0-Acetylsalicylic acid

Acetylsalicylic acid (uh-SEE-till-sal-in-SILL-ik As-id, or uh-se-TEEL-sal-ih-SEEL-ik AS-id), more commonly known as aspirin, is the world s most commonly used therapeutic drug. By one estimate, about 137 million aspirin tablets are taken every day throughout the world. The drug is also known by other names including o-acetoxybenzoic acid 2-(acetyloxy)-benzoic acid 2-carboxyphenyl acetate and benzoic acid, 2-hydroxyacetate, in addition to about ten other systematic names and many common names. 

The analgesic properties of willow tree bark, from which salicylic acid comes, have been known for well over 3,500 years. They were first described in Egyptian scrolls dating to about 1550 and were later recommended by a number of ancient authorities, including the famous Greek physician Hippocrates (c. 460-370 ), the Roman encyclopedist Aulus Cornelius Celsus (c. 10 -date of death unknown), the Roman philosopher Pliny the Elder (23 ce-ce), and the Greek physician Pedanius Dioscorides (40-90 ce). 

Acetylsalicylic acid. Red atoms are oxygen white atoms are hydrogen and black atoms are carbon. Striped sticks indicate a benzene ring, publishers 

In the period from 1828 to 1829, the active ingredient in willow bark was first isolated by three individuals, the German pharmacist Johann Buchner (dates not available), the French chemist Henri Leroux (dates not available), and the the Italian chemist, Raffaele Piria (1815-1865). Buchner gave the name salicin to the bitter-tasting yellow crystals extracted from willow bark after the Latin name for the willow tree, Salix. In 1853, the French chemist Charles Frederick Gerhardt (1816-1857) developed a method for reacting salicylic acid (the active ingredient in salicin) with acetic acid to make the first primitive form of aspirin. 

The name aspirin comes from a very old name for salicylic acid, spiraeic acid. 

The discovery, or perhaps more appropriately the rediscovery, of acetylsalicylic acid as a pain reliever is credited to Felix Hoffman (1868-1946), who was supposedly looking for a substitute for sodium salicylate to treat his father s arthritis. Hoffman uncovered and advanced the work of Gerhardt several decades before Gerhardt had produced acetylsalicylic acid in 1853 by reacting salicylic acid and acetyl chloride, but he abandoned the work because of difficulties in obtaining pure products. Other researchers working on salicylates produced acetylsalicylic acid years before Hoffman, but they could not find a feasible commercial process for its production. Hoffman reacted salicylic acid with acetic acid to produce acetylsalicylic acid in 1897  

Hoffmans next task was to convince his employer, Bayer, founded in 1861 by Friedrich Baeyer (1825-1880), to market the product. In 1899, Bayer began to market acetylsalicylic 

Just as aspirin continues to provide the same benefits as a century ago, it also produces some of the same problems. The major problem with aspirin is that it can upset the stomach. In the acidic environment of the stomach, aspirin can diffuse through the protective mucus lining and rupture cells and produce bleeding. Under normal doses, the amount of blood loss in most individuals is only a milliliter or two, but in some individuals who take heavy doses, gastrointestinal bleeding can be severe. To counteract this side effect, manufacturers include an antacid such as aluminum hydroxide and call the aspirin a buffered aspirin. This term is misleading because the antacid does not buffer the solution rather, it neutralizes some of the acidic effects of the aspirin. Another type of aspirin, called enteric aspirin, dissolves in the intestines where the environment is more basic. 

The formation of salicyloyl-specific antibodies implies a formation of salicyl-oyl-protein conjugates in the organism upon ingestion of acetylsalicylic acid. It has 

Being a carboxylic anhydride and a phenolic ester respectively, the acetylsalicylic acid contaminants are highly reactive. They have been shown to react readily 

Whittaker, V. (1990). The Contribution of Drugs and Toxins to Understanding of Cholinergic Function. Trends in Physiological Sciences 11 8-13. 

Basic Neuropharmacology. The Chemistry of the Nervous System. Available from http //www.ptd.neu.edu/neuroanatomy/cyberclass . 

