Alpha hydroxy acid

Last updated
a-, b- and g-hydroxy acids Hydroxycarboxylic acids Structural Formulae V.1.svg
α-, β- and γ-hydroxy acids

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 acid, and citric acid.


Although these compounds are related to the ordinary carboxylic acids and are therefore weak acids, their chemical structure allows for the formation of an internal hydrogen bond between the hydrogen at the hydroxyl group and one of the oxygen atoms of the carboxylic group. The net effect is an increase in acidity. For example, the pKa of lactic acid is 3.86, while that of the unsubstituted propionic acid is 4.87; a full pKa unit difference means that lactic acid is ten times stronger than propionic acid. [1] [2]

Industrial applications

Feed additives

2-Hydroxy-4-(methylthio)butyric acid is produced commercially as a racemic mixture to substitute for methionine in animal feed. [3] In nature, the same compound is an intermediate in the biosynthesis of 3-dimethylsulfoniopropionate, precursor to natural dimethyl sulfide. [4]

Lactide-based polymers

Synthesis and reactions

α-Hydroxy acids are classically prepared by addition of hydrogen cyanide to a ketone or aldehyde, followed by acidic hydrolysis of the resulting cyanohydrin product. [5]

Dilithiated carboxylic acids react with oxygen to give α-hydroxy acids after an aqueous workup: [6]

RCHLiCO2Li + O2 → RCH(O2Li)CO2Li
RCH(O2Li)CO2Li + 2 H+ → RCH(OH)CO2H + 2 Li+ + ...

α-Keto aldehydes undergo the Cannizaro reaction to give α-hydroxy acids: [7]

RC(O)CHO + 2 OH → RCH(OH)CO2 + H2O

α-Hydroxy acids are useful building blocks in organic synthesis. For example, α-hydroxy acids are precursors in the preparation aldehydes via oxidative cleavage. [8] [9] Compounds of this class are used on the industrial-scale and include glycolic acid, lactic acid, citric acid, and mandelic acid. [10] [11] They are susceptible to acid-catalyzed decarbonylation to give, in addition to carbon monoxide, a ketone/aldehyde and water. [12]

α-Hydroxy acids can form polyesters [13] and membraneless protocellular structures. [14] [15] [13] [16]


AHAs are generally safe when used on the skin as a cosmetic agent using the recommended dosage. The most common side-effects are mild skin irritations, redness and flaking. The severity usually depends on the pH and the concentration of the acid used. Chemical peels tend to have more severe side-effects including blistering, burning and skin discoloration, although they are usually mild and go away a day or two after treatment. [17]

The United States Food and Drug Administration has also warned consumers that care should be taken when using AHAs after an industry-sponsored study found that they can increase photosensitivity to the sun. [18] Other sources suggest that glycolic acid, in particular, may have a photoprotective effect. [19]

See also

Further reading

Related Research Articles

Alcohol (chemistry) Type of organic compound

In chemistry, an alcohol is a type of organic compound that carries at least one hydroxyl functional group (−OH) bound to a saturated carbon atom. The term alcohol originally referred to the primary alcohol ethanol, which is used as a drug and is the main alcohol present in alcoholic drinks. An important class of alcohols, of which methanol and ethanol are the simplest members, includes all compounds for which the general formula is CnH2n+1OH. Simple monoalcohols that are the subject of this article include primary, secondary and tertiary alcohols.

Carboxylic acid Organic compound

A carboxylic acid is an organic acid that contains a carboxyl group (C(=O)OH) attached to an R-group. The general formula of a carboxylic acid is R−COOH or R−CO2H, with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic acids occur widely. Important examples include the amino acids and fatty acids. Deprotonation of a carboxylic acid gives a carboxylate anion.

Aldehyde Organic compound containing the functional group R−CH=O

In organic chemistry, an aldehyde is an organic compound containing a functional group with the structure R−CH=O. The functional group itself can be referred to as an aldehyde but can also be classified as a formyl group. Aldehydes are common and play important roles in the technology and biological spheres.

Stanley Miller American scientist (1930–2007)

Stanley Lloyd Miller was an American chemist who made landmark experiments in the origin of life by demonstrating that a wide range of vital organic compounds can be synthesized by fairly simple chemical processes from inorganic substances. In 1952 he carried out the Miller–Urey experiment, which showed that complex organic molecules could be synthesised from inorganic precursors. The experiment was widely reported, and provided support for the idea that the chemical evolution of the early Earth had led to the natural synthesis of chemical building blocks of life from inanimate inorganic molecules. He has been described as the "father of prebiotic chemistry".

Lactic acid Group of stereoisomers

Lactic acid is an organic acid. It has a molecular formula CH3CH(OH)COOH. It is white in the solid state and it is miscible with water. When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as well as natural sources. Lactic acid is an alpha-hydroxy acid (AHA) due to the presence of a hydroxyl group adjacent to the carboxyl group. It is used as a synthetic intermediate in many organic synthesis industries and in various biochemical industries. The conjugate base of lactic acid is called lactate. The name of the derived acyl group is lactoyl.

