Arndt-Eistert homologation reaction

The Arndt-Eistert reaction is a comparatively simple method for converting an acid Into its next higher homologue or to a derivative of the homologous acid, such as an amide or an ester. The overall yield is generally good. The reaction... 

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 homologation of carboxylic acids is a reaction frequently needed in synthetic chemistry. The Arndt-Eistert reaction though aesthetically pleasing, is not preferred today, owing to the use of diazomethane and silver reagents. We provided47 a solution to this problem by the addition of carbon radicals to... 

The chemistry of these trapped sulfide adducts also provided no less than three distinct solutions to the problem of the homologation of carboxylic acids, thereby providing a mild radical alternative to the classical Arndt-Eistert reaction. Thus, as shown in Scheme 33, the a. nitrosulfides obtained using nitroethylene as the alkene trap could be converted by oxidation to carboxylic acids or hydrolyzed to aldehydes using aqueous titanium trichloride [29, 31]. 

The photochemical Arndt-Eistert reaction of (1), however, proceeds normally to give the homologated ester (3). The abnormal reaction leading to (2) may proceed by rearrangement of an intermediate carbenoid to a ketene. ... 

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. 

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). ... 

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... 

Wolff rearrangement in organic synthesis are the homologation of carboxylic acids (Arndt-Eistert reaction), the one-carbon ring contraction of cyclic a-diazoketones, and, more generally, the in situ production of ketenes and a-oxo-ketenes as reactive intermediates under additive-free and coproduct-free conditions (except for the inert N2 gas). 

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. 

The selective hydrolysis of the diester (18) the performance of the Arndt-Eistert reaction with the semiester obtained, Dieckmann cycliza-tion, and acid hydrolysis led to dZ-D-homoequilenin (21). By the same route the cis diacid (17) gave dZ-cis-D-homoequilenin (19) [149]. The replacement of methyl iodide by its homologs at the stage of angular alky-... 

The Arndt-Eistert synthesis allows for the conversion of carboxylic acids 1 into the next higher homolog 4. This reaction sequence is considered to be the best method for the extension of a carbon chain by one carbon atom in cases where a carboxylic acid is available. 

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 Kojima-Sakai approach, which makes use of trans-cis diester 626, is summarized in Scheme LVII This intermediate was homologated by the Arndt-Eistert method, converted to olefin 627, and oxidatively cleaved to produce ultimately the diester 628. Dieckmann condensation was used to construct the diquinane core which was subsequently transformed to 623 by standard reactions. 

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