NOVEL SYNTHESIS & APPLICATIONS OF DIAZOMETHANE

自1894年以来，重氮甲烷已被证明是最有价值的 和强大的试剂可供合成化学家使用。它是 容易成为最常见的羧酸甲基化试剂，以及 已被广泛应用于酚、醇、 烯醇，以及氮和硫等杂原子。最重要的是， 它一直是POST的主要亲电物种 不同N-亚硝基前体对DNA甲基化的影响 用于生成重氮甲烷作为甲基化试剂。确实有 几篇关于重氮甲烷在 有机和有机金属化学。众多应用程序中的一些应用程序 重氮甲烷的结构如下：a.酮的扩环反应。B. 扩链或亚甲基插入：将酸卤化物转化为 A-重氮酮是有价值的合成中间体，有三个 主要用途(制备α-卤代酮、Wolf重排、 卡宾前体)。C.环丙烷化：重氮甲烷作为 与不饱和环加成反应中的强1，3-偶极 系统。D.由烯烃和乙炔形成的吡唑啉环 先驱物。E.由异硫氰酸酯形成的噻二唑环 先驱物。F.环氧化：重氮甲烷与酮的加成反应 酯类化合物。由醛：单醛合成酮 与重氮甲烷反应生成同系酮。H.合成 二碘甲烷：重氮甲烷可在温和条件下与碘反应 二碘甲烷形成的条件，二碘甲烷是一种重要的试剂 西蒙斯-史密斯反应。标题：新型化合物的合成及应用 重氮甲烷(续)试剂是从 碱催化分解N-甲基-N-硝基-N-亚硝胺 (MNNG)使用各种不同的方法。重氮化重氮甲烷 最近还推出了Aldrich的套件形式 化学公司。尽管当作为稀释剂处理时相当安全 溶液和在惰性溶剂中的小规模合成， 重氮甲烷有毒、易爆，吸入后极具刺激性 在高浓度下。唯一商业上可以买到的前体 重氮化氚甲烷的原位生成 比活度为0.5~2的[~3H-甲基]-N-亚硝脲(MNU) Ci/MMole。这种化合物也被认为是一种高度致癌和 有毒物质。在接下来的一年里，我们建议开发一种简单、 高比活度氚的高效新合成 重氮甲烷，取决于存在时氟化物诱导的反应 完全氚的水。手术将在一口井中进行 设计安全的仪器，规模很小。我们预料到了这一点 进一步扩展原有化学和设备的途径 在NTLF开发的。

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. There are several review articles concerning diazomethane applications in organic and organometallic chemistry. Some of the many applications of diazomethane are as follows: a. Ring expansion of ketones. b. Chain extension or methylene insertion: conversion of acid halides to a-diazoketones which are valuable synthetic intermediates with three primary uses (the preparation of a-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. TITLE: Novel Synthesis and Applications of Diazomethane (Continued) The reagent has been synthesized from base-catalyzed decomposition of N-methyl-N-nitro-N-nitrosoguanidine (MNNG) using a variety of different methods. Deuteriated diazomethane has also recently become available in kit form from the Aldrich Chemical Company. Although quite safe when handled as a dilute solution and in small scale synthesis in an inert solvent, diazomethane is toxic and explosive and highly irritating if inhaled in high concentrations. The only commercially available precursor for in situ generation of tritiated diazomethane is [3H-methyl]-N-nitrosourea (MNU) at a specific activity of 0.5 to 2 Ci/mmole. This compound is also known as a highly carcinogenic and toxic material. Over the next year we propose to develop a simple, efficient and novel synthesis for high specific activity tritiated diazomethane, depending on a fluoride-induced reaction in the presence of fully tritiated water. The procedure will be performed in a well designed and safe apparatus, at very small scale. We expect this approach to further extend chemistry and equipment previously developed at the NTLF.