Anthranilic acid is an aromatic acid with the

formula In science, a formula is a concise way of expressing information symbolically, as in a mathematical formula or a ''chemical formula''. The informal use of the term ''formula'' in science refers to the general construct of a relationship betwe ...

C₆H₄(NH₂)(CO₂H) and has a sweetish taste. The molecule consists of a benzene ring, ''ortho''-substituted with a

carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an Substituent, R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl ...

and an

amine In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

. As a result of containing both acidic and basic

functional group In organic chemistry, a functional group is any substituent or moiety (chemistry), moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions r ...

s, the compound is amphoteric. Anthranilic acid is a white solid when pure, although commercial samples may appear yellow. The anion ₆H₄(NH₂)(CO₂)sup>−, 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.

Structure

Although not usually referred to as such, it is an

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

. Solid anthranilic acid typically consists of both the amino-carboxylic acid and the

zwitterion In chemistry, a zwitterion ( ; ), also called an inner salt or dipolar ion, is a molecule that contains an equal number of positively and negatively charged functional groups. : (1,2- dipolar compounds, such as ylides, are sometimes excluded from ...

ic ammonium carboxylate forms, and has a

monoclinic In crystallography, the monoclinic crystal system is one of the seven crystal systems. A crystal system is described by three Vector (geometric), vectors. In the monoclinic system, the crystal is described by vectors of unequal lengths, as in t ...

crystal structure with space group P2₁. It is triboluminescent. Above , it converts to an

orthorhombic In crystallography, the orthorhombic crystal system is one of the 7 crystal systems. Orthorhombic Lattice (group), lattices result from stretching a cubic crystal system, cubic lattice along two of its orthogonal pairs by two different factors, res ...

form with space group Pbca, which is not triboluminescent; a non-triboluminescent monoclinic phase with similar structure is also known.

History and etymology

In 1840-1841, Carl Julius Fritzsche was able to extract and crystallize two acids from the products of reaction of

indigo dye Indigo dye is an organic compound with a distinctive indigo, blue color. Indigo is a natural dye obtained from the leaves of some plants of the Indigofera#Uses, ''Indigofera'' genus, in particular ''Indigofera tinctoria''. Dye-bearing ''Indigofer ...

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 ''Indigofera suffruticosa'', commonly known as Guatemalan indigo, small-leaved indigo (Sierra Leone), West Indian indigo, wild indigo, and anil, is a flowering plant in the pea family, Fabaceae. ''Anil'' is native to the subtropical and tropi ...

''). The former was identified as ortho-carboxy anil of indoxyl-2-aldehyde only in 1910 while the latter was identified as salicylamide already in 1843 by Cahours.

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: :C₆H₄(C(O)NH₂)CO₂Na + HOCl → C₆H₄NH₂CO₂H + NaCl + CO₂ A related method involves treating

phthalimide Phthalimide is the organic compound with the formula C6H4(CO)2NH. It is the imide derivative of phthalic anhydride. It is a Sublimation (phase transition), sublimable white solid that is slightly soluble in water but more so upon addition of bas ...

with sodium

hypobromite The hypobromite ion, also called alkaline bromine water, is BrO−. Bromine is in the +1 oxidation state. The Br–O bond length is 1.82 Å. Hypobromite is the bromine compound analogous to hypochlorites found in common bleaches, and in immune cel ...

in aqueous sodium hydroxide, followed by neutralization. In the era when

was obtained from plants, it was degraded to give anthranilic acid. Anthranilic acid was first obtained by base-induced degradation of indigo.

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

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromat ...

via the attachment of phosphoribosyl pyrophosphate to the amine group. After then, cyclization occurs to produce

indole Indole is an organic compound with the formula . Indole is classified as an aromatic heterocycle. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indoles are derivatives of indole ...

Uses

Industrially, anthranilic acid is an intermediate in the production of

azo dye Azo dyes are organic compounds bearing the functional group R−N=N−R′, in which R and R′ are usually aryl and substituted aryl groups. They are a commercially important family of azo compounds, i.e. compounds containing the C−N=N−C l ...

s and saccharin. It and its

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

s are used in preparing

perfume Perfume (, ) is a mixture of fragrance, fragrant essential oils or aroma compounds (fragrances), Fixative (perfumery), fixatives and solvents, usually in liquid form, used to give the human body, animals, food, objects, and living-spaces an agre ...

s to mimic

jasmine Jasmine (botanical name: ''Jasminum'', pronounced ) is a genus of shrubs and vines in the olive family of Oleaceae. It contains around 200 species native to tropical and warm temperate regions of Eurasia, Africa, and Oceania. Jasmines are wid ...

and orange, pharmaceuticals (

loop diuretic Loop diuretics are pharmacological agents that primarily inhibit the Na-K-Cl cotransporter located on the luminal membrane of cells along the thick ascending limb of the loop of Henle. They are often used for the treatment of hypertension and e ...

s, such as furosemide) and UV-absorber as well as

corrosion inhibitor A corrosion inhibitor or anti-corrosive is a chemical compound added to a liquid or gas to decrease the corrosion rate of a metal that comes into contact with the fluid. The effectiveness of a corrosion inhibitor depends on fluid composition and ...

s for metals and mold inhibitors in

soy sauce Soy sauce (sometimes called soya sauce in British English) is a liquid condiment of China, Chinese origin, traditionally made from a fermentation (food), fermented paste of soybeans, roasted cereal, grain, brine, and ''Aspergillus oryzae'' or ''A ...

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

DEET ''N'',''N''-Diethyl-''meta''-toluamide, also called diethyltoluamide or DEET (, from DET, the initials of di- + ethyl + toluamide), is the oldest, one of the most effective, and most common active ingredients in commercial insect repellents. ...

. Fenamic acid is a derivative of anthranilic acid,Sriram D, Yogeeswari P
Medicinal Chemistry, 2nd Edition
Pearson Education India, 2010. which in turn is a nitrogen isostere of

salicylic acid Salicylic acid is an organic compound with the formula HOC6H4COOH. A colorless (or white), bitter-tasting solid, it is a precursor to and a active metabolite, metabolite of acetylsalicylic acid (aspirin). It is a plant hormone, and has been lis ...

, which is the active metabolite of

aspirin Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...

. Several non-steroidal anti-inflammatory drugs, including

mefenamic acid Mefenamic acid is a member of the Nonsteroidal anti-inflammatory drug#Anthranilic acid derivatives .28fenamates.29, anthranilic acid derivatives (or fenamate) class of nonsteroidal anti-inflammatory drugs (NSAIDs), and is used to treat mild to m ...

, tolfenamic acid, flufenamic acid, and meclofenamic acid are derived from fenamic acid or anthranilic acid and are called "anthranilic acid derivatives" or "fenamates".

Reactions

Anthranilic acid can be diazotized to give the diazonium cation ₆H₄(CO₂H)(N₂)sup>+. This cation can be used to generate benzyne, dimerized to give diphenic acid, or undergo diazonium coupling reactions such as in the synthesis of methyl red. It reacts with

phosgene Phosgene is an organic chemical compound with the formula . It is a toxic, colorless gas; in low concentrations, its musty odor resembles that of freshly cut hay or grass. It can be thought of chemically as the double acyl chloride analog of ...

to give isatoic anhydride, a versatile reagent. Chlorination of anthranilic acid gives the 2,4-dichloro derivative, which can undergo reductive coupling to form a biaryl compound.

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).

References

{{Amino acid metabolism intermediates