Mandelic acid

Last updated
Mandelic acid [1]
Kwas migdalowy.svg
(R)-Mandelic acid molecule ball.png
Mandlova kyselina.jpg
Names
Preferred IUPAC name
Hydroxy(phenyl)acetic acid
Other names
2-Hydroxy-2-phenylacetic acid
Mandelic acid
Phenylglycolic acid
α-Hydroxyphenylacetic acid
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.001.825 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 202-007-6
PubChem CID
RTECS number
  • OO6300000
UNII
  • InChI=1S/C8H8O3/c9-7(8(10)11)6-4-2-1-3-5-6/h1-5,7,9H,(H,10,11) Yes check.svgY
    Key: IWYDHOAUDWTVEP-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C8H8O3/c9-7(8(10)11)6-4-2-1-3-5-6/h1-5,7,9H,(H,10,11)
    Key: IWYDHOAUDWTVEP-UHFFFAOYAD
  • O=C(O)C(O)c1ccccc1
Properties
C8H8O3
Molar mass 152.149 g·mol−1
AppearanceWhite crystalline powder
Density 1.30 g/cm3
Melting point 119 °C (246 °F; 392 K) optically pure: 132 to 135 °C (270 to 275 °F; 405 to 408 K)
Boiling point 321.8 °C (611.2 °F; 595.0 K)
15.87 g/100 mL
Solubility soluble in diethyl ether, ethanol, isopropanol
Acidity (pKa)3.41 [2]
1.5204
Thermochemistry
0.1761 kJ/g
Pharmacology
B05CA06 ( WHO ) J01XX06 ( WHO )
Hazards
Flash point 162.6 °C (324.7 °F; 435.8 K)
Related compounds
Related compounds
mandelonitrile, phenylacetic acid, vanillylmandelic acid
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

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.

Contents

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". [3]

Mandelic acid is usually prepared by the acid-catalysed hydrolysis of mandelonitrile, [4] 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 hydrolyzed: [5]

Preparation of mandelic acid.png

Alternatively, it can be prepared by base hydrolysis of phenylchloroacetic acid as well as dibromacetophenone. [6] It also arises by heating phenylglyoxal with alkalis. [7] [8]

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. [9] Mandelate also arises from trans-cinnamate via phenylacetic acid, which is hydroxylated. [10] 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. [11]

It also arises from the biodegradation of styrene [12] 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. [13] It has also been used as an oral antibiotic, and as a component of chemical face peels analogous to other alpha hydroxy acids. [14]

The drugs cyclandelate and homatropine are esters of mandelic acid.

Related Research Articles

Pyrrole is a heterocyclic, aromatic, organic compound, a five-membered ring with the formula C4H4NH. It is a colorless volatile liquid that darkens readily upon exposure to air. Substituted derivatives are also called pyrroles, e.g., N-methylpyrrole, C4H4NCH3. Porphobilinogen, a trisubstituted pyrrole, is the biosynthetic precursor to many natural products such as heme.

<span class="mw-page-title-main">Quinoline</span> Chemical compound

Quinoline is a heterocyclic aromatic organic compound with the chemical formula C9H7N. It is a colorless hygroscopic liquid with a strong odor. Aged samples, especially if exposed to light, become yellow and later brown. Quinoline is only slightly soluble in cold water but dissolves readily in hot water and most organic solvents. Quinoline itself has few applications, but many of its derivatives are useful in diverse applications. A prominent example is quinine, an alkaloid found in plants. Over 200 biologically active quinoline and quinazoline alkaloids are identified. 4-Hydroxy-2-alkylquinolines (HAQs) are involved in antibiotic resistance.

Furfural is an organic compound with the formula C4H3OCHO. It is a colorless liquid, although commercial samples are often brown. It has an aldehyde group attached to the 2-position of furan. It is a product of the dehydration of sugars, as occurs in a variety of agricultural byproducts, including corncobs, oat, wheat bran, and sawdust. The name furfural comes from the Latin word furfur, meaning bran, referring to its usual source. Furfural is only derived from dried biomass. In addition to ethanol, acetic acid, and sugar, furfural is one of the oldest organic chemicals available readily purified from natural precursors.

