A clean procedure for the synthesis of 1,4-dihydropyridines via Hantzsch reaction in water

A clean and efficient procedure was established to synthesize 1,4-dihydropyridines via one-pot Hantzsch reactions in aqueous medium without the use of a catalyst and/or organic solvent. The reaction with stoichiometric molar ration could be carried out in a sealed vessel with a water steam, air, or nitrogen atmosphere to afford Hantzsch esters in good to excellent yields and purities. After the simple filtration, the 1,4-dihydropyridines were isolated, and the filtrate could be recycled and reused without significantly decreasing the yields and purities. The novel and clean methodology offers the advantages including short reaction time, good yields, operational simplicity, less leaks, and environmentally benign.

[1]  B. P. Reddy,et al.  Ionic liquid[tbmim]Cl2/AlCl3 under ultrasonic irradiation towards synthesis of 1,4-DHP’s , 2015 .

[2]  Xianfu Lin,et al.  Candida antarctica Lipase B‐Catalyzed the Unprecedented Three‐Component Hantzsch‐Type Reaction of Aldehyde with Acetamide and 1,3‐Dicarbonyl Compounds in Non‐Aqueous Solvent. , 2011 .

[3]  K. Sirisha,et al.  Synthesis, antibacterial and antimycobacterial activities of some new 4-aryl/heteroaryl-2,6-dimethyl-3,5-bis-N-(aryl)-carbamoyl-1,4-dihydropyridines. , 2011, European journal of medicinal chemistry.

[4]  Xianfu Lin,et al.  Candida antarctica lipase B-catalyzed the unprecedented three-component Hantzsch-type reaction of aldehyde with acetamide and 1,3-dicarbonyl compounds in non-aqueous solvent , 2011 .

[5]  G. Palmisano,et al.  Ultrasound-enhanced one-pot synthesis of 3-(Het)arylmethyl-4-hydroxycoumarins in water. , 2011, Ultrasonics sonochemistry.

[6]  J. Safari,et al.  Cellulose sulfuric acid catalyzed multicomponent reaction for efficient synthesis of 1,4-dihydropyridines via unsymmetrical Hantzsch reaction in aqueous media , 2011 .

[7]  Atul Kumar,et al.  A grinding-induced catalyst- and solvent-free synthesis of highly functionalized 1,4-dihydropyridines via a domino multicomponent reaction , 2011 .

[8]  A. Sobolev,et al.  Use of pyridinium ionic liquids as catalysts for the synthesis of 3,5-bis(dodecyloxycarbonyl)-1,4-dihydropyridine derivative , 2010 .

[9]  G. Nandi,et al.  Biginelli and Hantzsch-type reactions leading to highly functionalized dihydropyrimidinone, thiocoumarin, and pyridopyrimidinone frameworks via ring annulation with β-oxodithioesters. , 2010, The Journal of organic chemistry.

[10]  X. Qian,et al.  K2CO3-assisted one-pot sequential synthesis of 2-trifluoromethyl-6-difluoromethylpyridine-3,5-dicarboxylates under solvent-free conditions , 2010 .

[11]  A. Jafari,et al.  Synthesis of 3,4‐Dihydropyrimidin‐2(1H)‐ones and 1,4‐Dihydropyridines Using Ammonium Carbonate in Water. , 2010 .

[12]  M. Tajbakhsh,et al.  One-step, synthesis of Hantzsch esters and polyhydroquinoline derivatives using new organocatalyst , 2010 .

[13]  A. Jafari,et al.  Synthesis of 3,4-dihydropyrimidin-2(1H)-ones and 1,4-dihydropyridines using ammonium carbonate in water , 2010 .

[14]  E. Rafiee,et al.  Silica supported 12-tungstophosphoric acid catalysts for synthesis of 1,4-dihydropyridines under solvent-free conditions , 2009 .

[15]  Cédric Kalinski,et al.  Multicomponent Reactions asa Powerful Tool for Generic Drug Synthesis , 2008 .

[16]  C. S. Reddy,et al.  Facile ZrCl4 Promoted Four‐Component Coupling One‐Pot Synthesis of Polyhydroquinoline Derivatives Through Unsymmetric Hantzsch Reaction. , 2008 .

[17]  P. Goswami.  One pot synthesis of unsymmetrical dihydropyridines by green, catalyst free and environmentally benign protocol , 2008 .

[18]  Manabendra Saha,et al.  Microwave-assisted ammonium formate-mediated synthesis of Hanstzch dihydropyridines under solvent-free conditions – a green protocol , 2008 .

[19]  S. Kannan,et al.  Hantzsch pyridine synthesis using hydrotalcites or hydrotalcite-like materials as solid base catalysts , 2008 .

[20]  Alexander Dömling,et al.  Recent developments in isocyanide based multicomponent reactions in applied chemistry. , 2006, Chemical reviews.

[21]  J. H. Lee.  Synthesis of Hantsch 1,4-dihydropyridines by fermenting bakers’ yeast , 2005 .

[22]  C. Yao,et al.  Molecular iodine-catalyzed one-pot synthesis of 4-substituted-1,4-dihydropyridine derivatives via Hantzsch reaction , 2005 .

[23]  Jieping Zhu,et al.  Multicomponent Reactions: ZHU:MULTICOMPONENT REACTIONS O-BK , 2005 .

[24]  M. Zolfigol,et al.  Synthesis of 1,4-Dihydropyridines under Solvent-Free Conditions. , 2004 .

[25]  I. Chen,et al.  The new generation dihydropyridine type calcium blockers, bearing 4-phenyl oxypropanolamine, display α-/β-Adrenoceptor antagonist and long-Acting antihypertensive activities , 2002 .

[26]  I. Ugi,et al.  Multicomponent Reactions with Isocyanides. , 2000, Angewandte Chemie.

[27]  B. Yin.  Improved Synthesis and Aromatization of 1,4 - Dihydropyridines , 2000 .

[28]  F. Guengerich,et al.  Oxidation of 4-aryl- and 4-alkyl-substituted 2,6-dimethyl-3,5-bis(alkoxycarbonyl)-1,4-dihydropyridines by human liver microsomes and immunochemical evidence for the involvement of a form of cytochrome P-450. , 1987, Journal of medicinal chemistry.

[29]  Guengerich Fp,et al.  Oxidation of 4-aryl- and 4-alkyl-substituted 2,6-dimethyl-3,5-bis(alkoxycarbonyl)-1,4-dihydropyridines by human liver microsomes and immunochemical evidence for the involvement of a form of cytochrome P-450. , 1986 .

[30]  D. J. Triggle,et al.  New developments in calcium ion channel antagonists , 1983 .

[31]  A. Hantzsch.  Ueber die Synthese pyridinartiger Verbindungen aus Acetessigäther und Aldehydammoniak , 1882 .