CN118063325A - Method for synthesizing 1,2,4, 5-tetraaminobenzene hydrochloride - Google Patents

Abstract

The invention belongs to the field of chemical synthesis, and particularly discloses a method for synthesizing 1,2,4, 5-tetraaminobenzene hydrochloride. The invention mixes 2, 5-diaminobenzene-1, 4-dicarboxylic acid dimethyl ester (DATA) with hydroxylamine compound and low boiling point alcohol according to proper proportion, adjusts to proper pH value with alkali, controls proper temperature and time reaction, and generates 2, 5-diaminobenzene-1, 4-Dihydroxyamide (DHTA); carrying out rearrangement and degradation reaction on DHTA by a catalyst to generate a crude product of 1,2,4, 5-tetraminobenzene; adding proper amount of hydrochloric acid and active carbon into the crude product, heating at 80 ℃ for 0.5h, filtering while the crude product is hot, freezing the filtrate to separate out crystals, filtering, and vacuum drying the crystals at 50 ℃ by a water pump to obtain the high-purity 1,2,4, 5-tetraminobenzene hydrochloride. The invention provides a method for synthesizing 1,2,4, 5-tetraminobenzene hydrochloride with safety, environmental protection and low cost.

Description

Method for synthesizing 1,2,4, 5-tetraaminobenzene hydrochloride

Technical Field

The invention belongs to the field of chemical synthesis, and particularly relates to a method for synthesizing 1,2,4, 5-tetraaminobenzene hydrochloride.

Background

1,2,4, 5-Tetraaminobenzene (TAB) is often used in coordination chemistry and in the synthesis of polymers. The ultra-high performance fiber (M5) can be prepared by a mixed polycondensation method, so that the ultra-high performance fiber has durability, can participate in medicine preparation, and is also a common monomer for aerospace, military materials, civil engineering materials and the like.

The production method of 1,2,4, 5-Tetraminobenzene (TAB) is to make nitration reaction in concentrated mixed acid to obtain 4, 6-dinitro m-dichlorobenzene, then ammonify the 4, 6-dinitro m-dichlorobenzene in autoclave to obtain 1, 3-diamino-4, 6-dinitrobenzene, finally hydrogenate the autoclave to obtain TAB 4HCl. The production method not only realizes industrialization difficulty, but also generates a large amount of waste, so that the subsequent environmental improvement requires a large amount of manpower and material resources, and is in long-term contact with harmful health.

Chinese patent CN103102274A proposes to use m-dichlorobenzene as raw material, and make it undergo the processes of nitration, ammonolysis and reduction. Firstly, m-dichlorobenzene is nitrified in mixed acid to prepare 1, 3-dichloro-4, 6-dinitrobenzene, then the 1, 3-dichloro-4, 6-dinitrobenzene is ammonolyzed by ammonia to obtain 4, 6-dinitro-1, 3-phenylenediamine, finally the 4, 6-dinitro-1, 3-phenylenediamine is hydrogenated and reduced by Pd/C in distilled water to obtain a solution of 1,2,4, 5-tetraaminobenzene, and then the solution is poured into dilute acid solution to prepare high-purity 1,2,4, 5-tetraaminobenzene hydrochloride TAB 4HCl, so that byproducts are generated, a large amount of raw materials with strong corrosiveness and danger are needed in the preparation method, equipment and operators are easily damaged, a large amount of waste acid and waste salt are generated, the environment is polluted, and the noble metal catalyst is not only expensive, but also the recycling rate is low.

Chinese patent CN104725241 also discloses a similar technical route.

In a word, the prior production technology has complex technical process, operation danger, extremely large three wastes and high cost.

Disclosure of Invention

The invention aims to provide a method for synthesizing 1,2,4, 5-tetraaminobenzene hydrochloride (TAB.4HCl) with safety, environmental protection and low cost.

In order to achieve the above purpose, the invention adopts the following technical scheme:

Firstly, 2, 5-diaminobenzene-1, 4-dicarboxylic acid dimethyl ester (DATA) is mixed with hydroxylamine compound and alcohol with low boiling point according to proper proportion, alkali is used for adjusting the pH value to proper value, proper temperature and time are controlled for reaction to generate 2, 5-diaminobenzene-1, 4-Dihydroxyamide (DHTA), and crystal DHTA is obtained through concentration and crystallization.

And secondly, dissolving DHTA in a proper solvent, adding a proper catalyst, controlling a proper temperature under the protection of nitrogen, reacting for a proper time, and carrying out rearrangement degradation reaction to generate 1,2,4, 5-Tetraaminobenzene (TAB). Filtering while the mixture is hot, concentrating the filtrate under reduced pressure to recover the solvent, and obtaining residual liquid which is the TAB crude product.

