SUBSTITUTED CYCLIC ALCOHOLS,METHODS OF PREPARING AND COMPOSITIONS CONTAINING SAME

Abstract: Novel compounds useful as fragrance materials which have the structure (FORMULA) wherein the dashed line may be either a carbon-carbon single bond or a carbon-carbon double bond. The invention also provides methods of preparing these compounds from the reaction products of acetoacetic esters and 2, 2, 3-trimethyl-3-cyclopenten-1-acetaldehyde and fragrance compositions which include the compounds.

Description: SUBSTITUTED CYCLIC ALCOHOLS, METHODS OF PREPARING AND COMPOSITIONS CONTAINING SAME Background of the Invention The use of alkyl-substituted cyclohexenols and cyclohexa- nols as fragrance and flavoring materials is well known. One example is carveoi which has the general structure (-) -carveoi is a natural component of spearmint oil- (+) - carved " has been found in the oils of Fortunella margarita, Anethum graveolens and Heracleum canescens. Further exam¬ ples may be found in Actander, Perfume and Flavor Chemicals 20 (1969) . For example, trimethylcyclohexanol which has the structure is identified as compound no. 2998 in Actander. Its frag¬ rance is described therein as a powerful menthol-like odor 30 but more camphoraceous and less cooling than menthol. With regard to flavor, it is described as having a camphor¬ aceous, menthol-like taste. Actander compound no. 432 is ortho-tertiary-butylcyclohex- 35 anol which has the structure (CH 3 ) 3 •and is described as having a powerful camphoracεous-pine mostly minty and somewhat tarry odor of great tenacity. Compound no. 433 of Actander, para—tertiary-butylcyclohe anol, having the structure is described as having an extremely dry, woody, camphora cεous, almost tarry odor with a leather-like undertone. is useful in perfume compositions to lend power and diff iveness. It is used in soap fragrances along with woody notes, ionones, Cedarwood oil derivatives, and the like. 3-(ϊso-camphyl-5) -cyclohexanol, compound no. 566 of Acta er, has the structure This compound has a very tenacious, mild Sandalwood-type odor that is not as sweet and balsamic as Sandalwood oil and not nearly as powerful in active use. This material used in perfume, compositions for its Sandalwood characte and economical stability. Chemicals having the 2,3,3-trimethylcyclopentene skeleto are also well known in the art of perfumery and flavor chemistry. For example, 2,2,3-trimethyl-3-cycopenten-l- ' ace aldehyde having the structure ^ has been found in the oils of Juniperus communis L. and Lavandin. The corresponding acid has been found in Olibanum oil, U.S. Patent No. 4,052,341 discloses the use in fragrance com¬ positions of 3-methyl-5-(2,2,3-trimethylcyclopent-3-en-l-yl) - pentan-2-σl which has the structure This compound is described as possessing a strong, precious woody odor reminiscent of Sandalwood oil. Summary of the Invention In accordance with the present invention it has been found hat compounds having the structure wherein the dashed line may be either a carbon-carbon single bond or carbon-carbon double bond are useful as fragrance materials. It will be recognized that the chemicals of this invention can exist in several stereoisomeric forms. The foregoing structural formula is intended to embrace the in¬ dividual stereoisomers, as well as mixtures of the various stereoisomers of the substituted cyclic alcohols of this invention. The present invention also provides -efficient and economi- cal processes for preparing these compounds. Thus, for ex¬ ample, the compound having the structure can be prepared by reacting an acetoacetic ester having structure 0 wherein R is lower alkyl and 2,2,3-trimethyl-3-cyclopente acetaldehyde having the structure in the presence of a base to produce a compound having the structure The product of this reaction is then decarboxylated by c tional procedures, e.g. by treatment with a base to produ a compound having the structure O which upon reduction yields Compound !