Anthranilic acid

Last updated
Anthranilic acid
Anthranilsaure.svg
C=black, H=white, O=red, N=blue 2-Aminobenzoic-acid-3D-balls.png
C=black, H=white, O=red, N=blue
Names
Preferred IUPAC name
2-Aminobenzoic acid [1]
Systematic IUPAC name
2-Aminobenzenecarboxylic acid
Other names
  • Anthranilic acid
  • o-Aminobenzoic acid
  • 2-Aminobenzoic acid
  • Vitamin L1
  • Anthranilate (conjugate base)
  • 2-AA, 2AA, AA
Identifiers
3D model (JSmol)
3DMet
471803
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.003.898 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 204-287-5
3397
KEGG
PubChem CID
RTECS number
  • CB2450000
UNII
  • InChI=1S/C7H7NO2/c8-6-4-2-1-3-5(6)7(9)10/h1-4H,8H2,(H,9,10) Yes check.svgY
    Key: RWZYAGGXGHYGMB-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C7H7NO2/c8-6-4-2-1-3-5(6)7(9)10/h1-4H,8H2,(H,9,10)
    Key: RWZYAGGXGHYGMB-UHFFFAOYAS
  • O=C(O)c1ccccc1N
Properties
C7H7NO2
Molar mass 137.138 g·mol−1
Appearancewhite or yellow solid
Odor odorless
Density 1.412 g/cm3
Melting point 146 to 148 °C (295 to 298 °F; 419 to 421 K) [2]
Boiling point 200 °C (392 °F; 473 K) (sublimes)
0.572 g/100 mL (25 °C)
Solubility very soluble in chloroform, pyridine
soluble in ethanol, ether, ethyl ether
slightly soluble in trifluoroacetic acid, benzene
log P 1.21
Vapor pressure 0.1 Pa (52.6 °C)
Acidity (pKa)
  • 2.17 (amino; H2O)
  • 4.85 (carboxyl; H2O) [3]
-77.18·10−6 cm3/mol
1.578 (144 °C)
Thermochemistry
-380.4 KJ/mol
Hazards
GHS labelling:
GHS-pictogram-acid.svg GHS-pictogram-exclam.svg
Danger
H318, H319
P264, P280, P305+P351+P338, P310, P337+P313
NFPA 704 (fire diamond)
NFPA 704.svgHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
2
1
0
Flash point >150 °C (302 °F; 423 K)
>530 °C (986 °F; 803 K)
Lethal dose or concentration (LD, LC):
1400 mg/kg (oral, rat)
Safety data sheet (SDS) External MSDS
Legal status
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Anthranilic acid is an aromatic acid with the formula C6H4(NH2)(CO2H) and has a sweetish taste. [5] [6] [7] The molecule consists of a benzene ring, ortho-substituted with a carboxylic acid and an amine. As a result of containing both acidic and basic functional groups, the compound is amphoteric. Anthranilic acid is a white solid when pure, although commercial samples may appear yellow. The anion [C6H4(NH2)(CO2)]−, obtained by the deprotonation of anthranilic acid, is called anthranilate. Anthranilic acid was once thought to be a vitamin and was referred to as vitamin L1 in that context, but it is now known to be non-essential in human nutrition. [8]

Contents

Structure

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. [9] It is triboluminescent. [10] Above 81 °C (178 °F; 354 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. [10]

Production

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: [11]

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. [12] 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. [13]

Biosynthesis

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.

Anthranilate is the biosynthetic precursor to the amino acid tryptophan. Tryptophan biosynthesis (en).svg
Anthranilate is the biosynthetic precursor to the amino acid tryptophan.

Uses

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, [14] : 235  which in turn is a nitrogen isostere of salicylic acid, which is the active metabolite of aspirin. [14] : 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". [15] : 17 

Reactions

Anthranilic acid can be diazotized to give the diazonium cation [C6H4(CO2H)(N2)]+. This cation can be used to generate benzyne, [16] dimerized to give diphenic acid, [17] or undergo diazonium coupling reactions such as in the synthesis of methyl red. [18]

It reacts with phosgene to give isatoic anhydride, a versatile reagent. [19]

Chlorination of anthranilic acid gives the 2,4-dichloro derivative, which can undergo reductive coupling to form a biaryl compound. [20]

Safety and regulation

It is also a DEA List I Chemical because of its use in making the now-widely outlawed euphoric sedative drug methaqualone (Quaalude, Mandrax). [21]

See also

Related Research Articles

In chemistry, amines are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines, trimethylamine, and aniline. Inorganic derivatives of ammonia are also called amines, such as monochloramine.

<span class="mw-page-title-main">Ester</span> Compound derived from an acid

In chemistry, an ester is a compound derived from an acid in which the hydrogen atom (H) of at least one acidic hydroxyl group of that acid is replaced by an organyl group. Analogues derived from oxygen replaced by other chalcogens belong to the ester category as well. According to some authors, organyl derivatives of acidic hydrogen of other acids are esters as well, but not according to the IUPAC.

