Preparation method for 2- cyanogroup-4 '-methyl diphenyl

A technology of methyl biphenyl and cyano, which is applied in the preparation of 2-cyano-4'-methyl biphenyl and the preparation of antihypertensive drug intermediates, which can solve the problem of high catalyst price and lack of cost advantages. problems, to achieve the effect of enhancing catalytic efficiency, increasing catalyst activity, and improving reaction yield

Active Publication Date: 2014-10-01
SHANDONG HANXING PHARM TECH CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] The raw materials of this route are easy to obtain and the route is simple, but the price of the catalyst is relatively high, and sometimes a composite catalyst is required, which does not have a cost advantage

Method used

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  • Preparation method for 2- cyanogroup-4 '-methyl diphenyl
  • Preparation method for 2- cyanogroup-4 '-methyl diphenyl
  • Preparation method for 2- cyanogroup-4 '-methyl diphenyl

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] 1. Preparation of Compound (I) Grignard Reagent

[0042]

[0043] 506g of p-chlorotoluene and 500g of tetrahydrofuran are formulated into p-chlorotoluene solution, 96g of magnesium chips are added in the reaction flask, then 100g of the above-mentioned p-chlorotoluene solution is added, and 4g of initiator (1,2-dibromoethane) is added, Stir and heat up to 60-75°C. After a large number of bubbles are generated and the temperature rises significantly, slowly add the remaining p-chlorotoluene solution dropwise. During the dropping process, keep the temperature at 60-75°C. Qualified, add tetrahydrofuran 1500g to dilute the Grignard solution.

[0044] Two, the preparation of compound (Ⅱ)

[0045]

[0046] Preparation of application solution: 12g MnCl 2 Put it into the reaction bottle, add about 1500g of tetrahydrofuran to the reaction bottle in advance, stir and cool down to -5~5°C. Add 450g o-chlorobenzonitrile and 500g tetrahydrofuran mixed solution. Control the ...

Embodiment 2

[0051] 1. Preparation of compound (I) Grignard solution

[0052]

[0053] Add 96Kg of magnesium chips into the dry Grignard kettle, and at the same time, mix 506Kg of p-chlorotoluene and 500Kg of tetrahydrofuran evenly, and put them into the high-level tank. Dibromoethane (only for batch use), stir and heat up to 60-75°C, after a large number of bubbles appear and the temperature rises significantly, then slowly add the remaining p-chlorotoluene solution dropwise, keep the temperature at 60-75°C during the dropwise addition, add After completion, react at constant temperature for 4 hours. After the sampling test is qualified, 1500Kg of tetrahydrofuran is added to dilute the Grignard solution, and the temperature is lowered to 40-50°C for discharge. If the reaction does not meet the quality standard, the time can be extended or an appropriate amount of magnesium powder can be added.

[0054] Two, the preparation of compound (Ⅱ)

[0055]

[0056] Put 12Kg of catalyst man...

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PUM

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Abstract

The invention discloses a preparation method for 2- cyanogroup-4 '-methyl diphenyl. The preparation method comprises the following steps: (1), reacting in tetrahydrofuran in the presence of an initiator by using magnesium powder and parachlorotoluene to obtain a p-methylphenyl magnesium chloride Grignard reagent; (2), under catalysis of manganese chloride, dropwise adding the p-methylphenyl magnesium chloride Grignard reagent into tetrahydrofuran liquor of chlorobenzonitrile to carry out coupling reaction, treating part of reaction liquor to obtain 2- cyanogroup-4 '-methyl diphenyl; and (3), under catalysis of manganese chloride, by taking residual reaction liquor in the step (2) as a backing material, adding the tetrahydrofuran liquor of chlorobenzonitrile, dropwise adding the p-methylphenyl magnesium chloride Grignard reagent to carry out coupling reaction to obtain the 2- cyanogroup-4 '-methyl diphenyl. The preparation method disclosed by the invention strengthens catalytic efficiency of coupling reaction by using part of the reaction liquor, improves reaction conversion rate, reduces production of byproduct dimethyl biphenyl, and is suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of an antihypertensive drug intermediate, in particular to a preparation method of 2-cyano-4'-methylbiphenyl, which belongs to the field of medicine and chemical industry. Background technique [0002] 2-cyano-4'-methylbiphenyl, also known as sartan biphenyl, CAS No.: 114772-53-1, is an important pharmaceutical intermediate, widely used in a variety of new sartan antihypertensive Synthesis of drugs. Sartan antihypertensive drugs have huge market potential because of their obvious antihypertensive effect, good tolerance, unique curative effect and protective effect on cardiovascular diseases. [0003] At present, there are many ways to synthesize 2-cyano-4’-methylbiphenyl, which are mainly divided into traditional organic synthesis and transition metal catalyzed synthesis, which will be introduced respectively below. [0004] People such as Carini take salicylic acid or o-anisic acid as raw material, apply...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C253/30C07C255/50
Inventor 郭长法茅晔周雄飞徐健李星万国华刘杰庄程翰
Owner SHANDONG HANXING PHARM TECH CO LTD
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