JPH08169868A - Production of 4-cyano-4'-hydroxybiphenyl - Google Patents

Abstract

PURPOSE: To profitably obtain the subject compound useful as an intermediate for medicines and agrochemicals, a raw material for synthesizing liquid crystal materials, etc., in a high conversion, a high yield and a high selectivity by subjecting 4-acetoxybiphenyl to an iodination reaction, a cyanization reaction and subsequently a hydrolysis reaction. CONSTITUTION: A compound, 4-Acetoxybiphenyl of formula I is iodinated with iodine in the presence of an acid catalyst [e.g. sulfuric acid or (heterogeneous poly)phosphoric acid] and nitrogen dioxide, etc., as an oxidizing agent in a solvent such as dichloromethane to obtain 4-acetoxy-4'-iodobiphenyl of formula II. The compound is cyanized with a slightly excessive amount of cuprous cyanide, etc., in an aprotic polar solvent such as DMF and subsequently hydrolyzed in the presence of an alkali hydroxide, etc., in an alcoholic solvent to obtain the objective 4-cyano-4'-hydroxybiphenyl of formula III.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a process for producing 4-cyano-4'-hydroxybiphenyl, which is useful as a raw material for the synthesis of medical and agricultural chemical intermediates, liquid crystal materials and organic photoconductive materials.

[0002]

2. Description of the Related Art In recent years, 4-cyano-4'-hydroxybiphenyl has attracted attention as an intermediate for medicines and agricultural chemicals, a liquid crystal material or an organic photoconductive material, and it is desired to develop a synthetic method which can be produced at a lower cost. There is. Conventional manufacturing methods include, for example,
(Zh.Org.Khim., 1984, (20), 1310.) 4-cyanobiphenyl as a starting material, which is then subjected to nitration, reduction, diazotization, and then hydrolysis to 4-cyano-4'-hydroxy. The method of synthesizing biphenyl is also described in (J.Chem.Soc., Chem.Commun19
88, 203.) reported a photochemical synthesis method using 4-chlorobenzonitrile and 2,6-di-t-butylphenol as raw materials. However, these methods are economically difficult to adopt as industrial manufacturing methods.

On the other hand, Japanese Patent Publication No. 1-39474 uses 4-cyano-4'-hydroxybiphenyl as a raw material for synthesizing the liquid crystal material, and its synthesis method is also described. According to this, as shown in the following formula, 4-acetoxybiphenyl is used as a starting material, and this is brominated to hydrolyze the acetoxy group and 4-bromo-4'-hydroxybiphenyl is obtained by substituting the bromo group with a cyano group. I am synthesizing.

[0004]

[Chemical 4]

In the bromination using iodine as a catalyst in this method, the yield is low and the utilization efficiency of bromine is poor, which causes a cost increase. As a method for improving the bromination of 4-acetoxybiphenyl, a method of coexisting metal carbonate, etc.
(JP-A-1-172361) and a method of using an inert solvent insoluble in water (JP-A-5-286898) are disclosed. Although the yield and the like have been considerably improved by these methods, for example, in the method using a metal carbonate, it is necessary to pay close attention to reaction control, and a metal bromine salt produced in a large amount cannot be substantially recycled. Further, the method using water and an insoluble inert solvent has overcome such problems, but expensive hydrogen peroxide is required as an oxidant in order to increase the utilization efficiency of bromine. There is also the problem that peroxides are potentially explosive.

Further, in the case of synthesizing a cyano compound via a bromine compound as in the above process, it is practically difficult to reuse the copper bromide formed after the reaction, and therefore 4-cyano- When producing 4'-hydroxybiphenyl, the bromine used has the essential drawback that it results in total waste.

[0007]

The object of the present invention is to provide an economical and industrially feasible method for producing 4-cyano-4'-hydroxybiphenyl.

[0008]

The present invention provides 4-cyano-4'-
It has been completed as a result of various studies on a method for producing hydroxybiphenyl, and 4-acetoxy-biphenyl obtained by iodizing 4-acetoxybiphenyl (formula (I)).
By substituting the cyano group for the iodo group of 4'-iodobiphenyl (formula (II)) and hydrolyzing the acetoxy group, 4-cyano-4'-hydroxybiphenyl (formula
(III)).

[0009]

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[0010]

[Chemical 6]

[0011]

[Chemical 7]

It is particularly preferable to use nitrogen dioxide as the oxidizing agent used in this iodination reaction. That is,
When nitrogen dioxide is used as an oxidant, it is cheap and easy to handle,
In addition, it can be selectively iodinated under mild conditions. This nitrogen dioxide becomes nitric oxide after the reaction, and it easily regenerates the nitrogen dioxide upon contact with air, so that it can be recycled for the next reaction.

