Method for preparing chloro-substituted aromatic carboxylic acid aminoanilides

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of aromatic carboxylic acid aminoanilides, such as 21-chloro-4,41-diaminobenzanilide or bis-(2-chloro-4-aminophenol)terephthalamide used in production of thermostable, refractory and highly strength fibers. Method is carried out by acylation of 2-chloro-4-nitroaniline with 4-nitrobenzoic acid chloroanhydride or terephthaloyl chloride, respectively, in organic solvent medium at heating followed by reduction of formed chloro-substituted nitroanilide of aromatic carboxylic acid in a solvent. The acylation process is carried out in the presence of ferric chloride as a catalyst, at chloroanhydride excess with respect to 2-chloro-4-nitroaniline at graduate increase of temperature up to boiling of reaction mass under atmosphere pressure. Ferric chloride is used as anhydrous FeCl3 or crystal hydrate FeCl3 x 6H2O or an aqueous solution. In the reduction process a mixture of water and dipolar aprotonic solvent is used, and mother solutions after isolation of chloro-substituted nitroanilide and chloro-substituted aminoanilide are recovered to recycle at corresponding step of process. Before recovering to recycle at acylation or reduction step, respectively, mother solutions are treated with activated carbon. Invention provides preparing end products of high quality and decreasing amount of waste.

EFFECT: improved method of synthesis.

6 cl, 1 tbl, 22 ex

 

The present invention relates to the field of organic chemistry and relates to a method of obtaining chloride replaced aminoaniline aromatic carboxylic acids, such as 21-chloro-4,41-diaminobenzanilide (hereinafter DHBA) and bis-(2-chloro-4-AMINOPHENYL) terephthalamide (hereinafter BOTTA)-monomers used in the manufacture of heat-resistant, fire-resistant and high-strength fibers.

A method of obtaining 21-chloro-4,41-diaminobenzanilide (DHBA) by condensation of equimolar amounts of 2-chloro-4-nitroaniline (hereinafter HENNA) and 4-nitrobenzylamine (hereinafter PNBG) in glacial acetic acid, followed by reduction of the resulting 21-chloro-4,41-dinitrobenzamide (DNBA) 21-chloro-4,41-diaminobenzanilide hydrogen on skeletal Nickel catalyst in an environment of dimethylacetamide. Output DHBA is 60-64% of theoretical HENNA (RF Patent 2111978, C08G 69/32, D01F 6/74, publ. 27.05.98). The disadvantage of this method is the low yield of the target product.

The closest analogue of the proposed method of obtaining chloride replaced aminoaniline aromatic carboxylic acid is a method of obtaining N,N1bis-(4-amino-2-chlorophenyl) terephthalamide (BOTTA) by acylation HENNA by terephthaloylchloride taken in stoichiometric ratio, in the environment of hexamethylphosphorotriamide for the of 25 hours with the formation of N,N 1bis-(4-nitro-2-chlorophenyl) terephthalamide (hereinafter BNTF) with subsequent recovery in an environment of dimethyl hydrogen on skeletal Nickel catalyst and Visaginas by diluting the reaction solution with water. The output BOTTA 71,8% of theoretical, counting on HENNA (U.S. Patent 3673143, NCI 260-302, publ. 27.06.72). The disadvantage of this method is the use of expensive hard-to-solvent, binding the liberated hydrogen chloride with solvent, complicating the last regeneration, the long duration of the process of acylation, the low yield of the target product, a large amount of waste.

The present invention is to develop a method of obtaining chloride replaced aminoaniline aromatic carboxylic acids by use of solvents, providing reduced acylation, a high yield of the target products, the minimum amount of waste.

The problem is solved by the proposed method of obtaining chloride replaced aminoaniline aromatic carboxylic acid by acylation of 2-chloro-4-nitroaniline (HENNA) 4-nitrobenzofurazan (PNBG) or terephthaloylchloride (TFA) in an organic solvent under heating, followed by reduction of the resulting chloride replaced determination of aromatic carboxylic acids, great for the existing topics the acylation is carried out in the presence of ferric chloride as catalyst with an excess of the acid chloride with respect to 2-chloro-4-nitroaniline, the reaction mother liquor produced after extraction of chloride replaced nitroanilide return in recycling for the acylation, the recovery of lead in a mixture of water and a dipolar aprotic solvent and the reaction mother liquor after separation of the target product is sent to recycling for recovery.

To achieve these objectives it is necessary to observe a number of conditions.

