Arndt-Eistert method

The Arndt-Eistert method is useful for making aryl-acetic acids from benzoic acids. How would you carryout this conversion ... 

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. 

P-Amino acids are useful precursors for the construction of p-peptides, a-substituted p-amino acids and related compounds. They can be prepared enantiomerically pure by homologation of a-amino adds using the Arndt-Eistert method. 

VI) by the Arndt-Eistert method, and thence through the diazo ketone into homopilosinylacetoxymethyl ketone (VII). When this substance is treated with copper acetate, formaldehyde, and ammonia at 100° for one hour, pilosinidine (VIII) is obtained, and this on methylation yields pilosinine (II). A modified synthesis was also described by the same authors, and more recently N. A. Dryamova, S. I. Zav yalova, and N. 

An important reaction of diazoketones is the Wolff rearrangement. " The reaction is the key step in the well-known Arndt-Eistert method for converting a carboxylic... 

C. Increase of Chain Length by the Arndt-Eistert Method 336... 

The esterification and selective hydrolysis of the trans-diacid (15) led to a semiester with a free carboxy group in the side chain at 0 4. Extension of the side chain via the diazoketone by the Arndt—Eistert method gave the homologous diester (18). Dieckmann cyclization of the latter yielded the 16-methoxycarbonyl derivative (22) which underwent decarboxylation and demethylation on treatment with acids with the formation of t Z-equilenin (23). The c3 -isomer, identical in all respects with the natural product, was obtained by the resolution of the mixture via the Z-menthoxy-... 

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... 

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. 

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

Overall yields from Boc-a-amino acids are between 40 and 70% depending on the method and the R side-chain [200, 225], Although feasible, the double Arndt-Eistert homologation of Boc-protected a-amino acids proved unsatisfactory with only low yields of y-amino acids 124 (<20% over five steps) [200] (for previous studies with Z- and phfhalyl- protected a-amino acids, see [226, 227]). 

The current procedure starts with the ester, ethyl 1-naphthoate, and converts it into homologated product in 81% yield without isolation of any intermediates. Safe, commercially available materials are employed. Based on a recently published variation43 of our original homologation methods,4 1 It represents a general procedure applicable to esters 1 bearing aryl, alkenyl, alkynyl and primary, secondary or tertiary alkyl attachments R. Yields range from 67-90% (on a 25-mmol scale) and like the Arndt-Eistert sequence this procedure affords retention of stereochemistry for the... 

The use of the Arndt-Eistert protocol for the homologation of phthaloyl-protected a-amino acids was first established in the early 1950s.[11] Since then the method has been extended to cover carbamate protected a-amino acids and it has become an exceptionally useful method for the synthesis of (3-amino acid derivatives 3[12] (Scheme 3). 

These are usually prepared by the following methods (a) the Willgerodt reaction on the corresponding methyl ketone,82,98,337,485, 557 (6) hydrolysis of the corresponding cyanomethyl compound,77,337, 485,499,517,521,568 cyclization reactions (Section IV, C) (for 3-acetic acids only),143,209,310,311,313,351 or (d) the Arndt-Eistert reaction on the corresponding carbonyl chloride, which may lead directly to the acetic acid 689 or its amide.337, 568... 

Friedel-Crafts acylation of benzo[6]thiophene and its derivatives with succinic anhydride132,439,662,663 or the ester chloride of succinic acid614, 618, 650,662 gives a y-keto acid (or ester), which is reduced to the corresponding y-(benzo[6]thienyl)butyric acid by the Huang Minion or Clemmensen method. y-(Benzo[6]thienyl)butyric acids may alternatively be prepared by the diethyl malonate synthesis on the appropriate halide,439,499 by the Arndt-Eistert reaction on the corresponding propionyl chloride,409,618 or by cyclization.347,618 The ketones (317 R = Hor OMe)347 have been prepared by cyclization... 

Method 3. An ethereal solution of diazomethane free from ethanol may be prepared by this method such a solution is required, for example, in the Arndt-Eistert reaction with acid chlorides (compare Expt 5.130). In a 100-ml distilling flask provided with a dropping funnel and an efficient downward condenser, place a solution of 6 g of potassium hydroxide in 10 ml of water, 35 ml of carbitol (diethyleneglycol monoethyl ether) and 10 ml of water connect the condenser to two conical flasks in series containing 10 and 35 ml of ether respectively and cooled in an ice-salt bath (see Method 1). Heat the mixture on a water bath at 70-75 °C in a beaker of water placed upon a hot-plate incorporating a magnetic... 

Hendecanedioic acid has been prepared by hydrolysis of the corresponding dinitrile, obtained from 1,9-dibromononane or 1,9-diiodononane 4-6 by oxidation of 11-hydroxyhendecanoic acid 7,8 by the Arndt-Eistert synthesis from 9-carbethoxynonanoyl9 and nonanedioyl chloride 10 and by the Willgerodt reaction on un-decylenic acid.11 The present method, previously described briefly,12 13 appears to represent the most convenient preparation of dibasic acids having an odd number of carbon atoms greater than ten. It has been applied to several other dibasic acids.14... 

In summary, the method described here provides an efficient and convenient route to a variety of a-diazo ketones including unsaturated derivatives that were not previously available by diazo transfer. a-Diazo ketones serve as key intermediates in a number of important synthetic methods including the Arndt-Eistert homologation, the photo-Woltf ring contraction strategy, and the carbenoid-mediated cyclopropanation reaction. We anticipate that improved access to a-diazo ketones will serve to enhance the utility of these valuable synthetic strategies. 

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