Bromination of quinolin-4(1H)-ones as an efficient strategy for the development of new antibacterial agents
Keywords:quinolin-4-one, 2-alkylquinolin-4(1H)-ones, bromination, 4Qs, quorum sensing, antibiotic resistance, AMR
Aim. To study the reactivity of 2-methylquinolin-4(1H)-ones in the bromination reaction in order to develop target-oriented methods for the synthesis of compounds that can affect the Quorum sensing processes of various bacterial communities.
Results and discussion. Features of the reactivity of 2-methylquinoline-4(1H)-ones in the bromination reaction using two halogenating reagents – molecular bromine and N-bromosuccinimide (NBS) have been studied. It has been shown that in both cases the direction of halogenation depends on the presence and nature of the substituent in position C(3) of the heterocycle. It has been found that variations in reagents, solvents, and catalysts did not lead to changes in the qualitative composition of the reaction products and only slightly affected their yields.
Experimental part. The synthesis of bromo derivatives of quinoline-4(1H)-ones was carried out by acting on the initial compounds of a molecular bromine or NBS in glacial acetic acid or chloroform, respectively, in the presence of catalytic amounts of benzoyl peroxide or without it. The structure of the compounds synthesized was proven by the data of 1H NMR spectroscopy and elemental analysis.
Conclusions. The features of the bromination reaction in the series of 3-substituted 2-methylquinolin-4(1H)-ones have been studied. It has been found that depending on the nature of the substituent in position C(3) of quinolone, bromination occurs on the methyl group of position C(2), or on positions C(3) and C(6) of the heterocycle. In the case of 3-benzyl-2-methylquinolin-4(1H)-one, bromination takes place on the methyl group of position C(2) of quinolone to form 3-benzyl-2-(bromomethyl)quinolin-4(1H)-one, which can be used for developing a new class of drugs designed to affect the virulence factors of microorganisms. The reactivity of 3-benzyl-2-(bromomethyl)-quinolin-4(1H)-one has been studied on the example of n-hexylamine alkylation.
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