Synthesis and Odour of Bicyclo[2.2.2]octanone Derivatives: β-Hydroxy Ketones and Enones

6
FLAVOUR AND FRAGRANCE JOURNAL, VOL. 10, 287-292 (1995) Synthesis and Odour of Bicyclo[2.2.2]octanone Derivatives: P-Hydroxy Ketones and Enones Helmut Spreitzer, Christian Anderwald' and Gerhard Buchbauer* Institute of Pharmaceutical Chemistry, University of Vienna, Alihanstrasse 14, A-I090 Vienna, Austria From bicyclo[2.2.2]octan-2-one (1) the P-hydroxy ketones 2-13 were prepared by aldol reaction with various aldehydes. Dehydration of the ketols furnished the corresponding enones 14-22. The odour properties of these bicyclic, rigid hydroxy ketones as well as of the enones are described. KEY WORDS bicyclo[2.2.2]octan-2-one; homonorbornanones; aldol reaction; fragrance compounds; AH/B-system; structure-odour relationship; aniseed odour; spicy odour INTRODUCTION Compared with bicyclo[2.2. llheptane fragrance compounds -norbornane derivatives with olfac- tory pr~perties~~~-little is known about 'homon~rbornanes'~ (=bicyclo[2.2.2]octane derivatives in fragrance chemistry or in flavour chemistry. The easy accessibility of homonor- camphor (1)12,13 and positive experiences with isocamphanyl methyl ketones as starting carbonyl compounds to a series of new, olfactively interest- ing aldol product^,'^ prompted us to try this simple carbonyl reaction on bicyclo[2.2.2]octan- 2-one (1) and to evaluate the odour properties of the resulting ketols, and their corresponding enones. Moreover these bicyclo-octyl ketols repre- sent a suitable rigid molecule s stem which, according to Ohloff s hypothesis'' whereby an odour impression is preferentially noticed if the distance of the donor to the acceptor function of such disubstituted 'AHIB systems' does not ex- ceed 3 ,&, creates a suitable basis for a rational fragrance design. 4 0 EXPERIMENTAL IR: liquid film, NaC1, Perkin-Elmer 298 IR. GC- MS: Hewlett-Packard GC 5890 A, MSD 5970B, data system HP-9000/300, EI 70 eV, 40-450 amu, carrier gas helium (10 psi). Analytical GC: carrier gas N2, FID H2, column: fused-silica, Supelco SPB-1, 12m x 0.2mm id., temperature pro- ramme: 50°C (lmin), then 15"CImin to 280°C. 'H-NMR in CDCl 3, Bruker AC 80, TMS. Pre- parative TLC, silica gel 60F2s4, 2mm, 20 X 20, Merck-No. 5717 and 0.2mm, Merck-No. 5554. General Procedure for the Preparation of P-Hydroxy ketones 2-13 To a solution of diisopropylamine (1.41 ml, 1.01g, 10 mmol) in 7 ml dry ether in a dry, argon- flushed reaction flask, cooled to -78"C, a solution of BuLi in hexane (1.6 molar, 6.88ml) was added and stirred at 0°C-20°C for a period of 30 minutes. After cooling to -78°C a solution of bicyclo[2.2.2]octan-2-one (1) (1.24g, 10mmol) in a 4:1 mixture of dry etherIdry THF was added slowly under argon. This mixture was stirred at room temperature for 2 h during which a yellow, orange colour was noticed. If upon addition of 1 the precipitate is not completely dissolved, ad- ditional millilitres of dry ether will bring it into solution. Upon renewed cooling to -78°C a soh- tion of the aldehyde (18 mmol) in 3 ml dry ether was added very slowly by a syringe and the mix- ture was stirred for a period of 2 hours at -78°C to -65°C (!). After removal of the cooling bath the basic mixture was neutralized immediately with glacial acetic acid (1.5 ml in 5ml dry ether), filtered and the residue dissolved in water. The aqueous phase was extracted with ether (3 x CCC 0882-5734/95/050287-06 0 1995 by John Wiley & Sons, Ltd. Received 30 March 1994 Accepted 20 December 1994

Transcript of Synthesis and Odour of Bicyclo[2.2.2]octanone Derivatives: β-Hydroxy Ketones and Enones

Page 1: Synthesis and Odour of Bicyclo[2.2.2]octanone Derivatives: β-Hydroxy Ketones and Enones

