Anthranilic acid is an

aromatic acid Aromatic acids are a type of aromatic compound. Included in that class are substances containing an aromatic ring and an organic acid functional group. There are several categories of aromatic acids including: *Phenolic acids: substances containin ...

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 In chemistry, an amphoteric compound () is a molecule or ion that can react both as an acid and as a base. What exactly this can mean depends on which definitions of acids and bases are being used. Etymology and terminology Amphoteric is d ...

. 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 Triboluminescence is a phenomenon in which light is generated when a material is mechanically pulled apart, ripped, scratched, crushed, or rubbed (see tribology). The phenomenon is not fully understood but appears in most cases to be caused by the ...

. 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 Carl Julius Fritzsche (17 October 1808 in Neustadt in Sachsen, Neustadt – 8 June 1871) was a German pharmacist and chemist. He was a nephew of pharmacist Friedrich Adolph August Struve (1781–1840). After five years spent working at his un ...

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 Potassium hydroxide is an inorganic compound with the formula K OH, and is commonly called caustic potash. Along with sodium hydroxide (NaOH), KOH is a prototypical strong base. It has many industrial and niche applications, most of which utiliz ...

, 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 Phthalic anhydride is the organic compound with the formula C6H4(CO)2O. It is the anhydride of phthalic acid. Phthalic anhydride is a principal commercial form of phthalic acid. It was the first anhydride of a dicarboxylic acid to be used commer ...

, 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 The Hofmann rearrangement (Hofmann degradation) 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 gi ...

of the amide group, induced by

hypochlorite In chemistry, hypochlorite, or chloroxide is an oxyanion with the chemical formula ClO−. It combines with a number of cations to form hypochlorite salts. Common examples include sodium hypochlorite (household bleach) and calcium 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 Chorismic acid, more commonly known as its ion, anionic form chorismate, is an important biochemical intermediate in plants and microorganisms. It is a precursor for: * The aromatic amino acids phenylalanine, tryptophan, and tyrosine * Indole, ind ...

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 Phosphoribosyl pyrophosphate (PRPP) is a Sugar phosphates, pentose phosphate. It is a biochemical intermediate in the formation of purine nucleotides via Inosinic acid, inosine-5-monophosphate, as well as in pyrimidine nucleotide formation. Hence ...

to the

amine group 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 ...

. 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 Saccharin, also called saccharine, benzosulfimide, or E954, or used in saccharin sodium or saccharin calcium forms, is a non-nutritive artificial sweetener. Saccharin is a sultam that is about 500 times sweeter than sucrose, but has a bitter or ...

. 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 Orange most often refers to: *Orange (fruit), the fruit of the tree species '' Citrus'' × ''sinensis'' ** Orange blossom, its fragrant flower ** Orange juice *Orange (colour), the color of an orange fruit, occurs between red and yellow in the vi ...

, 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 Furosemide, sold under the brand name Lasix among others, is a loop diuretic medication used to treat edema due to heart failure, liver scarring, or kidney disease. Furosemide may also be used for the treatment of high blood pressure. It can ...

) 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 Anthranilate-based insect repellents include methyl anthranilate, dimethylanthranilic acid, ''N'',''N''-dimethylanthranilic acid (DMA), ethyl anthranilate (EA), and butyl anthranilate (BA). Chemically, they are esters of anthranilic acid. While the ...

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 Fenamic acid is an organic compound, which, especially in its ester form, is called fenamate. serves as a parent structure for several nonsteroidal anti-inflammatory drugs (NSAIDs), including mefenamic acid, tolfenamic acid, flufenamic acid, and ...

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 Classical Isosteres are molecules or ions with similar shape and often electronic properties. Many definitions are available. but the term is usually employed in the context of bioactivity and drug development. Such biologically-active compounds c ...

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 An active metabolite, or pharmacologically active metabolite is a biologically active metabolite of a xenobiotic substance, such as a drug or environmental chemical. Active metabolites may produce therapeutic effects, as well as harmful effects. ...

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 drug Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...

s, 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 Tolfenamic acid is a member of the anthranilic acid derivatives (or fenamate) class of NSAID drugs. Like other members of the class, it is a COX inhibitor and prevents formation of prostaglandins. It is used in the UK as a treatment for m ...

, flufenamic acid, and

meclofenamic acid Meclofenamic acid (used as meclofenamate sodium, brand name Meclomen) is a drug used for joint, muscular pain, arthritis and dysmenorrhea. It is a member of the anthranilic acid derivatives (or fenamate) class of nonsteroidal anti-inflammatory d ...

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 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 anthran ...

, or undergo diazonium coupling reactions such as in the synthesis of

methyl red Methyl red (2-(''N'',''N''-dimethyl-4-aminophenyl) azobenzenecarboxylic acid), also called C.I. Acid Red 2, is an indicator dye that turns red in acidic solutions. It is an azo dye, and is a dark red crystalline powder. Methyl red is a pH indica ...

. 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 Isatoic anhydride is an organic compound derived from anthranilic acid. A white solid, it is prepared by reaction of anthranilic acid with phosgene. Reactions Hydrolysis gives carbon dioxide and anthranilic acid. Alcoholysis proceeds similarly, ...

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

biaryl Biphenyl (also known as diphenyl, phenylbenzene, 1,1′-biphenyl, lemonene or BP) is an organic compound that forms colorless crystals. Particularly in older literature, compounds containing the functional group consisting of biphenyl less one ...

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 Methaqualone is a hypnotic sedative. It was sold under the brand names Quaalude ( ) and Sopor among others, which contained 300 mg of methaqualone, and sold as a combination drug under the brand name Mandrax, which contained 250 mg me ...

(Quaalude, Mandrax).

References

{{Amino acid metabolism intermediates