Homologation reaction
A homologation reaction, also known as homologization, is any chemical reaction that effects an overall increase of the carbon skeleton of a saturated reactant molecule.[1] The reactants undergo a homologation converting them into the next member of the homologous series. For example the reaction of aldehydes and ketones with diazomethane or methoxymethylenetriphenylphosphine effectively inserts a methylene (-CH2-) unit in the hydrocarbon chain and the reaction product is the next homologue.
Examples of homologation reactions include:
- Seyferth-Gilbert homologation
- Displacement of a halide by a cyanide group, which can be reduced to an amine
- Kiliani-Fischer synthesis, where an aldose molecule is elongated through a three-step process consisting of:
- Nucleophillic addition of cyanide to the carbonyl to form a cyanohydrin
- Hydrolysis to form a lactone
- Reduction to form the homologous aldose
- Wittig reaction of an aldehyde with methoxymethylenetriphenylphosphine, which produces a homologous aldehyde.
- Arndt-Eistert synthesis is a series of chemical reactions designed to convert a carboxylic acid to a higher carboxylic acid homologue (ie. contains one additional carbon atom)
- Kowalski ester homologation, an alternative to the Arndt-Eistert synthesis. Has been used to convert β-amino esters from α-amino esters through an ynolate intermediate.[2]
Some reactions increase the chain length by more than one unit. For example, the following are considered two-carbon homologation reactions:
- Nucleophilic addition to ethylene oxide, resulting in a ring-opening and producing a primary alcohol with two extra carbons.
- Malonic ester synthesis, which produces a carboxylic acid with two extra carbons.
See also
References
- ↑ Encyclopedia of Inorganic Chemistry doi:10.1002/0470862106.id396
- ↑ D. Gray, C. Concellon and T. Gallagher (2004). "Kowalski Ester Homologation. Application to the Synthesis of β-Amino Esters". J. Org. Chem. 69 (14): 4849–4851. doi:10.1021/jo049562h.