organic chemistry Organic chemistry is a subdiscipline within chemistry involving the science, scientific study of the structure, properties, and reactions of organic compounds and organic matter, organic materials, i.e., matter in its various forms that contain ...

, a homologation reaction, also known as homologization, is any

chemical reaction A chemical reaction is a process that leads to the chemistry, chemical transformation of one set of chemical substances to another. When chemical reactions occur, the atoms are rearranged and the reaction is accompanied by an Gibbs free energy, ...

that converts the reactant into the next member of the

homologous series In organic chemistry, a homologous series is a sequence of compounds with the same functional group and similar chemical properties in which the members of the series differ by the number of repeating units they contain. This can be the length of ...

. A homologous series is a group of compounds that differ by a constant unit, generally a methylene () group. The reactants undergo a homologation when the number of a repeated

structural unit In polymer chemistry, a structural unit is a building block of a polymer chain. It is the result of a monomer which has been polymerized into a long chain. There may be more than one structural unit in the repeat unit. When different monomers ar ...

in the molecules is increased. The most common homologation reactions increase the number of methylene () units in saturated chain within the molecule. For example, the reaction of

aldehyde In organic chemistry, an aldehyde () (lat. ''al''cohol ''dehyd''rogenatum, dehydrogenated alcohol) is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred ...

s or

ketone In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...

s with

diazomethane Diazomethane is an organic chemical compound with the formula CH2N2, discovered by German chemist Hans von Pechmann in 1894. It is the simplest diazo compound. In the pure form at room temperature, it is an extremely sensitive explosive yellow ga ...

methoxymethylenetriphenylphosphine Methoxymethylenetriphenylphosphorane is a Wittig reagent used for the homologization of aldehydes, and ketones to extended aldehydes, an organic reaction first reported in 1958. The reagent is generally prepared and used in situ. It has blood-red ...

to give the next homologue in the series. Examples of homologation reactions include: * Kiliani-Fischer synthesis, where an

aldose An aldose is a monosaccharide (a simple sugar) with a carbon backbone chain with a carbonyl group on the endmost carbon atom, making it an aldehyde, and hydroxyl groups connected to all the other carbon atoms. Aldoses can be distinguished from ket ...

molecule is elongated through a three-step process consisting of: *# Nucleophillic addition of cyanide to the carbonyl to form a

cyanohydrin In organic chemistry, a cyanohydrin or hydroxynitrile is a functional group found in organic compounds in which a cyano and a hydroxy group are attached to the same carbon atom. The general formula is , where R is H, alkyl, or aryl. Cyanohyd ...

*# Hydrolysis to form a

lactone Lactones are cyclic carboxylic esters. They are derived from the corresponding hydroxycarboxylic acids by esterification. They can be saturated or unsaturated. Lactones are formed by lactonization, the intramolecular esterification of the corresp ...

*# Reduction to form the homologous aldose *

Wittig reaction The Wittig reaction or Wittig olefination is a chemical reaction of an aldehyde or ketone with a triphenyl phosphonium ylide called a Wittig reagent. Wittig reactions are most commonly used to convert aldehydes and ketones to alkenes. Most o ...

of an aldehyde with

, which produces a homologous aldehyde. *

Arndt–Eistert reaction In organic chemistry, the Arndt–Eistert reaction is the conversion of a carboxylic acid to its homologue. It is named for the German chemists Fritz Arndt (1885–1969) and Bernd Eistert (1902–1978). The method entails treating an a ...

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 In organic chemistry, alkynols (''hydroxyalkynes'') are organic compounds that contain both alkyne and alcohol functional groups. Thus, as structural features, they have a C≡C triple bond and a hydroxyl group. Some alkynols play a role as inte ...

intermediate. *

Seyferth–Gilbert homologation The Seyferth–Gilbert homologation is a chemical reaction of an aryl ketone 1 (or aldehyde) with dimethyl (diazomethyl)phosphonate 2 and potassium tert-butoxide to give substituted alkynes 3. Dimethyl (diazomethyl)phosphonate 2 is often called th ...

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 The DeMayo reaction is a photochemical reaction in which the enol of a 1,3-diketone reacts with an alkene (or another species with a C=C bond) and the resulting cyclobutane ring undergoes a retro-aldol reaction to yield a 1,5-diketone: The net e ...

can be considered a two-carbon homologation reaction.

Chain reduction

Likewise the chain length can also be reduced: * In the

Gallagher–Hollander degradation In the Gallagher–Hollander degradation (1946) pyruvic acid is removed from a linear aliphatic carboxylic acid yielding a new acid with two carbon atoms fewer.Vincent P. Hollander and T. F. Gallagher PArtial synthesis of compounds related to adre ...

(1946)

pyruvic acid Pyruvic acid (CH3COCOOH) is the simplest of the keto acids, alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate acid, conjugate base, CH3COCOO−, is an metabolic intermediate, intermediate in several m ...

is removed from a linear aliphatic

carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an Substituent, R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl ...

yielding a new acid with 2 carbon atoms less. The original publication concerns the conversion of

bile acid Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver in peroxisomes. Bile acids are conjugated with taurine or glycine residues to give anions called bile ...

in a series of reactions:

acid chloride In organic chemistry, an acyl chloride (or acid chloride) is an organic compound with the functional group . Their formula is usually written , where R is a side chain. They are reactive derivatives of carboxylic acids (). A specific example o ...

(2) formation with

thionyl chloride Thionyl chloride is an inorganic compound with the chemical formula . It is a moderately Volatility (chemistry), volatile, colourless liquid with an unpleasant acrid odour. Thionyl chloride is primarily used as a Halogenation, chlorinating reagen ...

, diazoketone formation (3) with

, chloromethyl ketone formation (4) with

hydrochloric acid Hydrochloric acid, also known as muriatic acid or spirits of salt, is an aqueous solution of hydrogen chloride (HCl). It is a colorless solution with a distinctive pungency, pungent smell. It is classified as a acid strength, strong acid. It is ...

organic reduction Organic reductions or organic oxidations or organic redox reactions are redox reactions that take place with organic compounds. In organic chemistry oxidations and reductions are different from ordinary redox reactions, because many reactions car ...

of chlorine to methylketone (5),

ketone halogenation In organic chemistry, α-keto halogenation is a special type of halogenation. The reaction may be carried out under either acidic or basic conditions in an aqueous medium with the corresponding elemental halogen. In this way, chloride, bromide, a ...

to 6,

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. The one-step mechanism is known as the E2 reaction, and the two-step mechanism is known as the E1 r ...

with

pyridine Pyridine is a basic (chemistry), basic heterocyclic compound, heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom . It is a highly flammable, weak ...

to enone 7 and finally oxidation with

chromium trioxide Chromium trioxide (also known as chromium(VI) oxide or chromic anhydride) is an inorganic compound with the formula . It is the acidic anhydride of chromic acid, and is sometimes marketed under the same name. This compound is a dark-purple solid ...

to ''bisnorcholanic acid'' 8. : * In the

Hooker reaction In the Hooker reaction (1936) an alkyl chain in a certain naphthoquinone (phenomenon first observed in the compound lapachol) is reduced by one methylene unit as carbon dioxide in each potassium permanganate organic oxidation, oxidation.''On the ...

(1936) an alkyl chain in a certain

naphthoquinone Naphthoquinones constitute a class of organic compounds structurally related to naphthalene. Two isomers are common for the parent naphthoquinones: * 1,2-Naphthoquinone * 1,4-Naphthoquinone Natural products * Alkannin * Hexahydroxy-1,4-nap ...

(phenomenon first observed in the compound

lapachol Lapachol is a natural phenolic compound isolated from the bark of the lapacho tree.Record, Samuel J.. "Lapachol" pages 17-19. In: ''Tropical Woods'' (1925). This tree is known botanically as '' Handroanthus impetiginosus'', but was formerly kno ...

) is reduced by one methylene unit as

carbon dioxide Carbon dioxide is a chemical compound with the chemical formula . It is made up of molecules that each have one carbon atom covalent bond, covalently double bonded to two oxygen atoms. It is found in a gas state at room temperature and at norma ...

in each

potassium permanganate Potassium permanganate is an inorganic compound with the chemical formula KMnO4. It is a purplish-black crystalline salt, which dissolves in water as K+ and ions to give an intensely pink to purple solution. Potassium permanganate is widely us ...

oxidation Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...

.''On the Oxidation of 2-Hydroxy-1,4-naphthoquinone Derivatives with Alkaline Potassium Permanganate. Part II. Compounds with Unsaturated Side'' Chains Samuel C. Hooker and Al Steyermark J. Am. Chem. Soc. 1936; 58(7); pp 1179 - 1181; : :Mechanistically oxidation causes ring-cleavage at the alkene group, extrusion of

decarboxylation Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is ...

with subsequent ring-closure.

References

{{DEFAULTSORT:Homologation Reaction Carbon-carbon bond forming reactions

Chain reduction

See also

References