A base-promoted method for the synthesis of 4-cyanoimidazole derivatives

Abstract

The application relates to the technical field of organic synthesis, in particular to a base-promoted synthesis method of 4-cyano imidazole derivatives, which comprises the following steps: taking isothiocyanate, isocyanate and trimethyl cyanosilane as reaction raw materials, reacting in an organic solvent under the condition of the presence of a base, filtering and concentrating after the reaction is completed, washing the solid precipitate to obtain the target product 4-cyano imidazole derivatives. The synthesis method provided by the application realizes one-pot three-component desulfurization cross-coupling one-step construction of 4-cyano imidazole derivatives under the promotion of a base, has the advantages of easy availability of raw materials, simple and mild conditions, low cost, high yield, easy purification of products, and is favorable for large-scale preparation and production.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic synthesis, in particular to a synthesis method of base-promoted 4-cyano imidazole derivatives. BACKGROUND

[0002] The information disclosed in the background of the present application is only intended to increase the understanding of the overall background of the present application and should not be considered as acknowledging or implying in any form that the information constitutes prior art known to those skilled in the art.

[0003] Imidazole and its derivatives are an important class of organic heterocyclic compounds, which can be found everywhere in people's life and often exist in natural products, drugs, functional materials and organic ligands. Among them, imidazole derivatives have a wide range of applications, such as resisting various fungi and bacteria, treating eye diseases, photocatalysis and solar energy conversion, enhancing the curing ability of epoxy resin, and detecting cyanide in visible light and near-infrared water medium.

[0004] At present, there have been many reports on the preparation of imidazole derivatives. However, the previously reported synthesis methods all need to be pre-functionalized, that is, to synthesize functional imidazole first, and then to convert the functional group to 3-cyano imidazole derivative, which has the disadvantages of complicated process, expensive raw materials and difficult synthesis. So far, a simple and effective one-step method for directly constructing 4-cyano imidazole derivatives has not been developed. SUMMARY

[0005] In order to solve the shortcomings and deficiencies of the prior art, the purpose of the present application is to provide a synthesis method of base-promoted 4-cyano imidazole derivatives, which can realize one-pot three-component desulfurization cross-coupling to construct 4-cyano imidazole derivatives in one step under the condition of simple and mild base promotion.

[0006] To achieve the above purpose, the technical solution adopted by the present application is as follows:

[0007] A synthesis method of base-promoted 4-cyano imidazole derivatives, which comprises the following steps: taking a compound represented by structural formula a, a compound represented by structural formula b and trimethyl cyanosilane as reaction raw materials, and reacting in an organic solvent in the presence of a base, to obtain a 4-cyano imidazole derivative represented by general formula c after the reaction is completed.

[0008]

[0009] Among them, R 1 is aryl or alkyl; X is sulfur or selenium; R 2 is methyl or ethyl.

[0010] Further, the compound shown in formula a is isothiocyanate; the compound shown in formula b is isocyanate.

[0011] Further, the isothiocyanate is phenyl isothiocyanate, 4-methylphenyl isothiocyanate, 4-trifluoromethylphenyl isothiocyanate, 4-fluorophenyl isothiocyanate, 4-chlorophenyl isothiocyanate, 4-trifluoromethoxyphenyl isothiocyanate, 4-nitrophenyl isothiocyanate, 4-cyanophenyl isothiocyanate, 3-pyridyl isothiocyanate, 2-methylphenyl isothiocyanate, 2-iodophenyl isothiocyanate, 2-naphthyl isothiocyanate, 2-chlorophenyl isothiocyanate, benzoyl isothiocyanate or 2-phenylethyl isothiocyanate, etc.

[0012] The isocyanate is methyl isocyanate or ethyl isocyanate.

[0013] Further, the base is 1,8-diazabicyclo[5.4.0]undec-7-ene.

[0014] Further, the molar ratio of the compound shown in formula a, the compound shown in formula b, trimethylsilyl cyanide and the base is 1:1:1:3.

[0015] Further, the organic solvent is any one or two of methyl tert-butyl ether, 1,2-dibromoethane and acetonitrile, etc.

[0016] Further, the reaction is under air condition, the temperature is room temperature, and the time is 2-12 h.

[0017] Further, after the reaction is completed, the reaction liquid is further filtered and concentrated to obtain solid precipitate, and then elution is performed.

[0018] Further, the solid precipitate is eluted by using petroleum ether and / or ethyl acetate.

