SU1747442A1 - Method of imidazole synthesis - Google Patents

Abstract

Usage: as an intermediate in the synthesis of heterocyclic compounds. The essence of the invention: imidazole product. BF SzNd№, so pl. 89-90 ° C. Reagent 1: ammonium oxalate. Reagent 2: glyoxal. Reagent 3: formaldehyde. Reagent 4: ammonia. Reaction Conditions: at 50-90 ° C. 1 tab.

Description

The invention relates to the chemical technology of organic compounds, in particular the preparation of imidazole, one of the most important intermediate products, which is used in the synthesis of various medicinal preparations.

A number of processes for the preparation of imidazole are known. Based on the interaction of glyoxal, formaldehyde and ammonia.

The reaction may be carried out under various conditions. Thus, the interaction of the reagents is carried out at 165 ° C in pairs with a crude imidazole yield of 69% and subsequent purification at 200 ° C over Rene nickel. The total yield after two stages is 54%.

It is more convenient and safer to carry out the condensation reaction of glioxal with ammonia and formaldehyde in an aqueous medium. To increase the yield of imidazole, it was proposed to add a 35-40% solution of glyoxal at 65-70 ° C to a mixture of 15-25% ammonia and 30-40% formaldehyde, prepared at 0-5 ° C with a ratio of reagents 4J-4, 8 / 1.0-1.2 and then distilling the water under vacuum distillation to isolate the desired product.

The separation of the imidazole after carrying out the synthesis reaction is carried out by distillation of water and volatile products from the reaction mixture and subsequent imidazole by vacuum distillation. In order to be able to distil it at 130-140 ° C, it is necessary to maintain a vacuum of 5-6 mm OST. and the temperature in the cube is not lower than 160-180 ° C. This leads to the tarring of the resin in ky6e, to the formation of pitch (dark resinous mass), the removal of which from the apparatus is difficult, especially under production conditions.

The closest to the proposed method is the method, which consists in the fact that after carrying out the synthesis of imidazole, obtained by the reaction of an aqueous solution of succinic ammonium (0.25 mol), 40% aqueous glyoxal (0.25 mol) and 37% aqueous formaldehyde (0.25 mol) at 60 ° C and pH 5.2-5.8 (maintained by addition of aqueous NH40H), the reaction mixture is subjected to vacuum distillation. First, part of the water is distilled off, then butyl alcohol is added and a part of water is distilled off as an azeotrope, butyl alcohol is added to the residue, heated to 30 ° C and aqueous ammonia is added. Division yuk suko

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ammonium cinate, and a solvent is added to the aqueous phase and the mixture is subjected to vacuum distillation. The yield of imidazole is 81%.

The disadvantages of the prototype method are: the need for water stripping; the release of imidazole from its salt with succinic acid with an aqueous solution of ammonia, which leads to the need for re-distillation of water; the complication of the process associated with the need for vacuum distillation of imidazole and, accordingly, the formation of tar bottoms.

It should be noted that the raw imidazole obtained according to the method of the prototype, before the distillation stage, is a black resinous mass; etc.

The purpose of the invention is to simplify the technology and improve the quality of the raw product.

The delivered goal is achieved by changing the process conditions.

The essence of the proposed technical solution consists in the interaction of glyoxal, formalin with ammonium oxalate in water, followed by release of imidazole oxalate by filtration and treatment of the salt with anhydrous ammonia in an organic solvent.

Distinctive features of the proposed technical solution are: the use of ammonium oxalate (I) as the ammonium salt is new in relation to the known technical solutions; isolating the product in the form of a salt (II) is new with respect to the prototype, it is known in the field of organic chemistry; Treatment with anhydrous ammonia in an organic solvent (111) is new with respect to the prototype, known from other technical solutions, but is used with a new purpose.

To the suspension, 62 g (0.5 mol) of ammonium oxalate in 100 ml of water with stirring and a temperature of 50-90 ° C simultaneously dispense 50 g (0.34 mol) of 40% aqueous glyoxal and 430 g (0.34 mol) 37 % aqueous formaldehyde for 1 h. At the end of the dosage give an exposure of 0.5-3 h, after which the mass is cooled to 5-10 ° C and filtered. The precipitate is dried and suspended in an organic solvent, for example, methylene chloride, ethyl acetate, ethyl ether. 17 g (1 mol) of dry are passed through the suspension at 5-25 ° C and stirring

ammonia gas for 2 hours. Then the mass is filtered, the precipitate is returned to the condensation stage, and the filtrate is evaporated. The residue (raw imidazole) is a light beige powder, m.p. 83-86 ° C, the content of the basic substance 97-98%.

After crystallization from dichloroethane, imidazole was obtained with m.p. 87.5-89 ° C, the content of the basic substance of 99.0%. Output

85%. After crystallization from toluene, imidazole was obtained with m.p. 89-90 ° C, the content of the basic substance of 99.3%. Yield 96%.

The positive effect of the proposed technical solution is to simplify the technology by improving the quality of the raw product, which eliminates the stage of high-temperature vacuum distillation (table). Improving the quality of the raw product is achieved by

combining the stages of isolation and primary purification of the target product. In addition, the instrumentation of the process is simplified. When implementing the method uses available raw materials.

Claims (1)

Claims of Invention A method of producing imidazole by the interaction of glyoxal. formaldehyde and aliphatic ammonium salt dibasic acid in water when heated, followed by separation of the target product, characterized in that, in order to simplify the process technology and improve the quality of the target product, ammonium oxalate is used as the ammonium salt of aliphatic dibasic acid, the process is carried out at 50-90 ° C, and the isolation of the target product is carried out by filtering the reaction mixture and treating the resulting precipitate with anhydrous ammonia in an organic solvent.