JPS6340408B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing an optically active or racemic tetrahydronaphthalene derivative represented by formula ().

(In the formula, R represents hydrogen or an alkyl group.) The tetralin derivative represented by the formula () is a compound useful as an intermediate raw material for pharmaceuticals, fragrances, and the like. For example, acetylated compounds of formula () are important as raw materials. Among them, 7-acetyl-1,1,3,4,4,6
-Hexamethyl-1,2,3,4-tetrahydronaphthalene (trade name: ``Tonaritsudo'' or ``Beritone'') has a sycamore-like aroma that is valuable in the field of perfumery, and occupies an important position as a perfumery for cosmetics. There is. Among the compounds represented by formula (),
If R is a methyl group, this compound can be derived. What is noteworthy is that not only is the optically active tetrahydronaphthalene derivative represented by the formula () not known at all, but it is impossible to obtain the optically active derivative of the present invention using known methods. If we focus on the optical activity of fragrances, many interesting reports have been made. That is,
Since the sense of smell is one of the biological functions, different smells are perceived depending on the chirality of molecules. For example, in a detailed study of carvone, it has been reported that the dextrorotatory carvone has the odor of carvone, while the levorotary carvone has the odor of carvone (J.Agr.Food Chem., 19, 785
(1971). Therefore, for fragrances that are currently produced only in racemic form, if optically active forms are produced, fragrances with new value will be obtained, and the optically active forms represented by formula () form important compounds.

The present inventors first reacted 4-(2-methyl-propenyl)-5,5-dimethyl-tetrahydro-2-furanone, commonly known as pyrosine, with an aromatic hydrocarbon in the presence of a Friedel-Crafts catalyst, or We have developed a method for producing optically active or racemic tetrahydronaphthylacetic acid derivatives represented by formula () by alkylating pyrosine to aromatic hydrocarbons with an acid catalyst and then treating it in the presence of a Friedel-Crafts catalyst. .

(In the formula, R represents hydrogen or an alkyl group.) By halogenating and decarboxylating this compound, the present inventors can produce a new optically active or racemic compound represented by the formula (), Next, the inventors discovered that the desired optically active or racemic tetrahydronaphthalene derivatives (2) could be produced by hydrogenolyzing them, and after further various studies, the present invention was completed.

(In the formula, R represents hydrogen or an alkyl group) (In the formula, R has the same meaning as above, and X represents a halogen atom.) Various methods are used for halogenated decarboxylation, but for example, aromatic hydrocarbons, lead tetraacetate, lithium halide, etc. By heating in a solvent such as a halogenated hydrocarbon, the halogenation decarboxylation reaction easily proceeds, and a novel compound represented by the formula () can be obtained. The formula obtained in this way ()
By hydrogenolyzing the halide, an optically active or racemic tetrahydronaphthalene derivative represented by the formula () can be obtained.

Examples of the hydrogenolysis method include methods using metal hydrides and catalytic hydrogenolysis. As the metal hydride, there is a method using lithium aluminum hydride or a combination of lithium hydride and lithium aluminum hydride. In this case, the compound represented by the above formula () may be dissolved in an ether such as tetrahydrofuran, lithium aluminum hydride, etc. may be added, and the reaction may be carried out usually from 0° C. to the boiling point of the solvent used.

The amount of lithium aluminum hydride used is usually 1/4 mol to 2 mol, preferably 1/2 mol to 1 mol, per 1 mol of the halide of formula (). In the method using a combination of lithium hydride and lithium aluminum hydride, a combination of 1 to 2 moles of lithium hydride and 0.1 to 0.5 moles of lithium aluminum hydride is preferably used per 1 mole of the halide of formula (). .

The progress of the reaction can be determined by analytical means such as gas chromatography and thin layer chromatography.

The product has high purity as it is, but if necessary, it can be further purified by distillation or the like.

