Virus-T
Páginas: 2 (266 palabras)
Publicado: 9 de febrero de 2013
The synthesis is often carried out by subjecting an equimolar mixture of the aryl
hydrazine and aldehyde or ketone directly to the indolization conditions without isolationof the hydra~one.~S,~im ilarly, arylhydrazones, prepared by reduction of the corresponding aryldiazonium salt or N-nitro~oarylalkylamineo~r~ ~b y a palladium mediatedcoupling reaction," can be subjected to the indolization conditions directly inthe presence of the carbonyl moiety without isolation of the arylhydrazone. Suchmethods are usefulwhen the arylhydrazone intermediates are unstable or toxic.
3.4.2 Historical Perspective
The first indolization of an arylhydrazone was reported in 1983 by Fischer andJourdan" by treatment of pyruvic acid 1-methylphenylhydrazone 3 with alcoholic hydrogen chloride. However, it was not until the following year that Fischer and Hess12 identifiedthe product from this reaction as 1-methyl indole-2-carboxylic acid 4.
Over 100 years after the initial discovery, the Fischer indole synthesis remains the most commonlyemployed method for the preparation of ind01es.I~
3.4.3 Mechanism
A number of reaction pathways have been proposed for the Fischer indolization reaction.The mechanismproposed by Robinson and Robinson in 1918,14 which was extended by Allen and Wilson in 194315 and interpreted in light of modem electronic theory by Carlin and Fischer in 1948j6is now generally accepted. The mechanism consists of three stages: (I) hydrazone-ene-hydrazine equilibrium; (11) formation of the new C-C bond via a [3,3]-sigmatropicrearrangement; (111) generation of the indole nucleus by loss of ammonia. Illustrated below is the indolization of the hydrazone 5 formed from l-methylphenylhydrazine and acetone
hydrazine and aldehyde or ketone directly to the indolization conditions without isolationof the hydra~one.~S,~im ilarly, arylhydrazones, prepared by reduction of the corresponding aryldiazonium salt or N-nitro~oarylalkylamineo~r~ ~b y a palladium mediatedcoupling reaction," can be subjected to the indolization conditions directly inthe presence of the carbonyl moiety without isolation of the arylhydrazone. Suchmethods are usefulwhen the arylhydrazone intermediates are unstable or toxic.
3.4.2 Historical Perspective
The first indolization of an arylhydrazone was reported in 1983 by Fischer andJourdan" by treatment of pyruvic acid 1-methylphenylhydrazone 3 with alcoholic hydrogen chloride. However, it was not until the following year that Fischer and Hess12 identifiedthe product from this reaction as 1-methyl indole-2-carboxylic acid 4.
Over 100 years after the initial discovery, the Fischer indole synthesis remains the most commonlyemployed method for the preparation of ind01es.I~
3.4.3 Mechanism
A number of reaction pathways have been proposed for the Fischer indolization reaction.The mechanismproposed by Robinson and Robinson in 1918,14 which was extended by Allen and Wilson in 194315 and interpreted in light of modem electronic theory by Carlin and Fischer in 1948j6is now generally accepted. The mechanism consists of three stages: (I) hydrazone-ene-hydrazine equilibrium; (11) formation of the new C-C bond via a [3,3]-sigmatropicrearrangement; (111) generation of the indole nucleus by loss of ammonia. Illustrated below is the indolization of the hydrazone 5 formed from l-methylphenylhydrazine and acetone
Leer documento completo
Regístrate para leer el documento completo.