P*d
44
P4
3*
c0
PJ
p-
ca
Bd-
v;
Vj
p"
ch
PCD
cr
PB
P3
Rcr
*cr
Pp
d-
Hch
CO
p-
3*
PCO
SjR
P•d
•d
oP
ch
3*
4ca
4CD
Oq
4PB
4R
CO
ca
>d
P"p
d-
40
d-
Pca
oCH
RR
CO
peh
4P
Pra
ra
Pp-
B"P
B4
P4
cr
PP
0CD
Rp
p-
4p-
tr
irP
44
CD
co
3-
CD
R
0*
Rp-
p-
PCO
PR
>J
ch
ROH
?_
PW
3>
P-
Hi
OH
SIOH
BCD
RCJ.
•d
^4
P-
ch
Bo
- 97 -
hibited similar properties.
>Co J^> X/\J_
H <V^II III IV
Pig. XXVII: TRANSMISSION OF CONJUGATION
Another example of possible transmission of conjugation
may be found in the fi-amyrin derivatives prepared by
Spring.223^ The 13,27-cyclo-^(11^,15-12-keto-oleadienesystem, II, analogously to the cross-conjugated cyclo-
oleanenone system discussed earlier, is also in a very poor
conformation for transmission of conjugation. In the ultra¬
violet it exhibits the two partial chromophores, /Ln-v- 209 mu
(log 2=3.48) for the vinylcyclopropane, and } 232 mu
(log e=4.10) for the a,fi-unsaturated ketone. Similarly, the
introduction of a 15-keto group into the 13>27-cyclo-£^ -
12-keto-oleanene system produces absolutely no change in the
ultraviolet.
A final example of possible transmission of conjugation
has been reported by Buchi. Irradiation of B-ionone
produced a small amount of material to which he assigned the
structure of l-acetyl-3,3-dimethyl-7-methylenespiro(5:2)
octane, III. Once again there is high hinderance to trans¬
mission of conjugation. That the carbonyl is very strongly
hindered by the geminal dimethyl groups is confirmed by its
-1Inrelatively high absorption in the infrared, 1718 cm
the ultraviolet, the R band is at Xx
284 mu (log e=2.10).
A high end absorption, log e=3.36 at 210 mu, is indicative
of the vinylcyclopropane half-chromophore, although at a
shorter wavelength than usual. However, Buchi concludes that
the spectral data indicates that both the carbonyl and semi-
cyclic methylene conjugate weakly with the cyclopropyl ring.
- 98 -
Of interest is that ozonolysis in this case opens the cyclo-
propyl ring yielding 2,2-dimethyladipic acid.
Prom the foregoing examples, it might appear that
transmission of conjugation through the cyclopropyl ring is
always hindered. However, this is not necessarily the case,
and by proper ring fusion it should be quite easy to prepare
compounds which would exhibit maximal transmission of conju¬
gation. Two such examples are shown, IV and V in Pig. XXVII.
The similarity to the ideally conjugated nortricyclanone, IV
in Pig. XXV, and to isopropylenenortricyclane, III in Pig.
XXIV, should be obvious. A more convenient set of systems,
however, can be derived from cyclocholestane: A'
-cyclo-
cholestadiene, A-cyclocholestenone-2 and A-cyclocholesten-
one-6. In these three examples, and especially the last,
the conjugation with the cyclopropyl ring is fairly good so
that transmission of conjugation should be observed.
Cyclic Systems - Norcaradiene and Umbellulone. The cyclic
systems are especially interesting. Not only are transmis¬
sion of conjugation and cross-conjugation involved, but
pseudo-aromatic character may also be present. The first
such system, norcaradiene, II in Fig. XVII, has already been
discussed under valence tautomerism where it was shown that
due to the poor conjugation of the double bonds with the
cyclopropyl ring, it exists as its valence tautomer, cyclo¬
ne ptatriene. However, ethyl norcaradienecarboxylate is
stable, and it would be of great interest to measure
its ultraviolet spectrum, where it would be expected that a
weak interaction with the cyclopropyl ring should indeed be
observed.
Umbellulone,96'216'222) I in Pig XXVIII, has long been
of interest due to its unique ultraviolet spectrum, 2af.\ max
220 mu (log e^3.77) and 265 mu (log e=3-52). ' Of note is
the weakness of the K band and the strength of the R band as
- 99 -
well as the hypsochromic position of both bands. The first
problem in explaining these results is to find a suitable
model. Thymol, into which umbellulone is slowly and irrever¬
sibly converted, obviously plays no role. Attempts which
have been made to explain the spectrum on the basis of the
six ring analogues, piperitone, carone and santonin, are
clearly incorrect, for as a study of B-dihydroumbellulone
has shown, this system must be related to cyclopentenone,
In the ultra-96)
cyclopentadienone and dihydroumbellulone.-2
violet, 3-methyl-5-isopropyl-A-cyclopentenone-1 would be ex¬
pected to absorb at about 229 nw calculated on the basis of
cyclopentenone plus a B-substituent,217)
or on the basis that
cyclopentenones are approximately 10 mu lower in the ultra¬
violet than the corresponding cyclohexenones. The cor¬
responding cyclopentadienone would be expected to show an
appreciable hypsochromic shift due to the extra endocyclic
double bond and lack of aromaticity in the resulting four-
electron ionic system, so that it will behave essentially as
a dampened cross-conjugated ketone. B-Dihydroumbellulone
absorbs at i„„
210 mu (log e=3.4).ULElJC
A<—
Ila lib
Fig. XXVIII: UMBELLULONE
The cyclopropyl ring in umbellulone is oriented so that
only fair overlap of the thujene type can occur with either
chromophore, the double bond and the carbonyl lying in a plane
including one side of the cyclopropyl ring. Thus the effect
of the cyclopropyl ring must be far less than in B-dihydro¬
umbellulone. Since the cyclopropyl ring will preferentially
- 100 -
donate electrons and the oxygen will preferentially accept
electrons, we can then write two exited ionic states for
umbellulone, Ila and lib. The former corresponds to an ex¬
tension of the enone conjugation tc the cyclopropyl ring,
and would be expected to produce a hypsochromic shift due
to the lower charge separation. The latter, which is the
stabler due to the larger charge separation, corresponds to
cross-conjugation and would also be expected to produce a
hypsochromic shift in this case. Both forms are thus in
agreement with the observed shift of the K band of umbel¬
lulone as compared to methylisopropylcyclopentenone. The
low extinction coefficient of this band is undoubtedly re¬
lated to the poor orientation of the cyclopropyl ring for
conjugation, as well as the preferred electronegativity of
the cyclopentadiene ring. The question then arises as to
the nature of the band at 265 mu in umbellulone. It is
probably the R band, which is often quite strong in cross-
conjugated systems. The hypsochromic position is unusual,
but may be due to cross-conjugation as well as to the hypso¬
chromic effect that cyclopropyl ketones often seem to exert
on the R band.
In the infrared umbellulone has a carbonyl band at
1701 cm~, lower than any other thujone-type cyclopropyl
-1 96carbonyl and 14 cm lower than cyclopentenones in general,
indicating very high polarization of the carbonyl as expected
from Ila and b.
CHAPTER IV
SYNTHESIS OF TRICYCL0(4:4:1:0)UNDECANE
AND 10-METHYL-£L^-0CTA1IH
The synthesis of tricyclo(4:4:l:0)undecane (VIII in Fig. XXIX)
started from cyclobexanone which was converted into 2-carbeth-
oxycyclohexanone (II) via the cyclohexanone pyrollidine235)
enamine,'
or preferentially via ethyl 2-ketocyclohexyl-
glyoxalate. This was in turn condensed with l-(diethyl-237)
methylamino)butanone-3 iodideJ '
to yield the wellknown d,l-
10-carbethoxy-A -octalone-2 (III), which has been prepared
by similar procedures (25-73?» yield,120'23 '25*~5)as well as
by condensation of 2-carbethoxycyclohexanone with methyl vinyl
ketone and subsequent cyclization (60?£ yield), 'or conden¬
sation with formaldehyde and acetoacetic ester by aqueous base
(trace yields). The present procedure represents a con¬
siderable improvement over previous procedures by carrying out
the condensation of the Mannich base in neutral solution, and
subsequent cyclization with only l/10th mole base.
In order to remove the keto group without disturbing the ester
group or double bond, the ethylenethioketal was made in almost
24 3)
quantitative yield with borontrifluoride etherate,-" and sub-
244)
sequently desulfurated with deactivated Raney nickel ' to
yield d,l-10-carbethoxy-A^
-octalin (IV). Of interest was
the observation that the neutral washed Raney nickel could
saponify considerable portions of the ethyl ester. This was
subsequently prevented by, 1) washing the neutral Raney nickel
with 0.01N acetic acid to neutralize basic centers, and 2) ad¬
ding at least a ten mole excess of ethyl acetate to the de-
sulfurization solution.
