View source for Chemistry of ascorbic acid

{{cs1 config|mode=cs1|name-list-style=vanc}}
{{About|the molecular aspects of ascorbic acid|information about its role in nutrition|Vitamin C}}
{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 477350783
| Name = {{sm|l}}-Ascorbic acid
| ImageFile = L-Ascorbic acid.svg
| ImageClass = skin-invert-image
| ImageFile1 = Ascorbic-acid-from-xtal-1997-3D-balls.png
| IUPACName = (5''R'')-[(1''S'')-1,2-Dihydroxyethyl]-3,4-dihydroxyfuran-2(5''H'')-one
| OtherNames = Vitamin C
|Section1={{Chembox Identifiers
| IUPHAR_ligand = 4781
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = PQ6CK8PD0R
| SMILES1 = C([C@@H]([C@@H]1C(=C(C(=O)O1)O)O)O)O
| CASNo = 50-81-7
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 196
| CASNo_Ref = {{cascite|changed|??}}
| EINECS = 200-066-2
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 10189562
| PubChem = 5785
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00018
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 29073
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C6H8O6/c7-1-2(8)5-3(9)4(10)6(11)12-5/h2,5,7-10H,1H2/t2-,5+/m0/s1
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = CIWBSHSKHKDKBQ-JLAZNSOCSA-N
| SMILES = OC=1C(OC(=O)C=1O)[C@@H](O)CO
 }}
|Section2={{Chembox Properties
| C=6 | H=8 | O=6
| Appearance = White or light yellow solid
| Density = 1.65{{nbsp}}g/cm<sup>3</sup>
| MeltingPtC = 190 to 192
| MeltingPt_notes = decomposes 
| Solubility = 330{{nbsp}}g/L
| Solubility1 = 20{{nbsp}}g/L
| Solvent1 = ethanol
| Solubility2 = 10{{nbsp}}g/L
| Solvent2 = glycerol
| Solubility3 = 50{{nbsp}}g/L
| Solvent3 = propylene glycol
| SolubleOther = Insoluble in [[diethyl ether]], [[chloroform]], [[benzene]], [[petroleum ether]], [[oil]]s, [[fat]]s
| pKa = 4.10 (first), 11.6 (second)
  }}
|Section6={{Chembox Pharmacology
| ATCCode_prefix = A11
| ATCCode_suffix = GA01
| ATC_Supplemental = {{ATC|G01|AD03}}, {{ATC|S01|XA15}}
}}
|Section7={{Chembox Hazards
| ExternalSDS = [http://hazard.com/msds/mf/baker/baker/files/a7608.htm JT Baker]
| NFPA-H = 1
| NFPA-F = 1
| NFPA-R = 0
| MainHazards =
| FlashPt =
| AutoignitionPt =
| LD50 = 11.9{{nbsp}}g/kg (oral, rat)<ref>[https://web.archive.org/web/20070209221915/http://physchem.ox.ac.uk/MSDS/AS/ascorbic_acid.html Safety (MSDS) data for ascorbic acid]. [[University of Oxford]]</ref>
  }}
}}

'''Ascorbic acid''' is an [[organic compound]] with formula {{chem|C|6|H|8|O|6}}, originally called '''hexuronic acid'''. It is a white solid, but impure samples can appear yellowish.  It dissolves freely in water to give mildly acidic solutions.  It is a mild [[redox|reducing agent]].

Ascorbic acid exists as two [[enantiomer]]s (mirror-image [[isomer]]s), commonly denoted "{{sm|l}}" (for "levo") and "{{sm|d}}" (for "dextro"). The {{sm|l}} isomer is the one most often encountered: it occurs naturally in many foods, and is one form ("[[vitamer]]") of [[vitamin C]], an essential nutrient for humans and many animals. Deficiency of vitamin C causes [[scurvy]], formerly a major disease of sailors in long sea voyages. It is used as a [[food additive]] and a [[dietary supplement]] for its [[antioxidant]] properties. The "{{sm|d}}" form ([[erythorbic acid]]) can be made by chemical synthesis, but has no significant biological role.

==History==
<!--Please try to restrict this section to the history of the chemistry of the compound.  The medical aspects belong more properly to the [[scurvy]] and [[vitamin C]] articles.-->
The [[scurvy|antiscorbutic]] properties of certain foods were demonstrated in the 18th century by [[James Lind]]. In 1907, [[Axel Holst]] and [[Theodor Frølich]] discovered that the antiscorbutic factor was a water-soluble chemical substance, distinct from the one that prevented [[beriberi]]. Between 1928 and 1932, [[Albert Szent-Györgyi]] isolated a candidate for this substance, which he called "hexuronic acid", first from plants and later from animal adrenal glands. In 1932 [[Charles Glen King]] confirmed that it was indeed the antiscorbutic factor.

