KR820002007B1 - Process for preparation of methylene organoal-kyated compounds - Google Patents

Abstract

Active methylene cpd. is reacted with organoalkyl cpd. to produce methylene organoalkylated cpd. The active methylene cpd. is e.g. malnonitrile, malonic acid, diethylmalonate, acetylacetone, opt. substd. phenylacetic acid. The org. alkyl cpd. is alkyl halide, aralkyl halide, vinyl halide, haloacetate. The improvement is that the reaction is carried out in inert org. solvent dispersion of fine alkali hydroxide, in which the dispersion is treated to from hydroxide particles of dia. 100-500 microns. Prod. is obtd. in high yield and purity. They are useful as intermediates from agrochemicals and pharmaceuticals.

Description

Process for preparing methylene alkylate

The present invention relates to a method for preparing an active methylene alkylate. More specifically, the present invention is prepared by reacting an active methylene compound with a halogenated organic alkyl in the presence of a water-activated organic solvent dispersion of particulate alkali hydroxides having a unit of μm in a particle size ranging from 100 μm to 500 μm. A method for preparing methylene organic alkylates useful as intermediates is provided.

Conventionally, since alkali hydroxide has strong hygroscopicity, it was difficult to obtain particulate alkali hydroxide.

Moreover, in the condensation reaction which is reaction of a halide and the compound which has an active hydrogen atom, base aqueous solutions, such as alkali hydroxide and carbonate, have been used.

In the case of using an aqueous base solution in a condensation reaction such as hydrogen halide, the product may decompose due to the aqueous base solution. In order to overcome this problem, it has been thought that a solid base such as alkali hydroxides or carbonates should be used. However, alkali hydroxides are hygroscopic and insoluble in inert organic solvents.

However, these conventional methods are not satisfactory as industrial methods because of various drawbacks. In other words,

(1) Because the condensing agent reacts remarkably with water, the incorporation of water decreases the activity of the condensing agent, which leads to a decrease in the yield of the silent compound. And reaction manipulation is very demanding and disadvantageous.

(2) Because of the use of an aprotic polar solvent such as dimethyl sulfoxide, which is expensive and water-soluble, it is difficult to recover, which is disadvantageous from an economic point of view.

(3) As it uses expensive and water-soluble quaternary ammonium salts as catalysts, it increases the concentration of nitrogen in rivers, sea areas and lakes, causing environmental pollution. Do.

The present inventors have conducted research in order to overcome these drawbacks of the conventional methods.

It has been known to prepare methylene organic alkyl compounds by reacting an active methylene compound with a halogenated organic alkyl in the presence of an alkali hydroxide.

(1) The reaction is carried out in the presence of alkali hydroxides (Organization Vol. 9, p. 107).

(2) This reaction is carried out in a reaction medium of an aprotic polar solvent such as dimethyl sulfoxide (J. Org. Chem Vol. 34, p. 226, 1969).

(3) The reaction is carried out in the presence of a quaternary ammonium salt catalyst (Acta. Chem. Scand. Vol. 23, p. 2204, 1969; Tetrahedron Lett, vol. 15, 1273, 1973; Tetrahedron, vol. 32, 2235, 1976).

One important example of reacting an active methylene compound with a rohalogenated organoalkyl is to prepare α-isopropyl halophenyl acetonitrile, for example

(1) A method of reacting in the presence of these using an alkali metal, an alkali metal alcoholate, an alkali metal halide or an alkali metal amide as a catalyst (Japanese Laid-open Patent Publication No. 5350/1975).

(2) A method of reacting an alkali hydroxide as a condensing agent with dimethyl sulfoxide and dimethylformamide as a reaction solvent, respectively, in the presence thereof (Japanese Patent Publication No. 154217/1975).

(3) A method of reacting alkali hydroxide as a condensing agent with a quaternary ammonium salt as a catalyst, respectively, in the presence thereof (Japanese Laid-open Patent Publication No. 63145/1976) and the like are known.

An object of the present invention relates to a method for producing an active methylene compound by condensation reaction between a halogenated compound and a compound having active hydrogen in the presence of a particulate alkali hydroxide organic solvent dispersant having a particle size of 100 μm to 500 μ.