The question arises as to whether during the course of
lfplthis desulfurization the A double bond might have rear-
- 102 -
1(2)
ranged to the A position as has been shown to occur in
the desulfurization of the ethylene thioketal of 10-methyl-
A ^-octalone-2. 'However, in the steroid field the de¬
sulfurization of the corresponding grouping has been shown
to proceed without rearrangement, although desulfurization
of the ethylene thioketal of A -cholestenone-3 produces195)
cholestene-2. ' Evidence that the double bond has not rear¬
ranged is obtained from the infrared spectrum of IV where the
lack of a band at 675-750 cm~~ (CH out-of-plane deformation)
eliminates a symmetrically disubstituted cis olefin, while
the expected band at 815 cm" for a trisubstituted olefin is
212)present. An attempt was made to obtain a chemical proof
of the position of the double bond by ozonization followed by
oxidation of the resulting ozonide. However, neither 1-
carbethoxy-l-(lf-butyric acid)cyclohexanone-2 nor 2-carbethoxy-
2-(fl-propionic acid)cyclohexanoic acid could be isolated. It
is believed that the ozonide yielded higher oxidation products
with possibly both rings opened.
The carbethoxy group of IV was smoothly reduced with247)
lithium aluminum hydride' in almost quantitative yield to
d,l-10-hydroxymethyl-A -octalin (V). This, upon reaction
with methylsulfonyl chloride and pyridine at 20, yielded the
stable mesylate which upon attempted distillation began to
i
„1
decompose rabidly at 110 . Small amounts of VI could be iso¬
lated from the tarry decomposition products. Since an SN
ionization can be accelerated by both an increase in the
temperature as well as by the use of an ester of a stronger
acid (which will yield a more stable anion), the benzenesul-
fonate was prepared. This was observed to be considerably
less stable. Refluxing this ester overnight in anhydrous
pyridine yielded the desired d,ltricyclo(4:4:l:0)undecene-2
(VI). The product was, however, quite unstable. A parallel
attempt to produce the rearrangement by heating the benzene-
sulfonate at 110° for eighteen hours with an excess of active
- 103 -
alkaline alumina in an evacuated bomb led to a complicated
mixture rich in aromatics.
l)C4HgN2)ClC00Et
l)(C00Et),2)-C0
COOEt
IV
COOEt
Mannich
COOEt
Base ^^OEt
"
III
I) BF3/C2H6S22) Raney Nickel
CH2OH
LiAlH,
[jCgB^SOgCl/Py.2)Reflux pyridine
V**
VII
Fig. XXIX: SYNTHESIS OP TRICYCI0(4:4:1:0)UNDECANE
The infrared spectra of VI show four prominent bands
at 3058, 2990, 1013 and 874(?) cm as expected for the cyclo-
propyl ring (see Appendix I), as well as various bands indi¬
cating unsaturation. The lack of bands between 1370 and 1380
cm" as well as in the neighborhood of 2965 cm- indicate that
no methyl groups are present. In addition, the spectra are
atypical of aromatic compounds. However, the band at
1600 cm" as well as the maximum in the ultraviolet at 253 mu
(log e=2.7-3»5 depending on the preparation) indicates the
presence of 15-45$ of a conjugated diene system as an impurity,
probably bicyclo(5:4:0)undecadiene-8,10 formed by ring en-
- 104 -
largement of the intermediate carbonium ion (calculated U.V.:
^ 258 mu). Gas chromatography indicated that the product
was only 50f> pure with five impurities, the major one (31$)
probably being the conjugated diene. The orange-red color
produced with tetranitromethane is similar to that observed
with 13.27-cyclo-A -3B»28-dimesyloxyursene. The latter,
however, has an ultraviolet maximum at 224 mu (log e.=
3.66), whereas the K band maximum of VI is at 212 mu
(log £=4.1 extrapolated to 100$).
VI could be smoothly and rapidly reduced by platinum
in methanol with the absorption of 0.99 mole of hydrogen to
yield impure tricyclo(4:4:l:0)undecane (VII). The presence
of non-reducible double bonds could be shown by the strongend absorption in the ultraviolet as well as a positive re¬
action with osmium tetroxide. Gas chromatography indicated
52$ purity with four impurities, the major one (28$) probably
being bicyclo(5:4:0)undecene-10 with the double bond between
the rings. The infrared spectra are quite different in the
fingerprint region from those of VI, but prominent bands re¬
main at 3051, 2990, 1013 and 88l(?) cm" for the cyclopropyl
ring. Most of the olefin bands, especially in the region
1600-1700 cm" as well as at 3024 cm", haye completely disap¬
peared, although the bands at 1496 (overtone 743 cm- ?) and
743(s) cm" (triply substituted olefin?) remain. A very weak
band appears at 1378 cm" which could represent traces of
methyl group formed by 1,4-reduction of the vinylcyclopropane
system. However, this band is weak and the corresponding
methyl band at 2962-2972 cm" is absent.
VII was purified by treating with excess osmium
tetroxide, whereby about 34$ was removed, and then fractional¬
ly distilled to yield pure tricyclo(4:4:l:0)undecane (VII),
*) Zurcher reports it to be at 244 mu for this derivative,but this is believed to be a typographical error.
- 105 -
b.p. 76-7°/l0 mm., plus a small amount of a higher boil¬
ing substance. VII gave a light yellow color with
tetranitromethane as expected for the cyclopropyl
ring>89,117-8,194,203,245,250) had &n ^^ molecular
refraction of 4-7.5 (calcd. 47.2), ' and in its infrared
spectra still showed the bands for the cyclopropyl ring.
The weak band at 1378 cm" was still present, but the bands
at 743 and 1496 cm" were absent. Although the cyclopropyl
ring should show almost no end absorption in the ultraviolet
at 210 mu>l8>89,194,203,249) VII exhibited tw0 maxima at
216 mu (log e=1.4) and 237 mu (log £=1.1),;which probably
represent less than 0.5$ impurity. Gas chromatography in-
dicated that the product was at least 93$ pure.
The osmic ester remaining from the purification was
reduced with lithium aluminum hydride, but no pure product
could be isolated.
In order to obtain a chemical proof of structure,
VII was isomerized by heating for four hours with a few drops
of boron trifluoride etherate in acetic acid at 100 . The
resultant d.l-lO-methyl-^^-octalin (VIII in Pig. XXX) had
a strong end absorption in its ultraviolet spectrum at 220 mu,
and in its infrared spectra showed new bands at 3021, 1661 and
808 cm" for the trisubstituted double bond as well as strong
bands at 1381 and 2964 cm" for the methyl group. The cyclo¬
propyl bands were no longer present. Gas chromatography
showed that VIII was 71$ pure, and that the major byproduct
(28$) was different from those present in the precursors.
*) Zurcher's reduced vinylcyclopropane, 13>27-cyclo-3fl,28-diacetoxyursane, also absorbed in the ultraviolet, Am^r(shoulder) 235 mu (log £=1.6) plus an end absorption,
log 6=2.8 at 205 mu11').
**) VII was observed to isomerize to olefinic material
during gas chromatography.
- 106 -
Since VIII had not been previously reported in the
literature, it was synthesized by an independent route. Haney
nickel desulfurization of the ethylenethioketal of 10-methyl-
A -octalone-2 (IX) apparently proceeds with rearrangement245)
of the double bond. However, VIII was successfully pre¬
pared via a novel double Wagner-Meerwein rearrangement in¬
volving a pinacolone rearrangement followed by a retropina-*)
colone rearrangement.' The pinacol derived from cyclo-
pentanone, bicyclopentyl-1,1 -diol, was rearranged by dilute
sulfuric acid into spiro(4:5)decanone-6 (X).~
' As a
1 l'byproduct the as yet unreported
'
-bicyclopentene (XI) was
also obtained. X reacted smoothly with methyl magnesium
iodide to yield 6-methylspiro(4:5)decanol-6 (XII), which
upon treatment with boron trifluoride etherate in acetic acid
at room temperature yielded very pure VIII. The two preparat¬
ions of VIII were essentially identical in physical properties
and in their ultraviolet and infrared spectra, with however,
minor differences apparent due to impurities in the former
preparation. Gas chromatography showed that the two preparat¬
ions were the same.
To eliminate any doubt as to the identity of the two
preparations of VIII, they were both oxidized with tert.-butyl253) 1(9)
chromate to 10-methyl-A -octalone-2 (IX) and identified
as their semicarbazones. Both semicarbazones were not only
completely identical in their infrared spectrum with an
254)authentic preparation,
'but also had the same melting
point and showed no depression on admixture.
*) Proposed by Dr. D. Arigoni, E.T.H., on the basis of a
similar conversion of spiro(3=4)octanol-4 into bicyclo-(3:3:0)octene-l(5).241)
**) Preparation of this hydrocarbon has been attempted by de¬
hydration of the pinacol with dehydrated alum. Althoughthe product could not be purified, the maleic anhydrideand benzoquinone adducts were prepared.252)
- 107 -
VIII
t-butyl chromate
Mannich Base,
NaNH„
Pig. XXX: SYNTHESIS OF d,l-10-METHYL-A1^9^-0CTALIN
108
EXPERIMENTAL* ^
2-CARBETHOXYCYCLOHEXANONE (II).
A; Via Cyclohexanone Pyrollidine Enamine. ' 111 g.
(1.13 moles) of cyclohexanone, 100 g. (1.41 moles) of
technical grade pyrollidine and 500 ml. of benzene were re-
fluxed with a water separator until no more water could be
collected (2 1/2 hours). The solution was concentrated at
the aspirator and distilled. After a very small forerun,
14-5 g. (85$ yield) of colorless enamine was collected
boiling sharply at 102 /ll mm., which rapidly decomposed in
the presence of air.
Analysis M30306:Calcd. for C,0H _N: C, 79-40; H, 11.34; N, 9.26$.Pound:
±lC, 79-47; H, 11.31; N, 9.31$.
