CA1213613A

CA1213613A - Alicyclic ketone and alcohol derivatives

Info

Publication number: CA1213613A
Application number: CA000390234A
Authority: CA
Inventors: Brian J. Willis; Robert G. Eilerman; John M. Yurecko, Jr.
Original assignee: Fritzsche Dodge and Olcott Inc
Current assignee: Fritzsche Dodge and Olcott Inc
Priority date: 1981-11-17
Filing date: 1981-11-17
Publication date: 1986-11-04

Abstract

ABSTRACT OF THE DISCLOSURE

Alicyclic ketone and alcohol derivatives having the structure:
wherein the dotted line represents a carbon-carbon double bond or a carbon-carbon single bond; wherein Z is or ;
and wherein each of R1, R2, R3, R4, and R5 is hydrogen or lower alkyl are useful as odor-modifying ingredients in perfumes and perfumed products and as flavor-modifying ingredients in foodstuffs and tobacco products. These derivatives may be prepared from substituted phenols having the structure:

Description

1~13613 BACKGROUND OF THE INVENTION

There is considerable demand for materials which are useful in modifying, enhancing, or improving the organoleptic properties of consumab-le products. The natural oils which traditionally have been used for this purpose suffer the disadvantages of limited supply, high c05t, and variable quality. Accordi~gly, the search for synthetic compounds which can function as partial or total replacements for essential oils or which can be used to create new flavor and fragrance materials has intensified.

Various substituted cyclohexane derivatives~having useul organoleptic properties are known. For example, Arctander, Perfume and Flavor Chemicals, Vols. 1 and 2,tl969~ Mont-clair, N.J. (U.S.A.l~d~s the following compounds and their use in perfume and flavor compositions:
tl) "166 : para-tertiary-AM~LCYCLO~E3a~ONE

~

Very powerful, diffusive, woody-c~mphoraceou~ odor, slightly earthy, yet with some resem~lance to Orris root, overall very dry."

(2) "1749 : l-HYDROXY 2-METHYL-4-tertiary-AMYLCYCLOHEXANE

~

~213G1 3 qH

¢ ~

Woody-rootlike, dry-sweet and very tenacious odor with resemblance to Vetiver, Cedar and Amyris."

(3) "2061 : METHYL-2-iso-HEXYL-4-CYCLOHEXANONE-l ~ ~

~l 2~ ~arm, mild, but tenacious musky-orrislik~ odor. The camphoraceous notes so often encountered in cyclohex-anone derivatives, are pleasantly subdued and generally accepted as Orris-like rather ~han Camphor-like. n

(4) "3001 : 1,1,3-TRIMETHYL-2-CYCLOHEXANONE-4 2~4~4-Trimethyl-2-cyclohexen-l-one o 3Q ~

Powerful and rather pungent, but in dilution pleasant, warm-herbaceous and minty-camphoraceous odor, reminiscent of Tansy oil or Dalmation Sage oil."

1~13613 - In addition, Chemical Abstracts, 8~, 197052 k (Japanese Patent No. 78 895,942) discloses preparation o~ the compound having the structure:

rh Finally, Chemical Abstracts, 68, 39828~ej(L.M. Shulov, et al., Zh. Org. Khim., 3,1819 (1967) dïscioses preparation of the bicyclic derivative having the structure:

0~
This compound is described as having the fragrance of fresh greens.
Although the preceding compounds are known, no description of the compounds of this invention and no prediction of the compounds or of their advantageous organoleptic properties is known in the prior art.
3~

12~3613 Sl~MMARY OF THE INVENTION

Novel compounds, havLng the struct~re:

~ 3 ~2 wherein the dotted line represents either a carbon-carbon double bond or a carbon-carbon single bond; w~erein Z
is either ~ I ~ or ~ ~ ;

and wherein each of Rl, R2, R3, R4,and R5 is hydrogen or lower alkyl, are useul as odor-modifyi~g ingredients in perfumes and perfumed products and as flavor-modifying ingredients in foodstuffs and tobacco products.

The compounds may be prepared by treating substituted phenols havin~ the structure:

~ ' ~Z136~3 with isoprene or 3-methyl-3-buten-2-ol to fo~m prenylated phenols having the structure:
oa R ~ ; and R3 ~ 4 converting the prenylated phenols to the csmpound~ of this invention.

DETAILED DESCRIPTION O~ THE INVENTION
.
New flavors, flavoring compositions, perfumes, perfumed a~ticles, and tobacco products can be produced by including therein effective amounts of one or more novel 20 alicyclic ketone or alcohol derivative having the structural formula:

~ R3 wherein ~he dotted line represents a carbon-carbon double 3Q ~ond or a carbon-carbon single bond; wherein Z is either ~ or ~ ~ ;

12~3~1 3 and wherein each of Rl, R2, R3, R4, and R5 is hydrogen or lower alkyl, that is, Cl to C4 alkyl, particularly, methyl or ethyl. The compounds of this invention can exist in several stereoisomeric forms. Therefore, the structural formulae used herein are intended to embrace the individual stereoisomers as well as mixtures thereof.

In accordance with one embodiment of the invention, compounds I may be produced from substituted phenols having ~he structure:
OH
R ~ 1 II

wherein each of Rl, R2, R3, and R4 are a~ deined for compounds I. Treatment-of phenols II with either îsoprene or 3-methyl-3-buten-2-ol in the presence of a mineral acid according to k~own methodology (see, for example, J. Amer. Chem. Soc., 80, 3073 (1958) and Chemical Abstracts, 50, 1654 ~1956~ results in formation ofprenylated phenols having the structure: ~

R ~ ~Rl4 III

Phenols III may also ~e prepared by a modification of the method of Dewhirst and Rust (J. Org. Chem., 28, 798 (1963l) ~213~3 which involves reacting isoprene with phenols II in the presence of a catalytic quantity of the corr2sponding aluminum phenoxide.

