Novel Basic Mesoporous Catalysts for the Friedländer Reaction from 2‐Aminoaryl Ketones: Quinolin‐2(1H)‐ones versus Quinolines

Abstract

The quinoline ring [1] is present in a number of natural [2] and synthetic products often exhibiting interesting pharmacological activities or physical properties. [3,4] Different synthetic approaches for the preparation of quinolines have been reported; the Friedländer reaction (FR) being one of the simplest and most efficient methods. [5] FR is a base-or acid-catalyzed condensation of an aromatic 2-amino-substituted carbonyl compound (aldehyde or ketone) with a carbonyl derivative containing a reactive a-methylene group followed by cyclodehydration (Scheme 1). Generally, the annulation takes place by heating aqueous or ethanolic solutions of the reactants at reflux in the presence of bases or acids, or by heating at temperatures of 150-220 8C in the absence of any catalyst. [6] Numerous studies have been undertaken with the aim of developing new catalysts operating under milder conditions. [5] Concerning green chemistry, replacement of homogeneous catalysts with heterogeneous catalysts for the production of fine chemicals in industrial processes, remains a very active research area. FRs have been catalyzed by several heterogeneous catalysts, such as Al 2 O 3 , [7] H 2 SO 4 /SiO 2 , [8] NaHSO 4 /SiO 2 , [9] HClO 4 / SiO 2 , [10] silica gel-supported phosphomolybdic acid, [11] KAIA[12] and sulfonated cellulose. [13] Although the acid or base-promoted FR has been extensively studied with o-aminoaryl aldehydes, [5] the base-catalyzed reactions starting from the corresponding o-aminoaryl ketones are relatively scarce. In 1967, Fehnel [14] described that o-aminobenzophenone (1 a) failed to react with ethyl acetoacetate under basic classical FR conditions, only affording the 3-acetylquinolin-2-(1H)-one 2 a under thermal activation at 160 8C (Scheme 2).Alongside our recent results concerning the synthesis of quinolines in the presence of bases, [15] we are interested in the development of environmentally friendly and potentially reusable heterogeneous catalysts based on modified molecular sieves with different acid/base properties, and also in the comparison of their catalytic activity in the FR. We have prepared and characterized three different MCM-41 materials supporting aminopropyl (AP), methylaminopropyl (MAP), and diethylaminopropyl (DEAP) groups, and modified the acidic properties of Al-SBA-15 by incorporating cesium ions, [16] and tested all of them in the FR (Table 1) The thermal stability of the aminografted MCM-41 was examined by thermogravimetric (TG) experiments in a temperature range from room temperature to 200 8C. Herein, we report the results of the FR of o-aminoacetophenone (1 b) and o-aminobenzophenone (1 a) with ethyl acetoacetate catalyzed by the mesoporous materials.Initially, we screened for a suitable solvent. Unfortunately, the reaction of 1 b in the presence of 20 wt. % DEAP did not proceed in EtOH at 80 8C. However, when we performed the reaction in DMF or toluene at 100 8C, quinolin-2(1H)-one 2 b was isolated with yields of 36 % and 93 % after 7 h and 2 h, respectively (Scheme 2 and T...

Zeolites Promoting Quinoline Synthesis via Friedländer Reaction

“…Reaction products were characterized by 1 H NMR and MS spectrometry. Spectroscopy data for compounds 5a-b and 6a-b [19] and 5c-d [11,26] are in good agreement with those previously reported.…”

“…In addition, synthesis of quinolines starting from aniline and different aldehydes catalyzed by H-BEA, under vapour phase conditions, has been reported [18]. More recently, we reported on mesoporous materials as novel and efficient catalysts for the condensation between 2-aminoaryl ketones and ethyl acetoacetate via Friedländer reaction selectively leading to the corresponding quinolin-2(1H)-ones [19].…”

Acid‐Activated Carbon Materials: Cheaper Alternative Catalysts for the Synthesis of Substituted Quinolines

“…Whereas the condensation between 2-aminoaryl ketones 1 and ethyl acetoacetate (2) catalyzed by acidic solids [(Al)SBA-15 or SBA-15/S, the latter containing sulfonic acids] yielded mixtures of the corresponding quinolines 3 and 4, basic catalysts, particularly amino-grafted MCM-41, afforded exclusively quinolone 4 with excellent yield (Scheme 1). [23,24] Furthermore, bifunctional materials, such as SBA-15/APS (APS = 3-(propylamino)propane-1-sulfonic acid), bearing both amine groups and sulfonic acids, led preferentially to quinoline 3 with increased selectivity in comparison to SBA-15/S. [24] Nevertheless, we have recently reported on the first examples of Friedländer reaction promoted by a metal-organic framework, [Cu 3 (BTC) 2 ], a mesoporous material exhibiting the highest activity mainly because of the higher number of catalytic sites located on metallic centers.…”

Nuclear magnetic resonance, vibrational spectroscopic studies, physico-chemical properties and computational calculations on (nitrophenyl) octahydroquinolindiones by DFT method

“…Conventional methods of synthesis include the base-catalyzed Friedlander [10] and acid-catalyzed Knorr reactions [11]. Other reported methods are the Baylis-Hillman reaction [12], by the reduction of the nitro group into amino group using Zinc-Acetic acid followed by condensation sequence, and transition metal catalyzed cyclocarbonylation of 2-vinylanilines [13].…”