Hantzsch synthesis

The Hantzsch pyridine synthesis or Hantzsch dihydropyridine synthesis is a multi-component organic reaction between an aldehyde such as formaldehyde, 2 equivalents of a β-keto ester such as ethyl acetoacetate and a nitrogen donor such as ammonium acetate or ammonia.The initial reaction product is a dihydropyridine which can be oxidized in a subsequent step to a pyridine. The driving force for this second reaction step is aromatization. This reaction was reported in 1881 by Arthur Rudolf Hantzsch.

A 1,4-dihydropyridine dicarboxylate is also called a 1,4-DHP compound or a Hantzsch compound. These compounds are an important class of calcium channel blockers and as such commercialized in for instance nifedipine, amlodipine or nimodipine.

The reaction has been demonstrated to proceed in water as reaction solvent and with direct aromatization by ferric chloride or potassium permanganate in a one-pot synthesis

References

 Enantioselective Organocatalytic Hantzsch Synthesis of Polyhydroquinolines

Christopher G. Evans and Jason E. Gestwicki

Org. Lett., 200911 (14), pp 2957–2959

 

 

Theoretical Study of the Mechanism of Hantzsch Ester Hydrogenation of Imines Catalyzed by Chiral BINOL-Phosphoric Acids

Luis Simon and Jonathan M. Goodman

J. Am. Chem. Soc., 2008130 (27), pp 8741–8747

 

 

An efficient one-step synthesis of 1,4-dihydropyridines via a triphenylphosphine-catalyzed three-component Hantzschreaction under mild conditions
Tetrahedron LettersVolume 50, Issue 3716 September 2009Pages 5248-5250
Abdelmadjid Debache, Wassima Ghalem, Raouf Boulcina, Ali Belfaitah, Salah Rhouati, Bertrand Carboni

 

 

Bakers’ yeast catalyzed synthesis of polyhydroquinoline derivatives via an unsymmetrical Hantzsch reaction
Tetrahedron LettersVolume 48, Issue 2228 May 2007, Pages 3887-3890
Atul Kumar, Ram Awatar Maurya

 

 

Synthesis of polyhydroquinoline derivatives through unsymmetric Hantzsch reaction using organocatalysts
TetrahedronVolume 63, Issue 926 February 2007Pages 1946-1952
Atul Kumar, Ram Awatar Maurya

 

 

Ceric Ammonium Nitrate (CAN) catalyzes the one-pot synthesis of polyhydroquinoline via the Hantzsch reaction
TetrahedronVolume 62, Issue 3131 July 2006Pages 7293-7299
Shengkai Ko, Ching-Fa Yao

 

 

Molecular iodine-catalyzed one-pot synthesis of 4-substituted-1,4-dihydropyridine derivatives via Hantzsch reaction
Tetrahedron LettersVolume 46, Issue 3422 August 2005Pages 5771-5774
Shengkai Ko, M.N.V. Sastry, Chunchi Lin, Ching-Fa Yao

 

 

Facile Yb(OTf)3 promoted one-pot synthesis of polyhydroquinoline derivatives through Hantzsch reaction
TetrahedronVolume 61, Issue 67 February 2005Pages 1539-1543
Li-Min Wang, Jia Sheng, Liang Zhang, Jian-Wei Han, Zhao-Yu Fan, He Tian, Chang-Tao Qian

 

 

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