Studies with Enaminals. New Efficient Synthetic Route to Functionally Substituted Pyridines, Pyrazoles, and Pyrimidines

Studies were carried out to explore reactions of the enaminal, N,N-dimethylaminoacrolein (1c), with active methylene compounds. The results show that 1c reacts with 3-oxoalkanenitriles 2a and 2b to yield either the respective 2-(N,N-dialkylamino)pyridines 6a and 6b or pyridine-3-carbonitriles 7a and 7b depending on the reaction conditions. In addition, 1c reacts with malononitrile in ethanolic piperidine to produce N,N-dimethylamino- allylidenemalononitrile 9, whose structure was assigned by using X-ray crystallography. Coupling of 1c with p-chlorobenzenediazonium chloride in the presence of sodium acetate affords 2-(2-(4-chlorophenyl) - hydrazono) malonaldehyde 11, which is also generated by the reaction of 1,1,3,3-tetramethoxypropane with the same aryldiazonium salt. Also, a novel method to produce pyrazole-3-carboxaldehyde 13, involving reaction of 11 with chloroacetone in the presence of ethanolic triethylamine, was uncovered. Pyrazole-3-carboxaldehyde 13 was shown to be a precursor of 1,8-dioxo-octahydroxanthenes 15 and pyranopyrazole 17. Furthermore, 2-(2-(4-chlorophenyl)hydrazono)malonaldehyde 11 undergoes reactions with hydrazine hydrate and phenylhydrazine to give the respective arylazopyrazole derivatives 18a and 18b. Finally, the pyrimidone and thiopyrimidone derivatives 20a and 20b are formed by the reaction of 11 with urea and thiourea, respectively, in refluxing ethanol.