JP2001019651A - Production of trans-3-isocamphylcyclohexanol - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a production process for trans-3-isocamphylcyclohexanol that is an essential component for the manifestation of sandalwood oil-like perfume in which 3-isocamphylguaiacol is hydrogenated in high yield in no need of expensive catalyst, for example, ruthenium or the like or an expensive reducing reagent, for example, lithium borohydride or the like. SOLUTION: 3-isocamphylguaiacol is hydrogenated by using Raney nickel as a catalyst in at least one solvent selected from the group consisting of water, hydrocarbons, ethers, secondary alcohols, tertiary alcohols, nitriles, sulfoxides and amides. In the preferred embodiment, the hydrogenation is carried out in the presence of a base including an alkali metal or an alkaline earth metal.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing trans-3-isocamphylcyclohexanol. In particular, trans-3- having a specific conformation, which is useful as a fragrance component having a sandalwood oil-like odor.
The present invention relates to a method for producing isocampyl cyclohexanol.

[0002]

2. Description of the Related Art Sandalwood oil is an essential oil obtained from sandalwood mainly produced in eastern India, and is prized as a fragrance component. However, the production of natural sandalwood oil is limited due to restrictions on the cutting of sandalwood from the viewpoint of environmental and resource conservation. For this reason,
As an alternative to this, sandalwood oil-like flavor components obtained by chemical synthesis have been developed.

[0003] It is known that the unique main components of the aroma of natural sandalwood oil are α- and β-santalol. However, due to its chemical structure, Santaroll is difficult to synthesize in large quantities industrially. Therefore, in recent years, a substance having a chemical structure different from that of Santaroll but having a very similar aroma has been synthesized.

One of these substances is a substance obtained by reacting camphene and guaiacol with boron trifluoride and then hydrogenating using Raney nickel as a catalyst (West German Patent 834,593, Chemica).
l Abstracts 51: 17107d (195
7)). This material has been used as a sandalwood oil substitute in the form of a mixture of isobornyl or isocampyl substituted cyclohexanol.

[0005] In this mixture, the most important component that has an effect on sandalwood oil-like aroma is trans-3-isocamphylcyclohexanol, ie, (1S, 3)
S)-and (1R, 3R) -isocamphylcyclohexanol, and the other components are reported to have only a weak odor with inferior odor or to be odorless (E. Demole, Helv. Chimica Ac
ta, Vol. 47, p. 319-338 (196
4)).

Further, as a result of comparison with the structures of α- and β-santalol, which are the aroma components of sandalwood oil, 3-
Among the isocampyl cyclohexanols, sandals are trans isomers in which the isocampyl group substituted at the 3-position of the cyclohexane ring has an equatorial bond to the cyclohexane ring and the hydroxyl group substituted at the 1-position has an axial bond. It has been reported that it is essential for the expression of wood oil-like aroma (E. Demole, Helv. C.
himica Acta, Vol. 47, p. 1766
-1774 (1964)). The requirement that the hydroxyl group be an axial bond for the development of sandalwood oil-like aroma is also supported by conformational calculations relating to the structure-activity relationship of the compound (G. Buchbauer et al., Hel).
v. Chimica Acta, Vol. 77, p. 2
286-2296 (1994)).

[0007] However, in commercially available mixtures, the content of trans-3-isocamphylcyclohexanol is only about 8% by weight (for example, GK Language).
Other, Conference Proceeding o
f Fragrance Flavor Subs
t. Proc. Int. , Haarmann Reim
er Symp. , P. 111-121 (198
0)).

Accordingly, there is a need for a method for selectively synthesizing trans-3-isocamphylcyclohexanol,
Some have already been proposed. For example, a method via 2-isocamphyl phenol (E. Demole, H.
elv. Chimica Acta, Vol. 52,
p. 2286-2296 (1969)) and a method via 4-isocamphylphenol (RT Dahi).
11 et al. Org. Chem. , Vol. 35, p.
251-252 (1970)). However, these methods generate many isomers during the reaction,
In addition, since lithium aluminum hydride, which is difficult to handle in large quantities, is used, it is not suitable as an industrial production method.

Further, a mixture of cis- and trans-3-isocamphylcyclohexanol is oxidized to 3-isocamphylcyclohexanone, which is reduced with lithium borohydride substituted with a bulky alkyl group to obtain a trans-form. A method for synthesizing -3-isocamphylcyclohexanol has been proposed (GK Lange et al., Co.
nference Processed of Fr
aggression Flavor Subst. Pro
c. Int. , Haarmann Reimer Sy
mp. , P. 111-121 (1980)). But,
There is no description on the purity and yield of the obtained trans-3-isocamphylcyclohexanol. In addition, this method is expensive as a reagent used for the reduction reaction and is not suitable as an industrial production method.