_. The compound having the structure OH can be prepared by reacting an acetoacetic ester and 2,2,3- trimethyl-3-cyclopenten-l-acetaldehyde as described above. The product of this reaction is then decarboxylated and hydrogentated to produce Compound 2 ^ . It has also been found that an admixture of Compounds 1_ and _2_ is also useful as a fragrance material in place of either of the individual compounds. Such a mixture can be pre- pared directly by reacting an acetoacetic ester (3_) and 2,2, 3-trimethyl-3-cyclopenten-l-acetaldehyde (4_) in the presence of an organic base to produce Compound ]_. Decarboxylation of Compound _7 by treatment with a base yields Compound _8_ which upon reduction with a reagent such as sodium borohy- dride yields after workup a mixture of Compounds 1_ and _2. Finally, in accordance with the present invention it ~ has been found that fragrance compositions can be prepared by incorporating in these compositions Compound 1_ or Compound 2 or a mixture thereof in amounts effective to impart frag¬ rance to the composition. OMPI Λ,„ IPO . * Detailed Description of the Invention Compounds having the structure wherein the dashed line may be either a carbon-carbon sin bond or a carbon-carbon double bond have been prepared. compounds exhibit soft, warm woody notes with powdery nu¬ ances rendering these compounds useful as fragrance mater ials. These compounds exhibit similar odor characteristi and may be used individually or as mixtures in fragrance plications. Geometrical and optical isomers of these com pounds may be separated by techniques known to the art. However, such separation is not necessary, since such mix tures of isomers can be employed directly without further separation. Additionally, mixture of these compounds whe in the dashed line may be either a carbon-carbon single b or a carbon-carbon double bond exhibit fragrance properti similar to those of the individual compounds. The following reaction scheme illustrates the various pro esses of the present invention for conveniently and inexp sively preparing such compounds: OMPI " 9 OMPI A-Z - Specifically, Compound 3. can be prepared by reacting an acetoacetic ester (3_) wherein R is lower alkyl, that is, R is C-. to C , preferably methyl or ethyl and 2,2,3-trime yl-3-cyclopenten-l-acetaldehyde (4_) in the presence of amines such as piperidine, morpholine, and pyrolidine. T reaction proceeds through intermediate Compounds 5_ and 6_ yield Compound 1_. Although intermediate Compounds.5_ and j can be separately isolated, it is preferable in the prac- tices of the present invention that the reaction proceed directly to the formation of Compound 1_. Compound 1_ is t decarboxylated by conventional procedures, e.g. by treatm with base such as sodium hydroxide or potassium hydroxide or other known systems such as lithium bromide/dimethyl f amide or aqueous dimethyl sulfoxide/sodium chloride to pr duce Compound 8, which is reduced by treatment with a met hydride such as di-isobutyl aluminum hydride to yield Com pound 1_. Compound 2_ may be prepared in an analogous manner. First, an acetoacetic ester (3_) is reacted with 2,2,3-trimethyl- cyclopenten-1-acetaldehyde (4_) to produce 7_. Compound 1_ decarboxylated to produce Compound 8_ which is hydrogenate by a conventional technique such as by treatment with hyd gen gas