anthranilic acid

Although not usually referred to as such, it is an amino acid. Solid anthranilic acid typically consists of both the amino-carboxylic acid and the zwitterionic ammonium carboxylate forms, and has a monoclinic crystal structure with space group P2₁.{{Cite journal | doi = 10.1098/rspa.1968.0003| title = The crystal structure of anthranilic acid| journal = Proceedings of the Royal Society of London. Series A. Mathematical and Physical Sciences| volume = 302| issue = 1469| pages = 185–199| year = 1968| bibcode = 1968RSPSA.302..185B| last1 = Brown| first1 = C. J.| s2cid = 93221347}} It is triboluminescent. Above {{convert|81|C|F K}}, it converts to an orthorhombic form with space group Pbca, which is not triboluminescent; a non-triboluminescent monoclinic phase with similar structure is also known.{{cite journal |last1=Hardy |first1=Gordon E. |last2=Kaska |first2=William C. |last3=Chandra |first3=B. P. |last4=Zink |first4=Jeffrey I. |title=Triboluminescence-structure relationships in polymorphs of hexaphenylcarbodiphosphorane and anthranilic acid, molecular crystals, and salts |journal=Journal of the American Chemical Society |date=March 1981 |volume=103 |issue=5 |pages=1074–1079 |doi=10.1021/ja00395a014}}

In 1840-1841, Carl Julius Fritzsche was able to extract and crystallize two acids from the products of reaction of indigo dye with caustic potash, which he called chrysanilic and anthranilic acids after their colors before purification (golden yellow and black respectively) and the plant anil (Indigofera suffruticosa).{{Cite journal |last=Fritzsche |first=J. |date=1841 |title=Ueber die Producte der Einwirkung des Kali auf das Indigblau |url=https://books.google.com/books?id=-l42AQAAMAAJ&pg=PA67 |journal=Journal für Praktische Chemie |language=en |volume=23 |issue=1 |pages=67–83 |doi=10.1002/prac.18410230104 |issn=0021-8383|url-access=subscription }}{{Cite journal |last=Fritzsche |first=J. |date=1841 |title=Ueber die Produkte der Einwirkung von Kali auf Indigblau |url=https://books.google.com/books?id=OsMwAAAAYAAJ&pg=PA76 |journal=Justus Liebigs Annalen der Chemie |language=en |volume=39 |issue=1 |pages=76–91 |doi=10.1002/jlac.18410390104 |issn=0075-4617}} The former was identified as ortho-carboxy anil of indoxyl-2-aldehyde only in 1910{{Cite journal |last=Sheibley |first=Fred E. |date=March 1943 |title=Carl Julius Fritzsche and the discovery of anthranilic acid, 1841 |url=https://pubs.acs.org/doi/abs/10.1021/ed020p115 |journal=Journal of Chemical Education |language=en |volume=20 |issue=3 |pages=115 |doi=10.1021/ed020p115 |issn=0021-9584|url-access=subscription }} while the latter was identified as salicylamide already in 1843 by Cahours.{{Cite book |url=https://books.google.com/books?id=DAcAAAAAMAAJ&pg=PA536 |title=The Chemical Gazette |date=1843 |language=en}}

Many routes to anthranilic acid have been described. Industrially it is produced from phthalic anhydride, beginning with amination:

:C₆H₄(CO)₂O + NH₃ + NaOH → C₆H₄(C(O)NH₂)CO₂Na + H₂O

The resulting sodium salt of phthalamic acid is decarbonylated via a Hofmann rearrangement of the amide group, induced by hypochlorite:{{Cite book | doi = 10.1002/14356007.a03_555| chapter = Benzoic Acid and Derivatives| title = Ullmann's Encyclopedia of Industrial Chemistry| year = 2000| last1 = Maki| first1 = Takao| last2 = Takeda| first2 = Kazuo| isbn = 3527306730}}.

:C₆H₄(C(O)NH₂)CO₂Na + HOCl → C₆H₄NH₂CO₂H + NaCl + CO₂

A related method involves treating phthalimide with sodium hypobromite in aqueous sodium hydroxide, followed by neutralization.Vogel's Textbook of Practical Organic Chemistry, 4th Ed., (B. S. Furniss et al., Eds.) (1978), p.666, London: Longman. In the era when indigo dye was obtained from plants, it was degraded to give anthranilic acid.

Anthranilic acid was first obtained by base-induced degradation of indigo.{{Cite journal | doi = 10.1021/ed020p115| title = Carl Julius Fritzsche and the discovery of anthranilic acid, 1841| journal = Journal of Chemical Education| volume = 20| issue = 3| pages = 115| year = 1943| last1 = Sheibley| first1 = Fred E.| bibcode = 1943JChEd..20..115S}}

Anthranilic acid is biosynthesized from chorismic acid by the action of anthranilate synthase. In organisms capable of tryptophan synthesis, anthranilate is a precursor to the amino acid tryptophan via the attachment of phosphoribosyl pyrophosphate to the amine group. After then, cyclization occurs to produce indole.

File:Tryptophan biosynthesis (en).svg{{clear-left}}

Industrially, anthranilic acid is an intermediate in the production of azo dyes and saccharin. It and its esters are used in preparing perfumes to mimic jasmine and orange, pharmaceuticals (loop diuretics, such as furosemide) and UV-absorber as well as corrosion inhibitors for metals and mold inhibitors in soy sauce.

Anthranilate-based insect repellents have been proposed as replacements for DEET.

Fenamic acid is a derivative of anthranilic acid,Sriram D, Yogeeswari P. [https://books.google.com/books?id=tUSLclf_NoQC&pg=PA235 Medicinal Chemistry, 2nd Edition]. Pearson Education India, 2010. {{ISBN|9788131731444}}{{rp|235}} which in turn is a nitrogen isostere of salicylic acid, which is the active metabolite of aspirin.{{rp|235}} Several non-steroidal anti-inflammatory drugs, including mefenamic acid, tolfenamic acid, flufenamic acid, and meclofenamic acid are derived from fenamic acid or anthranilic acid and are called "anthranilic acid derivatives" or "fenamates".Auburn University course material. Jack DeRuiter, Principles of Drug Action 2, Fall 2002 1: [http://www.auburn.edu/~deruija/nsaids_2002.pdf Non-Steroidal Antiinflammatory Drugs (NSAIDS)]{{rp|17}}

Anthranilic acid can be diazotized to give the diazonium cation [C₆H₄(CO₂H)(N₂)]⁺. This cation can be used to generate benzyne,{{OrgSynth| last1= Logullo |first1= F. M. |last2= Seitz |first2= A. H. |last3= Friedman |first3= L. | title = Benzenediazonium-2-carboxy- and Biphenylene | page= 12 | volume= 48 | year = 1968| prep= CV5P0054}} dimerized to give diphenic acid,{{cite journal|doi=10.15227/orgsyn.007.0030|first1=E. R.|last1=Atkinson|first2=H. J.|last2=Lawler|title=Diphenic Acid|journal=Organic Syntheses|volume=7|pages=30|year=1927}} or undergo diazonium coupling reactions such as in the synthesis of methyl red.{{OrgSynth |first1= H. T. |last1= Clarke |first2= W. R. |last2= Kirner |title= Methyl Red |year= 1922 |volume= 2 |page= 47 |prep= cv1p0374}}

It reacts with phosgene to give isatoic anhydride, a versatile reagent.{{cite journal|journal=Org. Synth. |year=1947|volume=27|page=45 |doi=10.15227/orgsyn.027.0045|title=Isatoic anhydride|first1=E. C. |last1=Wagner |first2=Marion F. |last2=Fegley}}

Chlorination of anthranilic acid gives the 2,4-dichloro derivative, which can undergo reductive coupling to form a biaryl compound.{{OrgSynth |first1=Edward R. |last1=Atkinson |first2=Donald M. |last2=Murphy |first3=James E. |last3=Lufkin |title= dl-4,4',6,6'-Tetrachlorodiphenic Acid |year=1951 |volume=31 |page=96 |prep=CV4P0872}}

It is also a DEA List I Chemical because of its use in making the now-widely outlawed euphoric sedative drug methaqualone (Quaalude, Mandrax).{{cite journal | author = Angelos SA, Meyers JA | title = The isolation and identification of precursors and reaction products in the clandestine manufacture of methaqualone and mecloqualone | journal = Journal of Forensic Sciences | date = 1985 | volume = 30 | issue = 4 | pages = 1022–1047 | doi = 10.1520/JFS11044J | pmid=3840834}}

• Kynureninase
• 3-Aminobenzoic acid
• 4-Aminobenzoic acid
• Methyl anthranilate

{{Amino acid metabolism intermediates}}