Competitive formation of condensed azines and dihydropyridines in the reaction of ethyl 3,3-diaminoacrylate with o-halo carbaldehydes

Abstract

The reaction of ethyl 3,3-diaminoacrylate with quinoline-3-carbaldehydes and 3-nitrobenzaldehydes to give a dihydropyridine and condensed azine has been studied with respect to the number and reactivity of the halogen atoms in an ortho position to the formyl groups. For the series of quinoline-3-carbaldehydes it was found that the reaction course is determined by the number of chlorine atoms. 2-and 4-Chloroquinoline-3-carbaldehydes give dihydropyridines and a benzo[c][2,7-]naphthyridine is formed in the reaction with 2,4-dichloroquinoline-3-carbaldehyde. The main products in the case of nitrobenzaldehydes are dihydropyridines which points the deciding influence of the low electrophilicity of aromatic ring.In our recent study of the reaction of α-acylacetamidines (which exist in solution in the tautomeric enediamine form) with 2-fluoro-5-nitrobenzaldehyde (1) and 4,6-dichloro-2-methylsulfanylpyrimidine-5-carbaldehyde (2) the main reaction products are isoquinolines and pyrido[4,3-d]pyrimidines respectively [1,2]. α-Acylacetamidines react as C,N-dinucleophiles. The reaction occurs with a uniform chemo-selectivity: the amidine α-carbon substitutes the halogen atom in the aromatic ring and the amino group binds to the formyl carbon atom. However, in the case of the reaction of ethyl 3,3-diaminoacrylate (3) with the aldehyde 1 the cyclocondensation is accompanied by a concurrent Hantzsch type reaction to form the dihydropyridine 6. This reaction occurs using two molecules of the enediamine and one molecule of the aldehyde. Moreover, only the carbonyl group in the aldehyde reacts, the halogen atom at the aromatic ring being unaffected. In addition, a marked amount of the quinoline 5 is observed in the reaction which, as the dihydropyridine 6, is formed as a result of an attack by the carbon nucleophilic center of the enediamine at the formyl group. At the same time, the reaction of enediamine 3 with compound 2 gives only the corresponding pyrido[4,3-d]pyrimidine in virtually quantitative yield.

Facile synthesis of pyrido[2,3-d]pyrimidines via cyclocondensation of 4,6-dichloro-2-methylsulfanylpyrimidine-5-carbaldehyde with β-substituted β-aminoacrylic esters

“…Such influence of adjacent chlorine atoms on the reactivity of chlorinesubstituted quinoline-3-carbaldehydes in the reaction with ethyl 3,3-diaminoacrylate (2 X¼OEt) was reported in one of our previous works. 17 …”