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

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

chemical reaction A chemical reaction is a process that leads to the chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the positions of electrons in the forming and breakin ...

that converts the

reactant In chemistry, a reagent ( ) or analytical reagent is a substance or compound added to a system to cause a chemical reaction, or test if one occurs. The terms ''reactant'' and ''reagent'' are often used interchangeably, but reactant specifies a ...

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 can be branched or unbranched, or differ by molecular formula of and molec ...

. 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 () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl group ...

s or

ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bo ...

s with

diazomethane Diazomethane is the chemical compound 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 gas; thus, it is almost ...

or methoxymethylenetriphenylphosphine 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. Cyanohydrin ...

*# Hydrolysis to form a

lactone Lactones are cyclic carboxylic esters, containing a 1-oxacycloalkan-2-one structure (), or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. Lactones are formed by intramolecular esterification of the co ...

*# 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 of ...

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 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. Synthetically, t ...

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

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 R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...

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. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts. Primary ...

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 volatile, colourless liquid with an unpleasant acrid odour. Thionyl chloride is primarily used as a chlorinating reagent, with approximately per year bein ...

, diazoketone formation (3) with

, chloromethyl ketone formation (4) with

hydrochloric acid Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid. It is a component of the gastric acid in the digestiv ...

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 c ...

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 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, weakly alkaline, water-miscible liquid with ...

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 CrO3. It is the acidic anhydride of chromic acid, and is sometimes marketed under the same name. This compound is a dark-purple ...

to ''bisnorcholanic acid'' 8. : * In the Hooker reaction (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-napht ...

(phenomenon first observed in the compound lapachol) is reduced by one methylene unit as carbon dioxide in each

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

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

.''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 carbon dioxide in

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