FLAVOUR AND FRAGRANCE JOURNAL, VOL. 10, 287-292 (1995)

Synthesis and Odour of Bicyclo[2.2.2]octanone Derivatives: P-Hydroxy Ketones and Enones

Helmut Spreitzer, Christian Anderwald' and Gerhard Buchbauer* Institute of Pharmaceutical Chemistry, University of Vienna, Alihanstrasse 14, A-I090 Vienna, Austria

From bicyclo[2.2.2]octan-2-one (1) the P-hydroxy ketones 2-13 were prepared by aldol reaction with various aldehydes. Dehydration of the ketols furnished the corresponding enones 14-22. The odour properties of these bicyclic, rigid hydroxy ketones as well as of the enones are described.

KEY WORDS bicyclo[2.2.2]octan-2-one; homonorbornanones; aldol reaction; fragrance compounds; AH/B-system; structure-odour relationship; aniseed odour; spicy odour

INTRODUCTION

Compared with bicyclo[2.2. llheptane fragrance compounds -norbornane derivatives with olfac- tory p r~pe r t i e s~~~- l i t t l e is known about 'homon~rbornanes '~ (=bicyclo[2.2.2]octane derivatives in fragrance chemistry or in flavour chemistry. The easy accessibility of homonor- camphor (1)12,13 and positive experiences with isocamphanyl methyl ketones as starting carbonyl compounds to a series of new, olfactively interest- ing aldol product^,'^ prompted us to try this simple carbonyl reaction on bicyclo[2.2.2]octan- 2-one (1) and to evaluate the odour properties of the resulting ketols, and their corresponding enones. Moreover these bicyclo-octyl ketols repre- sent a suitable rigid molecule s stem which, according to Ohloff s hypothesis'' whereby an odour impression is preferentially noticed if the distance of the donor to the acceptor function of such disubstituted 'AHIB systems' does not ex- ceed 3 ,&, creates a suitable basis for a rational fragrance design.

4 0 EXPERIMENTAL

IR: liquid film, NaC1, Perkin-Elmer 298 IR. GC- MS: Hewlett-Packard GC 5890 A, MSD 5970B,

data system HP-9000/300, EI 70 eV, 40-450 amu, carrier gas helium (10 psi). Analytical GC: carrier gas N2, FID H2, column: fused-silica, Supelco SPB-1, 12m x 0.2mm i d . , temperature pro- ramme: 50°C (lmin), then 15"CImin to 280°C.

'H-NMR in CDCl 3 , Bruker AC 80, TMS. Pre- parative TLC, silica gel 60F2s4, 2mm, 20 X 20, Merck-No. 5717 and 0.2mm, Merck-No. 5554.

General Procedure for the Preparation of P-Hydroxy ketones 2-13

To a solution of diisopropylamine (1.41 ml, 1.01 g, 10 mmol) in 7 ml dry ether in a dry, argon- flushed reaction flask, cooled to -78"C, a solution of BuLi in hexane (1.6 molar, 6.88ml) was added and stirred at 0°C-20°C for a period of 30 minutes. After cooling to -78°C a solution of bicyclo[2.2.2]octan-2-one (1) (1.24g, 10mmol) in a 4:1 mixture of dry etherIdry THF was added slowly under argon. This mixture was stirred at room temperature for 2 h during which a yellow, orange colour was noticed. If upon addition of 1 the precipitate is not completely dissolved, ad- ditional millilitres of dry ether will bring it into solution. Upon renewed cooling to -78°C a soh- tion of the aldehyde (18 mmol) in 3 ml dry ether was added very slowly by a syringe and the mix- ture was stirred for a period of 2 hours at -78°C to -65°C (!). After removal of the cooling bath the basic mixture was neutralized immediately with glacial acetic acid (1.5 ml in 5ml dry ether), filtered and the residue dissolved in water. The aqueous phase was extracted with ether (3 x

CCC 0882-5734/95/050287-06 0 1995 by John Wiley & Sons, Ltd.

