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.[1][2] The initial reaction product is a dihydropyridine which can be oxidized in a subsequent step to a pyridine.[3] 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 ester. These compounds are an important class of calcium channel blockers[2] 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, manganese dioxide or potassium permanganate in a one-pot synthesis.[4]
Hantzsch reaction with ammonium acetate, ethyl acetoacetate, formaldehyde and ferric chloride
The Hantzsch dihydropyridine synthesis has been effected by microwave chemistry.[5]
^Hantzsch, A. (1881). "Condensationprodukte aus Aldehydammoniak und Ketonartigen Verbindungen". Chemische Berichte. 14 (2): 1637–8. doi:10.1002/cber.18810140214.
^ abLi, Jie Jack (19 July 2006). Name Reactions (3rd ed.). ISBN 3-540-30030-9.
^Li, Jie Jack (11 October 2004). Name reactions in heterocyclic chemistry. p. 304. ISBN 0-471-30215-5.
^Xia, J. J.; Wang, G. W. (2005). "One-Pot Synthesis and Aromatization of 1,4-Dihydropyridines in Refluxing Water". Synthesis. 2005 (14): 2379–83. doi:10.1055/s-2005-870022.
^van den Eynde, J. J.; Mayence, A. (2003). "Synthesis and Aromatization of Hantzsch 1,4-Dihydropyridines under Microwave Irradiation. An Overview" (PDF). Molecules. 8 (4): 381–91. doi:10.3390/80400381. S2CID 98443099.
and 21 Related for: Hantzsch pyridine synthesis information
NADH, a naturally occurring dihydropyridine. Hantzsch ester can be made with a Hantzschpyridinesynthesis where formaldehyde, two equivalents of ethyl...
The Hantzsch Pyrrole Synthesis, named for Arthur Rudolf Hantzsch, is the chemical reaction of β-ketoesters (1) with ammonia (or primary amines) and α-haloketones...
first synthesis of a heteroaromatic compound. The first major synthesis of pyridine derivatives was described in 1881 by Arthur Rudolf Hantzsch. The Hantzsch...
of the aldehyde or ketone. The Hantzschpyridinesynthesis, the Gewald reaction and the Feist–Benary furan synthesis all contain a Knoevenagel reaction...
hydrides Hantzschpyridinesynthesis, multi-component organic reaction between an aldehyde a β-keto ester and a nitrogen donor Hantzsch pyrrole synthesis, the...
The Hantzschpyridinesynthesis, a multi-component organic reaction, is named after him, as is the Hantzsch pyrrole synthesis and the Hantzsch thiazole...
laboratory methods exist for the organic synthesis of thiazoles. Prominent is the Hantzsch thiazole synthesis, which is a reaction between haloketones...
applications involves unstrained organic 5- and 6-membered rings. Included are pyridine, thiophene, pyrrole, and furan. Another large class of organic heterocycles...
and an amine. This multicomponent reaction is related to the Hantzschpyridinesynthesis. 2-Piperidinone 3-Piperidinone 4-Piperidinone Petrenko-Kritschenko...
thiazole (pyridines of the thiophene series), Berichte der deutschen chemischen Gesellschaft, 20 : 3118–3132, see p. 3119. See also: Hantzsch, A. (1888)...
the synthesis of asenapine: Organocatalytic transfer hydrogenation has been described by the group of List in 2004 in a system with a Hantzsch ester...
"Stereoselective Synthesis of all- trans -Isomers of 1,2,3,4-Tetrahydropyridines and Piperidines from Hantzsch-Type 1,4-Dihydropyridines". Synthesis. 1985 (2):...
rings, and borazines, which contain only boron and nitrogen in the rings). Hantzsch–Widman nomenclature is recommended by the IUPAC for naming heterocycles...
phosphorus, ring opening, or ring expansion. According to the extended Hantzsch-Widman system of naming heterocyclic parent hydrides, the saturated four-membered...
Global Information