Synthesis and Antimicrobial Activity of a Number of 3-substituted-8-allylbenzoxazines and their Hydrobromic Salts

In this study, novel 1,3-benzoxazines 3a–d were synthesized starting from 2-allylphenol (2), formaldehyde and primary amines under Mannich reaction conditions, as well as their ammonium salts 4a–d, which were prepared by reaction of compounds 3a–d with HBr. As primary amines aniline, propylamine, n-hexylamine and n-octylamine were used. Synthesized heterocyclic compounds and their ammonium salts (3a–d and 4a–d) were characterized by elemental analysis, IR and NMR spectra. The antimicrobial activity of the synthesized compounds 3a–d and 4a–d at concentration 15 and 30 mgL-1 against microorganisms (Staphylococcus aureus NCTC6571, Staphylococcus aureus ATCC®25923, Escherichia coli ATCC®25922, Candida albicans NSTC - 3255/ATCC2091, Shigella flexneri ATCC®12022, Salmonella enterica ATCC®13076, and Aspergillus niger [isolate obtained from water]) was studied by the disk-diffuse method. It was found that compounds 3a–c are very effective against bacteria Staphylococcus aureus - NCTC 6571, Staphylococcus aureus ATCC®25923, Escherichia coli ATCC®25922, Shigella flexneri ATCC®12022, and Salmonella enterica ATCC®13076, but slightly effective against Candida albicans and Aspergillus niger. However, analysis revealed that the surfactants 4a–d have antimicrobial activity against all the above microorganisms, i.e., 4a–d have both bactericidal and fungicidal activity, which is explained by the present in its structure of the bromine anion, an ammonium fragment and a multiple bond. For comparison, as references at the identical concentration (30 mgL-1) and conditions amoxicillin and fluconazole were used. It was revealed, that the substances 4a–d, in comparison with the references used, are much higher in bactericidal and fungicidal effectiveness. Bactericidal efficacy was also confirmed by electron microscopy studies of Escherichia coli ATCC®25922 cells in the present of heterocyclic compound 4c (contain in the structure N-hexyl and allyl fragments) and amoxicillin (reference). It was found that, in the present of the synthesized compound 4c complete destruction of Escherichia coli ATCC®25922 cells was carried out (unlike to the presence of amoxicillin, used as reference).

Gunay Muzakir Mehdiyeva, Musa Rza Bairamov, Eldar Kochari Gasimov, Fuad Huseynali Rzayev