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| Names | |
|---|---|
| Preferred IUPAC name 4-Hydroxybenzoic acid | |
| Other names p-Hydroxybenzoic acid para-Hydroxybenzoic acid PHBA 4-hydroxybenzoate | |
| Identifiers | |
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3D model (JSmol) | |
| ChEBI | |
| ChEMBL | |
| ChemSpider |
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| DrugBank |
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| ECHA InfoCard | 100.002.550 |
| EC Number |
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| KEGG |
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| UNII | |
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| Properties | |
| C7H6O3 | |
| Molar mass | 138.122 g·mol−1 |
| Appearance | White crystalline solid |
| Odor | Odorless |
| Density | 1.46 g/cm3 |
| Melting point | 214.5 °C (418.1 °F; 487.6 K) |
| Boiling point | N/A, decomposes[1] |
| 0.5 g/100 mL | |
| Solubility |
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| logP | 1.58 |
| Acidity (pKa) | 4.54 |
| Hazards | |
| Occupational safety and health (OHS/OSH): | |
Main hazards | Irritant |
| NFPA 704 (fire diamond) | |
| 250 °C (482 °F; 523 K) | |
| Lethal dose or concentration (LD, LC): | |
LD50 (median dose) | 2200 mg/kg (oral, mouse) |
| Safety data sheet (SDS) | HMDB |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
4-Hydroxybenzoic acid, also known asp-hydroxybenzoic acid (PHBA), is amonohydroxybenzoic acid, a phenolic derivative of benzoic acid. It is a white crystalline solid that is slightly soluble in water andchloroform but more soluble in polar organic solvents such asalcohols andacetone. 4-Hydroxybenzoic acid is primarily known as the basis for the preparation of itsesters, known asparabens, which are used as preservatives in cosmetics and some ophthalmic solutions. It isisomeric with 2-hydroxybenzoic acid, known assalicylic acid, a precursor toaspirin, and with3-hydroxybenzoic acid.
It is found in plants of the genusVitex such asV. agnus-castus orV. negundo, and inHypericum perforatum (St John's wort). It is also found inSpongiochloris spongiosa, a freshwater green alga.
The compound is also found inGanoderma lucidum, amedicinal mushroom with the longest record of use.
Cryptanaerobacter phenolicus is a bacterium species that producesbenzoate fromphenol via 4-hydroxybenzoate.[2]
4-Hydroxybenzoic acid can be found naturally incoconut.[3] It is one of the main catechinsmetabolites found in humans after consumption ofgreen tea infusions.[4] It is also found inwine,[5] invanilla, inMacrotyloma uniflorum (horse gram),carob[6] and inPhyllanthus acidus (Otaheite gooseberry).
Açaí oil, obtained from the fruit of theaçaí palm (Euterpe oleracea), is rich inp-hydroxybenzoic acid (892±52 mg/kg).[7] It is also found incloudy olive oil[citation needed] and in the edible mushroomRussula virescens (green-cracking russula).[citation needed]
p-Hydroxybenzoic acid glucoside can be found in mycorrhizal and non-mycorrhizal roots of Norway spruces (Picea abies).[8]
Violdelphin is an anthocyanin, a type of plant pigments, found in blue flowers and incorporating twop-hydroxybenzoic acid residues, onerutinoside and twoglucosides associated with adelphinidin.
Agnuside is the ester ofaucubin andp-hydroxybenzoic acid.[9]
Chorismate lyase is an enzyme that transformschorismate into 4-hydroxybenzoate and pyruvate. This enzyme catalyses the first step inubiquinone biosynthesis inEscherichia coli and other Gram-negative bacteria.
Benzoate 4-monooxygenase is an enzyme that utilizesbenzoate, NADPH, H+ and O2 to produce 4-hydroxybenzoate, NADP+ and H2O. This enzyme can be found inAspergillus niger.
4-Hydroxybenzoate also arises from tyrosine.[10]
The enzyme4-methoxybenzoate monooxygenase (O-demethylating) transforms4-methoxybenzoate, an electron acceptor AH2 and O2 into 4-hydroxybenzoate, formaldehyde, the reduction product A and H2O. This enzyme participates in2,4-dichlorobenzoate degradation inPseudomonas putida.
The enzyme4-hydroxybenzaldehyde dehydrogenase uses4-hydroxybenzaldehyde, NAD+ and H2O to produce 4-hydroxybenzoate, NADH and H+. This enzyme participates intoluene andxylene degradation in bacteria such asPseudomonas mendocina. It is also found in carrots (Daucus carota).
The enzyme that2,4'-dihydroxyacetophenone dioxygenase transforms2,4'-dihydroxyacetophenone and O2 into 4-hydroxybenzoate andformate. This enzyme participates inbisphenol A degradation. It can be found inAlcaligenes species.
The enzyme4-chlorobenzoate dehalogenase uses4-chlorobenzoate and H2O to produce 4-hydroxybenzoate andchloride. It can be found inPseudomonas species.
The enzyme4-hydroxybenzoyl-CoA thioesterase utilizes4-hydroxybenzoyl-CoA and H2O to produce 4-hydroxybenzoate and CoA. This enzyme participates in2,4-dichlorobenzoate degradation. It can be found inPseudomonas species.
The enzyme4-hydroxybenzoate polyprenyltransferase uses a polyprenyl diphosphate and 4-hydroxybenzoate to produce diphosphate and4-hydroxy-3-polyprenylbenzoate. This enzyme participates inubiquinone biosynthesis.
