Mandelic acid
{{chembox
| Watchedfields = changed
| verifiedrevid = 477003904
| Reference=Merck Index, 11th Edition, 5599.
| Name = Mandelic acid
| ImageFileL1 = kwas_migdałowy.svg
| ImageSizeL1 = 120px
| ImageAltL1 = Structural formula of mandelic acid
| ImageFileR1 = (R)-Mandelic acid molecule ball.png
| ImageSizeR1 = 120
| ImageAltR1 = Ball-and-stick model of the mandelic acid molecule
| ImageFile2 = Mandlová kyselina.jpg
| PIN = Hydroxy(phenyl)acetic acid
| OtherNames = 2-Hydroxy-2-phenylacetic acid
Mandelic acid
Phenylglycolic acid
α-Hydroxyphenylacetic acid
|Section1={{Chembox Identifiers
| PubChem = 1292
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = NH496X0UJX
| UNII1_Ref = {{fdacite|correct|FDA}}
| UNII1 = PPL7YW1M9W
| UNII1_Comment = (R)
| UNII2_Ref = {{fdacite|correct|FDA}}
| UNII2 = L0UMW58G3T
| UNII2_Comment = (S)
| InChI = 1/C8H8O3/c9-7(8(10)11)6-4-2-1-3-5-6/h1-5,7,9H,(H,10,11)
| InChIKey = IWYDHOAUDWTVEP-UHFFFAOYAD
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1609
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C8H8O3/c9-7(8(10)11)6-4-2-1-3-5-6/h1-5,7,9H,(H,10,11)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = IWYDHOAUDWTVEP-UHFFFAOYSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 90-64-2
| CASNo1_Ref = {{cascite|correct|CAS}}
| CASNo1 = 611-71-2
| CASNo1_Comment = (R)
| CASNo2_Ref = {{cascite|correct|CAS}}
| CASNo2 = 17199-29-0
| CASNo2_Comment = (S)
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 1253
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 35825
| SMILES = O=C(O)C(O)c1ccccc1
| EINECS = 202-007-6
| RTECS = OO6300000
}}
|Section2={{Chembox Properties
| C=8 | H=8 | O=3
| Appearance = White crystalline powder
| Density = 1.30 g/cm3
| MeltingPtC = 119
| MeltingPt_notes = optically pure: {{convert|132|to|135|C|F K}}
| BoilingPtC = 321.8
| Solubility = 15.87 g/100 mL
| SolubleOther = soluble in diethyl ether, ethanol, isopropanol
| pKa = 3.41Bjerrum, J., et al. Stability Constants, Chemical Society, London, 1958.
| RefractIndex = 1.5204
}}
|Section5={{Chembox Thermochemistry
| DeltaHf = 0.1761 kJ/g
}}
|Section6={{Chembox Pharmacology
| ATCCode_prefix = B05
| ATCCode_suffix = CA06
| ATC_Supplemental = {{ATC|J01|XX06}}
}}
|Section7={{Chembox Hazards
| FlashPtC = 162.6
}}
|Section8={{Chembox Related
| OtherAnions =
| OtherCations =
| OtherFunction =
| OtherFunction_label =
| OtherCompounds = mandelonitrile, phenylacetic acid, vanillylmandelic acid}}
}}
Mandelic acid is an aromatic alpha hydroxy acid with the molecular formula C6H5CH(OH)CO2H. It is a white crystalline solid that is soluble in water and polar organic solvents. It is a useful precursor to various drugs. The molecule is chiral. The racemic 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, an extract of bitter almonds, with diluted hydrochloric acid. The name is derived from the German "Mandel" for "almond".See:
- Winckler, F. L. (1831) [https://babel.hathitrust.org/cgi/pt?id=chi.095493840;view=1up;seq=400 "Ueber die Zersetzung des Calomels durch Bittermandelwasser, und einige Beiträge zur genaueren Kenntniss der chemischen Zusammensetzung des Bittermandelwassers"] (On the decomposition of calomel [i.e., mercury(I) chloride] by bitter almond water, and some contributions to a more precise knowledge of the chemical composition of bitter almond water), Repertorium für die Pharmacie, 37 : 388–418; mandelic acid is named on p. 415.
- Winckler, F. L. (1831) [https://babel.hathitrust.org/cgi/pt?id=chi.095493905;view=1up;seq=181 "Ueber die chemische Zusammensetzung des Bittermandelwassers; als Fortsetzung der im 37sten Band S. 388 u.s.w. des Repertoriums enthaltenen Mittheilungen"] [On the chemical composition of bitter almond water; as a continuation of the report contained in the 37th volume, pp. 388 ff. of the Repertorium], Repertorium für die Pharmacie, 38 : 169–196. On p. 193, Winckler describes the preparation of mandelic acid from bitter almond water and hydrochloric acid (Salzsäure).
- (Editor) (1832) [https://babel.hathitrust.org/cgi/pt?id=mdp.39015026322423;view=1up;seq=626 "Ueber einige Bestandtheile der Bittermandeln"] (On some components of bitter almonds), Annalen der Chemie und Pharmacie, 4 : 242–247.
- Winckler, F. L. (1836) [https://babel.hathitrust.org/cgi/pt?id=mdp.39015026322357;view=1up;seq=708 "Ueber die Mandelsäure und einige Salze derselben"] (On mandelic acid and some salts of the same), Annalen der Chemie und Pharmacie, 18 (3) : 310–319.
- Hermann Schelenz, Geschichte der Pharmazie [The History of Pharmacy] (Berlin, German: Julius Springer, 1904), [https://books.google.com/books?id=JtzQAAAAMAAJ&pg=PA675 p. 675.]
