JP3112995B2 - Method for producing biphenyl compound - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing a biphenyl compound. The biphenyl compound of the present invention is useful as an antioxidant, a deodorant and the like, and also as a synthetic intermediate such as a resin.

[0002]

BACKGROUND OF THE INVENTION Spice plant thyme (Thymmus bulgaris linne Thymus
vulgaris Linne ) from the following compounds

Embedded image Is known to have an antioxidant action and a deodorant action (see JP-A-2-160737).

[0003] However, the above-mentioned compounds contained in thyme are very small, and establishment of a synthesis method for them is required for industrial use. Under the circumstances described above, the inventors of the present invention have conducted intensive studies and, as a result, have completed the present invention.

[0004]

According to the present invention, general formula (II)

Embedded image (Wherein R ₁ represents a C _1-3 alkyl group) is prepared by treating cobalt perchlorate with α, α, α ′, α′-tetrakis- (1-methyl-1H-imidazole-2). -Il) -2,6-
Oxidation in the presence of a complex with pyridinedimethanol gives a compound of the general formula (I)

Embedded image (Wherein R ₁ has the same meaning as described above), and a compound represented by the general formula (I)
(I ')

Embedded image (Wherein R ₁ has the same meaning as described above).

[0005] In the above general formula, the alkyl group of R ₁ includes methyl, ethyl, propyl and isopropyl groups. R ₁ is preferably a methyl group or an isopropyl group. General formula (I) and compounds other than R ₁ is an isopropyl group in the compound of (I ') are novel compounds.

The oxidation of compound (II) to compound (I) is carried out by using cobalt perchlorate and α, α, α ′, α′-tetrakis- (1-methyl-1H-imidazol-2-yl) -2, The reaction is usually performed in an organic solvent inert to the reaction under an oxygen gas atmosphere in the presence of a 6-pyridinedimethanol complex.

The complex is formed by mixing equimolar amounts of cobalt perchlorate (for example, hexahydrate) and an imidazole compound in an organic solvent such as acetonitrile. The amount of the complex to be used is about 0.01 with respect to compound (II).
~ 1 equivalent. It is desirable that oxygen gas be blown into the complex in advance and used for the oxidation reaction.

The organic solvents inert to the reaction include acetonitrile, dimethylformamide, dimethylsulfoxide, tetrahydrofuran, dioxane, chloroform,
Dichloromethane and the like. However, it is not particularly limited to these. The oxidation reaction is performed in an oxygen gas atmosphere, the reaction temperature is from room temperature to a slightly elevated temperature, and the reaction time is 1 hour to 1 day.

The resulting compound (I) is isolated as a pure product by removing the complex by, for example, column chromatography, distilling off the solvent from the eluate, and recrystallizing the residue.
Can be purified.

The reduction of compound (I) to compound (I ')
Usually, the reaction can be carried out in an organic solvent inert to the reaction (the same solvent as mentioned in the above oxidation reaction can be applied) using a reducing agent such as sodium borohydride or lithium aluminum hydride. The reaction temperature is from room temperature to a slightly elevated temperature, and the reaction time is 1-2 hours. The amount of the reducing agent to be used is about 0.4-3.0 equivalents to the compound.
The produced compound (I ') decomposes the unreacted reducing agent present in the reaction solution, and can be easily separated and purified by a conventional method such as solvent extraction and recrystallization.

The general formula (I) obtained by the method of the present invention or
The compound (I ') has an antioxidant action and a deodorant action, and is useful as an antioxidant and a deodorant. Further, it can be used as a resin raw material such as polyester, polycarbonate, epoxy resin and the like, and further as an intermediate of dyes, medicines and agricultural chemicals.

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

Embedded image (In the formula, R ₁ has the same meaning as described above, and R ₂ means a protecting group for a phenolic hydroxyl group.)

