Qin Hongjian, Han Zijian, Bonku Emmanuel Mintah, Sun Haiguo, Odilov Abdullajon, Zhu Fuqiang, Abduahadi Safomuddin, Zhu Weiliang, Shen Jingshan, Aisa Haji A
Key Laboratory of Plant Resources and Chemistry in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, Xinjiang, PR China.
University of Chinese Academy of Sciences, Beijing, PR China.
Commun Chem. 2024 Apr 27;7(1):93. doi: 10.1038/s42004-024-01180-9.
Amides are important intermediates in organic chemistry and the pharmaceutical industry, but their low reactivity requires catalysts and/or severe reaction conditions for esterification. Here, a novel approach was devised to convert amides into esters without the use of transition metals. The method effectively overcomes the inherent low reactivity of amides by employing dimethylsulfate-mediated reaction to activate the C-N bonds. To confirm the proposed reaction mechanism, control experiments and density functional theory (DFT) calculations were conducted. The method demonstrates a wide array of substrates, including amides with typical H/alkyl/aryl substitutions, N,N-disubstituted amides, amides derived from alkyl, aryl, or vinyl carboxylic acids, and even amino acid substrates with stereocentres. Furthermore, we have shown the effectiveness of dimethylsulfate in removing acyl protective groups in amino derivatives. This study presents a method that offers efficiency and cost-effectiveness in broadening the esterification capabilities of amides, thereby facilitating their increased utilization as synthetic compounds in diverse transformations.
酰胺是有机化学和制药工业中的重要中间体，但它们的低反应活性需要催化剂和/或苛刻的反应条件来进行酯化反应。在此，人们设计了一种新颖的方法，无需使用过渡金属就能将酰胺转化为酯。该方法通过采用硫酸二甲酯介导的反应来活化C-N键，有效地克服了酰胺固有的低反应活性。为了证实所提出的反应机理，进行了对照实验和密度泛函理论（DFT）计算。该方法展示了广泛的底物范围，包括具有典型H/烷基/芳基取代的酰胺、N,N-二取代酰胺、源自烷基、芳基或乙烯基羧酸的酰胺，甚至是具有立体中心的氨基酸底物。此外，我们还展示了硫酸二甲酯在去除氨基衍生物中的酰基保护基团方面的有效性。这项研究提出了一种方法，该方法在拓宽酰胺的酯化能力方面具有效率和成本效益，从而有助于提高它们作为合成化合物在各种转化中的利用率。