Further, in the present invention, copper iodide produced after the cyanation reaction is prepared by using inexpensive nitric acid or nitrogen dioxide.
(Japanese Patent Publication No. 52-27633, 53-41118) Since iodine can be recovered and reused by the method described in (3), the production method of the present invention is
It is a manufacturing method that can significantly reduce the amount of waste while improving the economic efficiency. Furthermore, since the iodine and iodine compounds used or produced in the process of the present invention have less possibility of corrosion than bromine and bromine compounds, the production method of the present invention is industrially extremely advantageous.

The present invention will be described in detail below. The 4-acetoxybiphenyl used as a starting material in the present invention is easily synthesized by reacting 4-hydroxybiphenyl with a suitable acetylating agent such as acetic anhydride or acetyl chloride by a conventionally known method.

The iodination of 4-acetoxybiphenyl is carried out by adding nitrogen dioxide in the presence of iodine and an acid catalyst in a suitable solvent. The reaction temperature is 10 to 150 ° C, especially
The temperature is preferably 30 to 90 ° C, and the reaction time is suitably 0.5 to 15 hours, particularly 1 to 8 hours.

As the above solvent, lower alkyl cyanide such as acetonitrile, lower fatty acid such as acetic acid and propionic acid, halogenated hydrocarbons such as dichloromethane, chloroform and dichloroethane can be used.
Among these, halogenated hydrocarbons are preferable. This is because, in consideration of the post-treatment process after the reaction, it is preferable to use one that is difficult to mix with water. The amount of solvent used is 300 ml to 5000 ml, preferably 500 ml, per 1 mol of 4-acetoxybiphenyl.
~ 3000 ml. The amount of iodine used is about 1/2 molar ratio to 4-acetoxybiphenyl. That is, since the theoretical amount of iodine is consumed, if it is too large, a diiodo form is produced, and if it is too small, the yield of iodination is lowered. Iodine may be added in the total amount from the initial stage of the reaction, or may be sequentially added as the reaction progresses.

As the acid catalyst used in this iodination,
Nonvolatile protic acids and solid acid catalysts can be used. Specifically, as the non-volatile protonic acid, sulfuric acid,
Examples thereof include phosphoric acid and heteropolyphosphoric acid. Examples of solid acid catalysts include those in which the above-mentioned nonvolatile protonic acid is supported on an inorganic carrier, or unsupported silica gel. The method for preparing the supported catalyst is not particularly limited. It is prepared by a known appropriate method, for example, an impregnation method, an evaporation-drying method, a gelation method and the like. The amount of the catalyst used is 5 to 100% by weight, preferably 10 to 50% by weight, based on 4-acetoxybiphenyl.

The amount of nitrogen dioxide used as oxidant is
The amount is 1 to 5 times, preferably 2 to 5 times the mol of 4-acetoxybiphenyl. As for the method of adding nitrogen dioxide, the entire amount may be added from the initial stage of the reaction, it may be dissolved in a solvent to be used and then added sequentially, or it may be blown in a gaseous state. that time,
It may be entrained in an inert gas such as nitrogen gas.

The product separation can be easily carried out by filtration and solvent extraction. For further purification, the extract can be concentrated and recrystallized. Examples of the solvent used for recrystallization include alcoholic solvents such as methanol, ethanol and isopropanol.

Next, the cyanation reaction of 4-acetoxy-4'-iodobiphenyl is described in the literature (J. Org. Chem., 1961, Vol26, 25).
It can be carried out according to the method described in 22.). That is,
4-acetoxy-4'-iodobiphenyl and a small excess of cuprous cyanide in an aprotic polar solvent such as dimethylformamide (DMF) or dimethylsulfoxide (DMSO) at 120-200 ° C for 1-10 It can be easily performed in high yield by heating for a long time.

Subsequent hydrolysis is carried out according to a conventional method by adding 4-acetoxy-4'-cyanobiphenyl in an alcohol solvent.
By saponifying with an alkali hydroxide and treating the resulting alkali metal salt with an appropriate acid such as hydrochloric acid, it is possible to easily 4-
Cyano-4'-hydroxybiphenyl can be obtained.

The order of cyanation and hydrolysis may be exchanged. That is, 4-acetoxy-4'-iodobiphenyl is hydrolyzed to 4-hydroxy-4'-iodobiphenyl, which can be cyanated to give 4-cyano-4'-hydroxybiphenyl in almost the same yield. it can.