In 1933, sugar chemist [[Norman Haworth|Walter Norman Haworth]], working with samples of "hexuronic acid" that Szent-Györgyi had isolated from [[paprika]] and sent him in the previous year, deduced the correct structure and optical-isomeric nature of the compound, and in 1934 reported its first synthesis.<ref>[https://profiles.nlm.nih.gov/WG/Views/Exhibit/narrative/szeged.html Story of Vitamin C's chemical discovery]. Profiles.nlm.nih.gov. Retrieved on 2012-12-04.</ref><ref>{{cite book | last1 = Davies  | first1 = Michael B.  | last2 = Austin  | first2 = John  | last3 = Partridge  | first3 = David A. | title = Vitamin C: Its Chemistry and Biochemistry  | publisher = The Royal Society of Chemistry  | year = 1991  | page = 48  | isbn = 0-85186-333-7}}
</ref> In reference to the compound's antiscorbutic properties, Haworth and Szent-Györgyi proposed to rename it "a-scorbic acid" for the compound, and later specifically {{sm|l}}-ascorbic acid.<ref>{{citation | first1 = Joseph Louis | last1 = Svirbelf | first2 = Albert | last2 = Szent-Györgyi | author-link2 = Albert Szent-Györgyi | url = https://profiles.nlm.nih.gov/WG/B/B/G/W/_/wgbbgw.pdf | title = The Chemical Nature Of Vitamin C | journal = Science | volume = 75 | issue = 1944 | pages = 357–8 | date = April 25, 1932| bibcode = 1932Sci....75..357K | doi = 10.1126/science.75.1944.357-a | pmid = 17750032 | s2cid = 33277683 }}. Part of the [[National Library of Medicine]] collection. Accessed January 2007</ref>  Because of their work, in 1937 two [[Nobel Prize]]s: in Chemistry and in Physiology or Medicine were awarded to Haworth and Szent-Györgyi, respectively.

==Chemical properties==

===Acidity===
Ascorbic acid is a [[furan]]-based [[lactone]] of [[2-ketogluconic acid]]. It contains an adjacent [[enediol]] adjacent to the [[carbonyl]]. This −C(OH)=C(OH)−C(=O)− structural pattern is characteristic of [[reductone]]s, and increases the acidity of one of the enol [[hydroxyl group]]s. The deprotonated [[conjugate base]] is the [[ascorbate]] anion, which is stabilized by electron delocalization that results from [[resonance (chemistry)|resonance]] between two forms:

: [[File:Ascorbate resonance.png|400px|class=skin-invert-image]]

For this reason, ascorbic acid is much more acidic than would be expected if the compound contained only isolated hydroxyl groups.

===Salts===
The ascorbate anion forms [[salt (chemistry)|salts]], such as [[sodium ascorbate]], [[calcium ascorbate]], and [[potassium ascorbate]].

===Esters===
Ascorbic acid can also react with organic acids as an [[alcohol (chemistry)|alcohol]] forming [[ester]]s such as [[ascorbyl palmitate]] and [[ascorbyl stearate]].

===Nucleophilic attack===
[[Nucleophile|Nucleophilic attack]] of ascorbic acid on a proton results in a 1,3-diketone: 

:[[Image:Ascorbic diketone.png|class=skin-invert-image]]

===Oxidation===
{{Refimprove|section|date=March 2024}}
[[File:L-Semidehydroascorbinsäure.svg|right|thumb|220px|class=skin-invert-image|Semidehydroascorbate acid radical]]
[[File:Dehydroascorbic_acid_2.svg|right|thumb|220px|class=skin-invert-image|Pseudodehydroascorbate<!--Image incorrectly named as dehydroascorbic acid-->]]
{{Image frame|width=220|content=<div class="skin-invert-image">{{CSS image crop|Image = Ascorbic_acid_all.svg|bSize = 1250|cWidth = 220|cHeight = 142|oTop = 328|oLeft = 1006}}</div><!--Using cropped image until we can generate a new one-->|align=right|caption=Dehydroascorbate}}
The ascorbate ion is the predominant species at typical biological pH values. It is a mild [[reducing agent]] and [[antioxidant]], typically reacting with oxidants of the [[reactive oxygen species]], such as the [[hydroxyl radical]].

