RU2345988C2 - Method of obtaining 5(6)-amino-2-(4-aminophenyl) benzimidazole - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: present invention pertains to organic chemistry and method of obtaining 5(6)-amino-2-(4-aminophenyl)benzimidazole, which is a monomer for producing heat resistant and high-strength fibres. Description is given of a method of obtaining 5(6)-amino-2-(4-aminophenyl)benzimidazole, involving reduction of 2¹,4,4¹-trinitrobenzanilide to 2¹,4,4¹-triaminobenzanilide in the presence of a catalyst in an aqueous medium, cyclodehydration in an aqua acid medium and separation of the target product. The reaction mass obtained from the reduction process after separation of catalyst is processed with sulphuric acid. 2¹,4,4¹-triaminobenzanilide is separated in form of mono-sulphate salt, which is subjected to cyclodehydration through heating in an aqueous sulphuric acid with formation of a hydrate of mono-sulphate salt 5(6)-amino-2-(4-aminophenyl)benzidazole and the base is separated by further neutralisation.

EFFECT: perfection of the method with the aim of efficient low-waste production of a product with high degree of purity.

6 cl, 1 dwg, 1 tbl, 6 ex

Description

The present invention relates to the field of organic chemistry and relates to a method for producing 5 (6) -amino-2- (4-aminophenyl) benzimidazole - a monomer for the production of heat-resistant and high-strength fibers.

A known method for producing 2- (4 ^1- aminophenyl) -5-aminobenzimidazole by condensation of 4-nitrobenzoic acid with aniline, by dinitrogenation of the resulting N- (4 ^1- nitrobenzoyl) aniline to N- (4 ^1- nitrobenzoyl) 2,4-dinitroaniline, followed by reduction in 2 ¹ , 4,4 ¹ -triaminobenzanilide by treatment with sodium or ammonium hydrosulfide and cyclodehydration of triamine to the target product in hydrochloric acid under heating:

Diaminobenzimidazole is purified by recrystallization from ethanol (US Patent 4109093, NCI 548 / 310.7, publ. 08/22/1978). The disadvantages of the method are the high consumption of concentrated sulfuric and nitric acids, as well as sodium or ammonium hydrosulfide, which leads to the formation of a large amount of waste, alkaline hydrolysis of 2 ¹ , 4,4 ^1- trinitrobenzanilide in the recovery process, leading to a decrease in yield, contamination of the target product with compounds sulfur. This necessitates the purification of 2- (4 ^1- aminophenyl) -5-aminobenzimidazole by recrystallization from ethanol, product loss and complicates the process.

A known method of producing 5 (6) -amino-2- (4-aminophenyl) benzimidazole by hydrogenation of 2,4-dinitroaniline on Raney nickel or palladium in alcohol with the release of 1,2,4-triaminobenzene in the form of phosphate, followed by condensation with 4- aminobenzoic acid in a medium of polyphosphoric acid when heated to 140-145 ° C (A.S. USSR 498298, C07D 235/18, publ. 09/13/1976). The disadvantage of this method is the formation as an intermediate of an unstable, easily resins 1,2,4-triaminobenzene and the use of a large amount of expensive polyphosphoric acid, the formation of a significant amount of waste contaminated with organic compounds of phosphoric acid.

A known method of producing 2- (4 ^1- aminophenyl) -5-aminobenzimidazole by condensation of 4-nitro-1,2-diaminobenzene with 4-nitrobenzoyl chloride with the formation of 2 ¹ -amino-5 ^1- nitroanilide 4-nitrobenzoic acid, followed by reduction with hydrosulfide and simultaneous cyclodehydration in an alkaline medium when heated at 95-100 ° C for 10-12 hours:

The target product is isolated in the form of crystalline hydrate with a purity of 91-92% and a melting point of 140-142 ° C (US Patent 4192947, C07D 235/18, publ. 11.03.1980). The disadvantage of this method is the use of inaccessible and expensive 4-nitro-1,2-diaminobenzene, a low degree of purity of the target product.

A known method of producing 5 (6) -amino-2- (4 ¹ -aminophenyl) benzimidazole by cyclodehydration of 2 ¹ , 4,4 ¹ -triaminobenzanilide in hydrochloric acid under heating in the presence of formic acid (A.S. USSR 1438178, C07D 235 / 18, published on July 27, 1995). The disadvantage of this method is the use of concentrated hydrochloric acid when heated, the isolation of the target product in the form of trihydrochloride by fixing the reaction mass with a large amount of concentrated hydrochloric acid, followed by its neutralization, which leads to an increase in the corrosivity of the working medium and the formation of a large amount of waste contaminated with impurities of organic compounds.

A known method for producing 2 ¹ , 4,4 ^1- triaminobenzanilide - an intermediate of synthesis of 5 (6) -amino-2- (4-aminophenyl) benzimidazole by reduction of 2 ¹ , 4,4 ¹ -triamino-benzanilide with hydrogen in water in the presence of a catalyst under hydrogen pressure of 1.5 MPa and a temperature of up to 130 ° C (RF Patent 2041200, С07С 233/80, publ. 09.08.1995). After completion of the recovery process, a solution of 2 ¹ , 4,4 ¹ -triaminobenzanilide in water at 130 ° C is separated from the catalyst by filtration and the target product is isolated by crystallization by cooling the solution. The disadvantage of the recovery method with the allocation of 2 ¹ , 4,4 ¹ -triaminobenzanilide in the form of a base is the general tendency of amino compounds containing two or more amino groups in one aromatic core to oxidize (Vorozhtsov N.N. Fundamentals of the synthesis of intermediate products and dyes. / GCI, M ., 1955. - 839 p.). At the same time, their salts are stable. This is the basis for the isolation of triaminobenzene in the form of phosphate, used in the aforementioned method for producing DAFBI (AS USSR 498298, C 07 D 235/18, publ. 13.09.1976). In addition, 1,2,4-triaminobenzene, present as an impurity in 2 ¹ , 4,4 ¹ -triaminobenzanilide, is easily oxidized to benzoquinone, which reacts with 1,2,4-triaminobenzene to form 2,3,6-triaminophenazine , which determines the color of 2 ¹ , 4,4 ¹ -triaminobenzanilide and (6) -amino-2- (4-aminophenyl) benzimidazole. The presence of 2,3,6-triaminophenazine in DAFBI was confirmed by chromatography-mass spectroscopy (molecular weight 225).

A known method for producing 2 ¹ , 4,4 ^1- triaminobenzanilide by catalytic reduction of 2 ¹ , 4,4 ^1- triaminobenzanilide with hydrogen in an organic solvent on a palladium catalyst promoted with boron (A.S. USSR 546608, С07С 103/20, publ. 15.02 .1977). As solvents, dimethylformamide, isopropanol or dioxane are proposed. However, of the above solvents, isopropanol and dioxane are not suitable for the industrial production of 2 ¹ , 4,4 ¹ -triaminobenzanilide due to its low solubility and the associated difficulties in separating the triamine solution from the catalyst. Dimethylformamide has a high solubility with respect to 2 ¹ , 4,4 ¹ -triaminobenzanilide (table). However, the separation of DMF from solutions is a difficult technical problem, since it requires either a two-stage evaporation of a part of the solvent with separation of the crystallized triamine, the product being ground in this case, or isolation of 2 ¹ , 4,4 ¹ -triaminobenzanilide from the solution by dilution with a large amount of water, which leads to a sharp increase in the energy intensity of the solvent regeneration process.

One of the important industrial methods for the reduction of aromatic nitro compounds to the corresponding aromatic amines is iron reduction in an aqueous medium in the presence of an electrolyte:

4ArNO ₂ + 9Fe + 4H ₂ O → 4ArNH ₂ + 3Fe ₃ O ₄

The target amine is isolated from the reaction mass after it has been neutralized with bases by distillation or filtration of the solution of the amino compound from the by-product of iron oxide (Vorozhtsov N.N. Fundamentals of the synthesis of intermediate products and dyes. / GHI, M., 1955. - 839 p .; Efros L .S., Gorelik MV Chemistry and technology of intermediate products. - L .: Chemistry, 1980. - 544 p.). The disadvantage of this method is the formation after neutralization of hard-to-filter sludge of iron oxide.

The closest analogue of the proposed method is a method for producing 2- (4-aminophenyl) -5-amino-benzimidazole (DAFBI) by catalytic reduction of N- (4-nitrobenzoyl) -2,4-dinitroaniline (TNBA) with hydrogen in suspension in aqueous solutions of hydrochloric or phosphoric acid (US Patent 4417056, C07D 235/18, publ. 11/22/1983)

As catalysts, contacts are used that contain nickel, platinum, palladium, rhodium and ruthenium, both as such and supported on alumina, aluminosilicate, magnesium oxide, activated carbon, etc. The amount of metal is preferably from 0.025 to 0.5 g per 1 kg of TNBA. The initial content (C) of TNBA in the acid-water suspension varies from 0.15 to 1.5 mol / L. The molar ratio (A): acid / TNBA is from 2 to 20. The process proceeds at a hydrogen pressure of 5 to 100 bar [0.5-10 MPa] and a temperature (T) of 20 to 100 ° C, so that the product T × A × C is equal to or greater than 50.

The hydrogenation rate is high and the DAFBI salt formed during the reaction immediately passes into solution. When the reaction is complete, simple hot filtration allows the catalyst to be separated and returned. By cooling and, possibly, by evaporation of the filtrate, the DAFBI salt can be isolated in crystalline form. DAFBI can be isolated in the form of a free base by any well-known method. The examples show the neutralization of the DAFBI salt with sodium hydroxide.

When carrying out hydrogenation and cyclodehydration in the presence of phosphoric acid, the yield of DAFBI (according to the analysis by liquid chromatography under pressure by the method of the inverse phases) is 81-92.7%. Only in Example 1, the DAFBI base was isolated by neutralization with sodium hydroxide.

After recrystallization from ethanol, a DAFBI crystalline hydrate was obtained containing one molecule of DAFBI • H ₂ O water with a molecular weight of 242. Its composition was confirmed by elemental analysis and NMR spectroscopy. Melting points are not shown.

