A process for the preparation of 2-amino benzimidazoles

Abstract

The present application relates to a kind of 2-amino benzimidazole preparation method, belong to compound synthesis technical field.The preparation method is: in reactor, water is added, and o-phenylenediamine is uniformly dispersed;Then slowly add guanidine salt and uniformly dispersed, control the temperature of system during feeding process not higher than 70 DEG C;Add lye to adjust the pH of system to weak alkaline, then heat and keep warm reaction, after reaction is finished, 2-amino benzimidazole product is obtained after post-processing.The guanidine salt is at least one of guanidine hydrochloride, guanidine sulfate, guanidine nitrate.The molar ratio of o-phenylenediamine used and guanidine salt is 1: (1.1-1.5).When the o-phenylenediamine and guanidine salt react, the reaction temperature is 60-90 DEG C, and the reaction time is 6-10h.The raw material of the preparation method is cheap and easy to obtain, conversion rate is high, atom utilization rate is high, and has better industrial application prospect.

Description

TECHNICAL FIELD

[0001] The present application relates to a preparation method of 2-aminobenzimidazole, and belongs to the technical field of compound synthesis. BACKGROUND

[0002] Benzimidazole derivatives are a class of special structure heterocyclic compounds. They have wide application and far-reaching academic value in the pharmaceutical industry, high-performance composite materials, dyes and other aspects. In recent years, the synthesis and biological activity of such heterocyclic compounds have increasingly become a hot spot in the research of heterocyclic chemistry. 2-aminobenzimidazole (2-aminobenzimidazole, 2-AB for short), also known as N, N' o-phenyleneguanidine, is a class white to light brown crystalline powder with a melting point of 231-232℃. It is a fine chemical raw material with wide application value. In the field of pesticides, it has strong bactericidal and antibacterial effects on bacteria, fungi, viruses, microorganisms and mites, and can promote the metabolism of cotyledons and roots of asexual plants. In addition, it can also be used as a seed disinfectant. In the field of medicine, the imidazole ring and benzimidazole heterocycle contained in benzimidazole have parasiticidal, antibacterial, anti-inflammatory, anticancer, sedative, diuretic and other drug activities, which are of great significance to the coordination of physiological balance. In addition, it also has the effects of lowering blood pressure and improving cardiovascular activity, and can also be used as an antidote for animal poisoning. The existing synthesis method abroad (for example: Weiss S, Michaud H, Prietzel H, et al. Synthesis of 2-AB [J]. Angew Chem, 1973, 85(19): 866-867) has the disadvantages of difficult to obtain raw materials or long process. The patent application with publication number CN102863390A discloses a synthesis method of benzimidazole derivatives, which comprises the following steps: in a closed reactor, using o-phenylenediamine or N-methyl-o-phenylenediamine, glycine and inorganic acid (such as H2SO4, H3PO4 or HCl) are reacted at 100-150℃ for 36-72 hours, then the pH value is adjusted with ammonia water and cooled, and then dried by suction filtration, and finally the benzimidazole derivative is obtained by recrystallization and decolorization through distilled water. This method has a relatively long production cycle and is not suitable for industrial application.

[0003] In summary, 2-aminobenzimidazole is an important organic synthesis intermediate with wide application value. However, so far, there are few mature industrial process routes. Therefore, developing a scientific, green, safe and efficient synthesis method and route has a milestone significance and value for the industrial preparation of 2-aminobenzimidazole. SUMMARY

[0004] The present application provides a preparation method of 2-aminobenzimidazole, which has the advantages of cheap and readily available raw materials, high conversion rate, high atom utilization rate and better industrial application prospect.

[0005] The technical scheme for solving the above technical problem is as follows: a preparation method of 2-amino benzimidazole, the preparation method is that o-phenylenediamine and guanidine salt are reacted in a weak alkaline water system, after the reaction is completed, 2-amino benzimidazole product is obtained through post-treatment.

[0006] On the basis of the above technical scheme, the application can also be improved as follows:

[0007] Further, the guanidine salt is at least one of guanidine hydrochloride, guanidine sulfate and guanidine nitrate.

[0008] Further, the molar ratio of the used o-phenylenediamine to guanidine salt is 1: (1.1-1.5).

[0009] Further, when the o-phenylenediamine and guanidine salt are reacted, the reaction temperature is 60-90℃.

[0010] Further, when the o-phenylenediamine and guanidine salt are reacted, the reaction time is 6-10h.

[0011] Further, the pH of the water system is adjusted to 7.5-9.5 by adding alkali liquor.

[0012] Further, the alkali liquor is any one of sodium hydroxide aqueous solution, potassium hydroxide aqueous solution and ammonia water.

[0013] Further, the mass concentration of the alkali liquor is 10%-30%.

[0014] Further, the preparation method is that water is added in a reactor, and o-phenylenediamine is uniformly dispersed; then guanidine salt is slowly added and uniformly dispersed, the temperature of the system in the feeding process is controlled to be not higher than 70℃; alkali liquor is added to adjust the pH of the system to weak alkalinity, then heating and holding are performed, after the reaction is completed, 2-amino benzimidazole product is obtained through post-treatment.

[0015] Further, after the reaction is completed, the system is reduced to 20-25℃, 2-amino benzimidazole is obtained through solid-liquid separation, washing and drying.

[0016] The application has the following beneficial effects:

[0017] The preparation method of 2-amino benzimidazole is that o-phenylenediamine and guanidine salt are reacted in a water system to prepare 2-amino benzimidazole, the raw materials used in the preparation method are cheap and easy to obtain, the reaction is performed in water phase, belongs to the green synthesis range, the operation is simple, the three wastes are less discharged, the whole preparation process is green, safe, efficient, simple to operate, low in cost, and suitable for industrial application.

[0018] The preparation method can directly obtain 2-amino benzimidazole product with purity not less than 99%, and has high yield and simple post-treatment. In the post-treatment process, the filtrate of solid-liquid separation can be directly used as a solvent for the next batch of reaction, thereby reducing the generation of waste water and being more environmentally friendly. BRIEF DESCRIPTION OF DRAWINGS

[0019] Figure 1 A synthetic route of the preparation method of 2-amino benzimidazole;

[0020] Figure 2 A reaction scheme of the preparation method of 2-amino benzimidazole;

[0021] Figure 3 An HPLC spectrum of 2-amino benzimidazole prepared in Example 1.

[0022] Figure 4 An HPLC spectrum of 2-amino benzimidazole prepared in Comparative Example 1. DETAILED DESCRIPTION

[0023] In order to make the above objectives, features and advantages of the present application more apparent and comprehensible, the specific embodiments of the present application are described in detail below. In the following description, a large number of specific details are set forth in order to fully understand the present application. However, the present application can be implemented in many other ways different from those described herein, and those skilled in the art can make similar improvements without departing from the scope of the present application, and therefore the present application is not limited to the specific embodiments disclosed below.

[0024] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present application belongs. The terms used in the specification of the present application are only for the purpose of describing specific embodiments and are not intended to limit the present application.

[0025] A preparation method of 2-amino benzimidazole, the preparation method is that o-phenylenediamine and guanidine salt are reacted in a weak alkaline water system, after the reaction is completed, 2-amino benzimidazole product is obtained through post-treatment.

[0026] The synthetic route and the reaction scheme in the preparation method of 2-amino benzimidazole are shown in Figure 1 and Figure 2 respectively.

[0027] The structural formula of the 2-amino benzimidazole is . The structural formula of the guanidine salt is .

[0028] On the basis of the above technical solutions, the present application can also be improved as follows:

[0029] Specifically, the guanidine salt is at least one of guanidine hydrochloride, guanidine sulfate, and guanidine nitrate.

[0030] Specifically, the molar ratio of the used o-phenylenediamine to guanidine salt is 1: (1.1-1.5).

[0031] Specifically, when the o-phenylenediamine and guanidine salt are reacted, the reaction temperature is 60-90℃.

