CN115850188A - Synthetic method of 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole - Google Patents
Synthetic method of 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole Download PDFInfo
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- CN115850188A CN115850188A CN202211493307.0A CN202211493307A CN115850188A CN 115850188 A CN115850188 A CN 115850188A CN 202211493307 A CN202211493307 A CN 202211493307A CN 115850188 A CN115850188 A CN 115850188A
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- AINQDNSHRCFZKM-UHFFFAOYSA-N 2-(4-amino-2-chlorophenyl)-3h-benzimidazol-5-amine Chemical compound ClC1=CC(N)=CC=C1C1=NC2=CC(N)=CC=C2N1 AINQDNSHRCFZKM-UHFFFAOYSA-N 0.000 title claims abstract description 27
- 238000010189 synthetic method Methods 0.000 title description 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 24
- 238000000034 method Methods 0.000 claims abstract description 16
- QAYNSPOKTRVZRC-UHFFFAOYSA-N 99-60-5 Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1Cl QAYNSPOKTRVZRC-UHFFFAOYSA-N 0.000 claims abstract description 15
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims abstract description 11
- 238000005660 chlorination reaction Methods 0.000 claims abstract description 11
- 238000002360 preparation method Methods 0.000 claims abstract description 11
- 238000006482 condensation reaction Methods 0.000 claims abstract description 9
- LXQOQPGNCGEELI-UHFFFAOYSA-N 2,4-dinitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O LXQOQPGNCGEELI-UHFFFAOYSA-N 0.000 claims abstract description 7
- KTHNITVDTYAHFF-UHFFFAOYSA-N 2-chloro-4-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=C(C(Cl)=O)C(Cl)=C1 KTHNITVDTYAHFF-UHFFFAOYSA-N 0.000 claims abstract description 7
- -1 N- (2-chloro-4-aminobenzoyl) -2, 4-diaminobenzene Chemical compound 0.000 claims abstract description 5
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- 239000007858 starting material Substances 0.000 claims abstract description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 239000003054 catalyst Substances 0.000 claims description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 10
- 239000003960 organic solvent Substances 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- 230000002378 acidificating effect Effects 0.000 claims description 5
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 4
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-Lutidine Substances CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 claims description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 3
- 239000008096 xylene Substances 0.000 claims description 3
- 239000007868 Raney catalyst Substances 0.000 claims description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 2
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 2
- DSVGQVZAZSZEEX-UHFFFAOYSA-N [C].[Pt] Chemical compound [C].[Pt] DSVGQVZAZSZEEX-UHFFFAOYSA-N 0.000 claims description 2
- 239000003377 acid catalyst Substances 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 2
- 238000007363 ring formation reaction Methods 0.000 claims description 2
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 8
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000012065 filter cake Substances 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- 238000001816 cooling Methods 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 4
- 238000002514 liquid chromatography mass spectrum Methods 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
- 239000004642 Polyimide Substances 0.000 description 3
- 239000008367 deionised water Substances 0.000 description 3
- 229910021641 deionized water Inorganic materials 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 229920001721 polyimide Polymers 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 239000012295 chemical reaction liquid Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000010907 mechanical stirring Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- 229920002334 Spandex Polymers 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000012776 electronic material Substances 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 229920006253 high performance fiber Polymers 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 150000007522 mineralic acids Chemical group 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 238000004537 pulping Methods 0.000 description 1
- 239000004759 spandex Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
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Abstract
The invention discloses a preparation method of 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole, which comprises the following steps: (1) 2-chloro-4-nitrobenzoic acid is taken as a starting material, and chlorination reaction is firstly carried out to obtain 2-chloro-4-nitrobenzoyl chloride; then carrying out condensation reaction with 2, 4-dinitroaniline to obtain an intermediate N- (2-chloro-4-nitrobenzoyl) -2, 4-dinitrobenzene; (2) carrying out catalytic hydrogenation reaction on the intermediate N- (2-chloro-4-nitrobenzoyl) -2, 4-dinitrobenzene obtained in the step (1) to obtain N- (2-chloro-4-aminobenzoyl) -2, 4-diaminobenzene; then the 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole is obtained through a closed-loop reaction. The method has the advantages of high reaction yield, high product purity, relative environmental friendliness and suitability for industrial mass production.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a synthetic method of 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole.
