Acid chloride, Arndt-Eistert homologation

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. 

The Wolff rearrangement is the third step of the Arndt-Eistert homologation of carboxylic acids. Figure 11.25 picks up an example that was discussed in Section 7.2, that is, the homologation of trifluoroacetic acid to trifluoropropionic acid. The first step of the Arndt-Eistert synthesis consists of the activation of the carboxylic acid via the acid chloride. The Q elongation to an a-diazoketone occurs in the second step. 

Preparation of the sulfur analogue involves as the first step cyclization of the terephthalic acid derivative 92. The acid is then converted to the acid chloride and this is allowed to react with diazomethane. Rearrangement of the resulting diazoketone (95) under the conditions of the Arndt-Eistert reaction leads to the homologated acid. 

The Wolff rearrangement of a-diazocarbonyl compounds (8.58, R = H, alkyl, aryl, OR) has great synthetic importance because in most cases the ketenes formed react smoothly with water, alcohols, and amines (Scheme 8-34). An early application that still has considerable importance is the homologization of carboxylic acids (Arndt-Eistert reaction Arndt and Eistert, 1935). As shown in Scheme 8-34, the reaction starts from the chloride of the acid RCOOH, which leads to an a-diazo ketone with diazomethane (R = H), followed by the Wolff rearrangement and the hydrolysis of the ketene intermediate to give the homologous carboxylic acid (8.59, R =H). In alcohols and amines esters (8.60) and amides (8.61, R = H), respectively. 

When working on the acylation of diazomethane, Arndt and Eistert (1935) found the method for homologization of carboxylic acids in which acylation of the diazo ketone with the acid chloride is followed by a Wolff rearrangement (see discussion in Sect. 8.6). 

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. 

An alternative to the Arndt-Eistert reaction for the homologation of carboxylic acids uses lV-(acylmethyl)benzotriazoles prepared from acyl chlorides and iV-(trimethylsilyl)-methylbenzotriazole. Upon treatment with Tf20 these compounds are converted to the corresponding vinyl triflate, and then to the homologous ester by sequential treatment with sodium methoxide in acetonitrile and then HCl in methanol (eq 52). ... 

Nierenstein reaction is the reaction of an acid chloride 1 with diazomethane at room temperature to yield a a-chloroketone 2. It differs from the Arndt-Eistert reaction in that the latter specifically forms diazoketone, which is used to form the higher homolog of the substrate acid chloride. 

One-Carbon Homologation. When acid chlorides are unavailable or problematic, the Arndt-Eistert-type homologation of carboxylic acid derivatives is possible by adding TMSCHN2 to a... 

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