in the presence of a catalyst such as a palladiύm on-carbon catalyst to produce Compound 9_. Reduction ' of 9_ treatment with a suitable metal hydride, e.g. lithium alu num hydride, yields Compound 2_. Alternatively, Compound 2_ can be produced directly from C pound 8_ by reducing the double bond and the carbonyl grou of the six-membered ring with hydrogen at an elevated tem erature and pressure in the presence of a catalyst and a solvent such as butyl- or isopropyl-alcohol. As set forth hereinabove, mixtures of Compounds 1* an< ^ 2. exhibit fragrance properties similar to those of either o the individual compounds. Therefore, such a mixture can be readily substituted for either compound in fragrance a OMPI plications. Such a mixture can be prepared by mixing the separately prepared compounds in desired amounts. Addition¬ ally, the mixture can be prepared directly from Compound 8_ by reacting with a reducing agent such as sodium borohy- dride. Compound JL, Compound _2 or a mixture thereof are readily in¬ corporated into fragrance compositions for use in detergents, ' soaps, perfumes, bath preparations, hair preparations, cos¬ metic preparations and the like. When so employed the com¬ pound or mixture should desirably be present in an amount from about 0.1% to about 80% by weight based upon the weight of the composition. A number of examples are provided hereinafter to illustrate the preferred methods of synthesis of the compounds of this invention. The following instrumentation was used to. char¬ acterize the compounds of this invention: Gas Liquid Chromatography (GLC) ' analyses were obtained with a Hewlett-Packard Model 5840 A or Perkin-Elmer Model 3920 gas chrom ograph using either a 10 ft, 2mm ID glass column packed with 2% Carbowax 20M on Chromosorb G 100/120, or a 12 ft, 2mm ID glass column packed with 3% OV-101 on Chromo¬ sorb WHP 100/120. Nuclear Magnetic Resonance (NMR) spectra were recorded with a Varian Associates T-60A or XL 100 spectrometer, using tetramethylsilane as the internal ref¬ erence. Infrared (IR) spectra were obtained with a Perkin- Elmer 137 Infracord. Mass spectra (MS) , were obtained with a Hewlett-Packard 5985 Mass Spectrometer. Unless otherwise indicated weights are in grams, temp atures are in degrees centigrade and pressures are in mm There are also set forth hereinafter several examples ill trating fragrance compositions which include the compound of the present invention. All of these examples are inten only to illustrate the preferred embodiments of this inve tion and are not in any way intended to limit the scope t of. Piperidine (0.8 g) in ethanol (3.0 ml) was added over 0.5 to a stirred mixture of * ethyl acetoacetate (143 g, 1.1 mo and 2,2,3- -i_[tεthyl-3-cyclopenten-l-acetaldehyde (81.3 g, ca. 0.5 m maintaining the reaction temperature -5 to -10°C. The re tion mixture was then kept at 0° for 15 hr. A further qu tity of piperidine (0.3 g) in ethanol (3.0 ml) was added, * with agitation, and the mixture kept at 0° for a further hr. More piperidine (0.3 g) in ethanol (3.0 ml) was adde and the mixture agitated at 20° for 24 hr, then heated at flux for 7 hr. The piperidine, water and ethanol were ev orated to provide the product in crude form (149.5 g) . OMPI Example 2 CQ 2 C 2 H S The product of Example 1 (147 g) was dissolved in methanol (400 ml) , and a solution of sodium hydroxide (21.3 g, 0.53 mol) in water (400 ml) added in one portion, with agitation. The mixture was heated at gentle reflux for 19 hr, then cooled,, and poured into 5% sodium bicarbonate solution (800 ml) . The organic product was extracted with benzene (3 x 200 ml) , and the combined extracts