Chlorides, acyl reaction with diazomethane

A useful reaction of acyl chlorides is with diazomethane. The initial product, a diazo ketone, undergoes a rearrangement with the expulsion of nitrogen and the insertion of a methylene group. This Arndt-Eistert reaction is a useful chain-extension procedure (Scheme 3.69). 

One vital observation made by Nierenstein was that there was a considerable reluctance of acyl bromides to form the corresponding bromomethyl ketones. Acid bromides on reaction with diazomethane were also found to form substituted 1,4-dioxanes or specifically 3,6-dibromo-3,6-diphenyl-1,4-dioxane 8, resulting from the dimerization of adducts. The dimerization according to him could be attributed to the poor mobility of the bromide compared to the chloride group. 

Benzyl chloromethyl ketone has been prepared by the reaction of diazomethane with phenylacetyl chloride. The method of Clibbens and Nierenstein, in which one equivalent of diazomethane is added to the acyl chloride and the chloromethyl ketone obtained directly, could not be duplicated by Bradley and Schwarzenbach or by the submitters. 

The HC1 generated in this reaction destroys one equivalent of diazomethane. This can be avoided by including a base, such as triethylamine, to neutralize the acid.74 Cyclic z-diazoketones, which are not available from acyl chlorides, can be prepared by reaction of an enolate equivalent with a sulfonyl azide. This reaction is called diazo transfer 5 Various arenesulfonyl azides76 and methanesulfonyl azide77 are used most frequently. Several types of compounds can act as the carbon nucleophile. These include the anion of the hydroxymethylene derivative of the ketone78 or the dialkylaminomethylene derivative of... 

The reaction of diazomethane with acyl chlorides starts as a simple acylation to give a diazo-nium compound. If there is an excess of diazomethane, a second molecule acts as a base to remove a rather acidic proton between the carbonyl and the diazonium groups to give the diazocarbonyl compound. 

One important application of this reaction is the chain extension of acyl chlorides to their homologous esters, known as the Amdt-Eistert reaction. Notice that the starting material for the Wolff rearrangement is easily made from RCO2H by reaction of the acyl chloride with diazomethane the product is RCH2CO2H—the carboxylic acid with one more carbon atom in the chain. A CH2 group, marked in black, comes from diazomethane and is inserted into the C-C bond between R and the carbonyl group. 

Surface oxides on graphite undergo the reactions typical of carboxylic acids, phenols and alcohols. Methylation with diazomethane or dimethylsulfate, silanization of—OH groups by reaction with halosilanes, formation of acyl chlorides by reaction with thionyl chloride, further reactions of these acyl chlorides, neutralization of acidic surface groups with different bases, ion exchange and more special reactions are used to characterize surface oxides on carbon and to modify their properties for technical applications . 

It has been stressed that the presence in a benzene derivative of two bulky substituents, such as chlorines ortho with respect to the reaction site may cause severe steric hindrance. As expected, the perchloroaryl carboxylic acids are not esterified by Meyer s acid-catalysed procedure either, although their methyl esters are readily prepared with diazomethane (Riera, 1961). In general, the synthesis of alkyl esters is successfully performed by acylation of alcohols with the overcrowded acid chlorides, the latter being obtained smoothly from the corresponding acids with thionyl chloride. 

This reaction was first reported by Arndt and Eistert in 1935. It is the extension of carboxylic acid by one CH2 unit via the reaction of acyl chloride with diazomethane and is generally known as the Arndt-Eistert synthesis. In addition, this reaction is also occasionally referred to as the Arndt-Eistert acid synthesis, Arndt-Eistert homologation," and Arndt-Eistert reaction. This reaction has been extensively reviewed. Other reagents instead of diazomethane have been similarly applied to extend the length of the carboxylic acids7... 

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