Novel Synthetic and Mechanistic Approach of TFA Catalysed Friedländer Synthesis of 2‐Acylquinolines from Symmetrical and Unsymmetrical 1,2‐Diketones with o‐Aminoarylketones

Abstract

In focussing on the reaction mechanism of Friedländer synthesis in the presence of acid catalysts, novel regioselective synthesis of 2‐acetylquinolines from reacting a symmetrical 1,2‐diketone, butan‐2,3‐dione with o‐aminoarylketones was reported. Similar condensation of o‐aminoarylketones with unsymmetrical 1,2‐diketone, pentan‐2,3‐dione leads to the formation of 2‐propanoylquinoline. The proposed reaction mechanism is scrutinized through density functional calculations at B3LYP/6‐311G (d,p) and M06‐2X/6‐311G (d,p) level of theory and also all the relative energy barriers and activation energies of the reaction steps are found to be minimum at above level of theory. Results from theoretical study have further strengthened by FT‐IR, FT‐NMR chemical shifts and structural parameters which were achieved with the same level of theory and the corresponding results were substantiate with experimental observations.

Friedlӓnder's synthesis of quinolines as a pivotal step in the development of bioactive heterocyclic derivatives in the current era of medicinal chemistry

“…Alternatively, the reaction is performed by heating a mixture of the reactants at temperature ranging from 150 to 220°C in the absence of catalyst. Typical catalysts for the Friedländer reaction include bases (Coffen & Wong, 1974; Henecka, 1949; Kalluraya & Sreenivasa, 1998; Nishimura et al, 1999; Walser et al, 1973), such as piperidine (Leleu et al, 2004; Vasse et al, 2002), sodium ethoxide (Mori et al, 1996; Yang et al, 2002, 2007, 2008), sodium tert ‐butoxide (Bu & Deady, 1999; Chen et al, 2000), KOH (Altenbach et al, 2007), NaOH (Mabire et al, 2005; Maguire et al, 1994), MeONa (Cappelli et al, 1997), others involve protic acids (Agrawal & Joshipura, 2005; Fehnel, 1966; Fehnel & Cohn, 1966; Gatta et al, 1991; Jia et al, 2006; Suzuki et al, 1999, 2001; Vandana & Prasad, 2004; Wang et al, 2006), such as p ‐toluene sulfonic acid (Sliskovic et al, 1991; Walsh, 1980; P ‐TSA), polyphosphoric acid (Kempter et al, 1977), Eaton's reagent (Satheeshkumar et al, 2015, 2022; Satheeshkumar & Rajendra Prasad, 2017), Tritone B (Boger et al, 1985; Brown, 1949), silica sulfuric acid (Satheeshkumar et al, 2021; Shaabani et al, 2006; SSA), citric acid (Enugala et al, 2008), NH 2 SO 3 H (Yadav et al, 2005), HCl/microwave (MW; Muscia et al, 2006), H 3 PMo 12 O 40 /SiO 2 (Das et al, 2008), H 3 PW 12 O 40 (Dabiri & Bashiribod, 2009), HClO 4 ‐SiO 2 (Narasimhulu et al, 2007), oxalic acid (Minoo et al, 2007), proline (Jiang et al, 2008), CF 3 CO 2 H (Satheeshkumar et al, 2016; Shaabani et al, 2007) or Lewis acids such as CeCl 3 ·7H 2 O (Bose & Kumar, 2006; Jia et al, …”

Enhanced Method for the Synthesis and Comprehensive Characterization of 1-(4-Phenylquinolin-2-yl)propan-1-one

“…The quinoline skeleton is used as a template for several synthetic compounds with various pharmacological properties, including antimalarial, anti-inflammatory, antiasthmatic, antibacterial, antiviral, and antihypertensive and tyrosine kinase inhibiting agents. − Researchers continue to seek new methodologies and products for synthesizing quinoline-based moieties. Various classic techniques to synthesize quinoline moiety include the Skraup, , Doebner–von Miller, Pfitzinger, Conrad–Limpach, Combes syntheses, and Povarov reactions. , Among them, a notable approach for attaining quinolines and related poly-heterocycles involves Friedländer quinoline synthesis. − Among these methods, the Friedländer synthesis is the most effective and prominent protocol for the synthesis of quinolines in recent years. − It has become the evergreen synthetic approach to prepare quinoline derivatives by the condensation of easily accessible 2-aminoarylketones with carbonyl compounds possessing a reactive methylene group, followed by cyclodehydration. − The most exciting method for improving organic synthesis is continuously reporting new methodologies and catalytic reactions. A solvent-free synthesis is an essential synthetic approach from the perspective of synthetic organic chemistry.…”

Solvent‐Free Synthesis of New Quinoline Derivatives via Eaton's Reagent Catalysed Friedländer Synthesis

“…[14,15] Friedländer synthesis was developed by researchers to prepare quinoline derivatives by condensation of easily accessible 2-aminoarylketones with carbonyl compounds attaining a reactive methylene group cum cyclodehydration, [16][17][18][19] in recent scenario this method is focused immense output using various catalyst and methodology, such as Bronsted acids, Lewis acids, greener methods, nano catalysts, ionic liquids and using various solvents. [20,21,[30][31][32][33][34][35][36][37][38][39]22,[40][41][42][43][44][45][46][47][48][49][23][24][25][26][27][28][29] Recently, some heterogeneous catalysts, [50,51] reusable eco-friendly polymeric catalyst [52] and metal-organic framework (MOF) materials, [53,54] have been developed for Friedländer synthesis. The cyclization of 2aminoaryl ketones and alkynoates is noteworthy way to construct ester substituted quinoline core was used often for the discovery of bioactive and therapeutic products.…”