Perepoxide intermediates in the conversion of some p-halohydroperoxides to allylic hydroperoxides by base1a2

KARL R. KOPECKY, WAYNE A. SCOTT, PETER A. LOCKWOOD,' A N D CEDRIC MUMFORD Depnrrt?len/ of Chet?~is/ry, Utlil~ersih of Alberln, Edtnot~ to t~ , Al/n.. Cnnoclcl T6G2El

Received September 26, 1977

K A R L R. KOPECKY, WAYNE A. SCOTT, PETER A. LOCKWOOD, and CEDRIC MUMFORD. Can . J. Chem. 56, 11 14 (1978).

Migration of the hydroperoxy group occurs during the reaction between base and several 0-halohydroperoxides to give allylic hydroperoxides. An 86: 14 ratio of 3-hydroperoxy-2- (4-methoxypheny1)-3-methyl-I- butene-3-hydroperoxy-3-(4-methoxyphenyl)-2-methyl-I- butene was formed in 90% yield from 2-bromo-3-hydroperoxy-3-(4-methoxyphenyl)-2-methylbutane. From I-chloro-, I-bromo-, and I -iodo-I-(I-hydroperoxy-I-methylethy1)cyclohexane there were obtained I-(I-hydroperoxy-1-methylethyl)cyclohexene and I-hydroperoxy-I-(2-propeny1)- cyclohexane in ratios of 93:7, 94:6, and 94:6, respectively, in 98-100% yield. Isopro- pylidenecyclohexane was converted with singlet oxygen t o these allylic hydroperoxides in a 10:90 ratio. Only the latter allylic hydroperoxide was formed in the reaction between the alkene and triphenyl phosphite ozonide at -70°C. The p-nitrobenzoate esters of I-hydro- peroxy(1-chloro-, I-bromo-, and I-iodo-I-methylethyl)cyclopentane were converted quanti- tatively to I-(I-hydroperoxy-I-methylethyl)cyclopentene and I-hydroperoxy-I-(2-propeny1)- cyclopentane in 77:23, 73:27, and 70:30 ratios, respectively. Oxidation of isopropylidene- cyclopentane with triphenyl phosphite ozonide a t -70°C and singlet oxygen produced the allylic hydroperoxides in 62:38 and 58:42 ratios, respectively. The reactions of the p-halo- hydroperoxides proceed exclusively via perepoxide intermediates. T h e reactions between the alkenes and singlet oxygen or triphenyl phosphite ozonide do not involve perepoxide inter- mediates.

KARL R . KOPECKY, WAYNE A. SCOTT, PETER A. LOCKWOOD et CEDRIC MUMFORD. C a n . J. Chem. 56, 11 14 (1978).

La migration du groupe hydroperoxy se produit durant la reaction entre une base e t plu- sieurs a-halohydroperoxydes pour conduire aux hydroperoxydes allyliques. I1 se forme I'hydroperoxy-3 (mtthoxy-4 phenyl)-2 methyl-3 butene-1 et I'hydroperoxy-3 (mtthoxy-4 pheny1)-3 methyl-2 butene-1 dans un rapport de 86: 14 et avec un rendement de 90% a partir du bromo-2 hydroperoxy-3 (methoxy-4 ph6nyl)-3 methyl-2 butane. A partir des chloro-1 bromo-1 et iodo-1 (hydroperoxy-1 methyl-l ethyl)-1 cyclohexane, on obtient les(hydroperoxy-l methyl-1 ethyl)-1 cyclohexene et hydroperoxy-1 (propene-2 y1)-l cyclohexane dans un rapport de 93 : 7, 94: 6 et 94: 6, respectivement, avec des rendements de 98-1 00%. L'isopropylidene- cyclohexane se transforme sous l'influence de I'oxygene singulet dans ces hydroperoxydes allyliques dans un rapport de 10:90. 11 ne se forme que ledernier hydroperoxyde allylique dans la reaction de I'alcene et de I'ozonide de triphenylphosphite a -70'C. I1 y a une transformation quantitative des esters p-nitrobenzoate de I'hydroperoxy-1 (chloro-1, bromo-1 et iodo-l methyl-1 ethyl)-1 cyclopentane en (hydroperoxy-1 methyl-1 ethyl)-1 cyclopentene et I'hydro- peroxy-1 (propene-2 yl)-1 cyclopentane dans des rapports respectifs d e 77:23, 73:27 et 70:30. L'oxydation de I'isopropylidenecyclopentane avec l'ozonide de triphenylphosphite a - 70°C et I'oxygene singulet conduisent a la formation des hydroperoxydes allyliques dans des rapports respectifs de 62:38 et 58:42. Les reactions des a-halohydroperoxydes se produisent exclusive- ment par I'intermtdiaire de perepoxydes. Les reactions entre les alcenes et I'oxygene singulet ou I'ozonide d e triphenylphosphite n'impliquent pas d'intermediaires perepoxydes.

[Traduit par le journal]

Introduction

P-Halohydroperoxides derived from a variety of tetrasubstituted ethylenes are converted in high

'This research was supported in part by grants from the National Research Council of Canada and the Defense

.Research Board, Grant Number 9530-99. 2Presented in part a t the 57th Canadian Chemical Con-

ference of the Chemical Institute of Canada, Regina, Sas- katchewan, June 1974, Abstract No. 178.

3Holder of a National Research Council of Canada Scholar- ship 1970-1974.

yield to allylic hydroperoxides o n treatment with base (1). This reaction provides a n alternate route to the photosensitized oxygenation of such alkenes for the preparation of allylic hydroperoxides.

