CN110759903B - Novel synthesis method of thiabendazole - Google Patents

Novel synthesis method of thiabendazole Download PDF

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CN110759903B
CN110759903B CN201810840744.2A CN201810840744A CN110759903B CN 110759903 B CN110759903 B CN 110759903B CN 201810840744 A CN201810840744 A CN 201810840744A CN 110759903 B CN110759903 B CN 110759903B
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汪清民
王兹稳
李刚
刘玉秀
宋红健
李永强
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Nankai University
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    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
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Abstract

The invention relates to a new drug synthesis route with the common name of thiabendazole, which takes thiazole-4-formaldehyde as a raw material, condenses with hydroxylamine hydrochloride to obtain thiazole-4-formaldehyde oxime, reacts with aniline to obtain N-phenylthiazole-4-methylamine oxime after NCS chlorination, then reacts with p-trifluoromethyl benzoyl chloride to obtain amidoxime ester, and finally adopts free radical reaction of visible light catalysis to close a ring to obtain the thiabendazole. The invention firstly transports the free radical reaction of visible light catalysis to the synthesis of thiabendazole, avoids the reaction conditions of high temperature and strong acid in the traditional synthesis method, and the reaction is more green and mild. The method has broad spectrum and can be used for synthesizing imidazole compounds Ia-Ial.

Description

Novel synthesis method of thiabendazole
Technical Field
The invention relates to a new drug synthesis route with the general name of thiabendazole and application of the route in imidazole heterocyclic synthesis, belonging to the technical field of organic chemistry.
Background
Thiabendazole, which is chemically named 2- (4-thiazolyl) -1H-benzimidazole, is also called thiabendazole and thiabendazole, has been found to have good insect-repellent effect initially, and is used as a broad-spectrum insect-repellent. Later, the compounds are used as broad-spectrum bactericides because the compounds can prevent and control fungal diseases of various plants. In recent ten years, thiabendazole has the functions of preserving fruits and vegetables, preserving foods, preventing mildew of articles for daily use and the like, and becomes an excellent mildew-proof preservative.
So far, a number of literature patents have reported methods for synthesizing thiabendazole. The traditional method comprises three steps: 1) Condensing o-phenylenediamine, thiazole-4-carboxylic acid and derivatives thereof at high temperature under the action of acid; 2) Condensing o-phenylenediamine and thiazole-4-carbonitrile under the catalysis of trifluoromethanesulfonic anhydride; 3) The o-phenylenediamine and the thiazole-4-formaldehyde are oxidized and condensed under the action of an oxidant. As early as 1961, brown et al (Brown, H.D.et al.J.am.chem.Soc.,1961, 83, 1764-1765) reported a synthetic route as shown in equation one, i.e., thiazole-4-carboxamide, o-phenylenediamine and polyphosphoric acid were reacted at a high temperature of 250 ℃ for 3 hours to condense to give thiabendazole.
Figure BSA0000167897780000011
In 1965, grenda et al (Grenda, V.J.et al.J.org.chem.,1965, 30, 259-261) used N-phenylthiazole-4-carboxamidine hydrochloride as the starting material, and treatment of the Guan Benbing imidazole ring with sodium hypochlorite under alkaline conditions gave thiabendazole in higher yields, a significant improvement over the Brown process (as shown in equation two).
Figure BSA0000167897780000012
In 1994, duPont applied for invention patent (US 5310923A, US 5310924A) reported a process for the preparation of thiabendazole by reacting o-phenylenediamine with thiazole-4-carbonitrile and o-phenylenediamine. The patent relates to two reaction conditions, one is that water, n-butanol and vitamin C system are used, and trifluoromethane sulfonic anhydride is used for catalysis; the second is to use a system of water, methanol plus vitamin C and EDTA, maintaining the acidity of the system with hydrochloric acid. Both conditions allow the synthesis of thiabendazole in higher yields, but heating and the use of acid are unavoidable (as shown in equation three).
Figure BSA0000167897780000013
Figure BSA0000167897780000021
In 2015, meng Xiangbao et al (Meng X.et al. Bioorg.Med.chem.,2015, 23, 3774-3780) reported a method for synthesizing thiabendazole by the thermal condensation oxidation of thiazole-4-carboxaldehyde and o-phenylenediamine under the action of sodium metabisulfite. The reaction requires an excess of oxidant (as shown in equation four).
Figure BSA0000167897780000022
In 2015, bi Haidong (CN 104557902A) invented a new method for preparing thiabendazole. They are prepared by reacting acetone, which is a basic chemical raw material, with chlorine to obtain monochloroacetone, then closing a ring with thiourea to obtain 2-amino-4-methylthiazole, removing amino through diazotization, oxidizing methyl to obtain thiazole-4-formic acid, and then condensing with o-phenylenediamine and polyphosphoric acid at high temperature. The route is suitable for industrial large-scale production, but generates a large amount of waste acid and high-temperature energy consumption (as shown in a reaction formula five).
Figure BSA0000167897780000023
Although various methods for synthesizing thiabendazole have been reported, they generally have the characteristics of requiring acidic conditions, high heating temperature or excessive oxidizing agent, relatively strong reaction conditions and waste acid pollution, so that development of new synthetic methods and realization of green and efficient synthesis of thiabendazole are required.
Disclosure of Invention
The invention provides a novel synthesis method of Thiabendazole (1) (Thiabendazole, chemical name is 2- (4-thiazolyl) -1H-benzimidazole).
The specific synthetic route of the thiabendazole is shown as a reaction formula VI:
Figure BSA0000167897780000024
the invention comprises the following steps:
1. the intermediate 4 is synthesized by a commercial reagent thiazole-4-formaldehyde (1) through three-step reaction, and the alkali which can be used for obtaining the intermediate 4 by reacting the intermediate 3 with aniline comprises the following steps: pyridine, triethylamine, diisopropylethylamine, N-ethylpiperidine and triethylene diamine, and usable solvents include: diethyl ether, methyl tert-butyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane.
2. Intermediate 4 is reacted with p-trifluoromethylbenzoyl chloride to produce intermediate 5, and useful bases include: pyridine, triethylamine, diisopropylethylamine, N-ethylpiperidine, N-methylmorpholine, and useful solvents include: tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, dichloromethane, 1,2-dichloroethane.
3. Intermediate 5 in photocatalyst Ir [ dF (CF) 3 )ppy] 2 (dtbbpy)PF 6 The target compound I is obtained by visible light irradiation reaction under the action of the solvent, and the solvent comprises: n, N-dimethylformamide, N-diethylformamide, N-dimethylacetamide, dimethylsulfoxide, acetonitrile, acetone, dichloromethane, 1,2-dichloroethane, methyl t-butyl ether, tetrahydrofuran, 1,4-dioxane, and useful light sources include: white LED lamps of different wattages, blue LED lamps of different wattages, white CFL lamps of different wattages.