Conversion of prenylated p~enols III to compounds I may be accomplished ~y the routes outlined in Schemes A and B. Thus, as shown in Scheme A, compounds I may be lQ prepared by hydrogenation of III in the presence of a metal catalyst such as palladium on carbon, or Raney nickel. In this reac~ion, solvent~ such as lower alcohols, acetic acid, or mixtures thereof can be employed at t2mperatures ranging from about 25 to about 300C, and at variable pressures, the exact conditions depending upon the product desired. For example, hydrogenation of 2,6-dimethyl-4-(3-methyl-2-butenyllphenol in the presence of palladium on carbon at temperatures in the range from about 150 to 2000e and at pressures from about 200 to 300 psig results in formation of cyclohexanone V
1 R2 CH3; R3-= R4 = H) whic~ is useful in perfume a~d flavor compositions.

Alternatively, 2,6-dimethyl-4-(3-methyl-2-butenyl~phenol may be ~educed to alcohol IV (wherein Rl = R2 = CH3; R3 =
R4 = H) in acetic acid with platinum oxide at temperatures from about 50 to 100C and pressures from about 200 to 300 psig. The resulting alcohol also possesses interesting organoleptic properties.

~36~3

5 SCHEME A

OH QH
R~ ~I

5 )~
III /IV

~1 R2~Rl R3~R4 3~--R4 V

12~3~

g OH ~C~3 OCH 3 RRZ3~ ~ J~Rl ~R

III VII / VIII

30 ~4 E~R4 IX X

12~3613 In addition, alcohol IV may be oxidized with a suitable oxidizing agent such as "Jones" reagent, pyridinium chlorochromate, or sodium dichromate - sulfuric acild according to known methods to form the corresponding ketone V.(See H~ O. House, Modern Synthetic Reactions, 2nd ed., ~. A. BenjamIn, Inc.,p.257, (1972)).

Ketone V may ~e converted to alco~ol VI b~ reacting the ketone wit~ an organometallic derivative such as a Grignard reagent (e.g. R5MgX~ or an organol;t~ium compound (e.g. R5Li) wherein R5 i5 lower alkyl,that is, Cl to C4 alkyl. This reaction is desirably carried out with a stoichiometric quantity of the organolithium reagent or with excess ~2 or 3 equivalents) Grignard reagent.
~he reaction is preferably carried out i~ a suitable solvent such as diethyl ether or tetrahydrofuran under an inert atmosphere such as nitrogen or argon, and at temperatures in the range from about -10 to 50C.
Hydrolysis of the resulting organometallic adduct is accompiished with ice-cold dilute mineral acid,or preferably, with saturated ammonium chloride solution, and resul-ts in formation of alcohol VI. After recovery and purification, alcohol VI may be utilized in perfume or flavor compositions.

In a further embodiment of the invention outlined in Scheme B, the phenolic hydroxyl group in compound III
may be converted by etherification to methyl ether VII. This transformation may be effected by known techniques~ (See J. Mar~h, Advanced Organic Chemistry, 2nd ed., McGraw-Hill Book Company, p. 357, (1977)). For example, the phenol may be treated with an alkali metal hydroxide such as aqueous sodium hydroxide, followed by alkylation with dimethyl sulfate at a temperature from about 25 to 80C.

lZ13~13 If desired, reduction of the oleflnic bond in ether VII may be carried out with hydrogen gas in the presence of a hydrQgena~ion catalystA~uc~-as~-5%-palla~i~m o-n carbon or Raney nickel. This reaction,which is preferably carried out in a Parr reaction vessel at a pressure from about 20 to 80 psig results in production of saturated aromatic ether VIII. Ether VIII may then be converted to enone IX by subjecting the ether to dissolving metal reduction involving treatment with an alkali metal, such as lithium or sodium, in a mixed solvent system containing ammonia or a lower alkyl amine (e.g. CH3CH2NH2~, an ether such as diethyl ether or tetrahydrofuran, and a lower alcohol.
Desirably, the reaction is carried out with excess sodium ~5 to 10 e~uivalents) in liquid ammonia containing tetra-hydrofuran and t-butyl alcohol; the ratio of ammonia ;
tetrahydrofuran : t-but~l alcohol being 2 : 1 : 1. This results in production of an enol ether having the structure:-QC~3 R ~ XI
R3 ~ 4 ~ ~

which is purified by chromatography. The so-formed enol ether can be hydrolyzed in the presence of an aqueous mineral acid (e.g. HCl) containing a cosolvent such as acetone or tetrahydrofuran at room temperature to produce enone IX which has valuable organoleptic properties.

Reduction of the carbonyl in compound IX with a suitable metal hydride such as diisobutylaluminum hydride or lithium aluminum hydride yields alcohol X wherein R5 is hydrogen.
Alcohol X is also useful in perfume or flavor compositions~

Alternatively, the enone IX may be reacted with an approp-riate organometallic reagent (e.g. R5MgX where R5 is lower alkyl~under conditions similar to those de~cribed above for ketone V; this leads to formation of alcohol X wherein R5 is lower alkyl.

Recovery and purification of the varioas final products of the present invention is achieved by conventional techniques including extraction, distillation, crystalLîzation, preparative chromatographic separation and the like.

