Phloroglucinol

Phloroglucinol is a benzenetriol. It is an organic compound that is used in the synthesis of pharmaceuticals and explosives.

Austrian chemist Heinrich Hlasiwetz (1825-1875) is remembered for his chemical analysis of phloroglucinol.

Chemistry
This molecule exists in two forms, or tautomers, 1,3,5-trihydroxybenzene, which has phenol-like, and 1,3,5-cyclohexanetrione (phloroglucin), which has ketone-like character. These two tautomers are in equilibrium. Phloroglucinol is a useful intermediate because it is polyfunctional.



From water, phloroglucinol crystallizes as the dihydrate, which has a melting point of 116–117 °C, but the anhydrous form melts much higher, at 218–220 °C. It does not boil intact, but it does sublime.

Isolation
Phloroglucinol was originally isolated from bark of fruit trees.

Synthesis
It is synthesized via a number of processes, but representative is the following route from trinitrobenzene:
 * [[Image:Phlorosynth.png|600px]]

The synthesis is noteworthy because ordinary aniline derivatives are unreactive toward hydroxide. Because the triaminobenzene also exists as its imine tautomer, it is susceptible to hydrolysis.

Reactions
The compound behaves like a ketone in its reaction with hydroxylamine, forming the tris(oxime). But it behaves also like a benzenetriol (Ka1 = 3.56 × 10−9, Ka2 1.32×10−9), as the three hydroxyl groups can be methylated to give 1,3,5-trimethoxybenzene.

The Hoesch reaction allows the synthesis of 1-(2,4, 6-Trihydroxyphenyl)ethanone from phloroglucinol.

Leptospermone can be synthesized from phloroglucinol by a reaction with isovaleroylnitrile in the presence of a zinc chloride catalyst.

Natural occurrences
Phloroglucinols are secondary metabolites that occur naturally in certain plant species. For example, they (and sometimes their acyl dervatives) are present in the fronds of the coastal woodfern, Dryopteris arguta or in Dryopteris crassirhizoma. Formylated phloroglucinol compounds (euglobals, macrocarpals and sideroxylonals) can be found in Eucalyptus species. Hyperforin and adhyperforin are two phloroglucinols found in St John's wort. Humulone is a phloroglucinol derivative with three isoprenoid side-chains. Two side-chains are prenyl groups and one is an isovaleryl group. Humulone is a bitter-tasting chemical compound found in the resin of mature hops (Humulus lupulus).

Brown algae, such as species in the genus Zonaria, produce phloroglucinol derivatives. They also produce a type of tannins known as phlorotannins.

The bacterium Pseudomonas fluorescens produces phloroglucinol, phloroglucinol carboxylic acid and diacetylphloroglucinol.

Biosynthesis
In Pseudomonas fluorescens, cyclization of an activated 3,5-diketoheptanedioate leads to the formation of phloroglucinol.

The enzyme pyrogallol hydroxytransferase uses 1,2,3,5-tetrahydroxybenzene and 1,2,3-trihydroxybenzene (pyrogallol) to produce 1,3,5-trihydroxybenzene (phloroglucinol) and 1,2,3,5-tetrahydroxybenzene. It is found in the bacterium species Pelobacter acidigallici.

The legume-root nodulating, microsymbiotic nitrogen-fixing bacterium species Bradyrhizobium japonicum is able to degrade catechin with formation of phloroglucinol carboxylic acid, further decarboxylated to phloroglucinol, which is dehydroxylated to resorcinol and hydroxyquinol.

Phloretin hydrolase uses phloretin and water to produce phloretate and phloroglucinol.

Potential health effects
Phloroglucinols acylated derivatives have a fatty acid synthase inhibitory activity.

It is also used as a treatment for gallstones, spasmodic pain and other related gastrointestinal disorders. It has a non-specific spasmolytic action on the vessels, bronchi, intestine, ureters and gall bladder, and is used for treating disorders of these organs.

Applications
Phloroglucinol is mainly used as a coupling agent in printing. It links diazo dyes to give a fast black.

It is useful for the industrial synthesis of pharmaceuticals (Flopropione ) and explosives (TATB, trinitrophloroglucinol, 1,3,5-trinitrobenzene ).

Phloroglucinolysis is an analytical technique to study condensed tannins by means of depolymerisation. The reaction makes use of phloroglucinol as nucleophile. Phlobaphenes formation (tannins condensation and precipitation) can be minimized in using strong nucleophiles, such as phloroglucinol, during pine tannins extraction.