Synthesis of 2,3-functionalized quinolines

Quinoline and its derivatives represent the important class of nitrogen-containing heterocycles, which are useful intermediates in organic synthesis and exhibit a wide range of biological activity. In addition, the quinoline nucleus is a part of natural alkaloids and drugs that is why the synthesis of new quinoline derivatives is an actual task. The 2-chloroquinoline-3-carbaldehyde pays particular attention among a number of quinolines, which contains a chlorine atom and an aldehyde group, which make it an universal intermediate syntone in the synthesis of various bioactive quinoline derivatives. The purpose of this work is to synthesize Schiff bases based on 2-chloroquinoline-3-carbaldehyde. It was found that the interaction of 3-formyl-2-chloroquinoline with 1-aminopropanol-2 in an alcohol medium occures with the formation of 1-((2-chloroquinolin-3-yl) methylene) amino)propan-2-ol. To determine the impact of the nature of the alkyl substituent near the amino group, the condensation reactions of 2-chloroquinoline-3-carbaldehyde with amines containing cycloheptyl and cyclohexenyl fragment were performed. As results, Schiff bases with good yields (63%, 67%) have been received. The changing the alkyl substituent on the aromatic fragment in the amine molecule can increase the yields of the target azomethines to 75-97%. The use of amines with a heterocyclic moiety in the condensation reaction does not significantly impact on the yield of imines (71-77%). For further functionalization, the interaction of 1-(2-chloroquinolin-3-yl)-N-(4-fluorobenzyl)methanimine with 1,2,3,4-tetrahydroquinoline in ethyl alcohol has been performed. It results in 1-(3,4- dihydro-2H-[1,2'-biquinolin]-3'-yl)-N-(4-fluorobenzyl)methanimine, which contains two quinoline rings in its composition. The 3-(((2-chloroquinolin-3-yl)methylene)amino)tetrahydrothiophene 1,1-dioxide was converted to 3-((tetrazolo[1,5-a]quinolin-4-ylmethylene)amino)tetrahydrothiophene 1,1 -dioxide via reacting of the corresponding imine with sodium azide in dimethyl sulfoxide. Thus, bioperspective functionalized quinolines with imine, amine and azide moieties have been synthesized.