L. Méndez, V. Kouznetsov, J. Poveda
2001
Citations
0
Influential Citations
16
Citations
Journal
Heterocyclic Communications
Abstract
The chemistry of 4-N-arylamino-4-(8-quinolinyl)-l-butenes 1-5 and 3-aryl-2-(8-quinolinyl)-4thiazolidinones 15 has been studied. N-Furoylation, N-allylation, mediated-acid intramolecular cychsation. amino-Claisen transposition and aldol reactions were used to prepare new C-8 substituted quinolines with biological potential. Introduction Quinolines belong to an important group of natural products containing a heterocyclic ring. Moreover. i a large number of quinoline derivatives are used in the pharmaceutical industry for a wide range of biological purposes like several parasitical drugs that are based on the 8-aminosubstituted quinoline nucleus". Diverse biological activities have been associated with thiazolidinone derivatives". We recently reported the synthesis of 4-N-arylamino-4-(8-quinolinyl)-l-butenes and 3-aryl-2-(8-quinolinyl)^-thiazolidinones from quinoline-8carbaldehyde, via formation of Schiff bases and further allylation or cyclocondensation of mercapto acids'. The biological significance of this class of compounds encouraged us to develop these C-8 substituted quinolines with possible biological activity. As part of our research program on the chemistry of homoallylamines and thiazolidinones with a quinoline ring, we wish to report here some transformations of 4N-arylamino-4-(8-quinolinyl)1-butenes and 3-aryl-2-(8-quinolinyl)-4-thiazolidinones. Results and Discussion Chemical transformations of 4-N-arylamino-4-(8-quinolinyl)1-butenes 1-5 are shown in Scheme 1. Quinoline 3 was prepared from 8-[N-(p-ethoxyphenyl)formimidoyl]quinoline using an C-allylation reaction. The treatment of aminobutenes 3,4 with α-furoyl chloride in the presence of EtsN in dry benzene gave the respective quinoline amides 6 and 7 in 63-67% yields. The N-allylation of quinoline aminobutenes 1,2 was Vol. 7, No. 2, 2001 Transformation of4-N-arylamino-4-(8-quinolinyl)-l-butenes and 3-aryl-2-(8-quinolinyl) -4-thiazolidinones carried out with allyl bromide in the presence of K : C0 3 in dry acetone affording the derivatives 8 and 9. which are used in the amino-Claisen rearrangement. Under the conditions of this transformation (heating in BFjOEt;). the N-allylated derivative 9 gave a rearranged product 10 in 60% yield, meanwhile similar heating of product 8 afforded two different compounds: a rearranged product 11 (52%) and a quinoline 12 with the tricyclic lilolidine structure (42%). Intramolecular allyl cyclisation of the aminobutenes 3.5 was readily achieved heating these compounds in 82% H :S0 4 producing the 4-methyl-2-(8-quinolinyl)-1.2.3.4tetrahvdroquinolines 13,14 in 35-76% yields. The final products were purified by column chromatography on alumina. The structural assignments proposed for the C-8 substituted quinolines 6-14 were consistent with their IR. 'Hand C-NMR spectra and were supported by the mass spectrometric data. 1,8,11 R= CH3; 2,9,10 R=CH30; 3,6,13 R= CH3CH2O, 4,7 R= CI; 1-4,6-13 RpH; 5,14 R=R1=CH3 Scheme 1 Seeking substances with potential bioactivity among other series of C-8 substituted quinolines, we performed an aldol condensation reaction of 3-aryl-2-(8-quinolinyl)-4-thiazolidinones (Scheme 2). 15a,b H "> 15: a Ar = P-CH3C5H4; b Ar = p-OTjOC^H^ 16a,c,e,g,i Ar = p-CH3C6H^ 16b,d£h Ar = p-CH3OC6H4; 16a,bR=H 16c,dR = Cl; 16e/R = CI%0; 16g^R = (0%)2N; 16iR = OH