|Phenacetin Chemical Properties|
|Phenacetin Usage And Synthesis|
|Antipyretic analgesics||The antipyretic and analgesic effects of phenacetin are similar to that of acetylsalicylic acid, which is mainly used as anti-inflammatory drugs with a slow and long-lasting effect. It is an effective drug on the treatment of headache, neuralgia, joint pain and fever. However, it has a weak effect on treating anti-rheumatic, anti-inflammatory. Overdose can cause methemoglobinemia, resulting in hypoxia. Long-term medication can damage the kidneys, and even cause papillary necrosis, thus it should be taken with caution. Owing to its side effect and the rapid development of other similar drugs, the drug has been discontinued alone and just used as an active pharmaceutical ingredient for compound preparation with other drugs. It is often combined with aspirin, caffeine, for making aspirin compound (0.162 g of non-phenacetin, 0.227 g of aspirin, and 0.035 g of caffeine) for the treatment of colds with a small toxicity. Further addition of a small amount of the chlorpheniramine can produce chlorpheniramine cold tablets which can be applied to the treatment of colds, headache, neuralgia, rheumatism and so on. |
Phenacetin itself has no antipyretic analgesic effect in the body; it takes effect only after metabolically breakdown into acetaminophen (paracetamol) that is paracetamol. Its decomposition also produces dapsone ether, which not only has no antipyretic analgesic effect but also causes the non-main factors phenacetin side effects.
China has begun produced phenacetin since 1954. First produce nitrobenzene from ether reaction from nitro chlorobenzene and ethanol, and then reduce nitrobenzene into phenetidine to have acetylation reaction with acetic acid, and obtain the final product.
|Side Effects||Long-term taking of phenacetin-containing preparations can cause renal papillary necrosis, interstitial nephritis, renal pelvis and may even induce pelvis cancer and bladder cancer. Phenacetin can also easily lead to the formation of methemoglobin from hemoglobin, reducing the oxygen carrying capacity of the blood, thus causing cyanosis reaction. In addition, phenacetin can also cause hemolysis and hemolytic anemia, and have certain toxicity to retina. Long-term taking of phenacetin can also cause drug dependence. Foreign countries such as the United States, Britain, Germany, Japan and other countries have decided to cancel phenacetin, or stated that provision shall be marked on its packaging "can not be long-term use or large doses."|
Figure 1 Structure of Phenacetin
The above information is edited by the Chemicalbook of Dai Xiongfeng.
|Chemical property||White shiny flakes or white crystalline powder. Melting point: 137-138°C, Refractive index: 1.571. Insoluble in water, slightly soluble in ether and boiling water, soluble in alcohol and chloroform. No significant color when dissolved in concentrated sulfuric acid, nitric acid dropped into the solution causes orange yellow. Odorless and have a slightly bitter taste.
|Uses||1. Used for organic synthesis of raw materials and drug intermediates from acetaminophen ether. |
2. Antipyretic analgesics for the treatment of fever, headache, neuralgia.
3. Active pharmaceutical ingredient for Scientific Research.
|Methods of Production||(1) By acetylation reaction from a p-aminophenyl ether. Heat the mixture of benzene, acetic anhydride and amino benzene ether on an oil bath azeotropically for 4h. Then cool the reaction mixture after completion of the reaction, getting precipitate of statins. Filter, washed with cold benzene and then dry to get the final product. The yield usually can reach 86% of the theoretical amount. (2) By the reaction of sodium ethoxide and acetamidophenol: first add acetamidophenol into sodium ethoxide, and then slowly add ethyl iodide to heat and reflux for 1h, cool, filter, and the dissolve the crude product in ethanol. Filter and dilute the filtrate with water, and then cool, filter, and dried to obtain the final product. The yield can be 80% of the theoretical amount. At the first method, we can also use acetate instead of benzene as the solvent with the following process: heat 40% diluted acetic acid to boiling, add phenetidine and distill off the water. Add acetate when the temperature rise to 150 °C, reflux for 1h and continue to steam until the temperature rises above 150 °C, do sampling for determination of free amino benzene ether. Add certain amount of acetic anhydride based on the amount of residual phenetidine acetic anhydride, and the subject to reflux reaction for another 0.5h. Check the end, and reduce pressure if the product is qualified. Recycle acetate until the product contains 0.046 or less amino content and 0.2% or less acid. Press the reaction mixture back into the hot refined mother liquor, cool the mixture to 40 °C through stirring, filtrate and get the phenacetin crude product. For refining, add boiling water or refined mother liquor to phenacetin crude product, dissolve it through heated stirring, filter, and adjust the filtrate to pH = 4.5-4.7 with acid. Add activated carbon and sodium thiosulfates to stir for bleaching, filter and cool and crystal the filtrate liquid cooling crystallization, apply it to rejection filter, air dried to obtain phenacetin final product.
|Acute toxicity||Oral-rat LD50: 3600 mg/kg; Oral-Mouse LD50: 866 mg/kg.
|Inflammability and Hazardous Property||Fire combustible; thermally decomposed into toxic nitrogen oxide gases; Side effects: pale, liver damage, hemoglobin disorders.
|Storage Characteristics||Keep a ventilated, low-temperature and dry environment for storehouse; Store separately with reducing agents and food additives.
|Extinguishing agent||Water spray, foam, CO2, sand.|
|Chemical Properties||white crystalline powder|
|Usage||Analgesic, antipyretic. Component of APC tablets, analgesic mixture also containing aspirin and caffeine.
Phenacetin is reasonably anticipated to be a human carcinogen; analgesic mixtures containing Phenacetin are listed as known human carcinogens.|
|General Description||Odorless fine white crystalline solid with a lightly bitter taste. Used as an analgesic medicine.|
|Air & Water Reactions||Insoluble in water.|
|Reactivity Profile||Phenacetin react with oxidizing agents, iodine and nitrating agents.|
|Fire Hazard||Flash point data for Phenacetin are not available but Phenacetin is probably combustible.|
|Phenacetin Preparation Products And Raw materials|