JPS6335614B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION Technical Field The present invention relates to a method for producing cyclohexadiene derivatives.

DISCLOSURE OF THE INVENTION General formula of the object compound of the present invention [X is C=O or C(OR ₁ )(OR ₂ ), R ₁ ,
_{Cyclohexadiene} derivatives represented by the general formula It can be obtained by treating a compound represented by [X, R ₁ and R ₂ are the same as above] in the presence of an acidic catalyst. 1 to 4 carbon atoms represented by R ₁ and R ₂ above
Examples of the alkyl group include methyl, ethyl, propyl, and butyl.

The target compound of the present invention is a compound useful as a synthetic intermediate for pharmaceuticals, agricultural chemicals, and the like.

In the present invention, 2,6-dialkoxy-4-
methylidene-2,5-cyclohexadienone,
1,5,6,6-tetraalkoxy-3-methylidene-1,4-cyclohexadiene, etc. are 2,4,6-trialkoxy-4-methyl-2,
5-cyclohexadienone, 1,3,5,6,6
It can be obtained in good yield by treating -pentaalkoxy-3-methyl-1,4-cyclohexadiene or the like in the presence of an acidic catalyst.

Compound (), which is the starting material of the present invention, can be produced, for example, by the following method.

(R ₁ and R ₂ represent an alkyl group having 1 to 4 carbon atoms.) Representative examples of the above compound () include, for example, 2,4,6-trimethoxy-4-methyl-2,5
-Cyclohexadienone, 2,4,6-triethoxy-4-methyl-2,5-cyclohexadienone, 2,4,6-tripropoxy-4-methyl-
2,5-cyclohexadienone, 2,4,6-tryptoxy-4-methyl-2,5-cyclohexadienone, 2,6-dimethoxy-4-ethoxy-
4-methyl-2,5-cyclohexadienone,
2,6-dimethoxy-4-butoxy-4-methyl-2,5-cyclohexadienone, 2,6-diethoxy-4-propoxy-4-methyl-2,5-
Cyclohexadienone, 2,6-diethoxy-4
-butoxy-4-methyl-2,5-cyclohexadienone, 2,6-dipropoxy-4-methoxy-4-methyl-2,5-cyclohexadienone,
2,6-dipropoxy-4-ethoxy-4-methyl-2,5-cyclohexadienone, 2,6-dibutoxy-4-methoxy-4-methyl-2,5-
Cyclohexadienone, 2,6-dibutoxy-4
-Ethoxy-4-methyl-2,5-cyclohexadienone, 1,3,5,6,6-pentamethoxy-3-methyl-1,4-cyclohexadiene,
1,3,5,6,6-pentaethoxy-3-methyl-1,4-cyclohexadiene, 1,5,6-
Examples include tributoxy-3,6-diethoxy-3-methyl-1,4-cyclohexadiene.

According to the present invention, the target compound () can be easily obtained in a good yield by treating the above compound () in the presence of an acidic catalyst. Various types of acidic catalysts can be used, including protonic acids such as sulfuric acid, hydrochloric acid, hydrobromic acid, and perhalogenic acid, and Lewis acids such as aluminum chloride, zinc chloride, and ferric chloride. Can be done. The amount of catalyst added may be determined appropriately;
Usually, it is good to use about 0.5 to 10% by weight based on the compound (2), but from an economic point of view, about 1 to 3% by weight is sufficient. A solvent can be used in this reaction, such as halogenated hydrocarbons such as methylene chloride, chloroform, and carbon tetrachloride, aromatic hydrocarbons such as benzene, toluene, and xylene, ethyl ether, isopropyl ether, and butyl ether. and aliphatic hydrocarbons such as n-hexane and n-pentane. The amount of solvent to be used can be selected as appropriate, but it is usually about 100 to 3000 ml per 1 mole of the compound ().
Particularly preferred is a range of about 1000 to 2000 ml. The reaction temperature can be selected from a wide range, for example about 0 to 100°C,
In particular, a temperature in the range of about 20 to 50°C is preferred, and a reaction time of about 1 to 12 hours, particularly about 3 to 5 hours is sufficient.

Representative examples of the target compound (2) obtained under the above conditions include 2,6-dimethoxy-4-methylidene-2,5-cyclohexadienone, 2,6-diethoxy-4-methylidene-
2,5-cyclohexadienone, 2,6-dipropoxy-4-methylidene-2,5-cyclohexadienone, 2,6-diptoxy-4-methylidene-2,5-cyclohexadienone, 1,5,6,
6-tetramethoxy-3-methylidene-1,4-
Cyclohexadiene, 1,5,6,6-tetraethoxy-6-ethoxy-3-methylidene-1,4
-Cyclohexadiene, 1,5,6-trimethoxy-6-ethoxy-3-methylidene-1,4-cyclohexadiene, 1,5,6-triethoxy-
6-methoxy-3-methylidene-1,4-cyclohexadiene, 1,5,6-tripropoxy-6
-methoxy-3-methylidene-1,4-cyclohexadiene and the like.

The object compound () of the present invention can be purified by commonly known means such as concentration, extraction, distillation, recrystallization, column chromatography, etc.

Example The present invention will be explained below with reference to Examples.

Example 1 2,4,6-trimethoxy-4-methyl-2,
5-cyclohexadienone 198mg and benzene 10ml
Add 10 mg of concentrated sulfuric acid to the mixed solution and stir at room temperature for 2 hours. After the reaction, the solution is neutralized by adding sodium hydrogen carbonate, filtered, and concentrated under reduced pressure. After extracting the concentrated residue with dichloromethane, the solvent is removed under reduced pressure and concentration is performed. oily crude product
158mg recovered. This crude product was purified by silica gel column chromatography (benzene: ethyl acetate = 20:1) to obtain 153 mg of 2,6-dimethoxy-4-methylidene-2,5-cyclohexadienone. This yield is 92% of the theoretical yield.
corresponds to This compound was confirmed by NMR.