During a study to compare the product distribu- tions of the two modes of oxidation of an unsym- metrically deuterated 2,3-dimethyl-2-butene it was found that migration of the hydroperoxy group occurred on treatment of the derived mixture o f bromohydroperoxides with base (16) (Scheme 1). Both bromohydroperoxides were consumed a t t he

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KOPECKY ET AL.

CD3 OOH HOO CH3 CD2 OOH HOO CH2 I I I I \\ I I //

CD3C-CCH3 + CD3C-CCH, HO- , C-CCH3 + CD3C-C I I Br CH3

I I CD3 Br

/ I CD3 CH3

I \ CD3 CH3

same rate. It was concluded that the reaction pro- ceeded exclusively by way of a perepoxide inter- mediate and that a perepoxide was not an inter- mediate in the singlet oxygen oxidation of the alkene because of the different product distributions of the two reactions.

The present study was undertaken to search for further examples of hydroperoxy group migration in the reaction between P-halohydroperoxides and base, to determine whether the reaction proceeds ex- clusively by way of perepoxide intermediates in other systems as well and to obtain further evidence on whether or not perepoxides are formed in the singlet oxygen oxidation of alkenes to allylic hydroper- oxides.

Results and Discussion The reaction between base and 3-bromo-3-hydro-

peroxy-3-(4-methoxypheny1)-2-methylbutane pro- duces in 9 0 z yield a mixture of allylic hydroperoxides in which the product of hydroperoxy group migra- tion predominates greatly (Scheme 2). A very similar product distribution is obtained on singlet oxygen oxidation of the corresponding alkene (2). The singlet oxygen oxidation was repeated in the presence of 0.5 M sodium hydroxide. The product distribution was nearly the same as in the absence of base.

The product distributions from the oxidation of the unsymmetrical alkenes isopropylidenecyclohex-

ane 1 and isopropylidenecyclopentane 5 by singlet oxygen, by triphenyl phosphite ozonide and those from the reaction between base and the halohydro- peroxides derived from these alkenes are shown in Schemes 3 and 4. The three different halohydro- peroxides were prepared from each alkene to study the effect of the halogen leaving group on the prod- uct distribution.

The halohydroperoxides were prepared by the reaction between the alkene, 1,3-dihalo-5,5-dimethyl- hydantoin and hydrogen peroxide in ether at -20 to -40°C (1). The reactions with 1 were all regio- specific. Only the isomer with the hydroperoxy group on the carbon bearing the methyl groups appeared to be formed under a variety of condi- tions. The nmr spectra of the crude reaction mix- tures had no signals that could be attributed to the other isomer. Each of the halohydroperoxides de- rived from 1 was purified by low temperature crystallization from Skelly B to material with > 9 8 z active oxygen content. All three compounds were stable at 20°C for at least 10 min.

The degradation shown in Scheme 5 established the structure of the bromohydroperoxide 2-Br. The nmr signal (CDCI,) of the methyl groups of 2-Br appeared at r 8.5. The structures of 2-C1 and 2-1 followed from their nmr spectra. The methyl groups absorbed at r 8.6 and 8.4, respectively. The absorp- tions of the methyl groups of the isomeric halo-

HOO CH3 CH2 OOH HOO CH2 I 1 HO- , \\ I I 11

CH3C-CCH3 C-CCH3 + CH3C-C + Ar 0 C H 3 fl AH3

0CH3 4 0 C H 3 \cH3 86% 14%

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1 1 16 C A N . J . CHEM. VOL. 5 6 , 1978

OOH OOH HOO

[I] a&.3 C H ~ O H , HO- o0c ' @CH, + @ c ~ ~ ~ ~ b, CH3

Product Substrate distribution (%)

Total No. X Reaction 3 4 yield(%)

hydroperoxides would be expected to be 0.2 to 0.7 T units more downfield (I)."

The bromo- and iodohydroperoxides 6-Br and 6-1 of 5 also appear to have been formed regiospeci- fically with the halogen on the carbon atom bearing the methyl groups. These absorbed at r 8.12 and 7.94 respectively.' A mixture of chlorohydroperoxides 6-C1 and 9-CI was formed from 5. The isomer with the chlorine atom 011 the carbon atom bearing the inethyl groups predominated by a ratio of -2: 1. It was extremely difficult to separate 6-C1 and 9-C1, which were formed in low yield, from the other products of the reaction. Repetitive chromatography at -30 to -40°C afforded material which had 9 3 x of the theoretical active oxygen content and had sharp singlet absorptions at r 8.33 and 8.54, assigned

4After the work involving 1 and its derivatives had been completed it was reported (3) that both possible bromo- hydroperoxides were produced from 1 in proportions that depended upon the reaction conditions and that 2-Br pre- dominated. It was also concluded that there was no migration of the hydroperoxy group when the mixture of bromohydro- peroxides was treated with base. The small amount of re- arrangement that does occur (Scheme 3 of the present paper) was not detected. No experiments carried out with pure bromohydroperoxide were reported. It was observed, in agreement with the present work, that the reaction between singlet oxygen and 1 produces a product mixture very different from that obtained by treatment of the bromohydroperoxide with base.

'The regiospecificities of the addition reactions of 1 and 5 reported here have been noted already in the preparation of the bromohydrins of these alkenes and a rationale has been presented (4).

to the methyl groups of 6-C1 and 9-CI, respectively. It proved impossible to free 6-C1 completely from 9-C1, but the p-nitrobenzoate ester 6-CI-PNB could be made pure. It was also necessary to prepare the p-nitrobenzoate ester of 6-1 to ensure the purity of this material as 6-1 exploded within a minute after being freed of solvent. At 20°C 6-I-PNB was stable for some time as were 6-C1 and 9-CI, and 6-Br.

