Trifluoroacetic acid: A more effective and efficient reagent for the synthesis of 3-arylmethylene-3,4-dihydro-1H-quinolin-2-ones and 3-arylmethyl-2-amino quinolines from Baylis-Hillman derivatives via Claisen rearrangement

Trifluoroacetic acid has been discovered to be a highly effective and efficient reagent for the tandem Claisen rearrangement and cyclisation reaction to yield 3-arylmethylene-3,4-dihydro-1H-quinolin-2-ones from compounds obtained from the SN2 reaction between anilines and acetyl derivatives of Baylis-Hillman adducts of acrylates in the presence of DABCO. In contrast similar compounds obtained from the acetyl derivatives of Baylis-Hillman adduct of acrylonitrile on treatment with trifluoroacetic acid directly furnish 3-arylmethyl-2-amino-quinoline via tandem Claisen rearrangement, cylisation and isomerisation.

A general approach to the synthesis of substituted isoxazolo[4,3-c]quinolines via chalcones

A general and practical approach to the synthesis of substituted isoxazolo[4,3-c]quinolines from the substituted isoxazolines afforded by 1,3-dipolar cycloaddition between 2-nitrobenzonitrile oxide and chalcones is described. The SnCl2.2H2O-mediated reduction of the nitro group followed by intramolecular cyclization involving the amino and the keto groups in these substrates furnished a mixture of isoxazolo[4,3- c]-quinolines and 3,5-dihydro-isoxazolo[4,3-c]quinoline. In contrast, the reduction of these substrates with Fe-AcOH unexpectedly yielded 3-benzoyl-4-quinolinamine derivatives.

An alternate approach to quinoline architecture via Baylis-Hillman chemistry: SnCl2-mediated tandem reaction toward synthesis of 4-(substituted vinyl)-quinolines

An alternate approach to densely substituted quinolines from the products of SN2 nucleophilic substitution reaction between the acetyl derivatives of the Baylis-Hillman adducts obtained from 2-nitrobenzaldehydes and the carbonyl group containing carbon nucleophiles is described. Treatment of these compounds with SnCl2, trigger a tandem reaction wherein reduction of the nitro group is followed by a remarkably regioselective intramolecular cyclization and subsequent dehydrogenation to afford 4-(substituted vinyl)-quinolines.

Topological Descriptors in Modeling the Antimalarial Activity of 4-(3’, 5’-Disubstitutedanilino)quinolines

Two series of closely related antimalarial agents, 7-chloro-4-(3’,5’-disubstitutedanilino) quinolines, have been analyzed using Combinatorial Protocol in Multiple Linear Regression (CP-MLR) for the structure-activity relations with more than 450 topological descriptors for each set. The study clearly suggested that 3’- and 5’- substituents of the anilino moiety map different domains in the activity space. While one domain favors the compact structural frames having aromatic, heterocyclic ring(s) substituted with closely spaced F, NO2 and O functional groups, the other prefers structural frames enriched with unsaturation, loops, branches, electronic content and devoid of carbonyl function. Also, this study gives an indication in favour of the electron rich centres in the aniline substituent groups for better antimalarial activity; an observation in line with several of the previous reports too. The models developed and the participating descriptors suggest that the substituent groups of the 4-anilino moiety of the 4-(3’, 5’-disubstitutedanilino)quinolines hold scope for further modification in the optimisation of the antimalarial activity.