Hantzsch pyridine synthesis
Encyclopedia
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 blocker
s 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
.
The Hantzsch dihydropyridine synthesis is found to benefit from microwave chemistry
.
Multi-component reaction
In chemistry, a multi-component reaction , sometimes referred to as a "Multi-component Assembly Process" , is a chemical reaction where three or more compounds react to form a single product...
organic reaction
Organic reaction
Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, photochemical reactions and redox reactions. In organic synthesis,...
between an aldehyde
Aldehyde
An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....
such as formaldehyde
Formaldehyde
Formaldehyde is an organic compound with the formula CH2O. It is the simplest aldehyde, hence its systematic name methanal.Formaldehyde is a colorless gas with a characteristic pungent odor. It is an important precursor to many other chemical compounds, especially for polymers...
, 2 equivalents of a β-keto ester such as ethyl acetoacetate
Ethyl acetoacetate
The organic compound ethyl acetoacetate is the ethyl ester of acetoacetic acid. It is mainly used as a chemical intermediate in the production of a wide variety of compounds, such as amino acids, analgesics, antibiotics, antimalarial agents, antipyrine and aminopyrine, and vitamin B1; as well as...
and a nitrogen donor such as ammonium
Ammonium
The ammonium cation is a positively charged polyatomic cation with the chemical formula NH. It is formed by the protonation of ammonia...
acetate
Acetate
An acetate is a derivative of acetic acid. This term includes salts and esters, as well as the anion found in solution. Most of the approximately 5 billion kilograms of acetic acid produced annually in industry are used in the production of acetates, which usually take the form of polymers. In...
or ammonia
Ammonia
Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
. The initial reaction product is a dihydropyridine which can be oxidized in a subsequent step to a pyridine
Pyridine
Pyridine is a basic heterocyclic organic compound with the chemical formula C5H5N. It is structurally related to benzene, with one C-H group replaced by a nitrogen atom...
. The driving force for this second reaction step is aromatization. This reaction was reported in 1881 by Arthur Rudolf Hantzsch
Arthur Rudolf Hantzsch
Arthur Rudolf Hantzsch , was a German chemist.-Life and work:Hantzsch studied chemistry in Dresden and graduated at the University of Würzburg under Johannes Wislicenus...
.
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 blocker
Calcium channel blocker
A calcium channel blocker is a chemical that disrupts the movement of calcium through calcium channels.CCB drugs devised to target neurons are used as antiepileptics. However, the most widespread clinical usage of calcium channel blockers is to decrease blood pressure in patients with...
s and as such commercialized in for instance nifedipine
Nifedipine
Nifedipine is a dihydropyridine calcium channel blocker...
, amlodipine
Amlodipine
Amlodipine is a long-acting calcium channel blocker used as an anti-hypertensive and in the treatment of angina...
or nimodipine
Nimodipine
Nimodipine is a dihydropyridine calcium channel blocker originally developed for the treatment of high blood pressure...
.
The reaction has been demonstrated to proceed in water
Water
Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...
as reaction solvent and with direct aromatization by ferric chloride or potassium permanganate
Potassium permanganate
Potassium permanganate is an inorganic chemical compound with the formula KMnO4. It is a salt consisting of K+ and MnO4− ions. Formerly known as permanganate of potash or Condy's crystals, it is a strong oxidizing agent. It dissolves in water to give intensely purple solutions, the...
in a one-pot synthesis
One-pot synthesis
In chemistry a one-pot synthesis is a strategy to improve the efficiency of a chemical reaction whereby a reactant is subjected to successive chemical reactions in just one reactor...
.
Microwave chemistry
Microwave chemistry is the science of applying microwave irradiation to chemical reactions. Microwaves act as high frequency electric fields and will generally heat any material containing mobile electric charges, such as polar molecules in a solvent or conducting ions in a solid...
.