[0032] Specifically, when the o-phenylenediamine and guanidine salt are reacted, the reaction time is 6-10h.

[0033] Specifically, the pH of the water system is adjusted to 7.5-9.5 by adding a lye.

[0034] Specifically, the lye is any one of sodium hydroxide aqueous solution, potassium hydroxide aqueous solution, and ammonia water.

[0035] Specifically, the mass concentration of the lye is 10%-30%.

[0036] Specifically, the preparation method is: adding water in a reactor, and uniformly dispersing o-phenylenediamine; then slowly adding guanidine salt and uniformly dispersing, controlling the temperature of the system during the feeding process to be not higher than 70℃; adding a lye to adjust the pH of the system to weak alkaline, then heating and keeping warm to react, and after the reaction is completed, obtaining 2-aminobenzimidazole product through post-treatment.

[0037] Specifically, after the reaction is completed, the system is lowered to 20-25℃, and 2-aminobenzimidazole is obtained through solid-liquid separation, washing, and drying.

[0038] More specifically, in the preparation method of the 2-aminobenzimidazole, at least one of deionized water or reaction mother liquor (filtrate of solid-liquid separation after post-treatment) is used as a solvent for reaction.

[0039] More specifically, the mass of the used solvent is 2-5 times the mass of the o-phenylenediamine.

[0040] Example 1

[0041] A preparation method of 2-aminobenzimidazole, the preparation method is:

[0042] (1) adding purified water (solvent) in a reactor with reflux device, starting stirring, slowly adding o-phenylenediamine (232.5g, 2.15mol) while stirring, and uniformly stirring after the addition is completed. The mass of the solvent is 2 times the mass of the o-phenylenediamine.

[0043] (2) adding guanidine salt (guanidine hydrochloride) to the system of step (1), the molar ratio of the o-phenylenediamine to guanidine salt is 1:1.16, and the temperature in the reactor during the feeding process is controlled to be not higher than 70℃.

[0044] (3) To the system of step (2), add 10% sodium hydroxide aqueous solution, adjust the pH of the system to 7.5-8.0, start heating, start temperature control, control the temperature at 80℃, and keep the system pH in the range of 7.5-8.0 for 8h.

[0045] (4) After the incubation, cool to 25℃, filter, wash, and dry to obtain 2-aminobenzimidazole dry product. The yield is 95.2%, and the purity detected by HPLC is 99.2%. The HPLC test spectrum is shown in Figure 3 , and the specific data are shown in Table 1.

[0046] Table 1 Figure 3 Liquid chromatography data

[0047]

[0048] Example 2

[0049] A method for preparing 2-aminobenzimidazole, the method comprising:

[0050] (1) In a reactor with reflux device, add purified water (solvent), start stirring, and slowly add o-phenylenediamine (232.5g, 2.15mol) while stirring. After adding, stir evenly. The mass of the solvent is 2 times the mass of o-phenylenediamine.

[0051] (2) To the system of step (1), add guanidine salt (guanidine nitrate), wherein the molar ratio of o-phenylenediamine to guanidine salt is 1:1.1, and control the temperature in the reactor during the feeding process to be not higher than 70℃.

[0052] (3) To the system of step (2), add 10% potassium hydroxide aqueous solution, adjust the pH of the system to 7.5-8.0, start heating, start temperature control, control the temperature at 60℃, and keep the system pH in the range of 7.5-8.0 for 10h.

[0053] (4) After the incubation, cool to 25℃, filter, wash, and dry to obtain 2-aminobenzimidazole dry product. The yield is 95.1%, and the purity detected by HPLC is 99.1%.

[0054] Example 3

[0055] A method for preparing 2-aminobenzimidazole, the method comprising:

[0056] (1) Add purified water (solvent) into the reactor with reflux device, start stirring, slowly add o-phenylenediamine (2325 g, 21.5 mol) while stirring, and stir uniformly after the addition is completed. The mass of the solvent is 2 times the mass of o-phenylenediamine.

