Paracetamol
| Chemical formula | C8H9NO2 |
|---|---|
| Molar Mass(g/mol) | 151.17 |
| Density(g/cc) | 1.263 |
| Melting Point(°C) | 169 |
| Solubility in water(g/L) | 12.78 |
| NFPA 704 |  0
0
0
|
Uses
Primary
- Pharm: used in the medication paracetamol on the WHO LEM, WHO IEHK, DHS AMF, and EMS lists
Production
Synthesis
from 4-aminophenol
The main production methods differ over the method of acetylation
via acetic anhydride
Paraphrasing from his book[2]
Combine 4-aminophenol with acetic anhydride giving paracetamol
- 2 HO-C6H4-NH2 + (CH3CO)2O → 2 HO-C6H4-NH-COCH3 + H2O
via glacial acetic acid
Intermix the 4-aminophenol and glacial acetic acid at 115-120°C in a refluxing apparatus that distills off the water at the top.[3]
clay-promoted acetylation
Combine 4-aminophenol with glacial acetic acid in an Fe3+ (basic iron acetate?) enriched clay and mix at 160°C for 6 hours [4]
from 4-nitrophenol
The reduction and acylation steps are performed simultaneously
via tin/acid
Combine acetic acid, tin, and 4-nitrophenol
- O2NC6H4OH + 5 CH3COOH + 2 Sn → CH3COONHC6H4OH + 2 H2O + 2 Sn(CH3COO)2
via thioacetates
Combine 4-nitrophenol and potassium thioacetate.[5]
from hydroquinone
In 2014 a "one-pot" synthesis from hydroquinone has been described before the Royal Society of Chemistry.[6] The process may be summarized as follows:
- Hydroquinone, ammonium acetate, and acetic acid were mixed in an argon atmosphere and heated slowly to 230 °C. The mixture was stirred at this temperature for 15 hours. After cooling the acetic acid was evaporated and the precipitate was filtered, washed with water and dried to give paracetamol as a white solid.
The authors go on to claim an 88% yield and 99% purity.
See Also
References
- ↑ Wikipedia page
- ↑ Ellis, Frank (2002) "Paracetamol: a curriculum resource".
Royal Society of Chemistry, Cambridge, UK
ISBN: 0-85404-375-6 - ↑ US patent 9102589 "Reactive distillation process for preparation of acetaminophen", 2010
Link courtesy Google - ↑ US patent 6215024B1 "Process for the production of amides from amines", 1999
Link courtesy Google - ↑ "One-step reductive amidation of nitro arenes: application in the synthesis of Acetaminophen"
Tetrahedron Letters 47; pp1861-1864.
DOI:10.1016/j.tetlet.2005.09.196 - ↑ Joncour, Roxan; Duguet, Nicolas; Métay, Estelle; Ferreira, Amadéo; Lemaire, Marc (2014) "Amidation of phenol derivatives: a direct synthesis of paracetamol (acetaminophen) from Hydroquinone"
Green Chem. 16(6); pp2997–3002.
DOI:10.1039/C4GC00166D
link courtesy Royal Society of Chemistry (UK).