CN106083728A - Diaryl the synthetic method of Diazepines - Google Patents

Abstract

The present invention relates to a kind of synthetic method of diaryl diazepine compound, specifically: take o-halogenated aryl carbinol, 1,2-diamine arene, ruthenium catalyst, copper salt, ethylene glycol, and alkali Add it into an organic solvent, heat it under the protection of _N2 , extract, evaporate to dryness, and recrystallize to obtain the product after the reaction is completed; the present invention utilizes commercially available and relatively low-priced ruthenium and copper catalysts to co-catalyze the o-halogenated arylmethanol The reaction with 1,2-diamine aromatics generates diaryldiazepines in one step through hydrogen transfer reaction and carbon-nitrogen coupling reaction. This synthesis method is simple, economical and efficient, and has high yield. It has important Value.

Description

Synthetic method of diaryl diazepines

technical field

The invention relates to the technical field of organic synthesis, in particular to a synthesis method of diaryldiazepine compounds.

Background technique

Diaryldiazepines, a class of compounds with important physiological and pharmacological activities, are often used as antidepressants, anticonvulsants, sedatives, analgesics and other drugs. This kind of compound also has antifungal, antibacterial, antiviral and other effects, so the research on its synthesis method has been widely concerned by people. Traditional synthetic methods use o-haloarylamine, o-nitroarylamine or anthranilic acid as starting materials and synthesize them through multi-step reactions. These methods require the use of very toxic reagents, harsh reaction conditions, and low overall yields. Low, great environmental pollution. In recent years, coupling reactions catalyzed by transition metals have become an important means of organic synthesis, and are currently the most studied and most promising method. Among them, palladium-catalyzed carbon-nitrogen bond coupling reaction of halogenated aromatic hydrocarbons has been reported a lot, but the palladium catalyst is relatively expensive, which limits its industrial application.

Contents of the invention

The object of the present invention is to provide a kind of synthetic method of diaryl diazepine compound in order to solve the deficiency of above-mentioned technical problem.

In order to solve the deficiencies of the above-mentioned technical problems, the technical solution adopted by the present invention is: a synthesis method of diaryldiazepine compounds, specifically: taking o-halogenated arylmethanol, 1,2-diamine Aromatic hydrocarbons, ruthenium catalysts, copper salts, ethylene glycol and alkalis are added to organic solvents, heated under the protection of _N2 , after the reaction is completed, extraction, evaporation to dryness and recrystallization are carried out to obtain the product;

The preparation method of diaryl diazepines is as follows:

;

The structural formula of the o-halogenated aryl carbinol is as follows:

;

The structural formula of the 1,2-diamine arene is as follows:

;

Where: R is -H, -CH ₃ , -OCH ₃ , -F or -CF ₃ , R is located at any position on the aromatic ring 1-4; X is -Br or -I; R ₁ can be -H or -CH ₃ ; R ₂ is -H, -CH ₃ , -OCH ₃ , -COOMe, -CN, -F or -CF ₃ , R ₂ is located at any position on the aromatic ring 5-8;

The structural formula of the diaryl diazepines is as follows:

;

The R, R ₁ and R ₂ groups in the diaryldiazepine compound have the same meanings as the R, R ₁ and R ₂ groups of o-halogenated aryl carbinol and 1,2-diamine arene.

In the synthetic method of above-mentioned diaryl diazepine compound, the molar ratio of described o-halogenated aryl carbinol, 1,2-diamine arene, ruthenium catalyst, copper salt, ethylene glycol and alkali is 1 : 1～1.5: 0.03～0.1: 0.05～0.1: 2～6: 3～9.

In the synthesis method of the above-mentioned diaryldiazepine compounds, the heating reaction conditions are as follows: the reaction temperature is 80-120° C., the reaction time is 6-48 hours, and the product is purified by recrystallization after the reaction.

In the above synthesis method of diaryldiazepines, the ruthenium catalyst is p-cymene dichloride ruthenium dimer, RuH ₂ (PPh ₃ ) ₄ or Ru (PPh ₃ ) ₂ Cl ₂ .

In the above synthesis method of diaryldiazepines, the copper salt is cuprous iodide or cuprous chloride.

In the above synthesis method of diaryldiazepines, the copper salt is cuprous iodide or cuprous chloride.