The protecting group for the phenolic hydroxyl group of R ₂ includes a C _1-3 alkyl group such as methyl, ethyl and isopropyl; an aliphatic or aromatic sulfonyl such as methanesulfonyl, ethanesulfonyl, benzenesulfonyl and toluenesulfonyl. And the like. 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 taking as an example the case where R ₂ is a C _1-3 alkyl group, especially a methyl group. The dialkylphenol (1) is led to dialkoxybenzene (2) by reacting with an alkylating agent such as 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 1 to 20 hours. Dialkoxybenzene
(2) is treated with a halogenating agent to lead to a halogenated dialkylalkoxybenzene (3). As the halogenating agent, for example, benzyltrimethylammonium tribromide can be used (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 the 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). By reacting this with the remaining (3) in the presence of a catalytic amount of diphenylphosphinoalkane nickel dichloride, dialkoxybiphenyl compound (4) is obtained. The diphenylphosphinoalkane nickel dichloride includes diphenylphosphinomethane (or ethane or propane) nickel dichloride. These compounds diphenylphosphino alkane _{[(Ph) 2 P (CH} 2) nP (Ph) 2 ( wherein n is 1 to
3)] is reacted with an equivalent amount of nickel chloride (hexahydrate) in a lower aliphatic alcohol (for example, methanol or ethanol), and the solvent is recovered.

The dialkoxybiphenyl compound obtained
(4) is subjected to a deprotection reaction to lead to a biphenyl compound (5). 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.). The reaction is carried out by reacting a haloide (eg, chloride, iodide) to form a bistrimethylsilyl ether compound, and isolating or treating the compound without isolation with a mineral acid (eg, hydrochloric acid, sulfuric acid, hydrobromic acid, etc.). Is preferred. 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. The above reaction has been described by taking the case where R ₂ is an alkoxy group as an example.However, when another protecting group for a phenolic hydroxyl group is used, the above reaction can be carried out by modifying the above or using a technique known in the art. .

[0017]

EXAMPLES The present invention will be described below with reference to examples, but the present invention is not limited thereto.

Example 1 27.5 mg of cobalt perchlorate hexahydrate and α, α, α ′, α′-tetrakis- (1-methyl-1H-imidazol-2-yl)
After dissolving 38.6 mg of -2,6-pyridinedimethanol in 20 ml of acetonitrile and blowing oxygen into the solution for 1 hour,
607 mg of 4,4'-dihydroxy-5,5'-diisopropyl-2,2'-dimethylbiphenyl were added. After oxygen was blown into the solution for 30 minutes, the solution was stirred under an oxygen atmosphere for 24 hours.
After removing the solvent, the catalyst was removed with a silica gel column (mobile phase n-hexane: ethyl acetate = 2: 1). After removing the solvent, recrystallization was performed with n-hexane and a small amount of ethyl acetate, and 4′-hydroxy-5,5′-diisopropyl-2,
364 mg of 2'-dimethylbiphenyl-3,4-dione was obtained. Melting point 174.5-175.0 ° C IR νmax (KBr) cm ^-1 : 3400,2950,1650,1625,1602,1
385,1325,1208,1170 ¹ H-NMR (CDCl ₃ ) δ: 1.11 (6H, d), 1.25 (3H, d), 1.2
6 (3H, d), 1.76 (3H, d), 2.17 (3H, s), 2.98 (1H, sept), 3.2
2 (1H, sept), 5.11 (1H, brd), 6.62 (1H, s), 6.72 (1H, s),
6.91 (1H, s) MS m / z (%) (C 20 H 24 O 3): 312 (M + 2,100), 300 (18.
4), 299 (76.4), 284 (67.2)

Example 2 From 56.4 mg of 4,4'-dihydroxy-2,2 ', 5,5'-tetramethylbiphenyl, the procedure of Example 1 was repeated to give 4'-hydroxy-2,2', 5, 5'-tetramethylbiphenyl 3,4-dione 3
8.0 mg were obtained. Melting point 160.5-162.0 ° C IR νmax (KBr) cm ^-1 : 3410,2930,1640,1604,1365,1
308,1204,1100 ¹ H-NMR (CDCl ₃ ) δ: 1.74 (3H, s), 1.96 (3H, s), 2.1
6 (3H, s), 2.24 (3H, s), 5.05 (1H, brd), 6.66 (1H, s), 6.72
(1H, s), 6.84 ( 1H, s) MS m / z (%) (C 16 H 16 O 3): 258 (M + 2,100), 225 (29.
1), 167 (16.9), 149 (67.2)

