Multi-component reaction
Encyclopedia
In chemistry
, a multi-component reaction (or MCR), sometimes referred to as a "Multi-component Assembly Process" (or MCAP), is a chemical reaction
where three or more compound
s react to form a single product. By definition, multicomponent reactions are those reactions whereby more than two reactants combine in a sequential manner to give highly selective products that retain majority of the atoms of the starting material.
Isocyanide based MCRs are most frequently exploited because the isocyanide is an extraordinary functional group. It is believed to exhibit resonance between its tetravalent and divalent carbon forms. This induces the isocyanide group to undergo both electrophilic and nucleophilic reactions at the CII atom, which then converts to the CIV form in a exothermic reaction. The occurrence of isocyanides in natural products has also made it a useful functional group. The two most important isocyanide-based multicomponent reactions are the Passerini 3-component reaction to produce α-acyloxy carboxamides and the Ugi 4-component reaction, which yields the α-acylamino carboxamides.
Examples of three component reactions:
The exact nature of this type of reaction is often difficult to assess, in collision theory
a simultaneous interaction of 3 or more different molecules is less likely resulting in a low reaction rate
. These reactions are more likely to involve a series of bimolecular reactions.
New MCR's are found by building a chemical library
from combinatorial chemistry
or by combining existing MCR's. For example, a 7-component MCR results from combining the Ugi reaction
with the Asinger reaction
. MCR's are an important tool in new drug discovery. MCR's can often be extended into combinatorial, solid phase or flow syntheses for developing new lead structures of active agents.
Chemistry
Chemistry is the science of matter, especially its chemical reactions, but also its composition, structure and properties. Chemistry is concerned with atoms and their interactions with other atoms, and particularly with the properties of chemical bonds....
, a multi-component reaction (or MCR), sometimes referred to as a "Multi-component Assembly Process" (or MCAP), is a chemical reaction
Chemical reaction
A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, typically following the input of some type of energy, such as heat, light or electricity...
where three or more compound
Chemical compound
A chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...
s react to form a single product. By definition, multicomponent reactions are those reactions whereby more than two reactants combine in a sequential manner to give highly selective products that retain majority of the atoms of the starting material.
History and Types Multicomponent Reactions
Multicomponent reactions have been known for over 150 years. The first documented multicomponent reaction was the Strecker synthesis of α-amino cyanides in 1850 from which α-amino acids could be derived. A multitude of MCRs exist today, of which the isocyanide based MCRs are the most documented. Other MCRs include free-radical mediated MCRs, MCRs based on organoboron compounds and metal-catalyzed MCRs.Isocyanide based MCRs are most frequently exploited because the isocyanide is an extraordinary functional group. It is believed to exhibit resonance between its tetravalent and divalent carbon forms. This induces the isocyanide group to undergo both electrophilic and nucleophilic reactions at the CII atom, which then converts to the CIV form in a exothermic reaction. The occurrence of isocyanides in natural products has also made it a useful functional group. The two most important isocyanide-based multicomponent reactions are the Passerini 3-component reaction to produce α-acyloxy carboxamides and the Ugi 4-component reaction, which yields the α-acylamino carboxamides.
Examples of three component reactions:
- Alkyne trimerisationAlkyne trimerisationAn alkyne trimerisation reaction is a 2+2+2 cyclization reaction in which three alkyne molecules react to form an aromatic compound. The reaction is 'pseudo' pericyclic since it has not been observed to occur without the assistance of metal catalysis; and the metal catalyst assembles the ring...
- Biginelli reactionBiginelli reactionThe Biginelli reaction is a multiple-component chemical reaction that creates 3,4-dihydropyrimidin-2-ones 4 from ethyl acetoacetate 1, an aryl aldehyde , and urea 3. It is named for the Italian chemist Pietro Biginelli.This reaction was developed by Pietro Biginelli in 1891...
- Bucherer–Bergs reaction
- Gewald reactionGewald reactionThe Gewald reaction is an organic reaction involving the condensation of a ketone with a α-cyanoester in the presence of elemental sulfur and base to give a poly-substituted 2-amino-thiophene. -Reaction mechanism:...
- Hantzsch pyridine synthesisHantzsch pyridine synthesisThe 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...
- Kabachnik–Fields reaction
- Mannich reactionMannich reactionThe Mannich reaction is an organic reaction which consists of an amino alkylation of an acidic proton placed next to a carbonyl functional group with formaldehyde and ammonia or any primary or secondary amine. The final product is a β-amino-carbonyl compound also known as a Mannich base...
- Passerini reactionPasserini reactionThe Passerini reaction is a chemical reaction involving an isocyanide, an aldehyde , and a carboxylic acid to form a α-acyloxy amide. This organic reaction was discovered by Mario Passerini in 1921 in Florence, Italy...
- Pauson–Khand reactionPauson–Khand reactionThe Pauson–Khand reaction is a chemical reaction described as a [2+2+1] cycloaddition between an alkyne, an alkene and carbon monoxide to form a α,β-cyclopentenone...
- Strecker amino acid synthesisStrecker amino acid synthesisThe Strecker amino acid synthesis, devised by Adolph Strecker, is a series of chemical reactions that synthesize an amino acid from an aldehyde . The aldehyde is condensed with ammonium chloride in the presence of potassium cyanide to form an α-aminonitrile, which is subsequently hydrolyzed to give...
- Ugi reactionUgi reactionThe Ugi reaction is a multi-component reaction in organic chemistry involving a ketone or aldehyde, an amine, an isocyanide and a carboxylic acid to form a bis-amide.The reaction is named after Ivar Karl Ugi, who first published this reaction in 1959....
- Asinger reactionAsinger reactionThe Asinger-reaction was invented in 1956 by Friedrich Asinger . The Asinger-reaction is a multicomponent reaction and is classified as A-4CR :...
The exact nature of this type of reaction is often difficult to assess, in collision theory
Collision theory
Collision theory is a theory proposed by Max Trautz and William Lewis in 1916 and 1918, that qualitatively explains how chemical reactions occur and why reaction rates differ for different reactions. For a reaction to occur the reactant particles must collide. Only a certain fraction of the total...
a simultaneous interaction of 3 or more different molecules is less likely resulting in a low reaction rate
Reaction rate
The reaction rate or speed of reaction for a reactant or product in a particular reaction is intuitively defined as how fast or slow a reaction takes place...
. These reactions are more likely to involve a series of bimolecular reactions.
New MCR's are found by building a chemical library
Chemical library
A chemical library or compound library is a collection of stored chemicals usually used ultimately in high-throughput screening or industrial manufacture. The chemical library can consist in simple terms of a series of stored chemicals...
from combinatorial chemistry
Combinatorial chemistry
Combinatorial chemistry involves the rapid synthesis or the computer simulation of a large number of different but structurally related molecules or materials...
or by combining existing MCR's. For example, a 7-component MCR results from combining the Ugi reaction
Ugi reaction
The Ugi reaction is a multi-component reaction in organic chemistry involving a ketone or aldehyde, an amine, an isocyanide and a carboxylic acid to form a bis-amide.The reaction is named after Ivar Karl Ugi, who first published this reaction in 1959....
with the Asinger reaction
Asinger reaction
The Asinger-reaction was invented in 1956 by Friedrich Asinger . The Asinger-reaction is a multicomponent reaction and is classified as A-4CR :...
. MCR's are an important tool in new drug discovery. MCR's can often be extended into combinatorial, solid phase or flow syntheses for developing new lead structures of active agents.
See also
- A tandem reaction is a consecutive series of intramolecularIntramolecularIntramolecular in chemistry describes a process or characteristic limited within the structure of a single molecule, a property or phenomenon limited to the extent of a single molecule.- Examples :...
organic reactionOrganic reactionOrganic 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,...
s.