I.R. 6475: ^mayr 1641(s) cm-1 (olefin) and 1711(w) cm"1.
U.V.: An end absorption at 220 mu due to the double bond.
100 g. (0.66 mole) of freshly prepared enamine were
dissolved in 1 liter of sodium-dried ether, and 100 g.
(0.92 mole) of ethyl chloroformate in 300 ml. of ether were
added dropwise with thorough stirring. White crystals
inanediately started to separate.
*) Melting points are taken in an evacuated capillary in¬
serted in a copper block, and are uncorrected. U.V. spec¬tra are taken on a Beckmann spectrophotometer in ethanol.
I.R. spectra are taken on a Baird or Perkin-Elmer A21
spectrometer with a NaCl prism. For the region 2800-
3100 cm-,
a ferkin-Elmer single-beam double-pass spectro¬meter with a LiF prism was used. liquids are measured
without solvent in a layer 0.02 mm thick. Gas chromato-
grsms were made on both polar and apolar oil-on-Celite
columns operated at 150-180°. The compound was eluted with
helium and characterized by its pV value.
V°(compound) - V°(air)pV = log V6(n-decane) - V°(air}
**) These enamines are excellent intermediates for mono-
substitution on a methylene a to a carbonyl.
- 109 -
After the addition the solution was stirred for an hour and
then refluxed for two hours. The white precipitate was
rapidly filtered, immediately dissolved in watei; and allowed
to stand 15 minutes at 20 . The 2-carbethoxycyclohexanone
started to separate at once and was extracted twice with
ether; the extract was then washed with dilute hydrochloric
acid and sodium bicarbonate, dried with magnesium sulfate,
and concentrated. Distillation at the aspirator gave a
small forerun of cyclohexanone plus II, b.p. 95-105 /12 mm.'
2 ^6")B: Via Ethyl 2-Ketocyclohexylglyoxalate. This method was
found to be easier and to give more consistently high yields.
Glass flour (100 parts), boric acid (5 parts) plus iron
powder (1 part) was used as the decarbonylation catalyst.
d,l-10-CARBETH0XY-Z^9)-0CTAL0N.B-2 (III).
78.8 g. (0.55 mole) of freshly distilled 1-diethyl-
aminobutanone-3, b.p. 70.0-70.5 /ll mm., were dissolved
in 100 ml. of sodium-dried ether. The solution was cooled
in an ice bath with good protection from atmospheric moisture
and well stirred with a Hershberg wire stirrer while 150 g. of
methyl iodide dissolved in 100 ml. of dry ether were added
dropwise. The white crystalline methiodide immediately
started to precipitate and had to be well stirred to keep it
from clumping. After stirring for two hours at 0 and two
hours at 20°, the ether and excess methyl iodide were removed
by slowly applying suction from the aspirator without external
heating.' When the flask reached room temperature at a
*) The yields were variable. The boiling point is wide due
to the fact that the product is a mixture of keto form,
b.p. 102°/15 mm., and enol form, b.p. 115°/15 mm.269)
**) The stirrer is sealed to the guiding tube with a piece of
lubricated rubber tubing. This will hold a vacuum and
yet allow free rotation of the stirrer.
- 110 -
vacuum of 10 mm., the aspirator was disconnected and 250 ml.
of absolute ethanol were added. Without waiting for the
*)methiodide to dissolve, a solution, formed by rapidly ad¬
ding 85.1 g. (0.50 mole) of II to a solution of 12.6 g.
(0.55 mole) of sodium in 500 ml. of absolute ethanol,'was
added in about 15 minutes. During the addition the solution
was stirred constantly and kept at 20-25 . The methiodide
rapidly dissolved. The pale yellow opalescent solution was
allowed to stand 15 hours at 20°. 1.15g. (0.05m.) of sodium
dissolved in 50 ml. of absolute ethanol was then added and
the solution refluxed 4 hours. The solution was cooled, con¬
centrated at the aspirator, diluted with salt water, and ex¬
tracted twice with ether. The extracts were washed with di¬
lute hydrochloric acid and sodium carbonate, dried and concen¬
trated. The resulting yellow oil was distilled through a
short Vigreux column at the high vacuum pump using glass wool
instead of a capillary. After a small forerun (best removed
at 10 mm.), 83-92 g. (75-83$ yield) of colorless III were
collected up to the point where a yellow oil started to
distill. A center cut was redistilled for analysis.
Analysis M30193: Calcd. for C, H R0,: C, 70.24; H, 8.165b.Pound:
Xi ±0 iC, 70.01; H, 8.24y=.
U.V.: ;\max 237 mu (log £=4.15) .****}
*) The methiodide rapidly decomposed in ethanol to methylvinyl ketone.
**) Prepared just before use under nitrogen to prevent alde¬
hyde formation.
***) The boiling point was very sensitive to the rate of dis¬
tillation. Observed b. p. 174°A5 mm.; 165-l66°/lO mm.;
119-121°/0.25 mm.; 105°/0.03 mm.
****) Useful in checking that the crude product has eyclized.
- Ill -
I.R. 6405, 6529: ^ 1724, 1195 cm"?; (ester);1677, 1627 cm (a,B-unsaturated ketone).
The semicarbazone was prepared and recrystallized to
constant melting point from ethanol-benzene for analysis,
m.p. 186.5-191.5 with decomposition (reported 205-208
corr.).255)Analysis M30174: Calcd. for C. H„,0,N,: C, 60.19; H, 7.58$.
Pound:** ** 1 i
c> 60.24; H, 7.56$.
d, 1-10-CARBBTHOXY-^9 ^-OCTALIN (IV).
11.1 g. (0.05 mole) of III, 9.4 g. (0.10 mole) of
*)1,2-ethanedithiol, and 10 ml. of technical boron trifluor-
ide etherate were mixed. The solution immediately turned red
and became quite warm. After 15 minutes it was poured into
water and extracted twice with ether. The extracts were
washed with 2N sodium hydroxide until the excess mercaptan
was removed, dried and concentrated to give 14.9 g- (100$
yield) of an almost colorless, viscous, unpleasant-smelling
oil which could he used directly in the next step without
further purification. The thioketal was distilled twice for
analysis at high vacuum in a Hickmann flask using glass wool
instead of a capillary. It distilled sharply at 154-156 /
0.1 mm. (121°/0.03 mm.) with no forerun and only traces of
residue. It was easily soluble in methanol and hexane and
did not appear to crystallize from these solvents at dry ice
temperatures. In the ultraviolet it showed only an end ab¬
sorption at 220 mu due to the double bond.
Analysis M30353: Calcd. for C^H^O^S-: C, 60.39; H, 7.43$.Pound:
^ ^ ' *
C, 59-87; H, 7.39$.
100 g. of freshly prepared Raney nickel were
washed successively with distilled water until neutral,
twice with COIN acetic acid, several times more with dis-
*) This mercaptan has a very penetrating, poisonous and per¬
sistent evil odor. Strong sodium hydroxide solution may
be used to remove traces on glassware, etc.
- 112 -
tilled water, and then finally several times with dry ace-
244)tone. The nickel was deactivated by refluxing with
600 ml. of acetone-ethyl acetate 5:1 for two hours. A vibra¬
tor was necessary in order to keep the suspension from bump¬
ing. 14.9 g- of thioketal in a little acetone were then ad-*)
ded slowly to the refluxing suspension.' The reaction
mixture immediately evolved ethane, ceasing in about 7 hours.
After refluxing overnight, the nickel was allowed to settle
and the supernatant solution decanted and filtered through a
*)
pad of celite. ' The nickel was washed several times with
ethanol and decanted as before. The combined solvents were
removed on the steam bath, and the resulting pale yellow
liquid distilled from glass wool ' through a short Vigreux
column at the aspirator. After a small forerun of diacetone
alcohol, 5.7 g. (55$ yield; 64$ based on recovered III) of
colorless pleasant-smelling IV were collected, b.p. 120-130 /
12 mm. 1.6 g. of relatively pure III could be recovered by
distilling further until a yellow oil started to distill
(about 170-175°/!0 mm.). This was pure enough to treat
directly with 1,2-ethanedithiol as before. IV was redistilled
for analysis; b.p. 120-1210/10 mm. (ll8-119°/9 mm.), n^ 1.492,
yellow with tetranitromethane.
Analysis M30372: Calcd. for C, ,H9n0,,: C, 74.96; H, 9.68$.Pound:
±i ^C, 75.07; H, 9.61$.
I.R. 6735, 7423: ]mayr 1726(b), 1189 cm"1 (ester); 815 cm-1
(trisubstituted olefin) no bands 690-750 cm" for a cis
1,2-disubstituted olefin.
U.V.: A strong end absorption at 220 mu due to the double
bond.
*) If ethanol was used as the desulfurization solvent,lower yields of IV and higher recovery of III were ob¬
served.
**) The nickel sulfide is so finely divided that if filtered
directly it either goes through the filter or stops it up.
***) If a capillary open to the air was used, considerable
oxidation occured.
- 113 -
d.l-lO-HYDROXYMETHYL-^-^^-OCTALIN (V).
9.2 g. (0.044 mole) of IV in 40 ml. of sodium-dried
ether were added dropwise to a solution of 2.3 g. of
lithium aluminum hydride in 100 ml. of dry ether. After the
exothermic reaction had subsided, the solution was refluxed
for 4 hours. The excess hydride was destroyed by the slow
addition of ethyl acetate, and the reaction mixture acidified
with dilute sulfuric acid and extracted twice more with ether
as usual. The extracts were dried and evaporated to give
7.3 g- (100$ yield) of an off-white crystalline mass melting
at about 35 • The product was distilled in an inert atmos-
*)phere without a column in an apparatus for the distillation
of solids, b.p. 124-126 /10 mm., with almost no forerun and
only traces of residue. However, care was necessary to pre¬
vent sublimation of the distillate. The resulting snow-
o **)white product, m.p. 62-64.5 , was recrystallized three
times from pentane (15 ml./g.) at -10° to constant melting
point, 69.5-70 . It gave a strong yellow color with tetra-
nitromethane and showed only an end absorption in its U.V.
spectrum.
Analysis M30474: Calcd. for C,,H,fi0: C, 79-46; H, 10.92$.Pound:
±x xC, 78.88; H, 11.01$.
I.R. 6744, 6662: A broad strong band at 3290 cm" in Nujol
characteristic of polymeric hydroxyl association or a
weak band at 3620 cm- in carbon disulfide characteristic
of a free hydroxyl, plus 1036 cm" (allyl alcohol?). As
in IV, trisubstituted olefin at 817 cm", but none in
the region 690-750 cm .
*) This compound, like its precursor IV, is sensitive to air
oxidation at the double bond. It should be stored at -10
in the dark under R2« Sublimation at 65°/9 mm. yields an
oxygen-rich product unless carried out under Ng-
**) losses in recrystallization are high.
- 114 -
The pale yellow 3»5-dinitrobenzoate was prepared, and
the very soluble product recrystallized from both methanol
and pentane at -5° to constant melting point, 102-103.5 .
Analysis M31062: Calcd. for C,oH;:)n0,N„: C, 59-99; H, 5.59$.Found:
dU D d
C, 59.91; H, 5.46$.
d,l-TRICYCL0(4:4;l:0)UNDECENE-2 (VI).
8.3 g. (0.05 mole) of V were dissolved in 25 ml. of
dry pyridine, and 17.7 g. (0.10 mole) of benzenesulfonyl
chloride were added. The solution was cooled as necessary in
ice during the first hour to keep the temperature at 15-20
during which time pyridine hydrochloride slowly separated.
After leaving in the ice chest overnight, the pink reaction
mixture was poured onto 50 g. of ice. After standing for 15
minutes, water was added and the ester extracted twice with
ether. The extracts were washed with water, dried, and con¬
centrated. The last 100 ml. of ether were removed at the
*)aspirator without heating. A quantitative yield of a pale
brown hexane-insoluble oily benzenesulfonate was obtained.
This was dissolved in 250 ml. of dry pyridine and refluxed
overnight in the dark under nitrogen.' The light brown
solution was cooled under nitrogen and poured into a mixture
of 500 ml. of pentane, 300 ml. of cone, hydrochloric acid and
700 g. of cracked ice. The pentane layer was separated and
the water solution extracted a second time with 500 ml. of pen¬
tane. The extracts were washed with dilute hydrochloric acid
and sodium hydroxide, dried, and the pentane removed through
a Vigreux column. The residual oil was washed through 250 g.
of alkaline alumina (activity I) with one liter of pentane,
*) The benzenesulfonate turned brown rapidly upon heating on
the water bath, and slowly after several days in the ice
chest.
**) The tosylate was similarly unstable and semi-crystalline.***) The pyridine rapidly turned deep brown upon refluxing in
the air in a normally lighted room.
- 115 -
and the pentane removed through a Vigreux column. The re¬
sulting oil was distilled at the aspirator to yield 3-1 g.
(42$ yield) of colorless VI, b.p. 80-88°/H mm.» with
almost no forerun or residue. A center cut was redistilled
for analysis, b.p. 81-82 /10 mm.
Analysis M30895: Calcd. for C,,H..,: G, 89.12; H, 10.88$Found:
xx ±0C, 89.17; H, 10.70$
VI had a negative Beilstein reaction, gave a deep
orange-red color with tetranitromethane as
expected,' ' and was extremely sensitive to air. A
droplet left on a watch glass hardened within one hour to a
puckered resinous mass.
U.V. (cyclohexane): ),.
212 mu (log e=3.82)**^ for the
vinylcyclopropane; >__
253 mu (log £=2.7-3.5 depending
on the preparation) for bicyclo(5:4:0)undecadiene-
8,10 (?).
I.R. 6881, 6936, 7014, 7716, 7717, 7731: Vmov 3058, 2990,
-1
, max
1013 and 874(?) cm" (cyclopropyl ring), plus olefin
bands at 3024, 1666, 1641, 1600, 1496(overtone 743 cm"
(?), 829, 743(very strong),** ' and 690(w) cm" . The
bands at 1600 and 829 cm" (triply substituted olefin)
were strongest in those preparations which had a high
extinction coefficient in the ultraviolet at 253 mu.
Gas chromatogram: pV($)-apolar column pV($)-polar column
VI 0.501 (50$) 0.695 (58$)Bicycloundecadiene (?) 0.568 (31$) 0.772 (26$)
0.702 (10$) 0.849 ( 8$)0.622 ( 5$) 1.172 ( 8$)0.734 ( 2$)0.656 ( 1$)
*) Vinylcyclopropanes have been reported subject to air
oxidation to hydroperoxides.161'1'") VI may, however,be safely stored at -10° in the dark in a sealed nitro¬
gen filled ampule containing a trace of hydroquinone.
**) log e=4.1 when corrected to 100$ purity.
***) This band is also observed in 13,27-cyclo-& -3B,28-
diacetoxyursene, but disappears upon reduction.117,118)
- 116 -
TRICYCL0(4;4:1:0)UNDBCANE (VII).
*)2.4 g. of VI were dissolved in 30 ml. of methanol
and reduced with hydrogen at 20 and one atmosphere using
50 mg. of platinum oxide. The solution rapidly absorbed
hydrogen for 5 hours and came to a complete standstill after
8 hours with the absorption of 0.99 mole per cent of hydro¬
gen. The solution was filtered, diluted with water, and ex¬
tracted as usual with pentane. The extracts were dried and
the pentane removed through a short column. The resulting
colorless oil was distilled twice for analysis, b.p.
76-88°/lO mm.
Analysis M30899: Calcd. for C^H,.: C, 87.92; H, 12.08$Found:
^ 10
C, 87.94; H, 12.18$
The stable product showed a strong yellow color with
tetranitromethane, gave a black precipitate with osmium
tetroxide in ether, and had a high end absorption in its
U.V. spectrum, log e=3-H at 216 mu.
I.R. 6999, 7013, 7706, 7714, 7717, 7723:^max 3051, 2990. 1013
and 88l(?) cm- (cyclopropyl ring); a very weak band at
1378 cm", but none at 2962-2972 cm" representing pos¬
sible traces of methyl group; 1496(overtone ?) and
743(s) cm- (triply substituted olefin?). The other
bands indicative of a double bond had disappeared,'
and the fingerprint region was considerably altered.
Gas chromatogram: pV($)-apolar column pV($)-polar column
VII 0.481(52$) 0.602(52$)Bicycloundecene-10(?) 0.745(28$) 0.833(37$)
0.564(13$) 0.748( 6$)0.676( 7$) 0.718( 5$)0.782( 1$)
*) More than the minimum amount of methanol necessary for
solution of VI must be used to allow for the water
produced in the reduction of the catalyst.
**) Unfortunately, not enough material was available to
record the Raman spectrum, which unlike the I.R. spec¬
trum, would possess bands for the fully substituted doublebond.
- 117 -
VII was purified by adding 1.66 g. to a solution of lg.
of osmium tetroxide in 10 ml. of dry ether, sealing, and al¬
lowing to stand overnight at 20 in the dark. The ether and
excess osmium tetroxide were removed at the water pump with¬
out heating, and the black residue washed several times with
pentane. The pentane solution was washed through 17 g of al¬
kaline alumina (activity I) with 200 ml. of pentane. The
pentane was removed through a short column leaving 1.15 g of
colorless VII which still showed a faint positive test with
osmium tetroxide; it was, therefore, similarly treated a se¬
cond time with 200 mg. of osmium tetroxide to yield 1.09 g»
(66$ recovery) which no longer reactod with osmium tetroxide.
This was fractionally distilled through a short column to
yield 571 mg. of pure VII, b.p. 76-77°/l0mm., d^4 0.911,
n4 1.4876, MR- 47.5 (calcd. 47.2*'). It gave a pale yellow
color with tetranitromethane, and the boiling point corrected
to 760 mm. was 211 by the micro Siwoloboff method. 358 mg.
of a fraction distilling smoothly between 77-85 /10 mm. was
**)also collected.
Analysis M32205: Calcd for C, H,R: C, 87.92; H, 12.08$.Pound.
L1 xoC, 87.73; H, 12.18$.
I.E. 7721, 7722: Differed from that of unpurified VII mainly
in that the bands at 1496 and 743 cm- were absent.
U.V. (cyclohexane): )v
216 mu (log e=1.40) and 237 mu
(log e=l.lO).
