Acetylsalicyclic acid

It should be emphasised that salicylic acid can be readily acetylated by Method 1, and that the above preparation of acetylsalicyclic acid is given solely as an illustration of Method 2. To employ Method 1, add 10 g. of salicylic acid to 20 ml. of a mixture of equal volumes of acetic anhydride and acetic acid, and boil gently under reflux for 30 minutes. Then pour into about 200 ml. of cold water in order to precipitate the acetylsalicylic acid (11 g.) and finally recrystallise as above. Method 2, however, gives the purer product. 

A short while afterwards K. Kraut (4) reported the preparation of dimeric and tetrameric chain structures by intermolecu-lar esterification of acetylsalicyclic acid. In the same paper he assigned the analogous octameric chain formula to the... 

Landin, M., Casalderrey, M., Martinez-Pacheco, R., Gomez-Amoza, J.L., Souto, C., Concheiro, A., and Rowe, R.C., Chemical stability of acetylsalicyclic acid in tablets prepared with different particle size fractions of a commercial brand of dicalcium phosphate dihydrate, Int. ]. Pharm., 123, 143,1995. 

During the nineteenth century, chemists had a good deal of success in isolating and purifying natural products from plant sources. Morphine was isolated as a pure compound from crude opium in 1804. Quinine was isolated from the bark of the cinchona tree in 1820 and was initially employed as a fever reducer. However, its effectiveness against malaria was soon discovered and it found an alternative highly important medical use. Sodium salicylate was isolated from the bark of the willow tree in 1821 and was also shown to have analgesic, antipyretic, and antiinflammatory properties. It took an additional 76 years, until 1897, to synthesize the acetyl derivative, acetylsalicyclic acid, commonly known as aspirin. 

Consumption of analgesics and anti-inflammatory drags in other developed countries is also quite high as is reflected in Table 1.7. Most widely used almost across the board in those countries is acetylsalicyclic acid and paracetamol. Beyond these two, it is apparent that the pattern of use of the other pain medications is quite diverse, with some pain relievers more popular in some countries than in others. Although the statistics are not readily available, pain relief medications are also the most consumed per capita in developing countries. 

Acetylsalicyclic acid, aspirin, inhibits the cyclooxygenase-catalyzed first step in the biosynthesis of prostaglandins, prostacyclins and thromboxanes. These latter substances are responsible for the inflammatory and pyretic effects of infection. It is believed that the chemical inhibition reaction involves the acetylation of the enzyme by the aspirin. 

Other compounds producing some inhibition of ZDV conjugation were oxazepam, salicylic acid, and acetylsalicyclic acid. More recently, Trapnell et al. examined the inhibition of ZDV at a more relevant concentration of 20 pM in bovine serum albumin (BSA)-activated microsomes by atovaquone, methadone, fluconazole, and valproic acid at therapeutically relevant concentrations (127). Both fluconazole and valproic acid inhibited ZDV glucuronidation by more than 50% at therapeutic concentrations. Clinical interaction studies have been conducted with methadone, fluconazole, naproxen, probenecid, rifampicin, and valproic acid (see Table 10). 

Problem 19.15 Use phenol and any inorganic or aliphatic reagents to synthesize (a) aspirin (acetylsalicyclic acid), (b) oil of wintergreen (methyl salicylate). Do not repeat the synthesis of any compound. ... 

Many of the chemicals used in this course will be unfamiliar to you. Their properties can be looked up in reference books, a very useful one being the Aldrich Catalog Handbook of Fine Chemicals. It is interesting to note that 1,4-dichlorobenzene is listed as a toxic irritant and naphthalene is listed as an irritant. Both are used as moth balls. Camphor, used in vaporizers, is classified as a flammable solid irritant. Salicylic acid, which we will use to synthesize aspirin (Chapter 26) is listed as moisture-sensitive toxic. Aspirin (acetylsalicyclic acid) is classified as an irritant. Caffeine, which we will isolate from tea or cola syrup (Chapter 8), is classified as toxic. Substances not so familiar to you—1-naphthol and benzoic acid—are classified respectively as toxic irritants and irritant. To put things in some perspective, nicotine is classified as highly toxic. ... 