[0019] Advantages

[0020] The synthetic method provided by the present application is simple, uses simple and easily available isothiocyanate, isocyanate and silyl cyanide as raw materials, promotes under the action of a base, realizes one-pot three-component desulfurization cross-coupling one-step construction of 4-cyanoimidazole derivatives by using the principle of nucleophilic cyclization; the synthetic method provided by the present application has good substrate applicability, various cheap and easily available aryl isothiocyanates, alkyl isothiocyanates and even aryl isoselenocyanates have good applicability; the solid precipitate synthesized by the present application only needs to be filtered and recrystallized to obtain pure target product; the synthetic method provided by the present application has the advantages of easy availability of raw materials, simple and mild conditions, economical steps, high yield and easy purification of products, and has great application potential in the fields of medicine, pesticide and material, etc. DETAILED DESCRIPTION

[0021] The specific details of the present application are further described in the following description for sufficient understanding of the application. The terminology used in the description of the application is for the purpose of describing the preferred embodiments only and is not intended to be limiting of the application.

[0022] Unless otherwise defined, all technical and scientific terms used in the present application have the same meaning as those commonly understood by one of ordinary skill in the art to which this application belongs. The materials and methods used in the present application are used according to the product instructions or by using the conventional methods in the art, unless otherwise specified. The process of the present application is further described according to the specific embodiments.

[0023] Example 1

[0024]

[0025] In a dry round bottom flask (25.0 mL) was added phenyl isothiocyanate (2.0 mmol), ethyl isocyanoacetate (2.0 mmol), TMSCN (2.0 mmol), the system was added solvent EDB / MTBE (2.0 mL, v = 3:1) and DBU (6.0 mmol) in turn under air atmosphere, the reaction was stopped after 2 hours of reaction at room temperature, there was a large amount of precipitate in the system, the reaction system was diluted with petroleum ether. Subsequently, the desired product was obtained by reducing pressure filtration, and the solid precipitate was washed with petroleum ether, with a yield of 82%, as a yellow solid, and a column chromatography separation yield of 85%, with the following characterization data:

[0026] Melting point: 101-103 °C

[0027] NMR: 1 H NMR (500 MHz, CDCl3) δ 7.8 (s, 1H), 7.6 (m, 3H), 7.4 (dd, J = 7.8, 1.7 Hz, 2H), 4.4 (q, J = 7.1 Hz, 2H), 1.4 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 160.1, 142.1, 139.9, 133.8, 130.4, 130.3, 124.4, 109.7, 109.2, 61.9, 14.1.

[0028] High resolution: HRMS (ESI) m / z: [M+H] + calcd for C 13 H 11 N3O2: 242.0925; found: 242.0925.

[0029] Example 2

[0030]

[0031] In a dry round bottom flask (25.0 mL) was added phenyl 4-methylisothiocyanate (2.0 mmol), ethyl isocyanoacetate (2.0 mmol), TMSCN (2.0 mmol), the system was added solvent EDB / MTBE (2.0 mL, v = 3:1) and DBU (6.0 mmol) in turn under air atmosphere, the reaction was stopped after 2 hours of reaction at room temperature, there was a large amount of precipitate in the system, the reaction system was diluted with petroleum ether. Subsequently, the desired product was obtained as a yellow solid by reducing pressure filtration, and the solid precipitate was washed with petroleum ether, with a yield of 81%, and the characterization data were as follows:

[0032] Melting point: 123-125 °C

[0033] NMR: 1 H NMR (500 MHz, CDC13) δ 7.84 (s, 1H), 7.3 (d, J = 8.6 Hz, 2H), 7.3 (d, J = 8.5 Hz, 2H), 4.4 (q, J = 7.1 Hz, 2H), 2.4 (s, 3H), 1.4 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 160.2, 141.9, 140.8, 139.9, 131.3, 130.8, 124.2, 109.7, 109.3, 61.9, 21.2, 14.1.

[0034] High resolution: HRMS (ESI) m / z: [M+H] + calcd for C 14 H 13 N3O2: 256.1081; found: 256.1081.

[0035] Example 3

[0036]

[0037] In a dry round bottom flask (25.0 mL) was added phenyl 4-methylisothiocyanate (2.0 mmol), ethyl isocyanoacetate (2.0 mmol), TMSCN (2.0 mmol), the system was added solvent EDB / MTBE (2.0 mL, v = 3:1) and DBU (6.0 mmol) in turn under air atmosphere, the reaction was stopped after 2 hours of reaction at room temperature, there was a large amount of precipitate in the system, the reaction system was diluted with petroleum ether. Subsequently, the desired product was obtained as a yellow solid by reducing pressure filtration, and the solid precipitate was washed with petroleum ether, with a yield of 81%, and the characterization data were as follows:

[0038] Melting point: 150-152 °C

[0039] NMR: 1 H NMR (500 MHz, CDC13) δ 7.94 (s, 1H), 7.90 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 8.5 Hz, 2H), 4.49 (q, J = 7.1 Hz, 2H), 1.45 (t, J = 7.1 Hz, 3H). 13 CNMR (126 MHz, CDC13) δ 159.8, 142.6, 139.8, 136.5, 132.5 (q, J = 33.6 Hz), 127.6 (q, J = 3.6 Hz), 124.9, 123.5 (q, J = 273.2 Hz), 109.4, 108.9, 62.1, 14.1. 19 F NMR (471 MHz, CDC13) δ -62.9.

[0040] High resolution: HRMS (ESI) m / z: [M+H] + calcd for C 14 H 10 F3N3O2: 310.0798; found: 310.0796.

[0041] Example 4

[0042]

[0043] In a dry round bottom flask (25.0 mL) was added phenyl 4- trifluoromethoxyisothiocyanate (2.0 mmol), ethyl isocyanoacetate (2.0 mmol), TMSCN (2.0 mmol), the system was added solvent EDB / MTBE (2.0 mL, v = 3: 1) and DBU (6.0 mmol) under air atmosphere, the reaction was stopped after 2 hours of reaction at room temperature, there was a large amount of precipitate in the system, the reaction system was diluted with petroleum ether. Subsequently, the solid precipitate was washed with petroleum ether by reduced pressure filtration to obtain the desired product as a yellow solid with a yield of 85%, the characterization data are as follows:

[0044] Melting point: 132-134 °C

[0045] NMR: 1 H NMR (500 MHz, CDC13) δ 7.94 (s, 1H), 7.90 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 8.5 Hz, 2H), 4.49 (q, J = 7.1 Hz, 2H), 1.45 (t, J = 7.1 Hz, 3H). 13C NMR (126 MHz, CDCI3) δ 159.9, 150.2, 142.2, 140.0, 132.0, 126.3, 122.5, 120.7 (q, J = 262.6 Hz), 109.5, 109.2, 62.0, 14.0. 19 FNMR (471 MHz, CDCI3) δ -57.9. High resolution: HRMS (ESI) m / z: [M+H] + calcd for C 14 H 10 F3N3O3: 326.0747; found: 326.0747.

[0046] Example 5

[0047]

[0048] In a dry round bottom flask (25.0 mL) was added 4-nitrophenyl isothiocyanate (2.0 mmol), ethyl isocyanoacetate (2.0 mmol), TMSCN (2.0 mmol), the system was added solvent EDB / MTBE (2.0 mL, v = 3: 1) and DBU (6.0 mmol) in turn under air atmosphere, the reaction was stopped after 2 hours of reaction at room temperature, there was a large amount of precipitate in the system, the reaction system was diluted with petroleum ether. Subsequently, the desired product was obtained as a yellow solid by reducing pressure filtration, and the solid precipitate was washed with petroleum ether, with a yield of 85%, and the characterization data were as follows:

[0049] Melting point: 178-180 °C

[0050] NMR data: 1 H NMR (500 MHz, CDCI3) δ 8.50 (d, J = 8.9 Hz, 2H), 7.98 (s, 1H), 7.76 (d, J = 8.9 Hz, 2H), 4.50 (q, J = 7.1 Hz, 2H), 1.46 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, CDCI3) δ 159.7, 148.5, 143.0, 139.6, 138.4, 125.9, 125.3, 109.3, 108.8, 62.3, 14.1.

[0051] High resolution: HRMS (ESI) m / z: [M+H] + calcd for C 13 H 10 N4O4: 287.0775; found: 287.0773.

[0052] Example 6

[0053]

[0054] In a dry round bottom flask (25.0 mL) was added phenyl 4-cyanoisothiocyanate (2.0 mmol), ethyl isocyanoacetate (2.0 mmol), TMSCN (2.0 mmol), the system was added solvent EDB / MTBE (2.0 mL, v = 3: 1) and DBU (6.0 mmol) in turn under air atmosphere, the reaction was stopped after 2 hours of reaction at room temperature, there was a large amount of precipitate in the system, the reaction system was diluted with petroleum ether. Subsequently, the desired product was obtained as a yellow solid by reducing pressure filtration, and the solid precipitate was washed with petroleum ether, with a yield of 50%, and the characterization data were as follows:

[0055] Melting point: 150-152 °C

[0056] NMR: 1 H NMR (500 MHz, CDC13) δ 7.95 (d, J = 2.7 Hz, 1H), 7.93 (s, 1H), 7.69 (d, J = 8.6 Hz, 2H), 4.50 (q, J = 7.1 Hz, 2H), 1.45 (t, J = 7.1 Hz, 3H). 13 CNMR (126 MHz, CDC13) δ 159.8, 142.8, 139.6, 137.0, 134.3, 125.1, 117.0, 114.6, 109.3, 108.8, 62.2, 14.1.

