JPS5989653A - Preparation of 4-hydroxyphenylacetonitrile - Google Patents

Abstract

PURPOSE:To prepare the titled compound useful as an intermediate for the preparation of agricultural chemicals and pharmaceuticals, economically in an industrial scale, by reacting 4-benzyloxyphenyl-acetonitrile with hydrogen halide gas in a solvent, if necessary in the presence of an amine. CONSTITUTION:The objective compound is prepared by dissolving 4-benzyloxyphenyl-acetonitrile in a solvent such as benzene, introducing hydrogen halide gas in the solution, and heating the system at 30-100 deg.C thereby eliminating the benzyl group while keeping the nitrile group unchanged. A further desirable result can be attained by adding small amount of one or more amines, amides and quaternary ammonium salts to the reaction system. EFFECT:The objective compound can be prepared in high yield and purity using a raw material available easily in an industrial scale.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an industrially advantageous method for producing 4-hydroxyphenylacetonitrile. More details 1. (t-j
, 4-benzyloxyphenylcetonitrile (r
The present invention relates to a method for producing 4-hydroxyphenylacetonitrile, which is characterized by reacting 4-hydroxyphenylacetonitrile (referred to as PONPJ) with hydrogen gas/hydrogen gas in a solvent. 4-Hydroxyphenylacetonitrile 1-Iri is an important intermediate used in the production of substances useful as pesticides and medicines, especially when hydrolyzed to produce nitrile &i
By converting it into a mitido group, it can be used as an intermediate for the synthesis of β-blockers, and by hydrolyzing it and converting it into parahydroxyphenylacetic acid, it can be used as a compound.

Conventional method for producing 4-hydroxyphenyl (4-hydroxyphenyl) and 1. Here, we will discuss the method of reacting 4-chocetoxybennylacetate with potassium cyanide in methanol (H,
HF3. yaF3hi, S, 0hta, , Bu
lljIunt? C! method of heating to 130°C with sodium cyanide and sodium hydroxide (I) rum (Japanese Patent Application Laid-Open No. 148744/1982), halacresol was completely acetylated to 4-acetoxytoluene using a chlorinating agent, -acetoxybenzyl chloride and then reacting with potassium cyanide to obtain 4-hydrohydrochloride.
A method of converting it into 2-xyphenylacetonitrile (Japanese Unexamined Patent Publication No. 56-90052) is known. However, none of these methods can be called excellent industrial production methods because the starting materials are industrially available solid solutions or the intermediates have poor crystallinity and are extremely difficult to separate and purify.

The inventors of the present invention used industrially easily available raw materials as a result of intensive research to overcome the drawbacks of conventional methods.

The present invention was completed by discovering a method for synthesizing the target product with high yield and high purity. PCNPij, which is the starting material of the present invention, can be synthesized according to the following formula (% Open/Close Publication No. 57-149241).

In many alkoxyphenylacetonitriles, under reaction conditions that cleave the ether bond, the nitrile group is hydrolyzed to a carboxylic acid or ester, reduced to form an aminomethyl compound, or a H, 2)+1 group. It is difficult to obtain hydroxyphenylacetonitrile in a high yield under conditions where the ether bond is not cleaved under conditions where hydroxyphenylacetonitrile is maintained intact. The present inventors investigated the types of alkoxy groups and the ease of cleavage of ether bonds, and found that PCNP, a nitrile with a benzyl group, retains a nitrile group and is extremely easily cleaved under vine conditions to form a free hydroxyl group. I found it. The method of the present invention.

Be/Sen PCNP. After dissolving it in a solvent such as toluene, it is heated while introducing hydrogen halide gas to retain the nitrile group and eliminate the benzyl group. Hydrogen chloride and hydrogen bromide can be used as the hydrogen halide, but hydrogen chloride gas is preferred from an economic standpoint. Further promotes the reaction.

In order to suppress by-products and carry out the method of the present invention under milder conditions than zero reaction gold, amines such as dimethylamine hydrochloride, triethylamine, pyridine, quinoline, etc. [, N, N
Favorable results can be obtained by adding a small amount of one or more quaternary ammonium salts such as amides such as methylformamide and trioctylmethylammonium chloride, )+3ethylbenzylammonium chloride.

The reaction is preferably carried out in a temperature range of 50°C to 100°C; below 30°C, the benzyl group is removed too slowly and is not practical (
, 100° C. or higher is not preferable because the yield of the target product decreases.

In the method of the present invention, the ether bond is cleaved with hydrogen halide gas, and at that time, benzyl halide is quantitatively produced, which can be used as a raw material for the production of benzyl phenyl ether, which is the starting material for the production of PONPIi. One of the features of the present invention is that it can be recovered and reused. Further, by using the be/zyl group as a protecting group for the phenolic hydroxyl group, not only does the cleavage of the ether bond become easy, but also the crystallinity is good and purification at the raw material stage is extremely easy. After the reaction, 4-hydroxyphenylacetonitrile can be extracted from the reaction solution by distilling off the solvent and benzyl 10-genide, etc., and then obtaining it in a vacuum chamber, or by adding water and then extracting with a solvent such as ethyl acetate or methyl isobutyl ketone. It can be obtained in high yield by

The present invention provides a method for producing 4-hydroxyphenylacetonitrile tl- by using PCNPf as a raw material and cleaving the ether bond while retaining the nitrile group, and is highly economical (an industrially advantageous production method). be.

Embodiments of the present invention will be described in detail below, but the present invention is not limited thereto.

Example P CN P 12.4 f (0, [15 mol), toluene 25 ml, pyridine 3.95 f7! Hydrogen chloride gas was introduced into the solution at a rate of 20-7 minutes and heated to 80° C. with stirring. After continuing the reaction for 10 hours, the introduction of hydrogen chloride gas was stopped and toluene was distilled off under reduced pressure.5. Of
4-hydroxyphenylcetonitrile was obtained (yield: 75 cm). Melon p, 67-68℃ NMR (DM80-d, +CDQl,): δ3.68
(s, 2H), 6.80 (d, 2H, J==8.
5Hz)715(4,2H,J=8.5H2), 9
．． 50 (bs, IH) 6- Example 2 P CN P 6.24 f (0.02 mol) Introducing hydrogen chloride gas at a rate of 154/min into a solution of toluene 8.1 V, dimethylamine/hydrochloride 2.42 and heated to 80° C. with stirring. After continuing the reaction for 7 hours, the introduction of hydrogen chloride gas was stopped and toluene was distilled off under reduced pressure.
a-Hydroxyphenylacetonitrile was obtained (yield: 8
0chi).

Example 3 Trioctylmethylammonium chloride 0.66f in place of 2-methylamine hydrochloride, ) toluene 771, water 0
．． Example 2 except that 18f and reaction time 'ii were 6 hours.
The reaction was carried out in the same manner as in 17f, 4=hydroxyphenylacetonitrile'l! 7'C ([464chi).

Patent applicant: Nissan Chemical Industries, Ltd. -7 Helmet- 511-

Claims (2)

[Claims] (1) A method for producing 4-hydroxyphenylacetonitrile, which comprises reacting 4-benzyloxyphenylacetonitrile with hydrogen halide gas in a solvent. (2) The manufacturing method according to claim (1), characterized in that one or more of amines, amides, and quaternary ammonium salts are allowed to coexist.