Acetylsalicyclic acid melts with decomposition at temperatures reported from 128 to 137°C. It can be crystallized by dissolving it in ether. 

Kubota, L. T, Fernandes, J. C. B., Rover, L., and de Oliveiro Neto, G. Determination of acetylsalicyclic acid by FIA-potentiometric system in drugs after on-line hydrolysis. Talanta 50(3).-661-667,1999. 

Acetylation of the hydroxy group of salicylic acid gives aspirin, acetylsalicyclic acid. 

Pedersen, S., and H. G. Kristensen. 1994. Change in crystal density of acetylsalicyclic acid during compaction. S. T. P. Pharma. Sci. 4 201-206. 

In terms of the amount of literature developed, biochemical separations have been largely ignored by those in the field of LEM-mediated separations. One application that has enjoyed some experimental scrutiny is that of the use of LEMs in drug delivery and overdose prevention systems. They have been used to separate or release several different types of drugs including acetylsalicyclic acid (18), phenobarbital (19), and several barbiturates (20,21). 

Provided Aspirin (acetylsalicyclic acid), phenacetin (acetophenetidin), caffeine (theine 1,3,7-trimethylxanthine), methanol, mobile-phase solution (0.01 M sodium borate + 0.005 M ammonium nitrate). See Experiment 26 for the structures of aspirin, phenacetin, and caffeine. 

Lish and McKinney investigated the effects of methdilazine in a variety of anti-inflammatory tests. In the guinea-pig anaphylactic arthritis test methdilazine in subcutaneous doses of 12 mg/kg produces an inhibition similar to that of 300 mg/kg of acetylsalicyclic acid. The shape of the time response curves suggests that the effect of methdilazine is due to both a nonantihistamine and antihistamine action. When administered subcutaneously methdilazine is 10-20 times as potent as acetylsalicylic acid or phenylbutazone in reducing the size of the bradykinin-induced weal in rabbits. The authors conclude that methdilazine opposed excessive permeability of the minute vessels by its antihistamine, antiserotonin and antibradykinin actions, plus an anti-inflammatory action not related to any of these . The effects of methdilazine on rat-foot oedema produced by seven inflammatory agents has been reported by Winter. ... 

Most organic substances Acetylsalicyclic acid Chlorpheniramine maleate Colchicine... 

Figure 10.6 shows the soUd solubility of acetylsalicyclic acid (CAS-number 50-78-2) in two different solvents (water and ethanol). The application of the thermodynamic consistency tests showed high quality of the experimental data reported for this compound (acetylsalicyUc, CAS-number 50-78-2), with a quaUty factor of 0.89 for both cases. Test-3 and Test-4 were considered in this analysis once the experimental data does not report the information for the end points (jCj=0 and x,=1). The same was... 

The case of intramolecular participation in ester hydrolysis has been extensively studied using acetylsalicyclic acid (aspirin) and its derivatives. The kinetic data show that the anion is hydrolyzed more rapidly than the neutral species, indicating that the carboxylate group becomes involved in the reaction in some way. Three mechanisms can be considered ... 

Flenstrom G, Marsden NVB. Dextran permeability, electrical properties, and H secretion by isolated frog gastric mucosa after acetylsalicyclic acid. Gastroenterology 64 21%-284, 1973. 

As early as 1989, Tomalia et al. [137] demonstrated with carbon-13, spin-lattice relaxation (Ti) techniques that small molecules such as acetylsalicyclic acid or 2,4-dichlorophenoxyacetic acid could be encapsulated within the interior of carboxymethyl ester terminated PAMAM dendrimers exhibiting guestihost stoichiometries of 4 1 by weight or 3 1 on a molar basis. These encapsulations appear to be driven by simple ion pairing of the acidic guest molecules with the tertiary amine sites located within the PAMAM dendrimer host. More recently, extensive work by Twyman et al. [138,139] and others [140] has shown that dendrimers may function as very versatile host molecules for drug delivery systems. Figure 18 illustrates the incorporation of benzoic acid within the interior of a hydroxyl terminated PAMAM dendrimer. 

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