Amdt-Eistert

An ethereal solution of diazomethane free from alcohol may be prepared as follows such a solution is required, for example, in the Amdt-Eistert reaction with acid chlorides (compare Section VI,17). In a 100 ml. longnecked distilling flask provided with a dropping funnel and an efficient downward condenser, place a solution of 6 g. of potassium hydroxide in... 

Acetoacetic ester condensation Amdt-Eistert reaction Bart reaction. ... 

IsothiazoIe-5-carboxyIic acid, 3-methyI-bromination, S, 58 Isothiazolecarboxylic acid chlorides Amdt-Eistert reaction, 6, 157 Reissert reactions, 6, 157 Isothiazolecarboxylic acids esters... 

Rearrangement (ring contraction) of a-diazokelones to cartioxylic adds or their derivatives (esters, amides) via ketenes (see also Amdt-Eistert). 

At the laboratory scale, the a-bromoketone was prepared by an Amdt-Eistert reaction which gives the good isomer in a univocal way (eqn. 2). 

The reaction between acyl halides and diazomethane is of wide scope and is the best way to prepare diazo ketones. Diazomethane must be present in excess or the HX produced will react with the diazo ketone (10-74). This reaction is the first step of the Amdt-Eistert synthesis (18-8). Diazo ketones can also be prepared directly from a carboxylic acid and diazomethane or diazoethane in the presence of dicyclohexyl-carbodiimide. ... 

The use of copper as a catalyst in carbenoid transfer has its roots in the Amdt-Eistert reaction, Eq. 1 (3). Although the original 1935 paper describes the Wolff rearrangement of a-diazo ketones to homologous carboxylic acids using silver, the authors mention that copper may be substituted in this reaction. In 1952, Yates (4) demonstrated that copper bronze induces insertion of diazo compounds into the X-H bond of alcohols, amines, and phenols without rearrangement, Eq. 2. Yates proposal of a distinct metal carbenoid intermediate formed the basis of the currently accepted mechanistic construct for the cyclopropanation reaction using diazo compounds. 

ANDROSTAN-nU-OL, 52,122 Anthracene, cyanation, 50, 55 Amdt-Eistert reaction, modified, 50, 77 7-Aryl-0-diketones, general synthesis, 51, 131... 

The Kolbe synthesis of nitriles is an important method for the elongation of an alkyl chain by one carbon center (see also the Amdt-Eistert synthesis). The nitrile 2 can for example easily be converted to the corresponding carboxylic acid by hydrolysis. 

Hales and Paquette have observed that sequential reduction and hydrolysis of 805 can lead efficiently to endo,endo diacid 811 Amdt-Eistert homologation, conventional elaboration of bisfthioether) 813, and exhaustive oxidation was utilized to arrive at 813. The plan was to deploy the dianion of 813 in a manner which would lead to 814. However, the principal product proved to be the unwanted 815. 

Following Scheme 4, L-a-aminosuberic acid can be obtained from iV-tosyI -L-gl utamic acid (5, n=2), upon protection of the a-carboxy and tosylamino groups as an oxazolidone 6, by extension of the side chain with the Amdt-Eistert method via the diazo ketone 7 by one methylene moiety in each cycle to produce in subsequent steps the L-a-aminoadipic acid [(5)-2-aminohexanedioic acid, 8, n = 2], L-a-aminopimelic acid [(5)-2-aminoheptanedioic acid, 8, n = 3] and finally L-a-aminosuberic acid [(5)-2-aminooctanedioic acid, 8, n = 4]J22 Treatment with HBr in AcOH was the method of choice for the acidolytic hydrolysis of the tosyl group. 23 ... 

The equivalence of sulfur and oxygen in this ring system carries over to NSAIDs as well. Preparation of the sulfur analogue of isoxepac (6-4) starts with the alkylation of thiophenol (27-1) with benzyl chloride (26-1). Cyclization of the intermediate thioether (27-2) then affords the homothioxanthone (27-3). The carboxyl side chain is then extended by means of the Amdt-Eistert homologation reaction. The acid is thus hrst converted to its acid chloride by means of thionyl chloride. Reaction with excess diazomethane leads to the diazoketone (27-4). Treatment of that intermediate with silver benzoate and triethylamine leads the ketone to rearrange to an acetic acid. There is thus obtained tiopinac (27-5) [28]. 

Amino acids are useful precursors for the construction of 3-peptides,2,3 a-substituted 3-amino acids4 and related compounds.5 They can be prepared enantiomerically pure by homologation of a-amino acids using the Amdt-Eistert method. 

Often, esters are homologated by one carbon using the diazomethane-based Amdt-Eistert procedure. Kowalski homologation, addition of the inexpensive dibromomethane followed by -elimination, is a more scalable alternative. Timothy Gallagher of the University of Bristol recently reported (J. Org. Chem. 2004, 69, 4849) the use of Kowalski homologation to prepare P-amino esters from a-amino esters, including the conversion of 3 to 4. Note that the transformation can be carried out without protection of the OH, and that it proceeds without loss of stereochemical integrity. 

A number of examples to show that this method is more mild than the Amdt-Eistert reaction... 

Disadvantages of the silver-promoted method for Amdt-Eistert homologation are the large excess of nucleophile required and also the requirement for the use of the free amine during peptide formation procedures. 13 Activation of the diazo ketone by UV light has been shown to be suitable for this type of procedure and good yields are obtained using only 1.2 equivalents of a hydrochloride salt of an amino ester in the presence of triethylamine (Scheme 5). 14 ... 

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