JPH08268940A - (2r)-2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-1-butanol, its production and use - Google Patents

Abstract

PURPOSE: To provide a new optically active compound emitting intense, excellent and unique sandalwood-like fragrance and useful as a perfumery composition for various cosmetics, aromatic agents and other hygienic and sanitary materials. CONSTITUTION: This compound is (2R)-2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1- yl)-1-butanol expressed by formula I. The compound of formula I can be produced by the asymmetric hydrogenation of (A) 2-methyl-4-(2,2,3-trimethyl-3- cyclopenten-1-yl)-2-buten-1-ol of formula II in the presence of (B) a catalyst consisting of a ruthenium-optically active phosphine complex (e.g. a compound of formula, Rux Hy Clz (CBP)2 (NEt3 )w CBP is a t-phosphine of formula III [R<1> is a (substituted)phenyl or a (substituted)3-8C cycloalkyl, etc.]; Et is ethyl; x=2, z=4 and w=1 when y=0 and x=z=1 and w=0 when y=1}.

Description

Detailed Description of the Invention

[0001]

The present invention relates to a novel optically active compound (2R) -2-methyl-4- (2,2,3-trimethyl-3-cyclopenten-1-yl) -1-butanol, The manufacturing method, and the perfume composition containing the compound. (2R) -2-methyl-4- (2,2,
3-trimethyl-3-cyclopenten-1-yl) -1
-Butanol is a compound having an excellent odor like sandalwood, and the fragrance composition of the present invention containing the same can be effectively used for various cosmetics, fragrances and other health and hygiene materials.

[0002]

2. Description of the Related Art In general, among physiologically active substances having an asymmetric structure, useful substances are often specific optical isomers. This is especially the case in the fields of medicines, agricultural chemicals, pheromones, food additives and the like, and the formation of a racemic mixture may significantly reduce the effect or cause a negative effect. In the field of fragrances, some odors have little difference between the optical isomers, but some have a great difference. For example, (−)-menthol is useful for the odor of peppermint, and (+)-nutecatone is useful for the odor of grapefruit, both of which have different odors from other optical isomers or other optical isomers. It has a stronger smell.

Recently, due to the development of asymmetric synthesis methods and methods of separating and analyzing optically active substances, odor differences among optical isomers have been reported for more perfume compounds. For example, α-Damaskon [W. Pickenhan
gen, ACS Symposium Series, 388 (Flavor Chemistry),
pp. 151-157 (1989)], methyl jasmonate (Terry
E. Acree et al., J. Agric. Food Chem., Vol. 33, No. 3,
pp. 425-427 (1985)], dodecahydro-3a, 6, 6,
9a-Tetramethylnaphtho [2,1-b] furan [G.O.
hloff et al., Helv. Chim. Acta, Vol. 68, No. 7, pp. 20
22-2029 (1985)], 3- (2,6,6-trimethylcyclohexan-1-yl) propanol derivative
21642) and the like are reported to have very large odor differences among optical isomers. 3-methyl-5- (2, having a structure somewhat similar to the compound of the present invention
2,3-trimethyl-3-cyclopenten-1-yl)
With -4-penten-2-ol, it has been reported that the (2R, 3S) form has an odor that is 500 times stronger than the (2R, 3R) form (JP-A-61-282330).

As described above, there are many known examples in which the optical isomers have different odors such that the optical isomers are different compounds, but the difference occurs when the optically active compound has any structure. However, the correlation between the structure and the odor is almost unknown. That is, the difference in odor between optical isomers has a complicated factor that cannot be easily analogized, and under the present circumstances, there is no method other than synthesizing and confirming an optically active compound. By the way, 2-methyl-4-
(2,2,3-Trimethyl-3-cyclopentene-1-
(Il) -1-butanol has a sandalwood-like odor and is known to be used as a fragrance composition (JP-A-55).
-4374). In the same publication, this compound is an unsaturated carboxylic acid obtained by Wittig reaction of camphorenal and α-bromopropionic acid ester, using platinum, palladium or Raney nickel to catalyze the double bond in the side chain with hydrogen. Unsaturated aldehydes obtained by addition and then reduction of carboxylic acids to alcohols or by base-catalyzed aldol condensation of camphorenal and propionaldehyde are catalytically hydrogenated and then reduced to give aldehydes. It is disclosed that it is synthesized by the method using alcohol. Furthermore, if the raw material camphorenal is obtained from natural optically active α-pinene,
2-Methyl-4- (2,2,3-trimethyl-3-), which is optically active at the asymmetric carbon atom at the 1-position of the cyclopentene ring.
It is disclosed that cyclopenten-1-yl) -1-butanol can be obtained.

Regarding the relationship between the absolute configuration of the asymmetric carbon atom at the 1-position of the cyclopentene ring and the fragrance, (2,2,3-
Some compounds having a trimethyl-3-cyclopenten-1-yl) alkanol skeleton have the same scent as the racemic form in both the (R) form and the (S) form,
That is, it has been reported that this absolute configuration has no influence on the scent (Japanese Patent Laid-Open Nos. 52-133947 and 60-209537). However, 2-methyl-4-
(2,2,3-Trimethyl-3-cyclopentene-1-
Regarding the asymmetric carbon atom at the 2-position of the butanol chain of (yl) -1-butanol, the conventional synthesis method can only yield an equimolar mixture of the threo form and the erythro form. The (2R) -2-methyl-4- (2,2,3-trimethyl-3-cyclopenten-1-yl) -1-butanol of the present invention in which the asymmetric carbon atom is the (R) form was isolated or synthesized. No examples have been found so far, let alone the odor.