[0023]

EXAMPLES The present invention will be specifically described below with reference to examples. [Example 1] Iodination reaction step First, a phosphomolybdic acid-supported silica gel catalyst was prepared by a gelation method. That is, 5.0 g of phosphomolybdic acid was collected, and silica sol (CATALOID- manufactured by Catalyst Kasei Co., Ltd.) was collected.
S-30L, SO ₂ content 30 wt%) 66.7 g and mixed well. Next, the water was evaporated to dryness at 120 ° C. with stirring. The obtained solid was pulverized and calcined in an electric furnace at 300 ° C. for 4 hours to obtain a phosphomolybdic acid-supported silica gel catalyst. The supported amount of phosphomolybdic acid was 20 wt%. Next, in a three-necked flask equipped with a cooling tube, 2.13 g (10 mmol) of 4-acetoxybiphenyl, 1.29 g (5 mmol) of iodine, and 20 wt% of phosphomolybdic acid described above, Silica gel 1.
00 g was taken, and 20 ml of dichloroethane was added thereto. The contents were heated under reflux with stirring, and nitrogen gas containing a predetermined amount (about 3%) of nitrogen dioxide was blown into the contents for 3 hours. The amount of nitrogen dioxide used was 0.99 g (22 mmol). When the reaction product was analyzed by gas chromatography, 4-acetoxy-4'-iodobiphenyl was produced at a conversion rate of 4-acetoxybiphenyl of 100% and a selectivity of 74%.

After allowing the reaction solution to cool, the catalyst was filtered and separated.
The filtrate was washed with 5% sodium thiosulfate solution and then with 5% sodium carbonate solution, concentrated, and the residue was mixed with 50 ml of ethanol.
Was recrystallized to obtain 2.16 g of 4-acetoxy-4'-iodobiphenyl. The yield was 64% and the purity was 96%.

[Example 2] Iodination reaction step In a three-necked flask equipped with a cooling tube, 2.13 g (10 mmol) of 4-acetoxybiphenyl, 1.30 g (5 mmol) of iodine and 1.
02 g was taken and 20 ml of chloroform was added thereto. The contents were heated under reflux with stirring, and a nitrogen gas containing a predetermined amount of nitrogen dioxide was blown into the contents for 3 hours. The amount of nitrogen dioxide used was 1.72 g (37 mmol). When the reaction product was analyzed by gas chromatography, 4-acetoxy-4'-iodobiphenyl was produced at a conversion rate of 4-acetoxybiphenyl of 64% and a selectivity of 97%.

[Example 3] Cyanation reaction 4-acetoxy-4'-iodobiphenyl obtained in Example 1
1.71 g (4.9 mmol) and cuprous cyanide 0.53 g (5.9 mmol)
Place it in a three-necked flask equipped with a condenser and add 2.4 ml of DMF to it.
Was added. The contents were heated with stirring at a bath temperature of 160 ° C. for 5 hours. After allowing to cool, the content was diluted with 30 ml of chloroform, and the produced copper salt was separated by filtration. The filtrate was washed with a 10% aqueous ammonia solution and then with water, and then concentrated to dryness to obtain 1.13 g of 4-acetoxy-4'cyanobiphenyl. Yield 98%, purity
It was 95%.

Example 4 Hydrolysis Reaction 1.00 g (4.0 mmol) of 4-acetoxy-4′-cyanobiphenyl obtained in Example 3 was dispersed in 20 ml of ethanol, and 0.56 g of potassium hydroxide ( 10 mmol) in ethanol (10 ml)
Was dripped. After stirring at room temperature for 1 hour, 30% of 5% hydrochloric acid was added.
The resulting white precipitate was filtered and washed with distilled water,
After drying, 0.75 g of crude 4-cyano-4'-hydroxybiphenyl was obtained. This was recrystallized from 20 ml of isopropanol and recrystallized.
70 g of 4-cyano-4'-hydroxybiphenyl were obtained. yield
The purity was 90% and the purity was 99%.

[0028]

INDUSTRIAL APPLICABILITY According to the present invention, 4-acetoxy-biphenyl (formula (I)) is iodinated to obtain 4-acetoxy-
By substituting the cyano group for the iodo group of 4'-iodobiphenyl (formula (II)) and hydrolyzing the acetoxy group, 4-cyano-4'-hydroxybiphenyl (formula
(III)) can be produced.

Claims (2)

[Claims] 1. A 4-acetoxy biphenyl represented by the formula (II) obtained by iodizing 4-acetoxybiphenyl represented by the formula (I).
-4'-iodobiphenyl, a formula (III) consisting of a step of substituting a cyano group for the iodo group of the resulting 4-acetoxy-4'-iodobiphenyl and a reaction of hydrolyzing the acetoxy group. ) A method for producing 4-cyano-4′-hydroxybiphenyl represented by Embedded image Embedded image Embedded image 2. The method according to claim 1, wherein the step of iodating 4-acetoxybiphenyl is an iodination reaction using nitrogen dioxide as an oxidizing agent in the presence of iodine and an acid catalyst. -Method for producing cyano-4'-hydroxybiphenyl.