[0057] High resolution: HRMS (ESI) m / z: [M+H] + calcd for C 14 H 10 N4O2: 267.0877; found: 267.0877.

[0058] Example 7

[0059]

[0060] In a dry round bottom flask (25.0 mL) was added phenyl 4-cyanoisothiocyanate (2.0 mmol), ethyl isocyanoacetate (2.0 mmol), TMSCN (2.0 mmol), the system was added solvent EDB / MTBE (2.0 mL, v = 3: 1) and DBU (6.0 mmol) in turn under air atmosphere, the reaction was stopped after 2 hours of reaction at room temperature, there was a large amount of precipitate in the system, the reaction system was diluted with petroleum ether. Subsequently, the desired product was obtained as a yellow solid by reducing pressure filtration, and the solid precipitate was washed with petroleum ether, with a yield of 50%, and the characterization data were as follows:

[0061] Melting point: 140-142 °C

[0062] NMR: 1 H NMR (500 MHz, CDC13) δ 7.77 (s, 1H), 7.47 (m, 2H), 7.22 (dd, J = 11.3, 5.4 Hz, 2H), 4.40 (q, J = 7.1 Hz, 2H), 1.37 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 163.33 (d, J = 252.1 Hz), 160.0, 142.0, 140.0, 129.8 (d, J = 3.2 Hz), 126.7 (d, J = 9.0 Hz), 117.4 (d, J = 23.5 Hz), 109.5, 109.4, 62.0, 14.1. 19 F NMR (471 MHz, CDC13) δ -108.9.

[0063] High resolution: HRMS (ESI) m / z: [M+H] + calcd for C 13 H 10 FN3O2: 260.0830; found: 260.0830.

[0064] Example 8

[0065]

[0066] In a dry round bottom flask (25.0 mL) was added phenyl 4-chloroisothiocyanate (2.0 mmol), ethyl isocyanoacetate (2.0 mmol), TMSCN (2.0 mmol), the system was added solvent EDB / MTBE (2.0 mL, v = 3: 1) and DBU (6.0 mmol) in turn under air atmosphere, the reaction was stopped after 2 hours of reaction at room temperature, there was a large amount of precipitate in the system, the reaction system was diluted with petroleum ether. Subsequently, the solid precipitate was washed with petroleum ether by reduced pressure filtration to obtain the desired product as a yellow solid with a yield of 75%, the characterization data are as follows:

[0067] Melting point: 141-143 °C

[0068] NMR: 1 H NMR (500 MHz, CDC13) δ 7.77 (s, 1H), 7.47 (m, 2H), 7.22 (dd, J = 11.3, 5.4 Hz, 2H), 4.40 (q, J = 7.1 Hz, 2H), 1.37 (t, J = 7.1 Hz, 3H). 13C NMR (126 MHz, CDC13) δ 160.0, 142.2, 139.8, 136.6, 132.2, 130.5, 125.8, 109.5, 109.2, 62.0, 14.1.

[0069] High resolution: HRMS (ESI) m / z: [M+H] + calcd for C 13 H 10 ClN3O2: 276.0534; found: 276.0534.

[0070] Example 9

[0071]

[0072] In a dry round bottom flask (25.0 mL) was added phenyl 2-chloroisonthiocyanate (2.0 mmol), ethyl isocyanoacetate (2.0 mmol), TMSCN (2.0 mmol), the system was added solvent EDB / MTBE (2.0 mL, v = 3: 1) and DBU (6.0 mmol) in turn under air atmosphere, the reaction was stopped after 2 hours of reaction at room temperature, there was a large amount of precipitate in the system, the reaction system was diluted with petroleum ether. Subsequently, the desired product was obtained as a yellow solid by reducing pressure filtration, and the solid precipitate was washed with petroleum ether, with a yield of 62%, and the characterization data were as follows:

[0073] Melting point: 78-80 °C

[0074] NMR: 1 H NMR (500 MHz, CDC13) δ 7.80 (s, 1H), 7.66 (dd, J = 8.1, 1.2 Hz, 1H), 7.60 (m, 1H), 7.54 (m, 2H), 4.49 (q, J = 7.1 Hz, 2H), 1.46 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 160.0, 141.4, 140.9, 132.3, 131.3, 131.2, 131.2, 128.6, 128.3, 110.4, 109.1, 62.0, 14.1.