As the organic solvent for the acylation can be used solvents, forming with water azeotrope: chlorobenzene, p-xylene, o-xylene, ethylbenzene or toluene.

Excess acid chloride in relation to HENNA necessary for a more complete transformation of the latter into the target product as unreacted HENNA in terms of recovery becomes easily oxidized, osmolality 2-chloro-1,4-diaminobenzene, target pollutant chloride replaced aminoaniline.

Ferric chloride is necessary to increase the rate of acylation, reduction of the process time, increase the degree of conversion of the reactants, more complete reaction. So, when the acylation HENNA 4-nitrobenzotrifluoride in chlorobenzene at 120°C, the concentration of HENNA 0,082 mol/DM3and business continuity plan is 0,096 mol/ DM 3the rate of acylation process by increasing the concentration of ferric chloride with 5·10-5mol/DM3up to 2·10-4mol/DM3increase of 2.7·10-3mol·l-1·min-1to 8.2·10-3mol·l-1·min-1i.e 3 times.

Ferric chloride can be introduced in the process of acylation in the form of dry anhydrous ferric chloride by loading it directly into the reactor acylation or by adding it to the solution of acid chloride in an appropriate solvent before entering the last in the process. Ferric chloride can be introduced into the process in the form of hydrated FeCl3·6N2O or in aqueous solution by adding it to the HENNA with subsequent dehydration by azeotropic distillation with the solvent.

The process of acylation is carried out at a gradual increase in temperature up to the boiling point of the reaction mass, which helps prevent too intense emission of hydrogen chloride and the ejection of the reaction mass. For this purpose it is advisable to use a gradual flow of acid chloride of an aromatic carboxylic acid in the reaction zone at a temperature at which the reaction proceeds at high speed, for example at the boiling temperature of the reaction mass.

The mother liquor produced after extraction of chlorine substituted nitro is aminoaniline, sent to recycling in the following acylation. However, there was no reduction in the quality of the product of the acylation. Recycling of the mother liquor can be carried out repeatedly. This technique reduces the costs of raw materials, leads to a drastic reduction of waste production and reducing the cost of regeneration of the solvent.

To prevent accumulation in the reaction mass of excess solvent, which is fed with recirculated by the liquor with a solution of the acid chloride in an appropriate solvent or solution, suspension or paste of HENNA, in the reaction are the distillation of part of the solvent directly from the reactor acylation, combining the processes of acylation and removal of the solvent over time. In the result, there is no need for removal of the solvent additional equipment.

HENNA can be introduced in the process of acylation in the form of dry matter, or in paste form with an appropriate solvent or in the form of aqueous paste. In the latter case, before adding the mother liquor and acid chloride of an aromatic carboxylic acid is necessary to carry out the dehydration HENNA azeotropic distillation of the water with the solvent, which are acylation.

The restoration of the 21,4,41-trinitrobenzene 21,4,41-triaminobenzene is in aqueous medium can be carried out with hydrogen using a hydrogenation catalysts, such as skeletal Nickel, or using as the reducing system water-iron-electrolyte (NH4Cl FeCl2etc), where the source of hydrogen is water, and the system iron-electrolyte acts as a catalyst.

At the stage of recovery as solvent a mixture of water and a dipolar aprotic solvent of a number of dimethylformamide (DMF), dimethylacetamide (DMAA), N-organic (NM);

Use as a solvent a mixture of water and one of the solvents specified number of due to the fact that these systems are well dissolved as a source chlornitromycin, and the resulting chloraminated in a wide range of temperatures. This allows the recovery process in solution, prevents the resin formation, ensures stable operation of the catalyst. Carrying out the recovery process in solution simplifies the problem of separating the formed chloride replaced aminoaniline from catalyst recovery.

The mother liquor produced after extraction of chloride replaced aminoaniline, sent to recycling to the next recovery operation. However, there was no reduction in the quality of product recovery. Recycling of the mother liquor can be carried out repeatedly. This technique reduces the costs of raw materials, leads to a dramatically is the reduction of waste production, provides lower costs for regeneration of the solvent.

Compliance with these conditions allows to obtain chloride replaced diaminoanisole aromatic carboxylic acids with high quality output 88-94% of theoretical 2-chloro-4-nitroaniline.

The invention is illustrated by the following examples.

Example 1. Synthesis of 2l-chloro-4,41- dinitrobenzamide.

In a three-neck flask with a capacity of 2 DM3equipped with stirrer, reflux condenser, connected to the trapping of hydrogen chloride, and a thermometer, download 139,0 g (0,80 g-mol) HENNA, 163,24 g (0.88 g-mol) PNPH, of 0.68 g of anhydrous ferric chloride and 472 cm3of chlorobenzene. Excess PNPH is 10% molar. The reaction mass is heated with stirring. At a temperature of about 80°begins the evolution of hydrogen chloride. The mass is gradually heated for 1.5 hours, raising the temperature to boiling (134° (C), and give at this temperature exposure for 2 hours to complete the selection of hydrogen chloride.

Next, the reaction flask is cooled with water, and then in the refrigerator for up to 5-10°and the resulting suspension 21-chloro-4,41-dinitrobenzamide (DNBA) filtered on a Buechner funnel with vacuum. The precipitate was washed with 210 cm3of chlorobenzene. The main and the washing filtrates combined. Receive 665 cm3Harbin the Aulnay of liquor, containing, g/DM3: HENNA 1,10; PNPH 18,1; DNBA 15,32; 4-nitrobenzoic acid (NSC) of 3.25; FeCl30,5.

Pasta DNBA with steam distilled chlorobenzene, neutralized with ammonia, aqueous suspension DNBA filtered off, washed with water. Get 247,4 g DNBA (95.5% of theoretical). Melting point 198°; contents: HENNA - OTS.; NSC 0.01 wt.%.

Example 2. Synthesis of 21-chloro-4,41-dinitrobenzamide.

In the flask described in example 1, load 650 cm3the mother liquor obtained in example 1, 138,28 g HENNA; 151,48 g PNPH and 0.50 g FeCl3in the form of an anhydrous powder. The total number of reactants and the molar excess PNPH in relation to HENNA are the same as in example 1. The reaction mass is gradually heated with stirring. At 85°begins With intense emission of hydrogen chloride. Temperature for 1.5 hours increase to 135°With (boiling of the reaction mixture) and incubated for 2 hours to complete the selection of hydrogen chloride. In the process of aging distilled 170 cm3chlorobenzene, replacing the reflux condenser to direct combining, thus, the acylation processes and distillation of the excess solvent. Then the reaction mass is treated as described in example 1. Receive 672 cm3the reaction of the cells, similar to the reaction mother liquor obtained in example 1 and 256.5 g DNBA (99,0% from Theo who micheskogo). Melting point 198°; contents: HENNA - UTS., NSC - UTS.

Example 3. Synthesis of 21-chloro-4,41-dinitrobenzamide.

In a three-neck flask with a capacity of 1 DM3equipped with stirrer, reflux condenser and thermometer, download 640 cm3chlorbenzol reaction mother liquor from the 6th cycle of synthesis TNHB containing, g/DM3: HENNA 0,92; PNPH 17,90; DNBA of 14.57; NSC 3,10; FeCl30,45. Then make 56 g of activated charcoal OU-B in terms of 100%in the form of a suspension in 160 cm3chlorobenzene, previously dehydrated by azeotropic distillation of water with the solvent. Excess PNPH 10% molar. The suspension is heated to 80-100°with stirring, and incubated for 30 minutes, cooled to 40-50°and filtered from coal on a Buechner funnel with suction. Get 780 cm3purified solution containing, g/DM3: HENNA 0,83, PNPH 17,2, DNBA 14,1; NSC 0,21; FeCl30,37. The purified mother liquor is transferred into the flask described in example 1, add 138,47 g HENNA; 152,23 g PNPH and 0.44 g of FeCl3in the form of an anhydrous powder. The total number of reactants and the molar excess PNPH in relation to HENNA are the same as in example 1. Next, the synthesis are as described in example 2, waving in the process of acylation 310 cm3of chlorobenzene. Then the reaction mass is then cooled and allocate DNBA, as in examples 1,2. Get 255,2 g DNBA (98.5% of theoretical). Te is the temperature of melting point 199° With; the content of HENNA - 0.01 wt.%; the NSC content of 0.02 wt.%. Get 650 cm3the reaction mother liquor having the composition similar to that described above. This liquor is used in the next receive operation DNBA without treatment with activated charcoal.

Example 4. Synthesis of bis-(2-chloro-4-nitrophenyl) terephthalamide (BNTF).

In the flask described in example 1, the load 130, 8mm g (0,76 g-mol) HENNA, and 84.6 g (0,417 g-mol) of terephthaloylchloride, 0.9 g FeCl3and 1100 cm3of chlorobenzene. Excess terephthaloylchloride is 10% molar. The reaction mass is heated with stirring to 90°C. thus begins the evolution of hydrogen chloride. The reaction mass within 2 hours gradually heated to 134-135°With (boiling of the reaction mixture) and give exposure for 3 hours. After completion of the reaction the reaction mass is cooled down to 20-15°C. the Resulting suspension is filtered on a Buechner funnel using vacuum, the residue on the filter is washed 200 cm3of chlorobenzene. Primary and wash chlorbenzol the filtrates are combined and used in the next operation of the synthesis of BNTF.

Pasta BNTF on the filter sequentially washed with isopropyl alcohol and water. The aqueous paste of BNTF placed in 300 ml of water and neutralized with 0.25%aqueous ammonia solution to pH 8-9. The aqueous suspension is filtered, the precipitate washed with water. Get the aq is pasta, containing 173,8 g BNTF (96,5% of theoretical), melting point 340°With the content of HENNA UTS., the TFA content of 0.01 wt.%.

Output chlorbenzol of liquor 1100 cm3the content in the mother liquor, g/DM3: HENNA 0,4; TFH 4,6; TPA 0,8; FeCl30,26.

Example 5. Synthesis of bis-(2-chloro-4-nitrophenyl) terephthalamide (BNTF)

In a three-neck flask with a capacity of 1 DM3equipped with a mixer and direct refrigerator, upload to 150.6 g of water HENNA paste containing 130,4 g of the basic substance, 2 cm3an aqueous solution of ferric chloride containing 0,83 FeCl3and 390 cm3of chlorobenzene. The mass is heated with stirring and distilled water as azeotrope with chlorobenzene to achieve vapor temperature 131, 5mm°C.

Dehydrated suspension HENNA and FeCl3the chlorobenzene is transferred into a flask with a capacity of 2 DM3described in example 1, there also contribute 1080 cm3the mother liquor obtained in example 4, DeGroat 30 cm3chlorobenzene, HENNA, TPA and FeCl3in amounts corresponding to the downloads in example 4 with regard to the content of these substances in the mother liquor. The reaction mass is heated with stirring. The selection of hydrogen chloride begins at a temperature of about 90°C. the Reaction mass within 2 hours gradually heated to boiling (134-135°) and give exposure for 3 hours. During the exposure, using direct, chilling the nick, distilled 500 cm3of chlorobenzene. The reaction mass is then cooled and allocate BNTF same way as described in example 4. Get 1030 cm3the reaction of the cells with a composition similar to that described in example 4. This liquor is used in the next operation the receipt of BNTF. The output BNTF 178,3 g (99% of theoretical), melting point 339°, HENNA is not present, the content of TFA 0,006 wt.%.

The table shows additional examples 6-14, illustrating the synthesis of chlorine substituted nitroanilines aromatic carboxylic acids according to the proposed method.

Example 15 Synthesis of 21-chloro-4,41-diaminobenzanilide (DHBA). The restoration of the 21-chloro-4,41-dinitrobenzamide (DNBA) 21-chloro-4,41-diaminobenzanilide (DHBA) is carried out in the reactor of largescale volume 1 DM3equipped with stirrer , thermocouple, pressure gauge, fittings for input and output of gas embedded in the bottom of the unit filter, bottom valve with receiver-crystallizer from largescale equipped with a stirrer and a jacket for cooling.

Charged to the reactor 12,34 g DNBA, 1.2 g of skeletal Nickel catalyst and 175 cm330%aqueous solution of dimethylacetamide (30% of the bulk DMAA). The restoration carried out with hydrogen under a pressure of 1.2 MPa at a temperature of 60-90°C. the Process ends in 1 hour.

Rest the R DHBA perelavlivaet through the filter into the mould, cooled down to 15-10°C. the Precipitated crystals DHBA filtered on a Buechner funnel, washed with water. Get of 9.21 g DHBA (91,8% of theoretical), crystalline powder beige color, melting point 198°C.

The mother liquor in the amount of 150 cm3return to the reactor, DeGroat 25 cm3a 30%aqueous solution of DMAA, 12,34 g DNBA and carry out the restoration, using the catalyst from the previous experience. Obtain 9.4 g DHBA (93.6% of theoretical), crystalline powder beige color, melting point 197,5°C.

Example 16. Synthesis of 21-chloro-4,41-diaminobenzanilide (DHBA).

Recovery 12,34 DNBA in DHBA carried out as in example 15, using as solvent an aqueous solution of dimethylformamide (30% DMPA. Get 9,31 g DHBA (92,7% of theoretical). Crystalline powder beige color, melting point 198°C.

Example 17. Synthesis of 21-chloro-4,41-diaminobenzanilide (DHBA).

Recovery 12,34 g DNBA in DHBA carried out as in example 15, using as solvent an aqueous solution of N-methylpyrrolidone (30 volume% of the NRM). Get 9,04 g DHBA (90,1% of theoretical), crystalline powder beige color, melting point 197°C.

Example 18. Synthesis of 21-chloro-4,41-diaminobenzanilide (DHBA).

The restoration of the 21-chlor,4 1-dinitrobenzamide (DNBA) is carried out in a 3-necked flask, equipped with reflux condenser, stirrer and thermometer. The flask 60 g of dimethylacetamide (DMAA) and 140 g of water (30%aqueous solution DMAA), 23,25 g of iron powder, 2,95 cm3concentrated hydrochloric acid. The mixture is heated under stirring up to 96-100°C. When this occurs, the treatment of iron with hydrochloric acid and the formed electrolyte-iron chloride FeCl3. Later in the flask gradually add 12,34 g DNBA. Prodolzhitelnost add 40 minutes After adding DNBA the reaction mass is stirred at 98-100°C for 1 hour.

The reaction mass is filtered at a temperature of 90-100°to precipitate iron oxide, the solution is cooled to 15-20°C. the Precipitated crystals 21-chloro-4,41-diaminobenzanilide (DHBA) is filtered off and get 170 cm3the mother liquor and pasta DHBA, which was washed with water. Get 9,24 g DHBA in terms of dry substance. Powder light beige color, melting point 197°C. the Output is 92% of theoretical.

Example 19. Synthesis of 21-chloro-4,41-diaminobenzanilide (DHBA).

In the flask described in example 18, is placed 170 cm3the mother liquor from the previous experience, add 30 cm3a 30%aqueous solution of DMAA, so that the total amount of solvent was 200 cm 3. Next make 23,25 g of iron powder, heated to 96-100°and gradually enter 12,34 g DNBA. The reaction mass was stirred at 98-100°C for 40 minutes. Further processed as described in example 18. Get 175 cm3the mother liquor and to 9.57 g DHBA with a melting point 198°C. Output for 95.3% of theoretical.

Further, the mother liquor is used repeatedly, as described above.

Example 20. Synthesis of bis-(2-chloro-4-AMINOPHENYL)terephthalamide (BOTTA).

Recovery bis-(2-chloro-4-nitrophenyl)terephthalamide (BNTF) were carried out as in example 15. The reactor was placed 15.0 g of BNTF, 510 cm368%aqueous solution of dimethylacetamide (DMAA) and 1.5 g of skeletal Nickel catalyst. After recovery, and selection conditions described in example 15, get 480 cm3the mother liquor and 12.0 g BOTTA (92% of theoretical), light cream powder, melting point 262°C. After the recycling of the mother liquor in the reactor, load another 15,0 g DNRTFA and 30 cm3fresh 68%aqueous solution DMAA using the catalyst from the previous experience and the recovery and allocation similar to that described in example 15 receive an additional 12.3 g of BOTTA (94% of theoretical), light cream powder, melting point 261,5°C.

Example 21. Synthesis of bis-(2-chloro-4-AMINOPHENYL)terephthalamide (BOTTA).

Recovery bis-(2-chloro-nitrophenyl)terephthalamide (BNTF) is carried out in aqueous dimethylacetamide (DMAA) of iron powder in the presence as catalyst of iron chloride FeCl 3in a glass three-neck flask, equipped as described in example 18. The flask 510 cm368%aqueous solution of DMAA, of 22.4 g of iron powder and 0.71 cm335%hydrochloric acid. The mass is heated under stirring up to 98-100°C. Later in the flask gradually contribute 15.0 g of DNRTFA. When you are finished adding mass stirred at 98-104°C for 40 minutes. Next, the mass is filtered at a temperature of 90-100°to precipitate iron oxide, the filtrate is cooled to 5-10°C. the precipitation of BOTTA filtered off and get a 460 cm3the mother liquor. Pasta BOTTA washed with water. The output BOTTA 12.0 g (of 91.6% of theoretical), light cream powder, melting point 262°C.

The following synthesis of BOTTA carried out with the use of water-dimethylacetamide the mother liquor obtained in the previous recovery experience.

In the flask is charged with 460 cm3the mother liquor, 50 cm3fresh 68%aqueous solution of DMAA and 22.4 g of iron powder. Hydrochloric acid is not added as chloride iron is made with mother liquor from the previous experience. The mass is heated with stirring to 98-104°and gradually make 15,0 g DNRTFA. After exposure and processing, similar to that described above, obtain 12.5 g of BOTTA (95,3% of theoretical). Light cream powder, melting point 262°C.

The mother liquor from the second is vosstanovleniya used in the following synthesis of DAHTA.

Example 22. Synthesis of 21-chloro-4,41-diaminobenzanilide (DHBA).

In a three-neck flask with a capacity of 250 cm3equipped with stirrer, reflux condenser and thermometer, download 23.3 g of iron powder, 83 cm3waters, 44 cm3DMAA and 1 cm3concentrated 35%hydrochloric acid. The concentration of the aqueous solution DMAA formed in the flask is 35% by volume. The contents of the flask are heated with stirring to 95-100°C for 40 minutes. Next, under stirring and heating (the temperature in the flask 98-102° (C) gradually portions, contribute 12.3 g DNBA. Duration add DNBA 40 minutes. After complete addition, the reaction mass is stirred at a temperature of 100-102°C for 30 minutes and filtered without cooling on a Buechner funnel using vacuum. The precipitate of iron oxide on the filter is washed with 30 cm3a 35%aqueous solution of DMAA heated to a temperature of 90-95°C. Wash and core the filtrates are combined cooled to 5°C. Precipitated precipitated crystals DHBA is sucked off over a Buechner funnel with vacuum and washed with water. Light beige crystals DHBA dried. Get 6,9 g DHBA (63.9% of theoretical) and 142 cm3the mother liquor of the filtrate, which is used in the following recovery experience DNBA in DHBA carried out in the same manner as is use. While hydrochloric acid is not added, as formed in the first experiment chloride iron soluble in 35%DMAA and is present in the mother liquor in sufficient quantity.

After the third experience of recovery is slowing down the process of filtration of the suspension DHBA, because, obviously, the accumulation in the mother liquor impurities. In this regard, the mother liquor was subjected to purification by activated carbon. In a three-neck flask with a capacity of 250 cm3equipped with stirrer, reflux condenser and thermometer, is placed 150 cm3the mother liquor obtained in the third recovery experience, 2.1 g wet paste of powdered activated carbon containing 0.9 g of the basic substance. The suspension is heated under stirring up to a temperature of 80°C for one hour and filtered from coal on a Buechner funnel using vacuum. Get 140 cm3the mother liquor, which is used in the fourth recovery experience similar to that described above.

Below are the results of four sequentially conducted experiments with recycling of the mother liquor.

no experienceno recycle of the mother liquorDownload DNBA, gDownload the mother liquor from the previous experience, cm3Output DHBA, g/% of thearctic.The melting point of AHBA. °
1012,344 cm3DMAA and 83 cm3water6,90/63,9197
2112,31428,90/94,8196
3212,31508,60/to 91.6197
4*)312,31408,94/95,2197
*) used liquor from experience 3 after treatment with activated charcoal.

The mother liquor after the 4th of experience can be used in further experiments recovery.

Increase the yield DHBA in experiments with recycling of the mother liquor due to the fact that as a reaction medium is used, the liquor is already saturated DHBA. This provides a more complete selection DHBA during crystallization.

1. A method of obtaining a chloride replaced aminoaniline aromatic carboxylic acids, such as 21-chloro-4,41-diaminobenzanilide or bis-(2-chloro-4-AMINOPHENYL)terephthalamide, acylation of 2-chloro-4-nitroaniline the acid chloride 4-nitrobenzoic acid or terephthaloylchloride respectively in the medium of organic solvent under heating, followed restore what oulanem formed chloride replaced determination of aromatic carboxylic acid in a solvent, characterized in that the process of acylation is carried out in the presence of ferric chloride as catalyst with an excess of the acid chloride with respect to 2-chloro-4-nitroaniline with a gradual increase in temperature up to the boiling point of the reaction mass at atmospheric pressure, when recovering a mixture of water and a dipolar aprotic solvent and the mother solution after separation of chlorine substituted nitroanilide and chloride replaced aminoaniline return in recycling at the appropriate stage of the process.

2. The method according to claim 1, characterized in that the organic solvent by acylation using chlorobenzene, p-xylene, o-xylene, ethylbenzene or toluene.

3. The method according to claim 1, wherein the ferric chloride is used in the form of anhydrous FeCl3or it FeCl3·6N2On or aqueous solution.

4. The method according to claim 1, characterized in that when the acylation are the distillation of organic solvent.

5. The method according to claim 1, characterized in that as a dipolar aprotic solvent when restoring using dimethylformamide, dimethylacetamide or N-organic.

6. The method according to claim 1, characterized in that before returning to the recycling stage of acylation or restore, respectively, the mother solution is treated with activated charcoal.



 

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13 cl, 4 tbl, 12 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to methods for preparing N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine (nateglinide). Method for preparing nateglinide crystals of H-type is carried out by addition of inorganic acid to reaction mixture containing nateglinide to provide its acidification. The reaction mixture is prepared by interaction of trans-4-isopropylcyclohexylcarbonyl chloride with D-phenylalanine in a mixed solvent consisting of a ketone solvent and water in the presence of alkali. The ratio of water to ketone solvent is from 10:1 to 0.5:1. Temperature of the mixture is brought about to 58-72°C and concentration of ketone solvent - up to value above 8 wt.-% and less 22 wt.-% for carrying out precipitation of nateglinide crystals. Invention proposes variant for preparing nateglinide crystals of H-type. Also, invention proposes crystals of nateglinide of H-type showing average value of longitudinal axis from 1 to 5 mm and that for transverse axis from 0.1 to 0.5 mm. Invention provides enhancing effectiveness in isolation of nateglinide crystals.

EFFECT: improved preparing methods.

10 cl, 1 tbl, 13 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I): wherein Ar represents phenyl substituted with a group taken among isobutyl, benzoyl, isopropyl, styryl, pentyl, (2,6-dichlorophenyl)-amino-group, α-hydroxyethyl, α-hydroxybenzyl, α-methylbenzyl and α-hydroxy-α-methylbenzyl; R represents hydrogen atom; X means linear (C1-C6)-alkylene, (C4-C6)-alkenylene, (C4-C6)-alkynylene optionally substituted with group -CO2R3 wherein R3 means hydrogen atom, group (CH2)m-B-(CH2)n wherein B means oxygen atom; m = 0; n means a whole number 2; or B means group -CONH; m means a whole number 1; n means a whole number 2 and so on; R1 and R2 are taken independently among group comprising hydrogen atom, linear (C1-C4)-alkyl, hydroxy-(C2-C3)-alkyl and so on. Invention proposes a method for preparing compounds of the formula (I). Invention proposes inhibitors of C5-induced hemotaxis of polymorphonuclear leukocytes and monocytes representing (R)-2-arylpropionic acid omega-aminoalkylamides of the formula (I). Also, invention relates to a pharmaceutical composition possessing inhibitory activity with respect to hemotaxis of polymorphonuclear leukocytes and monocytes and comprising compounds of the formula (I) in mixture with suitable carrier. Proposes (R)-2-arylpropionic acid omega-alkylamides are useful for inhibition of hemotaxic activation induced C5a and other hemotaxic proteins.

EFFECT: improved preparing method, valuable medicinal properties of compounds and composition.

18 cl, 3 tbl, 23 ex

The invention relates to the production of polyamides from compounds aminocarbonyl acid

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I): wherein Ar represents phenyl substituted with a group taken among isobutyl, benzoyl, isopropyl, styryl, pentyl, (2,6-dichlorophenyl)-amino-group, α-hydroxyethyl, α-hydroxybenzyl, α-methylbenzyl and α-hydroxy-α-methylbenzyl; R represents hydrogen atom; X means linear (C1-C6)-alkylene, (C4-C6)-alkenylene, (C4-C6)-alkynylene optionally substituted with group -CO2R3 wherein R3 means hydrogen atom, group (CH2)m-B-(CH2)n wherein B means oxygen atom; m = 0; n means a whole number 2; or B means group -CONH; m means a whole number 1; n means a whole number 2 and so on; R1 and R2 are taken independently among group comprising hydrogen atom, linear (C1-C4)-alkyl, hydroxy-(C2-C3)-alkyl and so on. Invention proposes a method for preparing compounds of the formula (I). Invention proposes inhibitors of C5-induced hemotaxis of polymorphonuclear leukocytes and monocytes representing (R)-2-arylpropionic acid omega-aminoalkylamides of the formula (I). Also, invention relates to a pharmaceutical composition possessing inhibitory activity with respect to hemotaxis of polymorphonuclear leukocytes and monocytes and comprising compounds of the formula (I) in mixture with suitable carrier. Proposes (R)-2-arylpropionic acid omega-alkylamides are useful for inhibition of hemotaxic activation induced C5a and other hemotaxic proteins.

EFFECT: improved preparing method, valuable medicinal properties of compounds and composition.

18 cl, 3 tbl, 23 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to methods for preparing N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine (nateglinide). Method for preparing nateglinide crystals of H-type is carried out by addition of inorganic acid to reaction mixture containing nateglinide to provide its acidification. The reaction mixture is prepared by interaction of trans-4-isopropylcyclohexylcarbonyl chloride with D-phenylalanine in a mixed solvent consisting of a ketone solvent and water in the presence of alkali. The ratio of water to ketone solvent is from 10:1 to 0.5:1. Temperature of the mixture is brought about to 58-72°C and concentration of ketone solvent - up to value above 8 wt.-% and less 22 wt.-% for carrying out precipitation of nateglinide crystals. Invention proposes variant for preparing nateglinide crystals of H-type. Also, invention proposes crystals of nateglinide of H-type showing average value of longitudinal axis from 1 to 5 mm and that for transverse axis from 0.1 to 0.5 mm. Invention provides enhancing effectiveness in isolation of nateglinide crystals.

EFFECT: improved preparing methods.

10 cl, 1 tbl, 13 ex

FIELD: industrial organic synthesis.

SUBSTANCE: invention provides a simple method for preparing high-purity acylphenylalanine useful as starting material for pharmaceutical products. Process comprises Schotten-Bauman reaction stage wherein acid chloride reacts with phenylalanine in mixed solvent consisting of water-miscible organic solvent and water, while maintaining alkali pH (>10) of solvent medium with the aid of potassium hydroxide.

EFFECT: prevented formation of impurities.

13 cl, 4 tbl, 12 ex

FIELD: organic chemistry, detergents.

SUBSTANCE: claimed method includes interaction of ethylene diamine with tetraacetic acid. Obtained reaction mixture is treated with acetic anhydride at elevated temperature and N,N,N',N'-tetraacetylethylene diamine is isolated from reaction mass by crystallization. Reagent interaction is carried out in system of two continuous reactors acting in mixing-displacement regime at continuous raw material feeding such as ethylene diamine into top of the first reactor and acetic anhydride into top of the second reactor. Molar ratio of fresh acetic anhydride to ethylene diamine is 2.05-2.1. Temperature difference between top and bottom parts is maintained from 20 to 30°C for the first reactor and from 20 to 40°C for the second one. Compound of present invention is useful in detergent compositions.

EFFECT: target product of increased yield and purity, simplified process.

1 dwg, 1 tbl, 8 ex

FIELD: industrial organic synthesis.

SUBSTANCE: process involves formic acid-methylamine reaction via intermediate methylammonium formate salt, which is dehydrated in presence of molybdenum trioxide catalyst dissolved in aqueous methylamine and added to formic acid in amount 2.0-4.0 wt % based on the latter. Reaction is carried out for 1-2 h in reactor filled with inert packing material having developed surface without cooling of reaction mixture, whereupon volatile products are distilled away at bottom temperature up to 190°C for 60-90 min. Bottom residue containing catalyst, after isolation of desired product, is returned to reactor.

EFFECT: reduced reaction time, reduced power consumption, improved quality of product obtained at increased yield, and diminished production waste.

5 cl, 8 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of aromatic carboxylic acid aminoanilides, such as 21-chloro-4,41-diaminobenzanilide or bis-(2-chloro-4-aminophenol)terephthalamide used in production of thermostable, refractory and highly strength fibers. Method is carried out by acylation of 2-chloro-4-nitroaniline with 4-nitrobenzoic acid chloroanhydride or terephthaloyl chloride, respectively, in organic solvent medium at heating followed by reduction of formed chloro-substituted nitroanilide of aromatic carboxylic acid in a solvent. The acylation process is carried out in the presence of ferric chloride as a catalyst, at chloroanhydride excess with respect to 2-chloro-4-nitroaniline at graduate increase of temperature up to boiling of reaction mass under atmosphere pressure. Ferric chloride is used as anhydrous FeCl3 or crystal hydrate FeCl3 x 6H2O or an aqueous solution. In the reduction process a mixture of water and dipolar aprotonic solvent is used, and mother solutions after isolation of chloro-substituted nitroanilide and chloro-substituted aminoanilide are recovered to recycle at corresponding step of process. Before recovering to recycle at acylation or reduction step, respectively, mother solutions are treated with activated carbon. Invention provides preparing end products of high quality and decreasing amount of waste.

EFFECT: improved method of synthesis.

6 cl, 1 tbl, 22 ex

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