Department of Chemistry, Stanford University, Stanford, California 94305, United States.
Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247667, India.
J Am Chem Soc. 2023 Apr 12;145(14):7724-7728. doi: 10.1021/jacs.3c00773. Epub 2023 Apr 3.
The properties of water microdroplets strikingly differ from bulk water. Using room-temperature water microdroplets, we find that toluene can react with CO to form phenylacetic acid in one step without any catalyst with negative high voltage applied at the sprayer source. The chemical components of these microdroplets are identified by mass spectrometry, and product structures are confirmed by tandem mass spectrometry. In this manner, we generate three drug molecules in a single step: 4-aminophenylacetic acid (epithelial peptide transporter PepT1 inhibitor), 3,4-dihydroxyphenylacetic acid (dopamine metabolite neurotransmitter), and phenylacetic acid (sodium salt form; treatment of urea cycle disorder). Mechanistic studies show that benzyl radicals formed from hydroxyl radicals at the water microdroplet interface drive these carboxylation reactions. This water microdroplet chemistry is general, allowing activation and subsequent carboxylation of aryl α-C-H groups.
水微滴的性质与体相水有显著差异。我们使用室温下水微滴发现，在没有任何催化剂的情况下，施加在喷雾器源上的负高压可以使甲苯与 CO 一步反应生成苯乙酸。通过质谱鉴定了这些微滴的化学组分，并通过串联质谱确定了产物结构。通过这种方式，我们在一步中生成了三种药物分子：4-氨基苯乙酸（上皮肽转运蛋白 PepT1 抑制剂）、3,4-二羟基苯乙酸（多巴胺代谢物神经递质）和苯乙酸（钠盐形式；尿素循环障碍的治疗）。机理研究表明，水微滴界面上的羟基自由基形成苄基自由基，驱动这些羧化反应。这种水微滴化学是普遍的，可以激活和随后使芳基 α-C-H 基团羧化。
