KR100666191B1 - A preparation method for 4-cyanophenyl isocyanate - Google Patents

Abstract

Provided is a method for preparing 4-cyanophenyl isocyanate, which has no harmful factors in processing steps, avoids a need for an expensive material or catalyst, and includes simple processing steps. The method for preparing 4-cyanophenyl isocyanate comprises the steps of: (a) reacting 4-cyanobenzoate represented by the following formula (II) with hydrazine to obtain 4-cyanobenzhydrazide represented by the following formula (III); and (b) reacting the 4-cyanobenzhydrazide represented by formula (III) obtained from step (a) with an nitrous acid inorganic salt or nitrous acid ester to obtain 4-cyanophenyl isocyanate represented by the following formula (I). In the reaction scheme, R is H or a C1-C6 alkyl, and R' is a C1-C6 alkyl.

Description

A preparation method for 4-cyanophenyl isocyanate

The present invention relates to a method for producing 4-cyanophenyl isocyanate, which is an important intermediate for the preparation of medicines, herbicides, photosensitive materials and the like.

4-cyanophenyl isocyanate can be used for medicines related to blood, cell proliferation or enzyme inhibition (US 20030229099, WO 2003072549, EP 1315715, US 5430043), herbicides (WO 9324464, US 4806653), photosensitive recording materials (JP 61056348, US 4668610) It is an intermediate that has been utilized as a manufacturing intermediate.

Several publications have been made on the preparation of 4-cyanophenyl isocyanate. Most of the known production methods are prepared from expensive cyanoaniline, which is Japanese Patent No. 58008052, which is prepared by reacting 4-cyanoaniline with trichloromethyl chloroformate under activated carbon or iron oxide catalyst. Recently, Chinese Patent No. 1388116 discloses that 4-cyanoaniline was prepared by heating with triphosgene under an organic solvent. However, trichloromethyl chloroformate or triphosgene used above are derivatives of phosgene, which is a toxic gas, and these are all expensive raw materials.

German Patent No. 146043 discloses a method for preparing an isocyanate compound by reacting a nitro-substituted aromatic compound with a transition metal catalyst under carbon monoxide, which is difficult to handle industrially and uses carbon monoxide, a toxic gas. Since metal catalysts must be used, mass production is difficult in terms of economics and risks.

As such, the known methods of preparing 4-cyanophenyl isocyanate are potentially dangerous in the manufacturing process, and it is disadvantageous to use expensive cyanoaniline or expensive catalyst or raw materials. It is made up of ordinary processes.

Accordingly, the present inventors can easily produce 4-cyanophenyl isocyanate, which is widely used as an intermediate for manufacturing pharmaceuticals, herbicides, photosensitive materials, etc., but the yield is remarkably increased without using expensive raw materials. The method was studied to complete the present invention.

It is an object of the present invention to provide a method for economically producing a high yield of 4-cyanophenyl isocyanate, which is an important intermediate for the preparation of medicines, herbicides, photosensitive materials and the like.

In order to achieve the above object, a method for producing 4-cyanophenyl isocyanate of the present invention is a) 4-cyanobenzyl of formula (III) by reacting 4-cyanobenzoic acid ester of formula (II) with hydrazine Preparing a hydrazide; And b) reacting 4-cyanobenzhydrazide of formula (III) prepared in the step with a nitrite inorganic salt or nitrite ester to prepare 4-cyanophenyl isocyanate of formula (I) It features:

In the above formula, R is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and R 'is an alkyl group having 1 to 6 carbon atoms.

If necessary, the method further comprises filtering and washing the 4-cyanophenyl isocyanate of formula (I).

Hereinafter, the present invention will be described in detail.

The 4-cyanobenzoic acid ester of formula (II), which is used in the reaction of the 4-cyanobenzoic acid ester of formula (II) with hydrazine of step a), is commercially available and is chemically synthesized. Can be used.

The hydrazine used in step a) may use anhydrous hydrazine or an aqueous solution of hydrazine, but using anhydrous hydrazine or hydrazine hydrate having a low moisture content is preferable in terms of yield or purity in order to obtain 4-cyanobenzhydrazide as a product. In addition, hydrazine can be prepared 4-cyanobenzhydrazide of the formula (III) by using 1 to 2 equivalents to 4-cyanobenzoic acid methyl ester, it is economically preferable to use 1 to 1.1 equivalents Do.

The organic solvent used in the reaction of the 4-cyanobenzoic acid ester of Formula (II) and hydrazine of step a) is easy to react and has good workability as water, alcohols, ethers, nitriles, Sulfoxides, amides, carbon chlorides, aromatic organic solvents or mixed solvents thereof may be used, preferably methanol, ethanol, propanol, tetrahydrofuran, 1,4-dioxane or a mixed solvent thereof or These aqueous solutions are used.

The a) step may be reacted at 0 ~ 100 ℃, preferably from 20 to 30 ℃ is advantageous in terms of purity.

In step b), 4-cyanobenzhydrazide of the formula (III) is dissolved in an acid aqueous solution and reacted. As an aqueous acid solution for dissolving 4-cyanobenzhydrazide of formula (III), inorganic acids such as hydrochloric acid, bromic acid, sulfuric acid, phosphoric acid, or organic acids such as acetic acid and formic acid may be used, and preferably hydrochloric acid or sulfuric acid aqueous solution. The inorganic acid or organic acid is used in 1 equivalent or more, preferably 1 to 1.1 equivalents.

