RU2331634C1 - Method of obtaining 3-phenoxyphenylcyanohydrine - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention pertains to synthesis of nitriles, particularly to the method of obtaining 3-phenoxyphenylcyanohydrine, which can be used as a half-finished product in the synthesis of some biologically active substances. The method of obtaining 3-phenoxyphenylcyanohydrine with formula:

involves reaction of 3-phenoxybenzaldehyde with acetoncyanohydrine at high temperature for a period of 1.5-2 hours in the presence of a potassium carbonate catalyst with molar ratio 3-phenoxybenzaldehyde : acetoncyanohydrine : potassium carbonate equal to 1 : 1 : 0.015-0.02 with subsequent separation of the end product through re-crystallisation from a mixture of chloroform-hexane solvents in ratio of 1:1.5.

EFFECT: increased output and purity of proposed compound with shortening of the duration and simplification of the process.

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Description

The present invention relates to the field of synthesis of nitriles, in particular to a method for producing 3-phenoxyphenylcyanohydrin of the formula

which may be of interest as an intermediate in the synthesis of certain biologically active substances.

A known method of producing 3-phenoxyphenylcyanohydrin, which consists in the interaction of 3-phenoxybenzaldehyde with acetone cyanohydrin in a molar ratio of 3-phenoxybenzaldehyde: acetone cyanohydrin equal to 1: 2 in DMF with stirring under reflux and a temperature of 60-70 ° C for 5 hours, s subsequent neutralization with concentrated sulfuric acid to a pH of 2.3 and distillation on a water-jet pump at P = 15 mm Hg [a.s. 1809602 C07C 255/42. Publ. 06/30/94,].

The disadvantages of this method are the long process time, the use of a 2-fold excess of acetone cyanohydrin, a rather laborious stage of product isolation, and the yield of 3-phenoxyphenyl cyanohydrin does not exceed 80%.

The objective of the proposed technical solution is to develop a new technologically advanced method for producing 3-phenoxyphenylcyanohydrin in good yield and high purity, allowing synthesis in one stage with shorter process time.

The technical result is to increase the yield and purity of the claimed compound, reducing the process time, the absence of solvent, reducing the ratio of reagents and simplifying the stage of isolation of the final product.

The technical result is achieved in the method for producing 3-phenoxyphenylcyanohydrin of the formula

consisting in the interaction of 3-phenoxybenzaldehyde with acetone cyanohydrin at an elevated temperature for 1.5-2 hours in the presence of a potassium carbonate catalyst with a molar ratio of 3-phenoxybenzaldehyde: acetone cyanohydrin: potassium carbonate equal to 1: 1: 0.015-0.02, followed by isolation the final product by recrystallization from a mixture of solvents of chloroform-hexane in a ratio of 1: 1.5.

The essence of the proposed method is the cyanohydrination reaction of 3-phenoxybenzaldehyde with acetone cyanohydrin in the presence of potassium carbonate as a catalyst:

Removal of the formed acetone from the reaction zone shifts the equilibrium towards product formation and inhibits the occurrence of side processes. Thus, the yield and purity of 3-phenoxyphenylacetone cyanohydrin is increased.

As the studies showed, the optimal and technological condition for the reaction is to use a molar ratio of 3-phenoxybenzaldehyde: acetone cyanohydrin: potassium carbonate equal to 1: 1: 0.015-0.02. 3-phenoxybenzaldehyde and acetone cyanohydrin are taken in a stoichiometric ratio and the use of an excess of acetone cyanohydrin is impractical, since a quantitative yield of acetone is already achieved with a molar ratio. A decrease in the amount of catalyst increases the duration of the reaction, and an increase does not lead to an increase in the yield of the target product. The optimal process time is 1.5-2 hours. Reducing the reaction time leads to incomplete conversion of 3-phenoxybenzaldehyde and a decrease in the yield of the target product. The increase in reaction time is impractical, since for the specified interval 100% conversion is achieved.

