Method of methyliminoacetate's hydrochloride preparatio(

Said compound is an important reactive intermediate for the synthesis of substances with herbicidal and / or pharmaceutical effects.

Compound (1) is prepared by Pinner synthesis by reacting acetonitrile with methanol in an anhydrous medium in the presence of anhydrous hydrogen chloride according to the procedures summarized in the 3 relevant references in Chem. Rev., 61, 179 (1961) in the work of Robert Rogers and Douglas G. Nelson: The Chemistry of Imidates, resp. the free base of compound (1) can be prepared in very low yield by basic catalyzed reaction of acetonitrile with methanol, e.g. Fred C. Schaefer and Grace A. Peters: D. Org. Chem. 26, 412 (1961).

Pinner's synthesis is usually carried out at 0 ° C in the presence of an anhydrous solvent such as chloroform, nitrobenzene, dioxane, ether, dimethylcellosolve and occasionally in benzene, said solvents serving as diluent and protecting the imidate itself from atmospheric moisture and subsequent reactions. A slight excess, usually 1.1 moles of HCl per mole of nitrile, is used for hydrogen chloride. The most commonly used solvent is ether, which is a prevention for the isolation of crystalline imidate, since compound (1) and in general other imidates crystallize very difficult with occluded solvents and reaction products (see RHDe. Vol.) Carboxylic Ortho Acid Derivatives Press, New York-London, 1970 /. The disadvantage of the processes reported in the literature is usually the long crystallization of the imidate, which takes up to several days, predominantly by the use of ether, the yield of methyl iminoacetate hydrochloride reaching hardly 72% (see, for example, Peter PT Sah: L. Am. Chem. Soc. 50, 516, (1928), and therefore the preparation of an ethyl derivative which crystallizes better is reported much more frequently in the literature, and is more thermally stable and the yield reaches 8 to 95% of theory. However, for practical reasons, in many cases in the further synthesis it is more advantageous to ingest methyliminoacetate hydrochloride, because the methanol released by the reaction is better regenerated (does not form an azeotrope with water, etc.).

It has now been found that methyliminoacetate hydrochloride of formula (1) is very preferably prepared from acetonitrile in very high yield according to the invention.

According to the invention, the process for preparing methyliminoacetate hydrochloride consists in mixing anhydrous acetonitrile with anhydrous methanol in a molar ratio of 1: 1, 1. The solution thus obtained is poured into the present toluene (0.75 to 1 mol toluene / mol acetonitrile) and the resulting mixture is cooled to 0-12 [deg.] C. with stirring and then 1.1 mol of anhydrous HCl / mol of nitrile are introduced over a period of 2 to 2.5 hours at a constant flow rate of 165 to 202 ml of HCl / min, the temperature of the reaction mixture being kept at 2 to 12 ° C. After saturation, the reaction mixture is stirred under a dried nitrogen atmosphere for 5 to 6 hours at 15 to 18 [deg.] C., a white crystalline suspension of methyl iminoacetate hydrochloride slowly precipitates, which is then filtered off, washed with 0.17 mol toluene / mol nitrile and digested. the toluene paste of methyl iminoacetate hydrochloride is dried in a vacuum desorber over KOH or NaOH to constant weight at normal temperature so as not to emit HCl gas from the dried product. The mother toluene filtrate is recycled back to the next operation and used after any addition of fresh toluene in the same molar amount instead of a batch of fresh toluene. After four recirculations of the mother toluene filtrate, the quality of the dried methyl iminoacetate hydrochloride remained unchanged.

The quality of the product was monitored by potentiometric titration with AgNO 3 solution. Analyzes of the mother toluene filtrate were performed by means of a gas chromatograph. HCl saturation, was monitored by weighing the apparatus with reaction components ·

Said process for the preparation of methyl iminoacetate hydrochloride in toluene, with re

CS 268 639 81 by circulating the mother toluene filtrates and crystallizing the product from the reaction mixture at 15-18 ° C is completely original, significantly increasing the yield of isolated product by an average of 90% compared to previous processes, while significantly reducing the time required to crystallize the product and thereby suppressing undesired subsequent hydrolytic reactions which reduce the yield and selectivity of the reaction.

The preparation of methyl iminoacetate hydrochloride can be performed in industrial enamel reactors under a nitrogen atmosphere. According to the results of filtration tests, a pressure digging nut is the most advantageous for product separation. The drying of the product can advantageously be carried out in a rotary vacuum desorber. Prolonged storage of the dried product at a temperature of about + 5 ° C, eg in closed, water and airtight containers (barrels), is possible, but in practice subsequent processing into other products is assumed.

