CH641442A5 - METHOD FOR PRODUCING SUBSTITUTED malononitrile. - Google Patents

Description

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2nd

PATENT CLAIM

Process for the preparation of aromatically or heteroaromatically substituted malononitriles by reacting aromatically or heteroaromatically substituted acetonitrile with cyanogen chloride in the gas phase at elevated temperature, characterized in that the substituted acetonitrile and the cyanogen chloride are gaseous and separated from one another at temperatures which are close to the reaction temperature in the Reactor are fed in, the reaction is carried out at a temperature of 550 to 800 ° C and the reaction mixture is cooled immediately upon exiting the reactor and treated with an aqueous base.

The invention relates to a process for the preparation of aromatic or heteroaromatic substituted malononitrile by reacting aromatic or heteroaromatic substituted acetonitrile with cyanogen chloride in the gas phase at elevated temperature. The aromatic or heteroaromatic substituted malonic acid di-nitriles are among others starting substances for the production of active pharmaceutical ingredients, in particular barbituric acid rederivatives.

It is known that phenylmalononitrile can be produced in a reaction tube at a temperature of 575 to 640 ° C. by reacting phenylacetonitrile with cyanogen chloride in the gas phase. For this purpose, the starting substances are fed in liquid and evaporated at the entrance of the reaction tube (“Ind. Eng. Chem.,

Prod. Res. Div. ", 14 [1975], pp. 158 to 161). While this process achieves favorable conversions, the yield of pure phenylmalononitrile is only about 50%. The space / time yield is moderate. In addition, decomposition products, in particular soot, are deposited in the reaction tube, so that the tube becomes blocked after a relatively short period of operation, and the process is therefore unusable for use on an industrial scale.

A process has now been found for the production of aromatic or heteroaromatic substituted malononitriles by reacting aromatic or heteroaromatic substituted acetonitriles with cyanogen chloride in the gas phase at elevated temperature, which is defined in the patent claim. In this process, the yield of pure phenylmalononitrile is over 70%. High space / time yields are achieved. The reactor remains free of deposits over a long period of operation. The process can be used equally for the production of other aromatically substituted or heteroaromatic substituted malononitriles and is very well suited for being carried out on an industrial scale.

The process according to the invention is suitable for the production of aromatic or heteroaromatic substituted malononitrile of the formula:

CN

R - CH

I.

CN

(I)

in which R is in particular a phenyl, pyridyl or thienyl radical optionally substituted by halogen, preferably fluorine or chlorine.

To carry out the process, cyanogen chloride is reacted with an aromatic or heteroaromatic substituted acetonitrile, e.g. of the formula:

R - CH, - CN

(II)

implemented in which R has the meaning given for formula I. Examples include: phenylacetonitrile, o-, m-, p-fluorine

phenylacetonitrile, o-, m-, p-chlorophenylacetonitrile, pyridyl-2-aceto-nitrile, pyridyl-3-acetonitrile, pyridyl-4-acetonitrile, thienyl-2-acetonitrile and thienyl-3-acetonitrile.

The reaction temperature and the quantitative ratios of the substances to be added may depend on one another and may depend on the type of substances to be reacted.

The reaction is carried out at a temperature of 550 to 800 ° C, preferably between 600 and 700 ° C. Although the pressure can be chosen arbitrarily, that is to say it can be operated at normal pressure as well as at lower or higher pressure, it is generally advantageous not to deviate significantly from the normal pressure.

| 5 The molar ratio of substituted acetonitrile to cyanogen chloride can largely be chosen arbitrarily, both stoichiometrically and under- or over-stoichiometrically. In general, it is advantageous to take at least about 1 mol of the acetonitrile per mole of cyanogen chloride. 1 to 10, in particular n (12 to 6, mol) of acetonitrile are preferably used per mole of cyanogen chloride.

The process according to the invention is advantageously carried out in a continuous manner. For this purpose, a reactor of the type of a reaction tube, for example a tube bundle reactor, is expediently used.