Reactive oxygen species are damaging to animals and plants at the molecular level due to their possible interaction with [[nucleic acid]]s, proteins, and lipids. Sometimes these radicals initiate chain reactions. Ascorbate can terminate these chain radical reactions by [[electron transfer]]. The oxidized forms of ascorbate are relatively unreactive and do not cause cellular damage.

Ascorbic acid and its sodium, potassium, and calcium [[Salt (chemistry)|salt]]s are commonly used as [[antioxidant]] [[food additive]]s. These compounds are water-soluble and, thus, cannot protect [[fat]]s from oxidation: For this purpose, the fat-[[Solubility|soluble]] [[ester]]s of ascorbic acid with long-chain [[fatty acid]]s (ascorbyl palmitate or ascorbyl stearate) can be used as antioxidant food additives. Sodium-dependent active transport process enables absorption of Ascorbic acid from the intestine.<ref>{{cite web |title=Re-evaluation of ascorbic acid, sodium ascorbate and calcium ascorbate as food additives {{!}} EFSA |url=https://www.efsa.europa.eu/en/efsajournal/pub/4087 |website=www.efsa.europa.eu |publisher=European Food Safety Authority |language=en |date=6 May 2015}}</ref>

Ascorbate readily donates a hydrogen atom to [[radical (chemistry)|free radicals]], forming the [[radical anion]] semidehydroascorbate (also known as monodehydroascorbate), a resonance-stabilized [[semitrione]]:<ref name=Njus2020>{{cite journal |last1=Njus |first1=David |last2=Kelley |first2=Patrick M. |last3=Tu |first3=Yi-Jung |last4=Schlegel |first4=H. Bernhard |title=Ascorbic acid: The chemistry underlying its antioxidant properties |journal=Free Radical Biology and Medicine |date=November 2020 |volume=159 |pages=37–43 |doi=10.1016/j.freeradbiomed.2020.07.013|pmid=32738399 }}</ref>
:{{chem2|C6H7O6- + L• -> C6H6O6<sup>•</sup>- + LH}}

Loss of an electron from semidehydroascorbate to produce the 1,2,3-tricarbonyl pseudodehydroascorbate is thermodynamically disfavored, which helps prevent propagation of free radical chain reactions such as [[autoxidation]]:<ref name=Njus2020/>
:{{chem2|C6H6O6<sup>•</sup>- + O2}} <math>\not\rightarrow</math> {{chem2|C6H6O6 + O2<sup>•</sup>-}}

However, being a good electron donor, excess ascorbate in the presence of free metal ions can not only promote but also initiate free radical reactions, thus making it a potentially dangerous pro-oxidative compound in certain metabolic contexts.

Semidehydroascorbate oxidation instead occurs in conjunction with hydration, yielding the bicyclic [[hemiketal]] [[dehydroascorbic acid|dehydroascorbate]]. In particular, semidehydroascorbate undergoes disproportionation to ascorbate and dehydroascorbate:<ref name=Njus2020/>
:{{chem2|C6H6O6<sup>•</sup>- + L• + H2O + H+ -> C6H8O7 + LH}}
:{{chem2|2 C6H6O6<sup>•</sup>- + H2O + H+ -> C6H8O7 + C6H7O6-}}

Aqueous solutions of dehydroascorbate are unstable, undergoing hydrolysis with a half-life of 5–15&nbsp;minutes at {{convert|37|C}}. Decomposition products include [[diketogulonic acid]], [[xylonic acid]], [[threonic acid]] and [[oxalic acid]].<ref>{{cite book |url=https://books.google.com/books?id=45I3EQAAQBAJ&q=diketogulonic&pg=PA311 |title = Ingredient Interactions: Effects on Food Quality, Second Edition|isbn = 9781420028133|last1 = Gaonkar|first1 = Anilkumar G.|last2 = McPherson|first2 = Andrew |date = 2016-04-19| publisher=CRC Press }}</ref><ref>{{cite journal |last1=Linster |first1=Carole L. |author-link1=:lb:Carole Linster |last2=Van Schaftingen |first2=Emile |title=Vitamin C: Biosynthesis, recycling and degradation in mammals |journal=The FEBS Journal |date=January 2007 |volume=274 |issue=1 |pages=1–22 |doi=10.1111/j.1742-4658.2006.05607.x|pmid=17222174 }}</ref>{{rp|p=14}}

===Other reactions===
It creates volatile compounds when mixed with [[glucose]] and [[amino acid]]s at 90&nbsp;°C.<ref>{{cite journal |author1=Seck, S. |author2=Crouzet, J. | title = Formation of Volatile Compounds in Sugar-Phenylalanine and Ascorbic Acid-Phenylalanine Model Systems during Heat Treatment | journal = Journal of Food Science | year = 1981 | volume = 46 | issue = 3 | pages = 790–793 | doi = 10.1111/j.1365-2621.1981.tb15349.x }}</ref>