Benzonitrile is the chemical compound with the formula C6H5(CN), abbreviated PhCN. This aromatic organic compound is a colorless liquid with a sweet bitter almond odour. It is mainly used as a precursor to the resin benzoguanamine.

The Kolbe–Schmitt reaction or Kolbe process is a carboxylation chemical reaction that proceeds by treating phenol with sodium hydroxide to form sodium phenoxide, then heating sodium phenoxide with carbon dioxide under pressure, then treating the product with sulfuric acid. The final product is an aromatic hydroxy acid which is also known as salicylic acid.

The Cannizzaro reaction, named after its discoverer Stanislao Cannizzaro, is a chemical reaction which involves the base-induced disproportionation of two molecules of a non-enolizable aldehyde to give a primary alcohol and a carboxylic acid.

<span class="mw-page-title-main">Benzoin condensation</span> Reaction between two aromatic aldehydes

The benzoin addition is an addition reaction involving two aldehydes. The reaction generally occurs between aromatic aldehydes or glyoxals, and results in formation of an acyloin. In the classic example, benzaldehyde is converted to benzoin.

<span class="mw-page-title-main">Benzoin (organic compound)</span> Chemical compound

Benzoin ( or ) is an organic compound with the formula PhCH(OH)C(O)Ph. It is a hydroxy ketone attached to two phenyl groups. It appears as off-white crystals, with a light camphor-like odor. Benzoin is synthesized from benzaldehyde in the benzoin condensation. It is chiral and it exists as a pair of enantiomers: (R)-benzoin and (S)-benzoin.

<span class="mw-page-title-main">Hippuric acid</span> Chemical compound

Hippuric acid is a carboxylic acid and organic compound. It is found in urine and is formed from the combination of benzoic acid and glycine. Levels of hippuric acid rise with the consumption of phenolic compounds. The phenols are first converted to benzoic acid, and then to hippuric acid and excreted in urine.

<span class="mw-page-title-main">Reimer–Tiemann reaction</span> Chemical reaction for ortho-formylation of phenols

The Reimer–Tiemann reaction is a chemical reaction used for the ortho-formylation of phenols. with the simplest example being the conversion of phenol to salicylaldehyde. The reaction was first reported by Karl Reimer and Ferdinand Tiemann.

<span class="mw-page-title-main">Muconate lactonizing enzyme</span>

Muconate lactonizing enzymes are involved in the breakdown of lignin-derived aromatics, catechol and protocatechuate, to citric acid cycle intermediates as a part of the β-ketoadipate pathway in soil microbes. Some bacterial species are also capable of dehalogenating chloroaromatic compounds by the action of chloromuconate lactonizing enzymes. MLEs consist of several strands which have variable reaction favorable parts therefore the configuration of the strands affect its ability to accept protons. The bacterial MLEs belong to the enolase superfamily, several structures from which are known. MLEs have an identifying structure made up of two proteins and two Magnesium ions as well as various classes depending on whether it is bacterial or eukaryotic. The reaction mechanism that MLEs undergo are the reverse of beta-elimination in which the enolate alpha-carbon is protonated. MLEs can undergo mutations caused by a deletion of catB structural genes which can cause some bacteria to lose its functions such as the ability to grow. Additional mutations to MLEs can cause its structure and function to alter and could cause the conformation to change therefore making it an inactive enzyme that is unable to bind its substrate. There is another enzyme called Mandelate Racemase that is very similar to MLEs in the structural way as well as them both being a part of the enolase superfamily. They both have the same end product even though they undergo different chemical reactions in order to reach the end product.

<span class="mw-page-title-main">Nikolay Zinin</span>

Nikolay Nikolaevich Zinin was a Russian organic chemist.

<span class="mw-page-title-main">Erlenmeyer–Plöchl azlactone and amino-acid synthesis</span>

The Erlenmeyer–Plöchl azlactone and amino acid synthesis, named after Friedrich Gustav Carl Emil Erlenmeyer who partly discovered the reaction, is a series of chemical reactions which transform an N-acyl glycine to various other amino acids via an oxazolone.

