Application of modified Pictet–Spengler reaction for the synthesis of thiazolo- and pyrazolo-quinolines

Synthesis of novel ferrocenyl-containing pyrazolo[4,3-c]quinolines

“…The general proposed mechanism for the formation of dihydropyrazole involves first the formation hydrazone followed by the addition of NeH to the olephinic bond of the propenone moiety [22]. Such ring closure was confirmed by the presence of C]N stretching (1583e1607 cm À1 ) peak in FT-IR spectra of compounds and by the existence of ABX spin system due to three protons attached to the C-4 and C-5 carbon atoms of the dihydropyrazole ring in 1 H-NMR spectra of the compounds [14,20]. In ABX spin system, H A , H B and H x protons of dihydropyrazoles (5e6) were depicted by the signals at 2.92e3.30 ppm, 3.90e4.13 ppm and 5.65e6.60 ppm, respectively.…”

“…The synthesis of pyrazoles (7e8) was performed by the reaction of dihydropyrazoles (5e6) with DDQ in DCM/THF (1/1) at room temperature for 5 h and afforded 3-ferrocenylpyrazoles (7) in 48e60% yield [14]. However, synthesis of 3-phenyl substituted pyrazoles (8) could only be achieved by the treatment of 6 with DDQ in dry dioxane at reflux for 7 h with a yield of 45e68% [23].…”

“…For instance, condensation of ethyl 4-chloroquinoline-3-carboxylates [1a,13b], 2,3-dihydro-1H-quinolin-4-ones [4a] or o-chloro-derivatives of cyano quinolines [5c,d] with various arylhydrazines affords pyrazolo [4,3-c]quinoline ring systems. In contrast to these methods, Kundu et al [14] described a modified PicteteSpengler reaction which involves the generation of quinoline ring onto the pyrazole to form pyrazolo [4,3-c]quinolines. In general, a typical PicteteSpengler reaction is based on the condensation of an aldehyde with an aliphatic amine to form an iminium intermediate which undergoes 6-endo cyclization with sufficiently reactive aromatic moiety to form an N-heterocyclic ring in acidic medium [15].…”

“…In general, a typical PicteteSpengler reaction is based on the condensation of an aldehyde with an aliphatic amine to form an iminium intermediate which undergoes 6-endo cyclization with sufficiently reactive aromatic moiety to form an N-heterocyclic ring in acidic medium [15]. Kundu and his coworkers [14] modified the general procedure of PicteteSpengler reaction by using designed aromatic amines having an activated heterocyclic ring instead of traditional aliphatic amines. They reported that the iminium ion derived from the arylamine is more electrophilic than the aliphatic amine [14,16] and it facilitates CeC bond formation.…”

“…Kundu and his coworkers [14] modified the general procedure of PicteteSpengler reaction by using designed aromatic amines having an activated heterocyclic ring instead of traditional aliphatic amines. They reported that the iminium ion derived from the arylamine is more electrophilic than the aliphatic amine [14,16] and it facilitates CeC bond formation. In this respect, the modified PicteteSpengler reaction has attained considerable importance for the synthesis of various products and novel heterocycles of biological interest [17].…”