A kind of preparation method of 2-bromo-5-chlorobenzaldehyde

A technology of chlorobenzaldehyde and bromosuccinimide, applied in the field of pharmaceutical synthesis, can solve problems such as low total yield, long reaction steps, complicated operation and the like

Active Publication Date: 2021-09-10
JIANGHAN UNIVERSITY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although it has made great progress compared with the previous process, this process still has defects such as too long reaction steps, complicated operation, low overall yield, high production cost, and difficult to scale up production.

Method used

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  • A kind of preparation method of 2-bromo-5-chlorobenzaldehyde
  • A kind of preparation method of 2-bromo-5-chlorobenzaldehyde
  • A kind of preparation method of 2-bromo-5-chlorobenzaldehyde

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Put concentrated sulfuric acid (mass fraction 98%, 150mL) into the reaction kettle and stir to lower the temperature, control the temperature of the system to ≤10°C, slowly add compound A liquid (3-chlorobenzaldehyde, 0.5mol) dropwise, after the addition is complete, add an appropriate amount of catalyst I 2 (0.236-2.36mmol, the present embodiment is 30mg), add 3-chlorobenzaldehyde and catalyst I 2 When there is a relatively obvious exothermic phenomenon, it is necessary to control the reaction temperature of the system to ≤10°C;

[0036] System temperature control ≤ 15°C, add NBS (N-bromosuccinimide, 0.5mol) in batches for 5-10 times;

[0037] Insulate and react for 2 hours, slowly rise to 25°C, and then stir and react for 1 hour. GC detects that the content of 3-chlorobenzaldehyde in the raw material is ≤1%, and the reaction solution is post-processed and purified to obtain 98 g of needle-like off-white solid Compound B with a purity of 98.0%. Yield 90.1%.

Embodiment 2

[0039] Put concentrated sulfuric acid (mass fraction 98%, 100mL) into the reaction kettle and stir to lower the temperature, control the temperature of the system to ≤10°C, slowly add compound A liquid (3-chlorobenzaldehyde, 0.5mol) dropwise, after the addition is complete, add an appropriate amount of catalyst I 2 (0.236-2.36mmol, the present embodiment is 31.8mg), add 3-chlorobenzaldehyde and catalyst I 2 When there is a relatively obvious exothermic phenomenon, it is necessary to control the reaction temperature of the system to ≤10°C;

[0040] System temperature control ≤ 15°C, add NBS (N-bromosuccinimide, 0.5mol) in batches for 5-10 times;

[0041] Insulate and react for 2 hours, slowly raise to 25°C, and then stir for 1 hour. GC detects that the content of 3-chlorobenzaldehyde in the raw material is ≤1%, and the reaction solution is post-processed and purified to obtain 97.9 g of needle-like off-white solid compound B with a purity of 97.5%. , yield 90.0%.

Embodiment 3

[0043] Put concentrated sulfuric acid (98% mass fraction, 80mL) into the reaction kettle and stir to lower the temperature, control the temperature of the system to ≤10°C, slowly add compound A liquid (3-chlorobenzaldehyde, 0.5mol) dropwise, after the addition is complete, add an appropriate amount of catalyst I 2 (0.236-2.36mmol, the present embodiment is 63.5mg), add 3-chlorobenzaldehyde and catalyst I 2 When there is a relatively obvious exothermic phenomenon, it is necessary to control the reaction temperature of the system to ≤10°C;

[0044] System temperature control ≤ 15°C, add NBS (N-bromosuccinimide, 0.55mol) in batches for 5-10 times;

[0045] Insulate and react for 3 hours, slowly raise to 28°C, and then stir for 4 hours. GC detects that the content of 3-chlorobenzaldehyde in the raw material is ≤1%, and the reaction solution is post-processed and purified to obtain 98.5g of needle-like off-white solid Compound B with a purity of 98%. , yield 90.6%.

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Abstract

The invention discloses a preparation method of 2-bromo-5-chlorobenzaldehyde, which is characterized in that the steps are: a. In an inorganic strong acid solvent, control the temperature of the system to ≤10°C and slowly add 3-chlorobenzene successively dropwise Formaldehyde, iodine-containing catalyst; b. Control the temperature of the system to ≤15°C and add N-bromosuccinimide NBS several times in batches; c. After keeping the temperature for 2-10 hours, raise the temperature to 25-55°C to continue the reaction for 1- 6h; The solid product was obtained after post-processing. The present invention has one-step reaction, higher yield up to 90%, simpler operation, low cost, easy to obtain raw materials, less pollution to the environment, and only acid in the waste liquid, which can be neutralized with lye, more suitable The need for large-scale industrial production.

Description

technical field [0001] The invention relates to the field of drug synthesis, in particular to a preparation method of 2-bromo-5-chlorobenzaldehyde. Background technique [0002] 2-bromo-5-chlorobenzaldehyde (compound B), has the following structure: [0003] [0004] 2-Bromo-5-chlorobenzaldehyde is an important pharmaceutical intermediate, which can be used in the synthesis of various drugs. For the synthetic method of this compound, many articles of literature have reported its synthetic method at present, and general preparation method comprises the following steps (Scheme1): [0005] [0006] Use raw material C (2-bromobenzimide) to carry out simple chlorination in NCS (N-chlorosuccinimide) and sulfuric acid (≧98%) system to obtain 2-bromo-5-chlorobenzylformic acid; then 2-bromobenzimide -5-chlorobenzyl formic acid obtains compound D (2-bromo-5-chlorobenzylmethanol) by sodium borohydride and sulfuric acid (≧98%) system reduction; Finally 2-bromo-5-chlorobenzylmeth...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C47/55C07C45/63
CPCC07C45/63C07C47/55
Inventor 钱新华尹昊传尤庆亮李芳何丹黄园潘琼文朋胡博齐冯梦玲
Owner JIANGHAN UNIVERSITY
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