In organic chemistry, the Claisen–Schmidt condensation is the reaction between an aldehyde or ketone having an α-hydrogen with an aromatic carbonyl compound lacking an α-hydrogen. It can be considered as a specific variation of the aldol condensation. This reaction is named after two of its pioneering investigators Rainer Ludwig Claisen and J. Gustav Schmidt, who independently published on this topic in 1880 and 1881. An example is the synthesis of dibenzylideneacetone ( -1,5-diphenylpenta-1,4-dien-3-one).

In enzymology, a mandelate 4-monooxygenase (EC 1.14.16.6) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">(S)-mandelate dehydrogenase</span> Class of enzymes

In enzymology, (S)-mandelate dehydrogenase (MDH), is an enzyme that catalyzes the chemical reaction.

<span class="mw-page-title-main">Mandelonitrile lyase</span> Class of enzymes

The enzyme (R)-mandelonitrile lyase (EC 4.1.2.10, (R)-HNL, (R)-oxynitrilase, (R)-hydroxynitrile lyase) catalyzes the chemical reaction

<span class="mw-page-title-main">Mellitic anhydride</span> Chemical compound

Mellitic anhydride, the anhydride of mellitic acid, is an organic compound with the formula C12O9.

Benzaldehyde (C6H5CHO) is an organic compound consisting of a benzene ring with a formyl substituent. It is among the simplest aromatic aldehydes and one of the most industrially useful.

<span class="mw-page-title-main">Prunasin</span> Chemical compound

(R)-prunasin is a cyanogenic glycoside related to amygdalin. Chemically, it is the glucoside of (R)-mandelonitrile.

References

  1. Merck Index , 11th Edition, 5599.
  2. Bjerrum, J., et al. Stability Constants, Chemical Society, London, 1958.
  3. See:
  4. Ritzer, Edwin; Sundermann, Rudolf (2000). "Hydroxycarboxylic Acids, Aromatic". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a13_519. ISBN   3527306730.
  5. Corson, B. B.; Dodge, R. A.; Harris, S. A.; Yeaw, J. S. (1926). "Mandelic Acid". Org. Synth. 6: 58. doi:10.15227/orgsyn.006.0058.
  6. J. G. Aston; J. D. Newkirk; D. M. Jenkins & Julian Dorsky (1952). "Mandelic Acid". Organic Syntheses ; Collected Volumes, vol. 3, p. 538.
  7. Pechmann, H. von (1887). "Zur Spaltung der Isonitrosoverbindungen". Berichte der Deutschen Chemischen Gesellschaft. 20 (2): 2904–2906. doi:10.1002/cber.188702002156.
  8. Pechmann, H. von; Muller, Hermann (1889). "Ueber α-Ketoaldehyde". Berichte der Deutschen Chemischen Gesellschaft. 22 (2): 2556–2561. doi:10.1002/cber.188902202145.
  9. Kenyon, George L.; Gerlt, John A.; Petsko, Gregory A.; Kozarich, John W. (1995). "Mandelate Racemase: Structure-Function Studies of a Pseudosymmetric Enzyme". Accounts of Chemical Research. 28 (4): 178–186. doi:10.1021/ar00052a003.
  10. Lapadatescu, Carmen; Giniès, Christian; Le QuéRé, Jean-Luc; Bonnarme, Pascal (2000). "Novel Scheme for Biosynthesis of Aryl Metabolites from l-Phenylalanine in the Fungus Bjerkandera adusta". Applied and Environmental Microbiology. 66 (4): 1517–1522. Bibcode:2000ApEnM..66.1517L. doi:10.1128/AEM.66.4.1517-1522.2000. PMC   92016 . PMID   10742235.
  11. 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.
  12. Engström 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.
  13. Putten, P. L. (1979). "Mandelic acid and urinary tract infections". Antonie van Leeuwenhoek. 45 (4): 622–623. doi:10.1007/BF00403669. S2CID   28467515.
  14. Taylor, MB. (1999). "Summary of mandelic acid for the improvement of skin conditions". Cosmetic Dermatology . 21: 26–28.