Acetanilide

Acetanilide
Names
	Preferred IUPAC name N-Phenylacetamide
	Other names Acetanilide; N-Phenylethanamide
Identifiers
CAS Number	103-84-4 ;
3D model (JSmol)	Interactive image;
Beilstein Reference	606468
ChEBI	CHEBI:28884 ;
ChEMBL	ChEMBL269644 ;
ChemSpider	880 ;
ECHA InfoCard	100.002.864
EC Number	203-150-7;
Gmelin Reference	82833
KEGG	C07565 ;
PubChem CID	904;
RTECS number	AD7350000;
UNII	SP86R356CC ;
CompTox Dashboard (EPA)	DTXSID2022543 ;
	InChI InChI=1S/C8H9NO/c1-7(10)9-8-5-3-2-4-6-8/h2-6H,1H3,(H,9,10) Key: FZERHIULMFGESH-UHFFFAOYSA-N ; InChI=1/C8H9NO/c1-7(10)9-8-5-3-2-4-6-8/h2-6H,1H3,(H,9,10) Key: FZERHIULMFGESH-UHFFFAOYAA;
	SMILES O=C(Nc1ccccc1)C;
Properties
Chemical formula	C8H9NO
Molar mass	135.166 g·mol−1
Odor	Odorless
Density	1.219 g/cm3
Melting point	113–115 °C (235–239 °F; 386–388 K)
Boiling point	304 °C (579 °F; 577 K)
Solubility in water	<0.56 g/100 mL (25 °C)
Solubility	Soluble in ethanol, diethyl ether, acetone, benzene
log P	1.16 (23 °C)
Vapor pressure	2 Pa (20 °C)
Acidity (pKa)	0.5 (25 °C, H2O) (conjugate acid)
Dipole moment	2.71
Hazards
	GHS labelling:
Pictograms
Signal word	Warning
Hazard statements	H302
Precautionary statements	P264, P270, P301+P312, P330, P501
Flash point	174 °C (345 °F; 447 K)
Autoignition; temperature	545 °C (1,013 °F; 818 K)
Safety data sheet (SDS)	External MSDS
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). verify (what is ?) Infobox references

Acetanilide is the organic compound with the formula C₆H₅NHC(O)CH₃. It is the N-acetylated derivative of aniline.^[7] It is an odourless solid chemical of leaf or flake-like appearance. It is also known as N-phenylacetamide, acetanil, or acetanilid, and was formerly known by the trade name Antifebrin.

Preparation and properties

Acetanilide can be produced by reacting acetic anhydride with aniline:^[7]

C₆H₅NH₂ + (CH₃CO)₂O → C₆H₅NHCOCH₃ + CH₃COOH

The preparation used to be a traditional experiment in introductory organic chemistry lab classes,^[8] but it has now been widely replaced by the preparation of either paracetamol or aspirin, both of which teach the same practical techniques (especially recrystallization of the product) but which avoid the use of aniline, a suspected carcinogen.

Acetanilide is slightly soluble in water, and stable under most conditions.^[5] Pure crystals are plate shaped and appear colorless, white, or in between.

Applications

Acetanilide is used as an inhibitor of hydrogen peroxide decomposition and is used to stabilize cellulose ester varnishes.^[7] It has also found uses in the intermediation in rubber accelerator synthesis, dyes and dye intermediate synthesis, and camphor synthesis.^[9] Acetanilide is used for the production of 4-acetamidobenzenesulfonyl chloride, a key intermediate for the manufacture of the sulfa drugs.^[10]

In the 19th century acetanilide was one of a large number of compounds used as experimental photographic developers.

Pharmaceutical use

Acetanilide was the first aniline derivative found to possess analgesic as well as antipyretic properties, and was quickly introduced into medical practice under the names of Antifebrin by A. Cahn and P. Hepp in 1886.^[11] But its (apparent) unacceptable toxic effects, the most alarming being cyanosis due to methemoglobinemia and ultimately liver and kidney damage,^[12] prompted the search for supposedly less toxic aniline derivatives such as phenacetin.^[13] After several conflicting results over the ensuing fifty years, it was established in 1948 that acetanilide was mostly metabolized to paracetamol (acetaminophen) in the human body, and that it was this metabolite that was responsible for the analgesic and antipyretic properties.^[12]^[14] The observed methemoglobinemia after acetanilide administration was ascribed to the small proportion of acetanilide that is hydrolyzed to aniline in the body.