Michael W. Biochemistry of Neurotransmitters. Available from http // web.indstate. edu/ thcme/mwldng . 

Aspirin is one of the most widely used drugs in modem society. It is most frequently used to treat mild to moderate pain or to reduce fever. Because of its anti-inflammatory action, aspirin is prescribed to individuals who suffer from joint inflammation conditions such as rheumatoid arthritis and osteoarthritis. In addition to its antipyretic, anti-inflammatory, and analgesic properties, aspirin is also prescribed to patients at high risk for heart attack 

Hippocrates Greek physician of fifth century b.c.e. known as Father of Medicine  

Crystallization Vacuum filtration Melting point Esterification 

Aspirin (acetylsalicylic acid) can be prepared by the reaction between salicylic acid and acetic anhydride  

In this reaction, the hydroxyl group (—OH) on the benzene ring in salicylic acid reacts with acetic anhydride to form an ester functional group. Thus, the formation of acetylsalicylic acid is referred to as an esterification reaction. This reaction requires the presence of an acid catalyst, indicated by the above the equilibrium 

When the reaction is complete, some unreacted salicylic acid and acetic anhydride will be present, along with acetylsalicylic acid, acetic acid, and the catalyst. The technique used to purify the acetylsalicylic acid from the other substances is called crystallization. This technique, which was introduced in Experiment 3, will be studied in more detail in Experiment 11. The basic principle is quite simple. At the end of this reaction, the reaction mixture will be hot, and all substances will be in solution. As the solution is allowed to cool, the solubility of acetylsalicylic acid will decrease, and it will gradually come out of solution, or crystallize. Because the other substances are either liquids at room temperature or are present in much smaller amounts, the crystals formed will be composed mainly of acetylsalicylic acid. Thus, a separation of acetylsalicylic acid from the other materials will have been accomplished. The purification process is facilitated by the addition of water after the crystals have formed. The water decreases the solubility of acetylsalicylic acid and dissolves some of the impurities. 

The most likely impurity in the final product is salicylic acid itself, which can arise from incomplete reaction of the starting materials or from hydrolysis (reaction with water) of the product during the isolation steps. The hydrolysis reaction of acetylsalicylic add produces salicylic acid. Salicylic add and other compounds that contain a hydroxyl group on the benzene ring are referred to as phenols. Phenols form a highly colored complex with ferric chloride (Fe + ion). Aspirin is not a phenol, because it does not possess a hydroxyl group directly attached to the ring. 

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Acetylsalicylic Acid (Aspirin). C6H4[Pg.110]

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. 

Acetylsalicylic acid is largely used in medicine as an analgesic (t.e., for removing pain) and as an antipyretic (i.e., for reducing the body temperature). 

Phenols, unlike amines, cannot be acetylated satisfactorily in aqueous solution acetylation proceeds readily with acetic anhydride in the presence of a little concentrated sulphuric acid as catalyst. Salicylic acid (o-hydroxy-benzoic acid) upon acetylation yields acetylsalicylic acid or aspirin ... 

Place 10 g. of dry salicylic acid and 15 g. (14 ml.) of acetic anhydride in a small conical flask, add 5 drops of concentrated sulphuric acid, and rotate the flask in order to secure thorough mixing. Warm on a water bath to about 50-60°, stirring with the thermometer, for about 15 minutes. Allow the mixture to cool and stir occasionally. Add 150 ml. of water, stir well and filter at the pump. ReorystaUise the crude acetylsalicylic acid from a mixture of equal volumes of acetic acid and water. 

Acetylsalicylic acid decomposes when heated and does not possess a true, clearly-defined m.p. Decomposition points ranging from 128° to 135° have been recorded a value of 129-133° is obtained on an electric hot plate (Fig. II, 11, 1). Some decomposition may occur if the compound is recrystaUised from a solvent of high boiling point or if the boiling period during recrystallisation is unduly prolonged. 