The invention is illustrated by the following examples, which do not limit the scope of the invention in any way.

Example

41 g of dried acetonitrile (0.03% HgO), 35.24 g of methanol (commercially containing about 0.1% H 2 O) and 80 ml of toluene. The resulting batch was cooled to about 0 ° C with stirring and then a constant flow of anhydrous HCl (99.8%) was set and 40.1 g of HCl gas was introduced into the reaction mixture over 2 to 2.5 hours. The temperature of the reaction mixture is maintained at 2 to 12 ° C during saturation, but preferably at 2 to 7 ° C. The reaction with HCl is strongly exothermic. After saturation, the temperature of the reaction mixture is allowed to rise to 15-18 [deg.] C. and maintained at this temperature for 5-6 h until crystalline methyl iminoacetate hydrochloride precipitates, then the crystalline product is filtered off, washed with 25 ml of fresh toluene, extracted from the bottom and weigh the toluene paste of the product. Thus about 107 g of paste and about 90 ml of mother toluene filtrate were obtained.

Note; The weight of the toluene paste of the product is variable. It depends on the course of crystallization, filtration time and the like.

The isolated toluene paste of the product containing free HCl is dried in a vacuum oven over oven KOH or NaOH or better in a vacuum rotary desorber at normal temperature. About 90.84 g of product are obtained, i.e., 82.92% of theory with the acetonitrile present.

<td>Analysis</td><td>product:</td><td>32.7% Cl,</td><td>i.e. 101.0% of theory.</td>

<td>Analysis</td><td>parent</td><td>toluene</td><td>filtrate; methanol 0.8 g / l acetonitrile 0.3 g / l methyl acetate 1.3 g / l acetamide 31.0 g / l</td>

<td>To</td><td>reactor</td><td>shall be submitted</td><td>50 ml of toluene nitrate filtrate, - 30 ml of fresh toluene</td>

<td>enu, 41</td><td colspan="3">g of acetonitrile and 35.24 g of methanol and the batch is cooled again to 0 ° C. Next</td>

the procedure and processing is the same.

After filtration, about 121 g of toluene paste of product and 71 ml of mother toluene filtrate were obtained. After drying, ae yields 104.6 g of product, i.e. 95.4% of theory.

<td>Analysis</td><td>product:</td><td>32.4% Cl, ie 100.1%</td><td>theory</td>

<td>Analysis</td><td>parent</td><td>filtrate: methanol acetonitrile methyl acetate acetamide</td><td>2.7 g / l 12.3 S / l 4.5 g / l 38 g / l</td>

63 ml of the mother toluene filtrate obtained from the previous treatment, 17 ml of fresh toluene, 41 g of acetonitrile and 35.24 g of methanol are introduced into the reactor ae by the basic procedure.

118.8 g of product paste, 60 ml of mother toluene filtrate, are thus obtained.

CS 26Θ 639 Bl 3

After drying, resp. desorption of 105.2 g of product, i.e. 96% of theory.

Product analysis: 32.6% Cl ”, i.e. 100.8% of theory.

<td>Filtrate analysis: methanol</td><td>0.4 g / l</td>

<td>acetonite ril</td><td>2.5 g / l</td>

<td>methéla cet á t</td><td>1.3 g / l</td>

<td>acet amide</td><td>27 g / l</td>

52 ml of the mother toluene filtrate obtained by the pretreatment, 28 ml of fresh toluene, 41 g of acetonitrile and 35.24 g of methanol are introduced into the reactor and treated in the basic manner.

111 g of product paste are obtained, resp. 101.5 g of dried product, i.e. 92.65% of theory. Of filtrate 60 ml.

Product analysis: 32.1% Cl ”, ie 99.2% theory ··

Analysis of the filtrate: methanol 0.3 g / l acetonitrile 1.5 g / l methyl acetate 0.7 g / l acetamide 29 g / l

To the reactor, 58 ml of the mother toluene filtrate 4 are introduced and treated by the basic procedure; 22 ml of toluene, 41 g of acetonitrile and 35.24 g of methanol.

107.25 g of product paste are obtained, resp. 93.7 g of product, i.e. 85.5 from theory. Filtrate 63 ml.

Product analysis: 32.6 Z Cl, i.e. 100.8% of theory.

Filtrate analysis: methanol 0.6 g / l acetonitrile 4.6 g / l methyl acetate 4.1 g / l acetemide 34 g / l

Note: The amount of toluene filtrate fed back to the reaction can of course be quantitative, as the filtrate is recovered after filtration, in the example section the amount of recirculated toluene filtrate is reduced by the amount consumed for the analyzes.