The Arndt-Eistert 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 

18 applicable to aliphatic, aromatic, aUcyclic and heterocyclic carboxyUc acids. It involves three operations  

Formation of the acid chloride, e.g., with thionyl chloride or with phosphorus pentachloridc  

Reaction of the acid chloride with a cold solution of excess of diazomethane to yield a diazo ketone  

Rearrangement of the diazo ketone, with loss of nitrogen, in the presence of suitable reagents and a catalyst (colloidal silver, silver oxide, or silver nitrate in the presence of ammonia solution). An acid is formed In the presence of water, an amide results when ammonia or an amine is used, and an ester is produced in the presence of an alcohol  

The third operation, involving the conversion of the diazo ketone into an acid or a simple derivative thereof, is known as the Wolff rearrangement. 

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An a-diazo ketone 1 can decompose to give a ketocarbene, which further reacts by migration of a group R to yield a ketene 2. Reaction of ketene 2 with water results in formation of a carboxylic acid 3. The Woljf re arrangement is one step of the Arndt-Eistert reaction. Decomposition of diazo ketone 1 can be accomplished thermally, photochemically or catalytically as catalyst amorphous silver oxide is commonly used ... 

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 Arndt-Eistert reaction (Scheme 2.1) which involves the Wolff rearrangement of diazoketones 13 (prepared from the corresponding commercially available N-protected-a-amino acids 12 by reaction of their mixed anhydrides with diazomethane a cautionary note is warranted here the generation and handling of diazomethane require special precautions) has been used extensively by Seebach and coworkers for the preparation of N-protected /9 -amino acids 14 and /9 -amino acid esters 15 and 16. 

Can the organic chemists associated with so-called Named Reactions make the same claim as supermodel Heidi Klum Many scholars of chemistry do not hesitate to point out that the names associated with name reactions are often not the acmal inventors. For instance, the Arndt-Eistert reaction has nothing to do with either Arndt or Eistert, Pummerer did not discover the Pummerer rearrangement, and even the famous Birch reduction owes its initial discovery to someone named Charles Wooster (first reported in a DuPont patent). The list goes on and on... 

Esters, amides, and primary alcohols are obtained from benzo[6]-thiophene carboxylic acids by standard procedures.337 481,585 692 093,695 Acid chlorides undergo the Arndt-Eistert reaction,337,568,689 react with diethyl ethoxymagnesium malonate to give the corresponding methyl ketone,144 557 and are reduced to the aldehyde with 1 ithium tri-ferf-butoxy aluminohydride.33 7... 

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... 

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... 

Ethyl 1-naphthylacet.ate has been prepared by ethanolysis of 1-naphthylacetonitrile under acidic conditions5 and by the Arndt-Eistert reaction of l-(diazoacetyl)naphtha ene with ethanol and silver oxide.6... 

The photolytic rearrangement of sulfoxonium ylids is envisaged as taking place via a ketene in a process reminiscent of the Arndt-Eistert reaction viz. 

Katritzky, A. R., Zhang, S., Mostafa Hussein, A. H., Fang, Y., Steei, P. J. One-Carbon Homoiogation of Carboxyiic Acids via BtCH2TMS A Safe Aiternative to the Arndt-Eistert Reaction. J. Org. Chem. 2001, 66, 5606-5612. 

Though the structure of morphenol is sufficiently demonstrated by these reactions, its confirmation by synthesis has not been achieved, though it has been attempted by cyclization of the acid [xvii], prepared by the Arndt-Eistert reaction from [xvm], but this cyclization failed to give a phenanthrene derivative [27],... 

The reaction of ethyl thiophen-2-carboxylate with triphenylphosphine-CCI4 gave (159), which upon acidic hydrolysis afforded the dichloromethyl ketone. 2-Thenoyl chloride reacts with some piperazine derivatives. Trimethylsilyldiazomethane has been used as a safe reagent in the Arndt-Eistert reaction for the transformation of 2-thenoyl chloride into benzyl 2-thienylacetate. ... 

The first step in the reaction of diazomethane with an aldehyde or a ketone, known as the Arndt-Eistert reaction, is addition of the diazomethane to the carbonyl group ... 

Carbenes from a-Diazocarbonyl Compounds The Wolff Rearrangement and the Arndt-Eistert Reaction... 

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