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.
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