以甲醇为碳源的胺类化合物N-甲基化均相催化反应研究进展

Translated title of the contribution: Research progress in homogeneous catalysis of N-methylation of amine using methanol as carbon source

Qian Wang, Lei Qin, Zhiping Zheng

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

N-methyl substituted amines are important chemicals or valuable intermediates for the production of other end products including pesticides, dyes, drugs, natural products, and polymers. They are typically prepared by N-methylation reactions, starting from parent amines and using methylating reagents such as methyl iodide, diazomethane, and dimethyl sulfate that are frequently hazardous or carcinogenic. Other methods of achieving N-methylation of amines include Eschweiler-Clarke formaldehyde reductive amination, hydrogenation reduction of carbamate, and methylation using dimethyl carbonate, CO2, formic acid, and DMSO as carbon sources. However, these methods involve the use of generally toxic reagents or require harsh reaction conditions, often producing harmful by-products. Moreover, none of these methods have the control toward selective monomethylation or dimethylation. It is therefore desirable and significant to develop new methods with the use of more environmentally friendly methylation reagents and/or reaction conditions for more efficient and selective N-methylation of amines. Methanol, an easily accessible and inexpensive chemical, has been used as C1 source for a variety of organic transformations, including N-methylation. A commonly accepted mechanism, often referred to as the "hydrogen-borrowing" process, entails first dehydrogenation of methanol in the presence of a catalyst to form formaldehyde and the corresponding metal-hydride species, then the reaction of formaldehyde thus produced with an amine of interest to afford an imine intermediate upon the loss of one H2O molecule, and finally the reaction of the metal-hydride complex with the imine intermediate to afford the N-methylated product. Compared with the method of direct hydrogenation, the "hydrogen-borrowing" process is advantageous and practically more attractive due to the mild conditions used, the avoidance of hydrogen gas, and the high atom economy. However, the success of this method hinges upon the activity and selectivity of the accompanied catalysts. In this review, the recent advancements of N-methylation of primary and secondary amines and sulfonamides are summarized. Using representative examples from the literature, the advantages and limitations of various catalysts, including those containing Ru, Ir, Re, Fe, Mn, and Co, are discussed. For some systems, NMR spectroscopy and kinetic experiments were combined with DFT calculations to help gain in-depth understanding of the mechanism(s) possibly responsible for the N-methylation while revealing certain limitations among the various systems studied. It has been found that aromatic amines are less nucleophilic than aliphatic amines. As such, N-methylation products are generally obtained with aromatic amines, while the use of aliphatic amines tends to produce N,N-dimethylation products. In addition, most of these catalytic reactions require base as additives. In terms of substrate tolerance, a great variety of amines with various electron-donating and electron-withdrawing substituents as well as those featuring reducing groups such as double bonds, ester groups, carbonyl groups, and amide groups can be used. Beyond the fundamental methodological studies, the present N-methylation reaction has been successfully applied to the synthesis of certain drug molecules. Significant progress notwithstanding, further efforts are needed for the development of non-precious metal-containing catalysts and the selective production of monomethylated aliphatic amines and dimethylated aromatic amines; the obtainment of both remains challenging using the present N-methylation method. It is our sincere hope that this topical review provides not just a summary of the recent progress in the synthesis of this important family of compounds, but also some valuable perspectives as where future research may take us.

Translated title of the contributionResearch progress in homogeneous catalysis of N-methylation of amine using methanol as carbon source
Original languageChinese (Traditional)
Pages (from-to)3272-3285
Number of pages14
JournalKexue Tongbao/Chinese Science Bulletin
Volume66
Issue number25
DOIs
StatePublished - Sep 1 2021
Externally publishedYes

Keywords

  • "hydrogen borrowing" mechanism
  • C1 chemistry
  • Homogeneous catalysis
  • Methanol
  • N-methylation of amine

ASJC Scopus subject areas

  • General

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