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

Many pharmaceutical compounds contain chromophores that make them suitable for analysis by UV/Vis absorption. Products that have been analyzed in this fashion include antibiotics, hormones, vitamins, and analgesics. One example of the use of UV absorption is in determining the purity of aspirin tablets, for which the active ingredient is acetylsalicylic acid. Salicylic acid, which is produced by the hydrolysis of acetylsalicylic acid, is an undesirable impurity in aspirin tablets, and should not be present at more than 0.01% w/w. Samples can be screened for unacceptable levels of salicylic acid by monitoring the absorbance at a wavelength of... 

Several aspirin tablets are ground to a fine powder in a mortar and pestle. A 0.1013-g portion of the powder is placed in a 1-L volumetric flask and diluted to volume with distilled water. A portion of this solution is filtered to remove insoluble binders, and a 10.00-mL aliquot transferred to a 100-mL volumetric flask containing 2.00 ml of 4 M NaOH. After diluting to volume the fluorescence of the resulting solution is found to be 8.69. What is the %w/w acetylsalicylic acid in the aspirin tablets ... 

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. 

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. 

Students determine the concentrations of caffeine, acetaminophen, acetylsalicylic acid, and salicylic acid in several analgesic preparations using both CZE (70 mM borate buffer solution, UV detection at 210 nm) and HPLC (C18 column with 3% v/v acetic acid mixed with methanol as a mobile phase, UV detection at 254 nm). 

Acetylsalicylic acid [50-78-2] (i9-acetyoxyben2oic acid) was first synthesized in 1853 by reaction of acetyl chloride with sodium saUcylate. As a dmg, acetylsahcyhc acid was introduced in Germany in 1899 and into the United States in 1900. The first U.S. patent (35) for the manufacture of acetylsaUcyhc acid expired in 1917. Aspirin is a registered trademark of Bayer in many nations, but in the United States and the United Kingdom, aspirin is accepted as the generic name for acetylsahcyhc acid (36). 

The case of intramolecular participation in ester hydrolysis has been extensively studied using acetylsalicylic 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 ... 

Detection and result The chromatogram was dried in a stream of warm air for 10 min, immersed in the reagent solution for 3 s and then subjected to intense UV radiation (high pressure lamp, A = 365 nm) for up to 10 min. Terephthalic (hRf 0 - 5), pimelic (hRf 55), suberic (hRf 60), sebacic (hRf 65 — 70) and benzoic acids (hRf 70 — 75) together with sorbic, malic, adipic, citric, tartaric, lactic and fumaric acids only exhibited a reaction on silica gel layers at higher concentrations. 4-Hydroxybenzoic, salicylic and acetylsalicylic acids fluoresced light blue after irradiation. The detection limit per chromatogram zone was 0.5 pg for salicylic acid and more than 5 pg for benzoic acid. 

Rhodia Phamiaceutical Ingredients Division, 159 Rhodia Phosphate Products Division, 159 Rhodia Polyamide Division, 159 RHODINE , acetylsalicylic acid, 115 Rhodium metal, 115... 

So, consider a typical molecule such as aspirin (acetylsalicylic acid), shown in Figure 1.11. Such two-dimensional drawings can be made using ChemDraw or ISlSDraw, but all the features needed to construct a molecular mechanics force field are apparent. 

Consider then a HF/STO-3G calculation on aspirin (acetylsalicylic acid) ... 

The filtrate from this first batch will comprise a solution of 180 to 270 kg of unprecipitated acetylsalicylic acid (1.0 to 1.5 mols), 510 kg of acetic anhydrice (5.0 mols), 600 kg of acetic acid (10.0 mols) (obtained as a by-product in the acetylation step) and 1,200 kg of the diluent toluene. Into this filtrate, at a temperature of 15° to 25°C, ketene gas is now passed through a sparger tube or diffuser plate, with good agitation, until a weight increase of 420.5 kg of ketene (10 mols) occurs. The reaction mixture wiil now contain 180-270 kg of unprecipitated acetylsalicylic acid (1.0-1.5 mols) and 1,532 kg of acetic anhydride (15 mols) in 1,200 kg of toluene. This mother liquor is recycled to the first step of the process for reaction with another batch of 1,382 kg of salicylic acid. On recirculating the mother liquor, the yield of pure acetylsalicylic acid is 1,780 to 1,795 kg per batch. 

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