As the nitrite inorganic salt used in step b), sodium nitrite or potassium nitrite, which can be easily purchased, may be used, and as the nitrite ester, a lower alkyl ester having 1 to 6 carbon atoms may be used, It is preferable to use an alkyl ester, and nitrite ester or nitrite inorganic salt can use 1-2 equivalent, and it is preferable to use 1-1.1 equivalent.

In addition, step b) may be reacted at 0 ° C. to 60 ° C., preferably at 10 ° C. to 20 ° C., which is advantageous in terms of purity.

In the method for preparing 4-cyanophenyl isocyanate of formula (I) of the present invention, preferably, 4-cyanophenyl isocyanate of formula (I) prepared through the steps a) and b) is separated by filtration. And further comprising the step of washing.

The filtration separation and washing step is to separate the 4-cyanophenyl isocyanate of formula (I) as a solid from the reaction solution. The solid filtrate is preferably washed first with water and then with an organic solvent which can be mixed with water. As the organic solvent, ketones, nitriles, ether organic solvents or a mixed solvent thereof may be used as the organic solvent having good moisture removal and product drying, and acetone, tetrahydrofuran, acetonitrile is preferably used.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the following examples are only examples of the present invention, and the present invention is not limited thereto.

Example  4- Cyanobenzhydrazide  Produce

100.8 g (0.626 mol) of methyl 4-cyanobenzoate and 500 ml of methanol were added to a 1 L reactor and stirred at room temperature to dissolve. 43.05 g (0.688 mol) of hydrazine hydrates were stirred dropwise at 15 to 20 DEG C over 2 hours. After the addition, the mixture was stirred for about 6 hours at the same temperature and filtered. The filtered crystals were washed with about 20 ml of methanol.

The filtrate was concentrated in vacuo to about 150 mL, filtered and washed with 15 mL of methanol, followed by hot air drying at 60 ° C for 6 hours with the filtration crystals obtained above to obtain 97.27 g of 4-cyanobenzhydrazide.

4- Cyanobenzhydrazide

Yield: 95.9%

Melting Point: 195.2 ~ 197.5 ℃

IR (cm ^-1 ) 3267.7, 3187.6, 3003.9, 2226.1, 1650.7

Example  2. 4- Cyanophenyl  Preparation of Isocyanates

100 ml of water and 13.35 g (0.128 mol) of concentrated hydrochloric acid were added to a 250 ml reactor, and 20.76 g (0.128 mol) of 4-cyanobenzhydrazide obtained in Example 1 was added to dissolve with stirring. An aqueous solution of 10.02 g of sodium nitrite dissolved in 100 ml of water was added dropwise to the solution at 10-15 ° C. over 1 hour, stirred at the same temperature for 3 hours, and the resulting crystals were filtered. The filtrate was washed with 30 ml of water and then with 50 ml of acetonitrile and then vacuum dried at 40 ° C. for about 6 hours to give 17.71 g of 4-cyanophenyl isocyanate.

4- Cyanophenyl  Isocyanate

Yield: 96%

Purity: 99.6% (gas chromatography)

Melting Point: 97.5 ~ 99.0 ℃

4-Cyanophenyl isocyanate is an important intermediate for the manufacture of medicines, herbicides, photosensitive materials and the like. Existing methods are expensive raw materials such as 4-cyanoaniline, trichloromethyl chloroformate, and triphosgene. Although the process is high in the use of carbon monoxide and expensive catalysts and low in economic feasibility, according to the manufacturing method of the present invention, there is no risk of the process, and high yield using raw materials that are commercially easy to purchase and manufacture. This is a very useful invention because it can mass-produce 4-cyanophenyl isocyanate.

Claims (8)

a) reacting 4-cyanobenzoic acid ester of formula (II) with hydrazine to produce 4-cyanobenzhydrazide of formula (III); And b) reacting 4-cyanobenzhydrazide of formula (III) prepared in the step with a nitrite inorganic salt or nitrite ester to prepare 4-cyanophenyl isocyanate of formula (I) Method for producing 4-cyanophenyl isocyanate, characterized in that:

In the above formula, R is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and R 'is an alkyl group having 1 to 6 carbon atoms.  The method for preparing 4-cyanophenyl isocyanate according to claim 1, further comprising the step of filtering and washing 4-cyanophenyl isocyanate of formula (I) prepared in step b). The organic solvent used in the reaction of step a) is water, alcohols, ethers, nitriles, sulfoxides, amides, carbon chlorides, aromatic organic solvents, or a mixed solvent thereof. The manufacturing method of 4-cyanophenyl isocyanate made into. The method for preparing 4-cyanophenyl isocyanate according to claim 3, wherein the organic solvent is methanol, ethanol, propanol, tetrahydrofuran, 1,4-dioxane or a mixed solvent thereof or an aqueous solution thereof. The method for producing 4-cyanophenyl isocyanate according to claim 1, wherein the hydrazine is anhydrous hydrazine, hydrazine hydrate, or hydrazine aqueous solution. [4] The preparation of 4-cyanophenyl isocyanate according to claim 1, wherein the 4-cyanobenzhydrazide of step b) is dissolved and used in an aqueous solution of hydrochloric acid, bromic acid, sulfuric acid, phosphoric acid, acetic acid, or formic acid. Way. The method for preparing 4-cyanophenyl isocyanate according to claim 1, wherein the nitrite inorganic salt of step b) is sodium nitrite or potassium nitrite, and the nitrite ester is a lower alkyl ester having 1 to 6 carbon atoms. . The method for preparing 4-cyanophenyl isocyanate according to claim 2, wherein the organic solvent used for washing is a ketone, a nitrile, an ether organic solvent or a mixed solvent thereof.