JP3090940B2 - Biphenyl compounds - Google Patents

Description

The present invention relates to a biphenyl compound. The compounds of the present invention are useful as antioxidants and deodorants, and can be used as synthetic intermediates such as resins.

(B) Conventional technology Spice plant thyme (Tims Bulgaris Linne Th
ymus vulgaris Linne) from the following compounds Is known to have an antioxidant action and a deodorant action (see JP-A-2-160737).

However, the above-mentioned compounds contained in thyme are trace amounts, and compounds that can be synthesized for industrial use are required.

Under such circumstances, the inventors of the present invention have studied creation of a novel compound by synthesis, and have accomplished the present invention.

(C) Means for Solving the Problems According to the present invention, the general formula (I) (Wherein R ₁ represents a C _1-3 alkyl group).

R ₁ includes a methyl group, an ethyl group, a propyl group, and an isopropyl group. R ₁ is preferably a methyl group or an isopropyl group.

The biphenyl compound of the general formula (I) can be produced, for example, according to the following steps.

(Wherein R ₁ has the same meaning as described above, R ₂ represents a protecting group for a phenolic hydroxyl group, and X represents a halogen atom.) As the protecting group for the phenolic hydroxyl group of R ₂ , methyl,
Ethyl, C _1-3 alkyl group such as isopropyl, methanesulfonyl, ethanesulfonyl, benzenesulfonyl,
Examples thereof include an aliphatic or aromatic sulfonyl group such as toluenesulfonyl. In addition, it may be a group capable of protecting a phenolic hydroxyl group in a halogenation reaction, a Grignard reaction, or the like.

The above steps will be described by way of example where R ₂ is a C _1-3 alkyl group, especially a methyl group.

Dialkylphenol (1) is led to dialkoxybenzene (2) by reacting with an alkylating agent, for example, dimethyl sulfate. This reaction is usually performed in an aqueous medium in the presence of an alkali. The reaction is carried out at a temperature between ice-cooling and the boiling point of water. The reaction time is between 1 and 20 hours.

The dialkoxybenzene (2) is treated with a halogenating agent to be led to a halogenated dialkylalkoxybenzene (3). As the halogenating agent, for example, benzyltrimethylammonium tribromide can be used (see Chemistry Letters, 627-630 (1987)).
This halogenation is usually carried out in an organic solvent (dichloromethane, methanol, etc.) at room temperature or at a slightly elevated temperature. The reaction time is one to several hours.

Next, the halogenated dialkylalkoxybenzene (3) is converted into a dialkoxybiphenyl compound (4) by utilizing a Grignard reaction. That is, at least half of the halogenated dialkylalkoxybenzene (3) is converted to a Grignard reagent by heating at room temperature or, if necessary, in metallic magnesium and an organic solvent (eg, tetrahydrofuran). This is reacted with the remaining (3) in the presence of a catalytic amount of diphenylphosphinoalkane nickel dichloride to obtain a dialkoxybiphenyl compound (4). Examples of the diphenylphosphinoalkane nickel dichloride include diphenylphosphinomethane (or ethane or propane) nickel dichloride. These compounds are obtained by converting a diphenylphosphinoalkane [(Ph) ₂ P (CH ₂ ) n P (Ph) ₂ (where n is 1 to 3)] into an equivalent amount of nickel chloride in a lower aliphatic alcohol (eg, methanol or ethanol). (Hexahydrate), and is obtained by recovering the solvent.

The obtained dialkoxybiphenyl compound (4) is subjected to a deprotection reaction to be led to a biphenyl compound (I).
The deprotection reaction of the alkoxy group to the hydroxyl group is carried out in an organic solvent (eg, halogenated hydrocarbons such as chloroform, dichloromethane, dichloroethylene, ethers such as tetrahydrofuran and dioxane, dimethylformamide, acetonitrile, dimethylsulfoxide, etc.). Halide (eg chloride, iodide)
To a bistrimethylsilyl ether compound, which is preferably isolated or treated without isolation with a mineral acid (eg, hydrochloric acid, sulfuric acid, hydrobromic acid, etc.). The above deprotection reaction is carried out under heating from room temperature to the boiling point of the solvent. This deprotection reaction can be carried out by other methods such as a method of treating with hydrobromic acid in acetic acid.

Although the above reaction has been described by taking the case where R ₂ is an alkoxy group as an example, when using a protecting group for another phenolic hydroxyl group, the above reaction can be carried out by modifying the above or using a technique known in the art. .

The compounds of the present invention are useful not only as antioxidants and deodorants, but also as intermediates thereof, as resin raw materials such as polyesters, polycarbonates and epoxy resins, or as intermediates for dyes, drugs and agricultural chemicals. it can.

(D) Examples The present invention will be described below with reference to examples, but the present invention is not limited thereto.