It is a cofactor in [[tyrosine]] [[oxidation]], though because a crude extract of animal liver is used, it is unclear which reaction catalyzed by which enzyme is being helped here.<ref>{{cite journal | vauthors = Sealock RR, Goodland RL, Sumerwell WN, Brierly JM | title = The role of ascorbic acid in the oxidation of <small>L</small>-Tyrosine by guinea pig liver extracts | journal = The Journal of Biological Chemistry | volume = 196 | issue = 2 | pages = 761–7 | date = May 1952 | doi = 10.1016/S0021-9258(19)52407-3 | pmid = 12981016 | url = http://www.jbc.org/content/196/2/761.full.pdf | doi-access = free }}</ref> For known roles in enzymatic reactions, see {{section link|Vitamin C#Pharmacodynamics}}.

Because it reduces iron(III) and chelates iron ions, it enhances the oral absorption of non-heme iron.<ref name="pmid28189173">{{cite journal |vauthors=DeLoughery TG |title=Iron deficiency anemia |journal=Med Clin North Am |volume=101 |issue=2 |pages=319–32 |date=March 2017 |pmid=28189173 |doi=10.1016/j.mcna.2016.09.004 |type=Review}}</ref> This property also applies to its enantiomer.<ref>{{cite journal | title = Erythorbic acid is a potent enhancer of nonheme-iron absorption | last = Fidler | first = MC |author2=Davidsson L |author3=Zeder C |author4=Hurrell RF  | journal = American Journal of Clinical Nutrition |date=January 2004 | volume = 79 | issue = 1 | pmid = 14684404 | pages = 99–102 | doi=10.1093/ajcn/79.1.99| doi-access = free }}</ref>

====Conversion to oxalate====
In 1958, it was discovered that ascorbic acid can be converted to [[oxalate]], a key component of calcium oxalate [[kidney stone]]s.<ref name="pmid13525409">{{cite journal |vauthors=Hellman L, Burns JJ |title=Metabolism of L-ascorbic acid-1-C14 in man |journal=The Journal of Biological Chemistry |volume=230 |issue=2 |pages=923–30 |date=February 1958 |doi=10.1016/S0021-9258(18)70515-2 |doi-access=free |pmid=13525409 |url=https://www.jbc.org/article/S0021-9258(18)70515-2/pdf}}</ref><ref name="pmid27002809">{{cite journal |vauthors=Knight J, Madduma-Liyanage K, Mobley JA, Assimos DG, Holmes RP |title=Ascorbic acid intake and oxalate synthesis |journal=Urolithiasis |volume=44 |issue=4 |pages=289–97 |date=August 2016 |pmid=27002809 |pmc=4946963 |doi=10.1007/s00240-016-0868-7}}</ref><ref name="Kayis 2024">{{cite book |vauthors=Kayis C |title=Ascorbic Acid - Biochemistry and Functions |chapter=Effect of Ascorbic Acid on the Kidneys |publisher=IntechOpen |year=2024 |isbn=978-1-83768-562-2 |doi=10.5772/intechopen.111913 |doi-access=free |url=https://www.intechopen.com/citation-pdf-url/87322 |access-date=12 January 2025 |page=}}</ref> The process begins with the formation of [[dehydroascorbic acid]] (DHA) from the ascorbyl radical. While DHA can be recycled back to ascorbic acid, a portion irreversibly degrades to 2,3-diketogulonic acid (DKG), which then breaks down to both oxalate and the sugars [[erythrulose|L-erythrulose]] and [[threosone]].<ref name="pmid27002809"/><ref name="Kayis 2024"/><ref name="pmid38089442">{{cite journal |vauthors=Bao D, Wang Y, Zhao MH |title=Oxalate Nephropathy and the Mechanism of Oxalate-Induced Kidney Injury |journal=Kidney Diseases (Basel, Switzerland) |volume=9 |issue=6 |pages=459–468 |date=December 2023 |pmid=38089442 |pmc=10712969 |doi=10.1159/000533295}}</ref> Research conducted in the 1960s suggested ascorbic acid could substantially contribute to urinary oxalate content (possibly over 40%), but these estimates have been questioned due to methodological limitations.<ref name="pmid27002809"/><ref name="Kayis 2024"/><ref name="pmid14217884">{{cite journal |vauthors=Atkins GL, Dean BM, Griffin WJ, Watts RW |title=Quantitative Aspects Of Ascorbic Acid Metabolism In Man |journal=The Journal of Biological Chemistry |volume=239 |issue= 9|pages=2975–80 |date=September 1964 |doi=10.1016/S0021-9258(18)93840-8 |doi-access=free |pmid=14217884 |url=https://www.jbc.org/article/S0021-9258(18)93840-8/pdf}}</ref> Subsequent large cohort studies have yielded conflicting results regarding the link between vitamin C intake and kidney stone formation. The overall clinical significance of ascorbic acid consumption to kidney stone risk, however, remains inconclusive, although several studies have suggested a potential association, especially with high-dose supplementation in men.<ref name="pmid27002809"/><ref name="Kayis 2024"/><ref name="pmid36839235">{{cite journal |vauthors=Cupisti A, Giannese D, D'Alessandro C, Benedetti A, Panichi V, Alfieri C, Castellano G, Messa P |title=Kidney Stone Prevention: Is There a Role for Complementary and Alternative Medicine? |journal=Nutrients |volume=15 |issue=4 |date=February 2023 |page=877 |pmid=36839235 |pmc=9959749 |doi=10.3390/nu15040877|doi-access=free }}</ref><ref name="pmid30178451">{{cite journal |vauthors=Jiang K, Tang K, Liu H, Xu H, Ye Z, Chen Z |title=Ascorbic Acid Supplements and Kidney Stones Incidence Among Men and Women: A systematic review and meta-analysis |journal=Urology Journal |volume=16 |issue=2 |pages=115–120 |date=May 2019 |pmid=30178451 |doi=10.22037/uj.v0i0.4275}}</ref>

