JPS6312461B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel optically active or racemic tetralin derivative represented by formula () and a method for producing the same.

[In the formula, R represents hydrogen or an alkyl group. ] The compound represented by formula () is a compound useful as an intermediate raw material for medicines, agricultural chemicals, fragrances, 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 scent in the field of fragrances, and occupies an important position as a fragrance for cosmetics. Among the compounds represented by the formula (), if R is a methyl group, this compound can be derived.

The present invention also provides a method for producing an optically active or racemic tetralin derivative represented by formula (). That is, a formula characterized by reacting optically active or racemic 4-(2-methylpropenyl)-5,5-dimethyl-tetrahydro-2-furanone, commonly known as pyrosine, with an aromatic hydrocarbon in the presence of a Friedel-Crafts catalyst. This is a method for producing the compound shown in parentheses.

The present inventors have developed a method for producing a new compound represented by formula () in one step with high yield under mild conditions by reacting Virosin and aromatic hydrocarbons in the presence of a Friedel-Crafts catalyst. did. As the aromatic hydrocarbon, unsubstituted or alkyl-substituted benzenes such as benzene, toluene, ethylbenzene, propylbenzene, and butylbenzene are used.

The diagram is as follows.

Lewis acids effective in promoting this reaction include:
Those commonly used in Friedel-Crafts reactions, such as aluminum chloride and ferric chloride, are used. The amount used is usually equivalent to 1.5 times the molar equivalent, preferably equivalent to 1.2 times the molar equivalent.

When carrying out the method of the present invention, it is possible to use a solvent that does not essentially inhibit the 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 -20°C to below the boiling point of the aromatic hydrocarbon.

In order to produce Compound A predominantly in the above reaction formula, it is preferable to lower the reaction temperature, and the practical temperature range is -10°C to 30°C.

The reaction time varies depending on the reaction conditions, but is usually 5
You can reach your goal in 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.

The products (A) and (B) shown in the reaction formula can be produced preferentially by controlling the reaction conditions as described above, or in some cases, the products (A) and (B) can be produced preferentially by controlling the reaction conditions.
It is possible to separate (A) and (B) by normal separation means such as recrystallization.

If optically active pyrosine is used in this reaction, the resulting compound represented by the formula () also has optical activity, and the optical activity is maintained. For example, in the case of reaction with toluene, dextrorotatory pyrosine (ethanol solvent) produces a dextrorotatory product (benzene solvent).
However, levorotatory pyrosine (ethanol solvent) yields a levorotatory product (benzene solvent).
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.

The raw material pyrosine used in the method of the present invention is a thermal cleavage reaction of chrysanthemum acid (Botyu Kagaku, 15, 1).
(1950)) or 2,5-dimethyl-
A method in which 2,4-hexadiene is oxidized to form a monoepoxide, reacted with sodium malonic acid ester, and then hydrolyzed (Tetrahedron).
Letters, 1845-1846 (1978)) etc. Furthermore, optically active pyrosine can be synthesized by heating optically active chrysanthemum acid (Agr. Biol. Chem., 34, 1115 (1970)).

As explained above, the present invention not only enables the novel compound represented by the formula () and its production, but also enables it to be obtained as an optically active compound.

The method of the invention will now be explained by way of examples.

Example 1 (S)-4-(2-methylpropenyl)-5,
5-dimethyltetrahydro-2-furanone ([α]
_D -62.5゜(C0.5, ethanol)) 2.50g
(14.9 mmol) was dissolved in 30 ml of toluene, 2.10 g (15.8 mmol) of anhydrous aluminum chloride was added, and 10
Stirred at ℃ 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, and the aqueous layer was precipitated with dilute sulfuric acid and extracted with toluene. After washing with saturated brine, drying with Glauber's salt and distilling off toluene under reduced pressure, 3.79 g of product ([α]) ₅₄₆ -23.8° (C1, benzene)) was obtained.

After dissolving the product in heated n-hexane, cooling it,
Separate the precipitated crystals and concentrate the liquid to 3.42g.
(13.2 mmol, 88%) of (R)-3-(carboxymethyl)-1,1,4,4,6-pentamethyl-
1,2,3,4-tetrahydronaphthalene was obtained. Its optical rotation, NMR spectrum, and IR spectrum were as follows.

[α] ₅₄₆ -26.2° (C1, benzene) NMR spectrum (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) Example 2 Racemic 4-(2-methylpropenyl)-
5,5-dimethyltetrahydro-2-furanone
The same operation as in Example 1 was performed using 2.50 g (14.9 mmol), and 3.51 g (13.5 mmol, 91%) racemic 3-(carboxymethyl)-1,1,4,4,
6-pentamethyl-1,2,3,4-tetrahydronaphthalene was obtained.

The NMR and IR spectra were the same as those of Example 1.