In addition, as a catalytic hydrogenolysis method, palladium,
Examples include a method of hydrogen reduction in the presence of a catalyst such as nickel. In particular, the reaction proceeds suitably by using a palladium-based catalyst. In this case, the reaction will proceed smoothly if the base is present in about an equimolar amount to the halide. Suitable bases include organic acid salts of alkali metals (sodium acetate, potassium acetate, etc.), organic tertiary amines (triethylamine, pyridine, etc.), or amide compounds (N,N-dimethylformamide, N,N-diethylformamide, etc.). used. When carrying out the reaction, it is preferable to dilute the reaction as desired with a solvent that does not essentially inhibit the reaction. Examples of such solvents include alcohols such as ethanol, isopropanol, and tertiary butanol, and aromatic solvents such as benzene and toluene. and ethers such as tetrahydrofuran and dioxane. The palladium-based catalyst used for this reduction reaction is
Both non-supported and supported types can be used. Moreover, they may be used as powders, or may be molded into appropriate shapes and sizes. Examples of unsupported catalysts used include palladium black, palladium oxide, palladium chloride, and the like.
As the supported catalyst, for example, palladium-charcoal, palladium-silica, palladium-alumina, etc. with various supporting ratios are used. The amount of palladium catalyst used is not particularly limited, but in the case of a batch reaction, it is 0.001 to 1 equivalent, preferably 0.01 to 0.2 equivalent, per mole of raw material halide.

The hydrogen used in the reduction reaction is usually commercially available, and the amount used is not particularly limited as long as it is at least stoichiometric for the purpose of completing the reaction, and the reaction will proceed even at normal pressure. However, a method of applying pressure is also used to promote the reaction. Normally, 150 atmospheres or less is sufficient. The reduction reaction temperature is preferably heated to promote the reaction, but
In order to suppress side reactions, the temperature is preferably 100°C or less, preferably in the range of about 10°C to 80°C.

The compounds and methods of the present invention will be illustrated below with examples.

Example 1 9.56 g of lithium aluminum hydride in nitrogen
(0.252 mol) was suspended in 70 ml of THF (S)-3-
(Chloromethyl)-1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene ([α] ₅₄₆ +26.2° (C1, n-hexane)) 62.9g
(0.251 mol) of THF solution was added dropwise. After heating under reflux for 15 hours, the reaction solution was treated with nitrogen water-containing THF to reduce the concentration to 5%.
600 ml of hydrochloric acid was added and extracted with n-hexane. The extract was washed with saturated saline, dried, concentrated, and distilled to yield 46.0 g (0.213 mol, 85%) of (S)-1,1,
3,4,4,6-hexamethyl-1,2,3,4
-Tetrahydronaphthalene was obtained.

[α] ₅₄₆ −49.1° (C1, chloroform) bp ⁰⁵ = 91°C NMR (CCl ₄ ) δ (ppm) = 0.96 (3H, d), 1.03
(3H, s), 1.21 (3H, s), 1.24 (3H,
s), 1.28 (3H, s), 1.34-1.86 (3H,
m), 2.25 (3H, s), 6.71~7.14 (3H,
m) Example 2 (R)-(3-chloromethyl)-1,1,4,4,
Produced in the same manner as in Example 1 using 6-pentamethyl-1,2,3,4-tetrahydronaphthalene ([α] ₅₄₆ -26.1° (C1, n-hexane)) (R)-
1,1,3,4,4,6-hexamethyl-1,
2,3,4-tetrahydronaphthalene was obtained.

[α] ₅₄₆ −+48.9゜(C1, chloroform) bp,
The NMR spectrum was the same as that of Example 1.

Example 3 4.52 g (0.569 mol) of lithium hydride in nitrogen,
Lithium aluminum hydride 1.81g (0.048mol)
was suspended in THF, and 3-(chloromethyl)-1,
1,4,4,6-pentamethyl-1,2,3,4
-Tetrahydronaphthalene 94.69g (0.378mol)
A THF solution of was added dropwise to the mixture, and the mixture was heated under reflux for 36 hours. The reaction solution was treated with dilute hydrochloric acid and extracted with n-hexane.
After washing with saturated saline, drying, concentrating and distilling to 59.7
g (0.276mol, 73%) of 1,1,3,4,6-
Hexamethyl-1,2,3,4-tetrahydronaphthalene was obtained.