Received 30 March 1994 Accepted 20 December 1994

Page 2: Synthesis and Odour of Bicyclo[2.2.2]octanone Derivatives: β-Hydroxy Ketones and Enones

288 H. SPREITZER, C. ANDERWALD AND G . BUCHBAUER

30ml) and the combined organic layers were washed with water, NaHC03 solution and water again and dried with MgS04. After evaporation of the solvent the residue was distilled in a kugel- rohr apparatus at 1 Torr slowly during a period of 2 hours raising the temperature from 40°C to 70°C. By this procedure nearly all of the aldehyde and unreacted 1 could be distilled off. The residue (= raw p-hydroxy ketone) was purified by pre- parative TLC with the system a(or b, or c, or d), one, two- or manifold development (see Table 1). Upon detection with anisaldehyde/conc. H2SO4 three zones could be identified, of which the lowest one belongs to the desired target product.

&OH 0

2: R = CH3 4: R=C& 6: R = CH=C(CH&

3: R = CH2CH3 5: R = CH=CH2

7: R = CHGH -CsHs

General Procedure for the Preparation of the Enones 14-22

To a cold solution (-5°C) of lmmol hydroxy ketone in 0.5 ml CHZC12 a mixture of SOC12 (0.57 ml, 7.85mmol; distilled with quinoline and lin- seed oil prior to use) and dry pyridine (0.57m1, 7.1 mmol; distilled with CaH2 prior to use) was added drop by drop. After stirring for 10 minutes pentane (10ml) was added and again drop by drop, HCI (2 N , 3.6ml). Afterwards the organic layer was separated, washed with NaHC03 solu- tion and water and dried with MgS04. Upon eva- poration of the solvent the residue was dissolved immediately in dry CH2C12 and purified by pre- parative TLC (solvent system: ligroidethyl acetate = 9/1, twofold development). See Table

RESULTS AND DISCUSSION

Bicyclo[2.2.2]octan-2-one (1) is a very valuable starting ketone for many synthetic operations. Less rigid than its lower homologue norcamphor, but armed with a more shielded carbonyl group because of the proton substituents of the ethylene bridge, 1 nevertheless allows many carbonyl transformations of which the aldol reaction is described in this paper. Because of Bredt's rule the enolization of 1 is possible only between car- bon 2 and 3 and therefore reaction products bear the new substituent at C-3. Because of the sym- metry of bicyclo[2.2.2]octan-2-one also em- and endo-epimers do not exist.

Aldol reaction of 1 with lithium diisopropyl- amide (LDA) as the base14 and with various aldehydes leads to the new ketols 2-13. Because of the better solubility of LDA the solvent mix- ture ether/THF = 75/25 was favoured. A 1.8:l ratio of a1dehyde:l proved to be the best one. The yields of the P-hydroxy ketones vary between 43% and 62%, but the aldol product 13 could not be obtained in a yield more than 20%. All ketols are stable under the conditions of a kugelrohr distillation at about 80°C and 1 Torr: no dehy- dration products could be detected. Purification by preparative TLC was necessary in all cases prior to olfactory evaluation.

Common characteristic spectral data are noticed in the IR-spectra (3400cm-' (OH) and 1700- 1715cm-' (C=O)) as well as in the 'H-NMR spectra. Apart from the signal of the protons at C-4-C-8 the A 0.2-0.3 ppm downfield shift of the C-1-H signal of ketols with an aromatic sub-

& 0

& H3

0 22

L.

Page 3: Synthesis and Odour of Bicyclo[2.2.2]octanone Derivatives: β-Hydroxy Ketones and Enones

BICYCLO(2,2,2]OCTANONE DERIVATIVES

Table 1. Analytical data of the hydroxy ketones 2-13

289

no.

- 2

3

4

5

6

7

8

9

10

11

12

13

Compound Formula; TLC molecular solvent

- weight system

yellow oil b

168.23 c I,,H I 6 0 2

yellow oil a.2"' CI IH 1x0, 182.86

light a ycllow crystals CISHIXO 230.31

yellow oil a CI I H IOOZ 180.25

yellow oil a CI3H2l102 208.30

brown a crystals C13Hlh03 220.27

light a.e ycllow oil C14H2003 236.31

yellow a.2") crystals ClhH2003 260.33

white c,f,4(3) crystals CISH2402 236.35

yellow oil d,4(3) C17H3002 266.42

white d.4") crystals C2oHxKh 308.50

Melting IR bands point (cm-') ("C)

- ( I ) 3400. 1710

1 03 3480,3020 I700

I H - N M R signals &values (ppm)