The alicyclic ketones and alcohols of tki9 in~ention possess distinctive balsamic, woody, sweet, rooty, musty, earthy, leathery, citru~-like, herbaceous odors, and are useful in fine fragrances and in perfumed product~ such as soaps, detergents, deodorants, cosmetic preparations and the like.

One or more of the alicyclic ketones and alcohols and co~ventional ~ragrance ingredientg, for ex2mple, alcohols, aldehydes, ketones, nitriles, esters and essential oils, may be admixed in varying quantities to produce desired fragrances. In this manner, perume compositions may be prepared which are carefully balanced, harmonious blends and which include essential oils, aroma chemicals, resinoids and other extracts of natural odorou~ materials, each ingredient imparting a characteristic effect to the-total composition. In such compositions, one or more of the alicyclic ketones or alcohols of the invention can be employed to impart uniques characteristics.

Such compositions may contain up to about 80 percent by weight of at least one alicyclic ketone or alcohol of this invention. Ordinarily, at least about 0.001 percent ~y weight of alic~clic k~t~ne or alcohol is xequlred to impart significant odor charac~eris~i.cs~ Amoun~s in ~h~
range of from.afiout 1 ~o a~out 6~ perce~t hy ~eight are preferred. The alicyclic ketQnes and alcohols o~ this invention ma~ ~e formulated into con~c~trates containing from a~out 1 t~ a~out 6~ percent ~y weigh~ in~.an appropriate solvent. Suc~ concentrates may then ~e employed to fomulate such products as colog~es, soaps, etc., wherein the final concentration of the compound or compounds can vary from about 0.001 to about 7 percent ~y weight, depending upon the final product. F.or example, the concentration will be a~out 0.001 to about Q.l percent by weight in detergents, and about 0.01 to a~out 7 percent by weig~t in perfumes and colognes.

The alicyclic ketones and alcoho.l~ of thi5 invention are useful as olfactory components in detergent~ and soaps;
space odorants and deodorants; perfumes; colognes; toilet water; bath preparations such as bath oils and ~ath solids; hair preparations such as lacquers,. brilliantines, pomades and shampoo~; cosmetic preparations suGh as creams, deodorants, hand lotions and sunscreens; and powders such as talcs, dusting powders and face pcwders.

The alicyclic ketones and alcohols of this invention have also been found use~ul in altering t~e 1avor component or components.of flavor compositions. Thus, the compounds are effecti~e Ln imparting a certain na~ural character to artificial flavors.. The~ also can ~e employed to modify the organoleptlc prQperties of consumab.les such as che~ing gums, ~everages, pharmaceu~ical preparations, fruit juices, and the like.

12~3613 The specific 1avoring properties of the alicyclic ketones and alcohols of this invention depend upon the type of product to which ~hey are added. In general, they develop woody, earthy, minty, fruity, citrus-like flavor notes or combinations thereof. Therefore, they can be employed advantageously in certain citrus products such as orange oil to round off the taste and in pineapple flavors to lQ enhance the taste and aroma.

In flavor compositions,~he concentration of the alicyclic ketones and alcohols can also vary widely depending upon the organoleptic properties desired. Typically, interesting flavor effects can be obtained with concentrations from about 0.QQl to a~out 1 percent by weight of the compound or compounds in the final flavor compo~ition. In some situations, higher concentrations are required to produce special flavoring effects. For example, in arti~icial flavor compositions, one or more compounds may ~e incorporated in amounts such that the total is za percent by weight or higher.

One or more of the alicyclic ketone~ or alcohols of this invention may also ~e added to smoking tobacco or synthetîc tobacco where they impart woody, am~er-like, and cedarwood note~ to the tobacco aroma. In to~acco compositions,the concentrations are preferably between about 1 and about lQ0 ppm, although in certain situations, higher levels may be usefully employed.

The following examplas are set forth to illustrate preferred methods of synthesizing the compounds of this invention, and their use in flavor and fragrance compositions.
Where appropriate, data including data from nuclear mag-netic resonance, infrared, and mass spectra have heen lZ13~

included to conirm that various compounds have in fact been prepared. Unle~s o~herwise indicated, all percentages 5 are by weight. ~hese examples are intended only to illustrate the preferred embodiments of this invention, and are in no way meant to limit its scope.

Preparation of 2,6-Dimethyl-4-(3-methyl-2-butenyl~phents~
OH OH
15 ~ + ~~ >~
/

To a mixture of 2,6-dimethylphenol 1122 g, 1 moll and 85%
phosphoric acid (60 mL) was added 2-methyl-3-buten-2-ol (103 g, 1.2 moll with efficient stirring at 35 - 43C
during 1 h. After stirring for an additional 3.5 h at 25C, the mixture was quenched into ice and extracted with hexane. The conibined hexane extracts were~ washed success-ively with IN sodium hydroxide ~100 mL), 5% sodium bicarbo-nate (300 mL) and brine (200 mL) . The organic layer was dried, the solvent evaporated-, and the residue fractionated to yield 92 g of 2,6-dime~hyl-4-~3-methyl-2-butenyl) phenol bp 108 - 111e (1 mm). l~ CDC13) ~1.7 (6 H, s), 2.2 (6 3û H, s), 3.2 (2 EI, bd), 4.4 (1 H, s, exchanged with D201, 5.3 (1 H, m), 6.8 (2 H, sl. IR (film) 350û, 1225, 1150, 870 cm 1. MS (m/el 190 (M~), 175, 160, 135, 91.

