CN109265403B - A kind of synthetic method of benzimidazole and derivative thereof - Google Patents

Abstract

The invention provides a method for synthesizing benzimidazole and derivatives thereof. The method realizes the synthesis of multifunctional benzimidazole and 2-substituted benzimidazole through the cyclization of o-phenylenediamine catalyzed by imidazole chloride. Simple, economical and practical. The present invention does not have any other catalysts or additives, and the synthesis method has good functional group tolerance, excellent yield and purity, short reaction time, no harsh reaction conditions, and is suitable for industrial production.

Description

A kind of synthetic method of benzimidazole and derivative thereof

technical field

The present invention relates to benzimidazole and derivatives thereof, in particular to a synthesis method of benzimidazole and derivatives thereof.

Background technique

Benzimidazoles are a class of benzoheterocyclic compounds containing two nitrogen atoms, which are the building blocks of many drugs. Many benzimidazole compounds have significant biological activities and have important medical value in anti-tumor, anti-cancer, anti-virus, bactericidal, anti-inflammatory and anti-parasitic aspects. At the same time, benzimidazole compounds can also be used in the fields of corrosion inhibitors, transition metal ligands, simulating natural superoxidase (SOD) biological activity, surfactant treatment agents, new curing agents for epoxy resins, and chemiluminescence. The traditional synthesis methods of benzimidazole compounds are mainly divided into two types. One is prepared by reacting o-phenylenediamine and its derivatives with carboxylic acid compounds under the action of strong acids such as hydrochloric acid or polyphosphoric acid. Usually, higher reaction temperature and longer reaction time are required, and the yield is not ideal, and the equipment requirements are high. The other is obtained by cyclization of o-phenylenediamine and its derivatives and aldehyde compounds under the action of an oxidant. The reaction process is relatively simple, but there are many side reactions and separation is difficult. In recent years, on the basis of traditional synthetic routes, a series of new synthetic routes of benzimidazole compounds using Lewis acids and transition metal complexes as catalysts have appeared one after another. In 1995, Bourguignon reported the synthesis of benzimidazoles by treating o-phenylenediamine with DMF in the presence of dichloromethane (Desaubry L, Wermuth CG, Bourguignon JJ. Tetrahedron Lett. 1995:36:4249.). Over the next few years, the above reactions have been improved by using alternative catalysts. For example, Kamble and Bhanage reported an improved method to form benzimidazole from o-phenylenediamine and DMF, respectively. In their improved method, a large amount of corrosive concentrated hydrochloric acid or metallic Zn(OAc) ₂ was used as a catalyst (Kattimani PP , Kamble RR, Meti GY. RSC Advances. 2015:5:29447.; Nale DB, Bhanage BM. Synlett. 2015:26:2835.). Yadav reported a scalable _CO2 -mediated synthesis of benzimidazole via cyclization of o-phenylenediamine with DMF under harsh reaction conditions (5 MPa and 150 °C) (Rasal KB, Yadav GD. Org. Process. Res.Dev.2016:20:2067.).). However, the utility of these methods is offset by special reactors and stoichiometric catalysts. Recently, Sun proposed a new protocol using 4 equivalents of phenylsilicon (PhSiH3) as a cocatalyst for the synthesis of benzimidazoles (Zhu J, Zhang Z, Miao C, Liu W, Sun W. Tetrahedron. 2017:73 :3458.), but the results show that this synthetic method is incompatible when extended to substrates containing electron-donating groups.

SUMMARY OF THE INVENTION

The object of the present invention is to provide a kind of synthetic method of benzimidazole and derivatives thereof, the method realizes the synthesis of multifunctional benzimidazole and 2-substituted benzimidazole through the cyclization of o-phenylenediamine catalyzed by imidazole hydrochloric acid , the method is simple, economical and practical.

The object of the present invention is achieved in this way:

A method for synthesizing benzimidazole and its derivative (formula II) is prepared from a compound of formula I and a compound of formula III under the action of a catalyst, wherein the catalyst is imidazole hydrochloric acid.

The reaction route is as follows:

in,

R ₁ is each independently hydrogen, C _1-6 alkyl, methoxy, halogen, halogen-substituted methyl, nitro;

R ₂ is each independently hydrogen, C _1-6 alkyl, phenyl, pyrrole, methoxyphenyl, p-phenylphenyl.

In the compounds of formula I and II herein, R ₁ can be independently ortho, meta or para, can be substituted at the same time as ortho, meta and para, or can be substituted independently.