In the above synthesis method of diaryldiazepines, the copper salt is cuprous iodide or cuprous chloride.

Beneficial effect

The present invention utilizes commercially available and relatively low-priced ruthenium and copper catalysts to co-catalyze the reaction of ortho-halogenated aryl carbinol and 1,2-diamine aromatic hydrocarbons, and generates diaryl groups in one step through hydrogen transfer reaction and carbon-nitrogen coupling reaction The diazepine compounds provide a practical method for the synthesis of biologically active substituted diaryldiazepine derivatives. The method is simple to operate, economical and efficient, high in yield, and has important application value.

detailed description

The synthetic method of the present invention can prepare the biaryl azepin-5-ketone compound shown in the following table:

The following are specific examples of the synthesis invention of the present invention. The Arabic numerals in the above table represent the labels of each compound, and the compound labels in the examples are consistent with the compound labels in the above table.

Example 1

Preparation of diaryldiazepine compounds (1): Add 1.0mmol o-iodobenzyl alcohol, 1.0 mmol 1,2-o-phenylenediamine, 0.03 mmol Ru (PPh ₃ ) ₂ Cl ₂ , 0.03 mmol cuprous iodide, 2.0 mmol ethylene glycol, 2.0 mmol sodium hydroxide, and 5 ml toluene, replace the reaction tube with nitrogen 3 times, and then heated to 80° C. with an oil bath under magnetic stirring, and the reaction was refluxed for 6 hours. Remove the oil bath, and the water bath is lowered to room temperature; add 3ml of water to the reaction solution, extract _three times with 5ml of ethyl acetate, combine the organic phases and use anhydrous MgSO Dry for 30 minutes, filter; the filtrate is concentrated with a rotary evaporator, and the concentrated solid Using dichloromethane as solvent, the pure product 1 was obtained by recrystallization with a yield of 80%. The nuclear magnetic analysis data of this product are as follows: ¹ H NMR. (400 MHz, DMSO-d6): 8.13 (s, 1H), 7.07 (t, 1H), 6.99 (d, 1H), 6.89 (m, 2H), 6.71 (d, 1H), 6.64(m, 2H), 6.55 (t, 1H), 4.11 (s, 2H).

Example 2

Preparation of diaryldiazepine compounds (3): Add 1.0mmol o-bromobenzyl alcohol, 1.5 mmol 3-methyl-1,2-o-phenylenediamine, 0.05 mmol p-cymene dichloride ruthenium dimer, 0.1 mmol cuprous chloride, 6.0 mmol ethylene glycol, 9.0 mmol potassium hydroxide, and 5ml of dioxane was used to replace the reaction tube with nitrogen for 3 times, and then heated to 120° C. in an oil bath under magnetic stirring, and the reaction was refluxed for 48 hours. Remove the oil bath, and the water bath is lowered to room temperature; add 3ml of water to the reaction solution, extract _three times with 5ml of ethyl acetate, combine the organic phases and use anhydrous MgSO Dry for 30 minutes, filter; the filtrate is concentrated with a rotary evaporator, and the concentrated solid The pure product 3 was obtained by recrystallization with dichloromethane as solvent, and the yield was 80%. The nuclear magnetic analysis data of this product are as follows: ¹ H NMR. (400 MHz,DMSO-d6): 7.12 (t, 1H), 7.01 (d, 1H), 6.70-6.76 (m, 2H), 6.51-6.61 (m,3H), 5.89 (s, 1H), 5.84 (s, 1H), 4.26 (s, 2H), 2.20 (s, 3H).

Example 3

Preparation of diaryldiazepines (6): Under nitrogen protection, add 1.0mmol o-bromobenzyl alcohol, 1.2mmol 4-methoxy-1,2-o-phenylenediamine, 0.04mmol RuH ₂ (PPh ₃ ) ₄ , 0.06mmol cuprous chloride, 3.0mmol ethylene glycol, 5.0mmol potassium tert-butoxide, and 5ml di Replace the reaction tube with nitrogen for 3 times with toluene, then heat to 120°C with an oil bath under magnetic stirring, and reflux the reaction for 24 hours. Remove the oil bath, and the water bath is lowered to room temperature; add 3ml of water to the reaction solution, extract _three times with 5ml of ethyl acetate, combine the organic phases and use anhydrous MgSO Dry for 30 minutes, filter; the filtrate is concentrated with a rotary evaporator, and the concentrated solid Using dichloromethane as solvent, the pure product 6 was obtained by recrystallization with a yield of 86%. The nuclear magnetic analysis data of this product are as follows: ¹ H NMR. (400 MHz, DMSO-d6): 7.11 (t, 1H), 6.99 (d, 1H), 6.74 (m, 2H), 6.64 (d, 1H), 6.29 (m, 2H), 5.95(s, 1H), 4.24 (s, 2H), 3.76 (s, 3H).