References

^ ^a ^b "Front Matter". Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. p. 846. doi:10.1039/9781849733069-FP001. ISBN 978-0-85404-182-4. N-Phenyl derivatives of primary amides are called 'anilides' and may be named using the term 'anilide' in place of 'amide' in systematic or retained names of amides. (…) However, names expressing N-substitution by a phenyl group on an amide are preferred IUPAC names.
^ Haynes, William M., ed. (2016). CRC Handbook of Chemistry and Physics (97th ed.). CRC Press. pp. 5–88. ISBN 9781498754293.
^ Weast, Robert C., ed. (1981). CRC Handbook of Chemistry and Physics (62nd ed.). Boca Raton, FL: CRC Press. p. C-67. ISBN 0-8493-0462-8..
^ Acetanilide (PDF), SIDS Initial Assessment Report, Geneva: United Nations Environment Programme, September 2003.
^ ^a ^b "Safety data for acetanilide". Physical Chemistry Laboratory, University of Oxford. Archived from the original on 2002-06-23..
^ "HSNO Chemical Classification Information Database". New Zealand: Environmental Risk Management Authority. Archived from the original on October 13, 2022. Retrieved August 26, 2009.
^ ^a ^b ^c P. F. Vogt; J. J. Gerulis (2005). "Amines, Aromatic". Ullmann’s Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a02_037. ISBN 9783527303854.
^ See, e.g., The preparation of acetanilide from aniline, Department of Chemistry, University of the West Indies at Mona, Jamaica, retrieved 2009-08-26; Reeve, Wilkins; Lowe, Valerie C. (1979), "Preparation of Acetanilide from Nitrobenzene", J. Chem. Educ., 56 (7): 488, Bibcode:1979JChEd..56..488R, doi:10.1021/ed056p488: the latter preparation includes the reduction of nitrobenzene to aniline.
^ PubChem. "Acetanilide". pubchem.ncbi.nlm.nih.gov. Retrieved 2022-12-10.
^ Ashford's Dictionary of Industrial Chemicals (Third ed.). 2011. p. 33.
^ Cahn, A.; Hepp, P. (1886), "Das Antifebrin, ein neues Fiebermittel", Centralbl. Klin. Med., 7: 561–64.
^ ^a ^b Brodie, B. B.; Axelrod, J. (1948), "The estimation of acetanilide and its metabolic products, aniline, N-acetyl p-aminophenol and p-aminophenol (free and total conjugated) in biological fluids and tissues", J. Pharmacol. Exp. Ther., 94 (1): 22–28, PMID 18885610.
^ Bertolini, A.; Ferrari, A.; Ottani, A.; Guerzoni, S.; Tacchi, R.; Leone, S. (2006), "Paracetamol: new vistas of an old drug", CNS Drug Reviews, 12 (3–4): 250–75, doi:10.1111/j.1527-3458.2006.00250.x, PMC 6506194, PMID 17227290.
^
Multiple sources:
- Lester, D.; Greenberg, L. A. (1947), "Metabolic fate of acetanilide and other aniline derivatives. II. Major metabolites of acetanilide in the blood", J. Pharmacol. Exp. Ther., 90 (1): 68–75, PMID 20241897.
- Brodie, B. B.; Axelrod, J. (1948), "The fate of acetanilide in man" (PDF), J. Pharmacol. Exp. Ther., 94 (1): 29–38, PMID 18885611
- Flinn, Frederick B.; Brodie, Bernard B. (1948), "The effect on the pain threshold of N-acetyl p-aminophenol, a product derived in the body from acetanilide", J. Pharmacol. Exp. Ther., 94 (1): 76–77, PMID 18885618.

External links

NileRed (May 21, 2017). "Making an old pain and fever medication" by NileRed. YouTube.

[iupac2013-1] "Front Matter". Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. p. 846. doi:10.1039/9781849733069-FP001. ISBN 978-0-85404-182-4. N-Phenyl derivatives of primary amides are called 'anilides' and may be named using the term 'anilide' in place of 'amide' in systematic or retained names of amides. (…) However, names expressing N-substitution by a phenyl group on an amide are preferred IUPAC names.

