Mandelic acid is an

aromatic In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satur ...

alpha hydroxy acid α-Hydroxy acids, or alpha hydroxy acids (AHAs), are a class of chemical compounds that consist of a carboxylic acid with a hydroxyl group substituent on the adjacent (alpha) carbon. Prominent examples are glycolic acid, lactic acid, mandelic aci ...

with the molecular formula C₆H₅CH(OH)CO₂H. It is a white crystalline solid that is soluble in water and polar organic

solvent A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...

s. It is a useful precursor to various drugs. The molecule is

chiral Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object. An object or a system is ''chiral'' if it is distinguishable from ...

. The

racemic In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...

mixture is known as ''paramandelic acid''.

Isolation, synthesis, occurrence

Mandelic acid was discovered in 1831 by the German pharmacist Ferdinand Ludwig Winckler (1801–1868) while heating

amygdalin Amygdalin (from Ancient Greek: ' "almond") is a naturally occurring chemical compound found in many plants, most notably in the seeds (kernels) of apricots, bitter almonds, apples, peaches, cherries, and plums. Amygdalin is classified as a cy ...

, an extract of

bitter almond The almond (''Prunus amygdalus'', syn. ''Prunus dulcis'') is a species of tree native to Iran and surrounding countries, including the Levant. The almond is also the name of the edible and widely cultivated seed of this tree. Within the genus ...

s, with diluted

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 Acid strength is the tendency of an acid, symbol ...

. The name is derived from the

German German(s) may refer to: * Germany (of or related to) ** Germania (historical use) * Germans, citizens of Germany, people of German ancestry, or native speakers of the German language ** For citizens of Germany, see also German nationality law **Ge ...

"Mandel" for "almond". Mandelic acid is usually prepared by the acid-catalysed hydrolysis of

mandelonitrile In organic chemistry, mandelonitrile is the nitrile of mandelic acid, or the cyanohydrin derivative of benzaldehyde. Small amounts of mandelonitrile occur in the pits of some fruits. Occurrence Mandelonitrile is the aglycone part of the cyan ...

, which is the

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 ...

of benzaldehyde.

Mandelonitrile In organic chemistry, mandelonitrile is the nitrile of mandelic acid, or the cyanohydrin derivative of benzaldehyde. Small amounts of mandelonitrile occur in the pits of some fruits. Occurrence Mandelonitrile is the aglycone part of the cyan ...

can also be prepared by reacting benzaldehyde with

sodium bisulfite Sodium bisulfite (or sodium bisulphite, sodium hydrogen sulfite) is a chemical mixture with the approximate chemical formula NaHSO3. Sodium bisulfite in fact is not a real compound, but a mixture of salts that dissolve in water to give solutions ...

to give the corresponding adduct, forming

with

sodium cyanide Sodium cyanide is a poisonous compound with the formula Na C N. It is a white, water-soluble solid. Cyanide has a high affinity for metals, which leads to the high toxicity of this salt. Its main application, in gold mining, also exploits its hi ...

, which is

hydrolyzed Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysis ...

: : Alternatively, it can be prepared by base hydrolysis of phenylchloroacetic acid as well as dibromacetophenone. It also arises by heating

phenylglyoxal Phenylglyoxal is the organic compound with the formula C6H5C(O)C(O)H. It contains both an aldehyde and a ketone functional group. It is yellow liquid when anhydrous but readily forms a colorless crystalline hydrate. It has been used as a reag ...

with alkalis.

Biosynthesis

Mandelic acid is a substrate or product of several biochemical processes called the mandelate pathway.

Mandelate racemase Mandelate racemase () is a bacterial enzyme which catalyzes the interconversion of the enantiomers of mandelate via an enol intermediate. This enzyme catalyses the following chemical reaction : (S)-mandelate \rightleftharpoons (R)-mandelate I ...

interconverts the two enantiomers via a pathway that involves cleavage of the alpha-CH bond. Mandelate dehydrogenase is yet another enzyme on this pathway. Mandelate also arises from trans-

cinnamate Cinnamic acid is an organic compound with the formula C6H5-CH=CH- COOH. It is a white crystalline compound that is slightly soluble in water, and freely soluble in many organic solvents. Classified as an unsaturated carboxylic acid, it occurs na ...

via phenylacetic acid, which is

hydroxylate In chemistry, hydroxylation can refer to: *(i) most commonly, hydroxylation describes a chemistry, chemical process that introduces a hydroxyl group () into an organic compound. *(ii) the ''degree of hydroxylation'' refers to the number of OH gr ...

Phenylpyruvic acid Phenylpyruvic acid is the organic compound with the formula C6H5CH2C(O)CO2H. It is a keto acid. Occurrence and properties The compound exists in equilibrium with its E- and Z-enol tautomers. It is a product from the oxidative deamination of p ...

is another precursor to mandelic acid. Derivatives of mandelic acid are formed as a result of metabolism of

adrenaline Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...

and

noradrenaline Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...

by monoamine oxidase and

catechol-O-methyl transferase Catechol-''O''-methyltransferase (COMT; ) is one of several enzymes that degrade catecholamines (neurotransmitters such as dopamine, epinephrine, and norepinephrine), catecholestrogens, and various drugs and substances having a catechol structu ...

. The

biotechnological Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term ''biotechnology'' was first used ...

production of 4-hydroxy-mandelic acid and mandelic acid on the basis of

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...

was demonstrated with a genetically modified yeast ''

Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been o ...

'', in which the hydroxymandelate synthase naturally occurring in the bacterium ''

Amycolatopsis ''Amycolatopsis'' is a genus of high GC-content bacteria within the family Pseudonocardiaceae. The genus is known for producing many types of antibiotics, including * Epoxyquinomicin, related to ''Amycolatopsis sulphurea'', are a class of weak ...

'' was incorporated into a wild-type strain of yeast, partially altered by the exchange of a gene sequence and expressed.Mara Reifenrath,

Eckhard Boles Eckhard Boles (born September 4, 1963 in Altena) is a German microbiologist and biotechnologist. Since 2003 he is professor of microbiology at the Goethe University Frankfurt with a focus on the physiology and genetics of lower eukaryotes. He wor ...

: ''Engineering of hydroxymandelate synthases and the aromatic amino acid pathway enables de novo biosynthesis of mandelic and 4-hydroxymandelic acid with Saccharomyces cerevisiae.'' Metabolic Engineering 45, Januar 2018; S. 246-254. . It also arises from the biodegradation of styrene and

ethylbenzene Ethylbenzene is an organic compound with the formula . It is a highly flammable, colorless liquid with an odor similar to that of gasoline. This monocyclic aromatic hydrocarbon is important in the petrochemical industry as an reaction intermedia ...

, as detected in urine.

Uses

Mandelic acid has a long history of use in the medical community as an antibacterial, particularly in the treatment of urinary tract infections. It has also been used as an oral antibiotic, and as a component of chemical face peels analogous to other

s. The drugs

cyclandelate Cyclandelate is a vasodilator used in the treatment of claudication, arteriosclerosis Arteriosclerosis is the thickening, hardening, and loss of elasticity of the walls of arteries. This process gradually restricts the blood flow to one's or ...

and

homatropine Homatropine (Equipin, Isopto Homatropine) is an anticholinergic medication that is an antagonist at muscarinic acetylcholine receptors and thus the parasympathetic nervous system. It is used in eye drops as a cycloplegic (to temporarily paraly ...

are

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...

s of mandelic acid.

References

* {{Authority control Alpha hydroxy acids Benzene derivatives