Methylene carbonyl compound

PFITZINGER Quinoline synthesis QumoHne-4-cartx)xyHc acids from isatin and a-methylene carbonyl compounds. 

The Pfitzinger reaction entails the synthesis of quinoline-4-carboxylic acids 2 via condensation of isatic acids formed from isatins 1 and a-methylene carbonyl compounds in the presence of strong aqueous bases. Subsequent decarboxylation can afford the corresponding quinolines. " ... 

Quinolines 3 can be obtained from reaction of orr/zo-aminobenzaldehydes or o-aminoarylketones 1 with a-methylene carbonyl compounds.Various modified procedures are known a related reaction is the Skraup quinoline synthesis. 

The aminoketone 1, required as starting material, can be obtained by a Neber rearrangement from a A -tosylhydrazone. Another route to a-aminoketones starts with the nitrosation of an a-methylene carbonyl compound—often in situ—to give the more stable tautomeric oxime 7, which is then reduced in a subsequent step to yield 1 ... 

The dialkylaminomethyl ketones formed in the Mannich reaction are useful synthetic intermediates.184 Thermal elimination of the amines or the derived quaternary salts provides a-methylene carbonyl compounds. 

The Pfitzinger reaction of isatins with a-methylene carbonyl compounds is widely used for the synthesis of substituted quinoline-4-carboxylic acids. Ivachtchenko and colleagues have recently reported on the Pfitzinger reaction in a series of 5-sulfa-moylisatins (Scheme 6.239) [422]. Treatment of 5-sulfamoylisatins with diethyl mal-... 

Pyrrole synthesis from at-dicarbonyl compounds.15 A new approach to N-benzyl-pyrroles is formulated for biacetyl as starting material (equation I). The method is also suitable for annelation of a pyrrole group to an a-methylene carbonyl compound. 

The Gewald Reaction is a synthesis of 2-aminothiophenes via a multi-component condensation between sulfur, an a-methylene carbonyl compound and an a-cyanoester. 

The Gewald reaction can be conveniently performed via a multicomponent condensation between sulfur, an -methylene carbonyl compound, and an -cyanoester. The use of ionic liquids as solvents <2004SC3801>, or performing this condensation under microwave irradiation without solvent (Scheme 84) <2005SC1351>, leads to generally better yields of 2-aminothiophenes . 

PFITZINGER Quinoline synthesis ai ioline-4-cart xylic acids from isatin and o-methylene carbonyl compounds. 

Abdou, W.M., and El Khoshnieh, Y.O., Synthesis of fused thioxo-pyran systems from a-methylene carbonyl compounds and bz.vmclhylcnc-l, 3-dilhictanc, Synth. Commun., 29, 2657, 1999. 

The most direct synthesis of 1,4-dihydropyridines (7b) utilizes a procedure with either <5 + 1>, <3 + 2+1), or <2 + 1 + 2 + (1)> fragment combination. The latter represents the widely used classical Hantzsch s synthesis, which combines two molecules of an active a-methylenic carbonyl compound, an aldehyde, and an ammonia source (Scheme 3). 

Hosseini-Sarvaria (2011b) reported the synthesis of quinoline derivatives (60) by the condensation of 2-aminoaryl ketones (58) with methylene carbonyl compounds (59) catalyzed by nanoflake ZnO as a reusable heterogeneous catalyst under solvent-free conditions involving Friedlander heteroannulation (Scheme 9.14). The employed catalyst was synthesized from zinc acetate dihydrate and urea. It constitutes a simple, environmentally benign, and cost-effective method for the synthesis of quinolines. Tamaddon and Moradi (2013) reported the application of nano-ZnO as a reusable heterogeneous catalyst for the synthesis of Biginelli dihydropyrimidines... 

The Gewald reaction involves synthesis of 2-aminothiophenes via multicomponent condensation of a-methylene carbonyl compounds, cyano compounds, and sulfur. Recently, Tayebee et al. (2013) have successfully accomplished a rapid and efficient synthesis of 2-aminothiophenes (105) from ketones or aldehydes (103), malononi-trile (16), and sulfur (104) via a one-pot three-component Gewald reaction in the presence of a catalytic amount of ZnO nanoparticles (Scheme 9.31). The catalyst required for the reaction was synthesized through sedimentation of zinc acetate dihydrate in ethanol. 

A general method for the synthesis of a large number of coumarin derivatives and 2H-pyran-2-ones include a carbanion-induced ring transformation of lactones with methylene carbonyl compounds followed by DDQ-mediated unprecedented oxidative cleavage of oxaylidene intermediates (130BC5239). 

Many efforts have been made to find optimal synthetic routes of a-methylene carbonyl compounds. These simple but interesting molecules are used in a variety of applications, such as synthetic intermediates 14], to mimic biologically active natural products [15] and as potential antitumor drugs [16]. 

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