In addition, 3-isocamphylcyclohexanone is stereoselectively hydrogenated using a ruthenium complex as a catalyst in the presence of a base having an alkali metal or alkaline earth metal and an amine. A method for obtaining -3-isocamphylcyclohexanol has been proposed (JP-A-9-241195). However, this method is not suitable as an industrial production method because the catalyst used for the reduction reaction is expensive and it is difficult to recover and reuse the catalyst.

Although several methods for selectively synthesizing trans-3-isocamphylcyclohexanol have been proposed, an industrial production method has not yet been established.

[0012]

Accordingly, the present invention provides a method for hydrogenating 3-isocamphyl guaiacol without using an expensive catalyst such as ruthenium or an expensive reducing agent such as lithium borohydride. An object of the present invention is to provide a method for producing trans-3-isocamphylcyclohexanol which is a component essential for the expression of a sandalwood oil-like odor.

[0013]

Means for Solving the Problems In view of such circumstances, the present inventors have made intensive studies to solve the above-mentioned problems, and as a result, have found that 3-isocamphyl guaiacol is hydrogenated using a specific solvent. As a result, the present inventors have found that trans-3-isocamphylcyclohexanol can be produced in a high yield without using an expensive catalyst or reducing agent, thereby completing the present invention.

That is, the present invention relates to 3-isocamphyl guaiacol, which is composed of water, hydrocarbons, ethers, secondary alcohols, tertiary alcohols, nitriles, sulfoxides and amides. The present invention relates to a method for producing trans-3-isocamphylcyclohexanol, which is hydrogenated using Raney nickel as a catalyst in the presence of at least one selected solvent.

[0015]

DETAILED DESCRIPTION OF THE INVENTION The present invention is a process for producing trans-3-isocamphylcyclohexanol by hydrogenating 3-isocamphyl guaiacol in the presence of a solvent and Raney nickel as a catalyst.

The 3-isocamphyl guaiacol which is a reaction substrate of the present invention can be obtained, for example, by alkylating guaiacol with camphene. In the present invention, a composition containing 10 to 20% by weight of 3-isocamphyl guaiacol obtained by alkylating camphene with guaiacol may be used as it is, or may be isolated and purified by high performance liquid chromatography or the like. -Isocamphyl guaiacol may be used.

Raney nickel used as a catalyst is a Raney type nickel alloy obtained by a conventional method (Experimental Chemistry Course: 17; 302
Pp. 310-310) or commercially available developed Raney nickel may be used. The catalytic amount of the catalyst is about 0.000001 mol to about 1 mol, preferably about 0.005 mol to about 0.5 mol, based on 3-isocamphyl guaiacol as a reaction substrate.

As the solvent, water; hexane, heptane,
Hydrocarbons such as octane, nonane, decane and methylcyclohexane; ethers such as tetrahydrofuran, dioxane, dimethoxyethane and diisopropyl ether;
2-propanol, 2-butanol, 4-methyl-2-
Secondary alcohols such as pentanol; 2-methyl-2
-Tertiary alcohols such as propanol and 2-methyl-2-butanol; nitriles such as acetonitrile; sulfoxides such as dimethyl sulfoxide, diethyl sulfoxide and dibenzyl sulfoxide; formamide, N, N
And at least one solvent selected from the group consisting of amides such as -dimethylformamide and N, N-dimethylacetamide. Among them, application of secondary alcohols such as 2-propanol and 2-butanol, particularly 2-propanol is recommended. The ratio of the solvent is preferably 0.5 to 100 times the weight of the reaction substrate.
When a primary alcohol such as methanol, ethanol or 1-butanol is used as a solvent, trans-3-isocamphylcyclohexanol cannot be obtained in a sufficient yield, and 3 -Isocamphyl guaiacol may remain in the reaction product.
When primary alcohols are used, even if the reaction temperature is lowered, not only the selectivity cannot be increased but also the reaction hardly proceeds.

The hydrogenation of the present invention may be carried out using inexpensive and easily available hydrogen gas. Specifically, a predetermined amount of 3-isocamphyl guaiacol, a catalyst and a solvent are placed in a stainless steel autoclave or the like. It is preferable to perform a hydrogenation reaction (= hydrogenation reaction) while filling with hydrogen gas and stirring. In particular, when the amount of the catalyst to be used is small, it is preferable to perform mechanical stirring using a mechanical stirrer or the like.