Example 4

Preparation of diaryldiazepines (10): under nitrogen protection, add 1.0mmol o-iodobenzyl alcohol, 1.3 mmol 4-fluoro-1,2-o-phenylenediamine, 0.1 mmol RuH ₂ (PPh ₃ ) ₄ , 0.1 mmol cuprous iodide, 6.0 mmol ethylene glycol, 9.0 mmol sodium tert-butoxide, and 5 ml xylene, The reaction tube was replaced with nitrogen for 3 times, then heated to 120° C. in an oil bath under magnetic stirring, and the reaction was refluxed for 36 hours. Remove the oil bath, and the water bath is lowered to room temperature; add 3ml of water to the reaction solution, extract _three times with 5ml of ethyl acetate, combine the organic phases and use anhydrous MgSO Dry for 30 minutes, filter; the filtrate is concentrated with a rotary evaporator, and the concentrated solid The pure product 10 was obtained by recrystallization with dichloromethane as solvent, and the yield was 83%. The nuclear magnetic analysis data of this product are as follows: ¹ H NMR. (400 MHz, DMSO-d6): 7.14 (d, 1H), 7.02 (d, 1H), 6.78 (d, 1H), 6.74 (d, 1H), 6.60 (d, 2H), 6.47(d, 1H), 6.40 (d, 1H), 5.70 (s, 1H), 4.32 (s, 2H), 4.09 (s, 1H).

Example 5

Preparation of diaryldiazepines (12): under nitrogen protection, add 1.0mmol 4-trifluoroform to a 10 ml Schlek reaction tube (a glass instrument commonly used in anhydrous and oxygen-free operation) 1-bromobenzyl alcohol, 1.5mmol 1,2-o-phenylenediamine, 0.04mmol p-cymene dichloride ruthenium dimer, 0.08mmol cuprous iodide, 5.0mmol ethylene glycol, 5.0mmol sodium hydroxide, and 5ml of benzene, the reaction tube was replaced with nitrogen for 3 times, and then heated to 100° C. in an oil bath under magnetic stirring, and the reaction was refluxed for 30 hours. Remove the oil bath, and the water bath is lowered to room temperature; add 3ml of water to the reaction solution, extract _three times with 5ml of ethyl acetate, combine the organic phases and use anhydrous MgSO Dry for 30 minutes, filter; the filtrate is concentrated with a rotary evaporator, and the concentrated solid The pure product 12 was obtained by recrystallization with dichloromethane as solvent, and the yield was 87%. The nuclear magnetic analysis data of this product are as follows: ¹ H NMR.(400 MHz, DMSO-d6): 7.18 (t, 1H), 7.06 (d, 1H), 7.03 (d, 1H), 6.92 (s, 1H), 6.84 (t, 1H), 6.78 (d, 1H), 6.75 (d, 1H), 6.10 (s, 1H), 4.33 (s, 2H).

Example 6

Preparation of diaryldiazepines (15): under nitrogen protection, add 1.0mmol o-iodobenzyl alcohol, 1.4mmol 4-cyano-1,2-o-phenylenediamine, 0.03mmol Ru(PPh ₃ ) ₂ Cl ₂ , 0.09mmol cuprous iodide, 6.0mmol ethylene glycol, 5.0mmol sodium tert-butoxide, and 5ml di Replace the reaction tube with nitrogen for 3 times with toluene, then heat to 120°C with an oil bath under magnetic stirring, and reflux the reaction for 24 hours. Remove the oil bath, and the water bath is lowered to room temperature; add 3ml of water to the reaction solution, extract _three times with 5ml of ethyl acetate, combine the organic phases and use anhydrous MgSO Dry for 30 minutes, filter; the filtrate is concentrated with a rotary evaporator, and the concentrated solid The pure product 15 was obtained by recrystallization with dichloromethane as solvent, and the yield was 80%. The nuclear magnetic analysis data of this product are as follows: ¹ H NMR. (400 MHz, DMSO-d6): 7.19 (t, 1H), 7.06 (m, 2H), 6.92 (d, 1H), 6.86 (t, 1H), 6.80 (d, 1H), 6.70 (d, 1H), 6.18 (s, 1H), 4.31 (s, 2H).