~2~3~13 EX~MPLE 2 _ Preparation of 2~3,6-Trimethyl-4-(3-methyl-2-butenyl)phenol OH OH
10 ~ ~~ ~

2,3,6-Trimethylphenol ~68 g, 0.5 mol~ and formic acid (100 mL) were com~ined and warmed to 50 - 55C with vigorous agitation. To this mixture was added 2-me~hyl-3-buten-2 ol (47.3 g, 0.55 mol) dropwise over 0.25 h.
The reaction mixture was stirred for an additional 2 h at 50C, and then quenched into water (300 mL~. The crude product was isolated by extraction with toluene (3 x 100 mL) followed ~y washing with water (20a mL~, 5~ sodium bicarbonate ~2 x 1~0 mL~, and brine ~3 x 100 mL). Evaporation of the solvent and distillation afforded 61 g of the phenol, bp 145 - 15~C (2mm~. NMR (CDC1 ~1.7 (6 H, s~, 2.2 (9 H, s~, 3.2 (2 H, bd~, 4.4 ~1 H, s, exchanged with D2O), 502 ~1 H, m~, 6.8 (1 H, s~. T~
(film) 3700, 1460, 1200, 1090 cm 1. MS (m/e~ 204 ~M~ , 189, 174, 190, 136.
~XAMPLE 3 Pxeparation of 2,3,5,6-Tetramethyl-4-(3-methyl-2-butenyl)phenal The phenol was prepared by the method described in Exam-ple 2 ex~ept 2,3,5,6- teb~methylphen~l wa5 used ~ tead of t~e tri-~13613 methylphenol. ~e phenol was recrystallized from hexane, mp 105 -- 106C. N~R (.CDC13) 2.2 (12 ~, s), 2.7 ~6 X, 2 s), 3.3 (.2 H, d~, 4.5 (1 EL, s, exchanged with D2Ol. IR (C~C13~
3590, 2700, 1440, 1200, 1090 cm 1. MS (,m/e) 218 ~.~+~, 203, 188, 150, 135.

10 ' Hydrogenation of 2,6-Diméthyl-4~ .3-methyl-2-butenyl3 phenol OH O OH
15 ~ +

A B
The data set forth in Table I show the results obtained upon hydrogenation of 2,6-dimethyl-4-(.3-methyl-2-butenyl~
phenol using several di~ferent catalysts and solvents.
TABLE I

Example Catalyst Solvent Pre~sure Temp. Result (psiy) (C) 4 PtO2 HO~c:,200-30û 50 ~9596al~0hol B
5% Rh/C hexane50-7Q 25 50.% ketone A
50% alco~ol B

6 5% Pd/C neat200-300 175 70% ketone A
3û% alcohol B

7 5% Pd/C neat 300 200 40% ketone A
60% alcohol B

~2~3613

8--The reaction conditions of Example 4 resultedLn formation of 2,6-dimethyl-4-(3-methylbutyl)cyclo~exanol, ~p ~8 -101C (3 mml. GLC analysis of this alco~ol sho~s it to ~e mainly (86%) one isomer. NMR ~CDC13~ ~0.8 - 1.1 (12 H, m~, 1.1 - 2.0 (.13 H, complex pattern~, 3.5 ~1 H, b5~. IR (~ilml 3450, 1160, 970,. 935 cm . MS (m/e2 lg8 (M~), 109, 71, 59,85.

Preparation of 2,6-Dimethyl-4-(3-methylbutyl)cy~lohexanone-0~ 0 ~ ~ ~

Jones reage~ (.150 mL) was added dropwise at room temperature to a solution of 2,6-dimethyl-4-(.3-methy~utyllcyclo~exanol (100 g, 0.5 mol, produced according to Example 4) in acetone (3,000 mL). The reaction mixture wa~ stirred ~or 1 h and isopropanol added to decompose excess Jones reagent. T~e salts were removed ~y iltration and the solution concen-trated on a rotary evaporator. The residue was taken up in ethyl acetate and washed successively with ~ater ~400 mL~, 5% sodium bicarbonate (.200 mLl and brine (200 mL~. The organic layer was dried, the solvent evaporated, and the residue fractionated to yield 71 g of the ketone, bp 26 -100C (3 mm). NMR (CDC13~ ~ 0.8 - 1.1 (12 H, m), 1.1 - 3.2 ~12 H, m1. IR (.film) 1725, 114~, 990 cm . MS ¢m/e~ 196 ~M~), 69, 82, 97, 41.

EXAMPhE ~
Preparation o 1,2,6-~rimethyl-4-(3-methylbutyl~cy~lo~exanol ~ CH3MgI

To a Grignard solution prepared from magnesium (.14.5 g, ~.
g-atoml and methyl iodide (85.2 g, 0.6 mol) in anhydrous ether (5Q0 mL) wa~ added 2,6-dimethyl-4-~3-met~ylbutyll cyclohexanone (59 g, 0.3 mol, produced according to Example 8~ over 1 h at 15 - 20C. The mixture wa~ ~tirred for an additional 1 h and then quenched i~to-~aturated ammonium chloride solution. The layers ~ere separated and the aqueous solu~ion ~as extracted with ether. The combined extracts we~e washed with 5~ ~odium bicarbonate solution, brine and then dried. Solvent removal and di~tillation gave 40 g of the aLcohol, bp 92C (1 mm). NMR (CDC13~ ~ Q.8 - 1.1 (12 H, m), 1.1 - 2.2 (16 E, complex pattern with a ~inglet at 1.2~ (film) 3550, 1025, 920, 890 cm 1, MS (m/e 212 (M+~, 85, 43, 57, 86.