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

Nitrous acid is a weak and monoprotic acid known only in solution, in the gas phase and in the form of nitrite salts. Nitrous acid is used to make diazonium salts from amines. The resulting diazonium salts are reagents in azo coupling reactions to give azo dyes.

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

Diethyl malonate, also known as DEM, is the diethyl ester of malonic acid. It occurs naturally in grapes and strawberries as a colourless liquid with an apple-like odour, and is used in perfumes. It is also used to synthesize other compounds such as barbiturates, artificial flavourings, vitamin B1, and vitamin B6.

<span class="mw-page-title-main">Azo compound</span> Organic compounds with a diazenyl group (–N=N–)

Azo compounds are organic compounds bearing the functional group diazenyl.

Methylamine is an organic compound with a formula of CH3NH2. This colorless gas is a derivative of ammonia, but with one hydrogen atom being replaced by a methyl group. It is the simplest primary amine.

<span class="mw-page-title-main">Anisole</span> Organic compound (CH₃OC₆H₅) also named methoxybenzene

Anisole, or methoxybenzene, is an organic compound with the formula CH3OC6H5. It is a colorless liquid with a smell reminiscent of anise seed, and in fact many of its derivatives are found in natural and artificial fragrances. The compound is mainly made synthetically and is a precursor to other synthetic compounds. Structurally, it is an ether with a methyl and phenyl group attached. Anisole is a standard reagent of both practical and pedagogical value.

The Hofmann rearrangement is the organic reaction of a primary amide to a primary amine with one less carbon atom. The reaction involves oxidation of the nitrogen followed by rearrangement of the carbonyl and nitrogen to give an isocyanate intermediate. The reaction can form a wide range of products, including alkyl and aryl amines.

In organic chemistry, ozonolysis is an organic reaction where the unsaturated bonds are cleaved with ozone. Multiple carbon–carbon bond are replaced by carbonyl groups, such as aldehydes, ketones, and carboxylic acids. The reaction is predominantly applied to alkenes, but alkynes and azo compounds are also susceptible to cleavage. The outcome of the reaction depends on the type of multiple bond being oxidized and the work-up conditions.

<span class="mw-page-title-main">Thionyl chloride</span> Inorganic compound (SOCl2)

Thionyl chloride is an inorganic compound with the chemical formula SOCl2. It is a moderately volatile, colourless liquid with an unpleasant acrid odour. Thionyl chloride is primarily used as a chlorinating reagent, with approximately 45,000 tonnes per year being produced during the early 1990s, but is occasionally also used as a solvent. It is toxic, reacts with water, and is also listed under the Chemical Weapons Convention as it may be used for the production of chemical weapons.

<span class="mw-page-title-main">Diazonium compound</span> Group of organonitrogen compounds

Diazonium compounds or diazonium salts are a group of organic compounds sharing a common functional group [R−N+≡N]X− where R can be any organic group, such as an alkyl or an aryl, and X is an inorganic or organic anion, such as a halide.

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

Isatin, also known as tribulin, is an organic compound derived from indole with formula C8H5NO2. The compound was first obtained by Otto Linné Erdman and Auguste Laurent in 1840 as a product from the oxidation of indigo dye by nitric acid and chromic acids.

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

Thiophenol is an organosulfur compound with the formula C6H5SH, sometimes abbreviated as PhSH. This foul-smelling colorless liquid is the simplest aromatic thiol. The chemical structures of thiophenol and its derivatives are analogous to phenols. An exception is the oxygen atom in the hydroxyl group (-OH) bonded to the aromatic ring is replaced by a sulfur atom. The prefix thio- implies a sulfur-containing compound and when used before a root word name for a compound which would normally contain an oxygen atom, in the case of 'thiol' that the alcohol oxygen atom is replaced by a sulfur atom.

<span class="mw-page-title-main">Phthalimide</span> Organic Compound

Phthalimide is the organic compound with the formula C6H4(CO)2NH. It is the imide derivative of phthalic anhydride. It is a sublimable white solid that is slightly soluble in water but more so upon addition of base. It is used as a precursor to other organic compounds as a masked source of ammonia.

The Balz–Schiemann reaction is a chemical reaction in which a primary aromatic amine is transformed to an aryl fluoride via a diazonium tetrafluoroborate intermediate. This reaction is a traditional route to fluorobenzene and some related derivatives, including 4-fluorobenzoic acid.

<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.

<span class="mw-page-title-main">1-Methylimidazole</span> Chemical compound

1-Methylimidazole or N-methylimidazole is an aromatic heterocyclic organic compound with the formula CH3C3H3N2. It is a colourless liquid that is used as a specialty solvent, a base, and as a precursor to some ionic liquids. It is a fundamental nitrogen heterocycle and as such mimics for various nucleoside bases as well as histidine and histamine.