Example 7

Preparation of diaryldiazepines (17): under nitrogen protection, add 1.0mmol o-bromobenzyl alcohol, 1.2mmol 4-methylcarboxy-1,2-o-phenylenediamine, 0.06mmol RuH ₂ (PPh ₃ ) ₄ , 0.07mmol cuprous iodide, 5.0mmol ethylene glycol, 6.0mmol potassium tert-butoxide, and 5ml Replace the reaction tube with nitrogen for 3 times with toluene, then heat to 100°C with an oil bath under magnetic stirring, and reflux for 30 hours. Remove the oil bath, and the water bath is lowered to room temperature; add 3ml of water to the reaction solution, extract _three times with 5ml of ethyl acetate, combine the organic phases and use anhydrous MgSO Dry for 30 minutes, filter; the filtrate is concentrated with a rotary evaporator, and the concentrated solid The pure product 17 was obtained by recrystallization with dichloromethane as solvent, and the yield was 78%. The nuclear magnetic analysis data of this product are as follows: ¹ H NMR. (400 MHz,DMSO-d6): 7.49 (d, 1H), 7.39 (d, 1H), 7.16 (d, 1H), 7.04 (t, 1H), 6.77-6.84 (m, 2H), 6.70 (d, 1H), 6.26 (s, 1H) , 4.29 (s, 2H), 3.88 (s, 3H).

Example 8

Preparation of diaryldiazepines (20): Under nitrogen protection, add 1.0 mmol of 5-methyl-ortho Iodobenzyl alcohol, 1.3mmol 4-methoxy-1,2-o-phenylenediamine, 0.06mmol p-cymene dichloride ruthenium dimer, 0.08mmol cuprous chloride, 4.0mmol ethylene glycol, 4.0mmol Potassium hydroxide, and 5ml of dioxane, the reaction tube was replaced with nitrogen for 3 times, then heated to 110° C. in an oil bath under magnetic stirring, and the reaction was refluxed for 18 hours. Remove the oil bath, and the water bath is lowered to room temperature; add 3ml of water to the reaction solution, extract _three times with 5ml of ethyl acetate, combine the organic phases and use anhydrous MgSO Dry for 30 minutes, filter; the filtrate is concentrated with a rotary evaporator, and the concentrated solid Using dichloromethane as a solvent, the pure product 20 was obtained by recrystallization with a yield of 85%. The nuclear magnetic analysis data of this product are as follows: ¹ HNMR. (400 MHz, DMSO-d6): 7.09 (d, 1H), 6.97 (d, 1H), 6.76 (d, 1H), 6.63(d, 1H), 6.26 (s, 1H), 5.93 (s, 1H), 5.88 (s, 1H), 4.23 (s, 2H), 3.75 (s, 3H), 2.23 (s, 3H).

Example 9

Preparation of diaryldiazepines (22): under nitrogen protection, add 1.0mmol 5-cyano-ortho Bromobenzyl alcohol, 1.2 mmol 4-methyl-1,2-o-phenylenediamine, 0.05 mmol RuH ₂ (PPh ₃ ) ₄ , 0.06 mmol cuprous iodide, 3.0 mmol ethylene glycol, 5.0 mmol sodium hydroxide, and 5ml of toluene was used to replace the reaction tube with nitrogen for 3 times, and then heated to 100°C with an oil bath under magnetic stirring, and the reaction was refluxed for 24 hours. Remove the oil bath, and the water bath is lowered to room temperature; add 3ml of water to the reaction solution, extract _three times with 5ml of ethyl acetate, combine the organic phases and use anhydrous MgSO Dry for 30 minutes, filter; the filtrate is concentrated with a rotary evaporator, and the concentrated solid The pure product 22 was obtained by recrystallization with dichloromethane as solvent, and the yield was 87%. The nuclear magnetic analysis data of this product are as follows: ¹ H NMR. (400 MHz,DMSO-d6): 7.18 (d, 1H), 7.05 (d, 1H), 6.87 (d, 1H), 6.76 (d, 1H), 6.35 (s, 1H), 6.07 (s, 1H), 5.93 (s, 1H), 4.25 (s, 2H), 2.22 (s, 3H).