Gas chromatogram: pV($)-apolar column ' pV($)-polar column
180° 0.475(48$) 0.608(93$)0.511(52$) 0.835( 7$)
150° 0.475(55$)0.511(45$)
*) 9x4.647(CH2) + 2x2.591(C) + 0.45 (cyclopropane ring)- 2x0.15(cyclohexane ring).!"'?) The dispersion was
almost identical to that of hexane.
**) This may be a mixture of VII and 10-methyldecalins.***) This band splitting obviously results from decomposition
of VII on the column, with the second band representingan accumulation of the decomposition product. (Cont.p.118)
- 118 -
SPIBO(4:5)SECANONS-6 (X).
Bicyclopentyl-l,l'-diol was prepared by a pinacol re¬
duction of cyclopentanone with aluminum amalgam according to
251)the procedure of Zelinski and Elagina, and crystallized
from petroleum ether, m.p. 107-108° (reported 108-109°).
53.1 g. of diol were refluxed for 2 hours with 4-00 ml.
of 20$ sulfuric acid. The oily layer that separated was
steam distilled, and the distillate extracted with ether.
The extract was distilled at the aspirator to yield 38-5 g.
of a greenish-yellow oil with a peppermint-like odor, b.p.
84--91°/9mm. Its analysis M3264-3, I.E. spectrum No. 7901 and
U.V. spectrum show that the product contains about 20$ of
1 l'A' -bicyclopentene (XI). The I.R. spectrum showed a strong
carbonyl absorption at 1703 cm" (reported 1701 cm" ), ' '
plus a weak band at 1593 cm- for the conjugated diene im¬
purity and a shoulder at about 3010 cm" for a vinylic
hydrogen. X and XI were not separated until the next step
The semicarbazone was prepared and recrystallized
from aqueous ethanol and methanol-hexane to constant melting
point, 187.5-189.5° (reported 189-190°).251^Analysis K32897: Calcd. for C H ON : C, 63.12; H, 9.15$
Found:iy i
C, 63.14} H, 9-14$
Alkylated cyclopropanes are known to undergo facile
isomerization at higher temperatures. At lower tem¬
peratures less isomerization was observed to occur
in spite of the fact that the contact time in the
column was considerably greater. Additional evidence
eliminating the possibility that the second band is
an impurity in pure VII is obtained from the fact that
this "impurity" is present in neither crude VII nor
in the isomerized VIII, as well as the fact that the
product recovered from the chromatogram gave a very
strong reaction with osmium tetroxide in ether. In ad¬
dition, the second band formed a tail as would be ex¬
pected. The complexity of the chromatogram of crude VII
prevented a similar observation of decomposition. Signif¬icantly, however, the pV value of crude VII (O.48I) lies
between that of jure VII and its decomposition product.
- 119 -
d,l 6-METHYLSPIRO(4:5)DBCANOL-6 (XII).
5 g. of impure X in 10 ml. of dry ether were slowly
added to a solution of methyl magnesium iodide prepared from
10 g. of methyl iodide, 2.0 g. of magnesium and 20 ml. of dry
ether. The solution was then refluxed gently for 30 minutes
and the Grignard decomposed with water, acidified, and extrac¬
ted with ether as usual. The extract in pentane was absorbed
on 150 g. of alkaline alumina (activity I) and eluted first
with 750 ml. of pentane to separate XI, and then with 750 ml.
of wet ether. The brownish camphor-smelling oil eluted with
ether (4.4 g.) was distilled with no forerun and very little
residue at 102-105°/9 nun. to yield 4.1 g. of a pale yellow
oil, which was redistilled for analysis, n- 1.496.
Analysis M32683: Calcd. for C..,H9n0: C, 78.51; H, 11.98$.Pound:
±x ^C, 78.25; H, 11.88$.
I.R. 7931: Broad and deep bands at 3440 and 1110 cm-1
(hydroxyl); 1380 cm"1 (methyl).
The product was extremely soluble in pentane and could not be
crystallized from this solvent at -10°. A deep yellow color
was produced with tetranitromethane. There was no absorption
in the ultraviolet.
A'1 -BICYCLOPBNTENE (XI)
The colorless aromatic-smelling pentane eluate from
above (1.0 g.) represents XI present in the original impure
spiro(4:5)decanone-6 (X). XI distilled smoothly and quanti¬
tatively between 75-85 /9 mm. Redistilled for analysis,
b.p. 79 /9 mm., n~ 1.520, reddish-brown with tetranitrome-
thane.
Analysis K32669: Calcd. for C,nH,.: C, 89.49; H, 10.51$.Pound:
^ ^C, 89.29; H, 10.73$.
U.V.:^ 240 mu (log 6=4.32) plus a shoulder at 234 mu as is
characteristic of this type of diene.
I.R. 7930: -J^
3030 cm-1 (vinylic CH); 1591 cm"1 (conjugated
diene); 785 cm" (triply substituted olefin).
- 120 -
d,l 10-METHYL-/^(9^-0CTALIN (VIII).
A. From 6-methylspiro(4:5)decanol-6 (XII). 725 mg. of XII
were dissolved in 5 ml. of acetic acid, and 2 ml. of boron
trifluoride etherate were added. The solution immediately
turned red and after a few moments an oil started to sepa¬
rate. After two hours at room temperature, the mixture was
poured into water and extracted with pentane. The extract
was washed with sodium hydroxide and water, dried and con¬
centrated. The resulting pale yellow oil was absorbed on
70 g. of alkaline alumina (activity I) and eluted with 4-00 ml.
of pentane to yield 615 mg. (95$) of a colorless oil which
distilled sharply at 75°/9 mm. This was redistilled twice for
analysis, d^3 0.905, n£3 1.4951, MR^3 48.4 (calcd. 48.2*)).It gave a canary yellow color with tetranitromethane.
Analysis M32816: Calcd. for C,,H,R: C, 87.92; H, 12.08%Found:
±x ±0C, 87.97; H, 12.12$.
U.V.: Only an end absorption, log e=2.5 at 218 mu.
I.R. 7955, 7956: ^ 3025(m) cm'} (vinylic CH stretching);"^
2967(s) cin"£ (CHo stretching);1662(m) cm--, (C=C stretching);1378(s) cuff (CH-j deformation);807(s) cm (trisubstituted olefin).
Gas chromatogram: Only a single peak, pV=0.635 on the polar
column.
B. From Tricyclo(4:4:l:0)undecane (VII). 814 mg. of VII,
8.2 ml. of acetic acid and 1.3 ml. of boron trifluoride
etherate were heated on a water bath 4 hours under a nitro-
gen atmosphere.' The mixture was poured into water and
extracted with pentane. The extract was washed with sodium
*) 5.653(CH3) + 7x4.647(CH2) + 1.028(H) + 3x2.591(0) +
1.575(olefin)- 2x0.15O(cyclohexane ring).16')
**) Allowing the reaction to run overnight at room tempera¬ture produced incomplete isomerization, as shown by the
persistence of the cyclopropyl bands in the I.R. spectra,
Nos. 7718 and 7719-
- 121 -
hydroxide and water, dried, concentrated, and absorbed onto
25 g. of alkaline alumina (activity I). VIII was eluted with
200 ml. of pentane and distilled twice for analysis, b.p.
76-77°/l0 mm., n^ 1.4926, strongly yellow with tetranitro-
methane.
Analysis M32407: Calcd. for C,,ILR: C, 87.92; H, 12.08$.Pound: C, 87.67; H, 12.28$.
U.V.: Only an end absorption, log e=2.8 at 217 mu.
I.H. 7751, 7752 and 8035: v„ 3021(m), 2964(s), 1662(m),
1378(s) and 807(s)cm . The spectrum is essentially
identical to that prepared in A.
Gas chromatogram: pV($)-apolar column pV($)-polar column
VIII 0.484(71$) 0.636(70$)0.734(29$) 0.846(28$)
0.736( 2$)
d,l 10-METHYL-^9)-0CTAL0NB-2 (IX).
To 1 g. of VIII prepared from XII were added 10 ml. of253)
acetic acid and 25 ml. of tertiary butyl chromate.'
Cooling was necessary and a brownish precipitate started to
settle out. The mixture was left overnight at 20, and then
poured into water containing 7 g. of sodium bisulfite. IX
was extracted with ether, and the extract washed with sodium
hydroxide and water, dried, and concentrated. The resulting
oil distilled sharply at about 98°/0.1 mm. to give 500 mg. of
a colorless liquid with an U.V. maximum at 240 mu (log e=4.12)i
The semicarbazone was prepared as usual and crystallized for
analysis from aqueous ethanol and methanol-benzene to
constant melting point, 202-203 , I.R. spectrum No. 8009.
Analysis M32922: Calcd. for C,9H, ON,: C, 65.12; H, 8.65$.Found:
x xy iC, 65.05; H, 8.64$.
VIII, prepared from VII, was similarly oxidized.
Upon distillation, a lower boiling forerun was observed and
- 122 -
the U.V. spectrum of the main portion of the distillate had
a maximum at 240 mu (log £=3.74). This is consistent with
contamination of VII with saturated 10-methyldecalin which
would not have been oxidized. The semicarbazone was prepared
and crystallized for analysis to constant melting point,
198-198.5°, I.R. spectrum No. 8055-
Analysis No. M32946: Calcd. for C,pH,q0N,: C, 65.12; H, 8.65$.Found:
x y *C, 65.08; H, 8.665b.
In addition, the semicarbazone was prepared from a
*)known sample of IX and crystallized to constant melting
point for analysis, m.p. 202-203.5° (reported 203-205°),I.R. spectrum No. 7995.