Example 3 (R)-4-(2-methylpropenyl)-5,
5-dimethyltetrahydro-2-furanone ([α]
_D +62.5゜(C0.5, ethanol)) 2.50g
(14.9 mmol) was carried out in the same manner as in Example 1, and (S)-3-(carboxymethyl)-1,1,
4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene 3.35g (12.9mmol, 86%)
I got it.

[α] ₅₄₆ +26.3° (C1, benzene) The NMR and IR spectra were the same as those of Example 1.

Example 4 (S)-4-(2-methylpropenyl)-5,
5-dimethyltetrahydro-2-furanone ([α]
_D -62.5゜(C0.5, ethanol)〕16.6g
(98.8 mmol) was dissolved in 200 ml of toluene, and 15.8 g (118.5 mmol) of anhydrous aluminum chloride was added.
Stirred at ℃ for 2 hours. 70 ml of 18% hydrochloric acid was added and the mixture was separated and washed with diluted hydrochloric acid. After the toluene layer was extracted with 5% ammonia, the aqueous layer was precipitated with dilute sulfuric acid and extracted with toluene. After washing with saturated brine, drying with Glauber's salt and distilling off toluene under reduced pressure, 25.17 g of product was obtained.
This was recrystallized from n-hexane and 4.37g
(16.8mmol, 17%) of 2-carboxymethyl-
1,1,4,4,6-pentamethyl-1,2,
3,4-tetrahydronaphthalene was obtained.

Its NMR and IR spectra were as follows.

NMR spectrum (CDCl ₃ ); δ (ppm) = 1.08
(3H, s), 1.31 (6H, s), 1.35 (3H,
s), 2.30 (3H, s), 1.53-2.83 (5H,
m), 6.87-7.30 (3H, m), 12.17 (1H,
s) IR (cm ^-1 ): 1705 The recrystallization solution was concentrated to obtain 20.8 g of a mixture of positional isomers.

This compound has 1, 1, 2,
The structure could also be confirmed by deriving it into 4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene.

Reference example 1 (1) 2-carboxymethyl-1,1,4,4,6
-Pentamethyl-1,2,3,4-tetrahydronaphthalene 30g (0.115mol) was dissolved in 570g of benzene, and 66g (0.149mol) of lead tetraacetate and 11.5g (0.271mol) of anhydrous lithium chloride were added to the mixture at 80°C.
The temperature rose to After stirring for 6.5 hours, the reaction solution was washed with water and diluted hydrochloric acid, and the unreacted carboxylic acid was separated with 6% aqueous ammonia. The benzene layer was dried with Glauber's salt and concentrated to obtain 18.9 g (0.075 mol) of 2-chloromethyl-1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene. 9.8 g of unreacted carboxylic acid was recovered from the ammonia aqueous layer.

(2) 6.5g of lithium aluminum hydride in nitrogen
(0.171 mol) was suspended in tetrahydrofuran (THF), and 2-chloromethyl-1,1,4,
40.9g (0.163mol) of 4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene
A THF solution was added dropwise, and the mixture was stirred at 70°C for 15 hours.
After treating the reaction solution with aqueous THF, add diluted hydrochloric acid and
- Extracted with hexane. The extract was washed with saturated saline, dried with Glauber's salt, concentrated and distilled to give 31.0g.
(0.144mol, 88%) of 1,1,2,4,4,6
-Hexamethyl-1,2,3,4-tetrahydrophthalene was obtained. The physical properties such as NMR spectrum were as follows.

bp ^1.2 78℃ NMR (COl ₄ ); δ (ppm) = 0.95 (3H, d), 1.01
(3H, s), 1.21 (3H, s), 1.25 (6H,
s), ~1.85 (3H, m), 2.23 (3H, s),
6.63-7.12 (3H, m) This compound is a combination of 1,1,2,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene, which was separately synthesized from m-cymene, as shown in Reference Example 2. It showed the same NMR spectrum.

Reference example 2 m-cymene 3.35g (25.0mmol) and 2,3-
0.24 g (1.80 mmol) of aluminum chloride was added to 1.01 g (12.0 mmol) of dimethyl-1-butene, and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction solution, the liquid was separated, and then distilled to obtain 0.84 g (3.90 mmol) of 1, 1, 2, 4, 4,
6-hexamethyl-1,2,3,4-tetrahydronaphthalene was obtained.

The NMR spectrum was the same as that synthesized in Reference Example 1.

Claims (1)

[Claims] 1. An optically active or racemic tetralin derivative represented by the formula (). [In the formula, R represents hydrogen or an alkyl group. ] 2. The optically active or racemic tetralin derivative according to claim 1, which is represented by the formula (). [In the formula, R represents an alkyl group. ] 3 Optically active or racemic 4-(2-methylpropenyl)-5,5-dimethyltetrahydro-2
- A method for producing an optically active or racemic tetralin derivative represented by the formula (), which comprises reacting a furanone with benzene or an alkylbenzene in the presence of a Friedel-Crafts catalyst. [In the formula, R represents hydrogen or an alkyl group. ]