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 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 R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxyl ...

and an

amine 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 Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent su ...

. As a result of containing both acidic and basic

functional group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the res ...

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. One type of amphoteric species are amphip ...

. 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 hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

. 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. : With amino acids, for example, in solution a chemical equilibrium w ...

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 vectors. In the monoclinic system, the crystal is described by vectors of unequal lengths, as in the orthorhombic ...

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 lattices result from stretching a cubic lattice along two of its orthogonal pairs by two different factors, resulting in a rectangular prism with ...

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

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 comm ...

, 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 fewer carbon atom. The reaction involves oxidation of the nitrogen followed by rearrangement of the carbonyl and nitrogen to g ...

of the amide group, induced by

hypochlorite In chemistry, hypochlorite is an anion 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 (a component of ble ...

: :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 sublimable white solid that is slightly soluble in water but more so upon addition of base. It is used as a precursor ...

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

indigo dye Indigo dye is an organic compound with a distinctive blue color. Historically, indigo was a natural dye extracted from the leaves of some plants of the ''Indigofera'' genus, in particular '' Indigofera tinctoria''; dye-bearing ''Indigofera'' p ...

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 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, indole d ...

by the action of

anthranilate synthase The enzyme anthranilate synthase () catalyzes the chemical reaction :chorismate + L-glutamine \rightleftharpoons anthranilate + pyruvate + L-glutamate Function Anthranilate synthase creates anthranilate, an important intermediate in the biosynthes ...

. 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 aromati ...

via the attachment of

phosphoribosyl pyrophosphate Phosphoribosyl pyrophosphate (PRPP) is a pentose phosphate. It is a biochemical intermediate in the formation of purine nucleotides via inosine-5-monophosphate, as well as in pyrimidine nucleotide formation. Hence it is a building block for DNA ...

to the amine group. After then, cyclization occurs to produce

indole Indole is an aromatic heterocyclic organic compound with the formula C8 H7 N. It has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indole is widely distributed in the natural environme ...

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- ...

s and

saccharin Saccharin (''aka'' saccharine, Sodium sacchari) is an artificial sweetener with effectively no nutritional value. It is about 550 times as sweet as sucrose but has a bitter or metallic aftertaste, especially at high concentrations. Saccharin ...

. It and its

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...

s are used in preparing

perfume Perfume (, ; french: parfum) is a mixture of fragrant essential oils or aroma compounds (fragrances), fixatives and solvents, usually in liquid form, used to give the human body, animals, food, objects, and living-spaces an agreeable scent. ...

s to mimic

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

and

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

, pharmaceuticals (

loop diuretic Loop diuretics are diuretics that act on the Na-K-Cl cotransporter along the thick ascending limb of the loop of Henle in the kidney. They are primarily used in medicine to treat hypertension and edema often due to congestive heart failure or ...

s, such as

furosemide Furosemide is a loop diuretic medication used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It may also be used for the treatment of high blood pressure. It can be taken by injection into a vein or by mout ...

) and UV-absorber as well as

corrosion inhibitor In chemistry, a corrosion inhibitor or anti-corrosive is a chemical compound that, when added to a liquid or gas, decreases the corrosion rate of a material, typically a metal or an alloy, that comes into contact with the fluid. The effectiveness ...

s for metals and

mold inhibitor Fungicides are biocidal chemical compounds or biological organisms used to kill parasitic fungi or their spores. A fungistatic inhibits their growth. Fungi can cause serious damage in agriculture, resulting in critical losses of yield, quality, ...

s in soy sauce.

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

have been proposed as replacements for

DEET ''N'',''N''-Diethyl-''meta''-toluamide, also called DEET () or diethyltoluamide, is the most common active ingredient in insect repellents. It is a slightly yellow oil intended to be applied to the skin or to clothing and provides protection ag ...

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 co ...

salicylic acid Salicylic acid is an organic compound with the formula HOC6H4CO2H. A colorless, bitter-tasting solid, it is a precursor to and a metabolite of aspirin (acetylsalicylic acid). It is a plant hormone, and has been listed by the EPA Toxic Substanc ...

, which is the

active metabolite An active metabolite is an active form of a drug after it has been processed by the body. Metabolites of drugs An active metabolite results when a drug is metabolized by the body into a modified form which continues to produce effects in the body ...

aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat in ...

. 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 anthranilic acid derivatives (or fenamate) class of nonsteroidal anti-inflammatory drugs (NSAIDs), and is used to treat mild to moderate pain. Its name derives from its systematic name, dimethylphenylaminobenz ...

tolfenamic acid Tolfenamic acid (Clotam, Tufnil) is a member of the anthranilic acid derivatives (or fenamate) class of NSAID drugs discovered by scientists at Medica Pharmaceutical Company in Finland. Like other members of the class, it is a COX inhibitor an ...

flufenamic acid Flufenamic acid (FFA) is a member of the anthranilic acid derivatives (or fenamate) class of nonsteroidal anti-inflammatory drugs (NSAIDs). Like other members of the class, it is a cyclooxygenase (COX) inhibitor, preventing the formation of pr ...

, 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 Diazonium compounds or diazonium salts are a group of organic compounds sharing a common functional group 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. General properti ...

₆H₄(CO₂H)(N₂)sup>+. This cation can be used to generate benzyne, dimerized to give

diphenic acid Diphenic 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 s ...

, 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 indi ...

. It reacts with

phosgene Phosgene is the organic chemical compound with the formula COCl2. It is a toxic, colorless gas; in low concentrations, its musty odor resembles that of freshly cut hay or grass. Phosgene is a valued and important industrial building block, es ...

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 met ...

(Quaalude, Mandrax).

References

{{Amino acid metabolism intermediates