An Efficient One-Pot Synthesis of Polyhydroquinolines at Room Temperature Using HY-Zeolite

Abstract

In recent years heterogeneous catalysts have attracted a great attention due to efficiency, economic and environmental considerations. HY-zeolite is an important heterogeneous catalyst used in various chemical transformations, such as liquid phase acylation of amines,2) direct conversion of aldehydes into nitriles and ketones into amides, 3) selective removal of N-Boc protecting group from aromatic amines 4) and one-pot synthesis of 2,3-dihydro-2,2-dimethylbenzofurans. 5)Thus the remarkable catalytic activity together with easy availability, operational simplicity and recoverability of HYzeolite encouraged us to utilize this catalyst for the synthesis of polyhydroquinolines having 1,4-dihydropyridine moiety.1,4-Dihydropyridines exhibit a variety of biological properties. They can cure the disordered heart ratio as a chaincutting agent of factor IV channel and also possess the calcium channel agonist-antagonist modulation activities. [6][7][8] These compounds also behave as neuroprotectants, cerebral antiischaemic agents and chemosensitizers. 9,10) 1,4-Dihydropyridines were synthesized more than a century ago by Hantzsch by heating a mixture of an aldehyde, a b-ketoester and ammonia in ethanol under reflux for several hours.11) Different other heating approaches for the syntheses of polyhydroquinoline derivatives have subsequently been reported.12-16) However, these methods require drastic reaction conditions and long reaction times. Recently microwave irradiation has also been applied for the preparation of polyhydroquinolines.17) Yb(OTf) 3 18) or iodine 19) have been found to catalyze the Hantzsch reaction at ambient temperature but using the first catalyst the times required for the conversions were 2-8 h while using the second catalyst at room temperature the time of conversions was 1.5-6 h. The second catalyst should also properly be removed from the reaction mixture during work-up.In continuation of our work [20][21][22][23][24] on the applications of heterogeneous catalysts on organic transformations we report here a convenient and efficient method for the synthesis of polyhydroquinolines (containing 1,4-dihydropyridine moiety) using HY-zeolite as a catalyst. Four-component coupling reactions of aldehydes, ethyl acetoacetate, dimedone and ammonium acetate were carried out using this catalyst at room temperature (Chart 1).A series of polyhydroquinoline derivatives were prepared following the above method using various aldehydes (Table 1). Both aromatic and aliphatic aldehydes underwent the conversion smoothly. Aromatic aldehydes containing electron donating as well as electron withdrawing groups worked well. The aryl moiety having different groups or the same group at different positions did not show much differences in the yields of the products. Heterocyclic aldehyde like furfural also underwent the facile transformation. The polyhydroquinoline derivatives were formed within 2.0-2.5 h at room temperature in excellent yields (87-93%). In absence of the catalyst no product could be detected within 3 h at r...

Poly(vinylpyrrolidinium) perchlorate as a new and efficient catalyst for the promotion of the synthesis of polyhydroquinoline derivatives via Hantzsch condensation

“…These attempts resulted in the introduction of a variety of reagents for the promotion of the Hantzsch reaction, as a classical method used for this purpose. Some of these reagents are: ceric ammonium nitrate (CAN) [15], Cs 2.5 H 0.5 PW 12 O 40 [16], Hf(NPf 2 ) 4 [17], Grinding [18], Polymer [19], K 7 [PW 11 CoO 40 ] [20], MCM-41 [21], molecular iodine [22], nickel nanoparticle [23], ionic liquids [24], organocatalyst [25], p-TSA [26], BINOL-phosphoric acid derivatives [27], HClO 4 ÁSiO 2 [28], HY-zeolite [29], and montmorillonite K-10 [30].…”

Vanadatesulfuric Acid-catalyzed Novel and Eco-benign one-pot Synthesis of Polyhydroquinoline Derivatives under Solvent-free Conditions

“…Therefore, numerous promotions, such as using ionic liquids 13,14 , microwaves [15][16][17] , grinding 18 , silica-supported acids 19,20 , L-proline 21 , HY-zeolite 22 , Bu 4 NHSO 4 23 , boronic acids 24,25 , TMSCl-NaI 26 , ceric ammonium nitrate 27,28 , metal triflates 29,30 , p-TSA 31 , and baker's yeast 32,33 have been developed. However, many of these methods still suffer from several limitations, such as unsatisfactory yield, use of environmentally suspected organic solvents, long reaction time, high temperature, and using expensive and non reusable catalysts.…”

Efficient One-Pot Synthesis of Spirooxindole Derivatives Bearing Hexahydroquinolines Using Multicomponent Reactions Catalyzed by Ethylenediamine Diacetate

“…5 In view of the biological importance of hexahydroquinolines bearing a 1,4-dihydropyridine nucleus, several synthetic methods have been reported based on fourcomponent reactions between dimedone, aromatic aldehydes, malononitrile, and ammonium acetate (Scheme 1). [6][7][8][9][10][11][12][13][14][15][16][17][18][19] Microwaves, 6 ionic liquids, 7 ZnO nanoparticles, 8 Bu 4 NHSO 4 , 9 L-proline, 10 HY-zeolite, 11 silica-supported acids, 12 boronic acids, 7a,13 TMSCl/NaI, 14 ceric ammonium nitrate, 15 metal triflates, 16 polymers, 17 baker's yeast, 18 and p-TSA 19 have been used in these reactions as catalytic and stoichiometric reagents. Nevertheless, these known methods still suffer from several limitations, such as high reaction temperatures, long reaction times, the need for expensive catalysts, and unsatisfactory yields.…”

“…For example, reactions using 5-methylisatin (1b) with an electron-donating group on the benzene ring provided products 4g and 4h in 70 and 68% yield, respectively (entries 6, 7). Similarly, reactions using 5-bromoisatin, 5-chloroisatin, and 5-nitroisatin, which all possess an electron-withdrawing group on the benzene ring, gave products 4i-n in 60-84% yields (entries [8][9][10][11][12][13]. When 1-methylisatin (1f) or 1-phenylisatin (1g) was used, the desired products 4o-r were produced in 65-76% yields (entries [14][15][16][17].…”