The hydrogen may be used after being diluted with another gas which is inert to the hydrogenation of the present invention. For dilution,
For example, the dilution may be performed using at least one selected from the group consisting of methane, nitrogen, argon, helium, carbon dioxide, and the like.

The reaction temperature for hydrogenation is usually from 60 to 250 ° C.
It is. By being able to increase the selectivity of trans-3-isocamphylcyclohexanol, 60-150 ° C.
Preferably, it is in the range of 80 to 120 ° C. The reaction time varies depending on conditions such as the concentration of the reaction substrate used, the amount of catalyst, the temperature, and the hydrogen pressure.
It is about 40 hours. The completion of the reaction can be confirmed by gas chromatography or the like. The hydrogen pressure is usually 1
The range is from atmospheric pressure to 200 atm, preferably from 2 atm to 100 atm, more preferably from 2 atm to 30 atm.

In the present invention, it is preferable to carry out the reaction in the presence of a base having an alkali metal or an alkaline earth metal, since the hydrogenation reaction is promoted. As the base, for example, NaOH, KOH, Ca (OH ) 2, Mg (OH) 2, metal hydroxides such as _{LiOH, K 2 CO 3, Na 2} CO 3, CaCO 3 , etc. of a metal carbonate,
Metal alkoxides such as KOMe, KOtBu, LiOMe, LiOtBu, and NaOMe (Me represents a methyl group and tBu represents a t-butyl group). Among them, metal hydroxides are preferable, and NaOH is particularly preferably used. The amount of the base is usually
It is 0.01 to 100 equivalents, preferably 0.05 to 5 equivalents, based on the catalyst.

After the completion of the hydrogenation reaction of the present invention, purification may be carried out by a method such as filtration, concentration under reduced pressure, or distillation according to a conventional method. For example, about 10% to about 20% by weight of 3-isocamphyl guaiacol obtained from an alkylation reaction of guaiacol and camphene as a reaction substrate.
When a composition containing the compound is used, the isomer of 3-isocamphyl guaiacol may remain unreacted after the completion of the hydrogenation reaction. If this is removed by distillation purification, a composition containing about 10% by weight to about 25% by weight of trans-3-isocamphylcyclohexanol can be obtained. That is, commercial sandalwood oil substitutes contain only about 8% by weight of trans-3-isocamphylcyclohexanol which is a component essential for the development of sandalwood oil-like aroma. , The content can be greatly increased, and the fragrance can be enhanced.

The reaction product obtained by the production method of the present invention is a composition containing trans-3-isocamphylcyclohexanol, and is usually composed of (1S, 3S) -isocamphylcyclohexanol and (1R, 3R). ) -Isocamphyl cyclohexanol. Since these are all components necessary for expression of a sandalwood oil-like odor, they can be effectively used as a fragrance component as a mixture. Of course, (1S, 3S) -isocamphylcyclohexanol and (1R, 3R) -isocamphylcyclohexanol can be isolated and used by high performance liquid chromatography or the like.

[0025]

Industrial Applicability The production method of the present invention is economically advantageous, suitable for industrialization, in which trans-3-isocamphylcyclohexanol can be produced in high yield without using an expensive catalyst or reducing agent. It is a way. The resulting trans-3-isocamphyl cyclohexanol is known as an essential component for the expression of sandalwood oil-like odor,
It has a very excellent fragrance in both flavor and strength and is useful as a fragrance component.

[0026]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples. The following analytical instruments and measurement conditions were used for the measurements in the examples. Gas chromatography; equipment: HP-6890 (manufactured by Hewlett-Packard) Column: DB-FFAP (30 m × 0.25 mm × 0.25 μm) (J
& W Company) Measurement temperature: 150-230 ° C (heating at 20 ° C / min) Injection temperature: 230 ° C Carrier gas: helium (1.0 ml / min) Internal standard substance: 2-tridecanone

Example 1 Preparation of 3-isocamphyl guaiacol: 1088 g of camphene (reagent, manufactured by Tokyo Chemical Industry Co., Ltd.) and guaiacol (special grade of reagent, manufactured by Wako Pure Chemical Industries, Ltd.) 1984
g of boron trifluoride diethyl ether complex (reagent first grade, manufactured by Wako Pure Chemical Industries, Ltd.) while stirring at room temperature.
112 g was added dropwise over 1 hour. After completion of the dropwise addition, the mixture was stirred at room temperature for 1 hour, then at 40 ° C. for 3 hours, and toluene 8 was added.
80 g and 789 g of a 5% aqueous sodium hydroxide solution were added. After stirring at room temperature for 20 minutes, the organic layer was separated, and the aqueous layer was extracted three times with 500 g of toluene. The organic layer and the extract were combined and washed with 880 g of 20% saline. The water, toluene and guaiacol contained therein were removed by distillation to obtain 1893 g of a composition containing 13% by weight of 3-isocamphyl guaiacol.