Background
2- (2-chloro-4-aminophenyl) -5-aminoBenzimidazole with CAS number of 70500-01-5 and molecular formula of C 13 H 11 ClN 4 The relative molecular weight is 258.71, and the structural formula is as follows:
polyimide is widely applied to the fields of various materials such as films, foams, spandex and the like due to its excellent comprehensive properties such as heat resistance, high mechanical properties, low dielectric constant and the like. Among them, benzimidazole-containing polyimides have attracted much attention as a novel polyimide material because of their high molecular conjugation and high molecular chain rigidity, and thus have excellent heat resistance and dimensional stability. If polar groups such as chlorine atoms are further introduced, the thermal stability can be further improved, the solubility of the polymer is improved, the mechanical properties and other properties are improved, and the method has wide application prospects in the aspect of preparing electronic materials such as high-performance fibers, films, batteries and the like. Thus, 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole arose.
U.S. Pat. No. 4,929,947A discloses 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole which is prepared by reacting 4-nitrophthalenediamine and 2-chloro-4-nitrobenzoyl chloride as starting materials to obtain 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole.
The method has the following disadvantages: (1) the yield is low and is only 69%; (2) Although no numerical purity is disclosed, it is understood that the purity of 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole obtained by this method is not high (equivalent to 91 to 92%, or even inferior to 91 to 92%) based on examples 1 to 3 (the purity is only 91 to 92%) to which reference is made.
Disclosure of Invention
The present invention is intended to solve the above problems and to provide a method for producing 2- (4-amino-2-chloro-phenyl) -5-aminobenzimidazole having high reaction yield and high product purity.
The technical scheme for realizing the purpose of the invention is as follows: a process for the preparation of 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole having the steps of:
(1) 2-chloro-4-nitrobenzoic acid is taken as a starting material, and chlorination reaction is firstly carried out to obtain 2-chloro-4-nitrobenzoyl chloride; then carrying out condensation reaction with 2, 4-dinitroaniline to obtain an intermediate N- (2-chloro-4-nitrobenzoyl) -2, 4-dinitrobenzene;
(2) carrying out catalytic hydrogenation reaction on the intermediate N- (2-chloro-4-nitrobenzoyl) -2, 4-dinitrobenzene obtained in the step (1) to obtain N- (2-chloro-4-aminobenzoyl) -2, 4-diaminobenzene; then the 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole is obtained through a closed-loop reaction.
The reaction formula is as follows:
in the step (1), the molar ratio of the 2-chloro-4-nitrobenzoic acid to the 2, 4-dinitroaniline is 1: 0.9-1: 1.3.
In the step (1), the chlorination reagent adopted in the chlorination reaction is one of thionyl chloride, oxalyl chloride and triphosgene; the molar ratio of the 2-chloro-4-nitrobenzoic acid to the thionyl chloride is 1: 1-1: 1.2; the molar ratio of the 2-chloro-4-nitrobenzoic acid to the triphosgene is 1: 0.5-1: 0.6.
In the step (1), the chlorination reaction and the condensation reaction are both carried out in the presence of an organic solvent; the organic solvent is one or two of toluene, xylene and DMF; preferably a mixed solvent of one of toluene and xylene and DMF.
In the step (1), the temperature of the chlorination reaction and the condensation reaction are both reflux temperature.
In the step (1), the condensation reaction is carried out in the presence of a catalyst N, N-lutidine (hereinafter, referred to as DMAP); the dosage of the N, N-lutidine is 0.5 to 5 weight percent of the weight of the 2-chloro-4-nitrobenzoic acid.
In the step (2), the catalyst used for the catalytic hydrogenation reaction is a platinum-carbon catalyst, a palladium-carbon catalyst or raney nickel; the dosage of the catalyst is 0.5 to 10 weight percent of the weight of the intermediate N- (2-chloro-4-nitrobenzoyl) -2, 4-dinitrobenzene.
In the step (2), the catalytic hydrogenation reaction is carried out in the presence of an organic solvent; the organic solvent is one of methanol, ethanol, DMF and water.
In the step (2), the catalytic hydrogenation reaction temperature is 40 to 120 ℃, preferably 60 to 100 ℃.
In the step (2), the catalytic hydrogenation reaction pressure is 0.2 to 2.0MPa, preferably 0.5 to 1.0MPa.
In the step (2), the ring-closure reaction is carried out in the presence of an acidic catalyst; the acidic catalyst is inorganic acid such as hydrochloric acid and sulfuric acid or organic acid such as acetic acid.
In the step (2), the molar ratio of the intermediate N- (2-chloro-4-nitrobenzoyl) -2, 4-dinitrobenzene to the acid catalyst is 1: 0.8-1: 20, preferably 1: 2-1: 8.