washed with brine (3 x - 200 ml) . Solvent was evaporated and the residue distilled to provide. the desired product, b, g 126-133° (80.9 g) . NMR (CDC1 3 ) δ 0.8 (3H, s) , 1.0 (3H, s) , 1.6 (3H, m) , 2.0 (3H, m) , 5.3 (1H, m) , 5.9 (1H, m) , 1.0-3.0 (10H, complex) . IR (neat) 2995, 1675, 1650, 805 cm -1 " " MS( .m u 7e) 109, 122, 95 121, 232. Example 3 OMPI / t o IPO -* A solution of IN diisobutylaluminu hydride in hexane (26 ml, 0.27 mol) was added during 1 hr to a solution of the product of Example 2 (50 g, 0.22 mol) in toluene (500 ml) with stirring and cooling, such that the reaction tempera ture was maintained between -5 and -2°C. The cooling bat was removed and the mixture agitated for a further 1.5 hr (10-15°) . The cooling bath was replaced and methanol (25 added, dropwise over 0.5 hr. After a further 0.5 hr 6% h drochloric acid (250 ml) was added (0-5°) . The organic ' product was extracted with hexane (700.ml) and the extrac was washed successively with 2% hydrochloric acid (2 x 10 ml) , water- (2 x 200 ml) , 5% sodium bicarbonate solution ( ml) and water (3 x 150 ml) . The solvent was evaporated a the residue distilled to provide the desired product, b- 124° (22.0 g) . NMR (CDCl- j ) δ 0.8. (3H, s) , 1.0 (3H, s) , 1. (1H, exchanged with D 2 0) , 1.6 (6H, ) , 4.2 (1H, m) , 5.2 ( ) , 5.4 (1H, ) , 1.2-2.5 (complex) . IR (neat) 3300, 2900 1080, 805 cm ' -1 MS r .mye) 93, 109, 106, 91. Example 4 A solution of the product of Example 2 (10.0 g, 0.043 " mol in 0.3N ethanolic potassium hydroxide (30 ml), together w 10% palladium on carbon (0.2 g) was treated with hydrogen- gas at atmospheric pressure and at a temperature of 20° until one equivalent of gas had been taken up. Solids we removed by filtration and the filtrate poured into cold ( dilute hydrochloric acid (55 ml) . The organic product wa extracted with diethyl ether (200 ml) and the extract was successively with water (200 ml) , 5% sodium bicarbonate ( -f JREA OMPI ml) and water (3 x 50 ml) . The organic layer was dried, the solvent evaporated, and the residue distilled to provide the desired product b-^g 117-119° (8.0 g) . NMR (CDC1 3 ) δ 0.8 (3H, s) , 1.0 (6H, ) , 1.6 (3H, ) , 5.1 (IH, m) , 1.1-2.6 (11Ξ, complex) . IR (neat) 2900, 1710, 800 cm "1 . MS ( m /e) 124, 111, 109, 95, 234. Example 5 A solution of the product of Example 4' (4.0 g, 0.017 mol) in anhydrous diethyl ether (5.0 ml) was added during 1 hr to a stirred mixture of lithium aluminum hydride (0.8 g, 0.02 mol) in ether (60 ml) . After stirring for a further 1 hr the reac- tants were cooled (5°) , and water (1.0 ml) , 15% sodium hyd¬ roxide solution (1.0 ml), and then water (3.0 ml) added suc¬ cessively to effect granulation of the solids. The solids were removed by filtration and the organic layer washed suc- sessively with 5% sodium bicarbonate solution (100 ml) and water (3 x 50 ml) . The organic layer was dried, the solvent evaporated, and the residue distilled to provide the product b Q<5 117-119° (3.0 g) . NMR (CDC1 3 ) δ 0.8-1.0 (9H, complex), 1.2 (IH, exchanged with D 2 0) , 1.6 (3H, m) , 3.6 (IH, m) , 5 ' .2 (IH, m) , 1.0-2.4 (13H, complex) . IR (neat) 3300, 2900, 1090, e) 95, 109, 107, 67, 236. - - i //. WIPO . ^ l Λ\ Example 6 The product of Example 2 (116 g, 0.5 mol), butyl alcohol ( ml), potassium hydroxide (0.05 g) and copper chromite (7.0 were charged to a 500 ml autoclave, and the stirred mixtur heated at 155-160° under 300 psi of hydrogen. When the tpt of hydrogen gas had stopped the mixture was cooled (20°) a the autoclave evacuated before purging with nitrogen " . The reaction mixture was filtered, the solvent evaporated and residue immediately distilled to provide an oil (103 g) ,wh was shown-.by GLC and spectral analysis to be the desired product. Example 7 OMPI WIPO * methanol (25 ml) was added dropwise, over 0.8 hr, to a stirred solution of sodium borohydride (10.0 g, 0.26 mol) in methanol (125 ml) , with cooling, such that the reaction temperature was maintained -5 to -2°. The mixture was then allowed to warm to 20° and agitation continued for 4 hr. The mixture was once again cooled (0°) before acidification with dilute hydrochloric- acid (dropwise addition) . The or- ganiσ product was extracted with diethyl ether (3 x 100 ml) and the combined organic extracts washed successively with water (3 x 100 ml) , 5% sodium bicarbonate solution (100 ml) and water (3 x 100 ml) . The organic layer was dried, the solvent evaporated, and the residue distilled to provide an oil b 2 0 129-130° (43.0 g) , which was shown by GLC and spec¬ tral analysis to be a mixture of alcohols .1 and _2_. Example 8„ *• The following illustrates the utility of Compound 1_ in frag¬ rance compositions of the chypre type. Compound 1_ is the novel compound of this invention as previously defined. Chypre pts/wt Component 250 Oil Bergamot 130 Oil Orange Sweet 200 Methyl lonone 20 Oil Rose 50 Jasmin Absolute ■ 5 Oil Basil Sweet 5 Oil Estragon 3 Benzyl Salicylate 3 Oil Ylang Extra 6 Cinna ic Alcohol 18 Eugenol 3 Aldehyde C-14 2 10% Sol. Aldehyde C-12 MNA In Diethyl Phthalate Odorless pts/wt Component 10 10% Sol. Aldehyde C-ll ϋndecylenic in Diet Phthalate Odorless 10 Civet Absolute- 40 Coumarin 30 Labdanum Resinoid 30 Musk Ketone 30 Oak oss Absolute - 30 Oil Patchouly 5 Vanillin 50 Oil Vetiver Reunion 70 Compound 1 1000 Example 9 The following illustrates the utility of Compound 2_ of th invention in fragrance compositions exhibiting a woody flo bouquet. Compound 2 is a novel compound in accordance wi the present invention as previously defined. WOODY FLORAL BOUQUET pts/wt Component 20 Musk Ketone 40 Musk Ambrette 10 Heliotropin 5 Labdanum Resinoid 5 10% Sol. Vanillin in Diethyl Phthalate Odor 20 Coumarin 5 Oakmoss Absolute 5 Phenylethyl Phenylacetate 60 Rhodinol Extra 10 Lyral 40 Methyl Ionone Gamma 60 Oil Vetiver Reunion 80 Vetiveryl Acetate 10 10% Sol. Indol in Diethyl Phthalate Odorless 25 10%. Sol. ' Cyclamenaldehyde in Diethyl Phthalate- Odorless -5 Phenylethyl Iso Butyrate 10 Dimethyl Phenylethyl Carbinol. 80 Phenyl Ethyl Alcohol 20 A l Cinnamic Aldehyde 40 Linalool Synthetic 5 Linalyl Cinnamate 120 Hydroxy Citronellal 20 Oil Ylang Extra 40 Oil Rose Bulgarian 40 Jasmin Absolute 10 Oil Bergamot Rectified 5 Oil Geranium Reunion 5 10% Sol. Aldehyde C-9 in Diethyl Phthalate Odorless 5 10% Sol. Aldehyde C-10 in Diethyl Phthalate - Odorless 10 10% Sol. Aldehyde C-11 Undecylenic in Diethyl Phthalate Odorless 5 10% Sol.. Aldehyde C-12 MNA in " Diethyl Phtha¬ late Odorless 5 Oil Neroli Maroc 20 Benzyl Acetate 10 10% Sol. Aldehyde in Diethyl Phthalate Odor¬ less 80 Compound 2_ 10 Oil Styrax Distilled 40 Acetyl Cedrene 20 10% Sol. Pentadecanolide in Diethyl Phthalate Odorless 1000 Example 10 The following illustrates the utility .of a mixture of Com pounds 1_ and 2_ as described hereinabove in a fragrance co position exhibiting a Sandalwood base fragrance. SANDALWOOD BASE pts/wt Component 20 Oil Balsam Gurjon 80 Oil Amyris 100 Osyrol BBA 800 Mixture of Compounds 1_ and 2_ 1000 As will be obvious to one skilled in the art many modific tions, variations, and alterations can be made in t&e pra tices of this invention without departing from the spirit and scope thereof as set forth in the claims which follow - URE OMPI r, WIPO