Further, in the above synthesis method, the amount of catalyst imidazole hydrochloric acid used in the reaction is 0.1-0.3 equivalents (relative to o-phenylenediamine and its derivatives).

In the synthesis method of the present invention, the solvent used is selected from one or more combinations of DMF, benzene, acetonitrile and tetrahydrofuran; DMF is preferred.

In order to improve the yield and purity of the above synthesis method, the above reaction temperature is 80-140°C; preferably 120-140°C.

Specifically, a synthetic method of benzimidazole and its derivative (formula II) is prepared by the compound of formula I and the compound of formula III under the action of a catalyst, and it is characterized in that: the catalyst used in the reaction is imidazole hydrochloric acid, and its The dosage is 0.1-0.3 equivalents (relative to o-phenylenediamine and its derivatives); the solvent used in the reaction is DMF; the reaction temperature is 120-140°C;

The reaction route is as follows:

in,

R ₁ is independently hydrogen, C _1-6 alkyl, methoxy, halogen, halogen-substituted methyl, nitro; R ₂ is independently hydrogen, C _1-6 alkyl, phenyl, pyrrole, Methoxyphenyl, p-phenylphenyl.

beneficial effect

The invention provides a method for synthesizing benzimidazole and derivatives thereof (formula II). The method uses imidazole hydrochloric acid as a catalyst, and in the absence of any other catalysts or additives, is composed of o-phenylenediamine and derivatives thereof and DMF derivatives were used to synthesize benzimidazoles and 2-substituted benzimidazoles. The synthesis method of the invention has good functional group tolerance, can synthesize a large number of benzimidazole derivatives for research in medicine or other fields, and meanwhile has excellent yield and purity of the reaction, and has high process economy. Taking benzimidazole as an example, the current market price is about 120,000 yuan/ton, and the present invention can control the cost at about 40,000 yuan/ton, and has obvious economic value and cost advantage. The synthesis method of the invention does not use dichloromethane, corrosive concentrated hydrochloric acid and metal catalysts, does not require harsh reaction conditions, does not require an autoclave and a high temperature reaction of 150 DEG C, and has a short reaction time, which is suitable for industrial production.

Example

definition

The term "halogen" as used herein refers to fluorine, chlorine, bromine or iodine.

The term "C _1-6 alkyl" as used herein refers to a saturated straight or branched chain hydrocarbon group having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, n-butyl, isopropyl Butyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, etc.

The term "DMF" as used herein refers to N,N-dimethylformamide.

In order to make the objectives and technical solutions of the present invention clearer, the preferred embodiments of the present invention are described in detail below. It should be noted that the following examples are only used to further illustrate the present invention, and should not be construed as limiting the protection scope of the present invention. Some non-essential improvements and adjustments made by those skilled in the art according to the above content of the present invention belong to the protection scope of the present invention. The raw materials and reagents used in the present invention are all commercially available products.

Example 1

The compound of formula I and the compound of formula III of imidazole hydrochloride were added to a 10 mL three-neck round flask, and the resulting solution was heated and reacted with DMF as a solvent. After the reaction was completed, 25 mL of water was added, and the obtained mixture was extracted twice with 25 mL of ethyl acetate. The combined organic layers were washed sequentially with H ₂ O (50 mL), then brine (50 mL), then dried over anhydrous Na ₂ SO ₄ , filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography and recrystallized from petroleum ether and ethyl acetate or from petroleum ether/EA to give the desired product.

In the initial experiment, the inventors carried out the reaction of o-phenylenediamine and DMF to catalyze the cyclization to synthesize benzimidazole, and the results are listed in Table 1. The inventors found that under the condition of 140°C, o-phenylenediamine and DMF do not react without any additives. When imidazole is added, it is found that the yield is a trace amount, and when 0.2 equivalent of hydrochloric acid is added, it is found that the cyclization yield is 29 %. Further in the case of 0.2 equivalents, the temperature was then lowered to find that the yield was trace at 90°C. However, the coexistence of 0.2 equiv of imidazole hydrochloride and DMF significantly enhanced the reactivity, providing 95% good yield of benzimidazole at 140°C (Table 1, entries 6-8), suggesting that imidazole hydrochloride may be a Causes of DMF activation. Encouraged by this result, the inventors then tested the effect of the amount of catalyst on the reaction. Surprisingly, even with 0.1 equiv. of catalyst, the desired product could be obtained in good yield (Table 1, entry 9), demonstrating that imidazole hydrochloride is highly efficient for this reaction. Next, when the reaction temperature was varied between 30 °C and 140 °C, the conversion changed significantly, proving that higher temperature favored the reaction. Specifically, the target product was not detected at 30°C (Table 1, entry 11), and 68% of the product was isolated at 90°C (Table 1, entry 10). It was also observed that the reaction was carried out at 140°C (Table 1, entry 8) in satisfactory yield (95%). In addition, screening of reaction solvents showed that DMF was the best solvent for most reactions, with other solvents such as benzene, acetonitrile, and tetrahydrofuran having lower yields (Table 1, entries 12-15). Finally, the reaction was found to be efficient with 10 mol% catalyst in 2 mL DMF at 120°C with 94% yield of product in 6 hours. The reaction route is:

Table 1

^aReaction was performed with o-phenylenediamine (0.54 g, 5 mmol, 1 equiv), DMF (2 mL).

^b Isolated yield.

^c did not react.

^d DMF (0.46 mL, 6 mmol, 1.2 equiv), solvent (5 mL).

^etrace yield.

Next, the inventors started to study the generality of this reaction. The results, summarized in Table 2, show that this method is very general for the synthesis of benzimidazole derivatives from extensively substituted o-phenylenediamines to yield products in high yields. Specifically, o-phenylenediamines with both electron-donating and electron-withdrawing groups were well tolerated in this reaction and provided the corresponding benzimidazole derivatives in good yields (82-94 %). Mono- and di-substituents on the benzene moiety had no significant effect on the reaction results, yielding the desired products in good yields (Tables 2, 2b-2i). Notably, functional groups such as bromine (1e) or chlorine (1f) are tolerated under such conditions. Surprisingly, naphthalene-2,3-diamine also reacted efficiently and gave the desired product in 87% yield (Tables 2, 2j). Considering the synthetic usefulness of this reaction, the inventors further investigated its scalability. When the reaction was scaled up to 180 mmol (1a, 20 g scale), the desired product 2a was isolated in 90% yield. The reaction route is:

Table 2

^a Substituted o-phenylenediamine (1a-1j, 5 mmol) and DMF (2 mL) were reacted at 120° C. for 6 h, and the yield was isolated. ^b 20 gram scale, 90% yield.

Furthermore, to investigate the effect of different substituted amides on this reaction, the inventors investigated some DMF derivatives (Table 3). Although lower conversions were obtained in some cases and longer reaction times were required, the results show that the reaction is very general for a range of differently substituted amides under similar reaction conditions. Replacing H with methyl gave the corresponding products in moderate to good quality (65-84%, Tables 3, 3a-3f). However, for derivatives with ethyl groups, the substrate showed lower reactivity (Table 3, 3g, 63%). On the other hand, the aromatic-substituted substrates, reflecting the activity of the model reaction, gave poor yields (62-83%) (Tables 3, 3h-3j). N,N-Dimethyl-4-nitrobenzene with lower nucleophilicity compared to N,N-dimethyl-4-methoxybenzamide and N,N-dimethylbenzamide Formamide gave the corresponding product in lower yield. This may stem from the fact that electron withdrawing groups are not conducive to the formation of reactively activated intermediates. Furthermore, noting that the heteroaromatic substrates were also compatible, the reaction proceeded smoothly to afford 3k in 73% yield. The reaction route is:

table 3

^a The experiment was performed with o-phenylenediamine (5 mmol, 1 equiv) and DMA (2 mL) at 120° C. for 6 hours, yields isolated. . ^b reaction temperature 140 ℃. . ^c with substituted o-phenylenediamine (5 mmol, 1 equiv) and DMF derivatives (7.5 mmol, 1.5 equiv) in 5 mL of xylene at 140 ° C for 8 h, the yield was isolated. .

specific embodiment

Example 1 General method for the synthesis of benzimidazole derivatives (2a-3e)

To a 10 mL three-neck round flask was added 1a (0.54 g, 5 mmol), imidazole hydrochloric acid (0.09 g, 0.5 mmol) and 2 mL of N,N-dimethylformamide. The resulting solution was warmed to 120°C and the reaction was stirred at this temperature. TLC dot plate detection. When the reaction was complete, 25 mL of water was added and the resulting mixture was extracted twice with 25 mL of ethyl acetate. The combined organic layers were washed sequentially with H 2 O (50 mL), then brine (50 mL), then dried over anhydrous Na 2 SO 4 , filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography and recrystallized from petroleum ether and ethyl acetate or from petroleum ether/EA to give the desired product.