==Uses==
===Food additive===
The main use of {{sm|l}}-ascorbic acid and its salts is as food additives, mostly to combat oxidation and prevent discoloration of the product during storage.<ref>{{cite news |title=The Use of Ascorbic Acid as a Food Additive: Technical-Legal Issues |work=National Library of Medicine |date=2016 |publisher=National Center for Biotechnology Information|pmc=5076701 |volume=5 |issue=1 |page=4313 |doi=10.4081/ijfs.2016.4313 |pmid=27800425 | vauthors = Varvara M, Bozzo G, Celano G, Disanto C, Pagliarone CN, Celano GV }}</ref>  It is approved for this purpose in the EU with [[E number]] E300,<ref name="UK Food Standards Agency">UK Food Standards Agency: {{cite web |url=http://www.food.gov.uk/safereating/chemsafe/additivesbranch/enumberlist |title=Current EU approved additives and their E Numbers |access-date=2011-10-27}}</ref> the US,<ref name="USFDA">US Food and Drug Administration: {{cite web|url=https://www.fda.gov/Food/FoodIngredientsPackaging/FoodAdditives/FoodAdditiveListings/ucm091048.htm |title=Listing of Food Additives Status Part I |website=[[Food and Drug Administration]] |access-date=2011-10-27 |url-status = dead|archive-url=https://web.archive.org/web/20120117060614/https://www.fda.gov/Food/FoodIngredientsPackaging/FoodAdditives/FoodAdditiveListings/ucm091048.htm |archive-date=2012-01-17 }}</ref> Australia, and New Zealand.<ref name="Australia New Zealand Food Standards Code-2011">Australia New Zealand Food Standards Code{{cite web |url=http://www.comlaw.gov.au/Details/F2011C00827 |title=Standard 1.2.4 – Labelling of ingredients |date=8 September 2011 |access-date=2011-10-27}}</ref>

The "{{sm|d}}" enantiomer ([[erythorbic acid]]) shares all of the non-biological chemical properties with the more common {{sm|l}} enantiomer. As a result, it is an equally effective food antioxidant, and is also approved in processed foods.<ref>[http://www.food.gov.uk/safereating/chemsafe/additivesbranch/enumberlist Current EU approved additives and their E Numbers], Food Standards Agency</ref>

===Dietary supplement===
Another major use of {{sm|l}}-ascorbic acid is as a [[dietary supplement]]. It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO-2023">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref><ref>{{cite web |title=World Health Organization Model list of essential medicines |url=https://iris.who.int/bitstream/handle/10665/371090/WHO-MHP-HPS-EML-2023.02-eng.pdf |publisher=World Health Organization}}</ref> Its deficiency over a prolonged period of time could cause scurvy, which is characterized by fatigue, widespread weakness in connective tissues and capillary fragility.<ref>{{cite web |title=Office of Dietary Supplements - Vitamin C |url=https://ods.od.nih.gov/factsheets/VitaminC-HealthProfessional/ |website=ods.od.nih.gov |publisher=National Institue of Health |language=en}}</ref> It affects multiple organ systems due to its role in the biochemical reactions of connective tissue synthesis.<ref>{{cite web |title=Scurvy: Rediscovering a Forgotten Disease |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC10296835/ |publisher=National Library of Medicine}}</ref>