The invention firstly transports the free radical reaction of visible light catalysis to the synthesis of thiabendazole, avoids the reaction conditions of high temperature and strong acid in the traditional synthesis method, and the reaction is more green and mild.
The method has broad spectrum, can also be used for synthesizing imidazole compounds Ia-Ial, as shown in a reaction formula seven, 4a-4al can be directly synthesized without purification in the first three steps of reaction, then 5a-5al is obtained by introducing a guide group, and then Ia-Ial and R are obtained by ring closure under the condition of illumination 1 And R 2 The indicated groups are shown in the specific compound structure in the second embodiment.
Figure BSA0000167897780000031
The specific implementation mode is as follows:
the following examples are intended to further illustrate the invention but are not intended to limit the invention.
The first embodiment is as follows: synthesis of thiabendazole
And (3) synthesis of an intermediate 2:
thiazole-4-carbaldehyde (1) (2.26g, 20mmol) and ethanol (40 mL) were charged into a 100mL round-bottomed flask, and hydroxylamine hydrochloride (1.47g, 21mmol) and pyridine (1.67g, 21mmol) were added under stirring at room temperature, and after the addition, reaction was carried out for 1697 hours and TLC detection was carried out. The reaction solution was concentrated under reduced pressure, diluted with 50mL of ethyl acetate, poured into a separatory funnel, added with 30mL of saturated sodium carbonate solution, extracted, separated, the aqueous phase extracted with ethyl acetate (50 mL × 2), the organic phases combined, washed with saturated brine, dried over anhydrous sodium sulfate, and desolventized under reduced pressure to give 2.60g of a yellow solid with a yield of 99%. E/Z = 2: 1,E configuration: 1 H NMR(400MHz，CDCl 3 ) δ 10.72 (brs, 1H), 8.86 (d, J =2.0hz, 1h), 8.47 (d, J =2.0hz, 1h), 7.91 (s, 1H). Z configuration: 1 H NMR(400MHz，CDCl 3 )δ8.90(d，J＝2.0Hz，1H)，8.37(s，1H)，7.65(d，J＝2.0Hz，1H).
synthesis of intermediate 3:
thiazole-4-carbaldehyde oxime (2) (0.52g, 4.1 mmol) and DMF (4.1 mL) were added to a 25mL round bottom flask, cooled in an ice bath, added with 1/5 NCS (0.116g, 0.86mmol), reacted at 0 ℃ for 1h, then added with the rest NCS (0.464g, 3.5 mmol) in portions, allowed to warm up naturally, reacted for 2h, and a large amount of solid precipitated. 14mL of water was added, the reaction quenched and filteredThe filter cake was washed with 5mL of water and dried to give 0.55g of a white solid with a yield of 83%. 1 H NMR(400MHz，DMSO-d 6 )δ12.44(s，1H)，9.19(d，J＝2.0Hz，1H)，8.16(d，J＝2.0Hz，1H). 13 C NMR(100MHz，DMSO-d 6 )δ155.4，148.3，130.9，121.0.
Synthesis of intermediate 4:
in a 100mL round bottom flask was added chlorothiazole-4-carbaldehyde oxime (3) (0.54g, 3.3 mmol), protected with Ar, THF (20 mL) and aniline (0.325g, 3.3 mmol) were injected, triethylamine (0.68g, 6.6 mmol) was injected with stirring at room temperature, and the reaction was allowed to warm to 60 ℃ overnight. And (3) cooling the reaction liquid, performing suction filtration, washing a filter cake by using 10mL of tetrahydrofuran, performing decompression desolventization on a mother solution, and performing column chromatography on a crude product to obtain 0.34g of yellow solid with the yield of 47%. E/Z = 7.6: 1,E configuration: 1 H NMR(400MHz，CDCl 3 )δ8.75(s，1H)，7.58(s，1H)，7.14(t，J＝7.6Hz，2H)，6.97(t，J＝7.2Hz，1H)，6.72(d，J＝8.0Hz，2H). 13 C NMR(100MHz，CDCl 3 )δ153.0，147.5，146.8，139.6，128.8，123.2，121.3，120.1.HR-MS(ESI)：Calcd for C 10 H 10 N 3 Os[M+H] + 220.0539，found 220.0542.
synthesis of intermediate 5:
intermediate 4 (0.219g, 1mmol) amidoxime was added to a 100mL round-bottomed flask, dissolved in 10mL redistilled dichloromethane, 1.2mmol triethylamine was added, the mixture was cooled in ice bath, then 5mL dichloromethane solution containing 1.1mmol p-trifluoromethylbenzoyl chloride was slowly added dropwise, the reaction was carried out for 1h in ice bath, and TLC was monitored. Adding 25mL saturated sodium bicarbonate solution, extracting, separating, extracting the water phase with dichloromethane (40 mL × 2), combining the organic layers, washing with saturated salt water, drying with anhydrous sodium sulfate, desolventizing under reduced pressure, and performing silica gel column chromatography to obtain 0.32g of intermediate 5, which is a white solid, with the yield of 82% and the melting point of 150-151 ℃. 1 H NMR(400MHz，CDCl 3 )δ8.80(d，J＝2.0Hz，1H)，8.19(d，J＝2.0Hz，1H)，7.84(s，1H)，7.54(d，J＝8.8Hz，2H)，7.51(d，J＝8.8Hz，2H)，7.27(t，J＝7.6Hz，2H)，7.16-7.10(m，3H). 13 C NMR(100MHz，CDCl 3 )δ162.6，152.8，149.0，147.0，139.5，134.3(q，J＝32.5Hz)，132.2，129.8，128.9，125.2，125.1(q，J＝3.5Hz)，123.8，123.6(q，J＝271.1Hz)，120.9.HR-MS(ESI)：Calcd for C 18 H 13 F 3 N 3 O 2 S[M+H] + 392.0675，found 392.0677.
Synthesis of target compound I:
a25 mL Schlenk tube was charged with 0.2mmol of intermediate 5,1% photocatalyst Ir [ dF (CF) 3 )ppy] 2 (dtbbpy)PF 6 The reaction vessel is sealed, an argon balloon is inserted, gas is replaced for three to four times, then 1mL of methyl tert-butyl ether is injected, and the reaction vessel is placed in a photoreactor to be irradiated for room temperature reaction for 36h. After the reaction is finished, 15mL of ethyl acetate is added to dilute the reaction solution, the diluted solution is poured into a separating funnel, 10mL of saturated sodium carbonate solution is added to extract and separate the solution, the aqueous phase is extracted by ethyl acetate (20 mL multiplied by 2), the organic layers are combined, washed by saturated sodium chloride, dried by anhydrous sodium sulfate, desolventized under reduced pressure, and the crude product is separated by column chromatography to obtain 16mg of a target product I, namely a white solid, the yield is 40%, and the melting point is 297-298 ℃. 1 H NMR(400MHz，DMSO-d 6 )δ12.97(s，1H)，9.34(d，J＝1.8Hz，1H)，8.45(d，J＝1.8Hz，1H)，7.66(d，J＝7.2Hz，1H)，7.52(d，J＝7.2Hz，1H)，7.27-7.16(m，2H). 13 C NMR(100MHz，DMSO-d 6 )δ156.1，147.6，147.5，144.2，134.8，123.1，122.2，119.9，119.2，112.2.HR-MS(ESI)：Calcd for C 10 H 8 N 3 S[M+H] + 202.0433，found 202.0434.
Example two: extension of the Synthesis method, synthesis of Ia-Ial
The synthesis procedure is the same as in example one, and the compound data are as follows:
(E)-N′-hydroxy-N-phenylbenzimidamide(4a)
Figure BSA0000167897780000051
152.0，139.7，131.1，129.7，128.8，128.4，128.4，122.7，121.3.
(E)-N′-hydroxy-4-methyl-N-phenylbenzimidamide(4b)
Figure BSA0000167897780000052
128.3，128.0，122.7，121.4，21.4.HR-MS(ESI)：Calcd for C 14 H 15 N 2 O[M+H] + 227.1179，found 227.1180.
(E)-N′-hydroxy-4-methoxy-N-phenylbenzimidamide(4c)
Figure BSA0000167897780000053
160.7，151.7，139.9，129.8，128.7，123.4，122.6，121.3，113.8，55.3.HR-MS(ESI)：Calcd for C 14 H 15 N 2 O 2 [M+H] + 243.1128，found 234.1129.
(E)-4-cyano-N′-hydroxy-N-phenylbenzimidamide(4d)
Figure BSA0000167897780000054
150.7，139.0，135.7，132.2，129.1，128.9，123.6，121.7，118.3，113.3.HR-MS(ESI)：Calcd for C 14 H 12 N 3 O[M+H] + 238.0975，found 238.0975.
(E)-N′-hydroxy-4-nitro-N-phenylbenzimidamide(4e)
Figure BSA0000167897780000055
(100MHz，CDCl 3 )δ150.5，148.4，138.9，137.5，129.2，129.2，123.7，123.7，121.8.HR-MS(ESI)：Calcd for C 13 H 12 N 3 O 3 [M+H] + 258.0873，found 258.0874.
(E)-4-fluoro-N′-hydroxy-N-phenylbenzimidamide(4f)
Figure BSA0000167897780000061
139.5，130.4(d，J＝8.3Hz)，128.9，127.1(d，J＝3.0Hz)，123.0，121.6，115.6(d，J＝21.7Hz).HR-MS(ESI)：Calcd for C 13 H 12 FN 2 O[M+H] + 231.0928，found 231.0930.
(E)-4-chloro-N′-hydroxy-N-phenylbenzimidamide(4g)
Figure BSA0000167897780000062
129.7，129.6，128.9，128.8，123.1，121.6.HR-MS(ESI)：Calcd for C 13 H12ClN2O[M+H] + 247.0633，found 247.0635.
(E)-4-bromo-N′-hydroxy-N-phenylbenzimidamide(4h)
Figure BSA0000167897780000063
131.7，130.1，129.9，128.9，124.1，123.1，121.6.HR-MS(ESI)：Calcd for C 13 H 12 BrN 2 O[M+H] + 291.0128，found 291.0124.
(E)-N′-hydroxy-N-phenyl-4-(trifluoromethoxy)benzimidamide(4i)
Figure BSA0000167897780000064
150.2，139.3，130.0，129.6，128.9，123.2，121.6，120.7.HR-MS(ESI)：Calcd for C 14 H 12 F 3 N 2 O 2 [M+H] + 297.0845，found 297.0846.
(E)-3-chloro-N′-hydroxy-N-phenylbenzimidamide(4j)
Figure BSA0000167897780000065
(100 MHz，CDCl 3 )δ151.0，139.3，134.4，133.0，129.8，129.6，128.9，128.4，126.7，123.3，121.5.HR-MS(ESI)：Calcd for C 13 H 12 ClN 2 O[M+H] + 247.O633，found 247.0634.
(E)-2-chloro-N′-hydroxy-N-phenylbenzimidamide(4k)
Figure BSA0000167897780000066
131.8，131.0，130.5，130.0，128.8，126.9，123.1，120.8.HR-MS(ESI)：Calcd for C 13 H 12 ClN 2 O[M+H] + 247.0633，found 247.0634.
(E)-N′-hydroxy-N-phenylbenzo[d][1，3]dioxole-5-carboximidamide(4l)
Figure BSA0000167897780000071
151.7，148.9，147.6，139.8，128.8，124.9，122.8，122.7，121.2，108.7，108.4，101.4.HR-MS(ESI)：Calcd for C 14 H 13 N 2 O 3 [M+H] + 257.0921，found 257.0923.
(E)-N′-hydroxy-N-phenyl-[1，1′-biphenyl]-4-carboximidamide(4m)
Figure BSA0000167897780000072
140.2，139.6，129.6，128.9，128.8，127.7，127.1，127.1，122.9，121.5.HR-MS(ESI)：Calcd for C 19 H 17 N 2 O[M+H] + 289.1335，found 289.1335.
(E)-N′-hydroxy-N-phenyl-2-naphthimidamide(4n)
Figure BSA0000167897780000073
6.70(d，J＝7.6Hz，2H). 13 C NMR(100 MHz，DMSO-d 6 )δ149.6，142.0，133.5，133.0，131.0，128.9，128.7，128.2，128.0，127.4，127.1，126.9，125.7，121.0，120.1.HR-MS(ESI)：Calcd for C 17 H 15 N 2 O[M+H] + 263.1179，found 263.1183.
Methyl(E)-4-(N′-hydroxy-N-phenylcarbamimidoyl)benzoate(4o)
Figure BSA0000167897780000074
13 C NMR(100 MHz，CDCl 3 )δ166.6，151.3，139.3，135.5，131.1，129.7，128.9，128.4，123.2，121.6，52.3.HR-MS(ESI)：Calcd for C 15 H 15 N 2 O 3 [M+H] + 271.1077，found 271.1079.
(E)-N-(4-(N′-hydroxy-N-phenylcarbamimidoyl)phenyl)acetamide(4p)
Figure BSA0000167897780000075
13 C NMR(100 MHz，CDCl 3 )δ168.6，151.7，139.6，139.3，129.1，128.8，126.6，122.8，121.4，119.3，24.6.HR-MS(ESI)：Calcd for C 15 H 16 N 3 O 2 [M+H] + 270.1237，found 270.1238.