General Methods for Synthesis of Benzimidazole Derivatives (3f-3j)

A mixture of 1a (0.54 g, 5 mmol), imidazole hydrochloric acid (0.09 g, 0.5 mmol) and N,N-dimethylbenzamide (0.55 g, 7.5 mmol) in 5 mL of xylene was heated to 140 °C and placed in the The reaction was stirred at the temperature, checked by TLC dot plate, when the reaction was complete, 50 mL of water was added, and the resulting mixture was extracted twice with 50 mL of ethyl acetate. The combined organic layers were washed sequentially with H 2 O (50 mL), then brine (50 mL), then dried over anhydrous Na 2 SO 4 , filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using petroleum ether and ethyl acetate as eluents, or recrystallized from petroleum ether/EA to give the desired product.

NMR data of the target product

1H-benzimidazole (2a). Yellow solid (94%); ¹ H NMR (600 MHz, DMSO-d ₆ ) (δ, ppm): 12.48 (s, 1H), 8.25 (d, J=1.3 Hz, 1H ), 7.62 (dd, J=6.0, 3.4 Hz, 2H), 7.20 (dd, J=6.0, 3.1 Hz, 2H).; ¹³ CNMR (150 MHz, DMSO-d ₆ ) (δ, ppm): 142.4, 122.1 .

5-Methyl-1H-benzimidazole (2b). White solid (92%); ¹ H NMR (600 MHz, CDCl ₃ ) (δ, ppm): 9.20(s, 1H), 8.12(s, 1H), 7.60 (d, J=8.1 Hz, 1H), 7.48 (s, 1H), 7.15 (d, J=8.1 Hz, 1H), 2.50 (s, 3H).; ¹³ C NMR (150 MHz, CDCl ₃ ) (δ ,ppm): 140.5, 137.4, 136.3, 132.7, 124.4, 115.4, 114.8, 21.6.

5-Methoxy-1H-benzimidazole (2c). White solid (93%); ¹ H NMR (600 MHz, CDCl ₃ ) (δ, ppm): 8.87 (s, 1H), 8.05 (d, J= 10.8Hz, 1H), 7.56 (d, J=8.8Hz, 1H), 7.10 (d, J=2.1Hz, 1H), 6.93 (dd, J=8.8, 2.2Hz, 1H), 3.82 (s, 3H) .; ¹³ C NMR (150 MHz, CDCl ₃ ) (δ, ppm): 156.6, 140.5, 137.7, 133.0, 116.5, 112.6, 97.6, 55.8.

5,6-Dimethyl-1H-benzimidazole (2d). Yellow solid (93%); ¹ H NMR (600 MHz, CDCl ₃ ) (δ, ppm): 8.22(s, 1H), 8.01(s, 1H), 7.44 (s, 2H), 2.37 (s, 6H); ¹³ C NMR (150 MHz, CDCl ₃ ) (δ, ppm): 139.9, 136.2, 131.9, 115.5, 20.3.

5-Bromo-1H-benzimidazole (2e). White solid (88%); ¹ H NMR (600 MHz, DMSO-d ₆ ) (δ, ppm): 12.67 (s, 1H), 8.28 (d, J= 3.6Hz, 1H), 7.81 (s, 1H), 7.57 (d, J=8.4Hz, 1H), 7.34 (dd, J=8.5, 1.1Hz, 1H). ¹³ C NMR (150MHz, DMSO-d ₆ ) (δ,ppm): 143.7, 125.0, 114.4.

5-Chloro-1H-benzimidazole (2f). Yellow solid (85%); ¹ H NMR (600 MHz, DMSO-d ₆ ) (δ, ppm): 8.28 (s, 1H), 7.66 (s, 1H) , 7.60 (d, J=8.2 Hz, 1H), 7.21 (d, J=8.3 Hz, 1H).; ¹³ C NMR (150 MHz, DMSO-d ₆ ) (δ, ppm): 143.4, 126.1, 121.9, 116.3 , 115.2.

5,6-Dichloro-1H-benzimidazole (2g). Yellow solid (86%); ¹ H NMR (600 MHz, DMSO-d ₆ ) (δ, ppm): 12.74(s, 1H), 8.35(s , 1H), 7.94(s, 1H), 7.82(s, 1H).; ¹³ C NMR (150 MHz, DMSO-d ₆ ) (δ, ppm): 145.2, 143.1, 133.3, 124.9, 124.2, 120.7, 113.6.

