DE1668557B2 - PROCESS FOR MANUFACTURING 2-BENZIMIDAZOLE CARBAMIC ACID METHYLESTER - Google Patents

Description

CN-COOCH ₃

NK H
H

by reacting cyanamide or a cyanamide salt with methyl chloroformate and reacting the obtained Methyicyancarbamatverbindungen with o-phenylenediamine of the formula

NH,

NH,

characterized in that cyanamide is reacted in the presence of a basic alkali or alkaline earth metal compound or an alkali metal or alkaline earth metal cyanamide salt with methyl chloroformate in the presence of water at a pH of 6 to ¹ .3 and a temperature between 0 ° and 105 ⁰ C and the alkali metal obtained - Or alkaline earth metal methyl cyanocarbamate salt without isolation from the reaction mixture or the methyl cyanocarbamate isolated from the reaction mixture by acidification and extraction with organic solvents with o-pheny-In US Pat is reacted with dimethyl sulfate to form 2-methyl-thio-pseudourea sulfate. This reaction product is then reacted with an alkyl chloroformate and a base to give an acylated 2-methylthio-pseudourea, which is then reacted further with an o-phenylenediamine in the presence of a protonic acid to give the desired product. This process has the disadvantage that a relatively expensive material, namely thiourea, has to be used and that methyl mercaptan is formed.

It is also known from the published documents of the Belgian patent 6 66 795, 2-benzimidazole-carbamic acid alkyl ester to produce by alkyl chloroformates with cyanamide to form an alkyl cyanocarbamate and this product with a converts o-Phenylenediarnine. These reactions are carried out in organic solvents, expediently pyridine. The yields obtained 2-Benzimidazole-carbamic acid alkyl esters are very low.

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

The process according to the invention without isolation of the methyl cyanocarbamate salt can be carried out by the following Equations are presented:

step 1

CN

+ / nCl-C-OCH ₃ > MCI _1n + MIN-CO ₂ CH ₃

Cyanamidsal /. Methyl chloroformate methyl cyanocarbamate salt

Level 2

/ CN
M \ N-CO ₂ CH ₃ / ,,, + / Ji

Methyl cyano carbamate salt

NH ₂

+ 2mH ⁺ - m

NH ₂ o-phenylenediamine

CN-COOCH ₃ + m NH / + M '" ⁺

Methyl ester of 2-benzimidazole carbamic acid c

Here mean

M is an alkali metal or an alkaline earth metal and m is the valence of M.

H ^f can be derived from any acid.

In the above stage I, there is an alkali metal or alkaline earth metal cyanamide salt /. used the cyanamide is present in the aqueous solution in anion form. This ionization is from usually strong enough to produce the desired pH. Abe ~ too Cyanamide can be used in stage 1 as an aqueous solution if the solution is to be used for maintenance a basic alkali or alkaline earth metal compound is added to the desired pH. the Stage 1 in this embodiment is illustrated by the following equation:

step 1

ii

/ CN

/ HH ₂ HCN + mCl -C-OCH ₁ t-2M (OH) _n

Cyanamide methyl chlorine base

formate

M \ N-CO ₂ CH ₃ J _n , + MCl _n , + 2 _m H ₂ O
Methyl cyano carbamate salt

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

Suitable starting materials are in particular the magnesium, potassium, sodium and calcium salts of Cyanamides. Commercially available calcium cyanamide is the preferred starting material. Cyanamide, even in aqueous solution, is a preferred starting material.

If the methyl chloroformate is reacted with a cyanamide salt in the first stage, either a simple salt, that is to say M (HNCN) ,,,, or a double salt, that is to say M ₂ / _m NCN, can be used; 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; from economic However, high concentrations are usually chosen for reasons. The concentration of the Cyanamide in the aqueous solution can be from 5 to 50%, and since cyanamide is currently commercially available as 50% aqueous solution is available, such solutions are preferred. The concentrations of the alkali metal or alkaline earth metal cyanamide salts is only limited by the handling possibilities.

When an alkali metal or alkaline earth metal cyanamide salt is used, the methyl chloroformate is preferably added to the aqueous mixture with mixing Slurry or solution containing the alkali metal or alkaline earth methyl cyanamide salt is given. Of the Methyl chloroformate consumption is lowered when the pH of the cyanamide salt slurry is 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 can and the basic alkali or alkaline earth metal compound is added to the cyanamide solution at the same time will. During this simultaneous addition, the molar amount of base added should be added to each Point in time of the molar amount of methyl chloroformate preferably be equivalent or slightly There is an excess.

When an aqueous cyanamide solution is used, the preferred pH-Wi-rt range is 7-9. It is complied with by adding a basic alkali or alkaline earth metal compound. In case of For alkali metal or alkaline earth metal cyanamide salts, it is preferred to use the pH range between 8 and 10 keep.

The temperature of this first reaction stage is within the range from 0 to 105 ⁰ C 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 and the product is stable in the reaction medium. The reaction time is thus not critical, and the product can be used immediately in the ίο second stage or canceled for a period of time depending on what is desirable from the point of view of equipment. Generally depends the reaction time depends on the degree of heat transfer and can be from 5 minutes to 2 hours.

If technical grade alkali metal or alkaline earth metal cyanamide salts are used in the first stage have been, sometimes insoluble impurities and salts, for example calcium salts, remain included in the reaction mixture. These impurities are preferably filtered off before the second stage is passed over.

In the second reaction stage, o-phenylenediamine is the reaction product from the first stage, or if Alkali metal or alkaline earth metal cyanide salts are used have been added to the filtered reaction product in an aqueous, acidic medium to the To prepare the methyl ester of 2-benzimidazole carbamic acid. You can also use the reaction medium of the first Acidify stage, the released methyl cyanocarbamate by extraction with organic solvents isolate and react the isolated methyl cyanocarbamate with o-phenylenediamine.

