Anthranilic acid is an aromatic acid with the formula C₆H₄(NH₂)(CO₂H) and has a sweetish taste. The molecule consists of a benzene ring, ''ortho''-substituted with a carboxylic acid 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 Hydrogen is the chemical element wi ...

. 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 re ...

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 amphipro ...

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

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 s ...

crystal structure with space group P2₁. It is triboluminescent. Above , 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.

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

in aqueous sodium hydroxide, followed by neutralization. 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.

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. 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 aromatic ...

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 DN ...

to the

amine group 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 ...

. After then, cyclization occurs to produce

indole Indole is an aromatic heterocyclic organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other c ...

Uses

Industrially, anthranilic acid is an intermediate in the production of azo dyes 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 is ...

. 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 a ...

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. Th ...

s to mimic jasmine 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 ...

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 m ...

) 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 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
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 ...

of salicylic acid, which is the active metabolite of

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 inc ...

. 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, dimethylphenylaminoben ...

, tolfenamic acid,

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 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 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 to give isatoic anhydride, a versatile reagent.

Chlorination Chlorination may refer to: * Chlorination reaction In chemistry, halogenation is a chemical reaction that entails the introduction of one or more halogens into a compound. Halide-containing compounds are pervasive, making this type of transform ...

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 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