Generation of Diazomethane

When making methyl esters from carboxylic acids, diazomethane is generated first from diazald. Just as in the case of ozone in the ozonolysis reaction, the problem of determining oxidation states for atoms in different resonance structures of diazomethane is avoided since it is generated in situ. 

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Staudinger and Kiipfer s procedure [8] for the generation of diazomethane (Scheme 7.24) has been modified for phase-transfer catalytic conditions [9]. Using tetra-n-butylammonium bromide, a yield of 35% of diazomethane, based on the hydrazine consumed, is obtained (a slightly higher yield can be obtained when 18-crown-6 is used [9]). 

An ethereal solution of diazomethane is usually prepared immediately before it is required for reaction. A convenient precursor for the generation of diazomethane is IV-methyl-lV-nitrosotoluene-p-sulphonamide which is prepared by the action of nitrous acid on N-methyltoluene-p-sulphonamide. This latter is formed from toluene-p-sulphonyl chloride and methylamine in alkaline solution. The methylnitrosamide affords diazomethane on reaction with potassium hydroxide solution. 

For an aftemate procedure for generation of diazomethane from hydrazine chloroform and KOH see ref 4... 

Aldrich (1989) developed an apparatus for the non-hazardous preparation of diazomethane from l-methyl-3-nitro-l-nitroso guanidine (2.45, R = R = H), which is convenient for the generation of one mmole or less of diazomethane, and three kits for the generation from Ar-methyl-AT-nitroso-4-toluenesulfonamide (Diazald) for the preparation of up to 50, 100, or 200 mmoles, based in part on a design of Hudlicky (1980). These kits allow generation of diazomethane solutions in a closed system. Such systems are necessary due to the extreme toxicity of diazomethane, causing pulmonary edema when the vapor is inhaled. 

Proctor LD, Wart AJ. Development of a continuous process for the industrial generation of diazomethane. Org Process R D 2002 6 884-892. 

Based on the results of Fdstl et al., Struempel et al. investigated the in situ generation of diazomethane in microstmctured reactors from commercially available Diazald (33, N-methyl-N-nitroso-p-toluene sulfonamide) and KOH (Figure 6.17) [17]. Diazald (33) is irritating to eyes, skin, and respiratory tracts, but not explosive and cardnt enic. The formed diazomethane was quenched with benzoic add to the corresponding methyl ester 30, which was finally detected. 

As a result of flow rate variation in the first step, the in situ generation of diazomethane, a residence time dependence was observed in the capillary. When the microstructured reactor was utilized, no time dependence was reported. It... 

This equipment is commercially available [28]. An apparatus which allows the generation of diazomethane and its isolation without... 

The base-catalyzed decompositions of a large variety of iV-nitroso compounds to aliphatic diazo compounds are well known. Primary emphasis has been on methods for the generation of diazomethane. A number of these will be mentioned below. 

Researchers have also demonstrated the in situ generation of diazomethane 20 and its use in the synthesis of methyl benzoate (Scheme 6.10). Using commercially available Diazald (Sigma-Aldrich, St. Louis, MO) 21, Struempel et al. screened the effect of reactor temperature (0°C to 85°C) with a fixed reaction time of 5 seconds, observing... 

An alternative popular procedure for the generation of small quantities (1-50 mmol) of diazomethane from Diazald employs a commercial mini-Diazald apparatus with a dry-ice/acetone cold finger in place of the water-jacketed condenser. The generation of diazomethane is carried out by treatment of the Diazald with KOH in aqueous ethanol. ... 

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