In a 200 ml stainless steel autoclave equipped with a stirrer, 10.0 g of the above-obtained composition containing 13% by weight of 3-isocamphyl guaiacol, and Raney Nickel as a catalyst (trade name Raney Nickel NDT-65, manufactured by Ken Fine Chemicals Co., Ltd.) 2.0
7 g, 0.195 g of sodium hydroxide as a base, and 20 g of 2-propanol (reagent grade, manufactured by Wako Pure Chemical Industries, Ltd.) as a solvent were charged with hydrogen gas, and the mixture was stirred at a hydrogen pressure of 20 atm and a reaction temperature of 100 ° C. for 10 hours. To carry out a hydrogenation reaction. When the obtained reaction product was analyzed by gas chromatography, trans-3-isocamphylcyclohexanol was obtained in a yield of 54% in cis-3.
It was found that -isocamphylcyclohexanol was produced in a yield of 43%.

Example 2 A hydrogenation reaction was carried out in the same manner as in Example 1 except that the reaction temperature was changed from 100 ° C. to 200 ° C. and stirring was carried out for 3 hours and 30 minutes. When the obtained reaction product was analyzed by gas chromatography, trans-3-isocamphylcyclohexanol was obtained with a yield of 38% in cis-
It was found that 3-isocamphylcyclohexanol was produced in a yield of 61%.

Example 3 In Example 2, 20 g of 2-propanol was used as a solvent.
And a hydrogenation reaction was performed using 20 g of methylcyclohexane (reagent, manufactured by Wako Pure Chemical Industries, Ltd.). When the obtained reaction product was analyzed by gas chromatography, trans-3-isocamphylcyclohexanol was obtained with a yield of 38% in cis-
It was found that 3-isocamphylcyclohexanol was produced in a yield of 57%.

Comparative Example 1 10.0 g of a composition containing 13% by weight of 3-isocamphyl guaiacol obtained in Example 1 in a 200 ml stainless steel autoclave, developed Raney nickel (trade name: developed Raney nickel NDT-65, 2.07 g, manufactured by Kawaken Fine Chemical Co., Ltd.
195 g and 100 g of 1-butanol (special grade reagent, manufactured by Wako Pure Chemical Industries, Ltd.) were added, and hydrogen gas was charged thereinto.
The hydrogenation reaction was performed with stirring at 0 atm and a reaction temperature of 200 ° C for 17 hours and 20 minutes. When the obtained reaction product was analyzed by gas chromatography, trans-3
-Isocamphyl cyclohexanol is produced in a yield of 5.0%, cis-3-isocamphyl cyclohexanol is produced in a yield of 2.6%, and 86% of 3-isocamphyl guaiacol remains. I understood that.

 ────────────────────────────────────────────────── ─── Continued on the front page (72) Inventor Toru Haga 5-1, Sokai-cho, Niihama-shi, Ehime Sumitomo Chemical Co., Ltd. F-term (reference) 4H006 AA02 AC13 BA21 BA70 BB11 BB14 BB20 BB21 BB22 BB31 BC10 BC11 BE10 BE11 BE12 BE13 BE20 FC22 FC34 FE12 4H039 CA40 CB40 CB90

Claims (6)

[Claims] [Claim 1] 3-Isocamphyl guaiacol,
Water, hydrocarbons, ethers, secondary alcohols, tertiary alcohols, nitriles, sulfoxides, and Raney nickel as a catalyst in the presence of at least one solvent selected from the group consisting of amides And a method for producing trans-3-isocamphylcyclohexanol obtained by hydrogenation. 2. The method for producing trans-3-isocamphylcyclohexanol according to claim 1, wherein the hydrogenation is performed in the presence of a base having an alkali metal or an alkaline earth metal. 3. The method for producing trans-3-isocamphylcyclohexanol according to claim 1, wherein the solvent is a secondary alcohol. 4. The method for producing trans-3-isocamphylcyclohexanol according to claim 1, wherein the solvent is 2-propanol. The method for producing trans-3-isocamphylcyclohexanol according to any one of claims 1 to 4, wherein the hydrogenation is performed at 60 ° C to 250 ° C. The method for producing trans-3-isocamphylcyclohexanol according to any one of claims 1 to 5, wherein the hydrogenation is performed at a hydrogen pressure of 1 to 200 atm.