Diazonium salt, Japp-Klingemann hydrazone

JAPP KLINGEMANN Hydrazone Synthesis Synthesis of hydrazones from diazonium salts and an activated methylene group (or enamlne)... 

A related strategy is based on application of the Japp-Klingemann reaction as an alternative means for preparation of the required hydrazones. For example, the the diazonium salt 346 was reacted with the ketone 347 affording the hydrazone 348, which was subsequently cyclized to the tryptamine derivative 349 (Scheme 43) <2000H(53)665>. The Japp-Klingemann reaction has also been employed as a key step in syntheses of cyclopenta[3]indoles <2005JOG8385,... 

Elimination of carbon dioxide from a carboxylic acid in the presence of a diazonium salt leads to an aryl hydrazone (Japp-Klingemann). Subsequent hydrolysis in the presence of pyruvic acid furnishes the carbonyl Compound, as illustrated by the preparation of 2- -butyrylpyridine (81%). ... 

The Japp-Klingemann reaction was the key step during the first synthesis of the pentacyclic pyridoacridine marine cytotoxic alkaloid amoamine A by E. Delfoume et a P The diazonium salt was added to a vigorously stirred solution of ethyl-2-methyl-3-oxobutyrate in ethanol containing KOH, NaOAc and water. The resulting hydrazone was exposed to polyphosphoric acid to form the indole ring. 

Serotonin has been synthesised by several routes the method shown relies on a Fischer indole synthesis, the requisite aryl-hydrazone being constructed by a process known as the Japp-Klingemann reaction in which the enol of a 1,3-dicarbonyl compound is reacted with an aryl-diazonium salt, with subsequent cleavage of the 1,3-dicarbonyl unit. 

Sodium acetate Japp-Klingemann reaction with hydroxymethylene compounds Hydrazones from diazonium salts... 

In 2009 Welch and Lim described a synthesis of S-SFs-tryptamine (10) (09MI165). Their approach relied on the Japp—Klingemann reaction and started from 4-SF5-aniline (11), which was first diazotized by slow addition of aqueous NaN02 to its acidic methanoHc solution. Diazonium salt 12 reacted with 2-oxopiperidine-3-carboxylic acid (13) under mildly alkaline conditions and allowed isolation of hydrazone 14 in 88% yield. Fischer cychzation of 14 resulted in a formation of the 1-oxo-tetrahydro-p-carbohne 15 hydrolysis of the latter gave carboxylic acid 16. Decarboxylation of acid 16 provided S-SFs-tryptamine (10) in 21% yield. This five-step sequence from 11 gave tryptamine 10 in only 3% total yield (Scheme 4). 

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