Example 10

Preparation of diaryldiazepines (24): under nitrogen protection, add 1.0mmol 4-methoxy o-iodobenzyl alcohol, 1.4mmol 3-methyl-1,2-o-phenylenediamine, 0.07mmol Ru(PPh ₃ ) ₂ Cl ₂ , 0.05mmol cuprous iodide, 3.0mmol ethylene glycol, 3.0mmol tert-butanol Sodium, and 5ml of benzene, the reaction tube was replaced with nitrogen for 3 times, and then heated to 90°C with an oil bath under magnetic stirring, and the reaction was refluxed for 22 hours. Remove the oil bath, and the water bath is lowered to room temperature; add 3ml of water to the reaction solution, extract _three times with 5ml of ethyl acetate, combine the organic phases and use anhydrous MgSO Dry for 30 minutes, filter; the filtrate is concentrated with a rotary evaporator, and the concentrated solid The pure product 24 was obtained by recrystallization with dichloromethane as solvent, and the yield was 81%. The nuclear magnetic analysis data of this product are as follows: ¹ H NMR. (400 MHz,DMSO-d6): 7.11 (d, 1H), 7.02 (d, 1H), 6.68-6.75 (m, 2H), 6.46-6.55 (m, 2H), 5.86 (s, 1H), 5.82 (s, 1H), 4.24 (s, 2H), 3.73 (s, 3H), 2.23 (s, 3H).

Example 11

Preparation of diaryldiazepines (27): Under nitrogen protection, add 1.0 mmol o-iodobenzyl alcohol, 1.3 mmol 1,2-o-phenylene N-methyldiamine, 0.06 mmol Ru(PPh ₃ ) ₂ Cl ₂ , 0.09 mmol cuprous chloride, 5.0 mmol ethylene glycol, 3.0 mmol potassium tert-butoxide, and 5 ml xylene , the reaction tube was replaced with nitrogen for 3 times, and then heated to 120° C. in an oil bath under magnetic stirring, and the reaction was refluxed for 30 hours. Remove the oil bath, and the water bath is lowered to room temperature; add 3ml of water to the reaction solution, extract _three times with 5ml of ethyl acetate, combine the organic phases and use anhydrous MgSO Dry for 30 minutes, filter; the filtrate is concentrated with a rotary evaporator, and the concentrated solid Using dichloromethane as solvent, the pure product 27 was obtained by recrystallization with a yield of 79%. The nuclear magnetic analysis data of this product are as follows: ¹ H NMR. (400 MHz, DMSO-d6): 7.22 (d, 1H), 7.15 (d, 1H), 7.08 (m, 2H), 6.96 (d, 1H), 6.90 (d, 1H), 6.75-6.82 (m, 3H), 4.29 (s, 2H) , 3.22 (s, 3H), 2.81 (s, 3H).

Example 12

Preparation of diaryldiazepines (28): Under nitrogen protection, add 1.0 mmol o-iodobenzyl alcohol, 1.5mmol 4-methoxy-1,2-o-phenylene N-methyldiamine, 0.07mmol p-cymene dichloride ruthenium dimer, 0.1mmol cuprous iodide, 6.0mmol ethylene glycol, 6.0mmol Potassium hydroxide, and 5ml of dioxane, the reaction tube was replaced with nitrogen for 3 times, then heated to 120°C with an oil bath under magnetic stirring, and the reaction was refluxed for 30 hours. Remove the oil bath, and the water bath is lowered to room temperature; add 3ml of water to the reaction solution, extract _three times with 5ml of ethyl acetate, combine the organic phases and use anhydrous MgSO Dry for 30 minutes, filter; the filtrate is concentrated with a rotary evaporator, and the concentrated solid Using dichloromethane as solvent, the pure product 28 was obtained by recrystallization with a yield of 81%. The nuclear magnetic analysis data of this product are as follows: ¹ HNMR. (400 MHz, DMSO-d6): 7.10 (t, 1H), 6.97 (d, 1H), 6.72 (m, 2H), 6.61(d, 1H), 6.25 (m, 2H), 5.93 (s, 1H), 4.26 (s, 2H), 3.23 (s, 3H), 2.80 (s, 3H).

