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The use of alkylzinc bromides in the multicomponent Mannich reaction is described. Heteroleptic organozinc compounds were obtained in THF or 2-MeTHF by direct insertion of zinc dust into the C–Br bond of alkyl bromides. It was found that the presence of a stoichiometric amount of LiCl was essential for the efficiency of the subsequent three-component coupling with aldehydes and amines. A variety of primary, secondary, and tertiary organozinc reagents as well as secondary amines and aromatic aldehydes could be used for the straightforward preparation of α-branched amines. Interestingly, whereas previously reported work describing the preparation and reaction of organozinc iodides in acetonitrile showed higher reactivity of secondary organozinc reagents over primary ones, reactions in THF in the presence of LiCl led to opposite results, with higher reactivity of primary organozinc reagents.

Three heterocyclic diazenyl compounds were synthesized by diazotization of 3-aminopyridine and aniline, followed by coupling with 8-aminoquinoleine, morpholine, 1,2,3,4-tetrahydroquinoleine, respectively. The obtained azo compounds are brown to yellow in color and were characterized by various methods such as NMR and X-rays. The synthesized compounds were evaluated for their antimicrobial activity against Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Candida albicans. The MIC of the tested compounds, determined by the microdilution method, showed potential antimicrobial activity against all tested microorganisms. 1-(3-pyridyl)-2-(morpholin-4-yl)diazene (8) and 1-(3-pyridyl)-2-(tetrahydroquinolin-1-yl)diazene (10) showed strong activities against C. albicans with MIC values of 150 µM and 120 µM respectively. 1-(4-trifluoromethylphenyl)-2-(8-aminoquinolin-5-yl)diazene (4) showed the broadest spectrum of activity with good MICs of 1380–2760 µM on the four strains. These diazenyl compounds were also screened for their anticancer activity against breast (MCF-7), lung (Calu-3), pancreas (PANC-1) and prostate (PC-3) cancer cells and on normal fibroblasts. The results showed good anticancer activities on tumor lines with IC50 values ranging from 9.4 to 98 µM. The best anticancer activity was obtained with compound 4 on Calu-3 cancer cells with an IC50 of 9.4 µM. The results suggest that compound 4 is an interesting scaffold for pharmacomodulation as suggested by ADME study.

Two new heterocyclic 1,2,3-triazenes were synthesized by diazotation of 3-aminopyridine following respectively by coupling with morpholine or 1,2,3,4-tetrahydroquinoline. 4-[(Pyridin-3-yl)diazenyl]morpholine (I), C9H12N4O, has monoclinic P21/c symmetry at 100 K, while 1-[(pyridin-3-yl)diazenyl]-1,2,3,4-tetrahydroquinoline (II), C14H14N4, has monoclinic P21/n symmetry at 100 K. These 1,2,3-triazene derivatives were synthesized by the organic medium method by coupling reactions of 3-aminopyridine with morpholine and 1,2,3,4-tetrahydroquinoline, respectively, and characterized by 1H NMR, 13C NMR, IR, mass spectrometry, and single-crystal X-ray diffraction. The molecule of compound I consists of pyridine and morpholine rings connected by an azo moiety (–N=N–). In the molecule of II, the pyridine ring and the 1,2,3,4-tetrahydroquinoline unit are also connected by an azo moiety. The double- and single-bond distances in the triazene chain are comparable for the two compounds. In both crystal structures, the molecules are connected by C—H...N interactions, forming infinite chains for I and layers parallel to the bc plane for II.

Catalyst-free multicomponent reactions of mixed alkylzinc reagents with Michael acceptors and aldehydes, ketones or activated imines are described. Primary, secondary and tertiary alkylzinc reagents, pre-generated in acetonitrile from the corresponding iodoalkanes, were used in the process, leading to the very efficient formation of a variety of β-hydroxycarbonyl compounds. The imines showed more contrasting results, due to the direct addition of the organozinc compound to the C=N bond. Mechanistic assays involving TEMPO account for a polar instead of a radical character of the reaction.