The base-induced elimination of H-X from 2-C1, 2-Br, and 2-1 produced a quantitative yield (nmr) of the mixture of allylic hydroperoxides 3 and 4 in a ratio that did not vary with the halide ion leaving group. However, the amount of rearrangement of the hydroperoxy group is quite small with 3 greatly predominating in the product mixture. Treatment of the p-nitrobenzoate ester of 2-C1 with base produced the same product ratio as was obtained from 2-Cl itself.

Pure 3 was isolated readily by low temperature crystallization. The isomeric allylic hydroperoxide 4 is formed almost exclusively on singlet oxygen oxidation of 1 and is the sole product when 1 is treated with triphenyl phosphite ozonide. Thus, either of the two possible allylic hydroperoxides can be prepared from 1, as has been noted already (3).

Treatment of the halohydroperoxides, or their p-nitrobenzoate esters, derived from 5 with base produced a quantitative yield (nmr) of a mixture of allylic hydroperoxides 7 and 8 in which the product of rearrangement of the hydroperoxy group 8 pre- dominates by a ratio of nearly 3: 1. The ratio is not quite independent of the leaving halogen ion.

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KOFECKY ET AL.

ROO CH3 HOO OOH

[,I @#CH3 CD30D, DO- 22°C ' ' @ - c ~ ~ ~ : + e J C H 3

X I

CH3 6-X 7 8

Product Substrate distribution (%)

- Total No. X R Reaction 7 8 yield(%)

6 CI PNB" [3] 23 77 99 6 Br H 29 7 1 101

26 6 Br PNB [3] 74 95 6 1 H 13 1 29 7 1 -

6 1 H 13 1 30 70 99 5 1401 42 5 8 84 5 1461 39 6 1 80

"PNB = p-nilrobenzoyl.

Slightly more rearrangement occurred with 6-CI- PNB than with the bromo or iodo compounds. A 78:22 ratio of 8:7, essentially the same as was ob- tained from 6-CI-PNB, resulted when a mixture of -80% 6-C1 and -20% 9-CI, which had 93% of the theoretical active oxygen content, was treated with base. Also, a 79:21 ratio of 8:7 was obtained from a mixture, analytically pure, of 75% 6-C1-PNB and 25% 9-CI-PNB.

An attempt was made to monitor the reaction be- tween 6-Br and base by nmr spectroscopy at - 60°C. A spectrum taken within 30 s after mixing the reac- tant solutions had signals due only to 7 and 8, all 6-Br had already been consumed.

As was observed in the cyclohexyl system oxidation of the alkene 5 with either singlet oxygen or triphenyl phosphite ozonide produced 7 and 8 in ratios signi- ficantly different from those in the above reactions.

OOH OH

OOR

@H3

!HI

9-CI, R = H 9-CI-PNB, R = PNB

Discussion

The formation of 4 from 2-X and of 8 from 6-X is direct evidence that migration of a hydroperoxy group occurred in the reaction between the halo- hydroperoxides and base. The relative insensitivity of the product ratios to the nature of the leaving halide ion is evidence that both rearranged and un- rearranged product are produced by only one path- way involving a halogen-free intermediate. These results are in complete agreement with those ob- tained previously with the bromohydroperoxides of the partially deuterated 2,3-dimethyl-2-butene (Ib). As was discussed previously (lb) the halohydro- peroxides must be converted by base to perepoxide intermediates exclusively which then rearrange to allylic hydroperoxides as is shown in Scheme 6 for 6-X. The fact that mixtures of 6-C1 or 6-CI-PNB containing appreciable amounts of 9-C1 or 9-C1-PNB react to give the same ratio of 7:8 as is formed from pure 6-CI-PNB means that 9-C1 and 9-C1-PNB also are converted exclusively to the perepoxide. Little, if any, elimination can be occurring by a route that

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1118 C A N . J . C H E M . VOL. 56, 1978

does not involve the perepoxide. Thus, it appears that perepoxide formation in the reaction between base and halohydroperoxides of tetrasubstituted ethylenes must be quite general. Jn principle the rearrangement could also proceed by way of a 1,2-dioxetane but tetramethyl-1,2-dioxetane dis- appears only after days under the reaction condi- tions to produce the cleavage product acetone only (Ib). No allylic hydroperoxide could be detected.

The product ratios obtained on oxidation of the alkenes 1 and 5 with singlet oxygen and triphenyl phosphite ozonide are significantly different from those obtained from the halohvdroperoxides. The . . present work provides further examples to show that singlet oxygen oxidations of tetrasubstituted ethyl- enes, at least, t o allylic hydroperoxides do not proceed by way of perepoxide intermediates. The reaction must be concerted (5).

Recent suggestions, based on experimental evi- dence and on theoretical calculations, that singlet oxygen reacts to form the perepoxide as the initial product with at least some alkenes have been refuted. Photosensitized oxidation of adamantylideneada- mantane in pinacolone produces a mixture of dioxetane and epoxide (6). I t was proposed that the epoxide was formed from a perepoxide by transfer of an oxygen atom to pinacolone in a Bayer-Villiger type of reaction and that perepoxide not trapped in this way rearranged to the dioxetane. The suggested oxygen transfer reaction was based on some observa- tions made in ozonolysis reactions (7) which were soon shown to be incorrect (8). Further. there is . , recent evidence that singlet oxygen is not involved in the formation of adamantylideneadamantane epox- ide (9).

The argument has been made that the product distribution from the halohydroperoxide elimination results from a combination of direct elimination plus perepoxide whereas the singlet oxygen oxidation proceeds only through perepoxide (100). However, this cannot be correct since 6-X gives mainly 8 and more 8 is produced than in the singlet oxygen reaction with 5.