Example 1 i) 1.00 g of sodium hydroxide was dissolved in 10.0 ml of water, and 3.75 g of thymol was added thereto. While cooling with ice cooling, 3.15 g of dimethyl sulfuric acid was added dropwise thereto, and the mixture was stirred for a few minutes, and then stirred while being heated in a hot water bath for 1.5 hours.
1.00 g of sodium hydroxide, 10.0 ml of water, thymol
3.75 g of the mixed solution was added dropwise. After refluxing this for 15 hours, the organic layer was extracted with benzene and dried over calcium chloride. After removing the solvent, a large amount of hexane was added,
It was treated on an alumina column. After removing the solvent,
4.44 g of isopropyl-5-methylanisole was dissolved in a mixed solvent of 290 ml of dichloromethane and 120 ml of methanol.
After adding g, the mixture was stirred for 3 hours. The solvent was removed with an evaporator, the product was extracted with ether, washed well with an aqueous solution of sodium thiosulfate, dried over magnesium sulfate, and then the solvent was removed to obtain 4-bromo-2-isopropyl-5-methylanisole. 6.34 g were obtained.

ii) 3.86 g of 4-bromo-2-isopropyl-5-methylanisole and 430 mg of magnesium were added to tetrahydrofuran.
When heated in a nitrogen stream in addition to 10 ml, the mixture reacted while generating heat, generating a Grignard reagent. 2.48 g of 4-bromo-2-isopropyl-5-methylanisole and 45 mg of diphenylphosphinoethane nickel dichloride were dissolved in 10 ml of tetrahydrofuran, and the above-prepared Grignard reagent was slowly added thereto with a syringe under nitrogen. 20
After stirring at room temperature for minutes, the mixture was refluxed for 24 hours. An aqueous ammonium chloride solution was added, extracted with ether, washed several times with water, and dried with calcium chloride. The solvent was removed and recrystallized from methanol to give 5,5'-diisopropyl-4,4 '.
1.90 g of dimethoxy-2,2'-dimethylbiphenyl was obtained.

IRνmax (KBr) cm ^-1 : 2960,1610,1492,1240,1160,1041,8
04 ¹ H-NMR (CDCl ₃ ) δ: 1.13 (3Hx2, d), 1,25 (3Hx2, d),
2.02 (3Hx2, s), 3.29 (1H, sept), 3.80 (3Hx2, s), 6.65
(1H, s), 6.87 ( 1H, s) MSm / z (%) (C 22 H 30 O 2): 326 (M +, 100), 311 (92.2),
244 (6.2), 148 (19.8) iii) 5,5'-diisopropyl-4,4'-dimethoxy-2,
To 403 mg of 2'-dimethylbiphenyl, 710 mg of trimethylsilane iodide dissolved in 10 ml of dehydrated and distilled chloroform was slowly added by a syringe, and the mixture was refluxed for 48 hours under nitrogen. The product was extracted with ether, washed with an aqueous solution of sodium thiosulfate, and after removing the solvent, dissolved in a mixed solvent of 5 ml of 2N hydrochloric acid and 10 ml of THF, and stirred at room temperature for 24 hours. This was extracted with ether, and after removing the solvent, recrystallization was performed with n-hexane to obtain 167.6 mg of 4,4'-dihydroxy-5,5'-diisopropyl-2,2'-dimethylbiphenyl (6a). Was.
Melting point 162.0-163.0 ° C IRνmax (KBr) cm ^-1 : 3350,2910,1509,1345,1270,1250,1
175 ¹ H-NMR (CDCl ₃ ) δ: 1.24 (3Hx2, d), 1,25 (3Hx2, d),
1.98 (3Hx2, s), 3.18 (1Hx2, sept), 4.62 (1Hx2, brd),
6.65 (1H, s), 6.93 (1H, s) Example 2 i) From 5.80 g of 2,5-dimethylphenol, 4-bromo-2,5-dimethyl was obtained according to the procedures of i) and ii) of Example 1. Via phenol, 4,4'-dimethoxy-2,2 ', 5,5'
-1.25 g of tetramethylbiphenyl were obtained. 113.5-11
5 ℃ IRνmax (KBr) cm ^-1 : 2860,1613,1502,1470,1248,1160,1
055 ¹ H-NMR (CDCl ₃ ) δ: 2.04 (3Hx2, s), 2,18 (3Hx2, s),
3.85 (3Hx2, s), 6.71 (1Hx2, s), 6.85 (1Hx2, s) ii) From 100 mg of 4,4'-dimethoxy-2,2 ', 5,5'-tetramethylbiphenyl, iii of Example 1 ), 4,
34.2 mg of 4'-dihydroxy-2,2 ', 5,5'-tetramethylbiphenyl was obtained. 136.5-137.5 ° C IRνmax (KBr) cm ^-1 3420,2920,1493,1255,1160,1000,
880 ¹ H-NMR (CDCl ₃ ) δ: 1.98 (3Hx2, s), 2,22 (3Hx2, s),
4.67 (1Hx2, brd), 6.67 (1Hx2, brd), 6.83 (1Hx2, brd) (E) Effect of the Invention According to the present invention, a novel compound useful as an antioxidant and a deodorant by a chemical synthesis method is provided. Provided.

Continuation of the front page (56) References JP-A-62-77341 (JP, A) JP-A-58-41794 (JP, A) JP-A-2-160737 (JP, A) (58) Fields investigated (Int) .Cl. ⁷ , DB name) C07C 39/15 A61L 9/01 C09K 15/08 CA (STN) REGISTRY (STN)

Claims (1)

(57) [Claims] (1) Expression A biphenyl compound represented by the formula: