NOVEL SYNTHESIS & APPLICATIONS OF DIAZOMETHANE

自1894年以来，重氮甲烷已被证明是最有价值的 以及合成化学家可用的强大试剂。 是 容易地是羧酸的最常见的甲基化试剂，和 在酚，醇， 烯醇和杂原子如氮和硫。 最重要的是， 它一直是主要的亲电物种负责后 DNA甲基化时，各种不同的N-亚硝基前体， 用于生成作为甲基化试剂的重氮甲烷。 一些 重氮甲烷在有机和有机金属中的许多应用 化学成分如下：a.酮的扩环。 B.链 延伸或亚甲基插入：将酰卤转化为 - 重氮酮是有价值的合成中间体， 主要用途（-卤代酮的制备，Wolf重排， 卡宾前体）。 C.环丙烷化：重氮甲烷作为 强1，3-偶极在许多不饱和环加成反应中 系统. D.由烯属和炔属形成吡唑啉环 前体 e.由异硫氰酸酯形成噻二唑环 前体 F.环氧化：将重氮甲烷加成到酮中， 酯盐酸盐的褪 G.由醛合成酮：简单醛 与重氮甲烷反应生成同系酮。 H.合成 重氮甲烷可与碘在温和条件下反应， 条件，以形成亚甲基二碘，一种必要的试剂， 西蒙斯-史密斯反应 氚化重氮甲烷的合成， 基于氟化物诱导的三甲基甲硅烷基的脱甲硅烷基化 重氮甲烷在氚化水的存在下。 氟化铯和 四丁基氟化铵（TBAF）已经作为氟化物进行了研究 源 当严格干燥时，TBAF提供了最有效的， 可控制的脱甲硅烷基化结果。 的比活性 产生的重氮甲烷直接取决于比活度 生成的氚化水（来自PtO 2和T2）。 我们已经开始 研究重氮甲烷反应的细节，重点是 酸的甲基化，吡咯嗪的形成和重氮酮的合成， 在准备使用高比活度氚化的 重氮甲烷

Since 1894, diazomethane has proven to be one of the most valuable and powerful reagents available to the synthetic chemist. It is easily the most common methylating reagent for carboxylic acids, and has found wide application in the methylation of phenols, alcohols, enols, and heteroatoms such as nitrogen and sulfur. Most importantly, it has been the major electrophilic species responsible for post DNA-methylation when a variety of different N-nitroso precursors were used to generate diazomethane as the methylating reagent. Some of the many applications of diazomethane in organic and organometallic chemistry are as follows: a. Ring expansion of ketones. b. Chain extension or methylene insertion: conversion of acid halides to _-diazoketones which are valuable synthetic intermediates with three primary uses (the preparation of _-haloketones, Wolf rearrangement, carbene precursors). c. Cyclopropanation: diazomethane acts as a powerful 1,3-dipole in many cycloaddition reactions with unsaturated systems. d. Pyrazoline ring formation from olefinic and acetylenic precursors. e. Thiadiazole ring formation from the isothiocyanate precursors. f. Epoxidation: addition of diazomethane to ketones and esters. g. Synthesis of ketones from aldehyde: simple aldehydes react with diazomethane to form the homologous ketones. h. Synthesis of methylene diiodide: diazomethane can react with iodine under mild conditions to form methylene diiodide, an essential reagent in the Simmons-Smith reaction. The synthesis of tritiated diazomethane is based on the fluoride-induced desilylation of trimethylsilyl diazomethane in the presence of tritiated water. Cesium fluoride and tetrabutyl-ammonium fluoride (TBAF) have been investigated as fluoride sources. When rigorously dried, TBAF gives the most efficient and controllable desilylation results. The specific activity of the resulting diazomethane is directly dependent on the specific activity of the generated tritiated water (from PtO2 and T2). We have begun to investigate the details of the diazomethane reactions, focussing on methylation of acids, pyrolazine formation and diazoketone synthesis, in preparation for use of the high specific activity tritiated diazomethane.