Example 3 4'-Hydroxy-5,5'-diisopropyl-2,2'-dimethylbiphenyl-3,4-dione (106 mg) was dissolved in tetrahydrofuran (10 ml), and the mixture was hydrogenated with stirring at room temperature in a nitrogen stream. 30 mg of sodium boron was added, and the mixture was further stirred at room temperature for 1 hour. 30 ml of 5% hydrochloric acid was added, and the mixture was extracted with 50 ml of ether, washed with brine, dried over sodium sulfate, and the solvent was removed.
Hexane was added for crystallization, and 3,4,4'-trihydroxy-5,5'-diisopropyl-2,2'-dimethylbiphenyl 9
0.7 mg was obtained. 134.5-135.5 ° C IR νmax (KBr) cm ^-1 : 3560,3380,2960,1620,1430,1
340,1250,1175 ¹ H-NMR (CDCl ₃ ) δ: 1.24 (3Hx2, d), 1.25 (3Hx2, d),
1.95 (3H, s), 1.98 (3H, s), 3.18 (1Hx2, brd), 4.72 (1H, br
d), 5.05 (1H, brd), 5.19 (1H, brd), 6.53 (1H, s), 6.65 (1
H, s), 6.92 (1H , s) MS m / z (%) (C 20 H 26 O 3): 314 (M + 2,100), 299 (92.
4), 284 (5.9), 142 (17.6)

Example 4 3,4,4 'from 32.4 mg of 4'-hydroxy-2,2', 5,5'-tetramethylbiphenyl-3,4-dione in the same manner as in Example 3.
-25.0 mg of trihydroxy-2,2 ', 5,5'-tetramethylbiphenyl were obtained. Melting point 87.0-88.5 ° C IR νmax (KBr) cm ^-1 : 3310,2930,1620,1490,1400,
1255,1070 ¹ H-NMR (CDCl ₃ ) δ: 1.93 (3H, s), 1.97 (3H, s), 2.22
(3H, s), 2.24 (3H, s), 4.59 (1H, brd), 4.97 (1H, brd), 5.07 (1
H, brd), 6.48 (1H , s), 6.66 (1H, s), 6.82 (1H, s) MS m / z (%) (C 16 H 18 O 3): 258 (M +, 100), 242 (13.
6), 225 (27.1), 78 (21.1)

[0022]

According to the present invention, there are provided a biphenyl compound which is useful as an antioxidant and a deodorant and can be used as an intermediate of a compound having various usefulness, and a production method thereof which can be industrially applied. Is done.

────────────────────────────────────────────────── ─── Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI // C07B 61/00 300 C07B 61/00 300 C09K 15/08 C09K 15/08 C11B 9/00 C11B 9/00 N (58) Field surveyed (Int. Cl. ⁷ , DB name) C07C 46/06 C07C 37/07 C07C 39/15 C07C 50/28 C07B 61/00 300 C11B 9/00 C07C 46/04 CA (STN) REGISTRY (STN)

Claims (4)

(57) [Claims] 1. A compound of the general formula (II) (Wherein R ₁ represents a C _1-3 alkyl group) and cobalt perchlorate and α, α, α ′, α′-tetrakis-
Oxidation in the presence of a complex with (1-methyl-1H-imidazol-2-yl) -2,6-pyridinedimethanol yields a compound of general formula (I) (Wherein R ₁ has the same meaning as described above). 2. The compound of the formula (I) obtained in claim 1 is reduced to give the compound of the formula (I ') (Wherein R ₁ has the same meaning as described above). 3. The formula: A compound represented by the formula: 4. The formula: A compound represented by the formula: