Synthesis and Characterization of Benzopyridine Derivatives

Abstract

The research project “Synthesis and Characterization of Benzopyridine Derivatives” comprises of the derivatization of potential bioactive heterocyclic compound benzo[b]pyridine (generally known as quinoline) into novel compounds. A variety of compounds containing different scaffolds along with quinoline moiety have been synthesized in order to develop molecules with improved biological activities against multiple targets. In this regard, diverse renowned pharmacophores like thiophene, oxadiazole, imidazole, sulphonamide and pyrazole have been integrated to the benzo[b]pyridine to obtain the unique compounds. Primarily, substituted 2-chloro-3-quinolinecarbaldehydes 3(a-e) were synthesized via N-acetylation of substituted aromatic amines 1(a-e), followed by conventional Vilsmeyer Haack formylation. Keeping the diverse pharmacological applications of sulphonamides in view, the first series of substituted N-(2/4-(2-((2-chloroquinolin-3- yl)methylene)hydrazinecarbonyl)phenyl)benzenesulfonamides 4(a-p) was synthesized by condensation of β-chloroformylquinolines 3(a-e) with various N-sulphonylated benzoic acid hydrazides. The chloro group of the parent benzo[b]pyridine nucleus was substituted by piperidine functionality to obtain the precursors 6/8-methyl-2-(piperidin-1-yl)quinoline -3-carbaldehydes 5(a,b) using the new modified method. The synthesized aldehydes 5(a,b) as precursors, steered to the synthesis of a range of compounds as the compounds containing 2-(piperidin-1-yl)quinolinyl moiety are the least reported in literature. A series of chalcone derivatives 6(a-j) and 7(a-j) was synthesized by base catalyzed Claisen Schmidt condensation of 5(a,b) with diverse substituted acetophenones under conventional as well as ultrasonication and microwave irradiation conditions. In order to introduce structural variety, another library of heteroaryl chalcones 8(a-i) and 9(a-i) was prepared by reacting the precursors 5(a,b) with different acetyl thiophenes. Using the same reactant, novel 2-(piperidin-1-yl)quinolin-3-yl)methylene)hydrazinecarbothioamides 10(a-m) and 11(a-m) were synthesized by acid catalyzed condensation with a range of thiosemicarbazides, under microwave irradiation besides classical method. The same precursors were further exploited to obtain a library of N-acylhydrazones 12(a-m) and 13(a-l) by treating them with various aromatic acid hydrazides. An exclusive group of 1,3,4-oxadiazoline 14(a-f) derivatives was obtained by N-acetylation and subsequent cyclization of the N-acylhydrazones 12 in acetic anhydride. Another novel series of piperidinylquinolinyl – sulphonamide Schiff bases 15(a-g) was obtained by reacting 5(a,b) with N-sulphonylated benzoic acid hydrazides. A unique combination of bioactive heterocyclic rings was designed by incorporating imidazole ring to the 6/8- methyl-2-(piperidin-1-yl)quinoline-3-carbaldehydes 5(a,b). The innovative piperidinyl imidazolyl benzo[b]pyridine derivatives 16(a,b) and 17(a,b) were attained by the condensation of 5(a,b) with o-phenylene diamine followed by N-methylation of imidazole ring. Extending the scheme of work, benzo[b]pyridine was synergized with pyrazole ring to obtain pyrazolo[3,4-b]quinolines 18(a-c), the transformation was achieved by reacting 2-chloro-3-quinolinecarbaldehydes 3(a-c) with hydrazine monohydrate. N-Alkylation of 18(a-c) with methyl chloroacetate yielded a set of novel esters 19(a-c) that gave hydrazides 20(a-c) upon hydrazinolysis. Hydrazide 20a was reacted with an assortment of aromatic aldehydes to yield a series of N´-arylidenes. The structures of all the synthesized compounds were established by their characterization using different analytical techniques like fourier transform infrared, nuclear magnetic resonance; 1H-NMR as well as 13CNMR and mass spectroscopies.