[0075] High resolution: HRMS (ESI) m / z: [M+H] + calcd for C 13 H 10 ClN3O2: 276.0534; found: 276.0534.

[0076] Example 10

[0077]

[0078] In a dry round bottom flask (25.0 mL) was added 3-pyridyl isothiocyanate (2.0 mmol), ethyl isocyanoacetate (2.0 mmol), TMSCN (2.0 mmol), the system was added solvent EDB / MTBE (2.0 mL, v = 3:1) and DBU (6.0 mmol) in turn under air atmosphere, the reaction was stopped after 2 hours of reaction at room temperature, there was a large amount of precipitate in the system, the reaction system was diluted with petroleum ether. Subsequently, the desired product was obtained as a yellow solid by reducing pressure filtration, and the solid precipitate was washed with petroleum ether, with a yield of 51%, and the characterization data were as follows:

[0079] Melting point: 135-137 °C

[0080] NMR: 1 H NMR (500 MHz, CDC13) δ 8.83 (dd, J = 4.8, 1.0 Hz, 1H), 8.79 (d, J = 2.5 Hz, 1H), 7.93 (m, 2H), 7.58 (dd, J = 8.2, 4.8 Hz, 1H), 4.47 (q, J = 7.1 Hz, 2H), 1.43 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 159.8, 151.6, 145.3, 142.6, 139.8, 132.1, 130.7, 124.6, 109.3, 62.1, 14.1.

[0081] High resolution: HRMS (ESI) m / z: [M+H] + calcd for C 12 H 10 N4O2: 243.0877; found: 243.0877.

[0082] Example 11

[0083]

[0084] In a dry round bottom flask (25.0 mL) was added 2-naphthyl isothiocyanate (2.0 mmol), ethyl isocyanoacetate (2.0 mmol), TMSCN (2.0 mmol), the system was added solvent EDB / MTBE (2.0 mL, v = 3:1) and DBU (6.0 mmol) in turn under air atmosphere, the reaction was stopped after 2 hours of reaction at room temperature, there was a large amount of precipitate in the system, the reaction system was diluted with petroleum ether. Subsequently, the desired product was obtained as a yellow solid by reducing pressure filtration, and the solid precipitate was washed with petroleum ether, with a yield of 65%, and the characterization data were as follows:

[0085] Melting point: 115-117 °C

[0086] NMR: 1 H NMR (500 MHz, CDC13) δ 7.99 (d, J = 8.2 Hz, 1H), 7.91 (t, 1H), 7.79 (s, 1H), 7.56 (m, 4H), 7.24 (d, J = 8.2 Hz, 1H), 4.42 (q, J = 7.1 Hz, 2H), 1.37 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 160.2, 141.7, 141.4, 134.2, 131.5, 129.8, 129.0, 128.7, 128.6, 127.6, 125.1, 125.1, 121.0, 111.3, 109.3, 61.9, 14.2.

[0087] High resolution: HRMS (ESI) m / z: [M+H] + calcd for C 17 H 13 N3O2: 292.1081; found: 292.1076.

[0088] Example 12

[0089]

[0090] In a dry round bottom flask (25.0 mL) was added 2-phenylethyl isothiocyanate (2.0 mmol), ethyl isocyanoacetate (2.0 mmol), TMSCN (2.0 mmol), the system was added solvent acetonitrile (2.0 mL) and DBU (6.0 mmol) in turn under air atmosphere, the reaction was stopped after 12 hours of reaction at room temperature. Subsequently, acetonitrile was removed by reduced pressure concentration, and the target product was separated by column chromatography with petroleum ether and ethyl acetate as eluent, as a yellow solid, the separation yield reached 82%, the characterization data as follows:

[0091] Melting point: 71-73 °C

[0092] NMR: 1 H NMR (500 MHz, CDC13) δ 7.3 - 7.2 (m, 4H), 7.1 (d, J = 1.4 Hz, 1H), 7.0 (s, 1H), 4.43 (q, J = 7.1 Hz, 2H), 4.3 (t, J = 6.9 Hz, 2H), 3.1 (t, J = 6.9 Hz, 2H), 1.4 (t, J = 7.1 Hz, 3H). 13C NMR (126 MHz, CDCI3) δ 160.2, 141.2, 140.4, 135.6, 129.1, 128.5, 127.6, 109.7, 108.6, 61.8, 48.9, 36.8, 14.1.

[0093] High resolution: HRMS (ESI) m / z: [M+H] + calcd for C 15 H 16 N3O2: 270.1237; found: 270.1235.

