%0 Journal Article
%T ¡°On-Water¡± Catalyst-Free Ecofriendly Synthesis of the Hantzsch Dihydropyridines
%A Amit Pramanik
%A Manabendra Saha
%A Sanjay Bhar
%J ISRN Organic Chemistry
%D 2012
%R 10.5402/2012/342738
%X An eco-friendly ¡°on-water¡± protocol for efficient catalyst-free synthesis of the Hantzsch dihydropyridines from aryl, heteroaryl, alkyl, and vinylogous aldehydes has been developed with minimum auxiliary substances, toxic reagents, organic solvents, and disposal problems. 1. Introduction 4-Substituted 1,4-dihydropyridine framework has emerged as one of the most prolific chemotypes in the recent computational analysis of medicinal chemistry database due to its multifarious pharmaceutical applications. They serve as important analogues of NADH coenzymes [1] exhibiting neuroprotectant [2] and platelet anticoagulatory activity [3]. These compounds often act as cerebral anti-ischemic [3] agents in the treatments of Alzheimer¡¯s disease and as chemosensitizers [4] in tumour therapy. Due to their high efficiency as Ca2+ channel blockers, the Hantzsch dihydropyridines also find immense applications in the treatment of cardiovascular disorders and hypertension [5]. 1,4-Dihydropyridine skeleton is also present in many vasodilator, bronchodilator, antiatherosclerotic, antitumor, antidiabetic, geroprotective, and hepatoprotective agents. Moreover, these compounds serve as important synthetic intermediates [6, 7] for the preparation of various pyridine derivatives through oxidative aromatization sequences. A number of synthetic protocols for the construction of the dihydropyridine skeleton are available in the literature using ammonia [8], refluxing ammonium hydroxide in a closed vessel microwave synthesizer [9], urea-silica gel [10], ammonium acetate in ethanol under microwave irradiation [11], ammonium hydroxide in ethanol [12], 2,4,6-trichloro-1,3,5-triazine [13], magnesium nitride [14] in water at an elevated temperature in a sealed vessel using stoichiometric excess of organic reactants, and many others. Many of the aforesaid protocols use expensive and toxic reagents (often in excess amounts than required for reaction stoichiometry), have complicated reaction setup, require long reaction times, and form byproducts due to various side reactions. Often these reactions are performed in various organic solvents posing a serious threat of fire hazard, especially when they are carried out under microwave irradiation. Several solvent-free protocols [10] have been developed using supported reagents, but still they require toxic organic solvents during product isolation. Also the disposal of the left-over inorganic supports remains problematic [10] which causes perturbation in the environment. In recent times, ammonium acetate has been judiciously utilized [15, 16] as a
%U http://www.hindawi.com/journals/isrn.organic.chemistry/2012/342738/