The resulting 3-phenoxyphenylacetone cyanohydrin is soluble in most known solvents and insoluble in hexane. Therefore, for its purification by recrystallization, a solvent system of chloroform-hexane was selected in a ratio of 1: 1.5. This ratio is optimal, since with an increase in the amount of chloroform 3-phenoxyphenylacetone cyanohydrin does not crystallize, and with a decrease it does not completely dissolve when heated.

The proposed method allows to obtain 3-phenoxyphenylacetone cyanohydrin, in one stage with a high yield. Its advantages include preparative simplicity of synthesis and ease of isolation of the target product in its pure form.

The method is as follows.

3-Phenoxybenzaldehyde, acetone cyanohydrin and potassium carbonate are mixed in a reactor equipped with a thermometer and a top-down refrigerator with a receiver for collecting stripping acetone. Then the reaction mass is heated and maintained at the boil of the acetone released during the reaction until it is completely distilled off. The yield of acetone is quantitative. At the end of the process, the reaction mass is diluted with diethyl ether, potassium carbonate is filtered off and the ether is removed in a vacuum of a water-jet pump. The resulting product is purified by recrystallization from a mixture of chloroform-hexane in a ratio of 1: 1.5.

Purity 97.6% (according to GLC). Mp 128-130 ° C.

¹ H NMR spectrum, δ, ppm: 5.78 s (1H, -CH-), 3.219 s (1H, -OH), 6.89-8.944 (9H, C ₆ H ₅ OC ₆ H ₄ ) .

IR spectrum, ν, cm ^-1 : 3214 (ОН), 1456 (С-O), 1582-1522 (vibrations of the aromatic ring).

The invention is illustrated by the following examples.

Example 1

3-Phenoxybenzaldehyde (7.92 g, 6.88 ml, 0.04 mol), acetone cyanohydrin (3.4 g, 3.7 ml, 0) are mixed in a reactor equipped with a thermometer and a descending cooler with a receiver for collecting stripping acetone. 04 mol) and potassium carbonate (0.085 g, 0.0006 mol). Then the reaction mass is heated and maintained at the boil of acetone released during the reaction until it is completely distilled off (2 hours). The yield of acetone is quantitative (volume of distilled acetone 2.3 ml). At the end of the process, the reaction mass is diluted with diethyl ether, potassium carbonate is filtered off and the ether is removed in a vacuum of a water-jet pump. The resulting product is purified by recrystallization from a mixture of chloroform-hexane in a ratio of 1.:1.5. Yield 8.94 g (0.0397 mol, 99.3%).

Example 2

The procedure is similar to Example 1. Downloads: 3-phenoxybenzaldehyde (9.1 g, 7.9 ml, 0.046 mol), acetone cyanohydrin (3.91 g, 4.2 ml, 0.046 mol) and potassium carbonate (0.13 g, 0 , 0009 mol). The time is 1.5 hours. The yield of acetone is quantitative (volume of distilled acetone 2.65 ml). Yield 10.3 g (0.0458 mol, 99.5%).

findings

The proposed method for producing 3-phenoxyphenylcyanohydrin is technologically advanced and allows to reduce the reaction time to 2 hours, which is less than in the known method (5 hours), and to increase the yield to 100%, which is higher than in the known method (80%).

Claims (1)

A method of obtaining a 3-phenoxyphenylcyanohydrin of the formula

consisting in the interaction of 3-phenoxybenzaldehyde with acetone cyanohydrin at elevated temperature, characterized in that the interaction is carried out for 1.5-2 hours in the presence of a potassium carbonate catalyst at a molar ratio of 3-phenoxybenzaldehyde: acetone cyanohydrin: potassium carbonate equal to 1: 1: 0.015- 0.02, followed by isolation of the final product by recrystallization from a solvent mixture of chloroform-hexane in a ratio of 1: 1.5.