4-Aminophenol

4-Aminophenol

Names
Preferred IUPAC name 4-Aminophenol [1]
Other names p-Aminophenol para-Aminophenol
Identifiers
CAS Number	123-30-8  Y
3D model (JSmol)	Interactive image Interactive image
Beilstein Reference	385836
ChEBI	CHEBI:17602  Y
ChEMBL	ChEMBL1142  Y
ChemSpider	392  Y
ECHA InfoCard	100.004.198
EC Number	204-616-2
Gmelin Reference	2926
KEGG	C02372  Y
MeSH	Aminophenols
PubChem CID	403
UNII	R7P8FRP05V  Y
UN number	2512
CompTox Dashboard (EPA)	DTXSID3024499
InChI InChI=1S/C6H7NO/c7-5-1-3-6(8)4-2-5/h1-4,8H,7H2 Y Key: PLIKAWJENQZMHA-UHFFFAOYSA-N Y InChI=1/C6H7NO/c7-5-1-3-6(8)4-2-5/h1-4,8H,7H2 Key: PLIKAWJENQZMHA-UHFFFAOYAD
SMILES Oc1ccc(N)cc1 c1cc(ccc1N)O
Properties
Chemical formula	C6H7NO
Molar mass	109.128 g·mol−1
Appearance	Colorless to reddish-yellow crystals
Density	1.13 g/cm3
Melting point	187.5 °C (369.5 °F; 460.6 K)
Boiling point	284 °C (543 °F; 557 K)
Solubility in water	1.5 g/100 mL
Solubility	Very soluble in dimethylsulfoxide Soluble in acetonitrile, ethyl acetate, and acetone Slightly soluble in toluene, diethyl ether, and ethanol Negligible solubility in benzene and chloroform
log P	0.04
Acidity (pKa)	5.48 (amino; H2O) 10.30 (phenol; H2O) [2]
Structure
Crystal structure	orthorhombic
Thermochemistry
Std enthalpy of formation (ΔfH⦵298)	−190.6 kJ/mol
Hazards
GHS labelling:
Pictograms
Signal word	Warning
Hazard statements	H302, H332, H341, H410
Precautionary statements	P201, P202, P261, P264, P270, P271, P273, P281, P301+P312, P304+P312, P304+P340, P308+P313, P312, P330, P391, P405, P501
NFPA 704 (fire diamond)	2 1 0
Flash point	195 °C (383 °F; 468 K) (cc)
Lethal dose or concentration (LD, LC):
LD50 (median dose)	671 mg/kg
Related compounds
Related aminophenols	2-Aminophenol 3-Aminophenol
Related compounds	Aniline Phenol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Y  verify  (what is  YN ?) Infobox references

4-Aminophenol (or para-aminophenol or p-aminophenol) is an organic compound with the formula H₂NC₆H₄OH. It is a metabolite of acetaminophen which the body converts to N-arachidonoylphenolamine and this compound is responsible for all or part of acetaminophen's analgesic action ^[3] and anticonvulsant effects. ^[4] .

Commercially available as a white powder, ^[5] it is commonly used as a developer for black-and-white film, marketed under the name Rodinal.

Reflecting its slightly hydrophilic character, the white powder is moderately soluble in alcohols and can be recrystallized from hot water. In the presence of a base, it oxidizes readily. The methylated derivatives N-methylaminophenol and N,N-dimethylaminophenol are of commercial value.

The compound is one of three isomeric aminophenols, the other two being 2-aminophenol and 3-aminophenol.

Preparation

4-Aminophenol can be prepared by several routes. One route is hydrogenation of 4-nitrophenol over Raney nickel. ^[6]

HOC₆H₄NO₂ + 3 H₂ → HOC₆H₄NH2 + 2 H₂O

The nitrophenol can also be reduced by iron or by stannous chloride. ^{[7] [8]}

4-Aminophenol can be produced by reduction of nitrobenzene via the intermediate phenylhydroxylamine, which spontaneously rearranges to 4-aminophenol. ^{[9] [6]}

C₆H₅NHOH → HOC₆H₄NH₂

Uses

4-Aminophenol is a building block used in organic chemistry. Prominently, it is the final intermediate in the industrial synthesis of paracetamol. Treating 4-aminophenol with acetic anhydride gives paracetamol: ^{[10] [11] [12]}

It is a precursor to amodiaquine, mesalazine, AM404, parapropamol, B-86810 & B-87836 (cf. WO 2001042204  ).

4-Aminophenol converts readily to the diazonium salt. ^[13]

References

1. Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. p. 690. doi:10.1039/9781849733069-FP001. ISBN   978-0-85404-182-4.
2. Haynes, William M., ed. (2016). CRC Handbook of Chemistry and Physics (97th ed.). CRC Press. pp. 5–89. ISBN   978-1498754286.
3. Ottani A, Leone S, Sandrini M, Ferrari A, Bertolini A (February 2006). "The analgesic activity of paracetamol is prevented by the blockade of cannabinoid CB1 receptors". European Journal of Pharmacology. 531 (1–3): 280–281. doi:10.1016/j.ejphar.2005.12.015. PMID   16438952.
4. Deshpande LS, DeLorenzo RJ (January 2011). "Acetaminophen inhibits status epilepticus in cultured hippocampal neurons". NeuroReport. 22 (1): 15–18. doi:10.1097/WNR.0b013e3283413231. PMC   3052417 . PMID   21037491.
5. CRC Handbook of Chemistry and Physics 65th Ed.
6. Mitchell, Stephen C.; Waring, Rosemary H. (2000). "Aminophenols". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a02_099. ISBN   978-3-527-30385-4.
7. US2998450A,Godfrey, Wilbert&De, Angelis John,"Process of preparing nu-acetyl-p-amino phenol",issued 1961-08-29 
8. Bellamy, F. D.; Ou, K. (1984-01-01). "Selective reduction of aromatic nitro compounds with stannous chloride in non acidic and non aqueous medium" . Tetrahedron Letters. 25 (8): 839–842. doi:10.1016/S0040-4039(01)80041-1. ISSN   0040-4039.
9. Polat, K.; Aksu, M.L.; Pekel, A.T. (2002), "Electroreduction of nitrobenzene to p-aminophenol using voltammetric and semipilot scale preparative electrolysis techniques", Journal of Applied Electrochemistry, 32 (2), Kluwer Academic Publishers: 217–223, doi:10.1023/A:1014725116051, S2CID   54499902
10. Ellis, Frank (2002). Paracetamol: a curriculum resource. Cambridge: Royal Society of Chemistry. ISBN   0-85404-375-6.
11. Anthony S. Travis (2007). "Manufacture and uses of the anilines: A vast array of processes and products". In Zvi Rappoport (ed.). The chemistry of Anilines Part 1 . Wiley. p.  764. ISBN   978-0-470-87171-3.
12. Elmar Friderichs; Thomas Christoph; Helmut Buschmann. "Analgesics and Antipyretics". Ullmann's Encyclopedia of Industrial Chemistry . Weinheim: Wiley-VCH. doi:10.1002/14356007.a02_269.pub2. ISBN   978-3-527-30673-2.
13. F. B. Dains, Floyd Eberly (1935). "p-Iodophenol". Organic Syntheses. 15: 39. doi:10.15227/orgsyn.015.0039.