CH3 1.1; Cj-H 1.9; CI-H 2.1; C3-H 2.2; earbinol-H 3.9

CH3 0.8; C4-H 1.9; CI-H 2.1; C3-H 2.3; carbinol-H 3.8

C4-H 1.9; CI-H 2.3; C3- H 2.4; carbinol-H 4.8; ChHS 7.3

3450. 1690 C4-H 2.0; CI-H 2.1; C3- H 2.2; =CH2 5.1;

CH=CH2 5.7

(CH3)2C= 1.71, 1.75; C4- H 1.9; CI-H 2.1; C3-H 2.2; carbinol-H 4.5; =CH 5.0

C4-H 2.0: CI-H 2.3 C3-

CH=CH 6.0; ChHS-CH= CH 6.8; ChHS 7.3

carbinol-H 4.25; -

3480. 1700

3450. 3050 1710 H 2.4; carbinol-H 4.5; +-

76 3450. 1700 C4-H 1.9; CI-H 2.3; C3- H 2.6; carbinol-H 4.9; hetcroaromatic-H 6.25. 6.26. 7.3

3480. 1730 C4-H 1.9; Cl-H 2.1; C3- H 2.3; CH2-0 3.7, 4.5; carbinol-H 4.3: HC= 5.8

MS peaks mlz r.1. (%)

168 M+(2). 153(2), 150(21). 124(44), 107(15). 96(1oI)). 80(39). 67(25)

124(30), 107(17). 96(100). 80(52). 67(35)

164 M+-18(48). 136(18).

decomposition

162 M+-18(15). 134(13). 124(63), 105(8). 96(100), 80(73). 67(29)

190 M+-18(24). 175(100). 162(7). 147(17), 124(28). 96(21). 80(60), 67(23). SS(39)

238 M+-18(100). 210(40), 167(24), 161(14). 141(16). 115(27), 91(31). 77(11). 43(20)

220 M'(3). 202(65). 174(60), 146(34), 124(40). 117(20). 97(29). 96(100). 80(80), 67(48)

decomposition

105 3480. 1710 C4-H 1.9; CI-H 2.3: C3- 242 M+-18(100). 214(44). 1640 H 2.4; H3C-0 3.8; 186(40). 185(42). llS(24).

carbinol-H 4.8; Cc,H4 6.8. 7.2

96(37). 67(29). 43(67)

88 3460. 1705 Cj-H 2.0; Cl-H 2.1; C3- H 2.3; CI'-H 2.3; carbinol- H 3.7

3480. 1710 CH3 0.85; C4-H 2.1; CI- H 2.1; C3-H 2.3; carbinol- H 3.7

76 3480. 1710 CH3 0.85: C4-H 2.1; CI- H 2.1; C3-H 2.3; earbinol- H 3.8

218 M+-18(25), 190(48). 153(70). 124(54), 96(7 1 ) . 83(30). 80(59). 67(38). 55( 100)

163(16), 153(28). 135(14). 124(83), 107(13), 96(100), 80(53). 67(39). 55(45)

162(86). 150(43), 137(64). 124(100). 107(48). 98(88),

248 M+-18(29). 229(19),

290 M+-18(94). 262(50).

a: ligroinlether = 812; b: ligroinlethyl acetate = 713; c: ligroin/ethyl acetate = 9.1; d: ligroiniethyl acetate = 19/1; e: 5.6- dihydro-2H-pyran-3-carbaldehyde was used, see reference 16; f C6HI = c clohexyl. ( I ) neither melting nor boiling point determined; (') twofold development; (') twofold development on preparative TLC plates 2 mm, then another twofold development on TLC plates 0.2 mm.