Mandelic acid is usually prepared by the acid-catalysed hydrolysis of mandelonitrile,{{Ullmann| doi=10.1002/14356007.a13_519| chapter=Hydroxycarboxylic Acids, Aromatic|year=2000| last1=Ritzer| first1=Edwin| last2=Sundermann| first2=Rudolf| isbn=3527306730}} which is the cyanohydrin of benzaldehyde. Mandelonitrile can also be prepared by reacting benzaldehyde with sodium bisulfite to give the corresponding adduct, forming mandelonitrile with sodium cyanide, which is then hydrolyzed:{{cite journal| author = Corson, B. B.| author2 = Dodge, R. A.| author3 = Harris, S. A.| author4 = Yeaw, J. S. |journal=Org. Synth.| title = Mandelic Acid | volume= 6 | page = 58| year = 1926| doi=10.15227/orgsyn.006.0058}}
Alternatively, it can be prepared by base hydrolysis of phenylchloroacetic acid as well as dibromacetophenone.{{OrgSynth | author = J. G. Aston | author2 = J. D. Newkirk | author3 = D. M. Jenkins | author4 = Julian Dorsky | name-list-style=amp | title = Mandelic Acid | collvol = 3 | collvolpages = 538 | year = 1952 | prep = cv3p0538}} It also arises by heating phenylglyoxal with alkalis.{{cite journal|last1=Pechmann|first1=H. von|title=Zur Spaltung der Isonitrosoverbindungen|journal=Berichte der Deutschen Chemischen Gesellschaft|date=1887|volume=20|issue=2|pages=2904–2906|doi=10.1002/cber.188702002156|url=https://zenodo.org/record/1425483}}{{cite journal|last1=Pechmann|first1=H. von|last2=Muller|first2=Hermann|title=Ueber α-Ketoaldehyde|journal=Berichte der Deutschen Chemischen Gesellschaft|date=1889|volume=22|issue=2|pages=2556–2561|doi=10.1002/cber.188902202145|url=https://zenodo.org/record/1425555}}
=Biosynthesis=
Mandelic acid is a substrate or product of several biochemical processes called the mandelate pathway. Mandelate racemase interconverts the two enantiomers via a pathway that involves cleavage of the alpha-CH bond. Mandelate dehydrogenase is yet another enzyme on this pathway.{{cite journal |doi=10.1021/ar00052a003|title=Mandelate Racemase: Structure-Function Studies of a Pseudosymmetric Enzyme|year=1995|last1=Kenyon|first1=George L.|last2=Gerlt|first2=John A.|last3=Petsko|first3=Gregory A.|last4=Kozarich|first4=John W.|journal=Accounts of Chemical Research|volume=28|issue=4|pages=178–186}} Mandelate also arises from trans-cinnamate via phenylacetic acid, which is hydroxylated.{{cite journal |doi=10.1128/AEM.66.4.1517-1522.2000|title=Novel Scheme for Biosynthesis of Aryl Metabolites from l-Phenylalanine in the Fungus Bjerkandera adusta|year=2000|last1=Lapadatescu|first1=Carmen|last2=Giniès|first2=Christian|last3=Le QuéRé|first3=Jean-Luc|last4=Bonnarme|first4=Pascal|journal=Applied and Environmental Microbiology|volume=66|issue=4|pages=1517–1522|pmid=10742235|pmc=92016|bibcode=2000ApEnM..66.1517L }} Phenylpyruvic acid is another precursor to mandelic acid.
Derivatives of mandelic acid are formed as a result of metabolism of adrenaline and noradrenaline by monoamine oxidase and catechol-O-methyl transferase. The biotechnological production of 4-hydroxy-mandelic acid and mandelic acid on the basis of glucose was demonstrated with a genetically modified yeast Saccharomyces cerevisiae, in which the hydroxymandelate synthase naturally occurring in the bacterium Amycolatopsis was incorporated into a wild-type strain of yeast, partially altered by the exchange of a gene sequence and expressed.Mara Reifenrath, Eckhard Boles: 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. {{doi|10.1016/j.ymben.2018.01.001}}.
It also arises from the biodegradation of styreneEngström K, Härkönen H, Kalliokoski P, Rantanen J. "Urinary mandelic acid concentration after occupational exposure to styrene and its use as a biological exposure test" Scand. J. Work Environ. Health. 1976, volume 2, pp. 21-6. and ethylbenzene, 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.{{cite journal | doi = 10.1007/BF00403669 | title = Mandelic acid and urinary tract infections | year = 1979 | author = Putten, P. L. | journal = Antonie van Leeuwenhoek | volume = 45 | pages = 622–623 | issue = 4| s2cid = 28467515 }} It has also been used as an oral antibiotic, and as a component of chemical face peels analogous to other alpha hydroxy acids.{{cite journal | author = Taylor, MB. | year = 1999 | title = Summary of mandelic acid for the improvement of skin conditions | journal = Cosmetic Dermatology | volume = 21 | pages = 26–28 | url = https://nucelle.com/wp-content/uploads/2019/12/MandelicAcid-Efficacy.pdf | url-status = live | archiveurl = http://web.archive.org/web/20231214125329/https://nucelle.com/wp-content/uploads/2019/12/MandelicAcid-Efficacy.pdf | archivedate = December 14, 2023}}
The drugs cyclandelate and homatropine are esters of mandelic acid.
==See Also==
References
{{Reflist|30em}}
- {{EB1911|wstitle=Mandelic Acid|volume=17|page=559}}
{{Other antibacterials}}
{{Authority control}}