5-Fluoro-1H-benzimidazole (2h). Grey solid (84%); ¹ H NMR (600 MHz, DMSO-d ₆ ) (δ, ppm): 12.61 (s, 1H), 8.30 (s, 1H) , 7.62 (t, J=6.4Hz, 1H), 7.43 (d, J=9.6Hz, 1H), 7.08 (td, J=9.3, 2.6Hz, 1H). ¹³ C NMR (150MHz, DMSO-d ₆ ) (δ,ppm): 159.7, 158.1, 143.8, 110.3, 100.0.

5-Trifluoromethyl-1H-benzimidazole (2i). Yellow solid (82%); ¹ H NMR (600 MHz, DMSO-d ₆ ) (δ, ppm): 12.90(s, 1H), 8.47(s , 1H), 7.99(s, 1H), 7.80(d, J=8.4Hz, 1H), 7.53(dd, J=8.5, 1.1Hz, 1H). ¹³ C NMR (150MHz, DMSO-d ₆ ) (δ ,ppm): 144.7, 127.7, 125.9, 124.1, 122.5, 122.3, 118.4.

1H-naphthimidazole (2j). Black solid (87%); ¹ H NMR (600 MHz, DMSO-d ₆ ) (δ, ppm): 12.54(s, 1H), 8.49(s, 1H), 8.12(s , 2H), 8.01 (dd, J=6.3, 3.3 Hz, 2H), 7.53–6.97 (m, 2H). ¹³ C NMR (150 MHz, DMSO-d ₆ ) (δ, ppm): 146.9, 130.1, 128.2, 123.8.

2-Methyl-1H-benzimidazole (3a). White solid (84%); ¹ H NMR (600 MHz, DMSO-d ₆ ) (δ, ppm): 12.21 (s, 1H), 7.45 (dt, J =6.8, 3.2Hz, 2H), 7.11 (ddd, J=6.0, 3.2, 1.2Hz, 2H), 2.49 (s, 3H). ¹³ C NMR (150 MHz, DMSO-d ₆ ) (δ, ppm): 151.70 ,121.48,15.10.

2-Methyl-5-chloro-1H-benzimidazole (3b). Grey solid (75%); ¹ H NMR (600 MHz, DMSO-d ₆ ) (δ, ppm): 12.38 (s, 1H), 7.50 (s, 1H), 7.45 (s, 1H), 7.12 (d, J=8.3 Hz, 1H), 2.48 (s, 3H).; ¹³ C NMR (150 MHz, DMSO-d ₆ ) (δ, ppm): 153.2, 125.7, 121.6, 15.1.

2,5-Dimethyl-1H-benzimidazole (3c). Yellow solid (77%); ¹ H NMR (600 MHz, DMSO-d ₆ ) (δ, ppm): 12.05 (s, 1H), 7.31 ( d, J=8.0Hz, 1H), 7.23(s, 1H), 6.91(dd, J=8.1, 1.0Hz, 1H), 2.45(s, 3H), 2.38(s, 3H).; ¹³ C NMR( 150MHz, DMSO-d ₆ ) (δ, ppm): 150.8, 129.9, 122.3, 21.1, 14.5.

2-Methyl-5-nitro-1H-benzimidazole (3d). Yellow solid (65%); ¹ H NMR (600 MHz, DMSO-d ₆ ) (δ, ppm): 12.94 (s, 1H), 8.37(s, 1H), 8.06(dd, J=8.7, 1.5Hz, 1H), 7.64(d, J=8.0Hz, 1H), 2.57(s, 3H).; ¹³ C NMR (150MHz, DMSO-d) ₆ ) (δ, ppm): 142.5, 117.6, 15.3.

2,5,6-Trimethyl-1H-benzimidazole (3e) ^19. White solid (75%); ¹ H NMR (600 MHz, DMSO-d ₆ ) (δ, ppm): 14.97 (s, 1H) , 7.51(s, 2H), 2.78(s, 3H), 2.36(s, 3H).; ¹³ C NMR (150MHz, DMSO-d ₆ ) (δ, ppm): 150.2, 125.0, 129.6, 113.6, 20.2, 12.5.