Claims: What is claimed is: 1. A compound having the structure wherein the dashed line may be either a carbon-carbon single bond or a carbon-carbon double bond. " 2. A method of preparing a compound in accordance withClaim. * 1 wherein the dashed line is a carbon-carbon double bond which comprises reacting an acetoacetic ester having the structure 0 II C0 2 R wherein R is lower alkyl and 2,2,3-trimethyl-3-cyclopenten-l- acetaldehyde having the structure in the presence of a base to produce a compound having the structure OMPI Λ, WIPO decarboxylating- this compound to produce a compound- havin the structure Q and then reducing this compound. 3» A method of preparing a compound in accordance withCl 1 wherein the dashed line is a carbon-carbon single bond which comprises reacting an acetoacetic ester having the 5 structure 0 wherein R is lower alkyl and 2,2,3-trimethyl-3-cyclopente acetaldehyde having the structure 0 in the presence of a base to produce a compound having th structure decarboxylating this compound to produce a compound havin O -21- he structure hydrogenating this compound to produce a compound having the structure o and then further reducing this compound. 4. A method of preparing a compound in accordance with Claim 1 wherein the dashed line is a carbon-carbon single bond which comprises reacting an acetoacetic ester having the structure 0 II wherein R is lower alkyl and 2,2,3-trimethyl-3-cyclopenten-l-- acetaldehyde .- having the structure in the presence of a base -to produce a compound having the structure —2-2- decarboxylating this compound to produce a compound havi the structure and then hydrogenating this compound. 5. A mixture of compounds in accordance with Claim 1 wh in the dashed line may be a carbon-carbon double bond or carbon-carbon single bond. 6. A method of preparing a mixture in accordance with C 5 which comprises reacting ■ an acetoacetic ester having t structure wherein R is lower alkyl and 2,2,3-trimehtyl-3-cyclopent 1-acetaldehyde having the structure in the presence of a base to produce a compound having t structure -gT5RE __ OMPI decarboxylating this compound to produce a compound having the structure and reacting this compound with a reducing agent. 7. A fragrance composition which comprises the compound of Claim 1 in an amount effective to impart fragrance thereto. 8. The fragrance composition of Claim 7 wherein said frag¬ rance-imparting amount is from about 0.1% to about 80% by weight of said compound based upon the weight of said compo¬ sition. 9. A fragrance composition which comprises the mixture of Claim 5 in an amount effective to impart fragrance thereto. 10. The fragrance composition of Claim 9 wherein said frag¬ rance-imparting amount is from about 0.1% to about 80% by weight of said mixture based upon the weight of said compo¬ sition. 11. A method of preparing a fragrance composition which comprises incorporating in said composition an amount of the compound of Claim 1 effective to impart fragrance thereto. OMPI /., WIPO -Λ- 12. A method in accordance with Claim 11 wherein said fr rance-imparting amount is from about 0.1% to about 80% by weight of said-compound based upon the weight of said com sition. 13. A method of preparing a fragrance composition which comprises incorporating in said composition an amount of the mixture of Claim 5 effective to impart fragrance ther 14. The method of Claim 13 wherein said fragrance-impart amount is from about 0.1% to about 80% by weight of said ture based upon the weight of said composition.

Inventors: WILLIS B, YUREIKO J
Applicants: FRITZSCHE DODGE & OLCOTT INC
Application year: 1979
Main classification: A61K7
IPC codes: A61K8, A61Q13, C07C29, C07C35, C07C45, C07C49, C11B9