An efficient one‐pot strategy evolved in the synthesis of (E)‐4‐benzylidenylacridin‐1(2H)‐ones, (4 or 9) (E)‐2‐styryl quinoline‐3‐carboxamides (5 or 10) by sequential Suzuki–Miyaura coupling‐dehydrogenative Friedländer‐sp3 C–H activation. The 2‐amino‐5‐chloro benzhydrol 1, aromatic alcohol 2 or 6 ketones 3 or 3', and phenylboronic acid 7 underwent a smooth reaction in a basic deep eutectic solvent consisting of K2CO3 and ethylene glycol (DES‐1,1:1). DES‐1 could enable the Pd‐catalyzed Suzuki coupling reaction of 6, as well as the rapid oxidation of primary, secondary, and Suzuki coupled primary alcohols (2, 1, and 8) in the presence of an iridium catalyst and 1,10‐phenanthroline. The acidic DES‐2 (dimethyl urea/tartaric acid, 7:3) assists the Friedländer annulation and subsequent sp3‐C–H functionalization resulting in (E)‐4‐benzylidenylacridin‐1(2H)‐ones (4 or 9) and (E)‐2‐styryl quinoline‐3‐carboxamides (5 or 10).
Choline chloride (ChCl) based deep eutectic solvent (DES), facilitated the regioselective synthesis of (E)-1-(4-phenyl-2-styrylquinolin-3-yl)ethan-1-one (4), and (E)-3-phenyl-1-(4phenyl-2-((E)-styryl)quinolin-3-yl)prop-2-en-1-ones, (5) from the corresponding 2-amino-5-chloro benzhydrol, (1) in one-pot strategy. The 2-methyl-3-acetylquinoline generated in situ from the 2-amino-5-chloro benzhydrol, (1) and acetyl acetone, (2) via dehydrogenative Friedlander reaction in DES could enable subsequent regio-selective C-2 methyl group sp 3 C-H activation and rapid alkenylation with alcohols, (3) to provide the desired (E)-2-styrylquinolin-3-yl)ethan-1-ones, 4 in short reaction time [a] S.Figure 2. Choline chloride based DESs used in this work.quinolines employing different catalysts like Bronsted acids, [24] transition metals. [25] Friedlander reaction via an oxidative cyclization of 2-aminobenzyl alcohol with either ketones or alcohols were reported by Milstein, [26] Shim, [27] Yus, [28] Verpoort, [29] Kaneda, [30] employing Ru, Ir [31] and Pd [32] catalysis. Ahmed Kamal [33] and co-workers reported 5-nitrofuran-triazole derivatives by multicomponent reactions using CuSO 4 ·5H 2 O/sodium ascorbate/tBuOH/H 2 O. Recently, Xinhua Xu [34] and co-workers reported 3,4-dihydropyrimidin2-(1H)-ones/thiones using an air-stable zirconium(IV)-salophen perfluorooctanesulfonate complex as catalyst. Herein, we reported dehydrogenative cyclization of 2-amino-5-chloro benzhydrol with benzyl alcohol in presence of RuCl 2 (p-Cym) 2 using K 2 CO 3 :Glycol(1:1) and Ch-Cl:Oxalic acid(1:1) DESs. Ru catalyst was employed based on the oxidation studies of both primary and secondary alcohols. [26,27,35] The catalytic pathway of Ru catalysis and its role in the present reaction was evidneced from comparative reaction with and absence of the Ru catalyst, which indicated the necessitiy of RuCl 2 (pCym) 2. In the present study, other catalysts trials were ineffective. Further, optimised mol-% of RuCl 2 (p-Cym) 2 , with 5 mol-% a 60 % yield was observed while 15 mol-% provided 90 % yield (see supporting information). This strategy allowed the primary as well as secondary alcohols oxidization in K 2 CO 3 :Glycerol(1:1) [36] at pH 11 then tuned to acidic pH 1 by addition of Ch-Cl:Oxalic acid(1:1) DES for the in situ generation of quinoline. Likewise, the Ch-Cl:Oxalic acid (1:1) allowed the sp 3 C-H functionalization. Further tuning to the pH 12, with the addition of KOH facilitates the Knovenagel condensation. Results and DiscussionA convenient regioselective one-pot synthesis of Chimanine B analogues, for instances, the (E)-1-(4-phenyl-2-styrylquinolin-3yl)ethan-1-ones (4), and (E)-3-phenyl-1-(4-phenyl-2-((E)-styryl)quinolin-3-yl)prop-2-en-1-ones, (5) are presently reported from the corresponding 2-amino-5-chloro benzhydrol, (1), aromatic alcohols (3) as precursors. Interestingly, the 2-methylquinolone formed in situ in DES underwent regioselective methyl Csp 3 -H activation in one-pot to provide the alkenylated product, 4 in high yields and purity...
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