DE1207937B - Process for the preparation of cyanomethyl substituted heterocyclic compounds - Google Patents

Description

Process for the preparation of cyanomethyl substituted heterocyclic Compounds The preparation of 2-cyanomethylbenzimidazole by condensation of 1,2-diaminobenzene with ethyl cyanoacetate in boiling aniline is known (Journal of the American Chemical Society Vol. 65 [1943], pp. 1072-1075). Because the dangerousness of handling large amounts of ether, which leads to the failure of the Condensation product required, and an additional purification by recrystallization, this process is difficult to carry out on an industrial scale. If you use instead of the ethyl cyanoacetate the corresponding methyl ester, see above a sticky condensation product is obtained from which 2-cyanomethylbenzimidazole is obtained can be isolated in yields of only about 1001o of theory. On a nitrogen atom of the 1, 2-diaminobenzene substituted compounds or in the aromatic nucleus Residues such as phenyl, methyl or chlorine, substituted 1,2-diamines can be traced do not convert the known process to the corresponding 2-cyanomethylbenzimidazoles.

It has now been found that cyanomethyl-substituted heterocyclic compounds of the general formula which are pure and obtained in good yield can advantageously be obtained in which A denotes a benzene or naphthalene radical optionally substituted by halogen atoms, alkyl or alkoxy groups, which is substituted by the two nitrogen atoms in the ortho or peri position, and R1 denotes a hydrogen atom, alkyl groups optionally substituted by the hydroxyl or cyano group and aryl groups means by reacting compounds of the general formula with alkyl cyanoacetates of the general formula in which R2 denotes alkyl radicals with 1 to 8 carbon atoms, obtained at temperatures of 160 to 220 ° C. if the reaction is carried out in the absence of solvents and in the presence of aromatic sulfonic acids.

Examples of compounds of the formula II include in detail in consideration: 1,2-diaminobenzene, 1-amino-2-phenylaminobenzene, 1,2-diamino-4-methylbenzene, 1 - amino -2-methylaminobenzene, 1,2 - diamino - 4 - chlorobenzene, 1-amino-2- [p-cyanoethylamino] benzene, 1-Amino-2-methylamino-4-methylbenzene 1,2-, 2,3- or 1,8-diaminonaphthalene.

Examples of starting materials of the formula III include: methyl cyanoacetate, Ethyl cyanoacetate, n-propyl cyanoacetate, i-propyl cyanoacetate, N -butyl cyanoacetate, n-octyl cyanoacetate, isobutyl cyanoacetate.

The implementation of compounds of the formula II with compounds of the Formula III in the presence of preferably 0.5 to 50/0 of an aromatic sulfonic acid, such as p-toluene sulfonic acid, naphthalene-2-sulfonic acid or benzenesulfonic acid at temperatures of 160 to 220 ° C., the volatile substances formed during the reaction Products are distilled off.

Cyanoacetic acid esters of the formula III with R2 = C3H7 - to CsH17 - give the highest yields of cyanomethyl-substituted heterocycles; Connections of Formula III with Re = CH3 - and C2H5 - is therefore appropriately esterified to give the higher ones Esters, which can be further implemented as raw products.

The reaction products obtained in the reaction become useful with a solvent, e.g. B. a chlorinated benzene such as o-dichlorobenzene or Trichlorobenzene, stirred, which brought the product into a form that can be sucked off and is cleaned at the same time. A recrystallization is not more required as analytically pure products are obtained.

The reaction products in good yields and great purity incurred, can finally be isolated in the usual way.

The compounds obtainable according to the invention are intermediates for the manufacture of dyes and pharmaceuticals.

The parts and percentages given in the following examples are units of weight, unless otherwise stated. Parts of the room behave to parts by weight such as liters to kilograms under normal conditions.

Example 1 A mixture of 110 parts of 1,2-diamino-4-methylbenzene of melting point 83 "C, 155 parts of isobutyl cyanoacetate and 2 parts of p-toluenesulphonic acid is heated to 180 to 1900C, and 105 parts of liquid are distilled off. 70 parts of 1,2-dichlorobenzene are added to the 150 ° C. hot solution until it cools stirred to room temperature, the residue filtered off with suction, with a little 1,2-dichlorobenzene washed and dried at 80 ° C. under reduced pressure. 97 parts are obtained 2-Cyanmethyl-5 (6) -methylbenzimidazole, melting point 184 "C.