Several theoretical calculations using enlpirical ~nelhods have been made which show that pere- poxides should be readily formed in the reaction between singlet oxygen and alkenes (lo), but recent ab initio calculations show that perepoxides must be very unstable species (I I).

The reaction between triphenyl phosphite ozonide and alkenes to give allylic hydroperoxides must pro- ceed by still a third mechanism since the product distributions are quite different from those of the reactions involving perepoxides and the reagent does not produce singlet oxygen at the temperature where the reactions were carried out (12). The results can be rationalized by a n ionic mechanism (13), Scheme 7, in which only one zwitterion is formed from 1 but both possible zwitterions are formed from 2. This mechanism is consistent with the regioselec- tivities observed o n formation of the halohydro- peroxides of 1 and 5.

Experimental Microanalyses were performed by Mrs. Darlene Mahlow.

3-(4-Methoxyphetiyl) -2-t~iet/1yl-2-b~rte11e A solution of 51 g (0.5 mol) 3-hydroxy-3-methyl-2-butanone

in 100 ml ether was added dropwise to 1.2 mol of 4-methoxy- phenylmagnesium bromide in 750 ml ether which was stirred by a high speed stirrer. A glutinous mass formed during the addition. The mixture was heated under reflux for 1 h after the addition was complete and then hydrolyzed with a saturated ammoniun~ chloride solution. The glutinous mass was agitated manually during the hydrolysis and then washed several times with ether. The combined ether layers were dried, concen- trated and 40 g methoxybenzene was distilled under reduced pressure from the residual oil. The hot residue was stirred into 100 ml heptane. The solid which formed was recrystallized from carbon tetrachloride to give 79 g ( 7 5 z ) of 2-(4-rnethoxy- pheny1)-3-methyl-2,3-butanediol, mp 76-84°C. A small quan- tity was recrystallized again to give colorless crystals, mp 82-85°C (lit. (14) mp 87-88°C).

A mixture of 70 g (0.33 mol) of the above diol and 48.8 g (0.33 mol) of triethyl orthoformate was heated at 140°C (15). After 2 h 14.4 g ethanol had distilled and the temperature was then raised to 205'C. After 12 h 12.2 g more ethanol distilled and the temperature was raised to 225°C a t which point more

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KOPECKY E T AL. 1119

ethanol was distilled and carbon dioxide was evolved. Gas evolution ceased after 1 h and the residue was distilled to give 47.3 g (SO%',) of a colorless oil, bp 239-243'C/702 Torr , nDz6 1.5309 (lit. (16) bp 234"C/760 Torr , 1 7 , ~ ~ 1.5295).

Pl~otooxyget~atiot~ of 3-(4-Metl7oxypl1et7y1)-2-t77etliyl-2-b1rtet1e it1 tile Presence of Bose

A solution of 2.1 g of the alkene in 30 ml of 0.5 M methan- olic sodium hydroxide was subjected to Eosin sensitized photooxygenation (Ib). After 4 h oxygen uptake ceased, the reaction mixture was poured into 100 ml water, and the resulting mixture neutralized with acetic acid and extracted twice with 50 ml ether. After drying the ether solution was added to 1.0 g lithium aluminum hydride in 15 ml ether. After 1 h at reflux the mixture was hydrolyzed with aqueous potas- sium hydroxide and the ether layer concentrated t o give 2.1 g (92%) of a colorless oil; ' H nmr (CCI,) r : 2.83 (d, J = 9 Hz, ArH) 3.42 (d, J = 9 Hz, ArH), 4.70 (d, J = 1.7 Hz, =CHH), 4.90 (m, =CHH), 5.13 (d, J = 1.7 Hz, =CHH), 5.13 (m, =CHH), 6.27 (s, OCH,), 8.1 (s, OH), 8.42 (m, =C-CH,), 8.42 (s, benzylic CH,), 8.70 (s, C(CH,),). The isomer ratio, 2.5: 1, was determined from five integrations of the absorptions of the vinyl hydrogens at T 4.70 and 4.90 which were assigned to 3-hydroperoxy-2-(4-methoxyphenyl)-3-methyl-l-butene and 3-hydroperoxy-3-(4-methoxyphenyl)-2-methyl-l-butene, re- spectively. The assignments were made on the basis of the relative yields reported for the photooxygenation of the parent alkene in the absence of base (2).

T,entrner7t of 2-Brott~o-2-tt~etliyl-3-(4-t~ietl~oxypl~et~yl)-3-b1rtyl Hyrlroperoxide with Brrse

An 8.8 g quantity of 3-(4-methoxypheny1)-2-methyl-2- butene was treated with 98% hydrogen peroxide and 1,3- dibromo-5,5-dimethylhydantoin in ether using the described procedure for making bromo hydroperoxides (lo). Attempts to remove solvent from the reaction mixture after work-up resulted in loss of peroxide content and blackening of the product. Iodometric titration of the ether solution indicated that -70% of the bromo hydroperoxide had been formed. A portion of the ether solution was added to carbon tetrachloride and the resulting mixture evaporated under reduced pressure until the remaining liquid was ether-free; ' H nmr (CCI4) T : 2.32-3.33 (m, ArH), 6.23 (s, OCH,), 8.11 (s, benzylic CH,), 8.28 and 8.33 (s, C(CH,),); signals due to unreacted starting material were also present.