Preparation of 2,3,6-Trimethyl-4-(3-methylbutyl)cyclohexanol ~3~i3 -2a-~ OH

10 ~ 1 A mixture of 2,3,6-trimethyl-4-(3-methyl-2-butenyl)phenol ~30 g, 0.15 mol), platinum oxide (3 g~, and acetic acid (150 mL) was hydrogenated at 50C and 200 - 30n psig until hydrogen ~ptake ceased. The mixture was filtered to remove the catalyst and the filtrate pouxed into ~ater. The product was extracted with ethyl acetate and the extract washed successively with water, 5% sodium bicarbonate solu~ion, and brine. The organic layer was dried, the solvent removed, and the residue fractionated to afford 17 g of the desired alcohol, bp 105 - 110C ~1 mm~. NMR (CDC1 0.7 - 2.2 (27 H, complex pattern), 3.6 (1 H, bs). IR
(film~ 37aQ, 1500, 1020, 970 cm . MS ~m/e) 212 ~M+), 123, 35, 69, 95.

Hydrogentation of 2,3,5,6-Tetramethyl-4-(3-methyl-2-butenyl)phenol OH OH

Pd/C 7 12~3613 2~3~5~6-Tetramethyl-4-(3-methyl-2-~utenyl~phenol (lQ g, 0.046 mol, prepared according to Example 3)~ 5% palladium on carbon (1 g~, and cyclohexane ~2~ mL~ ~ere mixed ~n an a~toclave and heated to 160C under 250 - 30Q psig o~
hydrogen. When hydrogen uptake ceased, the mixture was cooled, an additional amount of 5% palladium on carbon (1 g) added, and hydrogenation continued until no more phenol was detected. The cooled reaction mixture was filtered, the solvent evaporated, and the residue distilled to yield 7 g of material, bp 92C (0.5 mm). Spectral analysis (nmr, glc/ms, ir) of the distillate confirmed the presence of both ketone and alcohol in the hydrogenation product (20% and 80% respectively2.
ketone: MS (m/e) 224 (M+~, 137, 83, 69, 85 alcohol: MS (m/e) 208 (Ml-18~, 137, 69, 83, 55 Preparation of 2,6-Dimethyl-4-(3-methylbutyl2anisole O~ OCH3 OCH3 ~ ~

A solution o~ dimethyl sulfate (100 g, 0.79 mol) and 2,6-dimethyl-4-(3-methyl-2-~utenyl)phenol ~40 g, 0.21 mol2 was added over 0.5 h at 30 - 50C to a solution of sodium hydroxide (50 g, 1.25 mol) in water (50 mLl con~aining Adogen 464 (6 g). The reaction mixture was agitated overnight followed by addition of water (200 mL~.

~Z~3613 The product was isolated by extraction ~ith toluene ~2 x 150 mL), and the combined extract5 washed with water. T~e solvent was evaporated and the residue distilled to afford 33.5 g of the desired ether, bp 109 - 110 ~3 mm). NMR
(CDC13) ~ 1.7 ~6 H, s), 2.1 (6 H, s), 3.2 (2 H, d), 3.7 (3 H, s), 5.3 (1 H, m), 6,B (2 H, g~. IR (film) 1225, 1150, 1050, 870 cm 1, MS (M/e~ 204 (~), 189, 173, 91.

A solution of 2,6-dimethyl-4-(3-methyl-2-butenyl!anisole (10 g, 0.05 mol) in isopropanol (20 mL), together with 5% palladium on car~on (0.1 g) was hydrogenated in a Parr apparatus until t~e theoretical amount of hydrogen had been consumed. The catalyst was removed by iltration and the solvent evaporated to give a clear residue which was ~ractionated to afford 7.1 g of the desired product, bp 102 - 105C (2 mm). NMR (CDC13) ~ 0.9 (6 H, d), 1.1 -2.0 ~3 H, m), 2.2 ~6 H, s), 2.5 (2 H, t~, 3.7 (3 H, s~, 6.85 (2 H, s~. IR (iLm) 30ao, 1225, 1025, 870 cm . MS
(m/e) 206 (M~), 149, 150, 135, 191.

Preparation of 2,6-D~methyl-4-(3-methylbutyl)2-cyclohexe~- 7 -oné.

~

A solution of 2,6-dimethyl-4-(3-methylbutyl)anisole (8.5 g, 12~36~3 0.042 mol, prepared according to Example 12l,in a mixture of t-butyl alcohol (180 mL~ and tetrahydrofuran ~180 mL~
was added Witl efficient stirring to ammonia at -30C.
To the resulting solution was added sodium metal (15 g, O.Ç5 g-atom) in small portions over 1 h. The mixture was stirred for an additional 3 h at -30C followed by cautious addition of methanol ~100 mL). The amm~nia was allowed to evaporate and water (500 mL) was added. The mixture was extracted with hexane, washed with water, and dried. Solvent removal afforded 8.0 g of the enol ether. A small sample was purified by chromatography to obtain spectral data. NMR (CDC13~ ~ 0.8 - 1.2 (9 H, m), 1.2 - 3.0 (9 H, complex pattern with broad singlet at 1.7), 3.6 ~3 H, ~), 5.4 (l H, bs). IR ~film~ 1672, 1450 cm l MS ~m/e] 208 (M~), 137, 71, 43, 91.

