Method for synthesizing 5-acetyl-3-chloroiminodibenzyl using palladium acetate as catalyst
Through palladium acetate catalyzed method, 5-acetyl-3-chloriminodibenzyl is synthesized from iminodibenzyl, which solves the problem of few synthesis methods and low yields in the prior art, and achieves high efficiency and high content Product generation meets the production needs of pharmaceutical intermediates.
Patent Information
- Application Number
- CN201910587632.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2019-07-02
- Publication Date
- 2024-12-10
- Estimated Expiration
- 2039-07-02
AI Technical Summary
In the prior art, there are few reports on the synthesis method of 5-acetyl-3-chloriminodibenzyl, and the total yield is not high, making it difficult to meet the production needs of pharmaceutical intermediates.
Using palladium acetate catalytic method, iminodibenzyl is used to form 5-acetyliminodibenzyl by acylation, and then react with N-chlorosuccinimide under the catalytic palladium acetate to form 5-acetyl 3-chloriminodibenzyl. The method includes the steps of uniform heating, insulation, cooling, heating and re-insulation, dilute acetic acid washing and ethanol purification in a three-neck flask with a reflux device.
The efficient synthesis of 5-acetyl-3-chloriminodibenzyl was achieved, with the product content reaching more than 99.31%, and the yield reached more than 67.01%, meeting the production needs of pharmaceutical intermediates.
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of organic synthesis and relates to a method for synthesizing 5-acetyl-3-chloroiminodibenzyl with the catalysis of palladium acetate. Background Art
[0002] 5-Acetyl-3-chloroiminodibenzyl is an important pharmaceutical intermediate, and it is an important intermediate for the synthesis of the antidepressant clomipramine. Clomipramine is a tricyclic antidepressant, and its main function is to block the reuptake of norepinephrine and 5-hydroxytryptamine in the central nervous system. It has a stronger blocking effect on the reuptake of 5-hydroxytryptamine, and exerts antidepressant and antianxiety effects, and also has sedative and anticholinergic effects.
[0003] 5-Acetyl-3-chloroiminodibenzyl is a new type of compound. There are few reports on its synthesis method. The synthesis methods that have been seen include: Wang Youzhi et al. studied that iminodibenzyl was used as the raw material, and acylation and nitration were performed to generate 5-acetyl-3-nitroiminodibenzyl; reduction reaction was performed to generate 5-acetyl-3-aminoiminodibenzyl; diazotization and Sandmeyer reaction were performed to generate 5-acetyl-3-chloroiminodibenzyl, and the total yield reached more than 51%. Summary of the invention
[0004] The present invention aims to provide a method for synthesizing 5-acetyl-3-chloroiminodibenzyl by using palladium acetate as catalyst. The method is characterized in that iminodibenzyl is used as a raw material, acylated to generate 5-acetyliminodibenzyl, and then reacted with N-chlorosuccinimide under the catalysis of palladium acetate to generate 5-acetyl-3-chloroiminodibenzyl.
[0005] The present invention is achieved by the following method:
[0006] In the first step, 1.0 mole of iminodibenzyl, 3.0-6.0 moles of acetic acid, 1.1-2.0 moles of acetic anhydride and 0.002-0.005 moles of perchloric acid are added to a three-necked flask with a reflux device, and the mixture is heated to 105-110° C. at a uniform rate. After being kept warm for 2-3 hours, the mixture is cooled to 20° C. to obtain an acetic acid solution of 5-acetyliminodibenzyl.
[0007] In the second step, add 0.001-0.003 mole of palladium acetate and 1.1-1.5 mole of N-chlorosuccinimide to the above solution. Heat to 100-105°C and keep warm for 8-15 hours. Then cool to 25-30°C, add 1.0-2.0 mole of water, stir for 0.5-1.0 hour, and cool to 5-10°C. Filter by suction, wash with dilute acetic acid, and purify the crude product with ethanol to obtain off-white 5-acetyl-3-chloroiminodibenzyl. DETAILED DESCRIPTION
[0008] The present invention will be further described below in conjunction with specific embodiments, but the present invention is not limited to these specific embodiments.
[0009] Example 1:
[0010] Add 197g of iminodibenzyl, 250g of acetic acid, 125g of acetic anhydride and 0.2g of perchloric acid into a three-necked flask with a reflux device, heat to 105-110°C at a uniform speed, keep warm for 2-3 hours, then cool to 20°C to obtain an acetic acid solution of 5-acetyliminodibenzyl.
[0011] Add 0.10g of palladium acetate and 135g of N-chlorosuccinimide to the above solution. Heat to 100-105°C and keep warm for 8-12 hours. Then cool to 25-30°C, add 15g of water, stir for 1.0-1.5 hours, and cool to 5-10°C. Filter by suction, wash with dilute acetic acid, and purify the crude product with ethanol to obtain 182.09g of off-white 5-acetyl-3-chloroiminodibenzyl, with a content of 99.31% and a yield of 67.01% (mp: 123.9~ 124.5°C).
[0012] Example 2:
[0013] Add 197 g of iminodibenzyl, 300 g of acetic acid, 113 g of acetic anhydride and 0.4 g of perchloric acid into a three-necked flask with a reflux device, heat to 105-110°C at a uniform rate, keep warm for 2-3 hours, then cool to 20°C to obtain an acetic acid solution of 5-acetyliminodibenzyl.
[0014] Add 0.13g of palladium acetate and 150g of N-chlorosuccinimide to the above solution. Heat to 100-105°C and keep warm for 10-12 hours. Then cool to 25-30°C, add 20g of water, stir for 0.5-1.0 hours, and cool to 5-10°C. Filter by suction, wash with dilute acetic acid, and purify the crude product with ethanol to obtain 183.06g of off-white 5-acetyl-3-chloroiminodibenzyl, with a content of 99.36% and a yield of 67.36% (mp: 124.1~ 124.5°C).
[0015] Example 3:
[0016] Add 197 g of iminodibenzyl, 350 g of acetic acid, 120 g of acetic anhydride and 0.3 g of perchloric acid into a three-necked flask with a reflux device, heat to 105-110°C at a uniform rate, keep warm for 2-3 hours, then cool to 20°C to obtain an acetic acid solution of 5-acetyliminodibenzyl.
[0017] Add 0.20g of palladium acetate and 160g of N-chlorosuccinimide to the above solution. Heat to 100-105°C and keep warm for 10-15 hours. Then cool to 25-30°C, add 25g of water, stir for 1.0-1.5 hours, and cool to 5-10°C. Filter by suction, wash with dilute acetic acid, and purify the crude product with ethanol to obtain 185.27g of off-white 5-acetyl-3-chloroiminodibenzyl, with a content of 99.51% and a yield of 68.18% (mp: 124.3~ 124.7°C).
Claims
1. A method for synthesizing 5-acetyl-3-chloroiminodibenzyl using palladium acetate as a catalyst, characterized in that iminodibenzyl is used as a raw material, acylated to generate 5-acetyliminodibenzyl, and then reacted with N-chlorosuccinimide under the catalysis of palladium acetate to generate 5-acetyl-3-chloroiminodibenzyl; The specific synthesis steps of the 5-acetyl-3-chloroiminodibenzyl are: The first step is to add 1.0 mole of iminodibenzyl, 3.0-6.0 moles of acetic acid, 1.1-2.0 moles of acetic anhydride and 0.002-0.005 moles of perchloric acid into a three-necked flask with a reflux device, heat to 105-110° C. at a uniform rate, keep warm for 2-3 hours, and then cool to 20° C. to obtain an acetic acid solution of 5-acetyliminodibenzyl; In the second step, 0.001-0.003 mole of palladium acetate and 1.1-1.5 mole of N-chlorosuccinimide are added to the above solution, heated to 100-105°C, kept warm for 8-15 hours, then cooled to 25-30°C, 1.0-2.0 mole of water is added, stirred for 0.5-1.0 hour, cooled to 5-10°C, filtered, washed with dilute acetic acid, and the crude product is refined with ethanol to obtain light yellow 5-acetyl-3-chloroiminodibenzyl.