[0006]

As described above, an optically active fragrance compound may have a difference in odor between optical isomers. In such a case, a racemic mixture is used in the fragrance composition. When used, the properties of one optical isomer may be canceled by the other optical isomer. It is therefore meaningful to develop optically active perfume compounds that have a different odor than the racemic mixture. The present invention contains (2R) -2-methyl-4- (2,2,3-trimethyl-3-cyclopenten-1-yl) -1-butanol having an excellent odor, which is different from the known racemic mixture. An object is to provide a perfume composition that does.

[0007]

In such circumstances, the present inventors have made 2-methyl-4- (2,2,3-trimethyl-3-cyclopenten-1-yl) -2-butene-1. -Ol is asymmetrically hydrogenated using a ruthenium-optically active phosphine complex as a catalyst, and the objective optically active compound is (2R) -2-methyl-4- (2,2,2).
3-trimethyl-3-cyclopenten-1-yl) -1
-Finding that butanol can be easily obtained,
Furthermore, this optical isomer, (2S) -2-methyl-4
-(2,2,3-Trimethyl-3-cyclopentene-1
-Yl) -1-butanol was synthesized and the difference in odor between both optical isomers and the racemic mixture was evaluated by a specialized panelist, and as a result, (2R) -2-methyl-4- (2,2,2
3-trimethyl-3-cyclopenten-1-yl) -1
-Butanol has a remarkably excellent odor as compared with its optical isomer or a racemic mixture, and it was found that it is very useful as a perfume material having a novel sandalwood-like odor, and completed the present invention.

That is, the present invention uses the following equation (1)

Embedded image

(2R) -2-methyl-4- represented by
(2,2,3-Trimethyl-3-cyclopentene-1-
Yl) -1-butanol and the following formula (2)

[Chemical 6]

2-methyl-4- (2,2,3 represented by
-Trimethyl-3-cyclopenten-1-yl) -2-
Butene-1-ol is asymmetrically hydrogenated using a ruthenium-optically active phosphine complex as a catalyst, and a fragrance containing the compound (1). A composition is provided.

The compound (2) which is a raw material of the compound (1) of the present invention, that is, 2-methyl-4- (2,2,3-trimethyl-3-cyclopenten-1-yl) -2-buten-1-ol. The commercially available product can be used as it is. It can also be obtained by synthesis.

As the synthesis method, for example, the method described in JP-B-56-36176 can be adopted. That is, camphorenal (= 2,2,3-trimethyl-3-cyclopentene-1-acetaldehyde) and propionaldehyde were aldol-condensed under a base catalyst such as sodium hydroxide to obtain 2-methyl-4. -(2,2,3
-Trimethyl-3-cyclopenten-1-yl) -2-
Butenal may be reduced using Raney nickel as a catalyst and a reducing agent such as lithium aluminum hydride or sodium tetrahydroborate. Incidentally, camphorenal is a known method [JB Lewis, J. Org. Chem., Vol.
30, p.4271 (1965)], α-pinene can be epoxidized with an organic peracid such as peracetic acid to isomerize the resulting pinene epoxide.
In addition, 2-methyl-4- (2,2,3-trimethyl-3-
Cyclopenten-1-yl) -2-buten-1-ol (2) has an asymmetric carbon atom at the 1-position of the cyclopentene ring, and depending on its configuration, the optical activity of the (S) and (R) isomers. Body and a mixture thereof exist, and each can be synthesized by using (S) -camphorenal, (R) -camphorenal, or camphorenal of a mixture thereof as a raw material. Can also be used. That is, according to the method of the present invention, 2-methyl-4- (2,2,3-trimethyl-3-cyclopenten-1-yl) -2-butene- which is a raw material is used.
The compound (1) of the present invention can be obtained while maintaining the 1-ol steric structure at the 1-position of the cyclopentene ring. The compound (1) is disclosed in the above-mentioned JP-A-52-133947 and JP-A-5-33947. As expected from JP-A No. 60-209537, whether the 1-position of the cyclopentene ring is the (S) form, the (R) form, or a mixture thereof is used as a flavoring material. It is useful.

2-Methyl-4- (2,2,3-trimethyl-3-cyclopenten-1-yl) -2-butene-1
As a catalyst for asymmetric hydrogenation of -ol, ruthenium-optically active phosphine complex is used, for example, those represented by the following formulas (3) and (4) are preferably used.

Ru _x H _y Cl _z (CBP) ₂ (NEt ₃ ) _w (3) (wherein CBP is R ¹ -BINAP or BIPHEP
Represents a tertiary phosphine represented by, Et represents an ethyl group, when y is 0, x is 2, z is 4, w is 1,
When y is 1, x is 1, z is 1, and w is 0. Incidentally, R
^1- BINAP is the following equation (5)

[Chemical 7]

[0015] indicates a tertiary phosphine represented by, R ¹
Is a phenyl group which may have a substituent or has 3 carbon atoms
~ 8 cycloalkyl groups are shown. Further, BIPHEP is expressed by the following equation (6).

Embedded image

[0016] indicates a tertiary phosphine represented by, R ²
Represents a phenyl group or a cyclohexyl group which may have a substituent, R ³ represents a methyl group or a methoxy group, R ⁴ represents a hydrogen atom, a methyl group or a methoxy group, and R ⁵ represents a hydrogen atom or a methyl group. Group, methoxy group or di-lower alkyl-substituted amino group. In addition, R ³ and R ⁴ may together form a tetrahydronaphthyl group together with the adjacent phenyl group)

Ru (CBP) (OAc) ₂ (4) (In the formula, CBP has the same meaning as described above, and Ac represents an acetyl group.) In the formulas (3) and (4), CBP is represented by the formula ( 5)
In the case of R ¹ -BINAP represented by, the phenyl group which may have a substituent represented by R ¹ means a para position of the phenyl group or a meta position of 1 or 2 positions, A lower alkyl group such as a methyl group and a tert-butyl group (“lower” means a straight or branched chain having 1 to 4 carbon atoms, the same applies hereinafter) or a lower alkoxyl group such as a methoxy group or an ethoxy group, Or, it means a phenyl group which may be substituted with a halogen atom such as a chlorine atom.
Further, the cycloalkyl group having 3 to 8 carbon atoms represented by R ¹ is particularly preferably a cyclopentyl group or a cyclohexyl group.

The following can be mentioned as specific examples of the tertiary phosphine represented by R ¹ -BINAP. Phosphine 1: 2,2'-bis (diphenylphosphino) -1,1'-binaphthyl (hereinafter simply referred to as "BINA
Abbreviated as “P”) Phosphine 2: 2,2′-bis [di- (p-tolyl) phosphino] -1,1′-binaphthyl (hereinafter, referred to as “Tol-
BINAP ") Phosphine 3: 2,2'-bis [di- (p-tert-
(Butylphenyl) phosphino] -1,1′-binaphthyl (hereinafter abbreviated as “t-Bu-BINAP”)

Phosphine 4: 2,2'-bis [di- (m
-Tolyl) phosphino] -1,1'-binaphthyl (hereinafter abbreviated as "m-Tol-BINAP") Phosphine 5: 2,2'-bis [di- (3,5-dimethylphenyl) phosphino] -1 , 1'-binaphthyl (hereinafter abbreviated as "DM-BINAP") Phosphine 6: 2,2'-bis [di- (p-methoxyphenyl) phosphino] -1,1'-binaphthyl (hereinafter,
(Abbreviated as "MeO-BINAP")

Phosphine 7: 2,2'-bis [di- (p
-Chlorophenyl) phosphino] -1,1'-binaphthyl (hereinafter abbreviated as "Cl-BINAP") Phosphine 8: 2,2'-bis (dicyclopentylphosphino) -1,1'-binaphthyl (hereinafter, " Cp-BI
Abbreviated as “NAP”) Phosphine 9: 2,2′-bis (dicyclohexylphosphino) -1,1′-binaphthyl (hereinafter, referred to as “Cy-BI”).
Abbreviated as "NAP") These tertiary phosphines are described in JP-A-61-63690,
JP 3-20290 A, JP 3-255090 A, JP
It can be prepared by the method described in JP-A 1-68386 or JP-A 4-74192.

In the above formulas (3) and (4), CB
When P is BIPHEP represented by the formula (6), R ²
The phenyl group which may have a substituent represented by
At the para position of the phenyl group or at one or two meta positions, a lower alkyl group such as a methyl group, a tert-butyl group or a methoxy group, a lower alkoxyl group such as an ethoxy group, or a chlorine atom. It means a phenyl group which may be substituted with a halogen atom. Also, R ⁵
When is a di-lower alkyl-substituted amino group, the lower alkyl group means a linear or branched alkyl group having 1 to 4 carbon atoms.

The following can be mentioned as specific examples of the tertiary phosphine represented by BIPHEP. Phosphine 10: 2,2'-dimethyl-6,6'-bis (diphenylphosphino) -1,1'-biphenyl (hereinafter abbreviated as "BIPHEMP") Phosphine 11: 2,2'-dimethyl-6. 6′-bis (dicyclohexylphosphino) -1,1′-biphenyl (hereinafter abbreviated as “BICHEP”) Phosphine 12: 2,2′-bis (diphenylphosphino) -5,5 ′, 6,6 ′ , 7,7 ′, 8,8′-octahydro-1,1′-binaphthyl (hereinafter, referred to as “H ₈ -BI
Abbreviated as "NAP")

Phosphine 13: 2,2'-dimethyl-
4,4'-bis (dimethylamino) -6,6'-bis (diphenylphosphino) -1,1'-biphenylphosphine 14: 2,2 ', 4,4'-tetramethyl-
6,6'-bis (diphenylphosphino) -1,1'-
Biphenyl phosphine 15: 2,2'-dimethoxy-6,6'-bis (diphenylphosphino) -1,1'-biphenyl phosphine 16: 2,2 ', 3,3'-tetramethoxy-6,6'- Bis (diphenylphosphino) -1,1 '
-Biphenyl

Phosphine 17: 2,2 ', 4,4'-tetramethyl-3,3'-dimethoxy-6,6'-bis (diphenylphosphino) -1,1'-biphenylphosphine 18: 2,2 '-Dimethyl-6,6'-bis [di- (p-tolyl) phosphino] -1,1'-biphenyl phosphine 19: 2,2'-dimethyl-6,6'-bis [di- (p-tert. -Butylphenyl) phosphino]
-1,1'-biphenyl phosphine 20: 2,2 ', 4,4'-tetramethyl-
3,3'-dimethoxy-6,6'-bis [di- (p-methoxyphenyl) phosphino] -1,1'-biphenyl

These tertiary phosphines are disclosed in JP-A-63-1.
35397, JP 3-275691, JP 4-139140
Publication, R. Schmid et al., Helv. Chim, Acta, Vol. 74, p.
p. 370-389 (1991), R. Schmid et al., Helv. Chim, Act.
a, Vol. 71, pp. 897-929 (1988) or N. Yamamoto
Chem. Phar. Bull., Vol. 39, pp. 1085-1087 (199
It can be prepared by the method described in 1).