Example 2 A mixture of 37 parts of 2-aminodiphenylamine, 43 parts Isobutyl cyanoacetate and 1 part of p-toluenesulfonic acid are added while stirring 190 to 200 "C. After distilling off 23 parts of liquid and the Customary work-up gives 32 parts of 1-phenyl-2-cyanomethylbenzimidazole with a melting point 112 "C.

Example 3 1,5-Dimethyl-2-cyanomethylbenzimidazole 13.6 parts of 1-methylamino-2-aminomethylbenzene with a melting point of 45 ° C. are heated to 1800 ° C. with 17 parts of isobutyl cyanoacetate and 1 part of p-toluenesulfonic acid Parts of volatile products, the cold residue is rubbed with 100 parts of toluene and filtered off with suction. 8 parts of 1,5-dimethyl-2-cyanomethylbenzimidazole with a melting point of 147 ° C. are obtained.

Example 4 IC) -Cyanäthyl-2-cyanmethylbenzimidazoi 16.1 parts of 1- ß - cyanoethylamino - 2 - aminobenzene, prepared according to the details of the US Pat. No. 2,809,985, are mixed with 17 parts of isobutyl cyanoacetate and 1 part of p-toluenesulfonic acid heated to 190 "C, with 12 parts by volume of volatile products distilling off. After cooling, the flask residue is recrystallized from ethanol. 14.6 parts of 1-β-cyanoethyl-2-cyanomethylbenzimidazole with a melting point of 237 to 239" C are obtained.

Example 5 1-ß-Hydroxyethyl-2-cyanmethylbenzimidazole 15.2 parts of 1-ß-hydroxyethylamino-2-aminobenzene with a melting point of 109 "C are heated to 197" C with 17 parts of isobutyl cyanoacetate and 1 part of p-toluenesulphonic acid. After 10 parts by volume of volatile products have been distilled off and cooled, the residue in the flask is rubbed with acetone, filtered off with suction and recrystallized from methanol. 9 parts of 1-fl-hydroxyethyl-2-cyanmethylbenzimidazole with a melting point of 170 to 171 ° C. are obtained.

Example 6 2-Cyanmethyl-5 (6) -methoxy-benzimidazole 69 parts of 4-methoxy-1,2-diaminobenzene Kp4mm = 152 ° C, 30 parts of ethyl cyanoacetate and 4 parts of p-toluenesulfonic acid are heated together to 180 to 1900C. After 33 parts of volatile products have been distilled off, the cooled contents of the flask are rubbed with acetone and filtered off with suction.

14 parts of 2-cyanomethyl-5 (6) -methoxybenzimidazole are obtained with a Melting point> 300 ° C.

Example 7 1-Methyl-2-cyanomethylbenzimidazole 36.6 parts of 1-methylamino-2-aminobenzene and 47 parts of isobutyl cyanoacetate are heated to 180 ° C. with 0.5 part of p-toluenesulfonic acid.

After 29 parts by volume of volatile products have been distilled off the cooled residue is heated to boiling with 100 parts of toluene. After cooling down, Sucking off and drying are 31 parts of 1-methyl-2-cyanomethylbenzimidazole melting point 129 "C received.

Claims (1)

Claim: Process for the preparation of cyanomethyl-substituted heterocyclic compounds of the general formula in which A denotes a benzene or naphthalene radical optionally substituted by halogen atoms, alkyl or alkoxy groups, which is substituted by the two nitrogen atoms in the ortho or peri position, and R1 denotes a hydrogen atom, alkyl groups optionally substituted by the hydroxyl or cyano group and aryl groups means by converting compounds of the general formula with alkyl cyanoacetates of the general formula in which R2 denotes alkyl radicals with 1 to 8 carbon atoms, at temperatures from 160 to 220 ° C., characterized in that the reaction is carried out in the absence of solvents and in the presence of aromatic sulfonic acids.