WO1980000915A1

WO1980000915A1 - Substituted cyclic alcohols,methods of preparing and compositions containing same

Info

Publication number: WO1980000915A1
Application number: PCT/US1979/000542
Authority: WO
Inventors: B Willis; J Yureiko
Original assignee: Fritzsche Dodge & Olcott Inc
Priority date: 1978-11-02
Filing date: 1979-07-26
Publication date: 1980-05-15
Also published as: EP0023485A4; JPS56500014A; JPH0222052B2; EP0023485A1

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 cyclohexanols as fragrance and flavoring materials is well known. One example is carveol which has the general structure

(-) -carveol is a natural component of spearmint oil (+) - carveol has been found in the oils of Fortunella margarita, Anethum graveolens and Heracleum canescens. Further examples may be found in Actander, Perfume and Flavor Chemicals (1969). For example, trimethylcyclohexanol which has the structure

is identified as compound no. 2998 in Actander. Its fragrance is described therein as a powerful menthol-like odor but more camphoraceous and less cooling than menthol.

With regard to flavor, it is described as having a camphoraceous, menthol-like taste.

Actander compound no. 432 is ortho-tertiary-butylcyclohexanol which has the structure

and is described as having a powerful camphoracεous-piney, mostly minty and somewhat tarry odor of great tenacity. Compound no. 433 of Actander, para-tertiary-butylcyclohexanol, having the structure

is described as having an extremely dry, woody, camphoraceous, almost tarry odor with a leather-like undertone. is useful in perfume compositions to lend power and diffusiveness. It is used in soap fragrances along with woody notes, ionones, Cedarwood oil derivatives, and the like.

3- (Iso-camphyl-5) -cyclohexanol, compound no. 566 of Actander, 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 is used in perfume, compositions for its Sandalwood character and economical stability.

Chemicals having the 2,3,3-trimethylcyclopentene skeleton are also well known in the art of perfumery and flavor chemistry. For example, 2,2, 3-trimethyl-3-cycopenten-1-acetaldehyde 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 compositions of 3-methyl-5-(2,2,3-trimethylcyclopent-3-en-l-yl)-pentan-2-ol 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 that 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 individual stereoisomers, as well as mixtures of the various stereoisomers of the substituted cyclic alcohols of this invention.

The present invention also provides efficient and economical processes for preparing these compounds. Thus, for example, the compound having the structure

can be prepared by reacting an acetoacetic ester having structure

wherein R is lower alkyl and 2,2,3-trimethyl-3-cyclopenten-1-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 conventional procedures, e.g. by treatment with a base to produce a compound having the structure

which upon reduction yields Compound 1.

The compound having the structure

can be prepared by reacting an acetoacetic ester and 2,2,3-trimethyl-3-cyclopenten-1-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 and2 is also useful as a fragrance material in place of either of the individual compounds. Such a mixture can be prepared directly by reacting an acetoacetic ester (3) and 2,2, 3-trimethyl-3-cyclopenten-1-acetaldehyde (4) in the presence of an organic base to produce Compound 7. Decarboxylation of Compound 7 by treatment with a base yields Compound 8 which upon reduction with a reagent such as sodium borohydride 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 fragrance to the composition. Detailed Description of the Invention

Compounds having the structure

wherein the dashed line may be either a carbon-carbon single bond or a carbon-carbon double bond have been prepared. compounds exhibit soft, warm woody notes with powdery nuances rendering these compounds useful as fragrance materials. These compounds exhibit similar odor characteristics and may be used individually or as mixtures in fragrance applications. Geometrical and optical isomers of these compounds may be separated by techniques known to the art. However, such separation is not necessary, since such mixtures of isomers can be employed directly without further separation. Additionally, mixture of these compounds wherein the dashed line may be either a carbon-carbon single bond or a carbon-carbon double bond exhibit fragrance properties similar to those of the individual compounds.

