Diazomethane

Abstract

[334-88-3] CH2N2 (MW 42.04) InChI = 1S/CH2N2/c1-3-2/h1H2 InChIKey = YXHKONLOYHBTNS-UHFFFAOYSA-N (methylating agent for various functional groups including carboxylic acids, alcohols, phenols, and amides; reagent for the synthesis of α-diazo ketones from acid chlorides, and the cyclopropanation of alkenes1) Physical Data: mp −145 °C; bp −23 °C. Solubility: diazomethane is most often used as prepared in ether, or in ether containing a small amount of ethanol. It is less frequently prepared and used in other solvents such as dichloromethane. Analysis of Reagent Purity: diazomethane is titrated2 by adding a known quantity of benzoic acid to an aliquot of the solution such that the solution is colorless and excess benzoic acid remains. Water is then added, and the amount of benzoic acid remaining is back-titrated with NaOH solution. The difference between the amount of acid added and the amount remaining reveals the amount of active diazomethane present in the aliquot. Preparative Methods: diazomethane is usually prepared by the decomposition of various derivatives of N-methyl-N-nitrosoamines. Numerous methods of preparation have been described,3 but the most common and most frequently employed are those which utilize N‐Methyl‐N‐nitroso‐p‐toluenesulfonamide (Diazald®; 1),4 1‐Methyl‐3‐nitro‐1‐nitrosoguanidine (MNNG, 2),5 or N-methyl-N-nitrosourea 3.2 The various reagents each have their advantages and disadvantages, as discussed below. The original procedure6 for the synthesis of diazomethane involved the use of N-methyl-N-nitrosourea, and similar procedures are still in use today. An advantage of using this reagent is that solutions of diazomethane can be prepared without distillation,7 thus avoiding the most dangerous operation in other preparations of diazomethane. For small scale preparations (1 mmol or less) which do not contain any alcohol, a kit is available utilizing MNNG which produces distilled diazomethane in a closed environment. Furthermore, MNNG is a stable compound and has a shelf life of many years. For larger scale preparations, kits are available for the synthesis of up to 300 mmol of diazomethane using Diazald as the precursor. The shelf life of Diazald (about 1–2 years), however, is shorter than that of MNNG. Furthermore, the common procedure using Diazald produces an ethereal solution of diazomethane which contains ethanol; however, it can be modified to produce an alcohol-free solution. Typical preparations of diazomethane involve the slow addition of base to a heterogeneous aqueous ether mixture containing the precursor. The precursor reacts with the base to liberate diazomethane which partitions into the ether layer and is concomitantly distilled with the ether to provide an ethereal solution of diazomethane. Due to the potentially explosive nature of diazomethane, the chemist is advised to carefully follow the exact procedure given for a particular preparation. Furthermore, since diazomethane has been reported to explode upon contact with ground glass, apparatus which do not contain ground glass should be used. All of the kits previously mentioned avoid the use of ground glass. Handling, Storage, and Precautions: diazomethane as well as the precursors for its synthesis can present several safety hazards, and must be used with great care.8 The reagent itself is highly toxic and irritating. It is a sensitizer, and long term exposure can lead to symptoms similar to asthma. It can also detonate unexpectedly, especially when in contact with rough surfaces, or on crystallization. It is therefore essential that any glassware used in handling diazomethane be fire polished and not contain any scratches or ground glass joints. Furthermore, contact with certain metal ions can also cause explosions. Therefore metal salts such as calcium chloride, sodium sulfate, or magnesium sulfate must not be used to dry solutions of the reagent. The recommended drying agent is potassium hydroxide. Strong light is also known to initiate detonation. The reagent is usually generated immediately prior to use and is not stored for extended periods of time. Of course, the reagent must be prepared and used in a well-ventilated hood, preferably behind a blast shield. The precursors used to generate diazomethane are irritants and in some cases mutagens and suspected carcinogens, and care should be exercised in their handling as well.