The reaction between the active methylene compound and the halogenated organic alkyl is carried out using an inert organic solvent dispersion of particulate hydroxide, thereby avoiding the use of expensive aprotic polar solvents such as dimethyl sulfoxide, and also the use of catalysts such as quaternary ammonium salts. A high purity methylene organic alkyl compound can be obtained in high yield without recovering.

A dispersion of alkali hydroxides is prepared by using an inert organic solvent which is swelling of alkali hydroxides and is suitable for the formation of paste-like alkali hydroxides under heating in a solvent. It is preferable that this inert organic solvent can be used under atmospheric pressure.

For reference, the manufacturing operation of a dispersion liquid is explained in full detail as follows.

Suitable inert organic solvents include aromatic hydrocarbons such as benzene, toluene and xylene, halogenated aromatic hydrocarbons such as chlorobenzene and chlorotoluene, halogenated aliphatic hydrocarbons such as chloroform and carbon tetrachloride and boiling points of 100 캜 or higher, preferably There are other solvents that are at least 120 ° C.

The stirring operation is carried out easily, the solid alkali hydroxide can be stirred in the inert organic solvent to prevent the absorption of alkali hydroxide, and the physical properties of the particulate alkali hydroxide can be improved.

The amount of inert organic solvent should be sufficient to stir the mixture, preferably at least twice the amount of alkali hydroxide.

Examples of stabilizers include compounds having the following structural formulas, polyoxyethylene type nonionic surfactants, fatty acid sorbitan esters, fatty acid glycerol monoesters, fatty acid esters, quaternary ammonium salts, fatty amines, and perfluoro Roalkyl surfactants.

Wherein R and R 'are each hydrogen or C ₁ -C ₄ alkyl, X is an oxygen atom or a sulfur atom, and m and n are each 1 or 1 or more numbers.

Suitable stabilizers include monoalkylglycols such as monomethyl, monoethyl and monopropyl or monostearylglycol ethers, dialkylglycol ethers such as dimethyl, diethyl and dipropyl or dibutylglycol ethers, Polymethylene glycol, ethylene glycol, diethylene glycol, triethylene glycol, tetraethyl butyl glycol, hexaethylene glycol, pentaethylene glycol, isopropylene glycol, polyethylene glycol, propylene glycol, di Glycols such as propylene glycol, tripropylene glycol, tetrapropylene glycol, and polypropylene glycol, monoalkyl sulfides such as 1,4-butanediol, polyvinyl ethers, monomethyl, monoethyl, and monopropyl; Dialkyl sulfides such as monobutyl sulfides, dimethyl, diethyl, dipropyl, dibutyl sulfides, ethylenethioglycools, di Thioglycols such as thiylenethioglycol, triethylenethioglycool, tetraethylenethioglycool, and polyethyleneoglycolate, polymethylenethioglycool, polyoxyethylene type nonionic surfactants, fatty acid sorbitan esters, fatty acids Glycerol monoesters, sugar esters, fatty amines, quaternary ammonium salts and perfluoroalkyl surfactants.

Suitable polyoxyethylene-type nonionic surfactants include polyoxyethylene alkyl ethers such as polyoxyethylene dodecyl ether, polyoxyethylene octadecyl ether and polyoxyethylene nonyl ether, and polyoxyethylene such as polyoxyethylene nonyl phenyl ether. Polyoxyethylene fatty acid esters such as alkylaryl ethers, stearic acid polyoxyethylene and distearic acid polyoxyethylene, polyoxyethylene sorbitan monolaurate,-monopalmitate,-monostearate,-monooleate,- Monooxyethyl sorbitan fatty acid esters such as tristearate and -trioleate, and polyoxyethylene alkylamines such as polyoxyethylene dodecylamine.

Suitable fatty acid sorbitan esters include sorbitan monolaurate,-monopalmirate,-monostearate,-monoolate,-tristearate,-trioleate and-sesquioleate.

Suitable fatty acid esters include glycerol monostearate and glycerol monooleate.

Suitable fatty acid amines include oleyldimethylamine, palm oil dimethylamine and lauryldimethylamine.

Suitable quaternary amines are lauryl trimethylammonium chloride and stearyl trimethylammonium chloride and alkylbenzyldimethyl ammonium chloride.

Suitable perfluoroalkyl surfactants include sulfonic acid perfluoroalkyls such as sulfonic acid perfluorooctyl, perfluorooctyl sulfonylamine hydrohalide, perfluorooctylsulfonyl propylamine ethylene dioxide adduct and sulfonyl Perfluoroalkylsulfonylamine derivatives such as benzylamine ethylene oxide adduct.

