Synlett 2007(14): 2304-2305  
DOI: 10.1055/s-2007-985576
© Georg Thieme Verlag Stuttgart · New York

Hantzsch 1,4-Dihydropyridine - An Effective and Convenient Reducing Agent

Yijun Huang*
Department of Chemistry, College of Science and Engineering, ­Texas Christian University, Fort Worth, TX 76129, USA
Further Information

Publication History

Publication Date:
13 August 2007 (online)


Hantzsch 1,4-dihydropyridine [C13H19NO4, CAS: 1149-23-1] is a well-known reducing reagent that has found many applications in organic transformations. [1] In general, chemical hydrogenations of double-bond-containing compounds often involve the use of hydrogen gas with expensive and even ­toxic organometallic catalysts or stoichiometric amounts of metal hydrides. [2] To circumvent these drawbacks, one of the best alternatives is to apply organoreductants that possess ­excellent reproducibility. [3] 1,4-Dihydropyridine (DHP) has been used in hydrogen transfer reactions as a synthetic NADH model for the reduction of olefins, carbonyl compounds, and imines. In recent years, synthetic chemists have made many efforts to develop DHP as a widely used reducing agent and have obtained good to excellent results. Along with the conjugate hydride and proton transfer, DHP is ­usually subsequently oxidized to the Hantzsch pyridine. [4]

Asymmetric reduction of double-bond-containing compounds by DHP is of particular interest from the viewpoint of NADH models as well as for their synthetic utility. [5] While chiral Hantzsch esters have been employed stoichiometrically, [6] the potential of their simple achiral derivatives as co­factors in catalytic asymmetric reductions has also been explored. In this paper, the applications of DHP as an effective and convenient reducing agent for new synthetic methods and the catalytic asymmetric versions are presented.

The classical method for the synthesis of DHP is a one-pot condensation of formaldehyde, ethyl acetoacetate, and ammonia. [7] Diazomethane crystallizes in yellow needles with green fluorescence, mp 183-185 °C and is commercially available. The title compound can also be easily prepared from a combination of ethyl acetoacetate, formaldehyde, and ammonium acetate under mild and solvent-free conditions. [8]


  • 1a Stout DM. Meyers AI. Chem. Rev.  1982,  82:  223 
  • 1b Ramachary DB. Kishor M. Reddy GB. Org. Biomol. Chem.  2006,  4:  1641 
  • 2 Larock RC. Comprehensive Organic Transformations: A Guide to Functional Group Preparations   2nd ed., Vol. 1:  Wiley; New York: 1999.  p.1-76  
  • 3 Kellogg RM. Comprehensive Organic Synthesis   Vol. 8:  Trost BM. Fleming I. Pergamon; Oxford: 1991.  p.79-106  
  • 4 Itoh T. Nagata K. Matsuya Y. Miyazaki M. Ohsawa A. J. Org. Chem.  1997,  62:  3582 
  • 5 Nishiyama K. Baba N. Oda J. Inouye Y. J. Chem. Soc., Chem. Comm.  1976,  101 
  • 6 Jouin P. Troostwijk CB. Kellogg RM. J. Am. Chem. Soc.  1981,  103:  2091 
  • 7a Hantzsch A. Justus Liebigs Ann. Chem.  1882,  215:  1 
  • 7b Singer A. McElvain SM. Org. Synth., Coll. Vol. II  1943,  214 
  • 8 Zolfigol MA. Safaiee M. Synlett  2004,  827 
  • 9 Yang JW. Fonseca MTH. List B. Angew. Chem. Int. Ed.  2004,  43:  6660 
  • 10 Menche D. Hassfeld J. Li J. Menche G. Ritter A. Rudolph S. Org. Lett.  2006,  8:  741 
  • 11 Ramachary DB. Kishor M. Ramakumar K. Tetrahedron Lett.  2006,  47:  651 
  • 12 Zhu X.-Q. Wang H.-Y. Wang J.-S. Liu Y.-C. J. Org. Chem.  2001,  66:  344 
  • 13 Garden SJ. Guimaraes CRW. Correa MB. Oliveira CAF. Pinto AC. Bicca de Alencastro R. J. Org. Chem.  2003,  68:  8815 
  • 14 Yang JW. List B. Org. Lett.  2006,  8:  5653 
  • 15 Ouellet SG. Tuttle JB. MacMillan DWC. J. Am. Chem. Soc.  2005,  127:  32