<i>N</i>-Acetylanthranilic acid Chemical compound

N-Acetylanthranilic acid is an organic compound with the molecular formula C9H9NO3. It is an intermediate product in catabolism of quinaldine in Arthrobacter sp., and is further metabolized to anthranilic acid.

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

Isatoic anhydride is an organic compound derived from anthranilic acid. A white solid, it is prepared by reaction of anthranilic acid with phosgene.

<span class="mw-page-title-main">Diphenic acid</span> Dicarboxylic acid of biphenyl

Diphenic acid, also known as Dibenzoic acid, is an organic compound with the formula (C6H4CO2H)2. It is the most studied of several isomeric dicarboxylic acids of biphenyl. It is a white solid that can be prepared in the laboratory from anthranilic acid via the diazonium salt. It is the product of the microbial action on phenanthrene.

References

  1. ↑ "Front Matter". Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. p. 748. doi:10.1039/9781849733069-FP001. ISBN   978-0-85404-182-4.
  2. ↑ IPCS
  3. ↑ Haynes, William M., ed. (2016). CRC Handbook of Chemistry and Physics (97th ed.). CRC Press. pp. 5–89. ISBN   978-1498754286.
  4. ↑ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-15.
  5. ↑ Acton, Q. Ashton (2013). Aminobenzoic Acids—Advances in Research and Application (2013 ed.). Atlanta: ScholarlyEditions. p. 23. ISBN   9781481684842 – via Google Books.
  6. ↑ Hardy, Mark R. (1997). "Glycan Labeling with the Flurophores 2-Aminobenzamide and Antranilic Acid". In Townsend, R. Reid; Hotchkiss, Arland T. Jr. (eds.). Techniques in Glycobiology. Marcel Dekker, Inc. p. 360. ISBN   9780824798222 – via Google Books.
  7. ↑ The Merck Index, 10th Ed. (1983), p.62., Rahway: Merck & Co.
  8. ↑ Davidson, Michael W. (2004). "Anthranilic Acid (Vitamin L)]". Florida State University . Retrieved November 20, 2019.
  9. ↑ Brown, C. J. (1968). "The crystal structure of anthranilic acid". Proceedings of the Royal Society of London. Series A. Mathematical and Physical Sciences. 302 (1469): 185–199. Bibcode:1968RSPSA.302..185B. doi:10.1098/rspa.1968.0003. S2CID   93221347.
  10. 1 2 Hardy, Gordon E.; Kaska, William C.; Chandra, B. P.; Zink, Jeffrey I. (March 1981). "Triboluminescence-structure relationships in polymorphs of hexaphenylcarbodiphosphorane and anthranilic acid, molecular crystals, and salts". Journal of the American Chemical Society. 103 (5): 1074–1079. doi:10.1021/ja00395a014.
  11. ↑ Maki, Takao; Takeda, Kazuo (2000). "Benzoic Acid and Derivatives". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a03_555. ISBN   3527306730..
  12. ↑ Vogel's Textbook of Practical Organic Chemistry, 4th Ed., (B. S. Furniss et al., Eds.) (1978), p.666, London: Longman.
  13. ↑ Sheibley, Fred E. (1943). "Carl Julius Fritzsche and the discovery of anthranilic acid, 1841". Journal of Chemical Education. 20 (3): 115. Bibcode:1943JChEd..20..115S. doi:10.1021/ed020p115.
  14. 1 2 Sriram D, Yogeeswari P. Medicinal Chemistry, 2nd Edition. Pearson Education India, 2010. ISBN   9788131731444
  15. ↑ Auburn University course material. Jack DeRuiter, Principles of Drug Action 2, Fall 2002 1: Non-Steroidal Antiinflammatory Drugs (NSAIDS)
  16. ↑ Logullo, F. M.; Seitz, A. H.; Friedman, L. (1968). "Benzenediazonium-2-carboxy- and Biphenylene". Organic Syntheses . 48: 12.
  17. ↑ Atkinson, E. R.; Lawler, H. J. (1927). "Diphenic Acid". Organic Syntheses. 7: 30. doi:10.15227/orgsyn.007.0030.
  18. ↑ Clarke, H. T.; Kirner, W. R. (1922). "Methyl Red". Organic Syntheses . 2: 47.
  19. ↑ Wagner, E. C.; Fegley, Marion F. (1947). "Isatoic anhydride". Org. Synth. 27: 45. doi:10.15227/orgsyn.027.0045.
  20. ↑ Atkinson, Edward R.; Murphy, Donald M.; Lufkin, James E. (1951). "dl-4,4',6,6'-Tetrachlorodiphenic Acid". Organic Syntheses . 31: 96.
  21. ↑ Angelos SA, Meyers JA (1985). "The isolation and identification of precursors and reaction products in the clandestine manufacture of methaqualone and mecloqualone". Journal of Forensic Sciences. 30 (4): 1022–1047. doi:10.1520/JFS11044J. PMID   3840834.
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