2-Methyl-5,6-dichloro-1H-benzimidazole (3f). White solid (69%); ¹ H NMR (600 MHz, DMSO-d ₆ ) (δ, ppm): 12.55 (s, 1H ), 7.72(s, 2H), 2.49(s, 3H).; ¹³ C NMR (150MHz, DMSO-d ₆ ) (δ, ppm): 154.9, 143.8, 134.4, 122., 121.6, 112.6, 15.1.

2-Ethyl-1H-benzimidazole (3g). Brown solid (63%); ¹ H NMR (600 MHz, DMSO-d ₆ ) (δ, ppm): 12.16 (s, 1H), 7.45 (s, 2H ), 7.10 (dd, J=5.9, 3.1 Hz, 2H), 2.82 (q, J=7.6 Hz, 2H), 1.32 (t, J=7.6 Hz, 3H).; ¹³ C NMR (150 MHz, DMSO-d ₆ ) (δ, ppm): 156.6, 144.2, 121.5, 22.4, 12.6.

2-(4-Nitrobenzene)-1H-benzimidazole (3h). Yellow solid (62%); ¹ H NMR (600 MHz, DMSO-d ₆ ) (δ, ppm): 13.31 (s, 1H), 8.64–8.19(m,4H),7.75(d,J=7.9Hz,1H),7.60(d,J=7.8Hz,1H),7.28(dt,J= ^14.8,7.0Hz ,2H).; NMR (150MHz, DMSO-d ₆ ) (δ, ppm): 149.4, 148.2, 144.3, 136.5, 135.7, 127.8, 124.7, 124.0, 122.7, 119.9, 112.2.

2-Phenyl-1H-benzimidazole (3i). White solid (77%); ¹ H NMR (600 MHz, DMSO-d ₆ ) (δ, ppm): 12.98 (s, 1H), 8.23 (d, J ＝7.9Hz, 2H), 7.64(s, 2H), 7.57(t, J＝7.6Hz, 2H), 7.51(t, J＝7.3Hz, 1H), 7.23(dd, J＝5.9, 3.1Hz, 2H) ). ¹³ C NMR (150MHz, DMSO-d ₆ ) (δ, ppm): .151.2, 130.1, 129.7, 128.9, 126.4, 122.1.

2-(4-Methoxyphenyl)-1H-benzimidazole (3j). White solid (83%); ¹ H NMR (600 MHz, DMSO-d ₆ ) (δ, ppm): 12.75 (s, 1H) ,8.12(d,J＝8.7Hz,2H),7.62(d,J＝7.5Hz,1H),7.50(d,J＝7.5Hz,1H),7.27-7.14(m,2H),7.12(d, J=8.7 Hz, 2H), 3.84 (s, 3H).; ¹³ C NMR (150 MHz, DMSO-d ₆ ) (δ, ppm): 161.0, 151.8, 144.3, 135.4, 128.4, 123.1, 121.9, 118.9, 114.8 , 111.4, 55.8.

2-(2-pyridine)-1H-benzimidazole (3k). White solid (73%); ¹ H NMR (600 MHz, DMSO-d ₆ ) (δ, ppm): δ 13.14 (s, 1H), 8.75(d,J＝4.6Hz,1H),8.35(d,J＝7.8Hz,1H),8.01(t,J＝7.4Hz,1H),7.73(d,J＝7.9Hz,1H),7.66– 7.42 (m, 2H), 7.21–7.24 (m, 2H). ¹³ C NMR (150 MHz, DMSO-d ₆ ) (δ, ppm): 151.2, 149.8, 149.0, 144.3, 138.0, 135.4, 125.1, 123.5, 122.3 ,121.8,119.7,112.5.

Claims (3)

1. a synthetic method of benzimidazole and derivative formula II thereof, obtained by compound of formula I and compound of formula III under catalyst action, it is characterized in that: the used catalyst of reaction is imidazole hydrochloric acid, and its consumption is relative to formula For compound I, it is 0.1-0.3eq; the solvent used in the reaction is DMF; the reaction temperature is 120-140°C; The reaction route is as follows:

in, R ₁ is independently hydrogen, C _1-6 alkyl, methoxy, halogen, halogen-substituted methyl, nitro; R ₂ is independently hydrogen, C _1-6 alkyl, phenyl, pyrrole, Methoxyphenyl, p-phenylphenyl. 2. The method of claim 1, wherein the halogen is selected from the group consisting of fluorine, chlorine, bromine or iodine. 3. method as claimed in claim 1 is characterized in that: described C _1-6 alkyl is selected from methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl.