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Synthesis method of N-cyclohexyl-5-(4-chlorobutyl)-1H-tetrazole

A synthetic method, the technology of chlorobutyl, applied in the direction of organic chemistry, can solve the problems of low purity and high cost, and achieve the effect of high purity, high stability and high safety

Pending Publication Date: 2020-06-05
上海立科化学科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] Tetrazolium, alias 1H-tetrazolium, molecular formula CH2N4, is a peptide coupling agent; used as a catalyst in the triester-based phosphine method of (dialkylamino)phosphine coupling reaction to synthesize oligonucleotides, tetrazoleacetic acid , has another name called tetrazole acetic acid, 1H-tetrazolium-1-acetic acid, is mainly used in the synthesis of cephalosporin antibiotics, and its downstream products are cefazolin, ceftezole etc., and the cost of existing tetrazole synthetic method is higher, The purity obtained is lower

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0013] A kind of synthetic method of N-cyclohexyl-5-(4-chlorobutyl)-1H-tetrazolium, the preparation of 5-chloro-N-cyclohexylpentanamide:

[0014] Add 500 grams of concentrated sulfuric acid to a 1L reagent bottle, cool with an ice-salt bath at 0-5°C, add a mixture of 5-chlorovaleronitrile (60 grams) and cyclohexanol (70 grams) dropwise into the reagent bottle, drop After the addition, keep warm for 30 minutes, heat the mixture, and then increase it by 5 degrees every 30 minutes. When the temperature in the reaction reaches 25-30°C, keep it warm for 4 hours, and follow the gas phase until the peak area of ​​5-chlorovaleronitrile Less than 1%, the above reaction solution is poured into 1500 grams of crushed ice, and 250 ml of methyl isobutyl ketone is added for extraction, the aqueous phase is extracted with methyl isobutyl ketone (250 ml × 3), the organic phases are combined, and then extracted with Wash with aqueous sodium bicarbonate, and when the aqueous phase is neutral, wa...

Embodiment 2

[0016] Preparation of N-cyclohexyl-5-(4-chlorobutyl)-1H-tetrazolium:

[0017] Under the protection of nitrogen, put 88 grams of sodium azide and 500ml of toluene into a 1L four-necked bottle respectively, and quickly drop 130 grams of trimethylchlorosilane at 35°C, the mixed solution will be slightly cloudy, with a faint The phenomenon of temperature rise occurs. After the dropwise addition, the temperature rises to 70°C within 2-3 hours, and the heating is stopped after 16 hours of heat preservation reaction. The mixture is naturally cooled to room temperature, and the stirring is stopped. Pour the above prepared mixture into Set aside in the dropping funnel.

[0018] 75 grams of 5-chloro-N-cyclohexylpentanamide prepared in Example 1 and 600 ml of toluene were respectively put into a 2L four-neck flask, stirred at room temperature for 50 minutes, and cooled to 0 with an ice-salt bath until the solid was completely dissolved. -5°C, add 75 grams of phosphorus pentachloride in ...

Embodiment 3

[0020] Preparation of N-cyclohexyl-5-(4-chlorobutyl)-1H-tetrazolium:

[0021] Under the protection of nitrogen, put 68 grams of sodium azide and 400ml of toluene into a 1L four-necked bottle respectively, and quickly drop 120 grams of trimethylchlorosilane at 35°C, the mixed solution will be slightly cloudy, with a faint The phenomenon of temperature rise occurs. After the dropwise addition, the temperature rises to 70°C within 2-3 hours, and the heating is stopped after 16 hours of heat preservation reaction. The mixture is naturally cooled to room temperature, and the stirring is stopped. Pour the above prepared mixture into Set aside in the dropping funnel.

[0022] 70 grams of 5-chloro-N-cyclohexylpentanamide prepared in Example 1 and 500 ml of toluene were put into a 2L four-neck flask respectively, and after stirring at room temperature for 50 minutes, the solid was completely dissolved and cooled to 0 with an ice-salt bath. -5°C, add 75 grams of phosphorus pentachlorid...

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PUM

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Abstract

The invention discloses a synthesis method of N-cyclohexyl-5-(4-chlorobutyl)-1H-tetrazole. The synthesis method comprises the following steps: firstly, synthesizing N, N-dimethylformamide; the synthesis method comprises the following synthesis steps: taking 5-chlorovaleronitrile and cyclohexanol as raw materials, controlling the molar ratio of the 5-chlorovaleronitrile to the cyclohexanol to be (1: 1)-(1: 1.5) and the reaction temperature to be 5-55 DEG C, and carrying out a catalytic reaction for 1-6 hours by virtue of concentrated sulfuric acid, so as to obtain 5-chloro-N-cyclohexylvaleramide; wherein the molar ratio of the 5-chlorovaleronitrile to the concentrated sulfuric acid for catalysis is (1: 3)-(1: 10); the preparation method comprises the following steps: treating 1, 5-chloro-N-cyclohexylvaleric amide with phosphorus pentachloride; wherein the molar ratio of the 3, 5-chloro-N-cyclohexylvaleric amide to the phosphorus pentachloride is (1: 1)-(1: 1.5) and the molar ratio of the 2, 5-chloro-N-cyclohexylvaleric amide to the phosphorus pentachloride is (1: 1)-(1: 1.5); according to the invention, trimethyl silicon azide is used as a cyclization reagent instead of azoic acid or sodium azide, so that the synthesis method has the advantages of higher stability, no explosion and higher safety, the cost can be effectively reduced, the synthesis method is environment-friendly,and the purity of the obtained product is high.

Description

technical field [0001] The invention relates to the technical field of drug synthesis, in particular to a synthesis method of N-cyclohexyl-5-(4-chlorobutyl)-1H-tetrazolium. Background technique [0002] Tetrazolium, alias 1H-tetrazolium, molecular formula CH2N4, is a peptide coupling agent; used as a catalyst in the triester-based phosphine method of (dialkylamino)phosphine coupling reaction to synthesize oligonucleotides, tetrazoleacetic acid , has another name called tetrazole acetic acid, 1H-tetrazolium-1-acetic acid, is mainly used in the synthesis of cephalosporin antibiotics, and its downstream products are cefazolin, ceftezole etc., and the cost of existing tetrazole synthetic method is higher, The purity obtained is lower. Contents of the invention [0003] The object of the present invention is to provide a kind of synthetic method of N-cyclohexyl-5-(4-chlorobutyl)-1H-tetrazolium, to solve the problem raised in the above-mentioned background technology. [0004]...

Claims

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Application Information

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IPC IPC(8): C07D257/04
CPCC07D257/04
Inventor 张芳江柴文玉曾海峰洪杰徐章利黄志
Owner 上海立科化学科技有限公司
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