Page 4: Synthesis and Odour of Bicyclo[2.2.2]octanone Derivatives: β-Hydroxy Ketones and Enones

290 H. SPREITZER, C. ANDERWALD AND G . BUCHBAUER

Table 2. Analytical data of the enones 14-22

Compound Formula; Melting IR bands 'H-NMR signals MS peaks no. molecular point (cm-l) 6-values (ppm) mlz r.1. (%)

weight ("C)

14

15

16

17

18

19

20

21

22

CiiH160 164.24

yellow 97 crystals

yellow oil -(2)

CllH140 162.23

brown 70 crvstals

white 77 crvstals

yellow 92 crystals

white 80 crystals CISH220 218.34

white 74 crystals C17H28O 248.41

1700, 1610 CH3 1.1; CH3CH2 2.3; CH-CO 2.4; CH-C=C 2.9; HC=C 6.6

1680, 1610 CH-CO 2.5; CH-C=C 3.4; CbH5 7.35; C~HS-CH 7.5

1700, 1615 CH-CO 2.4; CH-C=C 3.0; =CH2 5.5, 5.8; HC=CH2 6.7, 6.9

1690, 1630 CH-CO 2.5; CH-C=C 3.8; HC=C 6.5, heteroaromatic-H 6.7, 7.1, 7.5

3.0; H2C-0 3.7, 4.4; H- 1700, 1615 CH-CO 2.4; CH-C=C

C=C 6.2.6.8

1690, 1600 CH-CO 2.5; CH-C=C 3.4; H3C-0 3.8; C& 6.8, 7.3; HC=C 7.5

1700, 1610 C'I-H 2.3; CH-CO 2.4; CH-C=C 2.9; HC=C 6.4

1700, 1610 H3C 0.9; H2C-C=C 2.1; CH-CO 2.4; CH-C=C 2.9; HC=C 6.6

1715, 1645 H3C 1.7; CH-CO 2.3; CH-C=C 2.9;HC=C 6.6

164 M+(84), 136(69), 121(28), 107(100), 91(32), 81(25), 80(39), 79(88), 55(30)

212 M+(100), 184(37), 156(67), 141(20), 129(39), 128(46), 115(40), 91(27)

162 M+(85), 134(70), 119(55), 106(65), 91(100), 80(25), 79(64), 65(26) 202 M+(100), 174(91), 146(49), 117(21), 91(31), 81(20), 65(19)

218 M+(66), 190(23), 188(100), 160(22), 145(15), 131(14), 91(36), 79(20)

242 M+(100), 214(34), 186(29), 145(12), 91(30)

218 M+(38), 190(100), 147(31), 109(17), 96(10), 91(19), 79(22), 67(16)

248 M+(69), 220(39), 163(93), 150(28), 135(41), 124(71), 107(66), 96(50), 93(52), 91(46), 79(100), 67(69)

' 2 : 150 M+(100), 135(9), 122(95), 107(40), 94(36), 79(71), 67(30), 'E: 150 M+ (87), 135(13), 120(44), 107(83), 94(60), 79(100), 67(47)

~~ ~~ _ _ _ ~ ~~ ~~~~~ ~~~

(')Preparative TLC solvent system: ligroin/ether = 8/2; (2) neither melting nor boiling point determined

stituent (4, 7, 8, 10) compared to the C-1-H signal of the other hydroxy ketones and the signal of the carbinol proton between 3.7-4.8ppm (dependent on the adjacent substituent) are note- worthy. In the MS-fragmentation pattern only the molecular ion peak of the dehydration product could be found, with the exception of 2 and 8 and the loss of a 28-amu fragment by a retro-Diels- Alder reaction as well as the peak mlz=124 by a McLafferty rearrangement is also characteristic.

The organoleptic properties of the ketols 2-13

are listed in Table 3 . It seems interesting that ten among these hydroxy ketones possess a spicy- sweet fragrance and six of them a pronounced characteristic overall note of aniseed (anethole). Only two among these ketols show other charac- teristics: the odour of the benzaldehyde aldol pro- duct 4 is hardly perceptible (only a test person with a 'hyperosmia' against marzipan was able to notice it) and the flavour of 8 resembles bread- crust which may be due to the furan substituent. '' A woody note is detected in four ketols (6, 8, 11

Page 5: Synthesis and Odour of Bicyclo[2.2.2]octanone Derivatives: β-Hydroxy Ketones and Enones