[0057] (2) Add guanidine salt (guanidine hydrochloride) into the system of step (1), wherein the molar ratio of o-phenylenediamine to guanidine salt is 1:1.16, and the temperature in the reactor during the feeding process is controlled to be not higher than 70°C.

[0058] (3) Add 10% sodium hydroxide aqueous solution into the system of step (2), adjust the pH of the system to be 7.5-8.0, start heating, start temperature rising, control the temperature to be 80°C, and keep the pH of the system in the range of 7.5-8.0 during the incubation reaction for 8 h.

[0059] (4) After the incubation is completed, cool to 25°C, filter, wash, and dry to obtain 2-aminobenzimidazole dry product. The yield is 95.3%, and the purity detected by HPLC is 99.1%.

[0060] Example 4

[0061] A preparation method of 2-aminobenzimidazole, the preparation method comprises the following steps:

[0062] (1) Add purified water (solvent) into the reactor with reflux device, start stirring, slowly add o-phenylenediamine (232.5 g, 2.15 mol) while stirring, and stir uniformly after the addition is completed. The mass of the solvent is 3 times the mass of o-phenylenediamine.

[0063] (2) Add guanidine salt (guanidine sulfate) into the system of step (1), wherein the molar ratio of o-phenylenediamine to guanidine salt is 1:1.5, and the temperature in the reactor during the feeding process is controlled to be not higher than 70°C.

[0064] (3) Add 25% ammonia water into the system of step (2), adjust the pH of the system to be 7.5-8.0, start heating, start temperature rising, control the temperature to be 90°C, and keep the pH of the system in the range of 7.5-8.0 during the incubation reaction for 6 h.

[0065] (4) After the incubation is completed, cool to 20°C, filter, wash, and dry to obtain 2-aminobenzimidazole dry product. The yield is 95.0%, and the purity detected by HPLC is 99.1%.

[0066] Example 5

[0067] A preparation method of 2-aminobenzimidazole, the preparation method comprises the following steps:

[0068] (1) Add purified water (solvent) into the reactor with reflux device, start stirring, slowly add o-phenylenediamine (232.5 g, 2.15 mol) while stirring, and stir uniformly after the addition is completed. The mass of the solvent is 2 times the mass of o-phenylenediamine.

[0069] (2) Add guanidine salt (guanidine hydrochloride) into the system of step (1), wherein the molar ratio of o-phenylenediamine to guanidine salt is 1:1.16, and the temperature in the reactor during the feeding process is controlled to be not higher than 70°C.

[0070] (3) Add 30% potassium hydroxide aqueous solution into the system of step (2), adjust the pH in the system to be 8.5-9.0, start heating, start temperature rising, control the temperature to be 80°C, and keep the pH in the system in the range of 8.5-9.0, and keep the reaction for 7 h.

[0071] (4) After the incubation is completed, cool to 25°C, filter, wash, and dry to obtain 2-aminobenzimidazole dry product. The yield is 95.1%, and the purity detected by HPLC is 99.2%.

[0072] Example 6

[0073] A preparation method of 2-aminobenzimidazole, the preparation method comprises the following steps:

[0074] (1) Add purified water (solvent) into the reactor with reflux device, start stirring, slowly add o-phenylenediamine (232.5 g, 2.15 mol) while stirring, and stir uniformly after the addition is completed. The mass of the solvent is 5 times the mass of o-phenylenediamine.

[0075] (2) Add guanidine salt (guanidine hydrochloride) into the system of step (1), wherein the molar ratio of o-phenylenediamine to guanidine salt is 1:1.3, and the temperature in the reactor during the feeding process is controlled to be not higher than 70°C.

[0076] (3) Add 30% potassium hydroxide aqueous solution into the system of step (2), adjust the pH in the system to be 8.0-8.5, start heating, start temperature rising, control the temperature to be 70°C, and keep the pH in the system in the range of 8.0-8.5, and keep the reaction for 9 h.

[0077] (4) After the incubation is completed, cool to 25°C, filter, wash, and dry to obtain 2-aminobenzimidazole dry product. The yield is 95.1%, and the purity detected by HPLC is 99.2%.

