Phenacetin

Phenacetin may be conveniently prepared in the laboratory from p-amino-phenol. The latter is readily acetylated with acetic anhydride to give p-acetyl-aminophenol this Is ethylated in the form of the sodio derivative to yield acetyl p-phenetidine (phenacetin)  

Phenacetiii may also be prepared by acetylation of the commercially available p phenetidine  

Suspend 11 g. of p-aminophenol in 30 ml. of water contained in a 250 ml. beaker or conical flask and add 12 ml. of acetic anhydride. Stir (or shake) the mixture vigorously and warm on a water bath. The solid dissolves. After 10 minutes, cool, filter the solid acetyl derivative at the pump and wash with a little cold water. Recrystallise from hot water (about 75 ml.) and dry upon filter paper in the air. The yield of p-acetylaminophenol, m.p. 169° (1), is 14 g. 

Place 1 55 g. of clean sodium in a 250 ml. round-bottomed flask equipped with a reflux condenser. Add 40 ml. of absolute alcohol (or rectified spirit). If all the sodium has not disappeared after the vigorous reaction has subsided, warm the flask on a water bath until solution is complete. Cool the mixture and add 10 g. of p-acetylaminophenol. Introduce 15 g. (8 ml.) of ethyl iodide slowly through the condenser and reflux the mixture for 45-60 minutes. Pour 100 ml. of water through the condenser at such a rate that the crystalline product does not separate if crystals do separate, reflux the mixture until they dissolve. Then cool the flask in an ice bath collect the crude phenacetin with suction and wash with a little cold water. Dissolve the crude product in 80 ml. of rectified spirit if the solution is coloured, add 2 g. of decolourising carbon and filter. Treat the clear solution with 125 ml. of hot water and allow to cool. Collect the pure phenacetin at the pump and dry in the air. The yield is 9-5 g., m.p. 137°. 

Dissolve 14 g. of p-phenetidine (2) in 240 ml. of water to which 20 ml. of 5N hydrochloric acid (or 9 ml. of the concentrated acid) have been added stir the solution with about 5 g. of decolourising carbon for 5 minutes, warm, and filter the solution with suction. Transfer the cold filtered solution of p-phenetidine hydrochloride to a 700 ml. conical flask, add 13 g. (12 ml.) of acetic anhydride and swirl the contents to dissolve the anhydride. Immediately add a solution of 16 g. of crystallised sodium acetate in 50 ml. of water and stir (or swirl) the contents of the flask vigorously. Cool the reaction mixture in an ice bath, filter with suction and wash with cold water. RecrystaUise from hot water (with the addition of a little decolourising carbon, if necessary), filter and dry. The yield of pure phenacetin, m.p. 137°, is 12 g. 

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It is used as a dyestuffs intermediate. Its acetyl derivative is phenacetin. 

Acetyl-o-aniaidine Acetyl-m-anisidine Acetyl-p-anisldine Acetyl-o-phenetidine Acetyl-m-phenetidine Acetyl-p-phenetidine (or phenacetin) Acetyl-a-naph thy lam ine Acetyl- p-naphthylamine... 

The p-phenetidine is usually coloured and the procedure given permits a preliminary treatment with decolourising carbon, thus leading to an almo.st colourless phenacetin directly. 

The analysis of APC tablets (a mixture of aspirin, phenacetin, and caffeine) has been a common undergraduate laboratory experiment. This experiment describes modifications to the standard analysis for APC tablets in which paracetamol (also known as acetaminophen) replaces phenacetin. 

This experiment focuses on developing an HPLG separation capable of distinguishing acetylsalicylic acid, paracetamol, salicylamide, caffeine, and phenacetin. A Gjg column and UV detection are used to obtain chromatograms. Solvent parameters used to optimize the separation include the pH of the buffered aqueous mobile phase, the %v/v methanol added to the aqueous mobile phase, and the use of tetrabutylammonium phosphate as an ion-pairing reagent. 

Ethoxyacetanilide. This compound (22), also known as phenacetin, is a white crystalline powder. The compound is odorless and has a slightly bitter taste. It is sparingly soluble in cold water and more soluble in hot water, ethanol, diethyl ether, and chloroform. At relative humidities between 15 and 90% the equiUbtium moisture content is about 2% (25°C). 

Acetophenetidine (phenacetin) [62-44-2] M 179.2, m 136 . Crystd from H2O or purifred by soln in cold dilute alkali and reppted by addn of acid to neutralisation point. Air-dried. 

A synthesis of the analgesic substance phenacetin is outlined in the following equation. What is the structure of phenacetin ... 

The duration of action of acetaminophen is limited by the formation of water-soluble derivatives of the phenol (glucuronide and sulfate) that are then excreted via the kidney. Protection i)f the phenol as an ether inhibits such inactivation without diminishing biologic activity. Acetylation of p-ethoxyaniline iffords the widely used peripheral analgesic, phenacetin (25). ... 

Pentazocine j, 297 2 325 Pentobarbital 1, 268 Pentomone 3, 2T8 PentoxphylTine 466 Pentyl enetetrazole 281 Perazine 1, 381 Pergolide 249 Perlapine 425 Perphenazine 1, 383 Pethidine 1, 300 Phenacaine 19 Phenacemide 1, 95 Phenacetemide Phenacetin 111... 

Figure 11.5 Chromatograms of plasma samples obtained with fully automated on-line SPE-LC (a) dmg-ffee human plasma (b) human plasma spiked with omeprazole (100 ng/ml) and phenacetin (internal standard 1000 ng/ml). Reprinted from Journal of Pharmaceutical and Biomedical Analysis, 21, G. Garcia-Encina et al., Validation of an automated liquid chromatograpliic method for omeprazole in human plasma using on-line solid-phase exti action, pp. 371 - 382, copyright 1999, with permission from Elsevier Science.

Phenacetin, a substance formerly used in over-the-counter headache remedies, has the formula CloH1 N02. Phenacetin is neutral and does not dissolve in either acid or base. When warmed with aqueous NaOH, phenacetin yields an amine, CgHjjNO, whose lH NMR spectrum is shown. When heated with HI, the amine is cleaved to an aminophenol, C5IT7NO. What is the structure of phenacetin, and what are the structures of the amine and die aminophenol ... 

High performance liquid chromatography is used for the separation and quantitative analysis of a wide variety of mixtures, especially those in which the components are insufficiently volatile and/or thermally stable to be separated by gas chromatography. This is illustrated by the following method which may be used for the quantitative determination of aspirin and caffeine in the common analgesic tablets, using phenacetin as internal standard where APC tablets are available the phenacetin can also be determined by this procedure. 

Sample mixture. A suitable sample mixture is obtained by weighing out accurately about 0.601 g of aspirin, 0.076 g of phenacetin and 0.092 g of caffeine. Dissolve the mixture in 10 mL absolute ethanol, add 10 mL of 0.5M ammonium formate solution and dilute to lOOmL with de-ionised water. 

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