BICYCLO[2,2,2]OCTANONE DERIVATIVES 291

Table 3. Organoleptic properties of the ketols 2-13

Compound Odour description

2 3 4 5 6

7

8 9

10 11 12 13

~ ~ ~ ~ ~ ~ ~ ~ ~~~

aromatic, spicy, reminiscent to anethole, a bit sweet very weak odour, a bit spicy, reminiscent of anethole hardly perceptible, eventually reminiscent of marzipan weak sweet pleasant warm, woody odour, clean, also spicy, later sweet and somewhat vaguely reminiscent of sandalwood weak odour, but strongly reminiscent of 'pizza', rosemary, sweet, later also cinnamic woody reminiscent of bread-crust, warm, fatty, in the basis some animal notes weak, sweet, anethole, camphoraceous, floral, animal tonalities strong aniseed odour green, spicy, warm woody spicy, aniseed spicy, aniseed, later also warm, woody

and 13) among which the weak sandalwood tonality of 6 is noteworthy. Regarding the structure of this bicyclo[2.2.2]octanone derivative some vague similarity to other sandalwood fragrance com- pounds could be found." Finally it seems interesting to note that in the make-up of the odour of the two heterocyclic aldol products 8 and 8 also a certain animal tonality is perceptible.

Summarizing these olfactive properties we again discern the correctness of Ohloff's conception" also for this class of compounds. Upon regarding Dreiding models of these ketols the distance between the carbonyl oxygen and the proton of the hydroxyl group is about 2.5 A, thus meeting the requirements of this AH/B-concep- tion. The side chain at C-3 of the bicyclus is posi- tioned in such a way that the C-5-syn-proton of the ethylene bridge is located in the hollow formed by the carbinol proton, the hydroxyl group and the substituent of the side chain, thus avoiding any steric hindrance. The lack of a distinct odour impression of 4 on the other hand

Table 4. OrganoleDtic properties of the enones 14-22

Compound Odour description

14 15 16

17 18 19 20 21 22

herbaceous, aromatic, spicy, vermouth not perceptible weak woody, somewhat camphoraceous and balsamic fatty, spicy, reminiscent of bread-crust very weak, spicy, sweet weak, sweet, reminiscent of anethole weak, sweet, reminiscent of vanillin sweet, herbaceous, fatty herbaceous, green, leathery

is very probably due to its non-volatility. Dehydration of the ketols lead to the corre-

sponding new enones, but only eight compounds could be obtained in a pure form as trans-olefins owing to the cidtruns-isomerism of the double bond. The deh dration system SOC12/pyridine (Mot1 reagent)' proved to be the best in this re- spect even if its yields were only oor to moderate. Using p-toluene sulfonic acid' a 20530 mixture of (Z):(E)-olefins was obtained. P0Cl3 furnished a mixture of at least three side pro- ducts. The proof of the (E)-configuration of the above mentioned enones 14-21 is based on the signal shift of the olefinic proton in the 'H-NMR spectrum: the shift of the &-proton in 14 is calculated2' as 6.54ppm, the one of the trans- proton as 6.32 ppm. We found this signal located at 6.56ppm, hence the structure of the thermo- dynamic more stable (E)-olefin 14 is very prob- able. Also the lack of a NOE between C4-H and the olefinic proton of the exocyclic double bond favours the assumption of the (E)-configuration.

Common characteristic spectral data in the 'H- NMR spectrum are the shifts of the signal of C- 1-H (at 2.4-2.5ppm) and C-4-H (at 2.9 or 3.0ppm in 16 to 18, or 3.4ppm in 15, and 19; the high deshielding effect on this proton in 17 (to 3.8ppm) probably is caused by the oxygen atom of the furan nucleus). Under normal conditions the differentiation between C-1 -H and C-4-H is very difficult,21 especially if there is no sub- stituent at the exocyclic double bond. But due to the anisotropic effect of this structural unit one signal is shifted downfield to an extent of at least 0.5ppm, thus showing its vicinity to the 1~ elec- trons and therefore establishing a clear proof that

B !

Page 6: Synthesis and Odour of Bicyclo[2.2.2]octanone Derivatives: β-Hydroxy Ketones and Enones

292 H. SPREITZER, C. ANDERWALD AND G. BUCHBAUER

this proton is the C-4 one indeed. Contrary to the fragmentation pattern of the ketols a molecular peak of the enones is found in every case as well as the loss of an ethylene unit by a retro-Diels- Alder reaction.

Dehydration of 2 furnishes a 84:16 mixture of the (E):(Z)-enone 22, the only product which could not be separated into its two isomers by TLC. 22 therefore has been evaluated olfactively as a mixture. Its olfactive properties as well as those of the enones 14-21 are listed in Table 4. Contrary to the olfactory characteristics of the corresponding enols where a great homogeneity could be found, no such coherence is detected among the odours of the enones. Four of them possess sweet odours, three herbaceous ones and other three smell spicy. The compound 15 cannot be noticed at all.