Analysis No. M32842: Found: C, 65.05; H, 8.53?°.
None of the semicarbazones depressed the melting
point of one another, and the infrared spectra of all three
were absolutely identical.
*) Prepared by W. Kung, E.T.H.
CHAPTER V
HOMOALLYIIC SOLVOLYSIS IN THE OLEANOLIC ACID SERIES
3B,28-Dihydroxy-^3(l8^-oleanene, II in Pig. XXXI, is
another homoallylic system whose benzenesulfonate was solv-
olyzed in order to verify the generality of this type of re¬
action. The expected vinylcyclopropane is indeed produced,
although the rate of solvolysis is only of the same order of
magnitude as the model hydroxymethyloctalin (see page 46).
Correspondingly, the resulting vinylcyclopropane system is
not highly conjugated, absorbing in the ultraviolet at only
/^max 21^~21^ mx (l°g £=3.6-4.1) in spite of the exocyclic
position of the double bond and the extra alkyl substituent
(see page 76). Of interest is that the wavelength and ex¬
tinction coefficient of the maximum appear to be proportion¬
al to the polarity of the substituent at C3. Surprisingly,12
the ^ double bond of the vinylcyclopropane system is
easily reduced with hydrogen over platinum in acetic-dioxane
with the disappearance of the above absorption. In addition
some conjugate 1-4 reduction to the corresponding A -
oleanene appears to have taken place. All of the hexacyclic
products had bands in the infrared for the cyclopropyl ring
at 1025-1030 cm-1 (strong) and 3049-3058 cm-1 (weak). The
other cyclopropyl methylene stretching band (see Appendix I)
could not be cleanly resolved, although there were indicati¬
ons of a shoulder at about 3010 cm".
The reactions, as summarized in Pig. XXXI, started from
12methyl 32-acetoxy-A -28-oleanenate, I, which was first oxi¬
dized to 3B-acetoxy-&' -28-oleadienate with selenium
p C (L \
dioxide, and then reduced with hydrogen over platinum in
acetic acid-dioxane to methyl 3B-acetoxy-A" -oleanene,
which with lithium aluminum hydride yielded II. Treatment with
either mesyl chloride or benzenesulfonyl chloride in pyridine
overnight at 20° produced the very unstable disulfonate.
- 124 -
COOCH,l)SeO,2)H«/Pt/HOAc
^
3)IdAlH„
1) PhSO,Cl/Pyridine2) Reflux Pyridine
ch2or'
II, R=R' =H
'III, R=R* =SO„Ph
'IV, R=R' =Ac,V, R=Ac, R =H
VI, R=Ac, R' =S02CH,
XI, R=AcO
XII, P.=H
Figure XXXI:
HOMOALLYLIC SOLVOIYSIS TO 18,28-CYCLO-OLEANANE DERIVATIVES
- 125 -
The dibenzenesulfonate, III, was solvolyzed by reflux¬
ing for a half-hour with pyridine to produce an 89$ yield of
the difficult-to-purify hexacyclic monobenzenesulfonate, VII.
Refluxing the solution of II and benzenesulfonyl chloride in
pyridine led to a less pure product. VII was then reduced
with lithium aluminum hydride to produce a mixture of 18,28-
cyclo-fi" -oleanene (X) and 18,28-cyclo-fi" -oleanenol-3 (VIII)*)
which were easily separated by chromatography.'
However,
both fractions were impure and losses on recrystallization
were high. Solvolysis of the dimesylate would probably give
a more stable monomesylate which could be better purified,
and would probably also give cleaner products in the hydride
reduction, although with a lower X:VIII ratio. VIII and X
both gave a pale reddish-brown color with tetranitromethane.
VIII was further characterized by conversion to its acetate,
IX, which gave a similar color reaction, and had a good anal¬
ysis in contrast to VIII.
Although this route is probably the best to the hydro¬
carbon, a more convenient route to the hexacyclic acetate,**)
oIX, ' involves forming the diacetate, IV, m. p. 195-6 (re¬
ported 194—5°), which by partial saponification and
chromatography was converted into its 3-monoacetate, V: anal¬
ysis M34-306 correct for CkgH^O ; m.p. 233-4°; I.R. No. 8782,
i 3680 cm-1 (hydroxyl) and 1728 cm"1 (ester); Ex]_ -32.5°
(c=0.85). V was converted by mesyl chloride and pyridine in¬
to the corresponding mesylate, VI, which was quite unstable
and decomposed rapidly when heated at 100°. Solvolysis by
refluxing in pyridine for a half-hour yielded IX in good
yield and high purity.
*) This dual path of reduction of sulfonates by lithium
aluminum hydride has been often reported. References 79,
86, 89, 117, 118, 122, 196, 268.
**) This series of reactions was carried out by Mr. A. Melera
and Mr. Ursprung, E.T.H.
EXPERIMENTAl*
33.,28-DIHYDRCXY-A3(18}-OLjSAKiiNfi (Hi
1235 g. of methyl 35-acetoxy-A -28-oleanenate (I) and
17 g. of selenium dioxide were refluxed 3 hours in 2 liters
of glacial acetic acid. The selenium was filtered off and
the acetic acid removed at the aspirator. Water was added
and the mixture extracted with ether as usual. The extract
was washed with sodium hydroxide, dried and the ether re¬
moved. The reddish residue was absorbed onto 35o g. of
neutral alumina (activity II) from petroleum ether. The
same solvent eluted tricontane present as an impurity in I;11 13 f18)
benzene eluted fairly pure methyl 3^-acetoxy-A' JK
-28-
oleadienste as the desired product; methanol eluted the by¬
product, methyl 3S-acetoxy-12,19-dilceto-A11'15^18)-28-oleadienate. The benzene fraction was recrystallized twice
from methanol to yield 20 g. of colorless product, m.p.
223.5-225° (reported 225°).2 Traces of tricontane could
be removed by recrystallization from a little hexane, al¬
though losses in the mother liquor are high. The product
gave an orange color with tetranitromethane, and in the
ultraviolet absorbed at A 243 mu (log e=4.41), 251 murn.QX
(log £=4.47) and 26o mu (log £=4.28).
The methyl acetoxyoleadienate from above was reduced by
dissolving 8 g. in 1 liter of glacial acetic acid-dioxane 2:1
and reducing with 500 mg. of platinum oxide and hydrogen at
one atmosphere and 20 until no more hydrogen was absorbed.
The platinum was filtered off, and the almost saturated so¬
lution crystallized by heating to boiling and adding water
until crystallization began. An plmost quantitative yield of
#) See general experimental conditions, footnote p. 108.
Optical rotations were taken in chloroform solution in
a polarimeter tube 1 dm. long.
- 127 -
methyl 3B-acetoxy-^* -28-oleanenate was obtained, m.p.
238-240.5° (reported 241-2420),267) which gave a yellow color
with tetranitromethane and had only an end absorption at
220 mu in the ultraviolet.
The methyl acetoxyoleanenate was reduced by dissolving
8 g. in 800 ml. of dry ether and adding dropwise to 4 g. of
lithium aluminum hydride in 500 ml. of dry ether. After the
addition the reaction mixture was refluxed for 4 hours and
the excess hydride then destroyed with ethyl acetate. After
acidifying with dilute sulfuric acid, the difficultly soluble
diol was extracted with 2 liters of chloroform and worked up
as usual. Recrystallization once from benzene yielded 5.2 g.
(73$) of pure II, pale yellow color with tetranitromethane,
m.p. 271-271.5° (reported 269°)2*2' not raised by recrystal¬
lization. A sample was rapidly sublimed at 200 /0.01 mm.
for analysis.
Analysis K32890: Calcd. for C,nH n0„: C, 81.39; H, 11.38$.Pound:
->u ?u *C, 80.95; H, 11.28$.
I.E. No. 7991: v„
3300 cm"1. No bands 1500-2500 cm-1,max
[<x]21= -51° (c=0.73) [reported -45° (c=0.60)] .242^
3fl,28-DIHYDROXY-^3(lS^-0LEANENE DIBENZENESULFONATE (III).
To 2.6 g. of II dissolved in 75 ml. of pyridine were
slowly added with stirring and cooling 15 ml. of benzenesul-
fonyl chloride. After standing overnight at 20°, water was
slowly added to the reddish solution with cooling, then ex¬
tracted as usual with methylene-chloride/ether, and the
solvents removed at the aspirator without warming to yield
2.9 g. (89$) of III as a white amorphous powder, yellow
with tetranitromethane. Ill was very unstable and when pure
showed a decomposition point of 85-88 . The decomposition
was autocatalytic, and although III might be kept for a day
or two without change, decomposition, once started, was
quite rapid (several hours). Ill was precipitated several
- 128 -
times from methylene chloride by pentane for analysis.
Analysis M33045: Calcd. for C.?H ft0,S„: C, 69.77; H, 8.09#.Found:
*°° ° ^C, 70.31; H, 8.85/2.
I.E. No. 8156: ) 1183, 1198, 1373 and 1386 cm-1 (sul-max
fonate). No carbonyl or hydroxyl bands.
U.V.: 1„.
251 mu (log £ = 3-98), 24-1 mu (log e=3-95) plus an
end absorption, log £=4.51 at 220 mu.
l8>28-0YCL0-A12-0LEAN-3-YL BENZENESULFONATE (VII).