The enol ether was added to a mixture of acetone (150 mL~
and 6N HCl ~16 mL~ and stirred at room temperature for 20 h. The acetone waæ removed on a rotary evaporator and residual liquid extracted with hexane. The combined hexane extracts were washed with 5~ sodium bicarbonate and brine. The organic layer was dried, the solvent evaporated, and the crude enone purified by silica gel chromatoyraphy thexane/ethyl acetate 90:10~. ~he enone was a mixture of two isomers by glc (65:35). NMR (CDC13) ~ 0.7 - 1.2 (6 H, complex), 1.2 - 2.6 (12 H, complex with singlet at 1.8), 6.6 (1 H, bs). IR (film) 1690, 1490, 1050 cm . MS (m/e) 194 (M'), 95, 82, 96, 109.

-2~-Preparation of 2,6-Dimethyl-4-(3-methylbu~yl~-2-cyclohexen-1-ol '~ ~

J J

A suspension o lithium aluminum hydride ~0.5 g, 0.013 mol) in anhydrous diethyl ether (100 mL) was stirred at 10C
under nitrogen while 2,6-dimethyl-4-(3-methylbutyll-2-cyclohexen-l-one (5.8 g, 0.03 mol2 in anhydrous ether (10 mL) wa~ added over a period of 30 minutes. ~he mixture was stirred at room temperature for 3 hours;
then it was treated successively with ~at~r (0.5 mL), 15% NaOH solutiQn (0.5 mL~, and water (1.5 mL). The solution was filtered, dried and concentrated to give the crude alcohol. Short path distillation afforded 5.0 g of 2~6-dimethyl-4-(3-methylbutyl)-2-cyclohexen-1-ol, bp 90 - 95C (1 mm2, as a mixture of isomers by glc/ms (65.5%, 28%, and 5.5%). NMR (CDC132 ~ 0.9 - 1.6 (19 H, complex), 1.8 (3 H, bsl, 3.6 (1 ~, ml, 5.4 (1 H, m2.
IR (film) 3300, 1040, 1010 cm 1. MS (m/el 196 (M+), 98, 82, 125, 107.

~z~36~

Preparation of 3,5-Dimethyl-4-(3-methyl-2-butenyl)phenol A solution of 3,5-dimethy~henol (122 g, 1 mol) in dimethyl~
acetamide (200 mL) was added over 2 h at 30 - 40C to a ~lurry of 50~ sodium hydride (60 g, 1.25 mol) in dimethyl-acetamide (1500 mL). The reaction mixture was stirred at 50C for an additional 2 h, cooled to 30C and prenyl chloride (155 g, 1.5 mol~ was added over 1 h. After stirring at 50C overnight, the mixture was cooled and quenched into water ~4,000 mL~. The product was extracted with toluene (4 x 300 mL~, and the combined extracts washed with brine. The solvent was evaporated and the residue fractionated to give 142 g o~ the prenyl ether, bp 106 -110C (3 mm). NMR (CDC13~ ~ 1.8 (6 H, bs), 2.3 (6 H, s~, 4.4 (2 H, d), 5.5 ( 1 H, m~, 6.5 (3 H, s). IR (film2 1600, 12~0, 1050 cm~l. MS (m/e~ 190 (M~, 122, 107, 6~, 41.

The prenyl ether (80 g, 0.42 mol~ was heated in a nitrogen-purged autoclave for 24 h at 170 - 180C. The crude material o~tained by this process was distilled to afford 67.8 g o~ 3,5-dimethyl-4-(3-methyl-2-butenyl~phenol, lZ~3613 bp 115 - 120~C (0.5 mm~. The phenol ~as recrystallized from hexane, mp 64- 65C. NMR (CDC13) ~ 1.6 (3 H, bs), 1.8 (3 H, bs~, 2.2 ~6 H, s), 3.2 (2 H, b~), 4.9 (1 H, m~, 5.3 (L H, exchanged wi~h D~O), 6.5 (2 H, s). IR (CHC13) 3350, 159Q, 1210, 740 cm 1. MS (m/e) 190 (M+), 175, 134, 135, 160.

Hydrogenation of 3,5-Dimethyl-4-~3-methyl-2-butenyl2phenol 3,5-Dimethyl-4-~3-methyl-2-butenyl)phenol (25 g, Q.13 mol, prq~d according to Example 151, 5% palladium on carbon (1.25 g) and sec-butyl alcohol (10 mL) were mi~ed Ln an autoclave and heated to 200C under 250 - 300 psig of hydrogen. When the hydrogen uptake ceasea, the mixture -was cooled, an additional amount of 5% palladium on carbon (1.25 g) added, and hydrogenation continued until no more phenol was detected. The cooled reaction mixture was iltered, the solvent evaporated and the residue distilled to afford 19 g of material, bp 105 - 113C t3 mm). Spectral analysis tnmr, ir, glc, ms) of the distillate confirmed the presence of both ketone and alcohol (39~ and 61% res-pectively) in the hydrogenation product.

