JPS6236023B2 - - Google Patents

Description

[Detailed Description of the Invention] The present invention is represented by the formula () (In the formula, R represents hydrogen or an alkyl group)
The present invention relates to a method for producing an optically active or racemic tetralin derivative represented by the formula (), which comprises treating a lactone derivative in the presence of a Friedel-Crafts catalyst.

(In the formula, R has the same meaning as above.) The compound represented by the formula () is an important compound as an intermediate raw material for medicines, agricultural chemicals, perfumes, etc. For example, compounds represented by formula () that are decarboxylated and then acetylated are important as fragrances. Among them 7-acetyl-1,1,3,4,4,6
-Hexamethyl-1,2,3,4-tetrahydronaphthalene (trade name: Tonaritsudo) has a valuable sycamore-like aroma in the field of fragrances, and occupies an important position as a fragrance for cosmetics.

For example, among the compounds represented by formula (), if R is a methyl group, this compound can be derived.

The formula () and the method for producing the compound represented by the formula () will be described in detail below. The present inventors 4-
When (2-methylpropenyl)-5,5-dimethyltetrahydro-2-furanone, commonly known as pyrosine, is reacted with an aromatic hydrocarbon in the presence of an acid catalyst, a new compound represented by the formula () is successfully obtained under mild conditions. We have newly discovered that it can be synthesized at a high rate. As the aromatic hydrocarbon, unsubstituted or alkyl-substituted benzenes such as benzene, toluene, ethylbenzene, propylbenzene, and butylbenzene are used. The diagram is as follows.

Acids used in the reaction of the present invention include sulfuric acid, phosphoric acid,
Acids such as p-toluenesulfonic acid and naphthalenesulfonic acid can be used as catalysts.

When carrying out this reaction, it is possible to use a solvent that does not essentially inhibit this reaction, or it is also possible to use a large amount of aromatic hydrocarbon in advance to also serve as a solvent. The reaction temperature is usually from -30°C to below the boiling point of the aromatic hydrocarbon. Although the reaction time may vary depending on the reaction conditions, the desired reaction time can usually be achieved in 5 minutes to 10 hours. The reaction proceeds advantageously under mild conditions. A highly pure product can be obtained by ordinary isolation procedures, but if necessary, it can be purified by means such as recrystallization or chromatography.

If optically active pyrosine is used in this reaction, the lactone derivative represented by formula () can also be obtained as an optically active substance. Generally, biologically active compounds exhibit differences in activity depending on their chirality. Therefore, it is of great significance to develop a technology for producing optically active compounds. Therefore, for example, the above-mentioned tonalide derived from the compound of the present invention can be obtained as an optically active form, if desired. From this point of view as well, the present invention has special features.

Pyrosine, the raw material used in the method of the present invention, is produced by a thermal cleavage reaction of chrysanthemum acid (Botyu Kagaku, 15 , 1).
(1950)) or 2,5-dimethyl-2,
A method in which 4-hexadiene is oxidized to monoepoxide, reacted with sodified malonic acid ester, and then hydrolyzed (Tetrahedron Letters)
Tetrahedron Letters, 1845-1846 (1978)) etc. Furthermore, optically active pyrosine can be synthesized by heating optically active chrysanthemum acid (Agricultural Biological Chemistry Agr.Biol.Chem., 34 , 1115).
(1970)). Next, by treating the thus obtained optically active or racemic lactone derivative represented by the formula () in the presence of a Friedel-Crafts catalyst, the tetralin derivative represented by the formula () can be produced in high yield under mild conditions. . In this case the expression ()
By using the optically active form of the compound represented by the formula (), the compound represented by the formula () can be obtained as an optically active form. The compound () is also a new compound. The reaction formula is as follows.

As Lewis acids effective for promoting this reaction, those commonly used in Friedel-Crafts reactions, such as aluminum chloride and ferric chloride, are used. The amount used is usually an equimolar to 1.5 times the molar amount, preferably an equimolar to 1.2 times the molar amount.

When carrying out the method of the present invention, any solvent that does not essentially inhibit the reaction may be used. Examples of such solvents include aromatic hydrocarbons such as benzene and toluene, and halogenated hydrocarbons such as methylene chloride and dichloroethane. It is also possible to carry out this reaction subsequently without isolating the compound obtained by the reaction formula. Although the reaction temperature does not need to be strictly defined, it is usually sufficient to range from -20°C to the boiling point of the solvent used. Although the reaction time varies depending on the reaction conditions, the desired reaction time can usually be achieved in 5 minutes to 10 hours. The progress of the reaction can be determined by sampling a portion of the reaction solution and analyzing it by gas chromatography, thin layer chromatography, or the like.

As explained above, the present invention makes it possible to advantageously produce a novel compound represented by the formula (), a lactone derivative represented by the formula (), and a tetralin derivative represented by the formula ().

Next, the compounds and production methods of the present invention will be explained with reference to Examples.

Example 1 (Part 1) Production of lactone derivatives.

(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. Its physical property values are as follows.

[α] ₅₄₆ +32.5° (C1.03, 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 (Part 2) Production of tetralin derivatives (S)-5.5-dimethyl-4-(2-methyl-2
100 mg of -p-tolylpropyl)-tetrahydro-2-furanone was dissolved in 10 ml of toluene, 130 mg 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. Its physical property values are as follows.

[α] ₅₄₆ +26.3゜ (C1, benzene) NMRCCl 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.

Claims (1)

[Scope of Claims] 1. A method for producing an optically active or racemic tetralin derivative represented by formula (), which comprises treating an optically active or racemic lactone derivative represented by formula () with a Friedel-Crafts catalyst. (In the formula, R represents hydrogen or an alkyl group). (In the formula, R represents hydrogen or an alkyl group). 2 Optically active or racemic 4-(2-methylpropenyl)-5,5-dimethyltetrahydro 2
-By reacting furanone and benzene or alkylbenzene with acid as a catalyst, the formula () (wherein R represents hydrogen or an alkyl group) and then treated with a Friedel-Crafts catalyst (formula ()) (In the formula, R represents the same meaning as above.) A method for producing an optically active or racemic tetralin derivative represented by the following formula.