[CRC97-2] Haynes, William M., ed. (2016). CRC Handbook of Chemistry and Physics (97th ed.). CRC Press. pp. 5–88. ISBN 9781498754293.

[3] Weast, Robert C., ed. (1981). CRC Handbook of Chemistry and Physics (62nd ed.). Boca Raton, FL: CRC Press. p. C-67. ISBN 0-8493-0462-8..

[SIDS-4] Acetanilide (PDF), SIDS Initial Assessment Report, Geneva: United Nations Environment Programme, September 2003.

[MSDS-5] "Safety data for acetanilide". Physical Chemistry Laboratory, University of Oxford. Archived from the original on 2002-06-23..

[6] "HSNO Chemical Classification Information Database". New Zealand: Environmental Risk Management Authority. Archived from the original on October 13, 2022. Retrieved August 26, 2009.

[Ullmann-7] P. F. Vogt; J. J. Gerulis (2005). "Amines, Aromatic". Ullmann’s Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a02_037. ISBN 9783527303854.

[8] See, e.g., The preparation of acetanilide from aniline, Department of Chemistry, University of the West Indies at Mona, Jamaica, retrieved 2009-08-26; Reeve, Wilkins; Lowe, Valerie C. (1979), "Preparation of Acetanilide from Nitrobenzene", J. Chem. Educ., 56 (7): 488, Bibcode:1979JChEd..56..488R, doi:10.1021/ed056p488: the latter preparation includes the reduction of nitrobenzene to aniline.

[9] PubChem. "Acetanilide". pubchem.ncbi.nlm.nih.gov. Retrieved 2022-12-10.

[10] Ashford's Dictionary of Industrial Chemicals (Third ed.). 2011. p. 33.

[11] Cahn, A.; Hepp, P. (1886), "Das Antifebrin, ein neues Fiebermittel", Centralbl. Klin. Med., 7: 561–64.

[Ax&Brodie-12] Brodie, B. B.; Axelrod, J. (1948), "The estimation of acetanilide and its metabolic products, aniline, N-acetyl p-aminophenol and p-aminophenol (free and total conjugated) in biological fluids and tissues", J. Pharmacol. Exp. Ther., 94 (1): 22–28, PMID 18885610.

[pmid17227290-13] Bertolini, A.; Ferrari, A.; Ottani, A.; Guerzoni, S.; Tacchi, R.; Leone, S. (2006), "Paracetamol: new vistas of an old drug", CNS Drug Reviews, 12 (3–4): 250–75, doi:10.1111/j.1527-3458.2006.00250.x, PMC 6506194, PMID 17227290.

[14] Multiple sources:
Lester, D.; Greenberg, L. A. (1947), "Metabolic fate of acetanilide and other aniline derivatives. II. Major metabolites of acetanilide in the blood", J. Pharmacol. Exp. Ther., 90 (1): 68–75, PMID 20241897.

Brodie, B. B.; Axelrod, J. (1948), "The fate of acetanilide in man" (PDF), J. Pharmacol. Exp. Ther., 94 (1): 29–38, PMID 18885611

Flinn, Frederick B.; Brodie, Bernard B. (1948), "The effect on the pain threshold of N-acetyl p-aminophenol, a product derived in the body from acetanilide", J. Pharmacol. Exp. Ther., 94 (1): 76–77, PMID 18885618.

[15] Lester, D.; Greenberg, L. A. (1947), "Metabolic fate of acetanilide and other aniline derivatives. II. Major metabolites of acetanilide in the blood", J. Pharmacol. Exp. Ther., 90 (1): 68–75, PMID 20241897.

[16] Brodie, B. B.; Axelrod, J. (1948), "The fate of acetanilide in man" (PDF), J. Pharmacol. Exp. Ther., 94 (1): 29–38, PMID 18885611

[17] Flinn, Frederick B.; Brodie, Bernard B. (1948), "The effect on the pain threshold of N-acetyl p-aminophenol, a product derived in the body from acetanilide", J. Pharmacol. Exp. Ther., 94 (1): 76–77, PMID 18885618.

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