Ethyl(E)-2-(hydroxyimino)-2-(phenylamino)acetate(4q)
Figure BSA0000167897780000076
143.3，139.1，128.9，124.0，121.1，62.4，13.8.HR-MS(ESI)：Calcd for C 10 H 13 N 2 O 3 [M+H] + 209.0921，found 209.0922.
(E)-N′-hydroxy-N-phenylpivalimidamide(4r)
Figure BSA0000167897780000081
28.2.HR-MS(ESI)：Calcd for C 11 H 17 N 2 O[M+H] + 193.1335，found 193.1335.
(E)-N′-hydroxy-N-(p-tolyl)benzimidamide(4aa)
Figure BSA0000167897780000082
152.2，137.1，132.4，131.2，129.6，129.3，128.5，128.4，121.7，20.7.HR-MS(ESI)：Calcd for C 14 H 15 N 2 O[M+H] + 227.1179，found 227.1181.
(E)-N′-hydroxy-N-(4-methoxyphenyl)benzimidamide(4ab)
Figure BSA0000167897780000083
128.3，123.9，114.0，55.4.HR-MS(ESI)：Calcd for C 14 H 15 N 2 O 2 [M+H] + 243.1128，found 243.1128.(E)-N-(4-(tert-butyl)phenyl)-N′-hydroxybenzimidamide(4ac)
Figure BSA0000167897780000084
129.6，128.5，128.4，125.6，120.9，34.2，31.4.HR-MS(ESI)：Calcd for C 17 H 21 N 2 O[M+H] + 269.1648，found 269.1652.
(E)-N-(4-fluorophenyl)-N′-hydroxybenzimidamide(4ad)
Figure BSA0000167897780000085
130.8，129.8，128.5，123.4(d，J＝8.0Hz)，115.50(d，J＝22.5Hz).HR-MS(ESI)：Calcd for C 13 H 12 FN 2 O[M+H] + 231.0928，found 231.0928.
(E)-N-(4-chlorophenyl)-N′-hydroxybenzimidamide(4ae)
Figure BSA0000167897780000086
122.4.HR-MS(ESI)：Calcd for C 13 H 12 ClN 2 O[M+H] + 247.0633，found 247.0633.
Figure BSA0000167897780000087
-7.36(m，3H)，7.35-7.30(m，2H)，7.20(d，J＝8.8Hz，2H)，6.52(d，J＝8.8Hz，2H). 13 C NMR(100 MHz，CDCl 3 )δ151.5，138.8，131.8，130.6，130.0，128.6，128.3，122.7，115.5.HR-MS(ESI)：Calcd for C 13 H 12 BrN 2 O[M+H] + 291.0128，found 291.0119.
(E)-N′-hydroxy-N-(m-tolyl)benzimidamide(4ag)
Figure BSA0000167897780000091
(100 MHz，CDCl 3 )δ152.1，139.6，138.7，131.2，129.6，128.5，128.4，123.5，121.9，118.4，21.3.HR-MS(ESI)：Calcd for C 14 H 15 N 2 O[M+H] + 227.1179，found 227.1183.
(E)-N′-hydroxy-N-(o-tolyl)benzimidamide(4ah)
Figure BSA0000167897780000092
152.7，138.1，131.33，130.5，129.8，129.6，128.3，128.2，126.1，123.7，123.5，18.0.HR-MS(ESI)：Calcd for C 14 H 15 N 2 O[M+H] + 227.1179，found 227.1181.
(E)-N-(benzo[d][1，3]dioxol-5-yl)-N′-hydroxybenzimidamide(4ai)
Figure BSA0000167897780000093
DMSO-d 6 )δ150.2，147.4，142.2，136.4，133.3，129.3，128.6，128.3，113.9，108.1，103.3，101.2.HR-MS(ESI)：Calcd for C 14 H 13 N 2 O 3 [M+H] + 257.0921，found 257.0921.
(E)-N-(3，4-dichlorophenyl)-N′-hydroxybenzimidamide(4aj)
Figure BSA0000167897780000094
132.5，130.3，130.2，130.2，128.8，128.2，126.0，122.4，120.3.HR-MS(ESI)：Calcd for C 13 H 11 C 12 N 2 O[M+H] + 281.0243，found 281.0245.
(E)-N-(3，5-dimethylphenyl)-N′-hydroxybenzimidamide(4ak)
Figure BSA0000167897780000095
128.3，124.4，119.1，21.2.HR-MS(ESI)：Calcd for C 15 H 17 N 2 O[M+H] + 241.1335，found 241.1333.
(E)-N-(2，4-dimethoxyphenyl)-N′-hydroxybenzimidamide(4al)
Figure BSA0000167897780000096
J＝8.8Hz，1H)，6.13(dd，J＝8.8，2.4Hz，1H)，3.80(s，3H)，3.70(s，3H). 13 C NMR(100 MHz，CDCl 3 )δ156.2，152.4，151.7，131.6，129.4，128.4，128.2，122.9，122.4，103.3，99.0，55.6，55.4.HR-MS(ESI)：Calcd for C 15 H 17 N 2 O 3 [M+H] + 273.1234，found 273.1233.
(E)-N-phenyl-N′-((4-(trifluoromethyl)benzoyl)oxy)benzimidamide(5a)
Figure BSA0000167897780000101
138.7，134.5(q，J＝32.7Hz)，132.7，130.8，130.0，129.6，129.4，129.0，128.5，125.5(J＝3.2Hz)，124.5，123.6(q，J＝270.9Hz)，123.1.HR-MS(ESI)：Calcd for C 21 H 16 F 3 N 2 O 2 [M+H] + 385.1158，found 385.1159.
(E)-4-methyl-N-phenyl-N′-((4-(trifluoromethyl)benzoyl)oxy)benzimidamide(5b)
Figure BSA0000167897780000102
(ESI)：Calcd for C 22 H 18 F 3 N 2 O 2 [M+H] + 399.1315，found 399.1318.
(E)-4-methoxy-N-phenyl-N′-((4-(trifluoromethyl)benzoyl)oxy)benzimidamide(5c)
Figure BSA0000167897780000103
130.9，129.9，129.0，125.5(q，J＝3.7Hz)，124.3，123.6(q，J＝271.0Hz)，122.9，121.6，113.9，55.3.HR-MS(ESI)：Calcd for C 22 H 18 F 3 N 2 O 3 [M+H] + 415.1264，found 415.1263.
(E)-4-cyano-N-phenyl-N′-((4-(trifluoromethyl)benzoyl)oxy)benzimidamide(5d)
Figure BSA0000167897780000104
136.0，133.1，133.0(q，J＝31.8Hz)，132.8，130.93，130.6，129.2，126.0(q，J＝3.7Hz)，124.6，124.2，124.2(q，J＝271.7Hz)，118.7，113.4.HR-MS(ESI)：Calcd for C 22 H 15 F 3 N 3 O 2 [M+H] + 410.1111，found 410.1113.
Figure BSA0000167897780000105
J＝8.4Hz，2H)，8.16(d，J＝8.8Hz，2H)，7.75(d，J＝8.4Hz，2H)，7.71(d，J＝8.8Hz，2H)，7.33(s，1H)，7.22(t，J＝7.6Hz，2H)，7.11(t，J＝7.2Hz，1H)，6.84(d，J＝7.6Hz，2H). 13 C NMR(100 MHz，CDCl 3 )δ162.6，155.3，149.0，137.7，136.0，134.9(q，J＝32.7Hz)，132.2，130.5，130.0，129.4，125.7(q，J＝3.5Hz)，125.5，123.6，123.6，123.5(q，J＝271.1Hz).HR-MS(ESI)：Calcd for C 21 H 15 F 3 N 3 O 4 [M+H] + 430.1009，found 430.1013.
(E)-4-fluoro-N-phenyl-N′-((4-(trifluoromethyl)benzoyl)oxy)benzimidamide(5f)
Figure BSA0000167897780000111
Hz)，130.0，129.1，125.6(q，J＝3.5Hz)，124.8，123.5(q，J＝271.2Hz)，123.2，115.7(d，J＝21.9Hz).HR-MS(ESI)：Calcd for C 21 H 15 F 4 N 2 O 2 [M+H] + 403.1064，found 403.1068.
(E)-4-chloro-N-phenyl-N′-((4-(trifluoromethyl)benzoyl)oxy)benzimidamide(5g)
Figure BSA0000167897780000112
135.2，132.8(q，J＝31.8Hz)，132.8，131.0，130.37，129.6，128.6，128.5，125.5(q，J＝3.6Hz)，123.8，123.7(q，J＝271.3Hz)，123.4.HR-MS(ESI)：Calcd for C 21 H 15 ClF 3 N 2 O 2 [M+H] + 419.0769，found 419.0771.
(E)-4-bromo-N-phenyl-N′-((4-(trifluoromethyl)benzoyl)oxy)benzimidamide(5h)
Figure BSA0000167897780000113
125.4，124.9，123.5(q，J＝271.0Hz)，123.2.HR-MS(ESI)：Calcd for C 21 H 15 BrF 3 N 2 O 2 [M+H] + 463.0264，found 463.0262.
(E)-N-phenyl-4-(trifluoromethoxy)-N′-((4-(trifluoromethyl)benzoyl)oxy)benzimidamide(5i)
Figure BSA0000167897780000114
125.6(q，J＝3.7Hz)，125.0，123.5(q，J＝271.0Hz)，123.3，120.7，120.3(q，J＝256.8Hz).HR-MS(ESI)：Calcd for C 22 H 15 F 6 N 2 O 3 [M+H] + 469.0981，found 469.0984.
(E)-3-chloro-N-phenyl-N′-((4-(trifluoromethyl)benzoyl)oxy)benzimidamide(5j)
Figure BSA0000167897780000121
129.7，129.4，129.2，127.6，125.6(q，J＝3.6Hz)，125.0，123.5(q，J＝271.2Hz)，123.2.HR-MS(ESI)：Calcd for C 21 H 15 ClF 3 N 2 O 2 [M+H] + 419.0769，found 419.0771.
(E)/(Z)-2-chloro-N-phenyl-N′-((4-(trifluoromethyl)benzoyl)oxy)benzimidamide(5k)
Figure BSA0000167897780000122
32.8Hz)，133.8，132.4，131.8，130.1，130.0，130.90，129.6，128.9，127.0，125.6(q，J＝3.7Hz)，125.3，123.6(q，J＝271.4Hz)，123.2.HR-MS(ESI)：Calcd for C 21 H 15 ClF 3 N 2 O 2 [M+H] + 419.0769，found 419.0773.
(E)-N-phenyl-N′-((4-(trifluoromethyl)benzoyl)oxy)benzo[d][1，3]dioxole-5-carboximidamide(5l)
Figure BSA0000167897780000123
271.0Hz)，123.1，122.8，109.5，108.4，101.6.HR-MS(ESI)：Calcd for C 22 H 16 F 3 N 2 O 4 [M+H] + 429.1057，found 429.1060.
(E)-N-phenyl-N′-((4-(trifluoromethyl)benzoyl)oxy)-[1，1′-biphenyl]-4-carboximidamide(5m)
Figure BSA0000167897780000124
123.0.HR-MS(ESI)：Calcd for C 27 H 20 F 3 N 2 O 2 [M+H] + 461.1471，found 461.1472.
(E)-N-phenyl-N′-((4-(trifluoromethyl)benzoyl)oxy)-2-naphthimidamide(5n)
Figure BSA0000167897780000125
125.6(q，J＝3.5Hz)，125.6，124.5，123.6(q，J＝271.1Hz)，123.0.HR-MS(ESI)：Calcd for C 25 H 18 F 3 N 2 O 2 [M+H] + 435.1315，found 435.1312.
Methyl(E)-4-(N-phenyl-N′-((4-(trifluoromethyl)benzoyl)oxy)carbamimidoyl)benzoate(5o)
Figure BSA0000167897780000131
162.7，156.3，138.2，134.7(q，J＝32.5Hz)，134.0，132.4，132.0，130.0，129.7，129.5，129.2，125.6(q，J＝3.5Hz)，125.0，123.5(q，J＝271.0Hz)，123.3，52.4.HR-MS(ESI)：Calcd for C 23 H 18 F 3 N 2 O 4 [M+H] + 443.1213，found 443.1217.
(E)-N-(4-(N-phenyl-N′-((4-(trifluoromethyl)benzoyl)oxy)carbamimidoyl)phenyl)acetamide(5p)
Figure BSA0000167897780000132
130.8，130.3，129.0，126.0(q，J＝3.7Hz)，125.2，124.2(q，J＝271.2Hz)，123.8，123.4，118.8，24.6.HR-MS(ESI)：Calcd for C 23 H 19 F 3 N 3 O 3 [M+H] + 442.1373，found 442.1368.
Ethyl(E)-2-(phenylamino)-2-(((4-(trifluoromethyl)benzoyl)oxy)imino)acetate(5q)
Figure BSA0000167897780000133
145.1，138.3，134.6(q，J＝32.7Hz)，131.6，129.9，129.1，126.0，125.2(q，J＝3.7Hz)，124.0，123.5(q，J＝272.8Hz)，63.9，14.0.HR-MS(ESI)：Calcd for C 18 H 16 F 3 N 2 O 4 [M+H] + 381.1057，found 381.1056.