The disadvantages of the method are:

1. Carrying out the restoration in the environment of aqueous solutions of acids, which leads to the loss of precious metal catalyst for the reduction as a result of dissolution of the metal in an acidic environment (see drawing.)

2. High corrosiveness of the medium, which leads to the need for an autoclave working under high pressure and, therefore, material-intensive, to use expensive high-alloy metal - Hostella S alloy.

3. The description of the known method does not provide data on the isolation of DAFBI in the form of a dry base suitable for the preparation of polymers by polycondensation, and, as a result, there are no data to evaluate its purity. The example given in the description of the recrystallization of the base hydrate from ethanol cannot be used in industrial practice due to the low solubility of DAFBI in ethanol (table). It can be expected that the release of DAFBI in the form of a base of monomeric purity will be accompanied by significant losses and a decrease in product yield.

The objective of the present invention is to improve the method for producing 5 (6) -amino-2- (4-aminophenyl) benzimidazole from 2 ¹ , 4,4 ^1- trinitrobenzanilide in order to create an efficient low-waste production of a high-purity product.

This goal is achieved by the proposed method for the production of 5 (6) -amino-2- (4-aminophenyl) benzimidazole (DAFBI), including the reduction of 2 ¹ , 4,4 ^1- trinitrobenzanilide (TNBA) in 2 ¹ , 4,4 ¹ -triaminobenzanilide ( TABA) in the presence of a catalyst in an aqueous medium, cyclodehydration in an aqueous acid medium and isolation of the target product. The inventive method is characterized in that obtained by reduction of the 2 ^1, 4,4 ¹ -trinitrobenzanilida 2 ^1, 4,4 ¹ -triaminobenzanilid reaction mixture after separation of the catalyst is treated with sulfuric acid allocated 2 ^1, 4,4 ¹ -triaminobenzanilid as monosernokisloy salt, which is subjected to cyclodehydration by heating in aqueous sulfuric acid to form the dihydrate of the monosulfur salt of 5 (6) -amino-2- (4-aminophenyl) benzimidazole and then the base is isolated by neutralization.

Achieving this goal contributes to the observance of a number of conditions.

Since TABA is sparingly soluble in water at temperatures up to 100 ° C, and at temperatures above 100 ° C, hydrolysis of the initial TNBA can occur, it is advisable to use mixtures of water with a dipolar aprotic solvent selected from a number of dimethylformamide, dimethylacetamide, N-methylpyrrolidone. In this case, the concentration of solvent in water is advisable to maintain in the range up to 50 wt.%. In this case, a sufficiently high solubility of TABA is provided to separate it in the form of a solution from the catalyst (table).

The reduction of TNBA in TABA in an aqueous medium can be carried out with hydrogen using traditional hydrogenation catalysts - palladium on carbon, skeletal nickel, etc. or using a water-iron-electrolyte system (NH ₄ Cl, FeCl ₂ , etc.) as a reducing agent, where the hydrogen source is water, and the iron-electrolyte system acts as a catalyst.

The process of obtaining monosulfuric salt of TABA is carried out by the gradual addition of an aqueous solution of sulfuric acid to a solution or suspension of TABA after separation of the catalyst with stirring. Sulfuric acid is introduced into the process in an amount close to stoichiometric for the formation of monosulfate salt. In the process of adding sulfuric acid, cooling is used to prevent a sharp increase in temperature.

It was found that the monosulfuric salt of TABA is practically insoluble in water at ordinary temperature and can be washed with water from residual solvent. Sulfuric acid can be used in the form of an aqueous solution of various concentrations or in concentrated form. This technique allows TABA to be isolated from a solution in a mixed solvent without additional dilution with water to precipitate TABA, which allows the solvent to be regenerated by distillation.

Isolation of TABA in the form of sulfate is an effective purification method and ensures the stability of TABA, which in the form of a base is susceptible to oxidation, and its color increases.

The resulting suspension of TABA monosulphate salt is subjected to cyclodehydration in an aqueous solution of sulfuric acid directly or pre-filtered and an aqueous paste of monosulphate salt is used.

The cyclodehydration of the monosulphate salt of TABA is carried out with heating, the concentration of sulfuric acid in the reaction mass should be 10-13 wt.%.

The acidity of the cyclodehydration medium in order to suppress side reactions of TABA hydrolysis can be reduced by adding aqueous ammonia.

The selection of the product of cyclodehydration from the reaction mass is carried out by crystallization under cooling. In this case, the dihydrate of the monosulfuric salt DAFBI • Н ₂ SO ₄ • 2Н ₂ O is released.

Sulfuric acid mother liquor after separation of the salt DAFBI • H ₂ SO ₄ • 2H ₂ O by filtration is sent to recycling to the stage of cyclodehydration. If necessary, the sulfuric acid mother liquor can be cleaned with activated carbon. Recycling of the mother liquor can be carried out repeatedly.

DAFBI • H ₂ SO ₄ • 2H ₂ O dihydrate can be purified by recrystallization from 10-13% aqueous sulfuric acid, if necessary in the presence of activated carbon. The resulting sulfuric acid mother liquor can be recycled to the dihydrate recrystallization stage or to the cyclodehydration stage. The composition of the dihydrate is confirmed by X-ray diffraction and elemental analysis, as well as acid-base titration and thermogravimetry.

The free base, DAPBI, is isolated by adding the dihydrate of its monosulfate salt to an aqueous solution of ammonia or sodium hydroxide in the presence of complexon. This order of mixing of the reagents provides the mobility of the suspension. The completeness of neutralization is ensured by subsequent heating of the reaction mass to 50-90 ° C.

DAPHI isolated in the form of a base is dried in a stream of inert gas in a stepwise mode. To 5 (6) -amino-2- (4-aminophenyl) benzimidazole, a monomer for polycondensation, high demands are placed on the residual moisture content of not more than 0.2 wt.%. At the same time, the drying process of DAFBI is a difficult technical task, since DAFBI forms a crystalline hydrate of DAFBI · H ₂ O, which melts at a temperature of 135-140 ° C. In this case, the phenomenon of the so-called “caramelization” is observed, when the semi-solid mass crumbles, sticks together, covers the heat exchange surfaces, which extremely complicates the drying process. It is established that the phenomenon of "caramelization" can be prevented by using the stepwise mode of temperature increase - at the first stage 100-135 ° C and at the second final stage of drying 150-170 ° C.

The drawing shows the dependence of the loss of palladium during the processing of the palladium catalyst with hydrochloric acid on the concentration of hydrochloric acid and temperature.

The following examples illustrate the essence of the invention.

Example 1. Obtaining 5 (6) -amino-2- (4-aminophenyl) benzimidazole.

Obtaining monosulfur salt 2 ¹ , 4,4 ¹ -triaminobenzanilide.

In a stainless steel reactor with a volume of 2 dm ² with a stirrer, electric heating, a cooling coil, a pressure gauge, a thermocouple, a gas inlet fitting, an integrated filter and a bottom valve, 137 g of 2 ¹ , 4.4 ^1- trinitrobenzanilide, 225 cm ^{3 of} dimethylacetamide are loaded, 675 cm ^{3 of} water and 6 g of catalyst 0.8% Pd / C (palladium on charcoal). The reactor is sealed, purged with nitrogen, then with hydrogen and reduced at a temperature of 90-100 ° C and a hydrogen pressure of 15-5 MPa. The temperature is controlled by the supply of water to the reactor coil. The theoretical amount of hydrogen is absorbed in 10 minutes.

The reactor was purged with nitrogen and the solution of 2 ¹ , 4.4 ^l- triaminobenzanilide was filtered from the catalyst, taking the filtrate into a three-necked flask with a capacity of 2 dm ³ , equipped with a stirrer, a thermometer and a dropping funnel. The solution is cooled to 20 ° C and gradually, with cooling and stirring, is added 202.2 g of 20% sulfuric acid from a dropping funnel (stoichiometric amount relative to the calculated amount of 2 ¹ , 4,4 ¹ -triaminobenzanilide). A white precipitate of monosulfuric salt of 2 ¹ , 4,4 ¹ -triaminobenzanilide (TABA • H ₂ SO ₄ ) immediately precipitated. In the process of adding sulfuric acid, the reaction medium has a pH value of ~ 5, since sulfuric acid quickly binds to the TABA • H ₂ SO ₄ salt. Only after completion of the addition of sulfuric acid in the reaction mass is the pH ~ 3 set. The salt is filtered off, washed with water. 255.4 g of TABA • H ₂ SO ₄ salt paste are obtained. The paste contains 137.5 g of TABA • H ₂ SO ₄ (98% of theory) and 118 g of water. The H ₂ SO ₄ content of the isolated TABA • H ₂ SO ₄ salt, determined by volumetric titration with sodium hydroxide, 28.2 wt.% (Theoretical content of H ₂ SO ₄ 28.817 wt.%), Color 2.3. The aqueous extract has a pH of 5.2.

Preparation of 5 (6) -amino-2- (4-aminophenyl) benzimidazole monosulfur salt dihydrate.

5 (6) -amino-2- (4-aminophenyl) benzimidazole monosulphate salt dihydrate (DAPBI • H ₂ SO ₄ • 2H ₂ O) is obtained from the monosulphate salt of TABA • H ₂ SO ₄ in a medium of dilute sulfuric acid in the presence of ammonia with a molar the ratio of TABA • H ₂ SO ₄ : H ₂ SO ₄ : NH ₃ : H ₂ O = 1: 2.8: 1: 105. In a three-necked flask with a capacity of 2 dm ³ , equipped with a stirrer, reflux condenser and thermometer, 255.4 g of a water paste of TABA • H ₂ SO ₄ salt containing 137.5 g of the basic substance, 617 g of water, 117.7 g of 94.3 are loaded % sulfuric acid and 30 cm ³ 25% aqueous ammonia. The mass is heated with stirring to a temperature of 100-101 ° C and maintained at this temperature. The total duration of the synthesis of 4.5 hours. Next, the mass is cooled to 10-12 ° C, the precipitated crystals DAPBI • Н ₂ SO ₄ • 2Н ₂ O are filtered off, washed with water. Get 204.9 g of an aqueous salt paste containing 126 g of the basic substance (87% of theory). The sulfuric acid mother liquor formed during the filtration and washing of the salt is treated with activated carbon and recycled for the next synthesis of the DAFBI • Н ₂ SO ₄ • 2Н ₂ O salt. With successive recycling of the mother liquor, the yield of the DAFBI • Н ₂ SO ₄ • 2Н ₂ O salt increases to 95- 97% of theory.

Recrystallization of salt DAFBI • H ₂ SO ₄ • 2H ₂ O

Recrystallization is carried out in 12% sulfuric acid in the presence of activated carbon. In a three-necked flask with a capacity of 2 dm ³ , equipped with a stirrer, thermometer, reflux condenser, load 204.9 g of a water paste of salt DAFBI • Н ₂ SO ₄ • 2Н ₂ O containing 126 g of the basic substance, 973 cm ^{3 of} water, 131.5 g 94.3% sulfuric acid and 16 g of activated carbon OU-B. The mass is stirred at 100 ° C for 0.5 hours, filtered from coal. The charcoal on the filter is washed with 95 cm ^{3 of} 12% sulfuric acid, attaching a wash filtrate to the main one. The mother liquor is cooled to 10-5 ° C, the crystals of the salt DAFBI • Н ₂ SO ₄ • 2Н ₂ O are filtered off, washed with 95 cm ^{3 of} 12% sulfuric acid and 380 cm ^{3 of} water. Sulfuric acid filtrates are combined and used in subsequent salt recrystallizations. 129 g of an aqueous paste are obtained containing 107.2 g (85.1% of theory) of the DAFBI • H ₂ SO ₄ • 2H ₂ O salt. The salt is a bright yellow crystalline powder with a greenish tint. Its composition is confirmed by x-ray analysis and elemental analysis. Sulfur content in the sample dried at 165 ° C, wt.%: Found 9.72; 9.91; calculated 9.95. The color of salt is 29 units. Thermogravimetric analysis found that the salt loses crystallization water at a temperature of 100 ° C.

In subsequent experiments with the recycling of the sulfuric acid mother liquor, the yield of DAFBI • Н ₂ SO ₄ • 2Н ₂ O salt reaches 97-98% of the theoretical.

Isolation of the base of 5 (6) -amino-2- (4-aminophenyl) benzimidazole and its drying.

298.4 cm ^{3 of} water, 54.4 cm ^{3 of a} 25% aqueous ammonia solution and 29 cm ^{3 of a} 5% Trilon B solution are charged into a three-necked flask with a capacity of 1 dm ³ equipped with a stirrer, reflux condenser and thermometer. To the solution while stirring ammonia, 129 g of a salt water paste containing 107.2 g of DAFBI • H ₂ SO ₄ • 2H ₂ O is gradually added. The molar ratio of reactants to water at the neutralization stage is DAFBI • H ₂ SO ₄ : NH ₃ : H ₂ O = 1: 2, 413: 68.1. The suspension is stirred for 40 minutes, then heated to 90 ° C and maintained at this temperature for 1 hour. If necessary, adjust the pH of the medium by adding ammonia water to a pH of 8-9. The total exposure time at 90 ° C for 2 hours. Doughboy suspension in an aqueous ammonium sulfate solution was cooled to 30-40 ° C, filtered, washed with water until no ions SO ₄ ^- in the washing waters (the sample with barium chloride in the extract of pasta with an aqueous solution of sodium hydroxide).

An aqueous paste of 5 (6) -amino-2- (4-aminophenyl) benzimidazole is obtained, which is dried in a stream of inert gas at 100-135 ° C until most of the crystalline hydrate water is released, and then to constant weight at 150-160 ° C. Yield 67.1 g (96.6% of theory). The melting point is 234 ° C, the color is 2.5 units, the mass fraction of the residue after calcination is 0.004%, the mass fraction of water is 0.1%, impurities insoluble in an aqueous solution of hydrogen chloride are traces.

Example 2. In the reactor described in example 1, load 137 g of 2 ¹ , 4,4 ^1- trinitrobenzanilide, 27 cm ^{3 of} dimethylformamide, 630 cm ^{3 of} water and 6 g of catalyst 0.8% Pd / C. The process of recovering TNBA and isolating the TABA • H ₂ SO ₄ monosulfur salt is carried out similarly to that described in Example 1. 243 g of an aqueous paste of the TABA • H ₂ SO ₄ salt is obtained, containing 138.2 g of the basic substance (98.5% of theory). The content of H ₂ SO ₄ in the dried salt is 28.22 wt.%, Color 2.5 units. The aqueous extract has a pH of 6.1.

The DAFBI monosulphate salt dihydrate was prepared as described in Example 1, observing, when loading, the molar ratio TABA • H ₂ SO ₄ : H ₂ SO ₄ : NH ₃ : H ₂ O = 1: 2.8: 1: 105. From 138.2 g of TABA • H ₂ SO ₄ receive DAFBI • H ₂ SO ₄ • 2H ₂ O in the form of an aqueous paste containing 135.4 g of the basic substance (93% of theory). After recrystallization from aqueous sulfuric acid in the presence of 16 g of activated carbon OU-B under conditions similar to example 1, subject to the molar ratio of DAFBI • H ₂ SO ₄ : H ₂ SO ₄ : H ₂ O = 1: 3,612: 170, an aqueous paste is obtained purified salt DAFBI • H ₂ SO ₄ • 2H ₂ O, containing 119.2 g of the basic substance (88% of theory). The color of salt is 25.6 units.

To a solution of 27.93 g of sodium hydroxide in 390 cm ^{3 of} water, an aqueous paste of DAPBI • Н ₂ SO ₄ • 2Н ₂ O salt, containing 119.2 g of the basic substance, is gradually added with stirring. The mass is stirred for 0.5 hours, heated with stirring to 50 ° C, incubated and dried as described in example 1. 72.8 g of 5 (6) -amino-2- (4-aminophenyl) benzimidazole (94.3%) are obtained. from theoretical). The melting point is 234 ° C, the color is 3.2 units, the mass fraction of the residue after calcination is 0.006%, the mass fraction of water is 0.12%, impurities insoluble in an aqueous solution of hydrogen chloride are traces.

Example 3. In the reactor described in example 1, load 137 g of 2 ¹ , 4.4 ^l- trinitrobenzanilide, 270 cm ^{3 of} dimethylformamide, 630 cm ^{3 of} water and 6 g of catalyst 0.8% Pd / C. The process of reducing and isolating the TABA • H ₂ SO ₄ monosulfur salt is carried out similarly to that described in Example 1. 244 g of an aqueous paste of the TABA • H ₂ SO ₄ salt is obtained containing 138.6 g of the basic substance (98.8% of theory). The content of H ₂ SO ₄ in the dried salt is 28.20 wt.%, The color of 2.4 units. The aqueous extract has a pH of 6.0.

The DAFBI monosulphate salt dihydrate was prepared as described in Example 1, observing the molar ratio of TABA • H ₂ SO ₄ : H ₂ SO ₄ : NH ₃ : H ₂ O = 1: 2.8: 1: 105 when loading, but using sulfuric acid the mother liquor formed in the synthesis of DAFBI • H ₂ SO ₄ • 2H ₂ O dihydrate in Example 2, taking into account the content of sulfuric acid, ammonia and water in it. The synthesis charge is 244 g of an aqueous paste of TABA • H ₂ SO ₄ salt containing 138.6 g of the basic substance and 105, 4 g of water, 764.2 g of the mother liquor from Example 2, which was pretreated with 13 g of activated carbon OU-B with heating for 30 min, containing 94.4 g of sulfuric acid, 4.3 g of ammonia and 664.9 g of water, 18.5 g of 94.3% sulfuric acid and 11.6 ml of 25% aqueous ammonia . After the processing described in examples 1 and 2, receive DAFBI • H ₂ SO ₄ • 2H ₂ O in the form of an aqueous paste containing 140.5 g of the basic substance (96.2% of theory). The dihydrate is recrystallized from the sulfuric acid mother liquor from recrystallization obtained in Example 2, subject to the conditions given in Example 1. The recrystallization charge is 140.5 g of DAFBI • Н ₂ SO ₄ • 2Н ₂ O dihydrate, with which 105 g of water is added, 1157 g of sulfuric acid mother liquor with a sulfuric acid concentration of 12%, 180 ml of water and 16 g of activated carbon. After the treatment described in example 1, an aqueous paste of the purified salt DAFBI • H ₂ SO ₄ • 2H ₂ O containing 132.5 g of the basic substance (94.3% of theory) is obtained. Color 26.2 units.

After neutralization with an aqueous solution of ammonia and drying, 84.2 g of 5 (6) -amino-2- (4-aminophenyl) benzimidazole (98.1% of theory) are obtained in the same manner as described in Example 1. The melting point is 234 ° C, the color is 2.7 units, the mass fraction of the residue after calcination is 0.003%, the mass fraction of water is 0.13%, impurities insoluble in an aqueous solution of hydrogen chloride are traces.

Recycling of sulfuric acid mother liquors at the stages of the synthesis of DAFBI • H ₂ SO ₄ • 2H ₂ O dihydrate and its recrystallization can be carried out an unlimited number of times without reducing the quality of the product. At the same time, yields for each of the stages reach 97-98% of theoretical, the process becomes low-waste.

Example 4. In the reactor described in example 1, load 137 g of 2 ¹ , 4,4 ^1- trinitrobenzanilide, 180 cm ³ N-methylpyrrolidone, 720 cm ³ water, 6 g of catalyst 0.8% Pd / C. The recovery process, the allocation of monosulfuric salt TABA • H ₂ SO _{4 is} carried out similarly to that described in example 1. Receive 129.2 g of monosulfuric salt TABA • H ₂ SO ₄ (92.1% of theory) in the form of an aqueous paste. The content of H ₂ SO ₄ in the dried salt is 28.20 wt.%, Color 2.7 units. The aqueous extract has a pH of 6.4.

The DAFBI monosulphate salt dihydrate was prepared as described in Example 1, observing, when loading, the molar ratio TABA • H ₂ SO ₄ : H ₂ SO ₄ : NH ₃ : H ₂ O = 1: 2.8: 1: 105. From 129.2 g of TABA • H ₂ SO ₄ receive DAFBI • H ₂ SO ₄ • 2H ₂ O in the form of an aqueous paste containing 115.7 g of the basic substance (85% of theory). After recrystallization from aqueous sulfuric acid in the presence of 15 g of activated carbon OU-B under conditions similar to example 1, subject to the molar ratio DAFBI • H ₂ SO ₄ : H ₂ SO ₄ : H ₂ O = 1: 3.6: 170 receive aqueous paste of purified salt DAFBI • Н ₂ SO ₄ • 2Н ₂ O, containing 99.7 g of the basic substance (86.2% of theory).

The selection of the free base is carried out, as described in example 1, by neutralizing the salt with an aqueous solution of ammonia, while observing the molar ratio of DAFBI • H ₂ SO ₄ : NH ₃ : H ₂ O = 1: 2.4: 68. After drying at a stepwise increase in temperature, as described in Example 1, 62.8 g (97.2% of theory) of 5 (6) -amino-2- (4-aminophenyl) benzimidazole are obtained. The melting point is 234 ° C, the color is 2.4 units, the mass fraction of the residue after calcination is 0.003%, the mass fraction of water is 0.12%, and impurities insoluble in an aqueous solution of hydrogen chloride are 0.04 wt.%.

Example 5. In the reactor described in example 1, equipped on a drain from the bottom outlet with a stainless steel crystallizer with a capacity of 2 dm ³ , equipped with a stirrer, thermocouple, fittings for depressurizing, loading raw materials and a manometer, 73.64 g 2 ¹ , 4 are loaded , 4 ^1- trinitrobenzanilide, 975 cm ^{3 of} water and 2.8 g of a palladium catalyst of 0.8% Pd / C. The reactor is purged with nitrogen, then with hydrogen and a hydrogen pressure of 1.5 MPa is collected, the reactor is stirred, and the electric heating is activated. The temperature in the reactor is gradually increased to 130 ° C. After aging for 1 hour, the process ends. After purging hydrogen with an inert gas, the TABA solution in water is filtered from the catalyst at a temperature of 130 ° C, taking the filtrate into a crystallizer previously purged with an inert gas. At the same time, an inert gas pressure of 0.12 MPa is maintained in the mold to prevent boiling of the filtrate. After completion of the transfer of the TABA solution, 108.7 g of a 20% aqueous sulfuric acid solution are gradually added to the crystallizer from a dropping funnel with cooling and stirring. The suspension in the crystallizer is stirred for 20 minutes while cooling. After completion of the addition of sulfuric acid, the reaction mass has a pH of ~ 3, which indicates the binding of sulfuric acid to the TABA • H ₂ SO ₄ salt.

TABA • H ₂ SO ₄ forms a stable suspension with water, which can be directly used to produce DAFBI • H ₂ SO ₄ • H ₂ O dihydrate or pre-filtered. The salt yield of TABA • H ₂ SO _{4 was} 68.0 g (90.2% of theory).

Cyclodehydration, purification of the salt DAFBI • H ₂ SO ₄ • 2H ₂ O, the allocation of the base DAFBI and its drying is carried out, as in the examples above. 35.5 g of 5 (6) -amino-2- (4-aminophenyl) benzimidazole are obtained (71.4% of theory, based on the starting 2 ¹ , 4.4 ^1- trinitrobenzanilide). The melting point is 235 ° C, the color is 2.3 units, the mass fraction of water is 0.1%, impurities insoluble in an aqueous solution of hydrogen chloride are 0.03 wt.%.

Example 6. In a three-necked flask with a capacity of 2 dm ³ , equipped with a stirrer, thermometer and reflux condenser, load 348 cm ^{3 of} water, 257 g of finely divided iron powder, 7.5 cm ^{3 of} 36% hydrochloric acid and 38 cm ^{3 of} dimethylformamide. The mixture is heated with stirring to 98 ° C for 30 minutes and 120 g of 2 ¹ , 4,4 ^1- trinitrobenzanilide are gradually added in portions over 1.5 hours. In the flask in the boiling mode, the temperature is set to 100-101 ° C. After completion of the addition of TNBA, the mass is stirred for another 0.5 hours, 115 cm ^{3 of} dimethylformamide are added. The temperature in the reaction mass rises to 103-104 ° C. The mass is stirred for 20 minutes and filtered from a precipitate of iron oxide on a Druk filter under inert gas pressure at a temperature of 80-90 ° C. The precipitate of iron oxide on the filter is washed with 180 cm ^{3 of a} 30% solution of dimethylformamide in water, adding a washing filtrate to the main one. To a solution of TABA in a mixture of DMF • H ₂ O, 177 g of 20% sulfuric acid are gradually added. By the end of the addition of sulfuric acid, the pH of the medium decreases from 5 to 3. The suspension of the TABA • H ₂ SO ₄ salt is filtered, washed with water. 120.4 g of TABA • H ₂ SO ₄ salt are obtained (98% of theory).

Cyclodehydration, purification of the salt DAFBI • H ₂ SO ₄ • 2H ₂ O, the allocation of the base DAFBI and its drying is carried out, as in the examples above. Obtain 63.7 g of 5 (6) -amino-2- (4-aminophenyl) benzimidazole (78.6% of theory on 2 ¹ , 4.4 ^1- trinitrobenzanilide). The melting point is 234.5 ° C, the color is 3.7 units, the mass fraction of the residue after calcination is 0.003%, the mass fraction of water is 0.15%, and the impurities insoluble in an aqueous solution of hydrogen chloride are 0.015 wt.%.

Table Solubility of 2 ¹ , 4,4 ^1- trinitrobenzanilide and 2 ^l , 4,4 ^l- triaminobenzanilide in various solvents Solvent Solubility, wt.% At a temperature, ° C twenty 25 40 60 80 one hundred 110 120 130 140 2 ¹ , 4,4 ^1- trinitrobenzanilide Dimethylformamide (DMF) 12.6 - 17.9 28.0 37.9 47.8 52.6 57.6 - - Aqueous solutions of DMF with a content of DMF, wt.% fifty% 0.01 - 0.02 0.04 0.15 0.53 0.66 1.47 - - 80% 0.2 - 0.6 1.4 3,5 8.9 25.5 32,0 - - Dimethylacetamide (DMAA) An aqueous solution of DMAA, with a content of DMMA of 90 wt.% 0.6 - 5,4 12,4 25.6 39.6 - - - - N-methylpyrrolidone (NMP) 19.0 - 22.0 28.0 36.5 45,2 49.2 54.1 60.5 - Aqueous solutions of NMP, with the content of NMP, wt.% fifty% - 0.01 0.01 0,03 0.15 0.25 0.32 0.90 1.65 - 80% - 0.74 0.89 1.48 4,58 10,20 - - - - Ethanol - - - - 0.15 - - - - - Water 0.01 - 0.04 0.07 (137 ° C) 0.24 (153 ° C) 2 ¹ , 4,4 ¹ -triaminobenzanilide Dimethylformamide (DMF) 30.1 - 36,2 42,2 48,4 55,2 - 60.8 - - Aqueous solutions of DMF with a content of DMF, wt.% 10% 0.1 - 0.3 0.6 2.0 6.5 - 19.5 - - thirty% 0.6 - 1.3 3.0 6.6 21.0 - 46.0 - - fifty% 1,0 - 3.2 7.4 15.0 30.8 - 54.8 - - Dimethylacetamide (DMAA) > 43 - - - - - - - - - An aqueous solution of DMAA, with a content of DMMA, wt.% fifteen% 0.3 - - - - - - - - - 25% 0.55 - 1.3 3.0 6.5 10.0 - - - - N-methylpyrrolidone (NMP) - 1.8 11,2 24.6 38,4 - - - - - Aqueous solutions of NMP, with the content of NMP, wt.% twenty% 1,5 - 3.3 6.0 10.3 14.1 - - - - fifty% - 0.7 2,8 6.4 11,2 - - - - - 80% - 13.0 16,0 21.9 26.7 - - - - - Ethanol 0.44 - 0.73 1.30 2,55 - - - - - Water - - - 0.10 (50 ° C) 1.70 (90 ° C) 3.77 5.60 10.9 24.5 -

Claims (6)

1. The method of obtaining 5 (6) -amino-2- (4-aminophenyl) benzimidazole, comprising reducing 2 ¹ , 4,4 ^1- trinitrobenzanilide in 2 ¹ , 4,4 ¹ -triaminobenzanilide in the presence of a catalyst in an aqueous medium, cyclodehydration in an aqueous acid medium and isolating the desired product, characterized in that obtained by reduction of the 2 ^1, 4,4 ¹ -trinitrobenzanilida 2 ^1, 4,4 ¹ -triaminobenzanilid reaction mixture after separation of the catalyst is treated with sulfuric acid allocated 2 ¹ 4.4 ¹ -triaminobenzanilid monosernokisloy a salt which is subjected tsiklodegidrata ii by heating in aqueous sulfuric acid to form the dihydrate monosernokisloy salt of 5 (6) -amino-2- (4-aminophenyl) benzimidazole and then recovered by neutralization with a base. 2. The method according to claim 1, characterized in that the reduction of 2 ¹ , 4,4 ^1- trinitrobenzanilide to 2 ¹ , 4,4 ¹ -triaminobenzanilide is carried out in the presence of a palladium catalyst or iron and electrolyte. 3. The method according to claim 1, characterized in that water or a mixture of water and a dipolar aprotic solvent selected from the range of dimethylformamide, dimethylacetamide, N-methylpyrrolidone is used as the aqueous medium during reduction. 4. The method according to claim 1, characterized in that the cyclodehydration is carried out in the presence of ammonia. 5. The method according to claim 1, characterized in that the allocation of 5 (6) -amino-2- (4-aminophenyl) benzimidazole in the form of a base is carried out by adding the dihydrate of its monosulfate salt to an aqueous solution of ammonia or sodium hydroxide in the presence of complexon, followed by heating to 50-90 ° C. 6. The method according to claim 1, characterized in that 5 (6) -amino-2- (4-aminophenyl) benzimidazole isolated in the form of a base is dried in an inert gas stream in a stepwise mode at a temperature of 100-135 ° C in the first stage and 150-170 ° C in the second stage.

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