Cycloaromatization Reaction of 4‐Alkoxy‐1,1,1‐trifluoroalk‐3‐en‐2‐ones with 2,6‐Diaminotoluene: The Unexpected Regioselective Synthesis of 2,4,7,8‐Tetrasubstituted Quinolines

Abstract

This article reports a convenient and general method for the regioselective synthesis of a new series of 2‐alkyl(aryl)‐8‐methyl‐4‐trifluoromethyl‐7‐aminoquinolines in 86–93% yields, from cycloaromatization reactions of N‐(oxotrifluoroalkenyl)‐2,6‐diaminotoluenes in a strongly acidic medium polyphosphoric acid and absence of solvent. The enaminoketone intermediates were easily isolated from the reaction of 4‐alkoxy‐4‐alkyl(aryl)‐1,1,1‐trifluoroalk‐3‐en‐2‐ones [CF3C(O)CH═C(R)OR1, where R = H, Me, Ph, 4‐FPh, 4‐BrPh, 4‐MePh, and R1 = Me, Et] with 2,6‐diaminotoluene (2,6‐DAT) in methanol under mild conditions, in 46–70% yields. Another synthetic route also allowed the regioselective synthesis of 2‐aryl(heteroaryl)‐4‐methyl‐4‐trifluoromethyl‐7‐aminoquinolines from direct cyclocondensation reactions of 4‐alkoxy‐4‐aryl(heteroaryl)‐1,1,1‐trifluoroalk‐3‐en‐2‐ones with 2,6‐diaminotoluene in methanol under mild conditions, in 21–36% yields.

Synthesis and photophysical, thermal and antimycobacterial properties of novel 6-amino-2-alkyl(aryl/heteroaryl)-4-(trifluoromethyl) quinolines

“…40 The chemical shifts for the 2-CF 3 isomer showed quartets at 122.3 ppm ( 1 J CF = 275 Hz) for the CF 3 group and at 148.5 ppm ( 2 J CF = 34 Hz) for C-2; whereas, the 4-CF 3 isomer showed quartets at 124.2 ppm ( 1 J CF = 275 Hz) for the CF 3 group and at 134.8 ppm ( 2 J CF = 31 Hz) for C-4. In accordance with the data already described, 26,41,42 it was possible to confirm that the 6-aminoquinoline systems discussed herein present the trifluoromethyl group attached to 4-carbon. This, due to the chemical shifts obtained for the CF 3 group and C-4, was shown in the range of 123.9 ppm and 131.8 ppm, respectively.…”

“…The structural assignments for 3a-f are consistent with the spectral data described in the literature for similar compounds. [26][27][28][29][30] The E-isomers can be distinguished from the Z-isomers by the 1 H-NMR spectra, because the N-H signals of the E-form (in 4-8 ppm) appear at a much higher magnetic field than those of the Z-form (in 9-13 ppm), indicating the presence of an intramolecular hydrogen interaction. The 1 H-NMR chemical shift of the enamino hydrogens for 3a-f was observed in the range of 3.44 to 3.87 ppm, allowing one to assume that the enaminoketones 3a-f exist in the Z-form in CDCl 3 , which is stabilized by an intramolecular N-HÁ Á ÁOQC interaction.…”

A Convenient Synthesis of 4‐CF3‐Quinolines from 1‐Trifluoromethyl‐prop‐2‐yne 1‐Iminium Salts and Arylamines

“…The acid-catalyzed intramolecular cyclization of CF 3 -containing enaminoketones (Scheme 1a) is a straightforward method, which, however, often requires strong heating and in some cases yields mixtures of 2-CF 3 -and 4-CF 3quinolines. [8][9][10] The enaminoketones can be obtained from anilines and acetylenic ketones [8] or 4-methoxy-1,1,1-trifluorobut-3-en-2-ones. [10] When anilines and 1-CF 3 -1,3-diketones are heated in the presence of PPA, mixtures of regioisomeric 2-and 4-CF 3 -quinolines are formed in most cases.…”

“…[8][9][10] The enaminoketones can be obtained from anilines and acetylenic ketones [8] or 4-methoxy-1,1,1-trifluorobut-3-en-2-ones. [10] When anilines and 1-CF 3 -1,3-diketones are heated in the presence of PPA, mixtures of regioisomeric 2-and 4-CF 3 -quinolines are formed in most cases. [11] Schlosser et al have chosen the acid-catalyzed cyclization of 3-oxo-3-CF 3propanoic acid anilides to obtain 2-quinolones, which were then transformed into 2-bromo-4-CF 3 -quinolines (Scheme 1b).…”

Novel Alkyl(aryl)-Substituted 2,2-Difluoro-6-(trichloromethyl)-2H-1,3,2-oxazaborinin-3-ium-2-uides: Synthesis, Antimicrobial Activity, and CT-DNA Binding Evaluations

“…On the other hand, β-enaminoketones are interesting and easy obtainable synthetic intermediary. Enaminoketones have received attention due to their ambident nucleophilicity characteristics of amines, else with the ambident electrophilicity of enones ( Bonacorso et al, 2002a ; Bonacorso et al, 2010 ; Bonacorso et al, 2013 ).…”