(E)-N-phenyl-N′-((4-(trifluoromethyl)benzoyl)oxy)pivalimidamide(5r)
Figure BSA0000167897780000134
27.6.HR-MS(ESI)：Calcd for C 19 H 20 F 3 N 2 O 2 [M+H] + 365.1471，found 365.1472.
Figure BSA0000167897780000135
MHz，DMSO-d 6 )δ163.1，157.3，137.6，133.4，133.3，132.8(q，J＝31.3Hz)，131.3，130.9，130.8，129.7，129.5，128.8，125.9(q，J＝3.6Hz)，124.2(q，J＝270.9Hz)，124.1，20.7.HR-MS(ESI)：Calcd for C 22 H 18 F 3 N 2 O 2 [M+H] + 399.1315，found 399.1319.
(E)-N-(4-methoxyphenyl)-N′-((4-(trifluoromethyl)benzoyl)oxy)benzimidamide(5ab)
Figure BSA0000167897780000141
131.3，130.9，130.6，129.7，128.7，126.3，125.9(q，J＝3.8Hz)，124.3(q，J＝270.9Hz)，114.2，55.6.HR-MS(ESI)：Calcd for C 22 H 18 F 3 N 2 O 3 [M+H] + 415.1264，found 415.1267.
(E)-N-(4-(tert-butyl)phenyl)-N′-((4-(trifluoromethyl)benzoyl)oxy)benzimidamide(5ac)
Figure BSA0000167897780000142
131.0，130.6，130.2，129.1，128.4，125.4(q，J＝3.6Hz)，125.2，123.7(q，J＝271.1Hz)，122.6，33.9，31.0.HR-MS(ESI)：Calcd for C 25 H 24 F 3 N 2 O 2 [M+H] + 441.1784，found 441.1789.
(E)-N-(4-fluorophenyl)-N′-((4-(trifluoromethyl)benzoyl)oxy)benzimidamide(5ad)
Figure BSA0000167897780000143
＝8.3Hz)，123.5(q，J＝271.2Hz)，115.8(d，J＝23.0Hz).HR-MS(ESI)：Calcd for C 21 H 15 F 4 N 2 O 2 [M+H] + 403.1064，found 403.1070.
(E)-N-(4-chlorophenyl)-N′-((4-(trifluoromethyl)benzoyl)oxy)benzimidamide(5ae)
Figure BSA0000167897780000144
＝3.4Hz)，124.2，123.5(q，J＝271.0Hz).HR-MS(ESI)：Calcd for C 21 H 15 ClF 3 N 2 O 2 [M+H] + 419.0769，found 419.0768.
Figure BSA0000167897780000145
2H)，7.11(s，1H)，6.70(d，J＝8.8Hz，2H). 13 C NMR(100 MHz，CDCl 3 )δ162.8，156.7，137.7，134.6(q，J＝32.6Hz)，132.4，132.0，131.0，130.0，129.3，129.1，128.7，125.6(q，J＝3.8Hz)，124.5，123.5(q，J＝271.4Hz)，117.5.HR-MS(ESI)：Calcd for C 21 H 15 BrF 3 N 2 O 2 [M+H] + 463.0264，found 463.0267.
(E)-N-(m-tolyl)-N′-((4-(trifluoromethyl)benzoyl)oxy)benzimidamide(5ag)
Figure BSA0000167897780000151
MHz，CDCl 3 )δ162.8，157.1，139.0，138.5，134.5(q，J＝32.9Hz)，132.7，130.7，130.0，129.7，129.4，128.7，128.5，125.5(q，J＝3.5Hz)，125.3，123.6，123.6(q，J＝271.3Hz)，120.2，21.2.HR-MS(ESI)：Calcd for C 22 H 18 F 3 N 2 O 2 [M+H] + 399.1315，found 399.1320.
(E)-N-(o-tolyl)-N′-((4-(trifluoromethyl)benzoyl)oxy)benzimidamide(5ah)
Figure BSA0000167897780000152
130.8，130.8，129.9，129.1，128.4，127.6，126.5，125.6，125.6，125.5(q，J＝3.7Hz)，123.6(q，J＝271.1Hz)，18.1.HR-MS(ESI)：Calcd for C 22 H 18 F 3 N 2 O 2 [M+H] + 399.1315，found 399.1316.
(E)-N-(benzo[d][1，3]dioxol-5-yl)-N′-((4-(trifluoromethyl)benzoyl)oxy)benzimidamide(5ai)
Figure BSA0000167897780000153
132.7，132.6，130.6，130.0，129.5，129.4，128.4，125.5(q，J＝3.6Hz)，123.6(q，J＝271.0Hz)，117.5，108.0，106.0，101.5.HR-MS(ESI)：Calcd for C 22 H 18 F 3 N 2 O 2 [M+H] + 429.1057，found 429.1060.
(E)-N-(3，4-dichlorophenyl)-N′-((4-(trifluoromethyl)benzoyl)oxy)benzimidamide(5aj)
Figure BSA0000167897780000154
130.4，130.0，129.2，128.8，128.0，125.6(q，J＝3.6Hz)，124.2，123.5(q，J＝270.9Hz)，122.1.HR-MS(ESI)：Calcd for C 21 H 14 C 12 F 3 N 2 O 2 [M+H] + 453.0379，found 453.0377.
(E)-N-(3，5-dimethylphenyl)-N′-((4-(trifluoromethyl)benzoyl)oxy)benzimidamide(5ak)
Figure BSA0000167897780000161
Hz)，132.8，130.7，129.9，129.8，129.3，128.4，126.2，125.5(q，J＝3.6Hz)，123.6(q，J＝271.1Hz)，120.8，21.1.HR-MS(ESI)：Calcd for C 23 H 20 F 3 N 2 O 2 [M+H] + 413.1471，found 413.1475.
(E)-N-(2，4-dimethoxyphenyl)-N′-((4-(trifluoromethyl)benzoyl)oxy)benzimidamide(5al)
Figure BSA0000167897780000162
134.5(q，J＝32.6Hz)，132.9，130.5，130.0，129.8，129.2，128.3，125.5(q，J＝3.6Hz)，125.1，123.6(q，J＝270.8Hz)，120.7，103.7，99.0，55.6，55.5.HR-MS(ESI)：Calcd for C 23 H 20 F 3 N 2 O 4 [M+H] + 445.1370，found 445.1371.
2-phenyl-1H-benzo[d]imidazole(Ia)
Figure BSA0000167897780000163
126.4，122.5，121.6，118.8，111.3.HR-MS(ESI)：Calcd for C 13 H 11 N 2 [M+H] + 195.0917，found 194.0919.
2-(p-tolyl)-1H-benzo[d]imidazole(Ib)
Figure BSA0000167897780000164
139.5，129.5，127.4，126.4，121.9，20.9.HR-MS(ESI)：Calcd for C 14 H 13 N 2 [M+H] + 209.1073，found 209.1076.
