Methylation method for amine

A technology of methylation and methylaniline, applied in the field of methylation of amines, can solve the problems of high toxicity of methylation reagents and expensive catalysts, and achieve the effects of low cost, low toxicity and high yield

Active Publication Date: 2016-07-13
SHANGHAI TECH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The purpose of the present invention is to propose a new amine methylation catalytic method, to solve the existing amine methylation method methylation agent toxicity is high, or the catalyst is expensive and other shortcomings, thereby for N-methyl Preparation of amines offers another cheap, efficient route

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] Preparation of 4-fluoro-N,N-dimethylaniline:

[0017] 1) In the glove box, 0.25mmol 4-fluoro-N-methylaniline, 6equiv (1.5mmol) diphenylsilane, 10mol% (based on 4-fluoro-N-methylaniline) cesium carbonate, 1.6ml acetonitrile solvent Add to a 50ml N2 protected schlenk tube.

[0018] 2) Remove the N in the schlenk tube through a double row of tubes under freezing and vacuum operation. 2 replaced by CO 2 , CO 2 The pressure is 1 bar.

[0019] 3) Using the cesium carbonate as a catalyst, the carbon dioxide as a C1 source, and the diphenylsilane as a reducing agent, react the 4-fluoro-N-methylaniline in an acetonitrile solvent at 80°C 72 hours.

[0020] 4) After the reaction, add 0.2 mmol of ferrocene into the schlenk tube as the NMR internal standard.

[0021] 5) Through Bruker nuclear magnetic analysis, the nuclear magnetic spectrum of the obtained product is consistent with the literature (Z.Yang, B.Yu, H.Zhang, Y.Zhao, G.Ji, Z.Ma, X.Gao, Z.Liu, GreenChem. 2015, 17, ...

Embodiment 2

[0023] Preparation of N-methyl-N-benzylaniline:

[0024] 1) In the glove box, 0.25mmol N-benzylaniline, 6equiv (1.5mmol) diphenylsilane, 10mol% (based on N-benzylaniline) cesium carbonate, and 1.6ml acetonitrile solvent were added to 50mlN 2 Protect the tube under the schlenk.

[0025] 2) Remove the N in the schlenk tube through a double row of tubes under freezing and vacuum operation. 2 replaced by CO 2 , CO 2 The pressure is 1 bar.

[0026] 3) Using the cesium carbonate as a catalyst, the carbon dioxide as a C1 source, and the diphenylsilane as a reducing agent, react the 4-fluoro-N-methylaniline in an acetonitrile solvent at 80°C 72 hours.

[0027] 4) After the reaction, add 0.2 mmol of ferrocene into the schlenk tube as the NMR internal standard.

[0028] 5) Through Bruker nuclear magnetic analysis, the nuclear magnetic spectrum of the obtained product is the same as that reported in the literature (M.-C.Fu, R.Shang, W.-M.Cheng, Y.Fu, Angewandte Chemie International...

Embodiment 3

[0030] Preparation of N-methylamantadine:

[0031] 1) In the glove box, 0.25mmol amantadine, 6equiv (1.5mmol) diphenylsilane, 10mol% (based on amantadine) cesium carbonate, and 1.6ml acetonitrile solvent were added to 50mlN 2 Protect the tube under the schlenk.

[0032] 2) Remove the N in the schlenk tube through a double row of tubes under freezing and vacuum operation. 2 replaced by CO 2 , CO 2 The pressure is 1 bar.

[0033] 3) Using the cesium carbonate as a catalyst, the carbon dioxide as a C1 source, and the diphenylsilane as a reducing agent, react the amantadine in an acetonitrile solvent at 80° C. for 72 hours.

[0034] 4) After the reaction, add 0.2 mmol of ferrocene into the schlenk tube as the NMR internal standard.

[0035] 5) Through Bruker nuclear magnetic analysis, the nuclear magnetic spectrum of the obtained product and the corresponding pure material spectrum reported in the literature (P.Besenius, P.A.G.Cormack, R.F.Ludlow, S.Otto, D.C.Sherrington, Che...

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Abstract

The invention provides a methylation method for amine. The methylation method is characterized by comprising the following steps: taking carbonate as a catalyst, taking carbon dioxide as a C1 source, taking diphenylsilane as a reducing agent, and reacting primary amine or secondary amine in an acetonitrile solvent, thereby obtaining a corresponding methylation product. The invention develops a new methylation method for amine, wherein the used raw materials are low in cost and low in toxicity, the reaction operation is simple, and the yield is high.

Description

technical field [0001] The invention relates to a method for methylating amines. Background technique [0002] Methyl-substituted amines widely exist in natural products, and have important applications in large chemical industry, fine chemical industry, pharmaceuticals and dyes. The traditional industrial methylation is through the Eschweiler-ClarkeMethylation reaction, which uses toxic formaldehyde as the source of C1 and carboxylic acid as the reducing agent. In the laboratory, the commonly used methylating reagents are highly toxic methyl iodide, dimethyl sulfate, methyl p-toluenesulfonate, diazomethane, etc. In recent years, scientists have discovered a new methylation method: using non-toxic and cheap carbon dioxide as the source of C1 in the methylation of amines, and hydrogen or silane or borane as the reducing agent. Among them, the works of Cantat, Beller and Klankermayer groups are the most prominent. In 2013, the Cantat group developed an IPrZnCl 2 catalyst. ...

Claims

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Application Information

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IPC IPC(8): C07C209/00C07C211/48
CPCC07C209/00C07C211/48
Inventor林柏霖陆春磊方驰
OwnerSHANGHAI TECH UNIV