The remaining ether solution was cooled to 0°C and 100 ml of 0.5 M methanolic sodium hydroxide was stirred in over a 15 min period. After stirring for a further 30 min the mixture was poured into 100 ml water and the resulting mixture neu- tralized with acetic acid. The resulting mixture was extracted twice with 100 ml ether. The combined ether extracts were dried and added to a slurry of 2.5 g lithium aluminum hydride in 60 ml ether. Work-up as above provided a colorless oil which was chromatographed on 300 g basic alumina. Starting alkene, 33%, was eluted with pentane. Elution with 1 : l ether-pentane gave some unidentified solid, and elution with ether removed the mixture of allylic alcohols in 57% yield. The ' H nmr spectrum showed the same peaks as the mixture obtained on photosensitized oxidation. The isomer ratio, determined as before, was 6.3: 1.

I-(2-Propettyl) cyclol1exnt1ol This material was prepared from the reaction between

2-propenylmagnesium bromide (17) and cyclohexanone in 66% yield, bp 54OC12.5 Torr ; 1 7 , ~ ~ 1.4824; ir (CCI,) 3450 (OH), 1635 (C=C); ' H nmr (CCI,): 5.05 (s, l H , =CHH), 5.2 (s, l H , =CHH), 7.95 (s, l H , OH), 8.2 (d, J = 1 Hz, 3H, CH,), 8.45 (b, 10H, CHz). At~al . calcd. for C 9 H t 6 0 : C 77.14, H 11.42; found: C 77.13, H 11.41.

Isopropylidenecyclo/lexo,le ( I ) A solution of 28 g (0.2 mol) of the above conlpound and 10 g

ethanol dissolved in 50 ml ether was added t o a solution of 10 g (0.4 mol) sodium in 270 ml liquid ammonia at -33'C. A further 10 g ethanol was added and the solution was allowed to reflux for 2 h. Water was added until the blue color just dis- appeared and the ammonia was allowed t o evaporate over- night. Water, 100 ml, was added to the residue and the resulting mixture was extracted with ether three times. The combined ether extracts were washed with water until neutral, dried and concentrated. T h e residue was distilled to give 17.9 g colorless oil, bp 51-53"C/14 Torr, 17,'~ 1.4710 (lit. (18) bp 46-4SoC/13 Torr, 17,'~ 1.4714).

/-(2-Prope11yl) cyclopet~tat~ol The method used for the preparation o f I-(2-propeny1)-

cyclohexanol was used t o prepare this material in 509, yield, bp 72-75"C/18 Torr, tlD2' 1.4745; H nnlr (CCI,) T : 5.05 (s, IH, =CHH), 5.2 (m, l H , =CHH), 7.1 (b, l H , OH), 8.2 (d, J = l H z , 3H, CH,), 8.3 (b, 8H, CH2). ANN/. calcd. for CBH,,O: C76.19 ,H 11.11; found: C75.94, H 10.81.

Isopropylirlet~ecyc/opet~tot~e (5) The procedure used for the preparation of 1 was used to

make 5 in 50% yield, b p 133-134'C, 1 7 , ~ ~ 1.4574 (lit. (18) bp 135.5-1 37.5"c, t~~~~ 1.4585).

1-(I-Hydroperoxy- I-tt~ethyletl~yl) cycloliesvl Brott~idr (2-Br)

This material and the halohydroperoxides described below were prepared in the usual way (lo). From 12.4 g 1 was ob- tained 29.7 g of crude product as an oil which contained 76';: of the theoretical active oxygen content a s determined by iodonletric titration (19). Three recrystallizations from Skelly B yielded a white solid, m p 55-56'C, containing 99.79, of the theoretical active oxygen content; ' H nmr (CDCI,) 7: 3.0 ( b s, IH, O O H ) , 8.3 (b, 10H, CH,), 8.5 (s, 6H, CH,) .

I-(I-Hydroperoxy- 1 -tt~etl~yletl~yl) cyclol~e,~yl Iodirle (2-1) From 12.4 g 1, using 1,3-diiodo-5,5-dimethylhydantoin as

the halogenating agent, was obtained 35 g yellow solid which had 67% of the theoretical oxygen content. Several recrystal- lizations from Skelly B gave a white solid, m p 43 C (dec.), with 98% of the theoretical active oxygen content. This material deconlposed within several minutes at 25 C ; ' H nmr (CCI,) r : 2.7 (s, l H , OOH), 8.2 (b, IOH, CH2), 8.4 (s, 6 H , CH3).

1-(I-Hyrl,o/)ero.~y-1-111etIi~~IetIiy1) c y c l o l ~ e s ~ ~ l Cl7loricle (2-Cl) F r o m 1.24 g of conlpound 1, using I ,3-dichloro-5,5-di-

n~ethylhydantoin as halogenating agent a n d stirring the reac- tion mixture an extra 1.5 h at -3OCC, was obtained 2.1 g oil. This was added to 10 m l 2-methylbutane and the resulting mixture filtered. The filtrate was cooled t o -70'C and the resulting crystals were recrystallized several times from 2- methylbutane at -70°C t o yield 0.5 g (26Y,) of a white solid,' mp 4646.5"C, with 100% of the theoretical oxygen content; ' H nmr (CC1,) r : 2.5 (s, l H , OOH), 8.1-8.3 (b, 10H, CH,), 8.6 (s, 6 H , CH3).

The p-nitrobenzoate ester 2-CI-PNB was prepared (20) from 0.5 g 2-Cl and recrystallized from Skelly B t o give 0.27 g (30%) of a white solid, mp 102-C (dec.), containing, 98.59, of the theoretical active oxygen content; ' H n m r (CDCI,) r : 1.52 (d, J = 8.4 Hz, 2H, ArH) , 1.68 (d, J = 8.4 H z , 2H, ArH), 8.2 (b, IOH, CH,), 8.4 (s, 6 H , CH,). Atlol. calcd. for C1(IHZO- CINO,: C 56.23, H 5.90, N 4.10, C1 10.37; found: C 56.04, H 6.00, N 4.66, CI 10.59.

/-(l-Brot77o-l-t77etI7yIetl1y1)c~~clopet1tyl Hydroperoxide (6-Br) The crude material obtained in the usual way from 5.5 g 5

was recrystallized three times from 2-methylbutane at -70°C

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1120 C A N . J . CHEM. VOL. 56. 1978

to give 4.4 g (389,) white crystals, mp - I0 to -5'C, which had 99.29, of theoretical oxygen content; 'H nmr (CDCI,) r : 2.40 (b, IH, OOH), 8.0 (b, 8H, CH2), 8.12 (s, 6H, CH,). The crude product decomposed rapidly above 0 C but the pure product was stable for some time at 20 C.

The p-nitrobenzoate ester 6-Br-PNB had mp 94-96'C (dec.); 'H nmr (CDCI,) r : 1.66 (d, J = 8.4 Hz, 2H, ArH), 1.88 (d, J = 8.4 Hz, 2H, ArH), 8 (b, 8H, CH,), 8.04 (s, 6H, CH,). Atlnl. calcd. for Cl5Hl8BrNo5: C 48.40, H 4.87, N 3.76, Br 21.47; found: C 48.14, H 4.81, N 3.70, Br 21.49.

I-(I-Iodo-I-ttrrt/rj~/e/l~yl)cyclo~~etrtyl Hj~droperoxirlr (6-1) The crude product prepared in the usual way, using 1,3-

diiodo-5,5-dimethylhydantoin as a halogen source and keeping the temperature during the entire workup at 0-C or below, was purified by chromatography on silica gel at -40°C using Skelly B -ether 4 : 1 as eluent. Removal of solvent under vacuum at -20cC gave a colorless oil which had 987, of the theoretical active oxygen content. This material exploded within less than a minute after being warmed to 0°C; 'H nnir (CDCI,, -30-C) T: 0.46 (s, l H , OOH), 7.94 (s, 6H, CH3), 8.25 (b, 8H, CH2).

The D-nitrobenzoate ester 6-I-PNB was purified by chroma- I tograihy on silica gel at -40°C followed by crystallization i from ether - Skelly B. The material was applied to the column 1 in toluene. The yellow crystals decomposed without melting

at 75-80°C; ' H nnir (CDCI,) T: 1.68 (d, J = 8.4 Hz, 2H, ArH), 1.87 (d, J = 8.4 Hz, ZH, ArH), 7.86 (s, 6H, CH,), 8.0 ' (b, 8H, CH,). Atrnl. calcd. for C15H181N05: C 42.97, H 4.33, N 3.34,I 30.27; found: C43.24, H4.23, N 3.17, 130.20.

I- ( I- Cl~loro-l-t~re/lr~~le/I~yl) cyclopetr/~~I Hycioperoside (6-CI) I ntrd I-(~-Hyr/ropero,~y-~-nret~~~~/et/ry/)c~~c/opetrty~

Cl~lor icle (9-Cl) The crude product, prepared in the usual way using 1,3-

dichloro-5,5-dimethylhydantoin as a halogen source, was chromatographed on silica gel at -40°C using 109, ether in 2-niethylbutane as eluent. The fractions containing chloro- hydroperoxide were combined and rechroniatographed. This procedure was repeated twice more and then the fraction con- taining the purest chlorohydroperoxide was crystallized froni 2-niethylbutane at -70'C. The 'H nmr spectrum of the crystals, which melted well below O'C, indicated the presence of both 6-CI and 9-CI in a ratio of -80:20. Recrystallization produced material with the same isomer ratio that had 937, of the theoretical peroxide content; ' H nnir (CDCI,) r : 3.10 (s, IH, OOH), 8.2 (b, 8H, CH,), 8.33 (s, CH3 of 6-CI), 8.54 (s, CH3 of 9-CI).

A portion of the above niaterial was converted to the p- nitrobenzoate esters 6-CI-PNB and 9-CI-PNB. These were purified by chromatography on silica gel at -40'C and then recrystallization from Skelly B to yellow crystals, mp 73-75"C, that were a mixture of 759, 6-CI-PNB and 25% 9-CI-PNB as judged from the ' H nmr spectrum (CDCI,) T: 1.73 (d, J = 8.4 Hz, 2H, ArH), 1.89 (d, J = 8.4 Hz, 2H, ArH), 8.0 (b, 8H, CH,), 8.21 (s, CH3 of 6-CI-PNB), 8.36 (s, CH3 of 9-CI-PNB). Atlol. calcd. for C15H18CIN05: C 54.97, H 5.54, N 4.27, CI 10.81; found: C 54.96, H 5.61, N 3.98, CI 11.07.

The chlorohydroperoxide mixture from another preparation which contained 9 0 z 6-CI was converted to the p-nitroben- zoate esters. Two recrystallizations froni Skelly B gave 6-CI-PNB, whose 'H nmr spectrum had no trace of the signal due to the methyl hydrogens of 9-CI-PNB, mp 87-88'C (dec.). Atlol. found: C 54.63, H 5.54, N 4.20, CI 10.88.

Conversion of I-(I-Hydroperoxy-I-~rerhyle/l~)/)c)~clolrex~~l Bromide (2-Br) lo (I-Hydroxy-I-tne~l~)~le/l~yl)cyclol~exnne

To a solution of 2.62 g (0.01 mol) of triphenylphosphine in 50 nil Skelly B was added 2.37 g (0.01 mol) of 2-Br in 10 ml

Skelly B. The reaction mixture was stirred for I h and filtered. The filtrate was shaken with 309, hydrogen peroxide, filtered, and the resulting filtrate washed with water, dried, and con- centrated. The residue was eluted through a column of silica gel with 259, ether in Skelly B to yield 2 g (909,) of the color- less bromohydrin. This was taken up in 30 ml benzene and 2.9 g (0.01 mol) tributyltin hydride was added. The resulting solution was held at reflux for 12 h and then concentrated. The residue was eluted through a column of silica gel with 25% ether in Skelly B to yield 1.0 g (87z) of a colorless oil that was identical (ir, 'H nmr) with an authentic (21) sample of (1- hydroxy-1-methy1ethyI)cyclohexane.

I- (I-Hydroprro,~y- l-t~1etlrylr/l7yl) cyclol~exetre (3) A solution of 0.44 g (0.011 mol) sodiuni hydroxide in I nil

water and 3 ml niethanol was added to 2.37 g (0.01 niol) 2-Br in 60 ml methanol at 0°C. The resulting solution was stirred a t 0°C for 20 ~n in and then poured into a mixture of water and dichloroniethane. The aqueous layer was extracted three times with dichloromethane. The combined organic layers were washed with water, dried, and concentrated togive 1.5 g (87%) colorless oil. This was crystallized several times from 2- niethylbutane at -78'C to give white crystals, nip 24-26'C, which had 99.79, of the theoretical active oxygen content; ' H nmr (CCI,) T: 2.5 (s, l H , OOH), 4.35 (m, IH, =CH), 8.0 (b, 4H, allylic CH,), 8.4 (b, 4H, homoallylic CH,), 8.75 (s, 6H, CH3).

I-(2-Propet1yl)cyclol1ex~~I Hydroperoxirle ( 4 ) Triphenyl phosphite ozonide was prepared (12) froni 3.1 g

(0.01 niol) triphenyl phosphine in 40 ml dichloromethane a t -70'C. To this solution was added 1.2 g (0.01 mol) 1 and the resulting solution was allowed to stand at -701C for 12 h and then warmed to 20'C. The solvent was evaporated. A weighed quantity of 1,4-dimethoxybenzene was added. The ' H nnir spectrum indicated that 4 was produced in quantitative yield. No signals due to 3 could be detected. The reaction mixture was then diluted with 50 ml2-methyl-butane and the resulting mixture stirred and filtered. Solvent was evaporated froni the filtrate and the residue chromatographed on silica gel at -40°C using 259, ether in Skelly B as eluent. The fractions containing peroxide were combined and crystallized several times froni 2-methylbutane at -70'C to give white crystals, mp 17-19'C, which had 99.59, of the theoretical active oxygen content; 'H nmr (CCI,) r : 2.6 (s, IH, OOH), 5.05 (bs, 2H, =CHZ), 8.25 (d, J = 1 HZ, 3H, CH3), 8.5 (b, IOH, CH,).

Reduction of 1.2 g 4 with lithium aluminum hydride pro- duced 0.66 g of I-(2-propenyl)cyclohexanol which had ir and ' H nmr spectra identical to those of an authentic sample.

I-(I-Hyrl,.oxy-I-ttre/lryle/l~yl) cyclolreset~e A solution of 6.2 g I-acetylcyclohexene (22) in 10 nil ether

was added to a solution of methylmagnesium bromide made from 1.2 g magnesiuni and 5.0 g bromomethane in 40 n ~ l ether. After 15 min under reflux the reaction mixture was hydrolyzed with saturated ammonium chloride. The usual workup gave 4.3 g (629,) of a colorless oil, bp 85-87'C/14 Torr, 11," 1.4812; 'H nmr (CCI,) T: 4.3 (m, IH, =CH), 7.5 (s, l H , OH), 8.05 (ni, 4H, allylic CH2), 8.45 (b, 4H, honio- allylic CH,), 0.75 (s, 6H, CH,). Atrol. calcd. for C,H,,O: C77.14, H 11.42; found: C 76.28, H 11.62.

Reduction of 0.78 g of compound 3 with lithiuni aluniinum hydride produced 0.69 g (999,) of an oil which had ir and 'H nnir spectra identical to those of the above material.

Prod~ict Dislribliriotr fiottr Renctiotr of' 2- X nnd 2-CI-PNB ~vitlr Bnse

All the reactions were carried out according to the following procedure. To a solution of 2.37 g (0.01 mol) of 2-Br in 6 ml

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methanol at 0°C was added 0 60 g (0.01 1 rnol) sodium hy- droxide in I rnl water and 3 nil methanol, dropwise w~th stir- ring. The reaction mixture was stirred at 0-C for 1.5 h (it was later found that the reactions were complete in 30 s) and poured ~ n t o a mixture of 10 ml water and I0 ml dichloromethane. The aqueous layer was shaken with dichloromethane, 3 x 10 ml, the cornb~ned organic layers shaken once with water, dried and concentrated. To the residue was added 0.69 g (0.005 mol) 1,4-dimethoxyethane as internal standard. The resulting mix- ture was taken up in carbon tetrachlor~de and analyzed by ' H ninr spectroscopy. The relative yields'of 3 and 4 were deter- inrned by integrating the vinyl protons of each isomer. The yields ~n Scheme 3 are the average of three integrations. Values were reproducible to within t0 .5%.

The reaction with 2-CI-PNB was initially heterogeneous and was stirred until the reaction mixture became homogeneous.