2-(4-methoxyphenyl)-1H-benzo[d]imidazole(Ic)
Figure BSA0000167897780000165
151.8，128.4，123.1，118.9，114.8，111.5，55.8.HR-MS(ESI)：Calcd for C 14 H 13 N 2 O[M+H] + 225.1022，found 225.1025.
4-(1H-benzo[d]imidazol-2-yl)benzonitrile(Id)
Figure BSA0000167897780000166
Hz，1H)，7.59(d，J＝7.6Hz，1H)，7.36-7.14(m，2H). 13 C NMR(100 MHz，DMSO-d 6 )δ149.3，143.7，135.1，134.2，133.0，126.9，123.4，122.2，119.3，118.6，111.8，111.7.HR-MS(ESI)：Calcd for C 14 H 10 N 3 [M+H] + 220.0869，found 220.0871.
2-(4-nitrophenyl)-1H-benzo[d]imidazole(Ie)
Figure BSA0000167897780000171
MHz，DMSO-d 6 )δ149.0，147.7，143.8，136.0，135.2，127.3，124.2，123.5，122.3，119.4，111.8.HR-MS(ESI)：Calcd for C 13 H 10 N 3 O 2 [M+H] + 240.0768，found 240.0769.
2-(4-fluorophenyl)-1H-benzo[d]imidazole(If)
Figure BSA0000167897780000172
(100 MHz，MeOD-d 4 )δ164.0(d，J＝249.5Hz)，151.1，128.7(d，J＝8.6Hz)，126.1(d，J＝3.1Hz)，122.6，115.7(d，J＝22.3Hz)，114.5.HR-MS(ESI)：Calcd for C 13 H 10 FN 2 [M+H] + 213.0823，found 213.0826.
2-(4-chlorophenyl)-1H-benzo[d]imidazole(Ig)
Figure BSA0000167897780000173
2H)，7.55(d，J＝7.2Hz，1H)，7.23(t，J＝7.6Hz，2H). 13 C NMR(100 MHz，DMSO-d 6 )δ150.1，143.7，135.0，134.5，129.0，128.1，122.8，121.8，118.9，111.4.HR-MS(ESI)：Calcd for C 13 H 10 ClN 2 [M+H] + 229.0527，found 229.0528.
2-(4-bromophenyl)-1H-benzo[d]imidazole(Ih)
Figure BSA0000167897780000174
Hz，1H)，7.54(d，J＝7.6Hz，1H)，7.30-7.12(m，2H). 13 C NMR(100 MHz，DMSO-d 6 )δ150.2，143.8，135.1，132.0，129.4，128.3，123.2，122.7，122.0，118.9，111.4.HR-MS(ESI)：Calcd for C 13 H 10 BrN 2 [M+H] + 273.0022，found 273.0023.
2-(4-(trifluoromethoxy)phenyl)-1H-benzo[d]imidazole(Ii)
Figure BSA0000167897780000175
149.2，129.4，128.4，122.3，121.4，120.0(q，J＝256.8Hz)，111.5.HR-MS(ESI)：Calcd for C 14 H 10 F 3 N 2 O[M+H] + 279.0740，found 279.0742.
2-(3-chlorophenyl)-1H-benzo[d]imidazole(Ij)
Figure BSA0000167897780000176
135.4，134.2，132.6，131.4，130.0，126.5，125.5，123.4，122.4，119.6，112.0.HR-MS(ESI)：Calcd for C 13 H 10 ClN 2 [M+H] + 229.0527，found 229.0527.
2-(2-chlorophenyl)-1H-benzo[d]imidazole(Ik)
Figure BSA0000167897780000181
134.6，132.1，131.6，131.2，130.3，129.9，127.4，122.7，121.7，119.1，111.7.HR-MS(ESI)：Calcd for C 13 H 10 ClN 2 [M+H] + 229.0527，found 229.0529.
2-(benzo[d][1，3]dioxol-5-yl)-1H-benzo[d]imidazole(Il)
Figure BSA0000167897780000182
149.2，148.3，124.7，122.4，121.3，109.2，106.9，102.0.HR-MS(ESI)：Calcd for C 14 H 11 N 2 O 2 [M+H] + 239.0815，found 239.0814.
2-([1，1′-biphenyl]-4-yl)-1H-benzo[d]imidazole(Im)
Figure BSA0000167897780000183
2H)，7.74-7.36(m，5H)，7.24(s，2H). 13 C NMR(100 MHz，DMSO-d 6 )δ150.9，144.0，141.3，139.2，135.0，129.1，129.0，127.9，127.1，127.0，126.7，122.6，121.8，118.9，111.3.HR-MS(ESI)：Calcd for C 19 H 15 N 2 [M+H] + 271.1230，found 271.1228.
2-(naphthalen-2-yl)-1H-benzo[d]imidazole(In)
Figure BSA0000167897780000184
13 C NMR(100 MHz，DMSO-d 6 )δ151.2，133.4，132.8，128.5，128.4，127.8，127.6，127.1，126.9，125.8，123.9，122.1.HR-MS(ESI)：Calcd for C 17 H 13 N 2 [M+H] + 245.1073，found 245.1075.
Methyl 4-(1H-benzo[d]imidazol-2-yl)benzoate(Io)
Figure BSA0000167897780000185
NMR(100 MHz，DMSO-d 6 )δ165.8，150.0，143.8，135.1，134.3，130.3，129.8，126.6，123.1，122.0，119.2，111.6，52.3.HR-MS(ESI)：Calcd for C 15 H 13 N 2 O 2 [M+H] + 253.0972，found 253.0973.
N-(4-(1H-benzo[d]imidazol-2-yl)phenyl)acetamide(Ip)
Figure BSA0000167897780000186
(100 MHz，DMSO-d 6 )δ168.6，151.2，140.8，127.1，124.6，121.9，118.9，24.1.HR-MS(ESI)：Calcd for C 15 H 14 N 3 O[M+H] + 252.1131，found 252.1131.
Ethyl 1H-benzo[d]imidazole-2-carboxylate(Iq)
Figure BSA0000167897780000191
for C 10 H 11 N 2 O 2 [M+H] + 191.0815，found 191.0809.
5-methyl-2-phenyl-1H-benzo[d]imidazole(Iaa)
Figure BSA0000167897780000192
＝6.0Hz，2H)，7.65-7.27(m，5H)，7.04(s，1H)，2.45(s，3H). 13 C NMR(100MHz，DMSO-d 6 )δ151.6，151.2，144.6，142.4，135.7，133.5，132.3，130.8，130.1，129.4，126.7，124.4，123.7，119.1，118.9，111.5，111.3，21.8，21.8.HR-MS(ESI)：Calcd for C 14 H 13 N 2 [M+H] + 209.1073，found 209.1075.
