Synthesis of 1, 4-Dihydropyridine Derivatives using FeCl₃ as Catalyst under Solvent-free Condition

Introduction

Chemistry of dihydropyridines in 1882 with Arthur Hansh reports the β-keto ester, aldehydes and ammonia can be combined to form 1, 4-dihydropyridine was developed. Because of the many benefits of 1, 4-dihydropridine is presented and now as vital medicines to treat angina, high blood pressure and allergies have been introduced. The combination of amlodipine and infedipines as brand name drugs^1-5. Another successful treatment of 4-aryl -1, 4-dihydropridine is that they use as calcium channels blockers in the treatment of cardiovascular disease and hypertension. Calcium channel blockers are a class of drugs that control entrance of calcium into cells and exit of calcium from cellular stores. These compounds lower blood pressure by relaxing smooth muscle wall of heart and arteries and reduce their external resistance. According to the various applications of these compounds , different method for synthesis of derivatives of 1, 4-dihydroprydines in different conditions and different catalysts are presented ,considering that some of these methods are time consuming, less economical and are harmful for the environment, provide appropriate methods, with short time, high efficiency, environmental friendly is valuable^5-11.

Previously, we have synthesized a number of heterocyclic compounds^12-20. Although numerous methods are capable of affecting these synthesis has been previously reported. FeCl₃ has been used previously as a catalyst for synthesis of organic compound²¹, herein we report FeCl₃ a new catalyst for the synthesis of 1, 4-DHPs at one pot reaction with high yields and easy separation  under solvent-free condition (Scheme 1).

Scheme 1 Click here to View scheme

 

Experimental

General Procedure for the Preparation of 1, 4-dihydropyridine derivatives

A mixture of ethyl acetoacetate (2 mol), aromaticaldehyde (1 mol) and ammonium acetate (1 mol) and FeCl₃ (0.004 _g) was refluxed in 110^oC for 1h. The obtained solid was filtered; the solid was washed with water and recrystallized using absolute ethanol (5a-f).

Compound 5a: Diethyl 1,4-Dihydro-2,6-Dimethyl-4-Phenylpyridine-3,5-Dicarboxylate 

Compound 5b: Diethyl 1,4-Dihydro-2,6-Dimethyl-4-(3-Nitrophenyl)Pyridine-3,5-Dicarboxylate

Compound 5C: Diethyl 4-(2,4-Dichlorophenyl)-1,4-Dihydro-2,6-Dimethylpyridine-3,5-Dicarboxylate 

Compound 5d: Diethyl 1,4-Dihydro-2,6-Dimethyl-4-M-Tolylpyridine-3,5-Dicarboxylate

 Compound 5e: Diethyl 4-(4-(Dimethylamino)Phenyl)-1,4-Dihydro-2,6-Dimethylpyridine-3,5-Dicarboxylate

Compound 5f: Diethyl 1,4-Dihydro-2,6-Dimethyl-4-(4-Nitrophenyl)Pyridine-3,5-Dicarboxylate

Results and Discussion

Herein, we report FeCl₃ as catalyst which could provide an efficient, cheap, easy separation, high yield and simple route under solvent-free condition for the synthesis of 1,4-DHPs.

Acknowledgements

We gratefully acknowledge the financial support from the Research Council of Tonekabon Branch Islamic Azad University.

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