In order to carry out the condensation and the associated ring closure, must during the second 2nd stage the pH value can be kept between 2.5 and 4.5 by adding the necessary acid. For this any acid can be used, for example formic acid, acetic acid, hydrochloric acid, Sulfuric acid, phosphoric acid, hydroxyacetic acid or sulfamic acid. The o-phenylenediamine can optionally be added in the form of a mineral acid salt or as an aqueous solution. When o-phenylenediamine salts used is the amount of acid required to achieve the desired pH correspondingly smaller.

The second reaction occurs at temperatures above 40 ^° C .; heating is preferably carried out during this stage in order to accelerate the reaction to completion. The heat input is important because the reaction

so to the second stage at low temperatures would be slow. The reaction mixture should preferably be in the temperature range from 60 to 105 ° C being held. If desired, the second reaction stage can also be carried out under pressure will. When this happens, the temperature can rise to 130 ° C.

The desired product precipitates during the heating stage. The completion of the precipitation 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. For example, the reaction time at a temperature between 70 and 105 ^° C. can be from 5 to 30 minutes. If lower temperatures are used, the reaction time will be longer.

The desired product can then be obtained by any of the conventional methods, for example by

Spray drying, filtration or centrifugation, or it can be obtained by distillation of the Water can be transferred to any other liquid medium.

In the overall reaction, the reactants can be used in the molar equivalent ratios shown in the table below be used:

Cyanamide or cyanamide salts

Methyl chloroformial
o-phenylenediamine

MoI equivalent c

1 to 3

1 to 3

Before / uülc

Mc: -

Equivalents

1 to 2.2

1 to 1.8 1

It will be understood that the upper limit colar concentrations are not critical; however that is Process inexpedient or uneconomical at the higher concentrations. It is obvious that the Concentration in the second stage depends on the concentration in the first stage.

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

example 1

75.6 parts of methyl chloroformate are added with thorough stirring to a slurry of 80 parts of technical grade calcium cyanamide and 300 parts of water. The temperature is maintained by cooling in an ice bath at 40 to 5O ⁰ C. After stirring the reaction mixture for one hour, the mixture is filtered and the insolubles are partially washed with 100 parts of water.

43.2 parts of o-phenylenediamine are added to the filtrate combined with the washing solutions. The pH of the mixture is adjusted to 3.5 by adding concentrated hydrochloric acid. The solution is then rapidly heated to 90 ⁰ C, and the temperature maintained for 30 minutes long in the range from 90 to 98 ° C. During this time, the pH is kept at 2.5 to 3.1 by adding concentrated hydrochloric acid.

The reaction mixture is then filtered, and the solid is washed with water and acetone and then dried ^{at 120 ° C. in a vacuum oven.} This gives a yield of 64 parts of methyl 2-benzimidazole carbamate; M.p. 310-320 ° C (decomposition); Yield: 83.3%, based on the o-phenylenediamine.

Example 2

32 parts of a 50% cyanamide solution and 100 parts of water are placed in a jacketed reaction vessel equipped with filling openings, stirrer, reflux condenser and pH probe. 41.1 parts of methyl chloroformate and 67 parts of a 50% sodium hydroxide solution are introduced simultaneously derr.rt that the pH value of the solution at 7 to 7.5 and the reaction temperature at 40 to 50 ⁰ C are maintained. The solution is kept at 50 ^° C. for 45 minutes and then mixed with 36 parts of o-phenylenediamine. The pH of the solution is maintained at 3.9 to 4.1 by the gradual addition of 65 parts of 37% HCl. The Lösi'ng is heated to 105 ⁰ C and held for 30 minutes at this temperature. During this period the product begins to crystallize. The reaction mass is ^{cooled to 25 to 30 °} C., and the solid product is filtered, washed with water and acetone and dried ^{at 80 ° C. in a vacuum oven.} 59.6 parts of methyl 2-benzimidazole carbamate are obtained; F. 310-320 ⁰ C (decomposition); Yield: 93.5%, based on o-phenylenediamine.

Example I 3

In a 1-1 flask equipped with a stirrer and If a thermometer is fitted, 90.4 parts of a 47% strength cyanamide solution are added together with 122

2s parts of water. This solution is stirred and 97.5 parts of methyl chloroformate and 169 parts of a 50% strength sodium hydroxide solution are gradually and simultaneously added. The temperature is maintained at 45 to 50 ° C. and the pH of the mixture at 6.8 to 7.2 during the addition. The resulting solution is acidified with concentrated hydrochloric acid to 83 parts of a pH value of 1 and cooled to 20 ⁰ C. Then extracted 6 times with the solution 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 pale yellow oil obtained consists of 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%. based on cyanamide. The index of refraction of this compound is 1.439834.

49.5 parts of o-phenylenediamine, 140 parts of water and 54 parts of the prepared according to paragraph 1 are added

Methyl cyan carbamate in a round bottom flask equipped with charging ports, stirrer, reflux condenser and The measuring head is equipped for the pH value. The reaction mixture is heated to 95 ° C. and held for 1 hour 15 minutes at 95 to 97 ° C. Holds during this time

so the pH of the reaction mixture by adding concentrated hydrochloric acid at 3.8 to 4.2. 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 are obtained in this way

ss 2-benzimidazole-carbamic acid methyl ester; F.

310-320 ^u C (decomposition); Yield: 93% based on o-phenylenediamine.

Claims (1)

Claim: Process for the preparation of the 2-benzimidazolecarbamic acid methyl ester of the formula iendianiin in the presence of water at a pH of the reaction medium of 2.5 to 4.5 and a temperature of 40 to 130 ⁰ C.