The extract of III, after removal of the solvent, was
dissolved directly in 30 ml. of pyridine per gram and re-
fluxed for 30 minutes. Dilution with water and extraction
as usual with ether led to an 8955 yield of an off-white
crystalline mass with a negative Beilstein reaction. Al¬
though this did not start to decompose until 140 , recrys-
tallization led to high losses with only oils recoverable
from the mother liquor. VII was recrystallized thrice from
methylene chloride-hexane for analysis; m.p. 109-110 , pale
reddish-brown color with tetranitromethane.
Analysis M33093: Calcd. for C,,-H „0 S: C, 76.55; H, 9.28$.Found:
•3° ? •>C, 76.34; H, 9-16$.
I.R. 8234,8435,8436: >)„.
1175, 1187, 1350 and 1376 cm"1
(sulfonate), plus a medium band at 3058 cm- (combined
aromatic, cyclopropyl and vinylic C-H). No bands were
present in the region 1500-2700 cm" .
U.V. No. 0127 (ethanol): ^ 217.5 mu (log e=4.09)max
264 mu (log e=2.95)295 mu (log e=2.16).
18,28-CYCI.O-lP-OLEANENE (X) and l8,28-CYCLO-^2-OLEANENOL-3
mm-
500 mg. of the unpurified extract of VII were dissolved
in 10 ml. of dry ether and added slowly to 300 mg. of lithium
aluminum hydride in 50 ml. of ether. After the addition, the
solution was refluxed for 4 hours, the excess hydride des-
- 129 -
troyed with ethyl acetate, and the reaction mixture worked up
by acidifying and extracting as usual with ether. The ether
was washed thoroughly with 10$ sodium hydroxide to remove
phenyl mercaptan, dried, and evaporated to yield 380 mg. of
product which was chromatographed directly on 12 g. of
neutral alumina, activity II. Petroleum ether-benzene 10:1
eluted crude X which was partly-crystalline and had a strong
sulfur odor. Benzene and ether eluted crystalline VIII. Al¬
though the combined yield of VIII and X was better than 90$,
both fractions were quite impure, and the ratio of the two
fractions varied considerably in different preparations from
4:1 to 1:3* The reason for this variation is unknown. Both
gave a pale reddish-brown color with tetranitromethane.
Crude X was recrystallized from benzene-methanol to
constant melting point for analysis, m.p. 188.5-190.5 .
Analysis M33276: Calcd. for C,nH R: C, 88.16; H, 11.84$.Pound:
iU 4°C, 87.99; H, 11.65$.
I.R. 8441, 8442: ^mov 3049, 3010 and 1030 cm-1 (cyclopropyl),
and I658 cm~ (olefin). The vinylic C-H stretching band
could not be resolved.
U.V. Ho. 0123 (ethanol): X 216 mu (log s not measured).
No end absorption at 204 mu.
Crude VIII was recrystallized from hexane and methanol
to constant melting point, and finally from hexane for anal¬
ysis, m.p. 244.5-247.5 • It could not be sublimed due to
concurrent decomposition.
Analysis M33264: Calcd. for C,nH ft0: C, 84.80; H, 11.39$.Pound:
-*u 4°C, 82,92; H, 11.76$.
I.R. 8443, 8444, 8520: -0 3600(w) cm-1 in CC1. or-« 3H3.X *r
3300 cm- (broad and strong) in KBr for the hydroxyl;
1029 cm-1 (cyclopropyl); I64O and 804 cm"1 (olefin).
U.V. No. 0126 (ethanol): \ 217 mu (log e=3.82). No end'max
absorption at 204 mu.
- 130 -
3B-ACBTOXY-18,28-CYCL0-A12-0LEANENE (IX).
A. VIII was acetylated with acetic anhydride-pyridine as
usual and crystallized from benzene-methanol and from hexane
to constant melting point for analysis, m.p. 251.5-252 ,
light reddish-brown color with tetranitromethane.
Analysis M33294: Calcd. for C,„H n0p: C, 82.34; H, 10.80$.Pound:
^ 5U ^C, 82.32; H, 10.87$.
I.R. 8439, 8440, 8523: ^ 1733, 1247 cm"1 (acetate);
3056(w), 1027(b) cni* (cyclopropyl); 1653(w), 808(s)cm_1
(olefin). The vinylic C-H stretching band could not be
resolved.
U.V. No. 0125 (ethanol): Xmax 211 u (log £=3.64). No end ab¬
sorption at 204 mu.
Hj10 +24° (c=1.4).
*)
B. VIII was also prepared by solvolysis of VI. ' M.P.
246-247 , undepressed on admisture with VIII prepared above.
Analysis M33968: Calcd. for C ,H,n0,: C, 82.34; H, 10.80$.Found:
^ 5U *
C, 81.89; H, 11.10$.
[a]D +22° (c=0.85).
3B-A0ET0XY-18,28-CYCL0-0LEANANE (XI).
262 mg. of pure IX were dissolved in 60 ml. of glacial
acetic acid-dioxane 1:3, and reduced with hydrogen and 50 mg.
of platinum oxide at 20 and one atmosphere. The hydrogen
uptake came to a standstill after the absorption of 1.2 moles
of hydrogen. The platinum was filtered off and the solvent
removed at the aspirator from the almost saturated solution
of XI. The residue was recrystallized several times from
benzene-methanol and from hexane for analysis, m.p. 249.5-
250.5 , sharply depressed on admixture with IX. It gave a
yellow color with tetranitromethane. Although the IX used
was pure, the mother liquors from the recrystallizations of
*) Prepared by Mr. A. Melera and Mr. Ursprung.
- 131 -
XI were observed to contain mixed crystal types.
Analysis M33428: Calcd. for C,?H,.p09: C, 81.99; H, 11.18£.Pound:
* ?C, 81.55; H, 11.08?;.
I.R. 8437, 8438, 8522: 0 1733, 1247 cm-1 (acetate);
3058(w), 1025(s) cm~ (cyclopropyl). No bands are
present in the 1600-1700 or 660-850 cm- regions.
U.V. No. 0128 (ethanol): A 207.5 mu (log e=2.91) for a
ZSL3(18) olefin (?).
[a]J9 +22° (e=1.08).
18,28-CYOIO-OLEANANE (XII).
265 mg. of pure X were dissolved in 15 ml. of glacial
acetic acid plus 60 ml. of dioxane and reduced to a stand¬
still with 50 mg. of prereduced platinum oxide at 20 and
one atmosphere. The platinum was filtered off from the
almost saturated solution and the solvents removed at the
aspirator. XII was recrystallized to constant melting point
from benzene-methanol and from ethyl acetate, m. p. 197-199 ,
sharply depressed on admixture with X. It gave a pale lemon
yellow color with tetranitromethane. Although the X used
was very pure, the mother liquors from the recrystallizations
of XII seemed to contain mixed crystal types.
Analysis M33504: Calcd. for C,nH : C, 87.73; H, 12.27$.Pound:
JU 5UC, 87.81; H, 12.17?*.
I.R. 8449, 8450, 8459, 8521: 0„
3058(w), 3010 (shoulder),
1025(s) cm- (cyclopropyl). No olefin bands are
present.
U.V. No. 0124 (ethanol): Xmav 207 mu (log e=3.13) for a
^3(18) olefin (?).
[a]l3° +13° (e=1.16).
vmax
APPENDIX I
CYCLOPROPANE BANDS IN THE INFRARED
The infrared and Raman spectra of cyclopropane have
been thoroughly investigated.»•*»*'
From this, and espe¬
cially from a study of cyclopropyl ring-containing compounds,
a number of bands have been assigned to the cyclopropyl ring.
Universally accepted is a strong band at 1000-1030 cm" due
to unsymmetrical ring deformation. ' This band has been
found in the spectra of almost every cyclopropyl compound
yet investigated, although a few special cases may exceed
these limits. However, it has been pointed out that cyclo¬
propyl rings with a substituent on each carbon atom may not
show this band,'
perhaps due to symmetry. In addition,
the strong absorption of hydroxyl and ester groups in this
region may interfere with the assignment.
Many have also claimed a band at 865-900 cm- for the
cyclopropyl ring, but this band, if it belongs to the
cyclopropyl group at all, has been shown to be of little
value.212'2^2^)In addition there have also been found two bands in
the C-H stretching region for a methylene group in a cyclo¬
propyl ring. Although these bands can often be seen as a
shoulder in a normal double-beam spectrum with a sodium-
chloride prism, the use of a single-beam spectrometer with a
lithium fluoride prism is required for adequate resolution.
The weaker of these two bands has been noticed more often
since it occurs at a shorter wavelength, and is thus more
separated from the usual C-H stretching frequencies. It has
*) References 6, 30, 4-2, 4-5, 117, 118, 157, 199, 210, 212,213, 214, 224, 24-8, 24-9, 259, 260 and 263-
**) References 6, 30, 4-2, 45, 210, 212, 214-, 224 and 263-
- 133 -
been reported to occur in the range 3030-3110 cm", with
+ -1 *)**)
3050 - 10 cm usual. ' In carane, which has no methylene
on the cyclopropyl ring, this band is absent. The
stronger frequency is not as easily resolved and often
masked by other C-H bands, especially the asymmetrical
stretching mode of the methyl group. It has been reported,
or is shown on published spectra, in the range 2950-
3035 cm".
