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.

4-Hydroxybenzoic acid

Names
Preferred IUPAC name 4-Hydroxybenzoic acid
Other names p-Hydroxybenzoic acid para-Hydroxybenzoic acid PHBA 4-hydroxybenzoate
Identifiers
CAS Number	99-96-7 Y
3D model (JSmol)	Interactive image Interactive image
ChEBI	CHEBI:30763 Y
ChEMBL	ChEMBL441343 Y
ChemSpider	132 Y
DrugBank	DB04242 Y
ECHA InfoCard	100.002.550
EC Number	202-804-9
IUPHAR/BPS	5783
KEGG	C00156 Y
PubChemCID	135
UNII	JG8Z55Y12H Y
CompTox Dashboard(EPA)	DTXSID3026647
InChI InChI=1S/C7H6O3/c8-6-3-1-5(2-4-6)7(9)10/h1-4,8H,(H,9,10) Y Key: FJKROLUGYXJWQN-UHFFFAOYSA-N Y InChI=1/C7H6O3/c8-6-3-1-5(2-4-6)7(9)10/h1-4,8H,(H,9,10) Key: FJKROLUGYXJWQN-UHFFFAOYAQ
SMILES O=C(O)c1ccc(O)cc1 c1cc(ccc1C(=O)O)O
Properties
Chemical formula	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]
Solubility in water	0.5 g/100 mL
Solubility	Soluble inalcohol,ether,acetone Slightly soluble inchloroform Negligibly inCS2
logP	1.58
Acidity (pKa)	4.54
Hazards
Occupational safety and health (OHS/OSH):
Main hazards	Irritant
NFPA 704 (fire diamond)	2 0 0
Autoignition temperature	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). Y verify (what is YN ?) Infobox references

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 constantK_a =3.3×10⁻⁵ M at 19 °C.^{[citation needed]} Its acid dissociation follows this equation:

HOC₆H₄CO₂H ⇌HOC₆H₄CO−2 +H⁺

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 of its low toxicity. TheLD₅₀ is 2200 mg/kg in mice (oral).^[14]

4-Hydroxybenzoic acid hasestrogenic 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]

• Phenolic content in tea
• Phenolic content in wine

4-Hydroxybenzoic acid atPhenol-Explorer.eu