The stabilizer amount is usually 0.001% by weight or more, more preferably 0.001% by weight or more, and particularly preferably 0.01% by weight or more based on the alkali hydroxide.

Stabilizers may be used by mixing the above components.

By adsorbing a stabilizer on the surface of the particulate alkali hydroxide to prevent solidification of the dispersed alkali hydroxide in the inert melt, the formation of alkali hydroxide fine particles can be improved and the phenomenon of alkali hydroxide precipitation on the inner wall of the reactor can be prevented.

The stabilizer should be hydrophilic so that it can be adsorbed onto the surface of the alkali hydroxide in an inert organic solvent that is not a hydrophilic solvent.

It is preferable to perform heating and stirring of the mixture of an alkali hydroxide and an inert organic solvent near the boiling point of a solvent, and when a low boiling point inert oil uses a solvent, it is preferable to carry out under high pressure.

Moreover, it is preferable to carry out by stirring at the temperature of 120 degreeC or more under atmospheric pressure, and it can carry out by reducing a temperature under high pressure.

Agitation should be carried out sufficiently to disperse the alkali hydroxide in an inert organic solvent, with or without a stabilizer.

The stirring method is not so important, and the dispersion effect of the alkali hydroxide can be sufficiently obtained by using a suitable stirrer, homomixer, ultrasonic disperser or jet disperser.

In the case of using a stirrer, the rotation speed of the stirrer is preferably 500 r.p.m or more, and more preferably 1000 r.p.m or more.

In the case of using a homogenizer, the stirring speed can be set to 3000r.p.m or more, that is, 10,000r.p.m. In order to disperse | distribute alkali hydroxide by an ultrasonic dispersion operation or a jet dispersion operation, it is preferable to carry out mechanical stirring operation in parallel.

The melting point of the alkaline hydration products is usually 360.4 ° C. for potassium hydroxide and 328 ° C. for sodium hydroxide.

The alkali hydroxide is dispersed below the melting point of the alkali hydroxide during the dispersion operation, but the alkali hydroxide is preferably a paste in an inert organic solvent under heating.

Dispersants of particulate alkali hydroxides having units of mμ to μ, such as 100 μm to 500 μ, can be obtained by the method of the present invention. That is, the fine alkali hydroxide powder which can disperse | distribute an organic solvent and a dispersion liquid and disperse | distributes in a desired solvent by performing a filtration operation or a distillation operation can be obtained.

It is preferable to use an inert organic solvent for reaction of a halogenated compound and the compound which has an active hydrogen atom.

The dispersion liquid which disperse | distributed the particulate alkali hydroxide in the said water-active organic solvent can be used for reaction without solvent separation or exchange.

By the method of the present invention, it is possible to easily obtain a dispersion of fine alkali hydroxides, that is, fine alkali hydroxide powders, and to prevent the adhesion of alkali hydroxides to the inner wall of the reactor, which is a significant effect in the present invention. .

The particle size of the produced particulate alkali hydroxide can be obtained in a range of 100 μm to 500 μ by adjusting the stirring method.

Dispersions of fine alkali hydroxides are quite effective for condensation reactions such as chelation, especially alkylation, which introduces active methylene groups.

Inert solvent dispersions of alkali hydroxides are new important reactants for the reaction of active methylene compounds with halogenated organic alkyls.

Halogenated organoalkyl is added to an inert organic solvent dispersion of alkyl hydroxide, and an active methylene compound is added thereto to react them.

The reaction between the active methylene compound and the halogenated organic alkyl is carried out in a dispersion of fine alkali hydroxides having a particle diameter of less than several hundred microns as a condensing agent.

It is preferable to use a dispersion in which fine potassium hydroxide is dispersed in an inert organic solvent. This reaction is carried out slowly without any condensation agent, or with no specific solvent or particular catalyst, and high purity α-isopropyl halophenyl acetonitrile is obtained in high yield.

In the process of the present invention, the dispersion of fine alkali hydroxides is mixed with an organoalkyl halide, followed by addition of an active methylene compound to react them.

The reaction temperature is in the range of 0 to 150 ° C, preferably in the range of 20 to 60 ° C, and the reaction is carried out under atmospheric pressure, and the reaction time is preferably 0.5 to 1 hour, and not very important.