[0078] Example 7

[0079] A preparation method of 2-aminobenzimidazole, the preparation method comprises the following steps:

[0080] (1) Add purified water (solvent) into the reactor with reflux device, start stirring, slowly add o-phenylenediamine (232.5 g, 2.15 mol) while stirring, and stir uniformly after the addition is completed. The mass of the solvent is 2 times the mass of o-phenylenediamine.

[0081] (2) Add guanidine salt (guanidine nitrate) into the system of step (1), wherein the molar ratio of o-phenylenediamine to guanidine salt is 1:1.4, and the temperature in the reactor during the feeding process is controlled to be not higher than 70°C.

[0082] (3) Add 10% sodium hydroxide aqueous solution into the system of step (2), adjust the pH of the system to 8.0-8.5, start heating, start temperature rising, control the temperature at 85°C, and keep the pH of the system in the range of 8.0-8.5 for 8 h of incubation.

[0083] (4) After the incubation is completed, cool to 25°C, filter, wash, and dry to obtain 2-aminobenzimidazole dry product. The yield is 95.2%, and the purity detected by HPLC is 99.1%.

[0084] Example 8

[0085] A preparation method of 2-aminobenzimidazole, the preparation method comprising:

[0086] (1) Add solvent into the reactor with reflux device, start stirring, slowly add o-phenylenediamine while stirring, and stir uniformly after the addition is completed. The solvent used in this example 8 is the mother liquor after filtration in step (4) of example 1 and deionized water (wherein the volume ratio of the mother liquor to deionized water is 1:1), and the addition amount of o-phenylenediamine is adjusted so that the mass of the solvent is 2 times the mass of o-phenylenediamine.

[0087] (2) Add guanidine salt (guanidine nitrate) into the system of step (1), wherein the molar ratio of o-phenylenediamine to guanidine salt is 1:1.4, and the temperature in the reactor during the feeding process is controlled to be not higher than 70°C.

[0088] (3) Add 10% sodium hydroxide aqueous solution into the system of step (2), adjust the pH of the system to 8.0-8.5, start heating, start temperature rising, control the temperature at 85°C, and keep the pH of the system in the range of 8.0-8.5 for 8 h of incubation.

[0089] (4) After the incubation is completed, cool to 25°C, filter, wash, and dry to obtain 2-aminobenzimidazole dry product. The yield is 95.4%, and the purity detected by HPLC is 99.1%.

[0090] The mother liquor obtained from the filtration of step of this example 8 was mixed with deionized water again according to 1:1, and then was applied to the preparation of 2-aminobenzimidazole product again. After multiple cycles (not less than 3 times) of application according to the same method, the purity of the obtained 2-aminobenzimidazole product was all ≥ 99.0%.

[0091] Comparative Example 1

[0092] In this comparative example 1, the mother liquor was used as the solvent for the preparation of 2-aminobenzimidazole, and the specific preparation process was as follows:

[0093] (1) The solvent was added to a reactor with reflux device, and stirring was started. o-Tolidine was slowly added while stirring, and after addition was completed, stirring was uniform. In this comparative example 1, the solvent used was the mother liquor after filtration in step (4) of example 1. The amount of o-tolidine was adjusted so that the mass of the solvent was 2 times the mass of o-tolidine.

[0094] (2) Guanidine salt (guanidine nitrate) was added to the system of step (1), and the molar ratio of o-tolidine to guanidine salt was 1:1.4. The temperature in the reactor during the addition process was controlled to be not higher than 70°C.

[0095] (3) A 10% sodium hydroxide aqueous solution was added to the system of step (2) to adjust the pH of the system to 8.0-8.5. Heating was started, and the temperature was controlled at 85°C. The pH of the system was maintained at 8.0-8.5 during the reaction for 5h.

[0096] (4) After the incubation was completed, the temperature was lowered to 25°C, and filtration, washing and drying were performed to obtain 2-aminobenzimidazole dry product. The yield was 88.1%, and the purity detected by HPLC was 96.0%. The HPLC test spectrum is shown in Figure 4 , and the specific data is shown in Table 2.

[0097] Table 2 Figure 4 Liquid chromatography data in Table 2

[0098]

[0099] Comparative Example 2

[0100] 2-Aminobenzimidazole was prepared by the same method as in example 1, except that the pH in this comparative example 2 was 4.0-5.0. The specific preparation process was as follows:

[0101] (1) Purified water (solvent) was added to a reactor with reflux device, and stirring was started. o-Tolidine (232.5g, 2.15mol) was slowly added while stirring, and after addition was completed, stirring was uniform. The mass of the solvent was 2 times the mass of o-tolidine.

[0102] (2) To the system of step (1), add guanidine salt (guanidine hydrochloride), wherein the molar ratio of o-phenylenediamine and guanidine salt is 1:1.16, and the temperature in the reactor during the feeding process is controlled to be no higher than 70°C.

[0103] (3) To the system of step (2), add 10% sodium hydroxide aqueous solution, adjust the pH of the system to be 4.0-5.0 (the acidity of the system without adding alkali is very high, and the pH is adjusted to 4.0-5.0 by adding a small amount of alkali solution), start heating, begin to increase the temperature, control the temperature at 80°C, and keep the pH of the system in the range of 4.0-5.0 for 8h.

[0104] (4) After the incubation is completed, cool to 25°C, filter, wash, and dry to obtain 2-aminobenzimidazole dry product. The yield is 87.9%, and the purity detected by HPLC is 96.0%.

[0105] Comparative Example 3

[0106] 2-Aminobenzimidazole is prepared by the same method as in Example 1, except that the pH in this comparative example 3 is 11-12.5, and the specific preparation process is as follows:

[0107] (1) In a reactor with reflux device, add purified water (solvent), start stirring, and slowly add o-phenylenediamine (232.5g, 2.15mol) while stirring. After the addition is completed, stir uniformly. The mass of the solvent is 2 times the mass of o-phenylenediamine.

[0108] (2) To the system of step (1), add guanidine salt (guanidine hydrochloride), wherein the molar ratio of o-phenylenediamine and guanidine salt is 1:1.16, and the temperature in the reactor during the feeding process is controlled to be no higher than 70°C.

[0109] (3) To the system of step (2), add 10% sodium hydroxide aqueous solution, adjust the pH of the system to be 11-12.5, start heating, begin to increase the temperature, control the temperature at 80°C, and keep the pH of the system in the range of 11-12.5 for 8h.

[0110] (4) After the incubation is completed, cool to 25°C, filter, wash, and dry to obtain 2-aminobenzimidazole dry product. The yield is 87.3%, and the purity detected by HPLC is 96.1%.

[0111] Comparative Example 4

[0112] 2-Aminobenzimidazole is prepared by the same method as in Example 1, except that the reaction time is reduced in this comparative example 4, and the specific preparation process is as follows:

[0113] (1) Add purified water (solvent) into the reactor with reflux device, start stirring, slowly add o-phenylenediamine (232.5 g, 2.15 mol) while stirring, and stir uniformly after the addition is completed. The mass of the solvent is 2 times the mass of o-phenylenediamine.

[0114] (2) Add guanidine salt (guanidine hydrochloride) to the system of step (1), wherein the molar ratio of o-phenylenediamine to guanidine salt is 1:1.16, and the temperature in the reactor during the feeding process is controlled to be not higher than 70°C.

[0115] (3) Add 10% sodium hydroxide aqueous solution to the system of step (2), adjust the pH of the system to 7.5-8.0, start heating, start temperature rising, control the temperature at 80°C, and keep the pH of the system in the range of 7.5-8.0 for 3 h.

[0116] (4) After the incubation is completed, cool to 25°C, filter, wash, and dry to obtain 2-aminobenzimidazole dry product. The yield is 88.2%, and the purity detected by HPLC is 95.9%.

[0117] Comparative Example 5

[0118] 2-Aminobenzimidazole is prepared by the same method as in Example 1, except that the reaction time is extended in Comparative Example 5, and the specific preparation process is as follows:

[0119] (1) Add purified water (solvent) into the reactor with reflux device, start stirring, slowly add o-phenylenediamine (232.5 g, 2.15 mol) while stirring, and stir uniformly after the addition is completed. The mass of the solvent is 2 times the mass of o-phenylenediamine.

[0120] (2) Add guanidine salt (guanidine hydrochloride) to the system of step (1), wherein the molar ratio of o-phenylenediamine to guanidine salt is 1:1.16, and the temperature in the reactor during the feeding process is controlled to be not higher than 70°C.

[0121] (3) Add 10% sodium hydroxide aqueous solution to the system of step (2), adjust the pH of the system to 7.5-8.0, start heating, start temperature rising, control the temperature at 80°C, and keep the pH of the system in the range of 7.5-8.0 for 18 h.

[0122] (4) After the incubation is completed, cool to 25°C, filter, wash, and dry to obtain 2-aminobenzimidazole dry product. The yield is 87.6%, and the purity detected by HPLC is 95.7%.

[0123] Comparative Example 6

[0124] The same method as in Example 1 was used to prepare 2-amino benzimidazole, except that the reaction temperature was lowered in this Comparative Example 6, and the preparation process was as follows:

[0125] (1) Purified water (solvent) was added to a reactor with reflux device, stirring was started, and o-phenylenediamine (232.5 g, 2.15 mol) was slowly added while stirring. After the addition was completed, the mixture was stirred until uniform. The mass of the solvent was twice the mass of the o-phenylenediamine.

[0126] (2) Guanidine salt (guanidine hydrochloride) was added to the system of step (1), and the molar ratio of o-phenylenediamine to guanidine salt was 1:1.16. The temperature in the reactor during the addition was controlled to be no higher than 70°C.

[0127] (3) A 10% sodium hydroxide aqueous solution was added to the system of step (2) to adjust the pH of the system to 7.5-8.0. Heating was started, and the temperature was controlled at 40°C. The pH of the system was maintained at 7.5-8.0 during the reaction for 8 h.

[0128] (4) After the incubation was completed, the temperature was lowered to 25°C, and filtration, washing, and drying were performed to obtain 2-amino benzimidazole dry product. The yield was 88.3%, and the purity detected by HPLC was 93.2%.

[0129] Comparative Example 7

[0130] The same method as in Example 1 was used to prepare 2-amino benzimidazole, except that the reaction temperature was increased in this Comparative Example 7, and the preparation process was as follows:

[0131] (1) Purified water (solvent) was added to a reactor with reflux device, stirring was started, and o-phenylenediamine (232.5 g, 2.15 mol) was slowly added while stirring. After the addition was completed, the mixture was stirred until uniform. The mass of the solvent was twice the mass of the o-phenylenediamine.

[0132] (2) Guanidine salt (guanidine hydrochloride) was added to the system of step (1), and the molar ratio of o-phenylenediamine to guanidine salt was 1:1.16. The temperature in the reactor during the addition was controlled to be no higher than 70°C.

[0133] (3) A 10% sodium hydroxide aqueous solution was added to the system of step (2) to adjust the pH of the system to 7.5-8.0. Heating was started, and the temperature was controlled at 120°C. The pH of the system was maintained at 7.5-8.0 during the reaction for 8 h.

[0134] (4) After the incubation was completed, the temperature was lowered to 25°C, and filtration, washing, and drying were performed to obtain 2-amino benzimidazole dry product. The yield was 87.2%, and the purity detected by HPLC was 92.8%.

[0135] From the experimental results of the above examples and comparative examples, it can be seen that the 2-aminobenzimidazole product with high yield and high purity can be prepared by using the preparation method of the present application, and from the experimental results of Example 3, it can be seen that the stable target product with high yield and high purity can still be obtained by using the preparation method of the present application for scale-up pilot test. From the experimental results of Example 8, it can be seen that the mother liquor produced by the preparation method of the present application can be recycled, effectively reducing the generation of wastewater, which is beneficial to environmental protection, and the preparation method of the present application is more suitable for industrialized production application.

