Acid chlorides Arndt-Eistert synthesis, diazomethane

Diazoketones such as 307 can be formed from acid chlorides by reaction with diazomethane. Subsequent treatment with aqueous Ag20 leads to the Wolff rearrangement and formation of a carboxylic acid of one carbon more than the starting acid chloride. This sequence is known as the Arndt-Eistert synthesis.252 a synthetic example using this is taken from Weinreb s studies toward the synthesis of cylindrospermopsin,253 iu which 315 was treated with (1) oxalyl chloride, (2) CH2N2 and (3) Ag20, MeOH to give a mixture of products 22% of 316 and 39% of 317. 

Any reaction involving diazomethane followed by silver oxide is classifiable as an Arndt-Eistert synthesis. This reaction converts an acid chloride into the next higher homolog in the series. Realizing this, partial structures can be proposed for structures A, B and C. 

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... 

Arndt, F. Eistert, B. Ber. Dtsch. Chem. Ges. 1935, 68, 200. Fritz Arndt (1885—1969) was bom in Hamburg, Germany. He discovered the Arndt—Eistert homologation at the University of Breslau where he extensively investigated the synthesis of diazomethane and its reactions with aldehydes, ketones, and acid chlorides. Fritz Arndt s chain-smoking of cigars ensured that his presence in the laboratories was always well advertised. Bernd Eistert (1902-1978), bom in Ohlau, Silesia, was Arndt s Ph.D. student. Eistert later joined I. G. Earbenindustrie, which became BASE after the Allies broke the conglomerate up after WWII. 

Conversely, if the substituted phenylacetic acid or its chloride are not readily accessible, the diazo ketone obtained from the corresponding aromatic acid chloride and diazomethane may be treated directly with the substituted phenethylamine. An Arndt-Eistert type rearrangement occurs which leads directly to the phenethylamide of the respective homo acid. An example for this type of reaction may be found in the synthesis of 1-benzylhydrohydrastinine (61). 

Synthesis of -Amino Acids. /3-Amino acids can be prepared in an Arndt-Eistert-t) e reaction employing tosyl chloride for the activation of the carboxyl group of V-protected amino acids. Formation of the corresponding diazomethane derivatives proceeds in good yield and without racemization of the a-stereogenic center (eq 53). Wolff rearrangement then affords the corresponding -amino acids. 

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