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.

A diol is a chemical compound containing two hydroxyl groups. An aliphatic diol is also called a glycol. This pairing of functional groups is pervasive, and many subcategories have been identified.

Keratosis pilaris Skin condition characterized by small bumps caused by overproduction of keratin

Keratosis pilaris is a common, autosomal-dominant, genetic condition of the skin's hair follicles characterized by the appearance of possibly itchy, small, gooseflesh-like bumps, with varying degrees of reddening or inflammation. It most often appears on the outer sides of the upper arms, thighs, face, back, and buttocks; KP can also occur on the hands, and tops of legs, sides, or any body part except glabrous (hairless) skin. Often the lesions can appear on the face, which may be mistaken for acne or folliculitis.

Piperonal Chemical compound

Piperonal, also known as heliotropin, is an organic compound which is commonly found in fragrances and flavors. The molecule is structurally related to other aromatic aldehydes such as benzaldehyde and vanillin.

Calcium hypochlorite is an inorganic compound with formula Ca(OCl)2. It is the main active ingredient of commercial products called bleaching powder, chlorine powder, or chlorinated lime, used for water treatment and as a bleaching agent. This compound is relatively stable and has greater available chlorine than sodium hypochlorite. It is a white solid, although commercial samples appear yellow. It strongly smells of chlorine, owing to its slow decomposition in moist air.

Glyoxylic acid Chemical compound

Glyoxylic acid or oxoacetic acid is an organic compound. Together with acetic acid, glycolic acid, and oxalic acid, glyoxylic acid is one of the C2 carboxylic acids. It is a colourless solid that occurs naturally and is useful industrially.

The Strecker amino acid synthesis, also known simply as the Strecker synthesis, is a method for the synthesis of amino acids by the reaction of an aldehyde with ammonia in the presence of potassium cyanide. The condensation reaction yields an α-aminonitrile, which is subsequently hydrolyzed to give the desired amino acid. The method is used commercially for the production of racemic methionine from methional.

Exfoliation (cosmetology) Removal of dead skin cells from the epidermis

Exfoliation involves the removal of the oldest dead skin cells from the skin's surface. The word comes from the Latin word exfoliare. Exfoliation is involved in all facials and can be achieved by mechanical or chemical means, such as microdermabrasion or chemical peels. Exfoliants are often advertised as treatments that promote beauty, youthful appearance, or health.

A chemical peel is a technique used to improve and smooth the texture of the skin. Facial skin is mostly treated, and scarring can be improved. Chemical peels are intended to remove the outermost layers of the skin. To accomplish this task, the chosen peel solution induces a controlled injury to the skin. Resulting wound healing processes begin to regenerate new tissues. The dead skin eventually peels off. The regenerated skin is usually smoother and less wrinkled than the old skin. Some types of chemical peels can be purchased and administered without a medical license, however people are advised to seek professional help from a dermatologist or plastic surgeon on a specific type of chemical peel before a procedure is performed.

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 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 units in saturated chain within the molecule. For example, the reaction of aldehydes or ketones with diazomethane or methoxymethylenetriphenylphosphine to give the next homologue in the series.

2-Ethylhexanoic acid Chemical compound

2-Ethylhexanoic acid is the organic compound with the formula CH3(CH2)3CH(C2H5)CO2H. It is a carboxylic acid that is widely used to prepare lipophilic metal derivatives that are soluble in nonpolar organic solvents. 2-Ethylhexanoic acid is a colorless viscous oil. It is supplied as a racemic mixture.

Carbonylation refers to reactions that introduce carbon monoxide into organic and inorganic substrates. Carbon monoxide is abundantly available and conveniently reactive, so it is widely used as a reactant in industrial chemistry. The term carbonylation also refers to oxidation of protein side chains.

Jones oxidation

The Jones oxidation is an organic reaction for the oxidation of primary and secondary alcohols to carboxylic acids and ketones, respectively. It is named after its discoverer, Sir Ewart Jones. The reaction was an early method for the oxidation of alcohols. Its use has subsided because milder, more selective reagents have been developed, e.g. Collins reagent.

Hemithioacetal Organic chemical functional group

Hemithioacetal is an organic functional group with the general formula RCH(OH)SR. Hemithioacetals are also called thiohemiacetal. With four substituents on carbon, hemithioacetals are chiral. A related functional group is dithiohemiacetal, with the formula RCH(SH)SR. Although they can be important intermediates, hemithioacetals are usually not isolated since they exist in equilibrium with the thiol and aldehyde.

In organic chemistry, the Jocic reaction, also called the Jocic–Reeve reaction is a name reaction that generates α-substituted carboxylic acids from trichloromethylcarbinols and corresponding nucleophiles in the presence of sodium hydroxide. The reaction involves nucleophilic displacement of the hydroxyl group in a 1,1,1-trichloro-2-hydroxyalkyl structure with concomitant conversion of the trichloromethyl portion to a carboxylic acid or similar functional group.


