N -甲基-N-亚硝基脲（MNU）作为重氮甲烷前体参与的“一锅法”选择性甲基化反应研究

doi:10.6023/cjoc202510007

摘要/Abstract

我们以N-甲基-N-亚硝基脲（MNU）作为经济、安全的重氮甲烷前体,通过“一锅法”原位生成重氮甲烷,实现了羧酸的效选择性甲基化反应。该方法避免了高危险性重氮甲烷的分离和转移操作,显著提升了实验安全性。反应条件温和,具备良好的官能团耐受性和广泛的底物适应性,适用于多种羧酸、氨基酸、多肽及药物分子,以中等至优良的收率获得相应的甲酯产物。此外,该策略还可成功应用于羧酸生物电子等排体苯基四唑的N-甲基化反应,进一步展示了其在复杂分子后期修饰及药物化学合成中的潜在应用价值。

关键词: N-甲基-N-亚硝基脲, 重氮甲烷, 一锅法反应, 选择性甲基化

Herein, we report an efficient one-pot chemoselective methylation of carboxylic acids using N-methyl-N-nitrosourea (MNU) as an economical and safe precursor for diazomethane. This strategy enables the methylating agent to be generated and consumed in situ, thereby effectively avoiding the hazardous separation and transfer processes. The reaction proceeds under mild conditions with excellent functional group tolerance, accommodating a broad range of substrates including amino acids, peptides, and drug-like molecules to deliver the corresponding methyl esters in moderate to excellent yields. Furthermore, the methodology was successfully applied to the N-methylation of phenyltetrazole, a common carboxylic acid bioisostere, highlighting its utility for late-stage functionalization in pharmaceutical synthesis.

Key words: N-Methyl-N-Nitrosourea, Diazomethane, One-pot reaction, Chemoselective methylation

引用此文

刘轩宇, 姚嘉欣, 陈宇翔, 张天宇, 江雨晴, 胡智学, 孙宏顺, 褚雪强. N -甲基-N-亚硝基脲（MNU）作为重氮甲烷前体参与的“一锅法”选择性甲基化反应研究[J]. 有机化学, doi: 10.6023/cjoc202510007.

Xuan-Yu Liu, Jia-Xin Yao, Yu-Xiang Chen, Tian-Yu Zhang, Yu-Qing Jiang, Zhi-Xue Hu, Hong-Shun Sun, Xue-Qiang Chu. One-Pot Chemoselective Methylation Using N-Methyl-N-Nitrosourea (MNU) as Diazomethane Precursor[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202510007.

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