The enzyme4-hydroxybenzoate geranyltransferase utilizesgeranyl diphosphate and 4-hydroxybenzoate to produce3-geranyl-4-hydroxybenzoate and diphosphate. Biosynthetically,alkannin is produced in plants from the intermediates 4-hydroxybenzoic acid andgeranyl pyrophosphate. This enzyme is involved inshikonin biosynthesis. It can be found inLithospermum erythrorhizon.
The enzyme3-hydroxybenzoate—CoA ligase uses ATP,3-hydroxybenzoate and CoA to produce AMP, diphosphate and3-hydroxybenzoyl-CoA. The enzyme works equally well with 4-hydroxybenzoate. It can be found inThauera aromatica.
The enzyme4-hydroxybenzoate 1-hydroxylase transforms 4-hydroxybenzoate, NAD(P)H, 2 H+ and O2 intohydroquinone, NAD(P)+, H2O and CO2. This enzyme participates in2,4-dichlorobenzoate degradation. It can be found inCandida parapsilosis.
The enzyme4-hydroxybenzoate 3-monooxygenase transforms 4-hydroxybenzoate, NADPH, H+ and O2 intoprotocatechuate, NADP+ and H2O. This enzyme participates inbenzoate degradation via hydroxylation and2,4-dichlorobenzoate degradation. It can be found inPseudomonas putida andPseudomonas fluorescens.
The enzyme4-hydroxybenzoate 3-monooxygenase (NAD(P)H) utilizes 4-hydroxybenzoate, NADH, NADPH, H+ and O2 to produce 3,4-dihydroxybenzoate (protocatechuic acid), NAD+, NADP+ and H2O. This enzyme participates inbenzoate degradation via hydroxylation and2,4-dichlorobenzoate degradation. It can be found inCorynebacterium cyclohexanicum and inPseudomonas sp.
The enzyme4-hydroxybenzoate decarboxylase uses 4-hydroxybenzoate to producephenol and CO2. This enzyme participates inbenzoate degradation viacoenzyme A (CoA) ligation. It can be found inKlebsiella aerogenes (Aerobacter aerogenes).
The enzyme4-hydroxybenzoate—CoA ligase transforms ATP, 4-hydroxybenzoate and CoA to produce AMP, diphosphate and4-hydroxybenzoyl-CoA. This enzyme participates inbenzoate degradation via CoA ligation. It can be found inRhodopseudomonas palustris.
Coniochaeta hoffmannii is a plant pathogen that commonly inhabits fertile soil. It is known to metabolize aromatic compounds of low molecular weight, such asp-hydroxybenzoic acid.
The enzyme4-hydroxybenzoate 4-O-beta-D-glucosyltransferase transformsUDP-glucose and 4-hydroxybenzoate into UDP and4-(beta-D-glucosyloxy)benzoate. It can be found in the pollen ofPinus densiflora.
TheHammett equation describes a linear free-energy relationship relating reaction rates and equilibrium constants for many reactions involving benzoic acid derivatives with meta- and para-substituents.
4-Hydroxybenzoic acid is produced commercially from potassiumphenoxide andcarbon dioxide in theKolbe-Schmitt reaction.[11] It can also be produced in the laboratory by heatingpotassium salicylate withpotassium carbonate to 240 °C, followed by treating with acid.[12]
4-Hydroxybenzoic acid has about one tenth the acidity ofbenzoic acid, having anacid dissociation constantKa =3.3×10−5 M at 19 °C.[citation needed] Its acid dissociation follows this equation:
Vectran is a manufactured fiber, spun from aliquid crystal polymer. Chemically it is an aromatic polyester produced by the polycondensation of 4-hydroxybenzoic acid and6-hydroxynaphthalene-2-carboxylic acid. The fiber has been shown to exhibit strong radiation shielding used byBigelow Aerospace and produced byStemRad.[13]
4,4′-Dihydroxybenzophenone is generally prepared by the rearrangement ofp-hydroxyphenylbenzoate. Alternatively,p-hydroxybenzoic acid can be converted top-acetoxybenzoyl chloride. This acid chloride reacts with phenol to give, after deacetylation, 4,4′-dihydroxybenzophenone.
Examples of drugs made from PHBA includenifuroxazide,orthocaine,ormeloxifene andproxymetacaine.
4-Hydroxybenzoic acid is a popular antioxidant in part because it is rather nontoxic. TheLD50 is 2200 mg/kg in mice (oral).[14]
4-Hydroxybenzoic acid has weakestrogenic activity bothin vitro andin vivo,[15] and stimulates the growth of humanbreast cancer cell lines.[16][17] It is a common metabolite ofparabenesters, such asmethylparaben.[15][16][17] The compound is a relatively weak estrogen, but can produceuterotrophy with sufficient doses to an equivalent extent relative toestradiol, which is unusual for a weakly estrogenic compound and indicates that it may be afull agonist of theestrogen receptor with relatively lowbinding affinity for the receptor.[16][18][19] It is about 0.2% to 1% as potent as an estrogen as estradiol.[18]
4-Hydroxybenzoic acid has been used as a precursor to co-enzyme Q10 as an experimental treatment for mitochondrial encephalopathy caused by an inherited deficiency in 4-hydroxyphenylpyruvate dioxygenase-like protein.[20]