[0136] From the comparison of the experimental results of Comparative Example 2 and Example 1, it can be seen that if the pH of the reaction system is relatively low, the yield and purity of the 2-aminobenzimidazole product will decrease, because too low pH will lead to incomplete reaction of part of the raw materials, resulting in decrease of the yield and purity of the product.

[0137] From the comparison of the experimental results of Comparative Example 3 and Example 1, it can be seen that if the pH of the reaction system is relatively high and the basicity is too strong, the yield and purity of the 2-aminobenzimidazole product will decrease, because too high pH will lead to side reactions such as basic decomposition of part of the product, thereby resulting in decrease of the yield and purity of the product.

[0138] From the comparison of the experimental results of Comparative Example 4 and Example 1, it can be seen that if the reaction time is reduced, the yield will be low, because insufficient reaction time leads to incomplete conversion of the raw materials, resulting in decrease of the product.

[0139] From the comparison of the experimental results of Comparative Example 5 and Example 1, it can be seen that if the reaction time is too long, the yield and purity of the 2-aminobenzimidazole product will decrease, because too long reaction time will lead to increase of side reactions, thereby resulting in decrease of the yield and purity of the product.

[0140] From the comparison of the experimental results of Comparative Example 6 and Example 1, it can be seen that if the reaction temperature is too low, the yield and purity of the 2-aminobenzimidazole product will decrease, because it will lead to incomplete reaction of part of the raw materials, resulting in decrease of the yield and purity of the product.

[0141] From the comparison of the experimental results of Comparative Example 7 and Example 1, it can be seen that if the reaction temperature is too high, the yield and purity of the 2-aminobenzimidazole product will decrease, because too high temperature will lead to increase of side reactions, thereby resulting in decrease of the yield and purity of the product.

[0142] The above embodiments only express several implementation manners of the present application, and the description is more specific and detailed, but it should not be understood as a limitation on the scope of the patent. It should be noted that for ordinary skilled persons in the art, without departing from the concept of the present application, several modifications and improvements can be made, which are within the scope of protection of the present application. Therefore, the protection scope of the patent of the present application should be subject to the appended claims.

Claims

1. A process for the preparation of 2-amino-benzimidazole, characterized in that, The preparation method is that o-phenylenediamine and guanidine salt are reacted in a weak alkaline water system, and after the reaction, 2-amino benzimidazole product is obtained through post-treatment. The pH of the water system is adjusted to 7.5-9.5 by adding lye, and the o-phenylenediamine and guanidine salt are reacted at a reaction temperature of 60-90 ℃ and a reaction time of 6-10 h.

2. The process for the preparation of 2-amino benzimidazole as claimed in claim 1, wherein, The guanidine salt is at least one of guanidine hydrochloride, guanidine sulfate and guanidine nitrate.

3. The process for the preparation of 2-amino benzimidazole as claimed in claim 1, wherein, The molar ratio of the o-phenylenediamine to the guanidine salt is 1: (1.1-1.5).

4. The process for the preparation of 2-amino benzimidazole as claimed in claim 1, wherein, The lye is any one of sodium hydroxide aqueous solution, potassium hydroxide aqueous solution and ammonia water.

5. The process for the preparation of 2-amino benzimidazole as claimed in claim 1, wherein, The mass concentration of the lye is 10%-30%.

6. The process for the preparation of 2-amino benzimidazole as claimed in claim 1, wherein, The preparation method is that water is added into a reactor, and o-phenylenediamine is uniformly dispersed; then guanidine salt is slowly added and uniformly dispersed, and the temperature of the system in the feeding process is controlled to be not higher than 70 ℃; lye is added to adjust the pH of the system to weak alkalinity, and then the system is heated and reacted, and after the reaction, 2-amino benzimidazole product is obtained through post-treatment.

7. The process for the preparation of 2-amino benzimidazole as claimed in claim 1, wherein, After the reaction, the system is lowered to 20-25 ℃, and 2-amino benzimidazole is obtained through solid-liquid separation, washing and drying.

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