Cellulose-Sulfuric Acid as an Efficient Biosupported Catalyst in One-Pot Synthesis of Novel Heteroaryl Substituted 1 , 4-Dihydropyridines

An efficient method for the synthesis of new heteroaryl substituted dihydropyridine derivatives via a one-pot four-component coupling reaction of heteroaldehyde, 1,3-diketone, ethylacetoacetate, and amonium acetate in the presence of cellulose-sulfuric acid as a biosupported solid acid catalyst was developed. The reaction gave the new derivatives of fused 1,4-dihydropyridines in lower reaction times and excellent yields (85–95%).


Experimental
2.1.General.Melting points were measured on an electrothermal 9100 apparatus and are uncorrected. 1H NMR spectra were obtained on a Bruker DRX-500 Avance spectrometer, and 13 C NMR spectra were obtained on a Bruker DRX-125 Avance spectrometer.Chemical shifts of 1 H and 13 C NMR spectra were expressed in ppm downfield from tetramethylsilane.FT-IR spectra were recorded on a Shimadzu FT-IR-8400S spectrometer.Chemicals were purchased from Merck and Fluka and used without further purification.

Typical Procedure: Preparation of 3-Aryl-4-fromyl-1-phenylpyrazole.
In a round bottomed flask, cyanuric chloride (1.83 g, 10 mmol) was added to dimethyl formamide (2 mL) which resulted in a white solid.To this product a solution of phenylhydrazone acetophenone (1 g, 5 mmol) in dimethyl formamide (15 mL) was added and stirred for 16 h at room temperature.To the resulted mixture, 15% Na 2 CO 3 (20 mL) was added and the organic layer was extracted by diethylether (2 × 15 mL).The ethereal solution was dried by MgSO 4 and filtered, and the filtrate evaporated under vacuum to
The reactions (entries a, d and g) were also carried out in the absence of cellulose-sulfuric acid in the same conditions which furnished the desired products in much longer reaction times (120-125 min) and lower yields (Table 1).
In order to optimize the effect of the amount of catalyst on the efficiency of the reaction, the preparation of 5a was selected as model reaction under reflux condition.This study gave the optimized amount of the catalyst as 0.05 g/mmol of substrate.The effect of different solvents (EtOH, MeOH, CH 3 CN, 1,4-dioxane, and DMF) on the preparation of 5a showed that EtOH was the solvent of choice.Therefore, all the reactions described in this report were carried out under optimized conditions (Table 1).The catalyst which was prepared according to the literature reports [31][32][33] is recoverable and was run for three consecutive cycles, furnishing the product (5a) without loss of catalytic activity.
The structures of all products were deduced from 1 H NMR, 13 C NMR and IR spectral analyses. 1H NMR showed H-4 proton at 5.06-5.33ppm as singlet which clearly confirmed the formation of 1,4-dihydropyridine moiety.

Conclusions
In summary, we have developed a convenient and facile protocol for the synthesis of new heteroaryl substituted 1,4dihydropyridines in the presence of cellulose-sulfuric acid as an efficient biosupported solid acid catalyst in lower reaction times (37-45 min) and excellent yields (85-95%).The simple procedures combined with easy recovery and reuse of the catalyst make this method economic, environmentally benign, and user-friendly process for the synthesis of these biolabile fused 1,4-dihydropyridine derivatives.The method is amenable for iterative combinatorial library generation.