The tertiary phosphine represented by R ¹ -BINAP or BIPHEP has both (R) and (S) isomers, but the compound (2R) of the present invention represented by the above formula (1) In order to obtain 2-methyl-4- (2,2,3-trimethyl-3-cyclopenten-1-yl) -1-butanol, the (R) -form phosphine is used.
Incidentally, (2S) -2- which is an isomer of the compound (1) of the present invention.
To obtain methyl-4- (2,2,3-trimethyl-3-cyclopenten-1-yl) -1-butanol,
The (S) -form phosphine is used. The ruthenium-optically active phosphine complex represented by the formula (3) is, for example,
Method of T. Ikariya et al. [J. Chem. Soc., Chem. Commun.,
pp. 922-924 (1985)] or the method described in JP-A-61-63690. That is, [RuCl ₂ (COD)] _q (q represents a natural number) obtained by reacting ruthenium chloride with cycloocta-1,5-diene (hereinafter abbreviated as “COD”) in an ethanol solvent, and R ^1- BINAP or BIPHE
It can be produced by reacting a tertiary phosphine represented by P with a solvent such as toluene or ethanol in the presence of triethylamine by heating.

The following can be mentioned as specific examples of the ruthenium-optically active phosphine complex represented by the formula (3). The description of the configuration of the tertiary phosphine in the complex is omitted. Complex 1: Ru ₂ Cl ₄ (BINAP) ₂ NEt ₃ Complex 2: Ru ₂ Cl ₄ (Tol-BINAP) ₂ NEt
₃ Complex 3: Ru ₂ Cl ₄ (t-Bu-BINAP) ₂ NE
t ₃ Complex _{4: Ru 2 Cl 4 (m} -Tol-BINAP) 2 N
Et ₃ complex 5: Ru ₂ Cl ₄ (DM-BINAP) ₂ NEt ₃ complex 6: Ru ₂ Cl ₄ (MeO-BINAP) ₂ NEt
₃ complex 7: Ru ₂ Cl ₄ (Cl-BINAP) ₂ NEt ₃ complex 8: Ru ₂ Cl ₄ (Cp-BINAP) ₂ NEt ₃ complex 9: Ru ₂ Cl ₄ (Cy-BINAP) ₂ NEt ₃ complex 10: Ru _{2 Cl 4 (BIPHEMP) 2 NEt} 3 complex _{11: Ru 2 Cl 4 (BICHEP} ) 2 NEt 3 complex _{12: Ru 2 Cl 4 (H} 8 -BINAP) 2 NEt
₃ Complex 13: RuHCl (BINAP) ₂ Complex 14: RuHCl (Tol-BINAP) ₂ Complex 15: RuHCl (t-Bu-BINAP) ₂

The ruthenium-optically active phosphine complex represented by the above formula (4) can be obtained, for example, by the method described in JP-A-62-265293. That is, Ru ₂ Cl ₄ (CBP) ₂ NE which is a kind of the ruthenium-optically active phosphine complex represented by the above formula (3).
It can be produced by reacting t ₃ with anhydrous sodium acetate in an alcohol solvent such as methanol, ethanol or tert-butanol by heating.

The following can be mentioned as specific examples of the ruthenium-optically active phosphine complex represented by the formula (4). The description of the configuration of the tertiary phosphine in the complex is omitted. Complex 16: Ru (BINAP) (OAc) ₂ Complex 17: Ru (Tol-BINAP) (OAc) ₂ Complex 18: Ru (t-Bu-BINAP) (OAc) ₂ Complex 19: Ru (m-Tol-BINAP) (OAc)
₂ complex 20: Ru (DM-BINAP) (OAc) ₂ complex 21: Ru (MeO-BINAP) (OAc) ₂ complex 22: Ru (Cl-BINAP) (OAc) ₂ complex 23: Ru (Cp-BINAP) ( OAc) ₂ complex 24: Ru (Cy-BINAP) (OAc) ₂ complex 25: Ru (BIPHEMP) (OAc) ₂ complex 26: Ru (BICHEP) (OAc) ₂ complex 27: Ru (H ₈ -BINAP) (OAc) ) ₂

To carry out the method of the present invention, the raw material compound represented by the above formula (2) is added to a pressure vessel such as an autoclave which has been previously replaced with an inert gas such as nitrogen gas or argon gas. Methyl-4- (2,2,
3-trimethyl-3-cyclopenten-1-yl) -2
-Buten-1-ol and ruthenium-optically active phosphine complex are added, and a solvent is further added to make a homogeneous solution, and then agitated and reacted in a hydrogen atmosphere to carry out asymmetric hydrogenation. The amount of the ruthenium-optically active phosphine complex used as the catalyst is about 0.00 based on the starting compound represented by the formula (2).
It is advisable to set the molar ratio in the range of 01 to 0.02. If the amount is less than 0.0001 times by mole, the effect as a catalyst is not sufficiently exhibited, and if the amount is more than 0.02 times by mole, the effect corresponding to the amount used is not sufficiently obtained, which is uneconomical. Examples of the solvent used include alcohols such as methanol and ethanol, halogenated hydrocarbons such as methylene chloride and the like, and these may be used alone or as a mixture. Further, these solvents are preferably anhydrous solvents. Hydrogen pressure is about 5
100 kg / cm ^2, preferably from about 10 to 50 kg / cm ^2, the reaction temperature is about
10 to 120 ° C, preferably about 25 to 80 ° C, reaction time 5 to 72 ° C
The time is preferably 8 to 36 hours. After completion of the reaction, the solvent is distilled off and the product is purified by a conventional method such as distillation under reduced pressure to obtain the desired (2R) -2-methyl-4- (2,2)
2,3-trimethyl-3-cyclopenten-1-yl)
-1-Butanol can be easily obtained with high yield and high optical purity.

The thus obtained (2R) -2-methyl-4- (2,2,3-trimethyl-3-cyclopenten-1-yl) -1-butanol (hereinafter simply referred to as "(2
R) form ”) has an excellent sandalwood-like odor, which is an isomer (2S)-
2-Methyl-4- (2,2,3-trimethyl-3-cyclopenten-1-yl) -1-butanol (hereinafter sometimes simply referred to as “(2S) form”) and a mixture of both isomers A racemic mixture (hereinafter, simply “racemic form”)
It was confirmed that it was preferable and strong compared with the sandalwood-like odor. In addition, when the safety against the skin was examined, it was found that the (2R) isomer, that is, the compound (1) of the present invention is superior to the conventional racemic isomer.

Accordingly, by containing the compound (1) of the present invention, it is possible to provide a fragrance composition such as an aroma imparting agent, an aroma improving agent, an aroma enhancing agent, which is fresh, highly palatable and safe for the skin. You can The content of the compound (1) of the present invention in the fragrance composition of the present invention may be appropriately determined according to the purpose and is not particularly limited.
It is good to set it to 50% by weight. In addition, the fragrance composition of the present invention can be appropriately blended with a commonly used fragrance or a fragrance base. The thus-obtained fragrance composition of the present invention can provide various fragrances, fragrances and other health and hygiene materials containing the fragrance composition. That is, perfumes, colognes; shampoos, conditioners, treatments; hair tonics, hair creams,
Pomade and other cosmetic bases for hair; white powder, lipstick, and other cosmetic bases; detergents for detergents, dishwashing detergents, laundry detergents, soaps, etc .; softeners, bleaches, disinfectants, deodorants , Indoor fragrances, insecticides; oral compositions such as toothpaste, mouthwash, etc. can be blended with an appropriate amount capable of imparting the aroma, and the commercial value thereof can be increased.

[0033]

EXAMPLES Next, the present invention will be specifically described by way of examples, but the present invention is not limited to these. still,
The following analytical instruments were used for the analysis in the examples. Gas chromatography: 5890-A (manufactured by Hewlett Packard) Column: Chemical bonded column OV-1 (25 mm x 0.25 mm, ID 0.15 mm) (manufactured by GL Sciences Inc.) Temperature: 100 to 220 ° C (at 4 ° C / min. Temperature rise) Specific rotation: DIP-370 (manufactured by JASCO Corporation) Proton nuclear magnetic resonance spectrum ( ¹ H-NMR): AM-400 (400 MHz) (manufactured by Bruker)

Example 1 Preparation of (2R) -2-methyl-4-[(S) -2,2,3-trimethyl-3-cyclopenten-1-yl] -1-butanol: Argon gas was substituted beforehand. 200 ml
In an autoclave of 2-methyl-4-[(R) -2,
2,3-Trimethyl-3-cyclopenten-1-yl]
-2-buten-1-ol ((-) with an optical purity of 97% ee
Synthesized by a known method using -α-pinene as a raw material. That is, (−)-α-pinene was epoxidized with peracetic acid to give a pinene epoxide, which was then converted to JB Lewis
[J. Org. Chem., Vol. 30, p.4271 (1965)], and the resulting camphorenal was isomerized.
According to the method described in Japanese Patent No. 6176, aldol condensation with propionaldehyde followed by reduction) 5.0 g (25.7 mmo
l), Ru ₂ Cl ₄ [(R) -Tol-BINAP] ₂ NE
t ₃ 7.7 mg (4.3 μmol) and anhydrous methanol 20 ml were put, hydrogen pressure 50 kg / cm ² , reaction temperature 80 ° C., rotation rate 400 rpm.
And reacted with stirring.

Reaction initiation by gas chromatography
After 24 hours, starting material 2-methyl-4-[(R) -2,2,2
3-Trimethyl-3-cyclopenten-1-yl] -2
After confirming that all the butene-1-ol had disappeared, the reaction solution was taken out, the solvent methanol was distilled off under reduced pressure with a rotary evaporator, and then distilled under reduced pressure (9
6 to 100 ° C., 2.0 mmHg) to give the target compound (2R) -2-methyl-4-[(S) -2,2,3-trimethyl-3-cyclopenten-1-yl] -1- as a colorless oil. Butanol (hereinafter sometimes abbreviated as “(2R, S) form”) 4.4 g (22.5 mmol, yield 87.8%) was obtained. The physical properties of this product were as follows. Specific rotation: [α] _D ²⁵ = + 17.3 ° (Neat) ¹ H-NMR (CDCl ₃ ) δppm: 5.23 (bs, 1H), 3.54 (dd, J = 5.
7, 10.5Hz, 1H), 3.44 (dd, J = 6.5, 10.5Hz, 1H), 2.24
~ 2.37 (m, 1H), 1.76 ~ 1.86 (m, 1H), 1.63 ~ 1.75 (m,
2H), 1.60 (bs, 3H), 1.26 ~ 1.57 (m, 3H), 1.13 ~ 1.25
(m, 1H), 1.00 to 1.11 (m, 1H), 0.97 (s, 3H), 0.93 (d, J
= 6.7Hz, 3H), 0.76 (s, 3H)

Further, the diastereopurity of the obtained (2R, S) compound is determined by esterification with (R) -α-methoxy-α-trifluoromethylphenylacetic acid [abbreviated as "(R) -MTPA"]. The following formula (7) was synthesized and determined from the integrated value of ¹ H-NMR of this ester.

[Chemical 9]

That is, 26.1 mg (133.2 μmo) of the obtained (2R) -2-methyl-4-[(S) -2,2,3-trimethyl-3-cyclopenten-1-yl] -1-butanol.
l), (R) -MTPA 96.0 mg (410.3 μmol), dicyclohexylcarbodiimide 110.2 mg (534.1 μmol) and pyridine 1.0 g (12.6 mmol) were added, and the mixture was stirred at room temperature for 20 hours, then 5%.
Quenched in hydrochloric acid aqueous solution, then extracted the organic layer with hexane, filtered the liberated urea derivative, 5% hydrochloric acid aqueous solution,
The extract was washed with a saturated aqueous solution of sodium hydrogencarbonate and a saturated saline solution in that order, dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off, followed by purification by silica gel column chromatography using toluene as a solvent to obtain the target ester. .

When ¹ H-NMR of this ester was measured,
The proton peaks of the methylene group adjacent to the acyloxy group (corresponding to the methylene group adjacent to the chiral center of the compound (1) of the present invention) are due to the non-equivalent geminal coupling and the magnetic anisotropy effect of the phenyl group. Affected by the interaction of the coupling of the methine group, δ4.
It was observed at 0 to 4.3 ppm as shown in FIG. The integrated value of each peak of a, b, and c in the figure was calculated, and the diastereomer abundance ratio of the target methyl group was calculated from the following formula 1.

[0039]

## EQU1 ## (2R, S) body: (2S, S) body = (a + c): b [where the (2S, S) body is (2S) -2-methyl-4-[(S) -2,2,3-trimethyl-3-cyclopenten-1-yl] -1-butanol, and so on. ] Obtained difference in abundance ratio [(2R, S) body- (2S, S)]
Body], (2R) -2-methyl-4-[(S) -2,
2,3-Trimethyl-3-cyclopenten-1-yl]
The diastereopurity of -1-butanol was determined to be 74% de.

Next, in order to compare and evaluate the odor and safety of skin of the obtained (2R, S) body, the diastereoisomer (2R, S) was obtained by the following method (2).
S, S) body is produced, and (2R, S) body and (2S,
The S) -forms are mixed so as to have a ratio of 1: 1 in terms of diastereopurity 100% de, and 2-methyl-4-[(S) -2,2 in which the 2-position carbon is a racemic mixture. , 3-Trimethyl-3-cyclopenten-1-yl] -1-butanol (hereinafter sometimes abbreviated as “(racemic, S) form”) was obtained.

(2S) -2-methyl-4-[(S) -2,
2,3-Trimethyl-3-cyclopenten-1-yl]
Production of -1-butanol: The same raw material used in the production of the (2R, S) form, 2-methyl-4-[(R) -2,2,2.
3-Trimethyl-3-cyclopenten-1-yl] -2
- butene-1-ol 5.0g (25.7mmol), Ru ₂ Cl
₄ [(S) -Tol-BINAP] ₂ NEt ₃ 23.3 mg (12.
(9 μmol) and 20 ml of anhydrous methanol, hydrogen pressure 50 kg
/ cm ² , the reaction temperature was 50 ° C, and the reaction was stirred at a rotation rate of 300 rpm. Gas chromatographic analysis revealed that the starting material, 2-methyl-4-[(R) -2,2,3-trimethyl-3-cyclopenten-1-yl] -2-buten-1-ol, disappeared 8 hours after the start of the reaction. After confirming that the reaction was carried out, the reaction solution was taken out, the solvent methanol was distilled off under reduced pressure on a rotary evaporator, and then the residue was distilled under reduced pressure (98 to 10
2 ℃, 3.5mmHg), colorless oily target compound (2S)
-2-Methyl-4-[(S) -2,2,3-trimethyl-
3-Cyclopenten-1-yl] -1-butanol 4.4 g
(22.5 mmol, yield 87.8%) was obtained. The physical properties of this product were as follows. Specific rotation: [α] _D ²⁵ = + 6.3 ° (Neat) ¹ H-NMR (CDCl ₃ ) δppm: 5.23 (bs, 1H), 3.54 (dd, J = 5.
7, 10.5Hz, 1H), 3.44 (dd, J = 6.5, 10.5Hz, 1H), 2.24
~ 2.37 (m, 1H), 1.76 ~ 1.86 (m, 1H), 1.63 ~ 1.75 (m,
2H), 1.60 (bs, 3H), 1.26 ~ 1.57 (m, 3H), 1.13 ~ 1.25
(m, 1H), 1.00 to 1.11 (m, 1H), 0.97 (s, 3H), 0.93 (d, J
= 6.7Hz, 3H), 0.76 (s, 3H) Furthermore, when the diastereopurity was measured in the same manner as for the (2R, S) form, it was 78% de.

Evaluation of odor: (2R, S) isomer which is the compound of the present invention obtained above and its isomer (2S, S)
The results of body and (racemic, S) body odor evaluated by 5 expert panelists are shown in Table 1. still,
The threshold values in the table are the average values of the five lowest concentrations capable of detecting the odor when each sample compound was diluted with ethanol.

[0043]

[Table 1]

As is clear from Table 1, the compounds of the present invention are isomers (2S, S) and (racemic,
S) It had a strong, excellent and unique sandalwood-like odor that could be distinguished from the body odor.

Evaluation of safety to skin: (2R, S) form and (racemic, which are the compounds of the present invention obtained above
S) The body was subjected to a temporary skin irritation test by the following method to evaluate the safety to the skin. Sample solution: 20 weight each of each sample compound with ethanol
%, 10% by weight, and 5% by weight were used. Experimental animal: Male Hartley guinea pigs weighing about 270 g were preliminarily bred for 2 weeks, and healthy ones weighing 350 to 400 g were used. The test group consisted of 5 animals. Test method: Fix the shaved and shaved experimental animal in the abdominal position, 1.
Sample solution of 3 concentrations in each of 5 cm x 1.5 cm compartments.
02 ml was applied, and the condition of the skin after 24 hours was judged based on the criteria in Table 2, and the results are shown in Table 3.

[0046]

[Table 2]

[0047]

[Table 3] As is clear from Table 3, the compound of the present invention had less primary skin irritation and superior safety to the skin as compared with the (racemic, S) form.

Example 2 Preparation of (2R) -2-methyl-4-[(R) -2,2,3-trimethyl-3-cyclopenten-1-yl] -1-butanol: Argon gas was previously substituted. 200 ml
In the autoclave of 2-methyl-4-[(S) -2,
2,3-Trimethyl-3-cyclopenten-1-yl]
5.0 g (25.7 mmol) of 2-buten-1-ol (synthesized in the same manner as in the method described in Example 1 using (+)-α-pinene having an optical purity measured value of 97% ee as a raw material), Ru ₂ C
l ₄ [(R) -Tol-BINAP] ₂ NEt ₃ 7.7 mg
(4.3 μmol) and anhydrous methanol (20 ml) and hydrogen pressure 8
The reaction was carried out with stirring at 0 kg / cm ² , a reaction temperature of 50 ° C. and a rotation rate of 400 rpm. Reaction started by gas chromatography 24
After a lapse of time, the raw material 2-methyl-4-[(S) -2,2,3-
After confirming that all of trimethyl-3-cyclopenten-1-yl] -2-buten-1-ol had disappeared,
The reaction solution was taken out, the solvent methanol was distilled off under reduced pressure on a rotary evaporator, and then distilled under reduced pressure (99-
100 ° C., 2.0 mmHg), and colorless oily (2R) -2-methyl-4-[(R) -2,2,3-trimethyl-3-cyclopenten-1-yl] -1-butanol (hereinafter,
"(2R, R) body" may be abbreviated) 4.5g (22.9mmo
l, yield 89.1%) was obtained. The physical properties of this product were as follows. Specific rotation is [α] _D ²⁵ = -6.4 ° (Neat) ¹ H-NMR (CDCl ₃ ) δppm: 5.23 (bs, 1H), 3.54 (dd, J = 5.
7, 10.5Hz, 1H), 3.44 (dd, J = 6.5, 10.5Hz, 1H), 2.24
~ 2.37 (m, 1H), 1.76 ~ 1.86 (m, 1H), 1.63 ~ 1.75 (m,
2H), 1.60 (bs, 3H), 1.26 ~ 1.57 (m, 3H), 1.13 ~ 1.25
(m, 1H), 1.00 to 1.11 (m, 1H), 0.97 (s, 3H), 0.93 (d, J
= 6.7 Hz, 3H), 0.76 (s, 3H) Furthermore, when the diastereopurity was measured in the same manner as in Example 1, it was 76% de.

Next, in order to compare and evaluate the odor of the obtained (2R, R) body, the following method was used to obtain the (2S, R) body [(2S) -2- which is a diastereoisomer of this body.
Methyl-4-[(R) -2,2,3-trimethyl-3-cyclopenten-1-yl] -1-butanol, and the same below] was produced, and the (2R, R) compound and (2S, R) were prepared. Convert each body to 100% de purity of diastereo: 1:
2-methyl-4-[(R) -2,2,3-trimethyl-3-cyclopenten-1-yl] -1-, in which the carbon at the 2-position is a racemic mixture by mixing so as to have a ratio of 1 Butanol (hereinafter, may be abbreviated as “(racemic, R) form”) was obtained.

(2S) -2-methyl-4-[(R) -2,
2,3-Trimethyl-3-cyclopenten-1-yl]
Production of 1-butanol: In a 200 ml autoclave previously purged with argon gas, the same raw material used in the production of the (2R, R) form, 2-methyl-4-[(S)-
5.0 g (25.7 mmol) of 2,2,3-trimethyl-3-cyclopenten-1-yl] -2-buten-1-ol, Ru ₂
Cl ₄ [(S) -Tol-BINAP] ₂ NEt ₃ 7.7 m
g (4.3 μmol) and 20 ml of anhydrous methanol, add hydrogen pressure.
The reaction was carried out by stirring at 50 kg / cm ² , reaction temperature of 80 ° C., and rotation rate of 400 rpm. Reaction started by gas chromatography 24
After a lapse of time, the raw material 2-methyl-4-[(S) -2,2,3-
After confirming that all of trimethyl-3-cyclopenten-1-yl] -2-buten-1-ol had disappeared,
The reaction solution was taken out, the solvent methanol was distilled off under reduced pressure on a rotary evaporator, and then distilled under reduced pressure (97-
100 ℃, 3.5mmHg), colorless oily target compound (2
S) -2-Methyl-4-[(R) -2,2,3-trimethyl-3-cyclopenten-1-yl] -1-butanol
4.4 g (22.5 mmol, yield 87.8%) was obtained. The physical properties of this product were as follows. Specific rotation: [α] _D ²⁵ = -17.2 ° (Neat) ¹ H-NMR (CDCl ₃ ) δppm: 5.23 (bs, 1H), 3.54 (dd, J = 5.
7, 10.5Hz, 1H), 3.44 (dd, J = 6.5, 10.5Hz, 1H), 2.24
~ 2.37 (m, 1H), 1.76 ~ 1.86 (m, 1H), 1.63 ~ 1.75 (m,
2H), 1.60 (bs, 3H), 1.26 ~ 1.57 (m, 3H), 1.13 ~ 1.25
(m, 1H), 1.00 to 1.11 (m, 1H), 0.97 (s, 3H), 0.93 (d, J
= 6.7 Hz, 3H), 0.76 (s, 3H) Furthermore, when the diastereo purity was measured in the same manner as in Example 1, it was 73% de.

Odor evaluation: obtained above (2R, R)
Body, its isomers (2S, R) body and (racemic,
R) The body odor was evaluated by 5 expert panelists as in Example 1, and the results are shown in Table 4. The threshold value in the table is the average value of the lowest concentration of 5 persons who were able to detect the odor when each sample compound was diluted with ethanol.

[0052]

[Table 4]

As is clear from Table 4, the compounds of the present invention are isomers (2S, R) and (racemic,
R) It had a strong, excellent and unique sandalwood-like odor that could be distinguished from the body odor.