' ' The separation between the two bands is
reported to vary from 60-119 cm". Tricyclo(4:4:l:0)undecane
is an especially interesting case in that there are only two
different kinds of methylene groups present.
Theoretically there should also be bands in the C-H
261 ^
bending region unique to the cyclopropyl methylene group.'
It has been reported that the degree of complexity in this
region increases when a cyclopropyl group is present, and
that it may have a triplet band at 1420-1460 cm"1.213'264'
However, there is not yet enough data to confirm this,
especially as in most spectra the resolution is insufficient
to separate the different C-H bending bands.
*) References 6, 14, 17, 23, 30, 40, 42, 45, 88, 200,
210, 213, 214, 224, 259, 262, 264 and 265.
**) 13,27-Cyclo-3fi,28jdiacetoxyursane"' ' has a shoulder
at about 2990 cm" plus a weak peak at 3056 cm"1, I.R.
Nos. 8445-6.
***) References 6, 23, 30, 42, 45, 157, 210, 213, 214, 259
and 262.
APPENDIX II
The discussion below follows a paper presented by
Normant in which he points out the undeniable conjugative
ability of cyclopropyl rings. This discussion is of interest
not only for the personalities involved, but also as an il¬
lustration of the basically different approaches to the be¬
havior of the cyclopropyl system. Dr. Dewar claims a V-
complex intermediate for the dihydrofuran-cyclopropyl-
carboxaldehyde reversible rearrangement at 375° as well
as for the usual formation of cyclopropyl rings by base
closure. The first reaction is probably an equilibrium via
the ^complex of the s-cis cyclopropylcarboxaldehyde enol,
i.e.,ScHf^0CCHCH2—CKy
Dr. Winstein refutes the second claim. Although
cyclopropyl rings can be formed via TF-complexes, it is only
one of the two possible approaches (see p. 13). Thus, in a
cationic TP-complex, the paired electrons can distribute them¬
selves in more orbitals with resultant stabilization. An
anionic TT-complex, on the other hand, would be severely de¬
stabilized by the odd unpaired electron (compare p. 52).
Dr. Winstein also reports on the lack of rate effect on in¬
ternal displacements forming cyclopropyl rings. The rate
controlling factor is probably the rate of formation of the
anion. Although substituents on the halide carbon atom
would increase the rate of SN ionization and decrease the
2rate of SN displacement, they would have little effect or.
the rate of formation of the anion. On the other hand, the
rate of ring closure of substituted B-haloethylmalonic
esters would probably be highly affected by the substituents
as in this ease the a-methylene, being doubly activated,
- 135 -
would probably form an anion with extreme ease so that
this step would no longer be rate controlling.
Dr. Dewar: "The rearrangement of dihydrofuran into formyl-cyclopropane(IV) can hardly involve zwitterionic intermedi¬
ates; a 7T-complex representation can be given as follows:
"The migrating methylene group rises out of the planeof the molecule and begins to bond itself simultaneously to
the 3- and 4—CH groups; in the transition state it is then
attached to two n"-orbitals, weakening of one/*-bond and
strengthening of the other gives the 7P-complex, which with
suitable electronic adjustment is converted to IV. Similar
multiple processes probably account for the extraordinaryease of formation of 3-membered rings in general: 3-membered
rings are formed much more easily than rings of other size -
even "strainless* 5- and 6-membered rings. Yet the heat of
combustion of cyclopropane is much more (about 17 cals) than
half that of cyclohexane, indicating the strain in the former."
Dr. Winstein: *The use of a 7T-complex by Dewar as an inter¬
mediate for the formation of cyclopropyl cyanide on treatment
of f-chlorobutyronitrile with alkali is ill advised. Ex¬
perience has shown that the best use of bridged structures
(or 7r-cduplexes in Dewar's language) is in connection with
electron-deficient situations. The anion from reaction of
Jf-chlorobutyronitrile with a basic species is certainly not
an electron deficient structure. Formulation of this as a
f^-complex involves complexing between acrylonitrile and
chloromethide anion, not the cation as formulated by Dewar."
Dr. Bartlett: "The discussion as to whether an anionic
transition state can be stabilized by a 77^-complex character
emphasizes what is the greatest difficulty in basing a quali-ficative discussion of mechanisms upon the molecular orbital
notation. This difficulty is the failure of the notation to
distinguish between nucleophilic and electrophi]ic character
at the important points in a reacting system. If this de¬
ficiency could be overcome by some modification of the
notation of molecular orbitals, there would be much less
reason for using the more cumbersome language of resonance in
qualitative discussions.
"Dr. Dewar's suggestion would seem to predict that
three-membered rings should be closed more easily than four-
membered rings by reason of a lower energy of activation.
It is also to be expected that the entropies of activation
will favor the formation of three-membered rings, since a
chain of four atoms can assume many more configurations un¬
suitable for the initiation of ring closure than can a chain
of three atoms. In addition to these considerations of
- 136 -
mechanism, it is also suggested by the limited thermodynamicdata that the increase in deformation of bond angles from
cyclobutane to cyclopropane is not accompanied by as great a
rise in potential energy as might be expected from a com¬
parison of cyclobutane with cyclopentane."
Dr. Winstein: "Professor Bartlett has pointed out the un¬
usually small role of what we may call steric hinderance in
internal substitution giving rise to the 3-ring. There is
much more in the literature, which includes some of our own
publicated [sic] work, pointing to this lesser importance of
steric hinderance in small ring closure than in external
displacements. Further, we have done a certain amount of
work with ring closure by internal displacement with highlysubstituted cases which are very hindered to attack by ex¬
ternal nucleophilic agents, but in which the internal dis¬
placement is not decreased in rate."
- 137 -
SUMMARY
It has been shown that the production of vinylcyclo-
propanes by homoallylic ring closure of 10-hydroxymethyl-
£^y'-octalins is a general reaction. Solvolysis of a
sulfonate ester of the model compound above, as well as of
28-hydroxy-A '-oleanenes, proceeds analogously to that
12of a 27-hydroxy-£ -ursene.
A 7*-complex mechanism is postulated and the properties
of this type of intermediate are closely examined, especially
in regard to the accelerated rate of formation and the type
of product produced.
The conjugate properties of the resultant vinylcyclo-
propanes are correlated with those predicted from a compre¬
hensive examination of conjugation in cyclopropyl derivatives.
This theoretical study of 7T-complexes and of conju¬
gation with the cyclopropyl ring has led to a number of new
ideas. Research problems have been suggested which would
test these ideas.
- 138 -
ZUSAMMENPASSTJNG
Die in der vorliegenden Promotionsarbeit beschriebenen
Solvolyseversuche zeigen, dass Verbindungen vom Typus des
A^-lO-Hydroxymethyl-octalins (Pig. Xlb, S. 42) zum homoal-
lylischen Ringschluss allgeraein fahig sind. So lieferte das
Benzolsulfonat von Xlb als Hauptprodukt der Solvolyse das
bisher unbekannte (0,1,4,4)-^ -Tricyclo-undecen, dessen Kon-
stitution eindeutig bewiesen werden konnte.
Als Hebenprodukte der erwahnten Solvolyse entstanden
unter Umlagerung des Kohlenstoffgerustes zweifach unges'attig-
te, konjugierte, bicyclische Kohlenwasserstoffe, denen sehr
wahrscheinlich das Ringsystem des (0,4,5)-Bicyclo-undecans
zugrunde liegt.
Der Reinheitsgrad der verschiedenen fliissigen Solvoly-
seprodukte, sowie der synthetisch bereiteten Vergleichsprapa-
rate wurden gas-chromatographisch geprllft.
Es wurde auch eine analoge Solvolyse bei pentacycli-
schen Triteroenverbindungen untersucht. So lieferten das
Diraesylat, das Dibenzolsulfonat und das 3-Acetoxy-2S-benzol-
sulfonat von AL3'18-3(3,28-Dihydroxy-oleanen (Pig. Xlc) in ein-
heitlicher Reaktionsfolge hexacyclische, eine Vinylcyclopro-
pyl-Gruppe enthaltende Verbindungen.
Der Mechanismus dieser Reaktionen, sowie die spektro-
skopischen higenschaften der Vinylcyclopropan-Derivate wurden
eingehend diskutiert. hs resultierten dabei verschiedene
neue Gesichtspunkte ttber die konjugativen Eigenschaften des
Gyolopropans, velche zu weitern experimentellen Untersuchungen
anregen.
- 139 -
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269) Private communication Dr. Schreiber, 2.T.H.
BIOGRAPHICAL
I was born September 3, 1924, in New York. Although
I entered the Massachusetts Institute of Technology in the
fall of 1942, I did not receive my B.Sc. until 1948 due to
the war, when I served two years with the U.S. Navy as an
electronics specialist, mostly in Alaska. I entered the
University of Colorado in order to do my Ph.D., and at this
time was a teaching assistant in the organic and biochemistry
laboratories. After receiving my M.Sc. and completing the
course requirements for the doctorate, majoring in organic
chemistry and minoring in biochemistry and chemical engineer¬
ing, I came to the Swiss Federal Institute of Technology,
School of Chemistry, to do my thesis in the field of the
chemistry of natural products. Due to the different nature
of the requirements here, I did a complete doctorate under
Prof. Ruzicka and Prof. Jeger working on the elemi acids,
oleanolic acid, a-amyrin and several synthetic problems.
Zurich, August 21, 1956 John W. Rowe
