DE1795849A1 - PROCESS FOR THE PRODUCTION OF 2-BENZIMIDAZOLE CARBAMIC ACID METHYLESTER - Google Patents

Description

E. I. DU PONT DE NEMORS AND COMPANY lOth and Market Streets, Wilmington, Delaware 19898, V.St.A.

Process for the preparation of the 2-benzimidazole-carbamine-

acid methyl ester

The 2-benzimidazole carbamic acid methyl ester is a good one Fungicide.

In U.S. Patent 3,010,968 there is a method of manufacture of 2-benzimidazole-carbamic acid alkyl esters- described, taking thiourea with dimethyl sulfate to form 2-methyl thiopseudourea sulfate is implemented. This reaction product then becomes one with an alkyl chloroformate and a base acylated 2-methyl-thiopseudourea reacted, which then further with an o-phenylenediamine in the presence of a protonic acid is converted to the desired product. This procedure has the disadvantage that a relatively " expensive material, namely thiourea, has to be used, and that methyl mercaptan is produced.

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It is also known from the published documents of the Belgian patent 666.795. 2-Benzimidazole-carbamic acid alkyl ester by producing alkyl chloroformates with cyanamide to form an alkyl cyanocarbamate and this Reacts product with an o-phenylenediamine compound. These reactions are convenient in organic solvents Pyridine. The yields of 2-benzimidazole-carbamic acid alkyl ester obtained are very high small amount. .

The method according to the invention is defined in the patent claim.

In order to carry out the ring closure, the pH value must be between 1 and 5, preferably by adding the necessary acid kept between 2.5 and 4.5. You can do this. ■ use any acid, for example formic acid, acetic acid, hydrochloric acid, sulfuric acid, phosphoric acid, Hydroxyacetic acid or sulfamic acids The o-phenylenediamine can optionally be added in the form of a mineral acid salt or as an aqueous solution. When o-phenylenediamine salts are used, the amount of acid required to achieve the desired pH value is appropriate smaller.

The reaction occurs at temperatures above ho ⁰ C; heating is preferably carried out during this stage in order to accelerate the reaction to completion. The supply of heat is important because the reaction of the second stage would be too slow at low temperatures. That . Reaction mixture should preferably be maintained in the temperature range 60-105 ⁰ C. If desired, the second reaction stage can also be carried out under pressure. When this happens, the temperature can be up to 130 ⁰ C to rise.

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During the heating, the desired product precipitates. The cessation of the failure is thus an indication that the reaction mixture has been heated long enough to complete the reaction. The length of time is not critical and depends on the temperature and the pH. The reaction time can be at a temperature between 70 and 105 ° C 5 to 30 minutes. If lower temperatures are used, the reaction time is longer.

The desired product can then be selected according to any of the conventional methods, for example by spray drying, filtration or centrifugation, or it can be obtained can be converted into any other liquid medium by distilling the water.

In the overall reaction, the reactants in the Molecular equivalent ratios shown in the table below be used: ·

preferred molar reactants molar equivalents equivalents

Methyl cyanocarbamate 1 to 3 1 to 1.8

o-phenylenediamine or

Derivatives thereof 1 1

It will be understood that the upper limit molar concentrations are not critical; however, the procedure is inexpedient or uneconomical at the higher concentrations.

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The methyl cyanocarbamate used according to the invention can can be produced according to the following equations:

0 mM _{o /} NCN + -mCl-S-OCH

or

CN

M (N-CO ₀ CH,) c. 3 m

NH (CN) -CO ₂ CH ₃

mH ₂ HCN + InCl-C-OCH ₃

2M (0H)

CN

MCl

NH (CN) -CO ₂ CH ₃

Here mean

M is an alkali metal or an alkaline earth metal and

m the valence of M.

H can come from any acid.

If an alkali metal or alkaline earth metal cyanamide salt is used, the cyanamide will be in the aqueous solution in anion form. This ionization is inherent usually strong enough to produce the desired pH.

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Any basic alkali metal or alkaline earth metal compound can be used as a base. Alkali and alkaline earth hydroxides are preferred, although oxides are also preferred and carbonates can be used.

Suitable starting materials are in particular the magnesium, potassium, sodium and calcium salts of cyanamides. In trade available calcium cyanamide. the preferred starting material. Cyanamide itself is also an aqueous solution preferred starting material. "

When methyl chloroformate reacted with a cyanamide salt can either be a simple salt, that is M (HNCN), or a double salt, that is, M ", NCN, is used will; however, the cyanamide double salt is preferred for the reaction with the methyl chloroformate.