The following reaction scheme illustrates the various processes of the present invention for conveniently and inexpensively preparing such compounds:

Specifically, Compound 1. can be prepared by reacting an acetoacetic ester (3) wherein R is lower alkyl, that is,

R is C₁ to C₅, preferably methyl or ethyl and 2,2,3-trimethyl-3-cyclopenten-1-acetaldehyde (4) in the presence of amines such as piperidine, morpholine, and pyrolidine. This reaction proceeds through intermediate Compounds 5 and 6 to yield Compound 7. Although intermediate Compounds 5 and 6 can be separately isolated, it is preferable in the practices of the present invention that the reaction proceed directly to the formation of Compound 7. Compound 7 is then decarboxylated by conventional procedures, e.g. by treatment with base such as sodium hydroxide or potassium hydroxide or other known systems such as lithium bromide/dimethyl form amide or aqueous dimethyl sulfoxide/sodium chloride to produce Compound 8, which is reduced by treatment with a metal hydride such as di-isobutyl aluminum hydride to yield Compound 1. Compound 2 may be prepared in an analogous manner. First, an acetoacetic ester (3) is reacted with 2 ,2, 3-trimethyl-3-cyclopenten-1-acetaldehyde (4) to produce 7. Compound 7 is decarboxylated to produce Compound 8 which is hydrogenated by a conventional technique such as by treatment with hydrogen gas in the presence of a catalyst such as a palladium on-carbon catalyst to produce Compound 9. Reduction of 9 bytreatment with a suitable metal hydride, e.g. lithium aluminum hydride, yields Compound 2.

Alternatively, Compound 2 can be produced directly from Compound 8 by reducing the double bond and the carbonyl group of the six-membered ring with hydrogen at an elevated temperature 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 and 2. exhibit fragrance properties similar to those of either of the individual compounds. Therefore, such a mixture can be readily substituted for either compound in fragrance ap plications. Such a mixture can be prepared by mixing the separately prepared compounds in desired amounts. Additionally, the mixture can be prepared directly from Compound 8 by reacting 8 with a reducing agent such as sodium borohydride.

Compound 1, Compound 2 or a mixture thereof are readily incorporated into fragrance compositions for use in detergents,soaps, perfumes, bath preparations, hair preparations, cosmetic preparations and the like. When so employed the compound 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. characterize 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 chromatograph 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 Chromosorb 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 reference. 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, temper atures are in degrees centigrade and pressures are in mm Hg.

There are also set forth hereinafter several examples illus trating fragrance compositions which include the compounds of the present invention. All of these examples are intended only to illustrate the preferred embodiments of this inven tion and are not in any way intended to limit the scope there of.

Piperidine (0.8 g) in ethanol (3.0 ml) was added over 0.5 hr to a stirred mixture of ethyl acetoacetate (143 g, 1.1 mol) and 2,2,3-trimethyl-3-cyclopenten-1-acetaldehyde (81.3 g, ca. 0.5 mol), maintaining the reaction temperature -5 to -10°C. The reac tion mixture was then kept at 0° for 15 hr. A further quan tity of piperidine (0.3 g) in ethanol (3.0 ml) was added, with agitation, and the mixture kept at 0° for a further 24 hr. More piperidine (0.3 g) in ethanol (3.0 ml) was added and the mixture agitated at 20° for 24 hr, then heated atre flux for 7 hr. The piperidine, water and ethanol were evap orated to provide the product in crude form (149.5 g).

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_1.5126-133° (80.9 g). NMR (CDC1₃) 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/e) 109, 122, 95 121, 232.

A solution of IN diisobutylaluminum hydride in hexane (269 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 bath was removed and the mixture agitated for a further 1.5 hr (10-15°). The cooling bath was replaced and methanol (25 ml) added, dropwise over 0.5 hr. After a further 0.5 hr 6% hy drochloric acid (250 ml) was added (0-5°) The organic product was extracted with hexane (700 ml) and the extract was washed successively with 2% hydrochloric acid (2 x 100 ml), water (2 x 200 ml), 5% sodium bicarbonate solution (200 ml) and water (3 x 150 ml). The solvent was evaporated and the residue distilled to provide the desired product, b_2.0 124° (22.0 g). NMR (CDCl₃) δ 0.8. (3H, s), 1.0 (3H, s), 1.5 (1H, exchanged with D₂0), 1.6 (6H, m), 4.2 (1H, m), 5.2 (1H, m), 5.4 (1H, m), 1.2-2.5 (complex). IR (neat) 3300, 2900, 1080, 805 cm ^-1 MS (^m/e) 93, 109, 106, 91.

A solution of the product of Example 2 (10.0 g, 0.043 mol) in 0.3N ethanolic potassium hydroxide (30 ml), together with 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 were removed by filtration and the filtrate poured into cold (0º) dilute hydrochloric acid (55 ml). The organic product was extracted with diethyl ether (200 ml) and the extract washed successively with water (200 ml), 5% sodium bicarbonate (200 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_{1 .0} 117-119° (8.0 g) . NMR (CDC1₃) δ 0.8 (3H, s), 1.0 (6H, m), 1.6 (3H, m) , 5.1 (IH, m), 1.1-2.6 (11H, complex). IR (neat) 2900, 1710, 800 cm^-1. MS (^m/e) 124, 111, 109, 95, 234.

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 hydroxide solution (1.0 ml), and then water (3.0 ml) added successively 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_0.5 117-119° (3.0 g). NMR (CDC1₃) δ 0.8-1.0 (9H, complex), 1.2 (IH, exchanged with D₂O) , 1.6 (3H, m) , 3.6 (IH, m) , 5.2 (IH, m), 1.0-2.4 (13H, complex). IR (neat) 3300, 2900, 1090,

800 cm -1

MS (^m/e) 95, 109, 107, 67, 236.

The product of Example 2 (116 g, 0.5 mol), butyl alcohol (73 ml), potassium hydroxide (0.05 g) and copper chromite (7.0 were charged to a 500 ml autoclave, and the stirred mixture heated at 155-160° under 300 psi of hydrogen. When the uptake of hydrogen gas had stopped the mixture was cooled (20°) and the autoclave evacuated before purging with nitrogen. The reaction mixture was filtered, the solvent evaporated and the residue immediately distilled to provide an oil (103 g),which was shown by GLC and spectral analysis to be the desired product.

A solution of the product of Example 2 (70 g, 0.3 mol) in 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 organic 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 spectral analysis to be a mixture of alcohols 1 and 2.

Example 8.

The following illustrates the utility of Compound 1 in fragrance 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 Cinnamic 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 Undecylenic in Diet

Phthalate Odorless 10 Civet Absolute

40 Coumarin

30 Labdanum Resinoid

30 Musk Ketone

30 Oakmoss 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 this invention in fragrance compositions exhibiting a woody floral bouquet. Compound 2 is a novel compound in accordance with 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 Odorless 20 Coumarin

5 Oakmoss Absolute

5 Phenylethyl Phenylacetate

60 Rhodinol Extra

Example 10

The following illustrates the utility .of a mixture of Compounds 1 and 2 as described hereinabove in a fragrance composition 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 modifications, variations, and alterations can be made in the practices of this invention without departing from the spirit and scope thereof as set forth in the claims which follow.

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 with Claim. 1 wherein the dashed line is a carbon-carbon double bond which comprises reacting an acetoacetic ester having the structure

in the presence of a base to produce a compound having the structure

decarboxylating this compound to produce a compound having the structure

and then reducing this compound.

3. 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

wherein R is lower alkyl and 2,2, 3-trimethyl-3-cyclopenten-1-acetaldehyde having the structure

in the presence of a base to produce a compound having the structure

decarboxylating this compound to produce a compound having the structure

hydrogenating this compound to produce a compound having the structure

and then further reducing this compound.

4. A method of preparing a compound in accordance with Claim

in the presence of a base -to produce a compound having the structure

decarboxylating this compound to produce a compound having the structure

and then hydrogenating this compound.

5. A mixture of compounds in accordance with Claim 1 where in the dashed line may be a carbon-carbon double bond or a carbon-carbon single bond.

6. A method of preparing a mixture in accordance with Claim 5 which comprises reacting an acetoacetic ester having the structure

wherein R is lower alkyl and 2,2,3-trimehtyl-3-cyclopenten-1-acetaldehyde having the structure

in the presence of a base to produce a compound having the structure

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 fragrance-imparting amount is from about 0.1% to about 80% by weight of said compound based upon the weight of said composition.

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 fragrance-imparting amount is from about 0.1% to about 80% by weight of said mixture based upon the weight of said composition.

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.

12. A method in accordance with Claim 11 wherein said fragrance-imparting amount is from about 0.1% to about 80% by weight of said compound based upon the weight of said composition.

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 thereto.

14. The method of Claim 13 wherein said fragrance-imparting amount is from about 0.1% to about 80% by weight of said mixture based upon the weight of said composition.