Summarizing the results of this study a clear dependence of odour relationships on the struc- tures of the evaluated molecules is shown. Even if the enone-osmophor renders the olefinic ketones olfactively perceptible, the importance of the hydroxyl function of the presented p-hydroxy ketones to valuable fragrances in perfume and flavour chemistry is shown again. The alcohol group - apart from the ketone function - is the most important osmophoric group in fragrance molecules22 and just its vicinity to this other strong osmophor creates such an AH/B-system, which confers on these hydroxycarbonyl com- pounds a pronounced odour. Therefore the spacing principle of this bifunctional unit as ex- pressed in Ohloff's hypothesis proved itself again to be an excellent starting basis for a rational fragrance design.

Acknowledgements-The authors are grateful to Dr L. Jiro- vetz for recording of GC-MS and 'H-NMR spectra. to V. Hausmann and W. Hoppner (chief perfumers of DRAGOCO, Vienna) for the olfactory evaluation and to the DRAGOCO company for the keen interest in our work.

REFERENCES

1 . Ch. Anderwald, Diploma thesis, University of Vienna (1994).

2. G. Buchbauer and G. Popp, Chemiker-Ztg., 107, 327 (1983).

3 . G. Buchbauer, H. Spreitzer and B. Schwayer, Parf. & Kosmetik, 73, 72, 146, 232, 330, 403 (1992).

4. H. Spreitzer, Ch. Schiffer and G. Buchbauer, Liebigs Ann. Chem., 1578 (1986).

5. G. Buchbauer, H. Spreitzer and C. Mullauer, Pharmazie, 41,537 (1986), and further references cited there in chap- ters 3.6 and 4.8.

6. H. Spreitzer, G. Buchbauer and S. Reisinger, Helv. Chim. Acta, 72, 806 (1989).

7. K. Bruns, Th. Gerke and M. Virnig, Europ. Patent Appl., EP 340,645 (1989); Chem. Abstr., 112, 2162988 (1990).

8. Sh. Tang, J. Xue, X. Wang, Y. Cao and X. Wang, Chin. Chem. Letters, 2, 1 (1991); Chem. Abstr., 115, 114049~ (1991).

9. K. Toyohiko and T. Haruki, Europ. Patent Appl., EP 54,410 (1982); Chem. Abstr., 97, 115169g (1982).

10. W. J . Evers, B. D. Mookherjee, A. van Ouwerkerk and A. G. van Loveren, US Patent, 4434085 (1984); Chem. Abstr., 100, 197666j (1984).

11. H. Spreitzer, Monatsh. Chem., 123, 587 (1992). 12. R. L. Snowden and K. H. Schulte-Elte. Helv. Chim. Acta,

64, 2193 (1981). 13. P. K. Freeman, D. M. Balls and D. J. Brown, J . Org.

Chem, 33, 2211 (1968). 14. G. Buchbauer and E. Klissenbauer, Monatsh. Chem.,

109, 499 (1978). 15. G. Ohloff and W. Giersch, Helv. Chim. Acta, 63, 76

(1980). 16. H. Spreitzer, P. Muller and G. Buchbauer, Monatsh.

Chem., 121, 963 (1990). 17. G. Vernin and G. Vernin in The Chemistry of Heterocyclic

Flavouring and Aroma Compounds. ed. G. Vernin, p. 72, Ellis Horwood, Chichester (1982).

18. G. Buchbauer, A. Hillisch, K. Mraz and P. Wolschann, Helv. Chim. Acta, 77, 2286 (1994).

19. 0. Motl. V. Herout and F. Sorm, Colf. Czechosl. Chern. Comrnun., 23, 1293 (1958).

20. C. Pascual, .I. Meier and W. Simon, Helv. Chim. Acta, 49, 164 (1966).

21. D. Varech, M. J . Brienne and J . Jacques, J . Chem. Res ( M ) , 3628 (1979).

22. W. Sturm in Geruch- und Geschmackstoffe. Proceedings of the International Symposium of Haarmann & Reimer, 2-4 October 1974, Bad Pyrmont, Germany, ed. F. Drawert, p. 265, Hans Carl Verlag, Niirnberg, (1975).