Arylaminomethylenemalonates, cyclization thermal

Thermal cyclization of the arylaminomethylenemalonate afforded quinoline 3-carboxylate 630 whose reaction with 1,1-dibromoethane gave oxazolo[5,4,3-(/]quinoline 631. Acid hydrolysis and reaction with N-methylpiperazine gave 632 whose bactericidal activity is superior to that of pipemidic acid (82JAPK57203085) (Scheme 108). 

The thermal ring closure of Af-(het)arylaminomethylenemalonates gave bi- or polycondensed 4-hydroxypyridine-3-carboxy lates. This type of reaction is named the Gould-Jacobs reaction. (The reaction is illustrated in Scheme 40). The cyclized products may exhibit oxo-enol tautomerism. In this review, the hydroxy form is generally depicted. This type of tautomerism was discussed in an excellent review (76MI1). 

V-(3-trifluoromethylphenyl)aminomethylenemalonate (749, R = 3-CF3) proved unsuccessful in boiling phosphoryl chloride. The thermal cycliza-tion of ZV-ethyl-N-arylaminomethylenemalonates (749) and their ring closure in acetic acid, in acetic anhydride with zinc chloride, or in a melt of aluminium chloride were likewise unsuccessful (71JHC357). The corresponding quinoline was not obtained in a one-pot version when N-ethylani-line and EMME were reacted in polyphosphoric acid. Table V shows the yields of quinoline-3-carboxylic acid derivatives obtained from /V-ethyl-N-phenyl- and iV-ethyl-7V-(3,4-methylenedioxyphenyl)aminomethylene-malonates (749, R = H and 3,4-0CH20) under various acidic cyclization conditions. 

The thermal cyclization of arylaminomethylenemalonates (977, R = H, X = CH, N) and their N-methyl derivatives (R = Me) in Dowtherm A at 250°C for 15 min afforded the angular tricyclic derivatives (978) in excellent yields (87CCC2918 88MI11 89CCC713). 

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