Prod~rct Distriblttiotl frot~l Renctiotl between Bnse atld 6-X, 6- X-PNB, 9-CI, ntld 9-CI-PNB

All the reactions were based on the following procedure. A solution of 0.0876 g (3.94 x mol) of 6-Br and 0.01097 g (1.40 x mol) benzene in methanol-& was made up to 1 ml. A second solution of 0.0397 g (1.73 x lo-, mol) and deuterium oxide 0.0612 g (3.06 x lo-, mol) was made up to 2.0 ml with methanol-rl, Equal volumes of the two solutions

I were mixed at 20'C in a nmr tube. The 'H nmr spectrum was taken immediately and had signals at r : 2.68 (s, C6Hs), 4.44 (t, =CH of 8), 4.85 (s, HOD), 5.10 (m, =CHI of 7), 6.70 (m, H in CD,OD), 7.66 (b, allylic CH2 of 8), 8.2 (b, other CHI of 7 and 8 and CH, of 7), 8.68 (s, CH, of 8). The assignments are based on the spectra of 3 and 4. The relative y~elds of 7 and 8 were calculated from integrat~on of the vinyl proton signals at r 4.44 and 5.10. The average of three integrals was taken. These were reproducible to t 2 % . The results are presented in Scheme 4.

I The reactions using 6-X-PNB were heterogeneous, and the solid esters were added in four equal portions to a small amount of methanol-& followed by one quarter of the base solution. After each addition the mixture was shaken unt~l it became homogeneous.

Plrotooxygerrotiot~ of 1 nr~d 5 A solution of 1.0 g of 1 or 5, 0.1 g 2,6-di-tert-butylphenol,

0.1380 g 1,4-dimethoxybenzene, as Internal standard, and 0.05 g methylene blue in 30 ml methanol was irradiated untll oxygen uptake ceased and worked up as described (10). The product yield and distribution (Schemes 3 and 4) were de- termined by 'H nmr.

Trenttnetrt of 5 wit11 Tripllerryl Pllosplrrte O=orride This reaction was carrled out as described above for the

reaction wlth 1 using 0 5 g (0.0045 rnol) 5 and 1 4 g (0.0045 mol) tr~phenyl phosphite in 25 rnl dichloromethane. After 12 h at -78°C solvent was evaporated at - 35'C. The distillate was caught in a -70°C trap and found to contaln 0.18 g 5. The

residue was analyzed by ' H nmr spectroscopy. The results are presented in Scheme 4.

I. ( a ) K. R. KOPECKY. J . H. VAN DE SANDE, and C. MUM- FORD. Can. J. Chem. 46,25 (1968): (b) K. R . KOPLCKY and J. H. VAN DE SANDE. Can. J. Chem. 50, 4035 (1972); (c) K. R. KOPECKY, J. E. FILBY, C. MUMFORD, P A. LOCKWOOD, and J.-Y. DING. Can. J . Chem. 53. 1103 (1975).

2. C.S.Foor~andR.W.D~~~~.J.Am.Chem.Soc.93.5162 (1971).

3. J . E. BALDWIN and 0. W. LEVER. J. Chem. Soc. Chem. Commun. 343 (1973).

4. A. J . SISTI. Tetrahedron Lett. 3305 (1970). 5. A. NICKON and J. F. BAGLI. J. Am. Chem. Soc. 83, 1498

(1961). 6. A. P. SCHAAP and G. R . FALER. J . Am. Chem. Soc. 95,3381

(1973). 7. P. R. STORY, E. A. WHITED, and J . ALFORD. J . Am. Chem.

SOC. 94,2143 (1972). 8. K. R. KOPECKY. P. A. LOCKWOOD, J. E. FILBY, and R. W.

REID. Can. J. Chem. 51,468 (1973). 9. C. W. JEFFORD and A . F. BOSCHUNG. Tetrahedron Lett.

4771 (1976). 10. (a) M. J . S. DEWAR and W. THIEL. J. Am. Chem. Soc. 97,

3978 (1975); ( 6 ) M. J . S . DEWAR. A. C. GRIFFIN. W. T H I E L , and I. J . TURCHI. J . Am. Chem. Soc. 97,4439 (1975); (c) S. I N A G A K I and K. F U K U I . J. Am. Chem. Soc. 97.7480(1975).

II. L. B. HARDING and W. A. GODDARD 111. J. Am. Chem. SOC. 99,4520 (1977).

12. P. D. BARTLETT and G. D. MENDENHALL. J . Am. Chem. SOC. 92,210 (1970).

13. P. D. BARTLETT and A. P. SCHAAP. J . Am. Chem. SOC. 92, 6055 (1970).

14. C. G. OVERBERGER and H. GAINER. J. Am. Chem. Soc. 80, 4556 (1958).

15. G. CRANCK and F. W. EAST WOOD. A~ist. J . Chem. 17, 1392 (1964).

16. G. P. NEWSOROFF and G. STERNHILL. A u s ~ . J. Chem. 19. 1667 (1966).

17. H. 0. HOUSE, R. A. LATHAM, and C. D. SLATER. J. Org. Chem. 31,2667 (1966).

18. R. H . SIEGMANN, M. J . BEERS, and H. 0. HUISMAN. Recl. Trav. Chim. 83,67 (1964).

19. H. B. KNIGHT and D. SWERN. 111 Organic synthesis, Coll. Vol. 4. Edited by N . Rabjohn. John Wiley and Sons, Inc. New York. NY. 1963. p. 895.

20. R. L. SHRINER, R. C . FUSON, and D. Y. CURTIN. The systematic identification of organic compounds. 5th ed. John Wiley and Sons, Inc. New York, NY. 1964. p. 235.

21. C. F. W i ~ c o x , JR. and S. S. CHIBBER. J . Org. Chem. 27, 2332 (1962).

22. E. E. ROYALS and C. M. HENDRY. J. Org. Chem. 15, 1147 (1950).

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