Example 13

Preparation of diaryldiazepines (30): under nitrogen protection, add 1.0 mmol o-iodobenzyl alcohol, 1.4mmol 4-cyano-1,2-o-phenylene N-methyldiamine, 0.06mmol RuH ₂ (PPh ₃ ) ₄ , 0.08mmol cuprous chloride, 5.0mmol ethylene glycol, 5.0mmol potassium tert-butoxide, and 5ml of toluene, the reaction tube was replaced with nitrogen for 3 times, and then heated to 100° C. in an oil bath under magnetic stirring, and the reaction was refluxed for 38 hours. Remove the oil bath, and the water bath is lowered to room temperature; add 3ml of water to the reaction solution, extract _three times with 5ml of ethyl acetate, combine the organic phases and use anhydrous MgSO Dry for 30 minutes, filter; the filtrate is concentrated with a rotary evaporator, and the concentrated solid Using dichloromethane as solvent, the pure product 30 was obtained by recrystallization with a yield of 75%. The nuclear magnetic analysis data of this product are as follows: ¹ H NMR. (400 MHz,DMSO-d6): 7.16 (t, 1H), 7.05 (d, 2H), 6.89 (d, 1H), 6.84 (d, 1H), 6.76 (d,1H), 6.66 (d, 1H), 6.13 (s, 1H), 4.30 (s, 2H), 3.25 (s, 3H), 2.81 (s, 3H).

Example 14

Preparation of diaryldiazepines (32): under nitrogen protection, add 1.0 mmol o-bromobenzyl alcohol, 1.5mmol 3-trifluoromethyl-1,2-o-phenylene N-methyldiamine, 0.08mmol p-cymene dichloride ruthenium dimer, 0.1mmol cuprous iodide, 6.0mmol ethylene glycol, 9.0 Mmol potassium hydroxide and 5ml xylene were used to replace the reaction tube with nitrogen for 3 times, then heated to 120° C. in an oil bath under magnetic stirring, and the reaction was refluxed for 40 hours. Remove the oil bath, and the water bath is lowered to room temperature; add 3ml of water to the reaction solution, extract _three times with 5ml of ethyl acetate, combine the organic phases and use anhydrous MgSO Dry for 30 minutes, filter; the filtrate is concentrated with a rotary evaporator, and the concentrated solid The pure product 32 was obtained by recrystallization with dichloromethane as solvent, and the yield was 75%. The nuclear magnetic analysis data of this product are as follows: ¹ HNMR. (400 MHz, DMSO-d6): 7.15 (t, 1H), 7.03 (d, 1H), 7.01 (s, 1H), 6.90(s, 1H), 6.81 (t, 1H), 6.75 (d, 1H), 6.70 (s, 1H), 6.05 (s, 1H), 4.25 (s, 2H), 3.24 (s, 3H), 2.81 (s, 3H).

Example 15

Preparation of diaryldiazepines (34): under nitrogen protection, add 1.0mmol 5-methoxy o-iodobenzyl alcohol, 1.3mmol 4-methyl-1,2-o-phenylene N-methyldiamine, 0.08mmol RuH ₂ (PPh ₃ ) ₄ , 0.08mmol cuprous chloride, 5.0mmol ethylene glycol, 5.0mmol Sodium tert-butoxide, and 5ml of dioxane, the reaction tube was replaced with nitrogen for 3 times, then heated to 110° C. in an oil bath under magnetic stirring, and the reaction was refluxed for 36 hours. Remove the oil bath, and the water bath is lowered to room temperature; add 3ml of water to the reaction solution, extract _three times with 5ml of ethyl acetate, combine the organic phases and use anhydrous MgSO Dry for 30 minutes, filter; the filtrate is concentrated with a rotary evaporator, and the concentrated solid Using dichloromethane as solvent, the pure product 34 was obtained by recrystallization with a yield of 77%. The nuclear magnetic analysis data of this product are as follows: ¹ H NMR. (400MHz, DMSO-d6): 7.08 (d, 1H), 6.96 (d, 1H), 6.78 (d, 1H), 6.62 (d, 1H), 6.25 (s, 1H), 5.92 (s, 1H), 5.85 (s, 1H), 4.26 (s, 2H), 3.76 (s, 3H), 3.23(s, 3H), 2.80 (s, 3H), 2.23 (s, 3H).