===Niche, non-food uses===

* Ascorbic acid is easily oxidized and so is used as a reductant in photographic developer solutions (among others) and as a [[preservative]].{{Cn|date=July 2024}}
* In [[fluorescence microscope|fluorescence microscopy]] and related fluorescence-based techniques, ascorbic acid can be used as an [[antioxidant]] to increase fluorescent signal and chemically retard dye [[photobleaching]].<ref>{{cite journal | vauthors = Widengren J, Chmyrov A, Eggeling C, Löfdahl PA, Seidel CA | title = Strategies to improve photostabilities in ultrasensitive fluorescence spectroscopy | journal = The Journal of Physical Chemistry A | volume = 111 | issue = 3 | pages = 429–40 | date = January 2007 | pmid = 17228891 | doi = 10.1021/jp0646325 | bibcode = 2007JPCA..111..429W }}</ref>
* It is also commonly used to remove dissolved metal stains, such as iron, from fiberglass swimming pool surfaces.{{Cn|date=July 2024}}
* In plastic manufacturing, ascorbic acid can be used to assemble molecular chains more quickly and with less waste than traditional synthesis methods.<ref>{{citation |title=Vitamin C, water have benefits for plastic manufacturing |url=http://reliableplant.com/article.asp?pagetitle=Vitamin%20C,%20water%20have%20benefits%20for%20plastic%20manufacturing&articleid=3133 |publisher=Reliable Plant Magazine |year=2007 |access-date=2007-06-25 |archive-url=https://web.archive.org/web/20070927230356/http://www.reliableplant.com/article.asp?pagetitle=Vitamin+C%2C+water+have+benefits+for+plastic+manufacturing&articleid=3133 |archive-date=2007-09-27 |url-status = dead}}</ref>
* Heroin users are known to use ascorbic acid as a means to convert heroin base to a water-soluble salt so that it can be injected.<ref>{{cite journal | vauthors = Beynon CM, McVeigh J, Chandler M, Wareing M, Bellis MA | title = The impact of citrate introduction at UK syringe exchange programmes: a retrospective cohort study in Cheshire and Merseyside, UK | journal = Harm Reduction Journal | volume = 4 | issue = 1 | pages = 21 | date = December 2007 | pmid = 18072971 | pmc = 2245922 | doi = 10.1186/1477-7517-4-21 | doi-access = free }}</ref>
* As justified by its reaction with iodine, it is used to negate the effects of iodine tablets in water purification. It reacts with the sterilized water, removing the taste, color, and smell of the iodine. This is why it is often sold as a second set of tablets in most sporting goods stores as Potable Aqua-Neutralizing Tablets, along with the potassium iodide tablets.{{Cn|date=July 2024}}
*[[Intravenous therapy|Intravenous]] high-dose ascorbate is being used as a [[Chemotherapy|chemotherapeutic]] and [[Biological response modifiers|biological response modifying agent]].<ref>{{cite web |title=The Riordan IVC Protocol for Adjunctive Cancer Care: Intravenous Ascorbate as a Chemotherapeutic and Biological Response Modifying Agent|url=http://www.doctoryourself.com/RiordanIVC.pdf |archive-url=https://ghostarchive.org/archive/20221009/http://www.doctoryourself.com/RiordanIVC.pdf |archive-date=2022-10-09 |url-status=live|publisher=Riordan Clinic Research Institut|access-date=2 February 2014|date=February 2013}}</ref> It is undergoing clinical trials.<ref>{{cite web |title=High-Dose Vitamin C (PDQ): Human/Clinical Studies|url=http://www.cancer.gov/cancertopics/pdq/cam/highdosevitaminc/healthprofessional/page5|publisher=National Cancer Institute|access-date=2 February 2014|date=2013-02-08}}</ref>
* It is sometimes used as a urinary acidifier to enhance the antiseptic effect of [[methenamine]].<ref>{{cite journal|doi=10.1002/bdd.2510140106|title=Effect of urine pH and ascorbic acid on the rate of conversion of methenamine to formaldehyde|year=1993|last1=Strom|first1=J. Grady|last2=Jun|first2=H. Won|journal=Biopharmaceutics & Drug Disposition|volume=14|issue=1|pages=61–69|pmid=8427945|s2cid=11151179}}</ref><ref>{{cite journal|doi=10.1007/bf00545228|title=Effect of urinary acidifiers on formaldehyde concentration and efficacy with methenamine therapy|year=1982|last1=Nahata|first1=M. C.|last2=Cummins|first2=B. A.|last3=McLeod|first3=D. C.|last4=Schondelmeyer|first4=S. W.|last5=Butler|first5=R.|journal=European Journal of Clinical Pharmacology|volume=22|issue=3|pages=281–284|pmid=7106162|s2cid=31796137}}</ref>

==Synthesis==
Natural [[vitamin C|biosynthesis of vitamin C]] occurs through various processes in many plants and animals.

===Industrial preparation===
[[Image:Synthesis ascorbic acid.svg|thumb|500px|class=skin-invert-image|The outdated but historically significant industrial synthesis of ascorbic acid from glucose via the [[Reichstein process]]]]
Seventy percent of the world's supply of ascorbic acid is produced in China.<ref name="Vantage Market Research-2022" /> Ascorbic acid is prepared in industry from [[glucose]] in a method based on the historical [[Reichstein process]]. In the first of a five-step process, glucose is catalytically [[hydrogenation|hydrogenated]] to [[sorbitol]], which is then [[redox|oxidized]] by the [[microorganism]] ''[[Acetic acid bacteria#Acetobacter|Acetobacter]] suboxydans'' to [[sorbose]]. Only one of the six hydroxy groups is oxidized by this enzymatic reaction. From this point, two routes are available. Treatment of the product with [[acetone]] in the presence of an acid [[Catalysis|catalyst]] converts four of the remaining [[hydroxyl]] groups to [[acetal]]s. The unprotected hydroxyl group is oxidized to the carboxylic acid by reaction with the catalytic oxidant [[TEMPO]] (regenerated by [[sodium hypochlorite]]{{snd}} [[bleach]]ing solution). Historically, industrial preparation via the Reichstein process used [[potassium permanganate]] as the bleaching solution. Acid-catalyzed hydrolysis of this product performs the dual function of removing the two acetal groups and [[lactone|ring-closing lactonization]]. This step yields ascorbic acid. Each of the five steps has a yield larger than 90%.<ref>{{Ullmann | author = Eggersdorfer, M. |display-authors=etal| title = Vitamins | doi = 10.1002/14356007.a27_443 }}</ref>

A biotechnological process, first developed in China in the 1960s but further developed in the 1990s, bypassing acetone-protecting groups. A second [[genetically modified]] microbe species, such as mutant ''[[Erwinia]]'', among others, oxidises sorbose into 2-ketogluconic acid (2-KGA), which can then undergo ring-closing lactonization via dehydration. This method is used in the predominant process used by the ascorbic acid industry in China, which supplies 70% of the world's ascorbic acid.<ref name="Vantage Market Research-2022">{{cite press release |url=https://www.globenewswire.com/en/news-release/2022/11/08/2550571/0/en/Global-Vitamin-C-Market-Size-Share-to-Surpass-1-8-Bn-by-2028-China-Produces-80-of-Commercial-Vitamin-C-Vantage-Market-Research.html |title=Vantage Market Research: Global Vitamin C Market Size & Share to Surpass $1.8 Bn by 2028 |date=8 November 2022 |website=Globe Newswire |access-date=21 December 2023}}</ref> Researchers are exploring means for one-step fermentation.<ref>{{cite journal |vauthors=Zhou M, Bi Y, Ding M, Yuan Y |title=One-Step Biosynthesis of Vitamin C in Saccharomyces cerevisiae |journal=Front Microbiol |volume=12 |issue= |pages=643472 |date=2021 |pmid=33717042 |pmc=7947327 |doi=10.3389/fmicb.2021.643472 |url= |doi-access=free }}</ref><ref>{{cite journal |vauthors=Tian YS, Deng YD, Zhang WH, Yu-Wang, Xu J, Gao JJ, Bo-Wang, Fu XY, Han HJ, Li ZJ, Wang LJ, Peng RH, Yao QH |display-authors=5 |title=Metabolic engineering of Escherichia coli for direct production of vitamin C from D-glucose |journal=Biotechnol Biofuels Bioprod |volume=15 |issue=1 |pages=86 |date=August 2022 |pmid=35996146 |pmc=9396866 |doi=10.1186/s13068-022-02184-0 |url= |doi-access=free |bibcode=2022BBB....15...86T }}</ref>

===Determination===
The traditional way to analyze the ascorbic acid content is by [[titration]] with an [[oxidizing agent]], and several procedures have been developed.