[0094] Example 13

[0095]

[0096] In a dry round bottom flask (25.0 mL) was added phenyl isothiocyanate (2.0 mmol), methyl isocyanoacetate (2.0 mmol), TMSCN (2.0 mmol), the system was added solvent EDB / MTBE (2.0 mL, v = 3: 1) and DBU (6.0 mmol) in turn under air atmosphere, the reaction was stopped after 2 hours of reaction at room temperature, there was a large amount of precipitate in the system, the reaction system was diluted with petroleum ether. Subsequently, the desired product was obtained as a yellow solid by reducing pressure filtration, and the solid precipitate was washed with petroleum ether, with a yield of 66%, and the characterization data were as follows:

[0097] Melting point: 139-141 °C

[0098] NMR: 1 H NMR (500 MHz, CDCI3) δ 7.8 (s, 1H), 7.5 (m, 3H), 7.4 (m, 2H), 3.9 (s, 3H). 13 CNMR (126 MHz, CDCI3) δ 160.6, 141.8, 140.0, 133.7, 130.4, 130.3, 124.4, 109.6, 109.2, 52.6.

[0099] High resolution: HRMS (ESI) m / z: [M+H] + calcd for C 12 H9N3O2: 228.0768; found: 228.0766.

[0100] Example 14

[0101]

[0102] In a dry round bottom flask (25.0 mL) was added phenyl 2-methylisothiocyanate (2.0 mmol), methyl isocyanoacetate (2.0 mmol), TMSCN (2.0 mmol), the system was added solvent EDB / MTBE (2.0 mL, v = 3: 1) and DBU (6.0 mmol) in turn under air atmosphere, the reaction was stopped after 2 hours of reaction at room temperature, there was a large amount of precipitate in the system, the reaction system was diluted with petroleum ether. Subsequently, the desired product was obtained as a yellow solid by reducing pressure filtration, and the solid precipitate was washed with petroleum ether, with a yield of 70%, and the characterization data were as follows:

[0103] Melting point: 101-103 °C

[0104] NMR: 1 H NMR (500 MHz, CDC13) δ 7.65 (s, 1H), 7.42 (t, J = 7.1 Hz, 1H), 7.37 (m, 2H), 7.21 (d, J = 7.8 Hz, 1H), 4.41 (q, J = 7.1 Hz, 2H), 2.11 (s, 3H), 1.38 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 160.2, 141.3, 140.7, 134.7, 132.7, 131.8, 131.1, 127.5, 127.1, 110.4, 109.4, 61.9, 17.2, 14.1.

[0105] High resolution: HRMS (ESI) m / z: [M+H] + calcd for C 14 H 13 N3O2: 256.1081; found: 256.1081.

[0106] Example 15

[0107]

[0108] In a dry round bottom flask (25.0 mL) was added phenyl 2-methylisothiocyanate (2.0 mmol), methyl isocyanoacetate (2.0 mmol), TMSCN (2.0 mmol), the system was added solvent EDB / MTBE (2.0 mL, v = 3: 1) and DBU (6.0 mmol) in turn under air atmosphere, the reaction was stopped after 2 hours of reaction at room temperature, there was a large amount of precipitate in the system, the reaction system was diluted with petroleum ether. Subsequently, the desired product was obtained as a yellow solid by reducing pressure filtration, and the solid precipitate was washed with petroleum ether, with a yield of 70%, and the characterization data were as follows:

[0109] NMR: 1H NMR (500 MHz, CDCI3) δ 8.0 (dd, J = 7.6, 2.1 Hz, 2H), 7.9 (s, 1H), 7.4 (dd, J = 5.0, 2.5 Hz, 3H), 4.4 (q, J = 7.1 Hz, 2H), 1.4 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, CDCI3) δ 161.9, 155.5, 149.0, 130.4, 128.5, 128.4, 126.7, 126.6, 110.2, 61.4, 14.2.

[0110] High resolution: HRMS (ESI) m / z: [M+H] + calcd for C 14 H 11 N3O3: 270.0873; found: 270.0873.

[0111] Example 16

[0112]

[0113] In a dry round bottom flask (25.0 mL) was added ethyl isothiocyanate (2.0 mmol), ethyl isocyanoacetate (2.0 mmol), TMSCN (2.0 mmol), the system was added solvent acetonitrile (2.0 mL) and DBU (6.0 mmol) in turn under air atmosphere, the reaction was stopped after 12 hours at room temperature. Subsequently, the solvent was removed by reduced pressure concentration, and the target product was separated by column chromatography with petroleum ether and ethyl acetate as eluent, as a yellow solid, the separation yield reached 73%, the characterization data as follows:

[0114] Melting point: 76-78 °C

[0115] NMR: 1 H NMR (500 MHz, CDCI3) δ 7.69 (s, 1H), 4.45 (q, J = 7.1 Hz, 2H), 4.22 (q, J = 7.4 Hz, 2H), 1.58 (t, J = 7.4 Hz, 3H), 1.43 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, CDCI3) δ 160.2, 141.4, 139.6, 109.7, 108.6, 61.7, 42.5, 15.9, 14.1.

