A-Methylene carbonyl compounds

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. 

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). 

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. 

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]. 

Thus, the second version of Gewald reaction is a multi-component one-pot procedure that involves an a-methylene carbonyl compound 71, an a-activated acetonitrile 69 (malonodinitfile, cyanoacetic ester, or primary cyanoacet-amide), and sulfur (Scheme 12.23, Eq. 2). It is believed that the last one reacts with the a,p-unsaturated nitrile in situ generated from the other two reagents. In the case of the... 

Amino-a-methylene carbonyl compounds have been prepared in up to 92% ee via an aza-Morita-Baylis-Hillman reaction. A-Tosyl imines of, y-unsaturated a-ketoesters have been reacted with acrolein in the presence of two catalysts / -isocupridine (a chiral quinolol containing a DABCO moiety) and a bifunctional BINOL (or a 3 amine-thiourea). NMR and MS evidence supports a self-assembly of the catalysts, giving a multi-functional supramolecular catalyst. 

Quinoline-4-carboxylic acids from the condensation of isatic acids and a-methylene carbonyl compounds using base. 

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