Homologation reaction

In organic chemistry, a homologation reaction, also known as homologization, is any chemical reaction that converts the reactant into the next member of the homologous series. A homologous series is a group of compounds that differ by a constant unit, generally a methylene (−CH₂−) group. The reactants undergo a homologation when the number of a repeated structural unit in the molecules is increased. The most common homologation reactions increase the number of methylene (−CH₂−) units in saturated chain within the molecule.^[1] For example, the reaction of aldehydes or ketones with diazomethane or methoxymethylenetriphenylphosphine to give the next homologue in the series.

Examples of homologation reactions include:

• Kiliani-Fischer synthesis, where an aldose molecule is elongated through a three-step process consisting of:
  1. Nucleophillic addition of cyanide to the carbonyl to form a cyanohydrin
  2. Hydrolysis to form a lactone
  3. Reduction to form the homologous aldose
• Wittig reaction of an aldehyde with methoxymethylenetriphenylphosphine, which produces a homologous aldehyde.
• Arndt–Eistert reaction is a series of chemical reactions designed to convert a carboxylic acid to a higher carboxylic acid homologue (i.e. 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]
• Seyferth–Gilbert homologation in which an aldehyde is converted to a terminal alkyne and then hydrolyzed back to an aldehyde.

Some reactions increase the chain length by more than one unit. For example, the DeMayo reaction can be considered a two-carbon homologation reaction.