[0116] High resolution: HRMS (ESI) m / z: [M+H] + calcd for C9H 12 N3O2: 194.0924; found: 194.0922.

[0117] Example 17

[0118]

[0119] In a dry round-bottom flask (25.0 mL) was added isopropyl isothiocyanate (2.0 mmol), ethyl isocyanoacetate (2.0 mmol), TMSCN (2.0 mmol), the system was added solvent acetonitrile (2.0 mL) and DBU (6.0 mmol) in turn under air atmosphere, the reaction was stopped after 12 hours of reaction at room temperature. Subsequently, the solvent was removed by concentration under reduced pressure, and the target product was separated as a yellow oil by column chromatography with petroleum ether and ethyl acetate as eluent, with a separation yield of 67%, and the characterization data were as follows:

[0120] NMR: 1 H NMR (500 MHz, CDC13) δ 7.75 (s, 1H), 4.65 - 4.55 (m, 1H), 4.45 (q, J = 7.1 Hz, 2H), 1.64 (d, J = 6.8 Hz, 6H), 1.43 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 160.3, 141.3, 137.7, 109.9, 108.1, 61.8, 51.2, 22.9, 14.1.

[0121] High resolution: HRMS (ESI) m / z: [M+H] + calcd for C 10 H 14 N3O2: 208.1081; found: 208.1080.

[0122] Example 18

[0123]

[0124] In a dry round-bottom flask (25.0 mL) was added 2-iodophenyl isoselenocyanate (2.0 mmol), ethyl isocyanoacetate (2.0 mmol), TMSCN (2.0 mmol), the system was added solvent EDB / MTBE (2.0 mL, v = 3:1) and DBU (6.0 mmol) in turn under air atmosphere, the reaction was stopped after 12 hours of reaction at room temperature. Subsequently, the solvent was removed by concentration under reduced pressure, and the target product was separated as a yellow oil by column chromatography with petroleum ether and ethyl acetate as eluent, with a separation yield of 67%, and the characterization data were as follows:

[0125] Melting point: 95-97 °C

[0126] NMR:1 H NMR (500 MHz, CDC13) δ 7.97 (dd, J = 8.0, 1.1 Hz, 1H), 7.69 (s, 1H), 7.50 (td, J = 7.7, 1.2 Hz, 1H), 7.35 (dd, J = 7.9, 1.4 Hz, 1H), 7.26 (td, J = 7.8, 1.5 Hz, 1H), 4.43 (q, J = 7.1 Hz, 2H), 1.39 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 160.1, 141.4, 140.7, 140.6, 136.5, 132.6, 129.8, 128.2, 109.1, 96.1, 62.0, 14.1.

[0127] High resolution: HRMS (ESI) m / z: [M+H] + calcd for C 13 H 10 IN3O2: 367.9891; found: 367.9891.

[0128] Example 19

[0129]

[0130] In a dry round bottom flask (100.0 mL) was added phenyl isothiocyanate (10.0 mmol), ethyl isocyanoacetate (10.0 mmol), TMSCN (10.0 mmol), the system was added solvent EDB / MTBE (10.0 mL, v = 3: 1) and DBU (30.0 mmol) under air atmosphere, the reaction was stopped after 10 hours of reaction at room temperature, there was a large amount of precipitate in the system, the reaction system was diluted with petroleum ether. Subsequently, by reducing pressure, the solid precipitate was washed with petroleum ether to obtain the desired yellow solid product 2.412 g, the yield reached 87%.

[0131] Application Example 1

[0132]

[0133] In a dry round bottom flask (25.0 mL) was added the synthesized compound 1d (0.2 mmol) dissolved in EtOH (2.0 mL) at 0°C, then K2CO3 (0.4 mmol), H2O2 (1.0 mL) was added to the reaction system. Subsequently, the reaction system was stirred at 25°C for 12 hours, after the reaction was completed, the reaction liquid was concentrated by reducing pressure to remove the solvent, and the obtained solid residue was separated and purified by column chromatography with petroleum ether and ethyl acetate as eluent to obtain compound 1e, the yield was 98%, and the characterization data were as follows:

[0134] NMR: 1 H NMR (500 MHz, CDC13) δ 9.53 (s, 1H), 7.65 (s, 1H), 7.53 (m, 3H), 7.32 (m, 2H), 5.83 (s, 1H), 4.49 (q, J = 7.1 Hz, 2H), 1.48 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, CDC13) δ 164.7, 159.5, 140.2, 137.0, 133.0, 130.5, 129.0, 129.0, 125.8, 62.2, 14.2.