The popular [[iodometry]] approach uses [[iodine]] in the presence of a [[starch indicator]]. Iodine is reduced by ascorbic acid, and when all the ascorbic acid has reacted, the iodine is in excess, forming a blue-black complex with the starch indicator.  This indicates the end-point of the titration.

As an alternative, ascorbic acid can be treated with iodine in excess, followed by back titration with sodium thiosulfate using starch as an indicator.<ref>{{cite journal|url=http://www.saps.org.uk/attachments/article/556/simple_test_for_vitamin_c.pdf |title=A Simple Test for Vitamin C |journal=School Science Review |year=2002 |volume=83 |issue=305 |page=131 |archive-url=https://web.archive.org/web/20160704170133/http://www.saps.org.uk/attachments/article/556/simple_test_for_vitamin_c.pdf |archive-date=July 4, 2016}}</ref>

This iodometric method has been revised to exploit the reaction of ascorbic acid with [[iodate]] and [[iodide]] in [[acid]] solution. Electrolyzing the potassium iodide solution produces iodine, which reacts with ascorbic acid. The end of the process is determined by [[potentiometric titration]] like [[Karl Fischer titration]]. The amount of ascorbic acid can be calculated by [[Faraday's laws of electrolysis|Faraday's law]].

Another alternative uses [[N-Bromosuccinimide|''N''-bromosuccinimide]] (NBS) as the oxidizing agent in the presence of [[potassium iodide]] and starch. The NBS first oxidizes the ascorbic acid; when the latter is exhausted, the NBS liberates the iodine from the potassium iodide, which then forms the blue-black complex with starch.

== See also ==
* [[Colour retention agent]]
* [[Erythorbic acid]]: a [[diastereomer]] of ascorbic acid.
* [[Mineral ascorbates]]: salts of ascorbic acid
* [[Acids in wine]]

==References==
{{Reflist}}

== Further reading ==
{{refbegin}}
* {{cite book | vauthors = Clayden J, Greeves N, Warren S, Wothers P | title = Organic Chemistry | publisher = Oxford University Press | year = 2001 | isbn = 0-19-850346-6 | url-access = registration | url = https://archive.org/details/organicchemistry00clay_0 }}
* {{cite book | title = Vitamin C: Its Chemistry and Biochemistry | first1 = Michael B. | last1 = Davies | first2 = John | last2 = Austin | first3 = David A. | last3 = Partridge | publisher = Royal Society of Chemistry | isbn = 0-85186-333-7| year = 1991 }}
* {{cite book | title = Food: The Chemistry of Its Components | edition = 3rd | first = T. P. | last = Coultate | year = 1996 | publisher = Royal Society of Chemistry | isbn = 0-85404-513-9 | url-access = registration | url = https://archive.org/details/foodchemistryofi0000coul }}
* {{cite book | editor1-last = Gruenwald | editor1-first = J. | editor2-last = Brendler | editor2-first = T. | editor3-last = Jaenicke | editor3-first = C. | title = PDR for Herbal Medicines | url = https://archive.org/details/pdrforherbalmedi00joer_0 | url-access = registration | edition = 3rd | publisher = Thomson PDR | location = Montvale, New Jersey | year = 2004| isbn = 9781563635120 }}
* {{cite book | first1 = John | last1 = McMurry | title = Organic Chemistry | publisher = Thomson Learning | year = 2008 | edition = 7e | isbn = 978-0-495-11628-8}}
{{refend}}

== External links ==
{{Commons category}}
*{{ICSC|0379|03}}
*{{SIDS|name=<small>L</small>-Ascorbic acid|id=50817}}
*[http://www.inchem.org/documents/pims/pharm/ascorbic.htm IPCS Poisons Information Monograph (PIM) 046]
*[https://web.archive.org/web/20120117014447/http://www.bruker-axs.de/fileadmin/user_upload/SMART_X2S_Structure_Gallery/Structures/vitc_1006.html Interactive 3D-structure of vitamin C] with details on the x-ray structure

{{Gynecological anti-infectives and antiseptics}}
{{Vitamins}}
{{Enzyme cofactors}}
{{Antioxidants}}
{{Authority control}}

{{DEFAULTSORT:Ascorbic Acid}}
[[Category:Organic acids]]
[[Category:Antioxidants]]
[[Category:Dietary antioxidants]]
[[Category:Coenzymes]]
[[Category:Corrosion inhibitors]]
[[Category:Furanones]]
[[Category:Vitamers]]
[[Category:Vitamin C]]
[[Category:Biomolecules]]
[[Category:3-Hydroxypropenals]]