The reaction solvent is not so important, but inert organic solvents such as benzene, toluene, xylene, chlorobenzene and dichlorotoluene are preferred.

The dispersion of alkali hydroxide is mixed with an alkali hydroxide such as potassium hydroxide and a stabilizer and an inert organic solvent such as benzene, toluene, xylene, chlorobenzene and dichloro toluene to heat and stir the mixture, and then disperse and cool the alkali hydroxide. You can get it.

As stabilizers, compounds having the following structural formulas, polyoxy ethylene type nonionic surfactants, fatty acid sorbitan esters, fatty acid glycerol monoesters, fatty acid esters, quaternary ammonium salts, fatty amines and perfluoro Alkyl surfactants.

Wherein R, R and R 'are each a hydrogen atom or a C ₁ ~C ₄ alkyl group, X is an oxygen atom or a sulfur atom, m and n are each a number of 1 or more than 1.

The amount of alkali cone fine particles is preferably used in an amount of 1 to 10 mol based on the active methylene compound, and a 3 to 6 mol ratio is preferably used.

As active methylene compounds, various compounds having an active methylene group can be used.

Suitable active methyline compounds include malonic acid nitrile malonic acid, diethyl malonic acid, cyanoacetic acid, cyanoacetic acid, methyl, acetylacetic acid, acetylacetic acid, methyl, acetylacetone, phenylacetonitrile, 4-ethylphenylacetonitrile, 3,4-dimethylphenylacetonitrile, 3-trifluoromethylphenyl acetonitrile, phenylacetic acid, 4-chlorophenylacetic acid, 2-bromophenylacetic acid, 4-ethylphenylacetic acid, phenylthio acetonitrile, α-methylphenylacetonitrile , α-methoxyphenyl acetonitrile, β-cyanophenyl propionitrile, diphenylacetonitrile, propion aldehyde, cyclohexanone, 2-methylcyclohexanone and derivatives thereof.

Suitable organic alkyl halogen compounds include alkyl halides such as methyl, ethyl, propyl, butyl, pentyl, hexyl, octyl and nonyl, dihalides such as dihaloethanes, dihalopropanes and dihalobutanes, and the like. Archal halides such as trihalides, benzyl halides, vinyl halides, alkylvinyl halides, haloacetonitriles, and ground haloacetin compounds and haloacetates.

The organic alkyl compound is used in 1 to 5 molar ratio with respect to the active methylene compound.

Examples of preparation of α-isopropyl halophenyl acetonitrile will be described in detail below.

A typical example of producing α-isopropylhalophenyl acetonitrile by reacting halophenyl acetonitrile with isopropyl halide is also described.

The alkali hydroxide dispersion liquid in an inert organic solvent can be used in 1 to 10 molar ratio, preferably 3 to 6 molar ratio with respect to halophenyl acetonitrile.

Suitable halophenyl acetonitriles include 2-chlorophenyl acetonitrile, 3-chlorophenyl acetonitrile, 4-bromo phenylacetonitrile, 3-fluoroacetonitrile and 4-fluorophenyl acetonitrile.

Suitable isopropyl halides include isopropyl bromide and isopropyl chloride. Alkali hydroxides include sodium hydroxide and potassium hydroxide.

The method of the present invention is very effective, has the following remarkable effects compared to the conventional method, and has an advantage over industrial methods. In other words,

First, the following structural formula wherein Y is a halogen atom

Almost no dimers of halophenyl acetonitrile having and the amount of other by-products are considerably small, so that a high purity target compound can be obtained in high yield.

Secondly, since the aprotic polar solvent such as dimeltyl sulfoxide is not used, the solvent can be easily recovered, and α-isopropyl halophenylacetonitrile can be obtained by a low cost industrial method.

Third, since a catalyst such as quaternary ammonium salt is not used, the operation of recovering the catalyst is unnecessary, and since it is easy to drainage, it is possible to easily prevent environmental pollution.

Reference Example 1

52.08 g of solid potassium hydroxide (96% KOH), 200 ml of xylene and 0.05 g of polypropylene glycol (MW1,000) in a 500 ml reactor made of stainless steel (SUS) with agitator (0.1% by weight of KOH) ) Was charged, heated to 140 ° C., stirred for 15 minutes at a speed of 2,000 rpm, and then cooled to room temperature while stirring to obtain a xylene dispersion of fine potassium hydroxide.

As a result of the observation under a microscope, the particle size of the particulate potassium hydroxide was 100 μm to 10 μ, and no potassium hydroxide adhesion phenomenon was found on the inner wall of the reactor.

Reference Example 2

A xylene dispersion of particulate caltan hydroxide was prepared according to the method of Reference Example 1 except that polyethylene glycol (M.W. 60) was used instead of polypropyllian glycol.

The particle size of the particulate potassium hydroxide was in the range of 100 μm to 10 μ, and no adhesion of potassium hydroxide to the inner wall of the reactor was found.

Reference Example 3

A dispersion of particulate sodium carbonate was prepared according to the method of Reference Example 1 except that solid sodium hydroxide was used instead of solid potassium hydroxide.

The results were the same as those in Reference Example 1.

Reference Example 4

A xylene dispersion of fine particulate potassium hydroxide was prepared according to the method of Reference Example 1 except for stirring for 30 minutes using polyoxyethylene sorbitan monolaurate (E.O.20) instead of polypropylene glycol.

The particle size of the granular potassium hydroxide was 100 μm to 10 μ and no adhesion phenomenon of potassium hydroxide was found on the inner wall of the reactor.

Reference Example 5

A dispersion of sodium hydroxide was prepared according to the method of Reference Example 4 except that solid sodium hydroxide was used instead of solid potassium hydroxide.

The result was the same as the case in Reference Example 4.

Reference Example 6

Each dispersion was prepared for particulate potassium hydroxide according to the method of Reference Example 1 except for using chlorobenzene, chlorotoluene, toluene, chloroform or carbon tetrachloride instead of xylene.

The result was the same as that of the reference example 1.

Reference Example 7

Except for using polyoxyethylene, polyoxyethylene nonylphenyl ether, polyoxyethylene dodecyl ether, sorbitan monolaurate, fatty acid sugar ester, or glycerin monostearate, instead of polypropylene glyco, Each dispersion was prepared for particulate potassium hydroxide according to the method.

The results were the same as in the reference example, and the results were observed through a microscope by micrographs.

Reference Example 8

In a 500 ml reactor made of stainless steel (SUS) with a homo mixer, 52.08 g of solid potassium hydroxide 200 ml of xylene and 0.05 g of polyoxyethylene sorbitan monolaurate (EO20) were charged and heated at 140 ° C. Potassium hydroxide was grueled.

The homo mixer was spun for 30 minutes at a rotation speed of 10,000 r.p.m and the dispersion was cooled to room temperature with stirring.

When observed under a microscope, the particle size of the granular potassium hydroxide was 100 μm to 10 μ.

The adhesion of potassium hydroxide to the inner wall of the reactor could not be found.

Reference Example 9

Except for using solid sodium hydroxide in place of solid potassium hydroxide, except for the dispersion of fine sodium hydroxide in accordance with the method of Reference Example 8 and observed the results were the same as in the case of Reference Example 8.

Comparative Reference Example 1

A xylene dispersion of fine potassium hydroxide was prepared according to the method of Reference Example 1 except that polypropylene glycol was used.

A particulate potassium hydroxide dispersion was produced, but no adhesion of potassium hydroxide to the inner wall of the reactor was found.

Comparative Reference Example 2

A xylene dispersion of fine sodium hydroxide was prepared according to the method of Reference Example 1 except that no polypropylene glycol was used and sodium hydroxide was used instead of potassium hydroxide.

A dispersion of particulate sodium hydroxide was produced, but no adhesion of sodium hydroxide to the inner wall of the reactor was found.

[Comparative Reference Example 3]

A xylene dispersion of potassium hydroxide was prepared according to the method of Reference Example 1 except that polypropylene glycol was not used and stirred at room temperature.

The particles of potassium hydroxide were polygonal and bold.

Example 1

Into a 500 ml reactor made of stainless steel (SUS) with a stirrer was charged 52.08 g of solid potassium hydroxide (96% KOH), 200 ml of xylene and 0.05 g of polypropylene glycol (WW1,000) (0.1% by weight of KOH). And heated at 140 ℃ stirred for 15 minutes at a speed of 2,000rpm and then cooled to room temperature with stirring.

A xylene dispersion of fine potassium hydroxide was obtained.

Charge 26 g (0.33 mole) of isopropyl chloride to the dispersion, add 34 g (0.22 mole) of 4-chlorophenyl acetonitrile dropwise at room temperature over 10 minutes while stirring the mixture, and then add the mixture. They were further stirred at 70 to 80 ° C. for 50 minutes to react them.

After the reaction was completed, the reaction mixture was poured into 300 ml of water, the organic layer was separated, the xylene was concentrated and fractionated, and the product was distilled off under reduced pressure. 40.4 g of propyl-4-chlorophenyl acetonitrile were obtained.

Comparative Example 1

50 g (0.89 mol) of potassium hydroxide was ground in 200 ml of xylene in the mortar to obtain a fine xylene dispersion of potassium hydroxide.

The procedure was repeated according to the method of Example 1, except that the dispersion of particulate potassium hydroxide was used instead of the dispersion of particulate potassium hydroxide having a particle diameter of less than 100 mu in xylene, and the reaction time was changed to 8 hours. 29.8 g of α-isopropyl-4-chlorophenyl acetonitrile having a boiling point of 102 to 106 ° C / 1 mmHg (yield 70%) was obtained.

EXAMPLES 2-6

By the method of Example 1, corresponding a-isopropyl halophenylacetonitriles were obtained using halophenyl acetonitrile and isopropyl halide shown in the following table. The results are shown in the table below.

[table]

Example 7

The procedure was repeated according to the method of Example 1, except that 0.05 g of polyoxy ethylene sorbitan monolaurate was used instead of polypropylene glycol as a stabilizer, and the boiling point was 104 to 106 DEG C / mmHg (yield 94%). 40 g of α-isopropyl-4-chlorophenylacetonitrile was obtained.

[Examples 8 to 12]

As the stabilizer, halophenylacetonitrile and isopropyl halides described in the tables above were used by the method of Examples 2-6, except that polyoxy ethylene sorbitan monolaurate was used instead of polypropylene glycol. .

The results are shown in the table below.

[table]

Example 13

1.26 g (0.33 mole) of isopropyl chloride was charged into a xylene dispersion of particulate potassium hydroxide having a particle size of less than 100 µ in the method of Reference Example 1, and then 37.5 g (0.22 mole) of 4-chlorophenyl acetate in 500 ml of xylene. After the solution in which the solution was dissolved was added dropwise over about 10 minutes, the reaction was performed at 70 to 80 ° C. for 50 minutes.

After the completion of the reaction, the reaction mixture was poured into 300 ml of water, the organic layer was separated and concentrated to fractionate xylene, and the product was distilled under reduced pressure, and the melting point was 88-89 占 폚, and the yield was? -Isopropyl. 43 g of 4-chlorophenyl acetate were obtained.

Example 14

36 g (0.89 moles) of sodium hydroxide instead of 50 g (0.89 moles) of potassium hydroxide, and 40.6 g (0.33 moles) of isopropyl bromide instead of 36 g (0.33 moles) of isopropyl chloride According to the method of Example 13, 38.0 g of α-isopropyl-4-chlorophenyl acetic acid having a yield of 81.2% was obtained when the reaction and operation were performed.

[Examples 15 to 35]

According to the method of Example 13, the active methylene compounds and halides shown in the following table were used, and the corresponding products were obtained.

The results are shown in the table below.

[table]

Claims (1)

Malonic acid nitrile, malonic acid, diethyl malonate, cyanoacetic acid, methyl cyanoacetate, acetylacetic acid, methyl acetylacetic acid, acetylacetone, phenylacetonitrile, 4-ethylphenylacetonitrile, 3,4-dimethylphenyl acetonitrile, 3-trifluoromethylphenyl, acetonitrile, phenylacetic acid, 4-chlorophenylacetic acid, 2-bromo phenylacetic acid, 4-ethylphenylacetic acid, phenylthioacetonitrile, α-methylphenyl acetonitrile, α-methoxyphenylacetonitrile , active methylene compounds selected from the group consisting of β-cyanophenylpropionnitrile, diphenylacetonitrile, propionaldehyde, cyclohexanone and 2-methylcyclohexanone, alkyl halides, aralkyl halides, vinyl halides, alkylvinyl halides, Alkali hydroxide and inert organic solvent in the reaction of organic alkyl halogen alkyl compound selected from the group consisting of haloacetonitrile and haloacetate And mixing and treating the mixture to react in the presence of a particulate hydroxide dispersion having a particle size of 100 μm to 500 μ.