Example 16

Preparation of diaryldiazepines (36): under nitrogen protection, add 1.0mmol 5-cyano-ortho Bromobenzyl alcohol, 1.3mmol 4-methyl 1,2-o-phenylene N-methyldiamine, 0.05mmol p-cymene dichloride ruthenium dimer, 0.1mmol cuprous iodide, 6.0mmol ethylene glycol, 6.0 mmol of potassium tert-butoxide and 5 ml of xylene were used to replace the reaction tube with nitrogen three times, then heated to 120° C. in an oil bath under magnetic stirring, and the reaction was refluxed for 38 hours. Remove the oil bath, and the water bath is lowered to room temperature; add 3ml of water to the reaction solution, extract _three times with 5ml of ethyl acetate, combine the organic phases and use anhydrous MgSO Dry for 30 minutes, filter; the filtrate is concentrated with a rotary evaporator, and the concentrated solid The pure product 36 was obtained by recrystallization with dichloromethane as solvent, and the yield was 82%. The nuclear magnetic analysis data of this product are as follows: ¹ HNMR. (400 MHz, DMSO-d6): 7.19 (d, 1H), 7.08 (d, 1H), 6.89 (d, 1H), 6.77 (d, 1H), 6.38 (s, 1H), 6.09 (s, 1H), 5.96 (s, 1H), 4.29 (s, 2H), 3.25 (s, 3H), 2.82 (s, 3H), 2.25 (s, 3H).

Claims (7)

1. the synthetic method of diaryl Diazepines, it is characterised in that: take adjacent halogenated aryl methyl alcohol, 1,2-diamines Aromatic hydrocarbons, ruthenium catalyst, mantoquita, ethylene glycol and alkali join in organic solvent, at N₂The lower heating of protection, reaction terminate after extraction, It is evaporated, recrystallize and i.e. obtain product；

The structural formula of described adjacent halogenated aryl methyl alcohol is as follows:

；

The structural formula of described 1,2-diamines aromatic hydrocarbons is as follows:

；

Wherein: R is-H ,-CH₃、-OCH₃,-F or-CF₃, R is positioned at any position on aromatic ring 1-4；X is-Br or-I； R₁Can be- H or-CH₃；R₂For-H ,-CH₃、-OCH₃,-COOMe ,-CN ,-F or-CF₃, R₂It is positioned at any position on aromatic ring 5-8；

The structural formula of described diaryl Diazepines is as follows:

；

R, R in this diaryl Diazepines₁And R₂Group and adjacent halogenated aryl methyl alcohol, 1,2-diamines aromatic hydrocarbons R、R₁And R₂Group connotation is identical.

2. the synthetic method of diaryl as claimed in claim 1 Diazepines, it is characterised in that: described adjacent halogen For aryl methyl alcohol, 1,2-diamines aromatic hydrocarbons, the mol ratio of ruthenium catalyst, mantoquita, ethylene glycol and alkali is 1:1～1.5:0.03～0.1: 0.05～0.1:2～6:3～9.

3. the synthetic method of diaryl as claimed in claim 1 Diazepines, it is characterised in that: described heating The condition of reaction is: reaction temperature is 80-120 DEG C, reaction time 6-48h, and product is carried after terminating by reaction by recrystallization Pure.

4. the synthetic method of the diaryl as described in any claim in claim 1-3 Diazepines, its It is characterised by: described ruthenium catalyst is p-cymene ruthenous chloride dimer, RuH₂(PPh₃)₄Or Ru (PPh₃)₂Cl₂。

5. the synthetic method of the diaryl as described in any claim in claim 1-3 Diazepines, its It is characterised by: described mantoquita is cuprous iodide or stannous chloride.

6. the synthetic method of the diaryl as described in any claim in claim 1-3 Diazepines, its It is characterised by: described alkali is NaOH, potassium hydroxide, sodium tert-butoxide or potassium tert-butoxide.

7. the synthetic method of the diaryl as described in any claim in claim 1-3 Diazepines, its It is characterised by: described organic solvent is benzene,toluene,xylene or dioxane.