5-methoxy-2-phenyl-1H-benzo[d]imidazole(Iab)
Figure BSA0000167897780000193
CDCl 3 )δ156.7，151.5，130.0，129.9，129.1，126.4，112.6，55.8.HR-MS(ESI)：Calcd for C 14 H 13 N 2 O[M+H] + 225.1022，found 225.1026.
(tert-butyl)-2-phenyl-1H-benzo[d]imidazole(Iac)
Figure BSA0000167897780000194
138.8，137.4，130.0，130.0，129.1，127.1，121.0，114.8，111.2，34.8，31.8.HR-MS(ESI)：Calcd for C 17 H 19 N 2 [M+H] + 251.1543，found 251.1545.
5-fluoro-2-phenyl-1H-benzo[d]imidazole(Iad)
Figure BSA0000167897780000195
DMSO-d 6 )δ153.4，152.7，144.6，140.9，132.1，130.6，130.4，130.4，130.3，129.5，126.9，126.8，120.3，120.2，112.4，112.4，111.2，110.9，110.4，110.2，104.9，104.7，98.3，98.0.HR-MS(ESI)：Calcd for C 13 H 10 FN 2 [M+H] + 213.0823，found 213.0824.
5-chloro-2-phenyl-1H-benzo[d]imidazole(Iae)
Figure BSA0000167897780000196
8.19(d，J＝7.2Hz，2H)，7.74(s，0.5H)，7.69(d，d＝8.4Hz，0.5H)，7.64-7.47(m，4H)，7.29-7.18(m，1H). 13 C NMR(100 MHz，DMSO-d 6 )δ152.8，152.4，144.7，142.6，135.7，133.8，130.2，130.2，129.7，129.0，126.8，126.6，126.0，122.6，122.0，120.1，118.2，112.6，111.0.HR-MS(ESI)：Calcd for C 13 H 10 ClN 2 [M+H] + 229.0527，found 229.0528.
5-bromo-2-phenyl-1H-benzo[d]imidazole(Iaf)
Figure BSA0000167897780000201
(ESI)：Calcd for C 13 H 10 BrN 2 [M+H] + 273.0022，found 273.0020.
4-methyl-2-phenyl-1H-benzo[d]imidazole(Iag’)
Figure BSA0000167897780000202
131.3，131.2，130.1，128.0，124.4，123.9，17.2.HR-MS(ESI)：Calcd for C 14 H 13 N 2 [M+H] + 209.1073，found 209.1074.
6-methyl-2-phenyl-1H-benzo[d]imidazole(Iag”)
Figure BSA0000167897780000203
2.46(s，3H). 13 C NMR(100MHz，MeOD-d 4 )δ153.1，134.0，131.2，131.2，130.1，127.7，125.5，115.5，21.8.HR-MS(ESI)：Calcd for C 14 H 13 N 2 [M+H] + 209.1073，found 209.1075.7-methyl-2-phenyl-1H-benzo[d]imidazole(Iah)
Figure BSA0000167897780000205
131.3，131.2，130.1，128.0，124.5，123.9，17.2.HR-MS(ESI)：Calcd for C 14 H 13 N 2 [M+H] + 209.1073，found 209.1074.
4，5-dichloro-2-phenyl-1H-benzo[d]imidazole(Iaj’)and5，6-dichloro-2-phenyl-1H-benzo[d]imidazole(Iaj”)
Figure BSA0000167897780000206
NMR(400 MHz，MeOD-d 4 )δ8.05(dd，d＝6.4，2.8Hz，2H)，7.60-7.52(m，3H)，7.74(s，2H).Iaj’+Iaj”： 13 C NMR(100 MHz，MeOD-d 4 )δ155.5，155.4，139.8，138.8，138.2，132.5，132.2，130.4，130.2，129.9，129.4，128.4，128.2，127.6，125.8，120.2，117.1，114.4.HR-MS(ESI)：Calcd for C 13 H 9 Cl 2 N 2 [M+H] + 263.0137，found 263.0140.
4，6-dimethyl-2-phenyl-1H-benzo[d]imidazole(Iak)
Figure BSA0000167897780000211
126.5，124.7，20.3，15.7.HR-MS(ESI)：Calcd for C 15 H 15 N 2 [M+H] + 223.1230，found 223.1233.
5，7-dimethoxy-2-phenyl-1H-benzo[d]imidazole(Ial)
Figure BSA0000167897780000212
136.6，130.4，129.2，128.8，125.9，94.1，86.6，55.5，55.4.HR-MS(ESI)：Calcd for C 15 H 15 N 2 O 2 [M+H] + 255.1128，found 255.1133.

Claims (5)

1. the synthesis method of thiabendazole I is characterized by comprising the following synthesis steps:
Figure FSB0000200111920000011
synthesizing a commercial reagent thiazole-4-formaldehyde (1) through three-step reaction to obtain an intermediate 4, reacting the intermediate 4 with p-trifluoromethyl benzoyl chloride to prepare an intermediate 5, and reacting the intermediate 5 with a photocatalyst Ir [ dF (CF) 3 )ppy] 2 (dtbbpy)PF 6 And carrying out visible light irradiation reaction under the action to obtain the target compound I.
2. The process according to claim 1, wherein the intermediate 3 is reacted with aniline using one or more bases selected from pyridine, triethylamine, diisopropylethylamine, N-ethylpiperidine and triethylenediamine, and the solvent is one or more selected from diethyl ether, methyl tert-butyl ether, tetrahydrofuran, 2-methyltetrahydrofuran and 1,4-dioxane.
3. A process for the synthesis of thiabendazole I according to claim 1, characterized in that the base used for the reaction of intermediate 4 with p-trifluoromethylbenzoyl chloride is one or more of pyridine, triethylamine, diisopropylethylamine, N-ethylpiperidine, and N-methylmorpholine, and the solvent used is one or more of tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, dichloromethane, 1,2-dichloroethane.
4. A process according to claim 1 for the synthesis of thiabendazole I, characterized in that the photocatalyst used for the preparation of I from intermediate 5 is Ir [ dF (CF) 3 )ppy] 2 (dtbbpy)PF 6 The solvent is one or more of N, N-dimethylformamide, N-diethylformamide, N-dimethylacetamide, dimethyl sulfoxide, acetonitrile, acetone, dichloromethane, 1,2-dichloroethane, methyl tert-butyl ether, tetrahydrofuran and 1,4-dioxane, and the light source is one or more of a white LED lamp of 1-100 watts, a blue LED lamp of 1-100 watts and a white CFL lamp of 1-100 watts.
5. A synthesis process according to claim 1 for thiabendazole I, characterized in that the imidazole compounds Ia to Ial are prepared by changing the substituents of the starting materials using this process,
Figure FSB0000200111920000021
in the formula R 1 And R 2 Is a substituent group shown in the structure of a compound Ia-Ial.
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