NMR ( _CDCl3 , δ): 3.79 (s, 6H, _CH3O ), 5.50 (m, 2H, HC=), 6.25 (m, 2H, _H2C =).

Example 2 When carrying out the same procedure as in Example 1 using 226 mg of 2,6-diethoxy-4-methoxy-4-methyl-2,5-cyclohexadienone and 10 mg of perchloric acid, 180 mg of oily crude product was recovered. Ru. This crude product was transferred to a silica gel column (benzene: ethyl acetate = 20:
By purifying in step 1), 175 mg of 2,6-diethoxy-4-methylidene-2,5-cyclohexadienone was obtained. This amount corresponds to 90% of the theoretical yield. This compound was confirmed by NMR.

NMR (CDCl ₃ , δ): 1.29 (t, 6H, CH ₃ ), 3.92 (q, 4H, CH ₂ O), 5.54 (m, 2H, HC=), 6.20 (m, 2H, H ₂ C=) .

Example 3 When the same procedure as in Example 1 is carried out using 250 mg of 2,6-dipoxy-4-methoxy-4-methyl-2,5-cyclohexadienone and 20 mg of aluminum chloride, 234 mg of oily crude product is recovered. . This crude product was purified with a silica gel column (benzene: ethyl acetate = 20:1) to obtain 217 mg of 2,6-dipoxy-4-methylidene-2,5-cyclohexadienone. This amount is the theoretical yield of 87
Corresponds to %. This compound was confirmed by NMR.

NMR ( _CDCl3 , δ): 1.30 (s, 18H, _CH3 ), 5.48 (m, 2H, HC=), 6.25 (m, 2H, _H2C =).

Example 4 6 mg of concentrated sulfuric acid is added to a mixed solution of 244 mg of 1,3,5,6,6-pentamethoxy-3-methyl-1,4-cyclohexadiene and 10 ml of chloroform, and the mixture is stirred at room temperature for 1 hour. After the reaction, the solution is neutralized by adding sodium hydrogen carbonate, filtered, and concentrated under reduced pressure. After extracting the concentrated residue with dichloromethane, the solvent is removed under reduced pressure and concentration is performed. 210 mg of oily crude product is recovered. This crude product was transferred to a silica gel column (benzene: ethyl acetate = 20:
By purifying in step 1), 197 mg of 1,5,6,6-tetramethoxy-3-methylidene-1,4-cyclohexadiene was obtained. This amount corresponds to 93% of the theoretical yield. This compound was confirmed by NMR.

NMR (CDCl ₃ , δ): 3.20 (s, 6H, CH ₃ O), 3.77 (s, 6H, CH ₃ OC=), 4.97 (bs, 2H, HC=), 5.82 (bs, 2H, H ₂ C =).

Example 5 1,5,6-trimethoxy-3,6-diethoxy-3-methyl-1,4-cyclohexadiene
272mg, methylene chloride 10ml and perchloric acid 10mg were carried out in the same manner as in Example 4, an oily crude product was obtained.
230mg recovered. By purifying this crude product with a silica gel column (benzene: ethyl acetate = 20:1), 1,5,6-trimethoxy-6-
220 mg of ethoxy-3-methylidene-1,4-cyclohexadiene was obtained. This amount is the theoretical yield of 92
Corresponds to %. This compound was confirmed by NMR.

NMR (CDCl ₃ , δ): 1.25 (t, 6H, CH ₃ ), 3.42 (q, 4H, CH ₂ ), 3.75 (s, 6H, CH ₃ O), 4.95 (bs, 2H, HC=), 5.79 (bs, 2H, _H2C =).

Example 6 1,5,6-tryptoxy-3,6-dimethoxy-3-methyl-1,4-cyclohexadiene
334mg, ether 10ml and aluminum chloride 15mg
290 mg of oily crude product is recovered in the same manner as in Example 4. By purifying this crude product with a silica gel column (benzene: ethyl acetate = 20:1), 1,5,6-tributoxy-6
-Methoxy-3-methylidene-1,4-cyclohexadiene (268 mg) was obtained. This amount is the theoretical yield.
This corresponds to 89%. This compound was confirmed by NMR.

NMR (CDCl ₃ , δ) 1.30 (s, 18H, CH ₃ C), 3.24 (s, 6H, CH ₃ O), 4.94 (bs, 2H, HC=), 5.80 (bs, 2H, H ₂ C=) .

Claims (1)

[Claims] 1. General formula [X is C=O or C(OR ₁ )(OR ₂ ), R ₁ ,
R ₂ represents an alkyl group having 1 to 4 carbon atoms] is treated in the presence of an acidic catalyst. A method for producing a cyclohexadiene derivative represented by [X and R ₁ are the same as above]. 2 Halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, aromatic hydrocarbons such as benzene, toluene, xylene, aliphatic ethers such as ethyl ether, isopropyl ether, butyl ether, n-hexane, n-pentane, etc. The manufacturing method according to claim 1, wherein the reaction is carried out in the presence of a solvent such as an aliphatic hydrocarbon. 3. The production method according to claim 1, wherein the acidic catalyst is a protonic acid such as sulfuric acid, hydrochloric acid, hydrobromic acid, or perhalogenic acid, or a Lewis acid such as aluminum chloride, zinc chloride, or ferric chloride. 4. The manufacturing method according to claim 1, wherein the reaction temperature is 0 to 100°C.