:Picolinic acid
{{Short description|Pyridine-2-carboxylic acid; bidentate chelating agent}}
{{chembox
|Verifiedimages = changed
|Watchedfields = changed
|verifiedrevid = 464206292
|ImageFile1_Ref = {{chemboximage|correct|??}}
|ImageFile1 =Picolinic acid.svg
|ImageSize1 =180px
|ImageFile2 =
|ImageSize2 =180px
|PIN = Pyridine-2-carboxylic acid
|OtherNames = Picolinic acid
|Section1={{Chembox Identifiers
|ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
|ChemSpiderID = 993
|InChI = 1/C6H5NO2/c8-6(9)5-3-1-2-4-7-5/h1-4H,(H,8,9)
|InChIKey = SIOXPEMLGUPBBT-UHFFFAOYAC
|ChEMBL_Ref = {{ebicite|correct|EBI}}
|ChEMBL = 72628
|StdInChI_Ref = {{stdinchicite|correct|chemspider}}
|StdInChI = 1S/C6H5NO2/c8-6(9)5-3-1-2-4-7-5/h1-4H,(H,8,9)
|StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
|StdInChIKey = SIOXPEMLGUPBBT-UHFFFAOYSA-N
|CASNo_Ref = {{cascite|correct|CAS}}
|CASNo =98-98-6
|UNII_Ref = {{fdacite|correct|FDA}}
|UNII = QZV2W997JQ
|PubChem =1018
|ChEBI_Ref = {{ebicite|correct|EBI}}
|ChEBI = 28747
|SMILES = c1ccnc(c1)C(=O)O
}}
|Section2={{Chembox Properties
|C=6 | H=5 | N=1 | O=2
|Appearance = White solid
|MeltingPtC = 136 to 138
|Density = 1.526 g/cm³
|Solubility = Slightly soluble (0.41%) in water{{cite journal|last=Lide|first=DR|title=CRC Handbook of Chemistry and Physics, Internet Version 2005, http://hbcpnetbase.com, CRC Press, Boca Raton, Florida, 2005}}
}}
}}
Picolinic acid is an organic compound with the formula {{chem2|NC5H4CO2H}}. It is a derivative of pyridine with a carboxylic acid (COOH) substituent at the 2-position. It is an isomer of nicotinic acid and isonicotinic acid, which have the carboxyl side chain at the 3- and 4-positions, respectively. It is a white solid although impure samples can appear tan. The compound is soluble in water.
Production
On a commercial scale, picolinic acid is produced by ammoxidation of 2-picoline followed by hydrolysis of the resulting nitrile:
:{{chem2|NC5H4CH3 + 1.5 O2 + NH3 -> NC5H4C\tN + 3 H2O}}
:{{chem2|NC5H4C\tN + 2 H2O -> NC5H4CO2H + NH3}}
It is also produced by oxidation of picoline with nitric acid.{{Ullmann|first1=Shinkichi|last1=Shimizu|first2=Nanao|last2=Watanabe|first3=Toshiaki|last3=Kataoka|first4=Takayuki|last4= Shoji|first5=Nobuyuki|last5=Abe|first6=Sinji|last6=Morishita|first7=Hisao|last7=Ichimura|title=Pyridine and Pyridine Derivatives|year=2007|doi=10.1002/14356007.a22_399}}
In the laboratory, picolinic acid is formed from 2-methylpyridine by oxidation with potassium permanganate (KMnO4).{{cite journal |doi=10.15227/orgsyn.020.0079 |title=Picolinic Acid Hydrochloride |journal=Organic Syntheses |date=1940 |volume=20 |page=79|first1=Alvin W.|last1=Singer|first2=S. M. |last2=McElvain }}{{cite book|author=Harold Hart, Leslie E. Craine, David J. Hart, Christopher M. Hadad; Nicole Kindler|title='Organische Chemie 3. Auflage|publisher=Wiley-VCH|location=Weinheim|year=2007|isbn=978-3-527-31801-8|page=494}}
Reactions
Hydrogenation of picolinic acid gives piperidine-2-carboxylic acid, a precursor to the drug Mepivacaine.
Picolinic acid is a bidentate chelating agent of elements such as chromium, zinc, manganese, copper, iron, and molybdenum in the human body.{{cite journal |doi=10.3891/acta.chem.scand.23-3011 |title=The Crystal Structure of Zinc Picolinate Tetrahydrate, Zn(C6H4O2N)2(H2O)4 |date=1969 |last1=Lumme |first1=Paavo |last2=Lundgren |first2=Georg |last3=Mark |first3=Wanda |last4=Lundström |first4=Hans |last5=Borch |first5=Gunner |last6=Craig |first6=J. Cymerman |journal=Acta Chemica Scandinavica |volume=23 |pages=3011–3022 }}{{cite journal |doi=10.1021/ar5004626 |title=Bidentate, Monoanionic Auxiliary-Directed Functionalization of Carbon–Hydrogen Bonds |date=2015 |last1=Daugulis |first1=Olafs |last2=Roane |first2=James |last3=Tran |first3=Ly Dieu |journal=Accounts of Chemical Research |volume=48 |issue=4 |pages=1053–1064 |pmid=25756616 |pmc=4406856 }}
It is a substrate in the Mitsunobu reaction. In the Hammick reaction, picolinic acid reacts with ketones to give pyridine-2-carbonols:{{cite book |last=Fuchs |first=Philip L. |chapter=Picolinic acid |chapter-url=https://books.google.com/books?id=Cbc2AAAAQBAJ&q=picolinic%20acid |url=https://books.google.com/books?id=Cbc2AAAAQBAJ |title=Catalytic Oxidation Reagents |date=2013-07-29 |page=495ff |publisher=Wiley Inc. |oclc=954583821 |isbn=9781118704844}}
:{{chem2|NC5H4CO2H + R2C\dO -> NC5H4CR2(OH) + CO2}}
Biosynthesis
Picolinic acid is a catabolite of the amino acid tryptophan through the kynurenine pathway.{{cite journal | last1 = Tan | first1 = L. | display-authors = etal | date = December 2012 | title = The kynurenine pathway in neurodegenerative diseases: mechanistic and therapeutic considerations | journal = J Neurol Sci | volume = 323 | issue = 1–2| pages = 1–8 | doi = 10.1016/j.jns.2012.08.005 | pmid = 22939820 | s2cid = 6061945 }} Its function is unclear, but it has been implicated in a variety of neuroprotective, immunological, and anti-proliferative effects. In addition, it is suggested to assist in the absorption of zinc(II) ions and other divalent or trivalent ions through the small intestine.{{cite journal |last=Evans |first=Gary |year=1982 |title=The Role of Picolinic Acid in Metal Metabolism |url=http://naldc.nal.usda.gov/download/46436/PDF |journal=Life Chemistry Reports |publisher=Harwood Academic Publishers |volume=1 |pages=57–67 |access-date=20 March 2015 |archive-date=26 January 2016 |archive-url=https://web.archive.org/web/20160126125834/http://naldc.nal.usda.gov/download/46436/PDF |url-status=dead }}
Picolinates
Salts of picolinic acid (picolinates) include:
See also
References
{{reflist|33em}}
{{Glycinergics}}
{{Use dmy dates|date=March 2018}}