Unlock instant, AI-driven research and patent intelligence for your innovation.

Method for preparing 4,4'-dicyanobenzophenone

A technology of dicyanobenzophenone and dihalogenated benzophenone, which is applied in 4 fields, can solve the problems of high price, low yield, increased production cost, etc., and achieve the effect of mild reaction conditions and simple process

Active Publication Date: 2009-12-09
ZHEJIANG HISOAR PHARMA
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method has the following disadvantages: (1) because the crude product needs to be purified by column chromatography, it not only causes a low yield of only 42% but also makes the production efficiency low, and the ultralow temperature of -92~-98° C. in the reaction is also not suitable for industrialized production ; (2) High-risk n-butyllithium is used, which is prone to danger during production, transportation and storage
This method uses expensive palladium chloride, which greatly increases the production cost
[0007] US5073574 discloses the method of preparing 4,4'-dicyanobenzophenone by reacting cuprous cyanide with 4,4'-dibromobenzophenone under reflux in DMF solution, but the obtained product 4, 4'-dicyanobenzophenone can only be separated by column chromatography, the production efficiency is relatively low, and it is not suitable for industrial production

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for preparing 4,4'-dicyanobenzophenone
  • Method for preparing 4,4'-dicyanobenzophenone
  • Method for preparing 4,4'-dicyanobenzophenone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 14

[0019] Embodiment 14,4'-dicyanobenzophenone

[0020] Put 150g (0.687mol) 4,4'-difluorobenzophenone, 130g (2.653mol) NaCN, 10g tetrabutylammonium bromide and 1200ml N, N-difluorobenzophenone into a 2000ml four-necked reaction flask with a reflux device. Methylformamide, heated and stirred, and kept at 130°C for 4hrs. Then drop to 80°C and recover about 800ml of DMF under reduced pressure, then add 800ml of 30% sodium thiosulfate aqueous solution and stir for 1hr, filter, wash the filter cake with 100ml of water, and dry at 70°C under normal pressure to obtain 145g crude product, purity (HPLC) : 85%.

Embodiment 24

[0021] Embodiment 24,4'-dicyanobenzophenone

[0022] Put 60g (0.275mol) 4,4'-dibromobenzophenone, 40g (0.816mol) NaCN, 4g tetrabutylammonium bromide and 500ml dimethyl sulfoxide into a 1000ml four-necked reaction flask with a reflux device , heat up and stir, and keep warm at 150°C for 6hr. Then reduce to 100°C and recover about 350ml of dimethyl sulfoxide under reduced pressure, then add 300ml of 30% sodium thiosulfate aqueous solution and stir for 1hr, filter, wash the filter cake with 40ml of water, and dry at 70°C under normal pressure to obtain 55g of crude product. Purity (HPLC): 70%.

Embodiment 34

[0023] Example 34, 4'-dicyanobenzophenone

[0024] Put 150g (0.687mol) 4,4'-difluorobenzophenone, 110g (1.692mol) KCN, 10g tetrabutylammonium bromide and 1200ml N, N-difluorobenzophenone into a 2000ml four-necked reaction flask with a reflux device Methylformamide, heated up and stirred, and kept at 100°C for 16hr. Then reduce to 80°C and recover about 900ml of DMF under reduced pressure, add 500ml of 30% sodium thiosulfate aqueous solution and stir for 1hr, filter, wash the filter cake with 100ml of water, and dry at 70°C under normal pressure to obtain 137g crude product, purity (HPLC) : 81%.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a method for preparing 4,4'-dicyanobenzophenone, which comprises the step of performing the reaction of 4,4'-dihalobenzophenone and alkali cyanide in a solvent to obtain the 4,4'-dicyanobenzophenone. The method has simple process and mild reaction conditions, and is applicable to industrial production.

Description

technical field [0001] The present invention relates to a kind of preparation method of letrozole intermediate, be specifically related to a kind of preparation method of 4,4'-dicyanobenzophenone. Background technique [0002] Letrozole (Letrozole), chemical name: 4,4'-(1H-1,2,4-triazol-1-ylmethylene) dibenzonitrile, is the third generation aromatization agent developed by Novartis Enzyme inhibitors, highly selective, reduce estrogen levels by inhibiting aromatase, and are mainly used in the treatment of postmenopausal breast cancer. [0003] 4,4'-dicyanobenzophenone is an intermediate for the synthesis of letrozole. The US patent application number US20070100149 and the Chinese patent application number CN200710068474 all disclose the use of 4,4'-dicyanodiphenyl A method for synthesizing letrozole from ketone. [0004] Prior art literature Chemistry of Materials, 11 (7), 117-1783; The method for the synthesis of 4,4'-dicyanobenzophenone disclosed in 199 is under nitrogen ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07C255/56C07C253/14
Inventor 唐鹤吴纲陈仙明
Owner ZHEJIANG HISOAR PHARMA