The concentrations of the starting materials in the reaction mixture are not critical; however, high concentrations are usually chosen for economic reasons. The concentration of the cyanamide in the aqueous solution can be from 5 to 50 % and, since cyanamide is currently available commercially as a 50% aqueous solution, such solutions are preferred. The concentrations of the alkali metal or alkaline earth metal cyanamide salts are only limited by the possibility of handling.

If an alkali metal or alkaline earth metal cyanamide salt is used, the methyl chloroformate is preferred with mixing to the aqueous slurry or solution containing the alkali metal or alkaline earth metal cyanamide salt contains, given. The methyl chloroformate consumption is

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lowered when the pH of the cyanamide salt slurry in water before the addition of methyl chloroformate by adding mineral acid, initially from about 12 to 8-10 is reduced. If an aqueous cyanamide solution is used, the methyl chloroformate and the basic Alkali or alkaline earth metal compound can be added to the cyanamide solution at the same time. During this simultaneous Addition should be the molar amount of the added base at each point in time of the molar amount of the methyl chloroformate s preferably be equivalent or in minor There is an excess.

If an aqueous cyanamide solution is used, the preferred pH range is between 7 and 9 · Er xvird adhered to by adding a basic alkali or alkaline earth metal compound. In the case of alkali metal or alkaline earth metal cyanamide salts, it is preferred to use the Keep the pH range between 8 and 10.

The temperature is not within the range 0-105 G ⁰ critical. In general, the range from 25 to 60 ^° C. is preferred. If desired, this step can be carried out at higher temperatures under pressure.

The reaction is rapid, in general the reaction time depends on the degree of heat transfer and can be from 5 minutes to 2 hours «

The resulting solution is acidified. The methyl cyan carbamate can be obtained by extraction with organic solvents to be isolated.

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At s ρ ie 1

49.5 parts of o-phenylenediamine, 140 parts of water and 54 parts of methyl cyanocarbamate are added to a round-bottom flask equipped with charging openings, stirrer, reflux condenser and measuring head for the pH. The reaction mixture is heated to 95 ^° C. and kept at 95 to 97 ^° C. for 1 hour and 15 minutes. During this time, the pH of the reaction mixture is maintained at 3.8 to 4.2 by adding concentrated hydrochloric acid. The reaction mixture is cooled to 20 ^° C., the solid product is filtered off, washed with water and acetone and dried in the air. 80.3 parts of methyl benzimidazole carbamate are obtained; P-. 310-320 ⁰ C (decomposition); Yield: 93 % ₃ based on o-phenylenediamine.

The methyl cyanearbamate used is obtained as follows:

90.4 parts of a 47% strength cyanamide solution together with 122 parts of water are placed in a 1-1 flask equipped with a stirrer and a thermometer. This solution is stirred and 97> 5 parts of methyl chloroformate and 169 parts of a 50% sodium hydroxide solution are gradually added at the same time. The temperature is maintained at 45 to 50 ⁰ C and the pH of the mixture at 6.8 to 7j2 during the addition. The solution obtained is acidified with 83 parts of concentrated hydrochloric acid to a pH value of 1 and cooled to 20 ^° C. The solution is then extracted 6 times with 125 parts of methylene chloride. The combined methylene chloride solutions are dried over 35 parts of anhydrous sodium sulfate and the solution is concentrated. The light yellow oil obtained consists of

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84.59 parts of methyl cyanocarbamate. 0.5913 parts of this compound are titrated with 55.2 parts of 0.1 N sodium hydroxide solution against phenolphthalein. This gives a purity of 93.3 % and a yield of 79 % _s based on cyanamide. The refractive index of this compound is 1. ^ 39834.

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Claims (1)

BÄ-2736-Ä-2 Pat en ta η s ρ ruch Process for the preparation of 2-benzimidazole-carbamic acid methyl ester the formula CN COOCH. H ^: by reacting methyl cyanocarbamate of the general formula 0
CH ₃ OC-NH-CN with o-phenylenediamine of the formula -NH, .NH characterized in that the reaction is carried out in the presence of water at a pH of the reaction medium of 1 to 5 and a temperature of 40 ° to 130 ⁰ C / . - 9 709808/1098