Chemical synthesis method for 2,3,4,5-tetrahydro-1H-2-benzazepin-1-one derivatives

A -1H-2-, chemical synthesis technology, applied in the direction of organic chemistry, can solve the problems of difficult main products, difficult separation, low reaction yield, etc., and achieve the effect of improving yield

Inactive Publication Date: 2012-11-28
NANTONG UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In general, these two routes make it difficult for 2,3,4,5-tetrahydro-1H-2-benzazepine-1-one derivatives to become the main reaction due to the limitation of the rearrangement mechanism of the reaction itself. product
The reaction yield is very low, and the separation is difficult

Method used

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  • Chemical synthesis method for 2,3,4,5-tetrahydro-1H-2-benzazepin-1-one derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Synthesis of methyl o-bromobenzoate:

[0026] Add 20.0g o-bromobenzoic acid and 200ml methanol into a 500ml three-necked round bottom flask, stir to dissolve, add SOCl at room temperature 2 17.8g, reacted under reflux for 8h after dropping, concentrated the reaction solution, added 500ml of water, extracted with 500ml of methyl tert-butyl ether, combined the organic phases, and washed with saturated NaHCO 3 The solution was washed, washed with saturated brine, dried and concentrated to obtain 22.5 g of methyl o-bromobenzoate, with a yield of 98%.

[0027] Synthesis of 2-(2'-cyanovinyl) methyl benzoate:

[0028] Add 18.0g of methyl o-bromobenzoate, 8.4g of acrylonitrile, 15.9g of triethylamine, 0.3g of palladium acetate, 170ml of DMF and 0.8g of triphenylphosphine into a 500ml three-necked round-bottomed flask, stir mechanically, and heat Reflux for 10 h, cool to room temperature, add to ice water, extract with petroleum ether, wash the organic phase with 1M hydrochlor...

Embodiment 2

[0032] Synthesis of methyl 2-bromo-6-methoxybenzoate:

[0033] Add 23.1g of 2-bromo-6-methoxybenzoic acid and 200ml of methanol into a 500ml three-necked round-bottomed flask, stir to dissolve, and add SOCl at room temperature 2 17.8g, reacted under reflux for 8h after dropping, concentrated the reaction solution, added 500ml of water, extracted with 500ml of methyl tert-butyl ether, combined the organic phases, and washed with saturated NaHCO 3 The solution was washed, washed with saturated brine, dried and concentrated to obtain 23.5 g of methyl 2-bromo-6-methoxybenzoate, with a yield of 96%.

[0034] Synthesis of 2-(2'-cyanovinyl)-6-methoxybenzoic acid methyl ester:

[0035] Add 20.0g of methyl 2-bromo-6-methoxybenzoate, 8.4g of acrylonitrile, 15.9g of triethylamine, 0.3g of palladium acetate, 170ml of DMF and 0.8g of triphenylphosphine into a 500ml three-hole round bottom In the flask, stir mechanically, heat and reflux for 10h, cool to room temperature, add to ice water...

Embodiment 3

[0039] Synthesis of methyl 2-bromo-7-methoxybenzoate:

[0040] Add 23.1g of 2-bromo-7-methoxybenzoic acid and 200ml of methanol into a 500ml three-necked round-bottomed flask, stir to dissolve, and add SOCl at room temperature 2 17.8g, after dripping, react under reflux for 8h, concentrate the reaction solution, add 500ml of water, extract with 500ml of methyl tert-butyl ether, combine the organic phases, and wash with saturated NaHCO 3 The solution was washed, washed with saturated brine, dried and concentrated to obtain 23.2 g of methyl 2-bromo-7-methoxybenzoate, with a yield of 95%.

[0041] Synthesis of 2-(2'-cyanovinyl)-7-methoxybenzoic acid methyl ester:

[0042] Add 20.0g of methyl 2-bromo-7-methoxybenzoate, 8.4g of acrylonitrile, 15.9g of triethylamine, 0.3g of palladium acetate, 170ml of DMF and 0.8g of triphenylphosphine into a 500ml three-hole round bottom In the flask, stir mechanically, heat and reflux for 10h, cool to room temperature, add to ice water, extract w...

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Abstract

The invention discloses a chemical synthesis method for 2,3,4,5-tetrahydro-1H-2-benzazepin-1-one derivatives. The synthesis method of the invention includes: reacting a substituted ortho-halo benzoic acid as a raw material with an alcohol to obtain corresponding substituted acid ester; reacting with acrylonitrile to obtain a 2-(2'-cyano-alkenyl)benzoate derivative intermediate; and conducting a ring-closure reaction in the presence of alkoxide to obtain the 2,3,4,5-tetrahydro-1H-2-benzazepin-1-one derivative. The method has the advantages of fewer reaction steps and high yield.

Description

technical field [0001] The invention relates to a chemical synthesis method of 2,3,4,5-tetrahydro-1H-2-benzazepin-1-one derivatives. Background technique [0002] 2,3,4,5-tetrahydro-1H-2-benzazepine-1-one derivatives are an important class of pharmaceutical intermediates, especially in the medicines for schizophrenia and neurasthenia. Therefore, the synthesis of this type of compound has broad application prospects. [0003] At present, there are mainly two methods for the chemical synthesis of 2,3,4,5-tetrahydro-1H-2-benzazepin-1-one derivatives, Schmidt rearrangement and Beckmann rearrangement. The Schmidt rearrangement is based on 3,4-dihydro-1(2H)-naphthalenone and azide acid, and the Beckmann rearrangement is based on 3,4-dihydro-1(2H)-naphthalenone and hydroxylamine. The two synthetic reactions are as follows: [0004] [0005] In these two chemical synthesis methods, due to the kinetics of the aryl group migration being greater than that of the alkyl group durin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D223/14
Inventor 朱金丽汤艳峰孙同明朱国华王树清张素梅项蕊高鹏飞
Owner NANTONG UNIVERSITY
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