According to the invention, the starting substances, the substituted acetonitrile and the cyanogen chloride, are fed into the reactor in gaseous form and separately from one another. When entering the reactor, the substances therefore have temperatures which are above their boiling temperatures. The substances are fed into the reactor at temperatures which are close to the reaction temperature, that is to say for example at temperatures of 550 to 800 ° C., in particular between 600 and 700 ° C.

The reaction mixture can be diluted by inert gases such as nitrogen or water vapor. These can be added together with the substituted acetonitrile to be reacted and / or the cyanogen chloride or separately from these substances. It is generally expedient not to take more than 2 parts by volume of inert gas per part by volume of cyanogen chloride. The chlorine cyanide can be used in pure form or as a crude product, as is obtained in the preparation of the chlorine cyanide from chlorine and hydrogen cyanide.

The pure substituted malononitrile can be obtained from the reaction mixture in various ways, for example by distillation or alkaline extraction ("Ind. Eng. Chem., Prod. Res. Div."

45

14 [1975], p. 160). It is advantageous to cool the reaction mixture to a temperature below 100 ° C. immediately after leaving the reactor. This can be done in the usual way, in particular by washing the gas with a liquid, preferably water. Since it is also advantageous to treat the reaction mixture directly with a base, it is expedient to add substances with a basic action to the washing liquid. An aqueous solution of a basic substance, in particular of alkali metal hydroxide, alkali metal carbonate or alkali metal hydrogen carbonate, is preferably used for the washing.

Example 1:

An externally heated quartz tube 1 m long and 39 mm wide was used as the reactor. 37 g (0.6 mol) of cyanogen chloride, which had been preheated to 580 ° C., and 240 g (2.0 mol) of phenylacetonitrile, which had also been preheated to 580 ° C., were separated from one another into the tube in a uniform 60 stream fed separately. The reaction temperature was 650 ° C. In a gas scrubber immediately downstream of the reactor, the reaction mixture was treated with 21 5% aqueous sodium hydroxide solution per hour. The aqueous mixture that drained from the scrubber was extracted with dichloromethane. The unreacted phenylacetonitrile and the

3rd

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Extractant recovered. The remaining aqueous phase was adjusted to a pH below 2 with concentrated aqueous hydrochloric acid and then extracted with dichloromethane. The dichloromethane was distilled off from the extract and recovered. The phenylmalonic acid dinitrile remained as residue. The yield was 63 g per hour, corresponding to 74%, based on the cyanogen chloride used. The phenylmalonic acid dinitrile had a melting point of 64 to 65 ° C. Its purity, as determined by gas chromatography, was over 99%.

10th

Example 2:

The procedure was as in Example 1, but a quartz tube with a width of only 20 mm was used. 11 g (0.18 mol) of cyanogen chloride and 72 g (0.61 mol) of phenylacetonitrile, both of which had been preheated to 600 ° C., were fed separately into the tube per hour. The reaction temperature was 685e C. The yield of phenylmalononitrile was 21.2 g per hour, corresponding to 83%, based on the cyanogen chloride used. The phenylmalonic acid dinitrile was 99% pure.

Example 3:

The procedure was as in Example 1, but 37 g (0.6 mol) of cyanogen chloride and 259 g (1.9 mol) of p-fluorophenylacetonitrile were used per hour. The substances were preheated to 610 ° C. The reaction temperature was 680 ° C. The yield of p-fluorophenylmalononitrile was 62 g per hour, corresponding to 77%, based on the cyanogen chloride used. The substance was found to be over 98% pure, as determined by gas chromatography.

Example 4:

The procedure was as in Example 2, but 9.9 g (0.16 mol) of cyanogen chloride and 73.8 g (0.6 mol) of thienyl-3-acetonitrile were used per hour. The substances were preheated to 600 ° C. The reaction temperature was 650 ° C. The yield of thienyl-3-malononitrile was 12 g per hour, corresponding to 50%, based on the cyanogen chloride used. The substance was found to be over 97% pure, as determined by gas chromatography.

R