And thirdly, adding a proper amount of hydrochloric acid and active carbon into the TAB crude product, heating at 80 ℃ for 0.5h, filtering while the product is hot, freezing the filtrate to separate out crystals, and filtering. The crystals were dried in vacuo at 50℃with water pump to give high purity TAB 4HCl.

Further, the hydroxylamine compound in the first step is hydroxylamine hydrochloride or an aqueous hydroxylamine solution; hydroxylamine hydrochloride is crystalline; the weight concentration of the hydroxylamine aqueous solution is 30-50%.

Further, the low boiling point alcohol in the first step includes one or more of methanol, ethanol, n-propanol, isopropanol.

Further, the molar ratio of the DATA to the hydroxylamine compound in the first step is 1:2.2-2.5; the weight ratio of the DATA to the low-boiling alcohol is 1:4-8.

Further, the base in the first step comprises an inorganic base and an organic base; the inorganic base comprises one or more of NaOH and KOH; the organic base comprises one or more of sodium methoxide, potassium tert-butoxide and tetraethylammonium hydroxide; the amount of the alkali to be used is such that the pH of the reaction system is 11 to 14.

Further, the appropriate reaction temperature in the first step is 50-80 ℃; the appropriate reaction time is 8-18 h, as determined by intermediate sampling analysis of the DATA conversion.

Further, the concentration operation described in the first step is to filter the filtrate while it is still hot after the reaction is completed, evaporate an appropriate amount of low boiling point alcohol and water from the filtrate so that the weight of the residual liquid is substantially 2 times that of the fed DATA, and then crystallize the residual liquid in a refrigerator (-20 ℃ C.) to obtain crystalline DHTA.

Further, suitable solvents for dissolving DHTA as described in the second step are highly polar aprotic solvents including one or more of dimethyl sulfoxide (DMSO), dimethylformamide (DMF), dimethylacetamide (DMAC), N-methylpyrrolidone (NMP), sulfolane. Preferably DMSO, DMF, DMAC. NMP (atmospheric boiling point 204 ℃) and sulfolane (atmospheric boiling point 287 ℃) have too high boiling points, and side reactions are easily initiated during distillation and desolvation, resulting in yield reduction. The solvent is used in an amount of 3 to 5 times by weight based on the amount of DHTA.

Further, the catalyst in the second step comprises inorganic base and organic base; the inorganic base comprises one or more of potassium carbonate, potassium phosphate and cesium carbonate; the organic base includes one or more of sodium methoxide, potassium t-butoxide, 4-Dimethylaminopyridine (DMAP), 1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU). The catalyst dosage is as follows: catalyst dhta=1 to 5:10 (molar ratio).

Further, the suitable reaction temperature in the second step is 70 to 120 ℃, preferably 90 to 100 ℃.

Further, the reaction in the second step is suitably carried out for a period of time of 0.5 to 3 hours. Depending on the catalyst and the reaction temperature.

Further, the filtrate in the second step is concentrated under reduced pressure to recover the solvent by controlling a proper vacuum degree, so that the solvent is distilled off at a lower temperature to avoid damage to TAB caused by high temperature. From the viewpoint of the compromise between the mechanical energy consumption of vacuum pumping and the energy consumption of condensation, the recovery of the solvent by vacuum concentration at 60 to 80℃is suitable.

Further, the adding of the proper amount of hydrochloric acid in the third step means adding of industrial hydrochloric acid (common industrial product) with the weight concentration of 32%, and the dosage is as follows: industrial hydrochloric acid dhta=4.5 to 5.5:1 (molar ratio).

Further, the amount of activated carbon used in the third step is: active carbon dhta=2-6:100 (weight ratio).

Further, the heating treatment in the third step is to heat for 0.5h at 60-80 ℃ so that the activated carbon fully adsorbs colloid.

The invention has the beneficial effects that:

(1) The production process and operation safety of TAB.4HCl are simplified. The invention adopts the hydroxylamidation and rearrangement degradation method, and synthesizes TAB.4HCl by a simple process, and has mild reaction conditions, safe and simple operation. The traditional process adopts complex and dangerous operations such as mixed acid nitrification, ammonia amination, catalytic hydrogenation and the like, and has high requirements on equipment and production management and high running risk.

(2) Greatly reduces the discharge of three wastes generated by TAB.4HCl production. The present invention uses methanol (recyclable) as a by-product of hydroxylamidation, and carbon dioxide (about 0.16 tons of CO ₂, and 5.5 tons of wastewater per ton of TAB.4 HCl) as a by-product of rearrangement degradation. Whereas in the traditional process, mixed acid is nitrified, aminated and reduced, about 35 tons of wastewater is produced per ton of product.

(3) The production cost of TAB 4HCl is reduced. The invention has simple technique, mild operation condition, less material consumption and greatly reduced three-waste treatment cost. So the comprehensive production cost is low.

Description of the drawings:

FIG. 1 is a schematic diagram of a synthesis process of 1,2,4, 5-tetraaminobenzene hydrochloride;

FIG. 2 is a HPLC chart of the target product TAB.4HCl prepared in example 1;

FIG. 3 shows the nuclear magnetic resonance spectrum (D ₂ O,400 MHz) of TAB.4HCl as the target product prepared in example 1, wherein (a) is ¹ H-NMR and (b) is ¹³ C-NMR.

Detailed Description

The invention is further illustrated below with reference to examples.

Example 1:

In the first step, 45g of DATA (0.2 mol), 35g of hydroxylamine hydrochloride (0.5 mol) and 180g of methanol are added into a reactor, the pH value is adjusted to 11 by KOH powder, the mixture is reacted for 18 hours at 50 ℃, the mixture is filtered while the mixture is hot, the filtrate is distilled to obtain methanol at 65-70 ℃, and the distillation is stopped after the residue is equal to 90 g. The concentrated residue was crystallized in a refrigerator (-20deg.C) to give 39.82g of crystalline DHTA, which was 99.43% pure by HPLC analysis and was 87.52% yield.

In the second step, 34g of DHTA (0.15 mol) was dissolved in 102g of DMSO, 10.35g of potassium carbonate (0.075 mol) was added, and the mixture was reacted at 100℃for 2 hours under nitrogen protection, and then filtered while it was still hot. 100g of DMSO is distilled off from the filtrate at 60 ℃ under reduced pressure, and the residual liquid is the TAB crude product.

In a third step, 94g of industrial hydrochloric acid (32% by weight concentration) (0.825 mol) and 2g of activated carbon were added to the TAB crude product, which was treated at 60℃for 0.5 hours, filtered while it was still hot, and the filtrate was frozen (-20 ℃) to precipitate crystals, which were filtered and washed 1 time with 50ml of water. Vacuum drying at 50℃gave 31.64g of TAB 4HCl, which, by HPLC analysis, had a purity of 99.84% and a yield of 74.15%.

The quantitative analysis of the product and intermediates was High Pressure Liquid Chromatography (HPLC). The column was a WD-C18 column (5 μm), 4.6X250 mm, using a UV/Vis detector. The detection wavelength is 254nm. The sample was dissolved in water to a concentration of about 1% and then injected into HPLC with methanol as the mobile phase.

The DHTA content is 99.43%. The TAB 4HCl content was 99.84% (HPLC profile of TAB 4HCl is shown in FIG. 2).

The qualitative analysis of the product is performed by nuclear magnetic resonance spectroscopy. The nuclear magnetic resonance spectrum of the target product tab.4hcl (D ₂O,400MHz),¹ H-NMR is shown in fig. 3 (a). In the graph, δ=7.04 is the chemical shift of the hydrogen atom on-NH ₂ on TAB, while at δ=4.72 the hydrogen atom on the TAB benzene ring coincides with the hydrogen atom of deuterated reagent D ₂ O, and HCl does not show the peak. ¹³ C-NMR is shown in fig. 3 (b). In the graph, at δ= 125.09 the chemical shift of the carbon atom on TAB attached to amino group, and at δ= 115.30 the chemical shift of the carbon atom on the benzene ring.

Example 2

In the first step, 45g of DATA (0.2 mol) and 52.8g of aqueous hydroxylamine solution (30% strength by weight) (0.48 mol), 225g of ethanol were fed into the reactor, and the pH was adjusted to 12 with NaOH powder. After reacting for 15h at 60 ℃, filtering while the mixture is hot, and distilling ethanol and water from the filtrate at 75-95 ℃. After the residue was equal to 90g, the distillation was stopped. The concentrated residue was crystallized in a refrigerator (-20deg.C) to give 43.96g of crystalline DHTA, which was 99.15% pure by HPLC analysis and found to be 86.71% in yield.

In the second step, 34g of DHTA (0.15 mol) is dissolved in 136g of DMF, 5.8g of cesium carbonate (0.03 mol) is added, and under the protection of nitrogen gas, after reaction for 2.5 hours at 110 ℃, filtration is carried out while the mixture is hot, 132g of DMF is distilled off from the filtrate at 60 ℃ under reduced pressure, and residual liquid is the TAB crude product.

In a third step, 85.5g of industrial hydrochloric acid (32% by weight concentration) (0.75 mol) and 1.7g of activated carbon were added to the TAB crude product, and the mixture was treated at 70℃for 0.5 hours, filtered while it was still hot, and the filtrate was frozen (-20 ℃) to precipitate crystals, which were filtered. The crystals were rinsed 1 with 50ml of water. Vacuum drying at 50℃gave 32.14g of TAB 4HCl, which, by HPLC analysis, had a purity of 99.84% and a yield of 75.32%.

Example 3

In the first step, 45g of DATA (0.2 mol) and 38g of aqueous hydroxylamine solution (40% strength by weight) (0.46 mol), 270g of isopropanol were added to the reactor, and the pH was adjusted to 13 with sodium methoxide powder. After 10h of reaction at 70℃the mixture was filtered while hot. And distilling the filtrate to obtain isopropanol and water at 80-97 ℃, and stopping distillation after the residual liquid is equal to 90 g. The concentrated residue was crystallized in a refrigerator (-20deg.C) to give 39.80g of crystalline DHTA, which was 99.18% pure by HPLC analysis and gave a yield of 87.25%.

In the second step, 34g of DHTA (0.15 mol) is dissolved in 170g of DMAC, 6.8g of potassium tert-butoxide (0.06 mol) is added, the mixture is reacted for 0.5h at 120 ℃ under the protection of nitrogen, the mixture is filtered while the mixture is hot, 165g of DMAC is distilled off from the filtrate at 60 ℃ under the condition of reduced pressure, and residual liquid is a TAB crude product.

In a third step, 77g of industrial hydrochloric acid (32% by weight) (0.675 mol) and 0.68g of activated carbon were added to the TAB crude product, treated at 80℃for 0.5 hours, filtered while hot, and the filtrate was frozen (-20 ℃) to precipitate crystals, which were filtered. The crystals were rinsed 1 with 50ml of water. Vacuum drying at 50℃gave 31.21g of TAB 4HCl, which, by HPLC analysis, had a purity of 99.26% and a yield of 72.72%.

Example 4

In the first step, 45g of DATA (0.2 mol) and 29.5g of aqueous hydroxylamine (50% strength by weight) (0.44 mol) and 360g of isopropanol were introduced into the reactor, and the pH was adjusted to 14 with tetraethylammonium hydroxide. After reaction at 80℃for 10h, filtration was carried out while hot. Distilling the filtrate at 80-97 deg.c to obtain isopropyl alcohol and water. After the residue was equal to 90g, the distillation was stopped. The concentrated residue was crystallized in a refrigerator (-20deg.C) to give 39.91g of crystalline DHTA, which was found to have a purity of 99.21% by HPLC and a yield of 87.52%.

In the second step, 34g of DHTA (0.15 mol) was dissolved in 120g of NMP, 2.5g of sodium methoxide (0.045 mol) was added thereto, and the mixture was reacted at 80℃for 3 hours under the protection of nitrogen gas, followed by filtration while it was still hot. 115g of NMP is distilled off from the filtrate at 95 ℃ under reduced pressure, and the residual liquid is the TAB crude product.

In a third step, 85.5g of industrial hydrochloric acid (32% by weight) (0.75 mol) and 1.36g of activated carbon were added to the TAB crude product, the mixture was treated at 80℃for 0.5 hours, filtered while it was still hot, and the filtrate was frozen (-20 ℃) to precipitate crystals, which were filtered. The crystals were rinsed 1 with 50ml of water. Vacuum drying at 50℃gave 29.39g of TAB 4HCl with a purity of 98.86% by HPLC analysis and a yield of 68.20%.

Example 5

In the first step, 45g of DATA (0.2 mol) and 30.36g of aqueous hydroxylamine (50% strength by weight) (0.46 mol) and 360g of isopropanol were fed into the reactor, and the pH was adjusted to 14 with tetraethylammonium hydroxide. After 9h of reaction at 80℃the mixture was filtered off while it was hot. Distilling the filtrate at 80-97 deg.c to obtain isopropyl alcohol and water. After the residue was equal to 90g, the distillation was stopped. The concentrated residue was crystallized in a refrigerator (-20deg.C) to give 40.26g of crystalline DHTA, which was 99.24% pure by HPLC and 88.32% yield.

In a second step, 34g of DHTA (0.15 mol) was dissolved in 136g of DMF, 2.3g of DBU (0.015 mol) was added, and the mixture was reacted at 90℃for 3 hours under nitrogen protection, and then filtered while it was still hot. 133g of DMF was distilled off from the filtrate under reduced pressure at 60℃and the residue was the crude TAB product.

In a third step, 85.5g of industrial hydrochloric acid (32% by weight) (0.75 mol) and 1.36g of activated carbon were added to the TAB crude product, the mixture was treated at 80℃for 0.5 hours, filtered while it was still hot, and the filtrate was frozen (-20 ℃) to precipitate crystals, which were filtered. The crystals were rinsed 1 with 50ml of water. Vacuum drying at 50deg.C gave 33.04g of TAB.4HCl, which was 99.13% pure by HPLC and found to be 76.88% in yield.

Example 6

In the first step, 45g of DATA (0.2 mol) and 31.7g of aqueous hydroxylamine (50% strength by weight) (0.48 mol) and 360g of isopropanol were fed into the reactor, and the pH was adjusted to 14 with tetraethylammonium hydroxide. After reaction at 80℃for 8h, filtration was carried out while hot. Distilling the filtrate at 80-97 deg.c to obtain isopropyl alcohol and water. After the residue was equal to 90g, the distillation was stopped. The concentrated residue was crystallized in a refrigerator (-20deg.C) to give 40.33g of crystalline DHTA, which was 99.25% pure by HPLC and found to be 88.44% in yield.

In a second step, 34g of DHTA (0.15 mol) was dissolved in 136g of DMF, 4.6g of DBU (0.03 mol) was added, and the mixture was reacted at 90℃for 3 hours under nitrogen protection, and then filtered while it was still hot. The filtrate was distilled under reduced pressure at 60℃to yield about 133g of DMF, and the residue was the crude TAB product.

In a third step, 85.5g of industrial hydrochloric acid (32% by weight) (0.75 mol) and 1.36g of activated carbon were added to the TAB crude product, the mixture was treated at 80℃for 0.5 hours, filtered while it was still hot, and the filtrate was frozen (-20 ℃) to precipitate crystals, which were filtered. The crystals were rinsed 1 with 50ml of water. Vacuum drying at 50℃gave 33.10g of TAB 4HCl, which, by HPLC analysis, had a purity of 99.16% and a yield of 77.05%.

Example 7

In the first step, the procedure of example 5 was followed.

In the second step, 34g of DHTA (0.15 mol) was dissolved in 136g of DMF, 2.3g of DBU (0.015 mol) was added thereto, and the mixture was reacted at 100℃for 3 hours under nitrogen protection, followed by filtration while it was still hot. The filtrate was distilled under reduced pressure at 60℃to yield about 133g of DMF, and the residue was the crude TAB product.

In a third step, 85.5g of industrial hydrochloric acid (32% by weight) (0.75 mol) and 1.36g of activated carbon were added to the TAB crude product, the mixture was treated at 80℃for 0.5 hours, filtered while it was still hot, and the filtrate was frozen (-20 ℃) to precipitate crystals, which were filtered. The crystals were rinsed 1 with 50ml of water. Vacuum drying at 50℃gave 31.78g of TAB 4HCl, which, by HPLC analysis, had a purity of 99.23% and a yield of 74.03%.

Example 8

In the first step, the procedure of example 5 was followed.

In a second step, 34g of DHTA (0.15 mol) was dissolved in 136g of DMF, 2.3g of DBU (0.015 mol) was added, and the mixture was reacted at 110℃for 3 hours under nitrogen protection, and then filtered while it was still hot. The filtrate was distilled under reduced pressure at 60℃to yield about 133g of DMF, and the residue was the crude TAB product.

In a third step, 85.5g of industrial hydrochloric acid (32% by weight) (0.75 mol) and 1.36g of activated carbon were added to the TAB crude product, the mixture was treated at 80℃for 0.5 hours, filtered while it was still hot, and the filtrate was frozen (-20 ℃) to precipitate crystals, which were filtered. The crystals were rinsed 1 with 50ml of water. Vacuum drying at 50℃gave 24.85g of TAB 4HCl with a purity of 97.68% by HPLC analysis and a yield of 56.98%.

Example 9

In the first step, the procedure of example 5 was followed.

In a second step, 34g of DHTA (0.15 mol) was dissolved in 136g of DMF, 2.3g of DBU (0.015 mol) was added, and the mixture was reacted at 80℃for 3 hours under nitrogen protection, and then filtered while it was still hot. The filtrate was distilled under reduced pressure at 60℃to yield about 133g of DMF, and the residue was the crude TAB product.

In a third step, 85.5g of industrial hydrochloric acid (32% by weight) (0.75 mol) and 1.36g of activated carbon were added to the TAB crude product, the mixture was treated at 80℃for 0.5 hours, filtered while it was still hot, and the filtrate was frozen (-20 ℃) to precipitate crystals, which were filtered. The crystals were rinsed 1 with 50ml of water. Vacuum drying at 50℃gave 32.75g of TAB 4HCl, which, by HPLC analysis, had a purity of 99.10% and a yield of 76.19%.

Example 10

In the first step, the procedure of example 5 was followed.

In a second step, 34g of DHTA (0.15 mol) was dissolved in 136g of DMF, 2.3g of DBU (0.015 mol) was added, and the mixture was reacted at 90℃for 2 hours under nitrogen protection, and then filtered while it was still hot. The filtrate was distilled under reduced pressure at 60℃to yield about 133g of DMF, and the residue was the crude TAB product.

In a third step, 85.5g of industrial hydrochloric acid (32% by weight) (0.75 mol) and 1.36g of activated carbon were added to the TAB crude product, the mixture was treated at 80℃for 0.5 hours, filtered while it was still hot, and the filtrate was frozen (-20 ℃) to precipitate crystals, which were filtered. The crystals were rinsed 1 with 50ml of water. Vacuum drying at 50℃gave 31.25g of TAB 4HCl with a purity of 99.18% by HPLC analysis and a yield of 72.76%.

Example 11

In the first step, the procedure of example 5 was followed.

In a second step, 34g of DHTA (0.15 mol) was dissolved in 136g of DMF, 2.3g of DBU (0.015 mol) was added, and the mixture was reacted at 90℃for 1 hour under nitrogen protection, and then filtered while it was still hot. The filtrate was distilled under reduced pressure at 60℃to yield about 133g of DMF, and the residue was the crude TAB product.

In a third step, 85.5g of industrial hydrochloric acid (32% by weight) (0.75 mol) and 1.36g of activated carbon were added to the TAB crude product, the mixture was treated at 80℃for 0.5 hours, filtered while it was still hot, and the filtrate was frozen (-20 ℃) to precipitate crystals, which were filtered. The crystals were rinsed 1 with 50ml of water. Vacuum drying at 50℃gave 29.42g of TAB 4HCl with a purity of 98.74% by HPLC analysis in 68.20%.

Example 12

In the first step, the procedure of example 5 was followed.

In a second step, 34g of DHTA (0.15 mol) was dissolved in 136g of DMF, 2.3g of DBU (0.015 mol) was added, and the mixture was reacted at 90℃for 0.5h under nitrogen protection, and then filtered while it was still hot. The filtrate was distilled under reduced pressure at 60℃to yield about 133g of DMF, and the residue was the crude TAB product.

In a third step, 85.5g of industrial hydrochloric acid (32% by weight) (0.75 mol) and 1.36g of activated carbon were added to the TAB crude product, the mixture was treated at 80℃for 0.5 hours, filtered while it was still hot, and the filtrate was frozen (-20 ℃) to precipitate crystals, which were filtered. The crystals were rinsed 1 with 50ml of water. Vacuum drying at 50℃gave 21.48g of TAB 4HCl, 93.82% pure by HPLC and 47.31% yield.

Example 13

In the first step, the procedure of example 5 was followed.

In a second step, 34g of DHTA (0.15 mol) was dissolved in 136g of DMF, 2.3g of DBU (0.015 mol) was added, and the mixture was reacted at 70℃for 3 hours under nitrogen protection, and then filtered while it was still hot. The filtrate was distilled under reduced pressure at 60℃to yield about 133g of DMF, and the residue was the crude TAB product.

In a third step, 85.5g of industrial hydrochloric acid (32% by weight) (0.75 mol) and 1.36g of activated carbon were added to the TAB crude product, the mixture was treated at 80℃for 0.5 hours, filtered while it was still hot, and the filtrate was frozen (-20 ℃) to precipitate crystals, which were filtered. The crystals were rinsed 1 with 50ml of water. Vacuum drying at 50℃gave 26.43g of TAB 4HCl, 94.85% pure by HPLC and 58.85% yield.

Comparative example 1

Step 1, adding 200g of concentrated sulfuric acid and 60g of fuming HNO ₃ into a 500ml three-port bottle provided with a mechanical stirring and condensing reflux pipe under ice bath, and stirring for 15 minutes at about 10 ℃; 60g of m-dichlorobenzene (98%, 0.4 mol) was slowly added dropwise, the reaction temperature was controlled at-5℃and the dropwise addition was completed within 2 hours. The ice bath was removed and the reaction was allowed to warm to room temperature, heated to 104 ℃ over 30 minutes, and after 20 minutes, the heating was stopped, and allowed to cool naturally with stirring, yielding a large amount of yellow crystals. Then the mixed solution is poured into 300g of crushed ice, filtered, the filter cake is washed with cold water for three times (200 ml X3 times), then with 15% ammonia water for three times (200 ml X3 times), the filter cake is put into a baking oven at 45 ℃ for baking, 93.7g of yellow-green crystal crude product is obtained, the yield is 96.2%, and the purity detected by gas chromatography is 97.4%.

The crude product is recrystallized by a mixed solution of cyclohexane, ethanol=1:1 (volume ratio) to obtain 90.3g of light yellow needle-like crystals, 1.3-dichloro-4.6-dinitrobenzene, the purity of which is higher than 99 percent by gas chromatography detection, and the melting point of which is 101-103 ℃.

Step 2, 48g of 1, 3-dichloro-4, 6-dinitrobenzene and 150g of ammonia (weight content: 28%) were added to a 250ml autoclave, and nitrogen was replaced 2 times; heating to 155 ℃, controlling the pressure at 1.3MPa, stopping heating after reacting for 4 hours, and naturally cooling; filtering, washing the filter cake with water three times (100 ml X3 times), and drying to obtain 36.82g of 1, 3-diamino-4, 6-dinitrobenzene yellow powder, wherein the yield is 90.1%, and the purity is 96.8% by HPLC detection.

Step 3, 30.7g of 1.3-diamino-4.6-dinitrobenzene (0.15 mol), 180ml of distilled water purified by N ₂ and 1.5g Pd/C (10% Pd loading) are added into a 250ml hydrogenation autoclave, the mixture is replaced by N ₂ and H ₂ for 2 times after being capped, the temperature is raised to 85 ℃ for reaction, the pressure is controlled to be 1.5MPa, and the reaction is finished when the pressure in the autoclave is not reduced any more, and the reaction is carried out for 5.5 hours. After the temperature of the reaction system is reduced to 45 ℃,30 ml of concentrated HCl is poured into the reaction liquid under the protection of N ₂, and then the temperature is raised to 60 ℃ and the mixture is stirred for 10 minutes; after stopping heating, the catalyst is removed by filtration at about 45 ℃, and the filtrate is cooled to room temperature under the protection of nitrogen for standby.

And 4, pouring the obtained filtrate into a solution containing 40ml of concentrated HCl (32%wt) and 2.0g of SnCl ₂, naturally cooling, precipitating a white solid, filtering under the protection of N ₂, washing a filter cake with a cold mixed solution of ethanol and concentrated HCl for 3 times (100 ml of X3 times), drying the filter cake in a vacuum drying oven at 35 ℃, weighing to obtain 23.5g of TAB 4HCl, and detecting the purity by high performance liquid chromatography to 92.6%. The yield was 51.1%.

Compared with the invention of example 6, the traditional process is complex, the operation process is dangerous, a great amount of three wastes (33 Kg of wastewater is generated by producing 1Kg of TAB.4HCl in a folding way) are generated, and the yield is low and the cost is high. Thus, the advantages of the present invention are demonstrated (1 Kg of TAB.4HCl produced by the data of example 6 reduced to 5.5Kg of wastewater).

Comparative example 2

In the first step, 45g of DATA (0.2 mol) and 30.36g of an aqueous hydroxylamine solution (50% strength by weight) (0.46 mol) and 360g of isopropanol were introduced into a reactor, the pH was adjusted to 14 with tetraethylammonium hydroxide, and after 7 hours of reaction at 90℃the DATA was completely converted and filtered while it was still hot. Distilling the filtrate at 80-97 deg.c to obtain isopropyl alcohol and water. After the residue was equal to 90g, the distillation was stopped. The concentrated residue was crystallized in a refrigerator (-20deg.C) to give 36.21g of crystalline DHTA, which was 98.94% pure by HPLC analysis and 79.19% yield.

The procedure is as in example 5.

With the above-described preferred embodiments according to the present invention as an illustration, the above-described descriptions can be used by persons skilled in the relevant art to make various changes and modifications without departing from the scope of the technical idea of the present invention. The technical scope of the present invention is not limited to the description, but must be determined according to the scope of claims.

Claims (10)

1. A method for synthesizing 1,2,4, 5-tetraaminobenzene hydrochloride, comprising the steps of:

Firstly, mixing 2, 5-diaminobenzene-1, 4-dicarboxylic acid dimethyl ester, hydroxylamine compound and low-boiling point alcohol according to a proper proportion, regulating the mixture to a proper pH value by using alkali, heating the mixture to react, and concentrating and crystallizing the mixture to obtain crystal 2, 5-diaminobenzene-1, 4-dihydroxyamide;

Secondly, dissolving 2, 5-diaminobenzene-1, 4-dihydroxyamide in a proper solvent, adding a catalyst, carrying out rearrangement degradation reaction under the protection of nitrogen, filtering while the reaction is hot after the reaction is finished, concentrating the filtrate under reduced pressure, and recovering the solvent, wherein residual liquid is a crude product of 1,2,4, 5-tetraminobenzene;

thirdly, adding a proper amount of hydrochloric acid and active carbon into the crude product of the 1,2,4, 5-tetraminobenzene, heating, filtering while the crude product is hot, freezing the filtrate to separate out crystals, filtering, washing and drying to obtain the 1,2,4, 5-tetraminobenzene hydrochloride.

2. The method for synthesizing 1,2,4, 5-tetraaminobenzene hydrochloride according to claim 1, wherein the hydroxylamine compound in the first step is hydroxylamine hydrochloride or a hydroxylamine aqueous solution having a weight concentration of 30 to 50%; the molar ratio of the 2, 5-diaminobenzene-1, 4-dicarboxylic acid dimethyl ester to the hydroxylamine compound is 1:2.2-2.5;

and/or, the low boiling point alcohol comprises one or more of methanol, ethanol, n-propanol and isopropanol; the weight ratio of the 2, 5-diaminobenzene-1, 4-dicarboxylic acid dimethyl ester to the low-boiling-point alcohol is 1:4-8.

3. The method for synthesizing 1,2,4, 5-tetraaminobenzene hydrochloride according to claim 1, wherein the base in the first step comprises an inorganic base or an organic base; the inorganic base comprises one or more of NaOH and KOH; the organic base comprises one or more of sodium methoxide, potassium tert-butoxide and tetraethylammonium hydroxide;

and/or the pH value is 11-14.

4. The method for synthesizing 1,2,4, 5-tetraaminobenzene hydrochloride according to claim 1, wherein the heating reaction temperature in the first step is 50-80 ℃ for 8-18 h.

5. The method for synthesizing 1,2,4, 5-tetraaminobenzene hydrochloride according to claim 1, wherein the molar ratio of the catalyst to 2, 5-diaminobenzene-1, 4-dihydroxyamide in the second step is 1 to 5:10;

And/or the base catalyst is inorganic base or organic base; the inorganic base comprises one or more of potassium carbonate, potassium phosphate and cesium carbonate; the organic base comprises one or more of sodium methoxide, potassium tert-butoxide, 4-dimethylaminopyridine and 1, 8-diazabicyclo [5.4.0] undec-7-ene.

6. The method for synthesizing 1,2,4, 5-tetraaminobenzene hydrochloride according to claim 1, wherein the rearrangement degradation reaction temperature in the second step is 70-120 ℃ and the reaction time is 0.5-3 h.

7. The method for synthesizing 1,2,4, 5-tetraaminobenzene hydrochloride according to claim 1, wherein the solvent in the second step comprises dimethyl sulfoxide, dimethylformamide, dimethylacetamide, N-methylpyrrolidone, sulfolane;

the solvent is 3-5 times of the weight of the 2, 5-diaminobenzene-1, 4-dihydroxyamide.

8. The method for synthesizing 1,2,4, 5-tetraaminobenzene hydrochloride according to claim 1, wherein the temperature of recovering solvent by concentrating the filtrate under reduced pressure in the second step is 60-80 ℃.

9. The method for synthesizing 1,2,4, 5-tetraaminobenzene hydrochloride according to claim 1, wherein the weight ratio of the activated carbon to the 2, 5-diaminobenzene-1, 4-dihydroxyamide in the third step is 2-6:100;

And/or, the hydrochloric acid is industrial hydrochloric acid with the weight concentration of 32%; the mol ratio of the hydrochloric acid to the 2, 5-diaminobenzene-1, 4-dihydroxyacyl is 4.5-5.5:1.

10. The method for synthesizing 1,2,4, 5-tetraaminobenzene hydrochloride according to claim 1, wherein the heating treatment temperature in the third step is 60-80 ℃ for 0.5h.