The multicomponent reaction of 2-nitroacetophenone (or nitroacetone), acetaldehyde diethyl acetal, β-dicarbonyl compound, and ammonium acetate in an acetic acid solution allowed the acquisition of previously undescribed 4-methyl-substituted derivatives of 5-nitro-1,4-dihydropyridine in satisfactory yields. The oxidation of the obtained 5-nitro-1,4-dihydropyridine derivatives resulted in the corresponding 2,4-dimethyl-5-nitropyridines. In addition, for the first time in the synthesis of unsymmetrical 1,4-dihydropyridines by the Hantzsch reaction acetaldehyde, diethyl acetal was used as a source of acetaldehyde. The use of more volatile and sufficiently reactive acetaldehyde in this reaction did not lead to a controlled synthesis of unsymmetrical 5-nitro-1,4-dihydropyridines. The proposed multicomponent approach to the synthesis of 4-methyl-substituted 5-nitro-1,4-dihydropyridines and their subsequent aromatization into pyridines made it possible to obtain previously undescribed and hardly accessible substituted 5(3)-nitropyridines.

Previously, we synthesized methanobenzo[g][1,3,5]oxadiazocines and methanonaphtho[2,3-g]­[1,3,5]oxadiazocines via the Biginelli reaction using thiourea with acetoacetic ester or acetylacetone and salicylaldehyde or 2-hydroxy-1-naphthaldehyde under acidic catalysis and microwave irradiation. These compounds were then subjected to alkylation reaction with ethyl bromide in the presence of potassium carbonate in dimethylformamide. Under these mild reaction conditions, possible thione-thiol tautomerism of the oxadiazocines, as well as their structural analogs of cyclic thioureas, predominantly yielded in S-alkylation products with minor amounts of N-alkylation products. Further nucleophilic substitution reactions of S-ethyl-methanobenzo[g][1,3,5]oxadiazocines and S-ethyl-methanonaphtho[2,3-g][1,3,5]oxadiazocines revealed that alongside nucleophilic substitution by morpholine, elimination of phenol or naphthol occurred, followed by aromatization of the dihydropyrimidinone ring into an aromatic pyrimidine ring, resulting in the formation of 2-morpholinyl-substituted pyrimidines. Only a few examples and multi-step syntheses for obtaining such 2-amino-substituted pyrimidines are presented in the literature. Therefore, our newly discovered method for obtaining widely demanded derivatives of 2-aminopyrimidines is presented both relevant and promising.