[0135] High resolution: HRMS (ESI) m / z: [M+H] + calcd for C 13 H 14 N3O2: 244.1081; found: 244.1080.

[0136] Application Example 2

[0137]

[0138] In a dry round bottom flask (25.0 mL) was added the synthesized compound 1d (0.2 mmol), the air in the reaction system was replaced by nitrogen, under the protection of nitrogen, THF (2.0 mL), cyclohexyl magnesium bromide (0.6 mmol) were added respectively, and the reaction was stirred for 3 hours. Then H2O (0.23 mL), H2SO4 (10% aq., 0.43 mL) were added to the reaction system, and stirred for 30 minutes. Then, the pH was adjusted to 8 with NaOH (30% aq.). The reaction solution was extracted with dichloromethane for 3 times, the combined organic phase was dried over anhydrous sodium sulfate, and the solvent was removed by reduced pressure concentration. The obtained solid residue was separated and purified by column chromatography with petroleum ether and ethyl acetate as eluent to obtain compound 1f with a yield of 94%, and the characterization data were as follows:

[0139] NMR: 1 H NMR (500 MHz, CDC13) δ 9.53 (s, 1H), 7.65 (s, 1H), 7.53 (m, 3H), 7.32 (m, 2H), 5.83 (s, 1H), 4.49 (q, J = 7.1 Hz, 2H), 1.48 (t, J = 7.1 Hz, 3H). 13C NMR (126 MHz, CDCI3) δ 159.6, 142.5, 139.9, 133.9, 130.3, 130.3, 124.4, 109.8, 109.0, 74.6, 31.4, 25.3, 23.5.

[0140] High resolution: HRMS (ESI) m / z: [M+H] + calcd for C 17 H 18 N3O2: 296.1394; found: 296.1392.

[0141] In addition, the new type of 4-cyano imidazole derivatives will have great application potential in the fields of medicine, pesticide and material.

[0142] The above only illustrates several embodiments of the present application, and therefore cannot be understood as a limitation on the scope of the patent of the present application. It should be noted that for other persons in the art, modifications, substitutions, improvements, etc. can be made without departing from the concept and scope of the present application, and these all belong to the protection scope of the present application. Therefore, the patent protection scope of the present application should be subject to the description according to the claims.

Claims

1. A base-promoted synthesis of 4-cyanoimidazole derivatives of the general formula c ###0001### characterized in that, The synthesis method involves using the compound shown in structural formula a, the compound shown in structural formula b, and trimethylnitrile silane as reactants, and reacting them in an organic solvent in the presence of a base. After the reaction is completed, the 4-cyanoimidazole derivative shown in general formula c is obtained. The compound of structural formula a is phenyl isothiocyanate, 4-methylphenyl isothiocyanate, 4-trifluoromethylphenyl isothiocyanate, 4-fluorophenyl isothiocyanate, 4-chlorophenyl isothiocyanate, 4-trifluoromethoxyphenyl isothiocyanate, 4-nitrophenyl isothiocyanate, 4-cyanophenyl isothiocyanate, 3-pyridyl isothiocyanate, 2-methylphenyl isothiocyanate, 2-iodophenyl isothiocyanate, 2-naphthyl isothiocyanate, 2-chlorophenyl isothiocyanate, benzoyl isothiocyanate, or 2-phenylethyl isothiocyanate; R 2 is methyl or ethyl; The base is 1,8-diazabicyclo[5.4.0]undec-7-ene.

2. The method of synthesis of claim 1, wherein, The molar ratio of the compound represented by structural formula a, the compound represented by structural formula b, trimethylnitrile silane, and the base is 1:1:1:

3.

3. The method of synthesis according to claim 1, wherein, The organic solvent is any one or two of methyl tert-butyl ether, 1,2-dibromoethane, and acetonitrile.

4. The method of synthesis of claim 1, wherein, The reaction is carried out in air at room temperature for 2-12 hours.

5. The method of synthesis of claim 1, wherein, After the reaction is completed, the reaction solution needs to be filtered and concentrated to obtain a solid precipitate, which is then eluted.

6. The method of synthesis of claim 5, wherein, The solid precipitate was eluted using petroleum ether and / or ethyl acetate.

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