Example 3 Floral flavoring composition: Example 1 according to the following formulation
(2R) -2-methyl-4-[(S) -2,2,3 obtained in
-Trimethyl-3-cyclopenten-1-yl] -1-
A buttery floral flavoring composition was prepared by blending butanol.

Ingredients By Weight (2R) -2-Methyl-4-[(S) -2,2,3-trimethyl-3-cyclopenten-1-yl] -1-butanol 20 1-obtained in Example 1 Citronellol 200 Phenylethyl alcohol 100 l-Hydroxycitronellal 80 4- (4-Hydroxy-4-methylpentyl) -3-cyclohexene-1-carboxaldehyde 70 p-tert-Butyl-α-methylhydrocinnamic aldehyde 100 p -Isobutyl-α-methylhydrocinnamic aldehyde 20 benzyl acetate 100 linalool 100 α-hexyl cinnamic aldehyde 120 α-terpineol 40 strass 40 5% indole benzyl benzoate solution 10 ───────────── ──────────────────────── Total 1000

Instead of the (2R, S) form, (racemic,
S) A comparative composition containing the body was prepared and compared with the odor of the above-mentioned flavor composition of the present invention. All five expert panelists found that the (2R, S) body was incorporated into the flavor composition of the present invention. Was more clean and natural, had an elegant floral odor, and was evaluated to have a much higher preference.

Example 4 Floral Perfume Composition: In the formulation of Example 3,
Instead of the (2R, S) form, the (2R) -obtained in Example 2 was used.
2-methyl-4-[(R) -2,2,3-trimethyl-3
-Cyclopenten-1-yl] -1-butanol was blended to prepare a highly flavorful floral fragrance composition. Also, instead of this (2R, R) form (racemic,
When a comparative composition containing the (R) body was prepared and compared with the odor of the above-mentioned perfume composition of the present invention, all five expert panelists found that the (2R, R) body was mixed with the perfume composition of the present invention. Was evaluated to be clean and natural, and had an elegant woody floral odor, and was by far higher in palatability.

Example 5 Musk flavoring composition: (2R) -2-methyl-4-[(S) -2,2,3-trimethyl-3-cyclopentene-obtained in Example 1 according to the following formulation 1-yl] -1-butanol was blended to prepare a musk-like flavoring composition having high palatability.

Ingredients By Weight (2R) -2-Methyl-4-[(S) -2,2,3-trimethyl-3-cyclopenten-1-yl] -1-butanol 70 obtained in Example 1 Ethylene brush Rate 200 Ethylene dodecanoate 100 1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-γ-2-benzopyran 150 Cyclopentadecanolide 50 Muscon 20 Amyl Salicylate 40 Bergamot Oil 40 Geranium Oil 25 Heliotropin 40 Acetyl Cedrene 30 p-Isobutyl-α-Methylhydrocinnamic Aldehyde 10 Coumarin 10 Methyl Dihydrojasmonate 20 Lavender Oil 45 Rose Absolute 5 Lemon Oil 20 l-Citronellol 10 Benzyl acetate 10 Oak Moss resin 5 Dipropylene glycol 100 ─────────── ───────────────────────── total of 1000

Instead of the (2R, S) form (racemic,
S) A comparative composition containing the body was prepared and compared with the odor of the above-mentioned flavor composition of the present invention. All five expert panelists found that the (2R, S) body was incorporated into the flavor composition of the present invention. Is stronger, and the characteristics of musk appear well,
It was evaluated to have a high degree of preference.

Example 6 Musk flavoring composition: In the formulation of Example 5, (2
Instead of the (R, S) form, the (2R) -2-obtained in Example 2 was used.
Methyl-4-[(R) -2,2,3-trimethyl-3-cyclopenten-1-yl] -1-butanol was blended to prepare a highly palatable musk tone fragrance composition. Further, a comparative composition was prepared in which a (racemic, R) form was blended in place of the (2R, R) form, and when compared with the odor of the fragrance composition of the present invention, all five specialized panelists
The fragrance composition of the present invention containing the (2R, R) form is
It was evaluated to have a high degree of preference.

[0062]

According to the present invention, a novel optically active compound (2R) -2-methyl-4- (2,2,3-trimethyl-3-cyclopenten-1-yl) -1-butanol is added. In addition, it can be easily obtained in high yield and with high optical purity (diastereo purity). This compound has a strong and excellent unique sandalwood-like odor that can be differentiated from the conventional ones, and the fragrance composition of the present invention containing this compound is used in various cosmetics, fragrances and other health care products. It can be effectively used in a wide range of fields such as sanitary materials.

[Brief description of drawings]

FIG. 1 shows the compounds (1) and (R) of the present invention obtained in Example 1.
¹ is a part of ¹ H-NMR spectrum of an ester with -α-methoxy-α-trifluoromethylphenylacetic acid.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code Agency reference number FI Technical display location // C07B 61/00 300 C07B 61/00 300 C07M 7:00

Claims (3)

[Claims] 1. The following formula (1) Is represented by (2R) -2-methyl-4- (2,2,3-
Trimethyl-3-cyclopenten-1-yl) -1-butanol. 2. The following formula (2): 2-Methyl-4- (2,2,3-trimethyl-3-cyclopenten-1-yl) -2-butene-1-
The following formula (1): wherein all is asymmetrically hydrogenated using a ruthenium-optically active phosphine complex as a catalyst. Is represented by (2R) -2-methyl-4- (2,2,3-
Method for producing trimethyl-3-cyclopenten-1-yl) -1-butanol. 3. The following formula (1): Is represented by (2R) -2-methyl-4- (2,2,3-
A fragrance composition comprising trimethyl-3-cyclopenten-1-yl) -1-butanol.