~Z13~;13 ketone : MS ~m/e~ 196 (M+~, 69, 41, 55, 57 alcohol : ~S (m/e) 180 (M~-18~, 109, 43, 55, 57 A perfume base wa~ prepared by mixing the foliowing:
10 Component %
Isobutyl quinoline/l~ in DEP 0.1 Furfural/l~ in ~EP Q.l Geraniol 0.1 Methyl nonyl ketone 0.1 15 Cedrol 0.2 Gera~yl aceta~e 2.6 Terpinyl acetate 4.0 Dipropylene glycol 7.0 Ionone residue 8.2 20 Oil Copaiba 13.1 Cedarwood acetate 13.2 Oil Guaiacwood 16.3 2,6-Dimeth~1-4-(3-methylbutyl~ 35.0 cyclohexanol 100 . O

A perfume base was prepared by mixïng the following:
30 Component %
Oil Copaiba 1.0 Benzyl.cinnamate 2.0 Oil Guaiacwood 2.5 Cedrenyl acetate 5.0 35 Oil Balsam gurjon 85.Q
2,6-Dimethyl-4-(3-methylbutyl~ 4.5 cyclohexanone 100 . O

lZ~3P~3 A floral bouquet was prepared by mixing th.e ollowing;
Component %
Musk ketone 1.0 Coumarin: 1.Q
Methyl everninate 0.5 Oakmoss absolute Q.5 10 Geraniol 10.Q
Phenylethyl alcohol 16.Q
Citronellol 2.0 Geranyl acetate l.Q
Indole 10% 1.0 15 Rose otto 3,Q
Rose oxide 10% l.Q
~ydroxycitronellal 14.Q
Pentadecanolide l.Q
Methyl dihydrojasmonate lQ.Q
20 Hexyl cinnamic alcohol lQ.Q
Benzyl acetate 1.0 Oil Ylang extra Q.5 Cinnamic alcohol Q.5 Phenylethyl acetate Q.5 25 Gamma undecalactone 10~ 0.5 Cyclamen aldehyde Q.5 Ionone alpha Q.5 Methylionone gamma 4.0 Cedroxyde 4,0 30 Acetyl cedrene 8.0 Oil Bergamot rect. 3.0 2,6-Dimethyl-4-~3-methylbutyl~ 5.0 cyclohexanone 100 .0 ~213613 A viole~ fragrance composition was prepared ~y mixing 5 the following:
Component %
Musk ambrette 0.6 Jasmin absolute 0.3 Violet lea~es absolute Q.l l0 ~eliotropin l.0 Methylionone 3.0 Benzoin Siam 2.Q
Oil Cedarwood 20.0 Oil Sandalwood 30.~0 15 Oil Orris Root 4Q.0 Mixture of 3,5-dimethyl-4-~3-me.thylbutyl~
cyclohexanone and 3,5-dimethyl-4-~3-methyLb.utyl) cyclohexanol ~from process of Example 161 3~0 l00.0 A fou~ere type perfume compositi~n was prepared by mixing the following:
25 comPonent %
Coumarin 5.0 Musk ambrette 5.0 Musk aldehyde FDO 5.0 Methylionone gamma 4.0 30 Isoamyl salicylate 4.0 Oil Galbanum 0~5 Delta decalactone (.1% in DEP2 0.5 Santol FDO 4.0 : Oil Patchouly 6.0 35 Oakmoss absolute incolore 4.0 :~ Oil Neroli - Base 7.Q

~Z~3613 Oil Geranium Naroc lQ.0 Phenylethyl alcohol 3.0 Oil Bergamot 7.0 Linalool synthetic 6.0 Oil Lavender 50 - 52~ 10.0 Eugenol extra 2.Q
Isoeugenol 1.0 10 Benzyl benzoate 4.0 2,6-Dimethyl-4-(3-methylbutyl~
cyclohexanol 12.0 100 . O

An oil vetiver ~ubstitute was prepared by mLxing the following:
Component %
Oil Patchouly 1.0 20 Geraniol ex Palmarosa 1.0 Ionone residue 3. a Oil Copaiba 12.Q
Cedryl acetate 13.0 Oil Guaiacwood 16.Q
25 Oil CedarWOOd 15.0 Terpineol 5.0 Oil Bois de Rose 9,0 Mixture of 2,6-dimethyl-4-~3-methylbutyl) cyclohexanone and 2,6-dimethyl-4-(3-methylbutyl) cyclohexanol (from process 30 of Example 6) 25.
100.0 ~3613 EXAMPLE_23 A jasmin ~ragrance was prepared ~y mixlng the follo~ing:
Component Gamma undecalactone 0.5 p-Cresyl phenylacetate Q.5 Ethyl cinnamate Q.9 Oil Ylang extra 7.0 Geranyl acetate 6.0 10 Amylcinnamic aldehyde 5.0 Linalool synthetic 10.0 Benzyl acetate 20.0 Phenylethyl alcohol 20.0 Hydroxycitronellal 30'.0 2,6-Dimethyl-4-(3-methylbutyll-2- Q.l cyclohexen-l-one 100 . O

EXAMP~E 24 Modified Orange Flavor Component A(%l B~) C~%) Oil Orange 53.9 53.9 53.9 Oil Lemon 10.0 10.0 10.0 1,l-Diethoxyethane 1.5 1.5 1.5 Ethyl butyrate 3.2 3.2 3.2 Allyl hexanoate 0.6 0.6 0.6 ~inalool. 2.6 2.6 2.6 Undecanol 2.4 2.4 2.4 Benzyl alcohol 25.824.8 24.8 2,6-Dimethyl-4-(3-methylbUtyll -- 1.0 --30 cyclohexanol 2,6-DLmethyl-4-(3-methylbutyl) -- -- 1.0 cyclohexanone 10Q.0 100.0 100.0 , .

~21361 3 The above formulations ~ere added at a level of 20 ppm to a beverage medîum consisting of sugar, acid, and water.
In tests, composi.tions B and C were bot~ pre~erred over the control flavor. T~e contribution of both 2,6-dimethyl-4-(,3-methylbutyl~ cyclohexanol and 2,6-dimethyl-4-~3-methylbutyl~, cyclohexanone to the overall flavor character was.attributed to the development of a "cooked" citrus quality in the final composition.