The hydrogen chloride gas generated in the step (1) is recovered with deionized water and then can be used in the step (2).
The invention has the following positive effects: the method has the advantages of high reaction yield, high product purity, environmental friendliness and suitability for industrial mass production.
Drawings
FIG. 1 is a spectrum of a methanol solution of 2-chloro-4-nitrobenzoyl chloride obtained in step (1) of example 1 by a medium-controlled LC-MS method.
FIG. 2 is a LC-MS spectrum of the intermediate N- (2-chloro-4-nitrobenzoyl) -2, 4-dinitrobenzene obtained in step (1) of example 1.
FIG. 3 is a spectrum of the center-controlled LC-MS of N- (2-chloro-4-aminobenzoyl) -2, 4-diaminobenzene obtained in the step (2) of example 1.
FIG. 4 is a LC-MS spectrum of the objective 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole obtained in the step (2) of example 1.
Detailed Description
(example 1)
The process for the preparation of 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole according to this example had the following steps:
(1) 201.6g of 2-chloro-4-nitrobenzoic acid (1.0 mol), 600mL of toluene and 1mL of DMF are sequentially added into a 1L four-mouth bottle provided with a reflux condenser tube and a mechanical stirring device, under the protection of nitrogen, 154.3g of triphosgene (0.52 mol) is added while stirring, the temperature is raised to reflux after the addition, the reaction is stirred for 2 to 3 hours, and the mixture is sampled, dissolved in a methanol solution and subjected to LC-MS detection, and the result is shown in figure 1.
As can be seen from fig. 1: the 2-chloro-4-nitrobenzoic acid is totally converted into 2-chloro-4-nitrobenzoyl chloride.
After the reaction is finished, stopping heating, cooling to 60 ℃, adding 190.8g of 2, 4-dinitroaniline (1.04 mol) and 2.7g of DMAP into the reaction liquid in batches, heating again until reflux is reached after the addition is finished, gradually separating out a large amount of yellow solid accompanied by the discharge of hydrogen chloride gas, collecting the hydrogen chloride gas by using deionized water, and using the obtained hydrochloric acid in the step (2).
After continuously stirring for 8h, the reaction is finished, the temperature is reduced to room temperature, the reaction is filtered, a small amount of toluene is used for leaching a filter cake, vacuum drying is carried out for 16h at the temperature of 60 ℃, 347.2g of intermediate N- (2-chloro-4-nitrobenzoyl) -2, 3-dinitrobenzene is obtained, the HPLC purity is 99.5 percent, the yield is 94.7 percent, and the melting point is 119-202 ℃.
The LC-MS spectrum of this intermediate is shown in fig. 2, from which it can be seen in fig. 2: the molecular weight of this intermediate is 366.0 (MS: M-H), which is essentially identical to N- (2-chloro-4-nitrobenzoyl) -2, 4-dinitrophenyl.
(2) 50g (0.137 mol) of intermediate N- (2-chloro-4-nitrobenzoyl) -2, 3-dinitrobenzene obtained in the step (1) and 200mL of 10wt% diluted hydrochloric acid (0.575 mol) are added into a 500mL high-pressure reaction kettle, then 2.5g of 5wt% Pt/C catalyst are added, after three times of hydrogen replacement, the reaction is stirred for 3 hours under the pressure of 0.6MPa and the temperature of 60 ℃, the hydrogen absorption speed is obviously slowed down, a sample is taken and subjected to LC-MS detection, and the result is shown in figure 3.
As can be seen from fig. 3: the nitro reduction is substantially complete and the product molecular weight is 276.1 (MS: M + H), which is substantially consistent with the molecular weight of N- (2 chloro-4-aminobenzoyl) -2, 4-diaminobenzene.
Keeping the temperature and pressure, continuously stirring and reacting for 8 hours, filtering while the reaction is hot after the reaction is finished, recycling the Pt/C catalyst, reducing the temperature of the filtrate to room temperature, standing for 16 hours, separating out a large amount of white solid, filtering (the acidic filtrate can be directly used for the next batch reaction after being supplemented with a small amount of concentrated hydrochloric acid), washing the filter cake with a small amount of methanol, adding 70mL of 28wt% ammonia water for pulping, filtering, and drying in vacuum at 80 ℃ for 12 hours to obtain 32.7g of a white finished product with the purity of 99.83% (HPLC), the yield of 92.7% and the melting point of 280 ℃.
