Aspirin preparations

In addition to salicylic and acetic acids, very small quantities of acetylsalicylanhy-dride (0.0012 to 0.024%) and acetylsalicylsalicylic acid (0.03 to 0.1%) have been found in aspirin preparations. The former has been determined by gas chromatography,1 0 TLC170 and spectrophotometry,171 the latter by gas chromatography. 14 0,1 a controversy is still ongoing (cf. 152) whether the occasionally observed hypersensitivity against aspirin is caused by these two impurities and whether the basis of the adverse reaction is immunological. 

The accepted value for the melting point of aspirin is 137°C. What do the melting points obtained for the sample of aspirin prepared in this experiment tell us ... 

Suggest a technique that could be used to purify the aspirin prepared in this experiment. 

From what naturally occurring compound is aspirin prepared ... 

What would happen to your percent yield if in step no. 11 of the procedure you failed to dry completely your aspirin preparation by omitting the drying between filter paper ... 

Petroski, D. Endoscopic comparison of various aspirin preparations. Gastric mucosal adaptability to aspirin restudied. Curr. Ther. Res. Clin. Exp. 1989, 45, 945-954. 

Watanbe Y, Kogoshi T, Amagai Y, Matsumoto M. Preparation and evaluation of enteric granules of aspirin prepared by acylglycerols. Int J Pharm 1990 64 147-154. 

A number of aluminium aspirin preparations have also been described, to which different structures have been assigned . One of these compounds, aluminium aspirin NF, was found to be poorly absorbed compared with acetylsalicylic acid. Aloxiprin (Palaprin) is a different form of aluminium aspirin, being a polymeric condensation product of aluminium oxide and acetylsalicylic acid, with the formula Al302(C8H4(o-OCMe)-COO)s 9B. This compound is therapeutically as effective as acetylsalicylic acid it produces less gastric irritation and gastro-intestinal blood loss, but has a slight tendency to cause constipation. ... 

Impurities contaminating commercial aspirin preparations could be responsible for appearance of urticaria and angioedema in some patients (de Weck 1971 Bundgaard and de Weck 1975). These contaminants include acetylsalicylic anhydride, acetylsalicylic salicylic acid and cw-disalicylide. A rapid and convenient colorimetric method has been described recently for the quantitative determination of these immunogenic impurities in aspirin (Bundgaard 1976). 

Patients who are on a sodium-restricted diet should avoid taking buffered aspirin preparations that contain a high concentration of sodium. 

Aspirin, prepared industrially by selective electrophilic aromatic substitution of phenol, is arguably the blockbuster drug of all times. Its active metabolite, 2-hydroxybenzoic acid (salicylic acid), obtained from the bark of the white willow tree, has been used for four millennia for the treatment of inflammation and to relieve pain or discomfort caused by arthritis, soft-tissue injuries, and fever. Aspirin was discovered by the German company Bayer in the late 19th century and ironically marketed together with another drug, heroin, whose addictive side effects were not recognized then. 

CioHjjNOi. White crystals, m.p. 137-138°C. Prepared from phenol, via />-nitro-phenol, p-nitrophenetole and /7-phenetidine. It is used medicinally as an antipyretic analgesic similar to aspirin. It has chronic toxicity towards the kidney. 

Phenol was first isolated m the early nineteenth century from coal tar and a small por tion of the more than 4 billion lb of phenol produced m the United States each year comes from this source Although significant quantities of phenol are used to prepare aspirin and dyes most of it is converted to phenolic resins used m adhesives and plastics... 

The key compound m the synthesis of aspirin salicylic acid is prepared from phe nol by a process discovered m the nineteenth century by the German chemist Hermann Kolbe In the Kolbe synthesis also known as the Kolbe—Schmitt reaction, sodium phen oxide IS heated with carbon dioxide under pressure and the reaction mixture is subse quently acidified to yield salicylic acid... 

Section 24 10 The Kolbe-Schmitt synthesis of salicylic acid is a vital step m the preparation of aspirin Phenols as their sodium salts undergo highly regioselective ortho carboxylation on treatment with carbon dioxide at elevated temperature and pressure... 

The preparation of an ion-selective electrode for salicylate is described. The electrode incorporates an ion-pair of crystal violet and salicylate in a PVC matrix as the ion-selective membrane. Its use for the determination of acetylsalicylic acid in aspirin tablets is described. A similar experiment is described by Creager, S. E. Lawrence, K. D. Tibbets, C. R. in An Easily Constructed Salicylate-Ion-Selective Electrode for Use in the Instructional Laboratory, /. Chem. Educ. 1995, 72, 274-276. 

Aluminum acetylsaHcylate is a tasteless, nonbasic, stable, alternative therapeutic salt to aspirin (83). Also called aluminum aspirin, it is an insoluble white to off-white powder prepared by reaction of aluminum isopropoxide with sodium acetylsaHcylate in an organic solvent. The product precipitates from the reaction mixture (83). Standards requke that aluminum aspirin contain not less than the equivalent of 80% aspirin, corresponding to 90% purity on an anhydrous basis. The aluminum oxide assay must be 12—17% (81). 

Various processes involve acetic acid or hydrocarbons as solvents for either acetylation or washing. Normal operation involves the recovery or recycle of acetic acid, any solvent, and the mother Hquor. Other methods of preparing aspirin, which are not of commercial significance, involve acetyl chloride and saHcyHc acid, saHcyHc acid and acetic anhydride with sulfuric acid as the catalyst, reaction of saHcyHc acid and ketene, and the reaction of sodium saHcylate with acetyl chloride or acetic anhydride. 

Salicylic acid, the starting material for the preparation of aspirin. 

The best known aryl ester is O-acetylsalicylic acid, better known as aspirin. It is prepared by acetylation of the phenolic hydroxyl group of salicylic acid ... 

Kolbe-Schmitt reaction (Section 24.10) The high-pressure reaction of the sodium salt of a phenol with carbon dioxide to give an o-hydroxybenzoic acid. The Kolbe-Schmitt reaction is used to prepare salicylic acid in the synthesis of aspirin. 

The popularity of aspirin has led to the preparation of a liost of relatively simple derivatives in the hope of finding a ilrug that would be either superior in action or better tolerated. i alicylamide (5), for example, is sometimes prescribed for pa-I Lents allergic to aspirin. It should be noted, however, that I his agent is not as active as the parent compound as an antiinflammatory or analgesic agent. This may be related to the fact I hat salicylamide does not undergo conversion to salicylic acid i 11 the body. 

Conversion of Acid Anhydrides into Esters Acetic anhydride is often used to prepare acetate esters from alcohols. For example, aspirin (acetylsalicylic acid) is prepared commercially by the acetylation of o-hydroxybenzoic acid (salicylic acid) with acetic anhydride. 

Chemistry is a quantitative science. The experiments that you carry out in the laboratory and the calculations that you perform almost always involve measured quantities with specified numerical values. Consider, for example, the following set of directions for the preparation of aspirin (measured quantities are shown in italics). 

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