Pineapple Flavor Composition Component At,%), B~%) C~%) Allyl cyclohexane propionate 1.4 1.4 1.4 Geranyl propionate 0.5 0.5 0.5 Allyl caproate 13.0 13.0 1.3.0 Ethy.l isovalarate 1,.0 1.0 1. a Ethyl butyrate 1.0 1.0 1.0 Vanillin 0,5 0.5 0.5 Oil Orange 1.0 1.0 1.0 Maltol 2.0 2.0 2.0 Ethyl alcohol ~95%~ . 48.5 47.5 47.5 Propylene glycol 31.1 31.1 31.1 25 2,6-Dimethyl-4-(3 methylbutyl), -- l.a --cyclohexanone 2,6-Dimethyl-4-(,3-met~ylbutyl~ -- -- 1.0 cyclohexanol 100.0 100.0 100.0 The above pineapple flavor compositions were evaluated by a panel at a Level of 30 ppm in a standard beverage medium consiæting.of sugar, acid,.and water. Compositions B and C
were both preferred over the control. There was a marked improvement in the overall flavor character resulting in a more natural flavor.

lZ13613 A chypre type perfume composition was prepared by mixing the following:
5 Component %
Oil Angelica Root 0.5 Castoreum absalute 0.5 Oil Rose 1.0 Civet absolute 1.O
10 Oakmoss absolute 1.0 Musk ~mbrett~ 2.0 Labdanum resinoid 3.0 Oil YIang extra 5.0 Benzyl acetate 6.0 15 Oil Sandalwood 7.0 Vanillin 6.0 Benzyl alcohol 9.O
Jasmin extract 12.0 Coumarin 12.Q
20 Phenylethyl alcohol 12.0 Oil Bergamot 20.0 2,6-Dimethyl-4~3-methylbutyl~ 2- 2,0 cyclohexen-l-ol lQQ .a EXÆMPLE 27 A 1% ethanol solution of 2,6-dimethyl-4-(3-methylbutyl2 cyclohexanone was sprayed on a typical smoking to~acco in an amount suficient to provide a tobacco composition containing 20 ppm of the flavor additive on a dry hasis.
Cigarettes were prepared from the treated tobacco and evaluated by a panel. In the panel evaluation against controL cigarettes the taste of flavored cigarettes was described as light and woody. The 2,6-dimethyl-4-~3-methylbutyl~cyclohexanone increased the body and fullnessof the tobacco flavor and enhanced the overall flavor character in the smoke.

Claims

WHAT IS CLAIMED IS:

1. A compound having the structure:

where in the dotted line represents either a carbon-carbon double bond or a carbon-carbon single bond; wherein Z
is either or ;

and wherein each of R1, R2, R3, R4, and R5 is hydrogen or C1 to C4 alkyl.

2. A compound in accordance with Claim 1 having the structure:

3. A compound in accordance with Claim 1 having the structure:

4. The compound of Claim 2 having the structure:

5. The compound of Claim 2 having the structure:

6. The compound of Claim 2 having the structure:

7. The compound of Claim 2 having the structure:

8. The compound of Claim 2 having the structure:

9. The compound of Claim 3 having the structure:

10. The compound of Claim 3 having the structure:

11. The compound of Claim 3 having the structure:

12. The compound of Claim 3 having the structure:

13. The compound of Claim 3 having the structure:

14. The compound of Claim 3 having the structure:

15. A fragrance composition which comprises at least one compound in accordance with Claim 1 in an amount effective to impart fragrance thereto and conventional fragrance ingredients.

16. A fragrance composition which comprises at least one compound in accordance with Claim 2 in an amount effective to impart fragrance thereto and conventional fragrance ingredients.

17. A fragrance composition which comprises at least one compound in accordance with Claim 3 in an amount effective to impart fragrance thereto and conventional fragrance ingredients.

18. The fragrance composition of Claim 16 wherein the compound has the structure:

19. The fragrance composition of Claim 16 wherein the compound has the structure:

20. The fragrance composition of Claim 16 wherein the compound has the structure:

21. The fragrance composition of Claim 16 wherein the compound has the structure:

22. The fragrance composition of Claim 16 wherein the compound has the structure:

23. The fragrance composition of Claim 17 wherein the compound has the structure:

24. The fragrance composition of Claim 17 wherein the compound has the structure:

25. The fragrance composition of Claim 17 wherein the compound has the structure:

26. The fragrance composition of Claim 17 wherein the compound has the structure:

27. The fragrance composition of Claim 17 wherein the compound has. the structure:

28. The fragrance composition of Claim 17 wherein the compound has the structure:

29. A flavor composition useful for improving, modifying or enhancing the organoleptic properties of a foodstuff which comprises at least one compound in accordance with Claim 1 in an amount effective to impart flavor thereto and conventional flavoring ingredients.

30. A smoking composition comprising a smoking material and at least 0.0001% by weight of at least one compound in accordance with Claim 1.

31. A method of preparing a compound having the structure:

wherein the dotted line represents a carbon-carbon double-bond or a carbon-carbon single bond, wherein Z is either or ;

and wherein each of R1, R2, R3, R4 , and R5 is hydrogen or C1 to C4 alkyl which comprises:
reacting a substituted phenol having the structure:

with isoprene or 3-methyl-3-buten-2-ol to form a prenylated phenol having the structure:

; and converting the prenylated phenol to said compound.