The overall molar yield in the two steps was 87.8%.
The LC-MS spectrum of this product is shown in fig. 4, from which it can be seen in fig. 4: the molecular weight of the product is 258.0 (MS: M + H), and is basically consistent with the molecular weight of the target product 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole.
The reaction formula of this example is as follows:
(example 2)
The process for the preparation of 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole according to this example had the following steps:
(1) 201.6g of 2-chloro-4-nitrobenzoic acid (1.0 mol), 600mL of toluene and 1mL of DMF are sequentially added into a 1L four-neck flask provided with a reflux condenser tube and a mechanical stirring device, 124.9g of thionyl chloride (1.05 mol) is added under nitrogen protection while stirring, the temperature is raised to reflux after the addition, and the reaction is stirred until all the 2-chloro-4-nitrobenzoic acid is converted into 2-chloro-4-nitrobenzoyl chloride (the detection method is the same as that in example 1).
After the reaction is finished, stopping heating, cooling to 60 ℃, adding 190.8g of 2, 4-dinitroaniline (1.04 mol) and 2.7g of DMAP into the reaction liquid in batches, heating again until reflux is reached after the addition is finished, gradually separating out a large amount of yellow substances accompanied with the discharge of hydrogen chloride gas, and collecting the hydrogen chloride gas by using deionized water.
After stirring for 8 hours, the reaction is finished, the temperature is reduced to room temperature, the reaction is filtered, a filter cake is rinsed by a small amount of toluene and dried in vacuum for 16 hours at the temperature of 60 ℃, 344.9g of intermediate N- (2-chloro-4-nitrobenzoyl) -2, 4-dinitrobenzene is obtained, the HPLC purity is 99.3 percent, and the yield is 94.1 percent.
(2) 50g (0.137 mol) of the intermediate N- (2-chloro-4-nitrobenzoyl) -2, 3-dinitrobenzene obtained in step (1), 250mL of ethanol and 2.5g and 5wt% of Pt/C catalyst were charged into a 500mL autoclave, and after three times of hydrogen substitution, the reaction was stirred at a pressure of 0.6MPa and a temperature of 60 ℃ until the nitro reduction was completed (the detection method was the same as in example 1).
After the reaction is finished, filtering while hot, recovering and recycling the Pt/C catalyst, cooling the filtrate to room temperature, standing for 16h, separating out a large amount of white solid, filtering, putting the filter cake and 250mL of 20wt% dilute sulfuric acid (0.575 mol) into a 500mL three-port bottle, stirring and reacting for 3h at the temperature of 90 ℃ under the protection of nitrogen, cooling to room temperature, adding ammonia water to adjust the pH value to be alkaline, separating out a large amount of white solid, filtering, washing the filter cake with a small amount of methanol, and drying in vacuum at the temperature of 80 ℃ for 12h to obtain 30.1g of a white finished product with the purity of 99.71% (HPLC) and the yield of 85.3%.
The total molar yield in two steps was 80.3%.
The reaction formula of this example is as follows:
Claims (9)
1. a process for the preparation of 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole having the steps of:
(1) 2-chloro-4-nitrobenzoic acid is taken as a starting material, and chlorination reaction is firstly carried out to obtain 2-chloro-4-nitrobenzoyl chloride; then carrying out condensation reaction with 2, 4-dinitroaniline to obtain an intermediate N- (2-chloro-4-nitrobenzoyl) -2, 4-dinitrobenzene;
(2) carrying out catalytic hydrogenation reaction on the intermediate N- (2-chloro-4-nitrobenzoyl) -2, 4-dinitrobenzene obtained in the step (1) to obtain N- (2-chloro-4-aminobenzoyl) -2, 4-diaminobenzene; then the 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole is obtained through a closed-loop reaction.
2. The process for the preparation of 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole according to claim 1, characterized in that: in the step (1), the molar ratio of the 2-chloro-4-nitrobenzoic acid to the 2, 4-dinitroaniline is 1: 0.9-1: 1.3.
3. The process for the preparation of 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole according to claim 1, characterized in that: in the step (1), the chlorination reagent adopted in the chlorination reaction is one of thionyl chloride, oxalyl chloride and triphosgene; the molar ratio of the 2-chloro-4-nitrobenzoic acid to the thionyl chloride is 1: 1-1: 1.2; the molar ratio of the 2-chloro-4-nitrobenzoic acid to the triphosgene is 1: 0.5-1: 0.6.
4. The process for preparing 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole according to claim 1, characterized in that: in the step (1), the chlorination reaction and the condensation reaction are both carried out in the presence of an organic solvent; the organic solvent is one or two of toluene, xylene and DMF; the temperature of the chlorination reaction and the condensation reaction are both reflux temperature.
5. The process for the preparation of 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole according to claim 1, characterized in that: in the step (1), the condensation reaction is carried out in the presence of a catalyst, namely N, N-dimethylpyridine; the dosage of the N, N-lutidine is 0.5 to 5 weight percent of the weight of the 2-chloro-4-nitrobenzoic acid.
6. The process for the preparation of 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole according to claim 1, characterized in that: in the step (2), the catalyst used for the catalytic hydrogenation reaction is a platinum-carbon catalyst, a palladium-carbon catalyst or raney nickel; the dosage of the catalyst is 0.5 to 10 weight percent of the weight of the intermediate N- (2-chloro-4-nitrobenzoyl) -2, 4-dinitrobenzene.
7. The process for the preparation of 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole according to claim 1, characterized in that: in the step (2), the catalytic hydrogenation reaction is carried out in the presence of an organic solvent; the organic solvent is one of methanol, ethanol, DMF and water.
8. The process for preparing 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole according to claim 1, characterized in that: in the step (2), the temperature of the catalytic hydrogenation reaction is 40-120 ℃; the pressure of the catalytic hydrogenation reaction is 0.2-2.0 MPa.
9. The process for the preparation of 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole according to claim 1, characterized in that: in the step (2), the ring-closure reaction is carried out in the presence of an acidic catalyst; the molar ratio of the intermediate N- (2-chloro-4-nitrobenzoyl) -2, 4-dinitrobenzene to the acid catalyst is 1: 0.8-1: 20; the acidic catalyst is hydrochloric acid or sulfuric acid or acetic acid.
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| CN202211493307.0A Pending CN115850188A (en) | 2022-11-25 | 2022-11-25 | Synthetic method of 2- (2-chloro-4-aminophenyl) -5-aminobenzimidazole |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4109093A (en) * | 1975-01-14 | 1978-08-22 | Produits Chimiques Ugine Kuhlmann | Process for making 2-(4'-aminophenyl) 5-amino benzimidazole |
| US4192947A (en) * | 1977-09-19 | 1980-03-11 | Cassella Aktiengesellschaft | Process for the production of aminophenylaminobenzimidazoles |
| RU2013136948A (en) * | 2013-08-07 | 2015-02-20 | Общество с ограниченной ответственностью "Фенил" (ООО "Фенил") | METHOD FOR PRODUCING 5 (6) -AMINO-2- (4-AMINOPHENYL) BENZIMIDAZOLE |
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2022
- 2022-11-25 CN CN202211493307.0A patent/CN115850188A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4109093A (en) * | 1975-01-14 | 1978-08-22 | Produits Chimiques Ugine Kuhlmann | Process for making 2-(4'-aminophenyl) 5-amino benzimidazole |
| US4192947A (en) * | 1977-09-19 | 1980-03-11 | Cassella Aktiengesellschaft | Process for the production of aminophenylaminobenzimidazoles |
| RU2013136948A (en) * | 2013-08-07 | 2015-02-20 | Общество с ограниченной ответственностью "Фенил" (ООО "Фенил") | METHOD FOR PRODUCING 5 (6) -AMINO-2- (4-AMINOPHENYL) BENZIMIDAZOLE |
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| Title |
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| MIKROYANNIDIS, JOHN A.: "Heat-resistant matrix resins based on addition-type bisimidobenzimidazoles", EUROPEAN POLYMER JOURNAL, vol. 27, no. 2, 31 December 1991 (1991-12-31), pages 199 - 203 * |
| ZAVPLOVO, N. V.; VULAKH, F. L.: "Low-waste technology for production of 2\'4, 4\'-trinitrobenzanilide, intermediate product for synthesis of 5(6)-amino-2-(4\'-aminophenyl)benzimidazole", KHIMICHESKAYA PROMYSHLENNOST SEGODNYA, no. 7, 31 December 2016 (2016-12-31), pages 26 - 36, XP009529754 * |
| 金宁人;刘琛;肖庆军;施云龙;倪哲明;: "高纯度2-(4-氨基苯基)-1H-苯并咪唑-5-胺的合成", 化工进展, no. 05, 5 May 2009 (2009-05-05), pages 847 - 851 * |
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