  1. Dawson RM, et al. (1959). Data for Biochemical Research. Oxford: Clarendon Press.
  2. Handbook of Chemistry and Physics, CRC Press, 58th edition, page D147 (1977)
  3. Lemme, A.; Hoehler, D.; Brennan, JJ; Mannion, PF (2002). "Relative effectiveness of methionine hydroxy analog compared to DL-methionine in broiler chickens". Poultry Science. 81 (6): 838–845. doi:10.1093/ps/81.6.838. PMID   12079051.
  4. Curson, Andrew R. J.; Liu, Ji; Bermejo Martínez, Ana; Green, Robert T.; Chan, Yohan; Carrión, Ornella; Williams, Beth T.; Zhang, Sheng-Hui; Yang, Gui-Peng; Bulman Page, Philip C.; Zhang, Xiao-Hua; Todd, Jonathan D. (2017). "Dimethylsulfoniopropionate biosynthesis in marine bacteria and identification of the key gene in this process" (PDF). Nature Microbiology. 2 (5). doi:10.1038/nmicrobiol.2017.9. PMID   28191900. S2CID   21460292.
  5. Vollhardt KP, Schore NE (2018-01-29). Organic chemistry : structure and function (8th ed.). New York. ISBN   9781319079451. OCLC   1007924903.
  6. Smith, Michael B.; March, Jerry (2007), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th ed.), New York: Wiley-Interscience, p. 813, ISBN   978-0-471-72091-1
  7. Smith, Michael B.; March, Jerry (2007), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th ed.), New York: Wiley-Interscience, p. 1864, ISBN   978-0-471-72091-1
  8. Ôeda H (1934). "Oxidation of some α-hydroxy-acids with lead tetraacetate". Bulletin of the Chemical Society of Japan. 9 (1): 8–14. doi: 10.1246/bcsj.9.8 .
  9. Nwaukwa S, Keehn P (1982). "Oxidative cleavage of α-diols, α-diones, α-hydroxy-ketones and α-hydroxy- and α-keto acids with calcium hypochlorite [Ca(OCl)2]". Tetrahedron Letters. 23 (31): 3135–3138. doi:10.1016/S0040-4039(00)88578-0.
  10. Miltenberger K (2000). "Hydroxycarboxylic Acids, Aliphatic". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a13_507. ISBN   978-3527306732.
  11. Ritzer E, Sundermann R (2000). "Hydroxycarboxylic Acids, Aromatic". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a13_519. ISBN   978-3527306732.
  12. Chandler NR (1993). Principles of organic synthesis. Coxon, J. M. (James Morriss), 1941- (3rd. ed.). London: Blackie Academic & Professional. ISBN   978-0751401264. OCLC   27813843.
  13. 1 2 Chandru K, Guttenberg N, Giri C, Hongo Y, Butch C, Mamajanov I, Cleaves HJ (2018-05-31). "Simple prebiotic synthesis of high diversity dynamic combinatorial polyester libraries". Communications Chemistry. 1 (1). doi: 10.1038/s42004-018-0031-1 . ISSN   2399-3669.
  14. Jia TZ, Chandru K, Hongo Y, Afrin R, Usui T, Myojo K, Cleaves HJ (August 2019). "Membraneless polyester microdroplets as primordial compartments at the origins of life". Proceedings of the National Academy of Sciences of the United States of America. 116 (32): 15830–15835. doi: 10.1073/pnas.1902336116 . PMC   6690027 . PMID   31332006.
  15. Parker ET, Cleaves HJ, Bada JL, Fernández FM (September 2016). "Quantitation of α-hydroxy acids in complex prebiotic mixtures via liquid chromatography/tandem mass spectrometry". Rapid Communications in Mass Spectrometry. 30 (18): 2043–51. Bibcode:2016RCMS...30.2043P. doi:10.1002/rcm.7684. PMID   27467333.
  16. Chandru K, Mamajanov I, Cleaves HJ, Jia TZ (January 2020). "Polyesters as a Model System for Building Primitive Biologies from Non-Biological Prebiotic Chemistry". Life. 10 (1): 6. doi: 10.3390/life10010006 . PMC   7175156 . PMID   31963928.
  17. "AHA LÀ GÌ? CÔNG DỤNG CHÍNH CỦA AHA TRONG MỸ PHẨM". Y Khoa Blog (in Vietnamese). 2021-09-08. Retrieved 2021-10-04.
  18. Perricone NV, DiNardo JC (May 1996). "Photoprotective and antiinflammatory effects of topical glycolic acid". Dermatologic Surgery. 22 (5): 435–7. doi:10.1111/j.1524-4725.1996.tb00343.x. PMID   8634805. S2CID   37313380.