Example 4 In an autoclave, 3-(chloromethyl)-
1,1,4,4,6-pentamethyl-1,2,
3,4-tetrahydronaphthalene 200mg
(0.798mmol) in isopropanol solution (10ml),
Sodium acetate trihydrate 120mg (0.882mmol), 10%
Add 160 mg of Pd-C, apply hydrogen pressure of 80 Kg/cm ² , and
Stirred at ℃ for 12 hours. After cooling, Pd-C is filtered out,
Water was added and extracted with n-hexane. After washing with saturated sodium bicarbonate solution, dry and concentrate to 172 mg.
(0.796 mmol) of 1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene was obtained.

Example 5 (1-1) (S)-4-(2-methylpropenyl)-5,5
-dimethyltetrahydro-2-furanone ([α] _D
-62.5゜(C0.5, ethanol)) 2.50g (14.9mmol)
was dissolved in 30 ml of toluene, 2.10 g (15.8 mmol) of anhydrous aluminum chloride was added, and the mixture was stirred at 10°C for 5 hours. After adding 10 ml of 18% hydrochloric acid to separate the layers, the mixture was washed with diluted hydrochloric acid. The toluene layer was extracted with 5% aqueous ammonia, acid-precipitated with 50% sulfuric acid, and extracted with toluene. After washing with saturated brine, it was dried over Glauber's salt, and toluene was distilled off under reduced pressure to obtain 3.79 g of product. ([α] ₅₄₆ −
The 23.8° (C1, benzene) product was dissolved in heated n-hexane, cooled, the precipitated crystals were filtered off, and the filtrate was concentrated to give 3.42 g (18.2 mmol, 88%) of (R)-
3-(carboxymethyl)-1,1,4,4,6-
Pentamethyl-1,2,3,4-tetrahydronaphthalene was obtained.

[α] ₅₄₆ −26.2° (C1, benzene) NMR (CDCl ₃ ) δ (ppm) = 1.10 (3H, s), 1.28
(6H, s), 1.34 (3H, s), 2.30 (3H,
s), 1.54-2.83 (5H, m), 6.86-7.31
(3H, m), 12.17 (1H, s) IR (cm ^-1 ) 1705 (C=0) (1-2) (R)-4-(2-methylpropenyl)-5,5
-dimethyltetrahydro-2-furanone ([α] _D
+62.0゜(C0.54, ethanol)) 0.35g
(2.08 mmol) was dissolved in 10 ml of toluene, 0.3 ml of concentrated sulfuric acid was added, and the mixture was stirred at room temperature for 1 hour. The toluene layer was washed with an aqueous sodium hydroxide solution, dried over sodium sulfate, and the solvent was distilled off under reduced pressure to give 0.27 g (1.05 mmol, 50
%) of (S)-5,5-dimethyl-4-(2-methyl-2-p-tolylpropyl)-tetrahydro-
2-furanone was obtained.

mp73.8゜〔α〕 ₅₄₆ +32.5゜ (C1, benzene) NMR (CDCl ₃ ) δ (ppm) = 1.16 (3H, s), 1.29
(3H, s), 1.30 (6H, s), 1.60~
1.85 (5H, m), 2.28 (3H, s), 7.04
(4H, s) IR (cm ^-1 ) 1760 (1-3) (S)-5,5-dimethyl-4-(2-methyl-
2-p-tolylpropyl)-tetrahydro-2-
Dissolve 100mg of furanone in 10ml of toluene to obtain 130mg
of anhydrous aluminum chloride was added, and the mixture was stirred at 70°C for 30 minutes. The reaction solution was washed with dilute hydrochloric acid, dried, concentrated, and isolated to yield 95 mg of (S)-3-(carboxymethyl)-1,1,4,4,6-pentamethyl-1,
2,3,4-tetrahydronaphthalene was obtained.

NMR (CCl ₄ ) δ (ppm) = 1.08 (3H, s), 1.25.
(6H, s), 1.34 (3H, s), 2.26 (3H,
s), 1.52-2.79 (5H, m), 6.75-7.15
(3H, m), 12.17 (1H, s) IR (cm ^-1 ) 1705 [α] ₅₄₆ +26.3゜ (C1, benzene) (2-1) (R)-3-(carboxymethyl)-1, 1, 4,
Dissolve 2.00 g (7.69 mmol) of 4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene ([α] ₅₄₆ -23.8° (C1, benzene)) in 30 ml of benzene and dissolve 4.00 g (9.02 mmol) of lead tetraacetate. 0.80 g (18.9 mmol) of anhydrous lithium chloride was added, and the mixture was heated under reflux for 6 hours. After washing the reaction solution with water and then diluted hydrochloric acid,
% aqueous ammonia to remove unreacted carboxylic acid.
The benzene layer was dried, concentrated, and purified by column chromatography to obtain 1.22 g (4.87 mmol) of (S)-3-
(Chloromethyl)-1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene was obtained. 0.35g (1,
34 mmol) of unreacted carboxylic acid was recovered. The yield was 77% based on consumed carboxylic acid.

[α] ₅₄₆ +26.1゜ (C1, n-hexane) NMR (CCl ₄ ) δ (ppm) = 1.08 (3H, s), 1.24
(3H, s), 1.32 (3H, s), 1.39 (3H,
s), 1.48-1.95 (3H, m), 3.23 (1H,
t), 3.87 (1H, dd), 6.77-7.20 (3H,
m) (2-2) (S)-3-(carboxymethyl)-1,1,4,
(R)-3 was carried out in the same manner as in Reference Example 4 using 4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene ([α] ₅₄₆ +23.8° (C1, benzene)).
-(chloromethyl)-1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene was obtained.

[α] ₅₄₆ −26.2° (C1, n-hexane), the NMR spectrum was the same as that of (2-1).

Reference example 1 (S)-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene ([α] ₅₄₆ -49.1° (C1, n-hexane)) 100.0 g
(0.463mol) in 300g of 1,2-dichloroethane and 38.0g (0.484mol) of acetyl chloride.
71.0g (0.533mol) of anhydrous aluminum chloride was added and stirred at 20°C for 1 hour. 300ml of reaction solution 10
After treatment with % hydrochloric acid, the layers were separated. The organic layer was washed with dilute hydrochloric acid and then with a saturated aqueous sodium carbonate solution, dried, concentrated and distilled to give 107.5 g (0.417 mol, 90%) of (S)-
7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene was obtained.

bp ⁰

Claims (1)

[Claims] 1. Optically active or racemic 4-(2-methyl-
(propenyl)-5,5-dimethyl-tetrahydro-2-furanone and an alkylbenzene in the presence of a Friedel-Crafts catalyst, or in the presence of an acid catalyst followed by cyclization in the presence of a Friedel-Crafts catalyst. By expression () (In the formula, R represents hydrogen or an alkyl group.) An optically active or racemic tetrahydronaphthyl acetic acid derivative represented by the formula is obtained, and then this is halogenated and decarboxylated to obtain the formula () (In the formula, R has the same meaning as above, and X represents a halogen atom.) It is characterized by obtaining a halide of an optically active or cerami tetrahydronaphthalene derivative represented by the formula, and then hydrogenolyzing this. formula() (In the formula, R represents the same meaning as above.) A method for producing an optically active or racemic tetrahydronaphthalene derivative represented by the following. 2. The method for producing a tetrahydronaphthalene derivative according to claim 1, wherein hydrogen reduction is carried out using a metal hydride or a palladium-based catalyst as the hydrogenolysis method.