Multi-component reaction

In chemistry, a multi-component reaction (or MCR) is a chemical reaction where three or more compounds react to form a single product.^[1]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.^[2]

Examples of three component reactions:

• Alkyne trimerisation
• Biginelli reaction ^[8,9]
• Bucherer–Bergs reaction
• Gewald reaction
• Hantzsch pyridine synthesis ^[5,6,7]
• Kabachnik–Fields reaction
• Mannich reaction
• Passerini reaction
• Pauson–Khand reaction
• Strecker amino acid synthesis

Examples of four component reactions:

• Ugi reaction
• Asinger reaction

Atul Kumar group has reported enzyme catalysed Biginelli and Hantzsch reaction^[7,9] Dr Atul Kumar has also reported organocatalysed synthesis of Biginelli and Hantzsch reaction<[5,6,8]

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.^[3] For example, a 7-component MCR results from combining the Ugi reaction with the Asinger reaction.^[4] MCR's are an important tool in new drug discovery.

See also

• A tandem reaction is a consecutive series of intramolecular organic reactions.

References

1. ^Armstrong1996 Armstrong, R. W.; Combs, A. P.; Tempest, P. A.; Brown, S. D.; Keating, T. A. Acc. Chem. Res. 1996, 29, 123-131.

2. ^ Presentation on Multicomponent Reactions, Akul Mehta, 2009 (Presentation on Multicomponent Reactions).

3. ^ Recent progress in the chemistry of multicomponent reactions Ivar Ugi Pure Appl. Chem. 2001, 73, 187-191. (Online article)

4. ^ The discovery of new isocyanide-based multi-component reactions Alexander Dömling Current Opinion in Chemical Biology 2000, 4, 318-323. (Online article)

5. Atul Kumar & R.A.Muarya Synthesis of polyhydroquinoline derivaties through unsymmetrical Hantzsch reaction using organocatalyst Tetrahedron 2007, 63, 1946-1952.

6. Atul Kumar*, R.A.Muarya Efficient Synthesis of Hantzsch Esters and Polyhydro- quinoline Derivatives in Aqueous Micelles SYNLETT 2008,883

7. Atul Kumar*, R.A.Muarya A Baker’s yeast catalysed efficient synthesis of polyhydroquinoline derivatives Tetrahedron Letters 2007 48, 3887-3890.

8. Atul Kumar*, R.A.Muarya Organocatalyzed three-component domino synthesis of 1,4-dihydropyridines under solvent free conditions Tetrahedron 2008,64, 3477-3482

9. Atul Kumar* & R.A.Muary Baker’s yeast catalysed efficient synthesis of Biginelli derivatives Tetrahedron Letters 48, 2007, 4569-4571.

External links

• Multicomponent reactions
• Presentation on Multicomponent Reactions
• [5] from organic-reaction.com