CS256818B1 - Method of 6-chloro-2-metoxybenzonitrile preparation - Google Patents

Abstract

Process for preparing 6-chloro-2-methoxybenzonitrile 2 (b-dichlorobenzonitrile) with sodium methoxide in anhydrous medium methanol at 35 to 30 ° C. 2,6-dichlorobenzonitrile is obtained by amoxidation 2,6-dichlorotoluene.

Description

The present invention relates to a process for preparing 6-chloro-2-methoxybenzonitrile by reacting 2,6-dichlorobenzonitrile with sodium methoxide in anhydrous methanol.

Known methods of preparing 6-chloro-2-methoxybenzonitrile are based on 2-amino-3-chloroanisole, which is converted to the nitrile by the Sandmeyr reaction of the diazonium salt of this compound with cuprous cyanide. From other sources, it is known to prepare 5-chloro-2-methoxybenzonitrile from 2,5-dichloronitrobenzene, which is converted into 5-chloro-2-methoxynitrbbenzene with sodium methoxide in methanol and converted to the corresponding amine by Sandmeyer reaction to give the final nitrile .

It is apparent from the above overview that the routes published so far for the preparation of the desired 6-chloro-2-methoxybenzonitrile and possibly also of the substitution derivatives are very complex, complicated and not attractive from a technological point of view.

It has now been found that 6-chloro-2-methoxybenzonitrile is preferably prepared by the process of this invention by reacting 2,6-dichlorobenzonitrile obtained by amoxidation of 2,6-dichlorotoluene with sodium methoxide in anhydrous methanol at temperatures of 35-80 ° C.

The nucleophilic substitution of chlorine in 2,6-dichlorobenzonitrile with the methoxylate anion is carried out by suspending 2,6-dichlorobenzonitrile in methanolic sodium methanolate solution under stirring and at normal temperature and then heating the mixture to boiling. As soon as the substrate begins to react (it results in an increase in the boiling intensity), heating is interrupted or the heating intensity is reduced and waiting for the wxothermal reaction to take place. After completion of the reaction, the reaction mixture is kept under reflux for 30-60 minutes to react the starting substrate. The reaction mixture was then cooled to 20-25 ° C and filtered

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- 2 se. The crude product was washed first with methanol and then with water.

The washed product is dried in an oven at 90-100 ° C.

The methanolic filtrate is filtered again as necessary to yield an additional crop of product and then methanol is recovered by distillation.

The reaction is rapid, the desired product is obtained in ca 80% yield without further purification. Other optionally isolated fractions from the mother methanol filtrate already contain a mixture of 6-chloro-2-methoxybenzonitrile and 2,6-dimethoxybenzonitrile with lower melting points.

The advantage of this process is simple and quick preparation and low demands on energy consumption, labor force and considerably lower and easily disposable waste. The disadvantage is working with anhydrous methanol (max. Water content 0.1%).

The example below illustrates an embodiment of the invention.

Example.

g of 2,6-dichlorobenzonitrile is suspended in 300 ml of 20.65% sodium methoxide in anhydrous methanol (Na content 8.79%, specific gravity 0.923 g / cm @ 2) in an apparatus equipped with a propeller stirrer, a reflux condenser with a moisture barrier and the batch is heated in an oil bath to about 65 ° C. The reaction starts already at normal temperature and has a significantly exothermic course at temperatures above 65 ° C. Once methanol is distilled, heating of the batch is interrupted and the exothermic reaction is complete. After completion of the reaction, the reaction mixture is kept under reflux for a further 30 to 60 minutes to allow the starting substrate to react. The progress of the reaction was checked by TLC chromatography in cyclohexane: acetone (4: 1) and the reaction was complete when the 2,6-dichlorobenzonitrile spot disappeared. The reaction mixture was then cooled to 20-25 ° C and filtered on a vacuum pad. The crude product under suction is washed twice with 50 ml of anhydrous methanol (or regenerated methanol) and the mother filtrate, including the washing filtrate, is combined and after standing for about 2 hours a further portion of the product can be filtered off. From the filtrate obtained, methanol is recovered by distillation, which is used to prepare sodium methanolate or to wash the crude product.

After washing with methanol and washing the product under suction, four more times with 100 ml of distilled water. The washed product is dried in an oven at 90-100 ° C. 38.7 g of 6-chloro-2-methoxybenzonitrile were obtained (yield 79.5%) and m.p. M.p. = 116-117 ° C (pure chromatography).

Filtration of the methanolic filtrate yielded 1.7 g and 1.2 g of product from the water filter. However, both of these fractions already contained minor amounts of 2,6-dimethoxybenzonitrile and are therefore a technical grade product.

Claims (1)

A process for the preparation of 6-chloro-2-methoxybenzonitrile having the structural formula characterized in that 2,6-dichlorobenzonitrile is reacted with sodium methoxide in anhydrous methanol at temperatures of 35-80 ° C.