Homologation reaction
Encyclopedia
A homologation reaction, also known as homologization, is any 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...

 that converts the reactant into the next member of the homologous series
Homologous series
In chemistry, a homologous series is a series of compounds with a similar general formula, possessing similar chemical properties due to the presence of the same functional group, and showing a gradation in physical properties as a result of increase in molecular size and mass...

. A Homologous series
Homologous series
In chemistry, a homologous series is a series of compounds with a similar general formula, possessing similar chemical properties due to the presence of the same functional group, and showing a gradation in physical properties as a result of increase in molecular size and mass...

 is a group of compounds that differ by a constant unit, generally a (-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
Methylene
Methylene is a chemical species in which a carbon atom is bonded to two hydrogen atoms. Three different possibilities present themselves:* the -CH2- substituent group: e.g., dichloromethane ....

 (-CH2-) units in saturated chain within the molecule. For example the reaction of 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....

s or ketone
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...

s with diazomethane
Diazomethane
Diazomethane is the chemical compound CH2N2. It is the simplest of diazo compounds. In the pure form at room temperature, it is a extremely sensitive explosive yellow gas, thus it is almost universally used as a solution in diethyl ether...

 or methoxymethylenetriphenylphosphine
Methoxymethylenetriphenylphosphine
Methoxymethylenetriphenylphosphine is a Wittig reagent with used as an reagent in the homologization of aldehydes and ketones to extended aldehydes, an organic reaction first reported in 1958 ....

 to give the next homologue in the series.

Examples of homologation reactions include:
  • Kiliani-Fischer synthesis
    Kiliani-Fischer synthesis
    The Kiliani–Fischer synthesis, named for German chemists Heinrich Kiliani and Hermann Emil Fischer, is a method for synthesizing monosaccharides. It proceeds via synthesis and hydrolysis of a cyanohydrin, thus elongating the carbon chain of an aldose by one carbon atom while preserving...

    , where an aldose
    Aldose
    An aldose is a monosaccharide that contains only one aldehyde group per molecule. The chemical formula takes the form Cnn. The simplest possible aldose is the diose glycolaldehyde, which only contains two carbon atoms....

     molecule is elongated through a three-step process consisting of:
    1. Nucleophillic addition of cyanide to the carbonyl to form a cyanohydrin
      Cyanohydrin
      A cyanohydrin is a functional group found in organic compounds. Cyanohydrins have the formula R2CCN, where R is H, alkyl, or aryl. Cyanohydrins are industrially important precursors to carboxylic acids and some amino acids...

    2. Hydrolysis to form a lactone
      Lactone
      In chemistry, a lactone is a cyclic ester which can be seen as the condensation product of an alcohol group -OH and a carboxylic acid group -COOH in the same molecule...

    3. Reduction to form the homologous aldose
  • Wittig reaction
    Wittig reaction
    The Wittig reaction is a chemical reaction of an aldehyde or ketone with a triphenyl phosphonium ylide to give an alkene and triphenylphosphine oxide....

     of an aldehyde with methoxymethylenetriphenylphosphine
    Methoxymethylenetriphenylphosphine
    Methoxymethylenetriphenylphosphine is a Wittig reagent with used as an reagent in the homologization of aldehydes and ketones to extended aldehydes, an organic reaction first reported in 1958 ....

    , 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
    Kowalski ester homologation
    The Kowalski ester homologation is a chemical reaction for the homologation of esters.This reaction was designed as a safer alternative to the Arndt-Eistert synthesis. The Kowalski reaction is named after its inventor, Conrad J. Kowalski....

    , an alternative to the Arndt-Eistert synthesis. Has been used to convert β-amino esters from α-amino esters through an ynolate
    Ynolate
    Ynolates are chemical compounds with a negatively charged oxygen attached to an alkyne functionality. They were first synthesized in 1975 by Schöllkopf and Hoppe via the n-butyllithium fragmentation of 3,4-diphenylisoxazole....

     intermediate.
  • Seyferth–Gilbert homologation in which an aldehyde is converted to a terminal alkyne and then hydrolyzed back to a aldehyde.


Some reactions increase the chain length by more than one unit. For example, the following are considered two-carbon homologation reactions.

Chain reduction

Likewise the chain length can also be reduced:
  • In the Gallagher-Hollander Degradation (1946) pyruvic acid
    Pyruvic acid
    Pyruvic acid is an organic acid, a ketone, as well as the simplest of the alpha-keto acids. The carboxylate ion of pyruvic acid, CH3COCOO−, is known as pyruvate, and is a key intersection in several metabolic pathways....

     is removed from a linear aliphatic carboxylic acid
    Carboxylic acid
    Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...

     yielding a new acid with 2 carbon atoms less. The original publication concerns the conversion of bile acid
    Bile acid
    Bile acids are steroid acids found predominantly in the bile of mammals. Bile salts are bile acids compounded with a cation, usually sodium. In humans, the salts of taurocholic acid and glycocholic acid represent approximately eighty percent of all bile salts. The two major bile acids are cholic...

     in a series of reactions: acid chloride (2) formation with thionyl chloride
    Thionyl chloride
    Thionyl chloride is an inorganic compound with the formula SOCl2. It is a reactive chemical reagent used in chlorination reactions. It is a colorless, distillable liquid at room temperature and pressure that decomposes above 140 °C. Thionyl chloride is sometimes confused with sulfuryl...

    , diazoketone formation (3) with diazomethane
    Diazomethane
    Diazomethane is the chemical compound CH2N2. It is the simplest of diazo compounds. In the pure form at room temperature, it is a extremely sensitive explosive yellow gas, thus it is almost universally used as a solution in diethyl ether...

    , chloromethyl ketone formation (4) with hydrochloric acid
    Hydrochloric acid
    Hydrochloric acid is a solution of hydrogen chloride in water, that is a highly corrosive, strong mineral acid with many industrial uses. It is found naturally in gastric acid....

    , organic reduction of chlorine to methylketone (5), ketone halogenation
    Ketone halogenation
    In organic chemistry ketone halogenation is a special type of halogenation.The position alpha to the carbonyl group in a ketone is easily halogenated, due to the ability to form an enolate in basic solution, or an enol in acidic solution...

     to 6, elimination reaction
    Elimination reaction
    An elimination reaction is a type of organic reaction in which two substituents are removed from a molecule in either a one or two-step mechanism...

     with 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...

     to enone
    Enone
    An enone is an unsaturated chemical compound or functional group consisting of a conjugated system of an alkene and a ketone. The simplest enone is methyl vinyl ketone or CH2=CHCOCH3....

     7 and finally oxidation with chromium trioxide
    Chromium trioxide
    Chromium trioxide is the inorganic compound with the formula CrO3. It is the acidic anhydride of chromic acid, and is sometimes marketed under the same name.This compound is a dark-red/orange brown solid, which dissolves in water concomitant with hydrolysis...

     to bisnorcholanic acid 8.

  • In the Hooker reaction (1936) an alkyl chain in a certain naphthoquinone
    Naphthoquinone
    Naphthoquinone is a class of natural phenols based on the C6-C4 skeleton.1,4-Naphthoquinone can be viewed as derivatives of naphthalene through the replacement of two hydrogen atoms by two ketone groups....

     (phenomenon first observed in the compound lapachol
    Lapachol
    Lapachol is a natural organic compound isolated from the lapacho tree . Chemically, it is a derivative of naphthoquinone, related to vitamin K....

    ) is reduced by one methylene
    Methylene
    Methylene is a chemical species in which a carbon atom is bonded to two hydrogen atoms. Three different possibilities present themselves:* the -CH2- substituent group: e.g., dichloromethane ....

     unit as carbon dioxide
    Carbon dioxide
    Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...

     in each 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...

     oxidation.
Mechanistically oxidation causes ring-cleavage at the alkene group, extrusion of carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...

 in decarboxylation
Decarboxylation
Decarboxylation is a chemical reaction that releases carbon dioxide . Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carbonation, the addition of CO2 to...

with subsequent ring-closure.
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