Acetylsalicylic acid, structure

Therapeutic Function Analgesic, Antipyretic, Antiinflammatory Chemical Name 2-(Acetyloxy)benzoic acid Common Name Acetylsalicylic acid Structural Formula ... 

Only four years after Kekule proposed the ring structure for benzene, and before the configuration of salicylic acid was established, Kraut concluded on the basis of sound chemical evidence that the products obtained on heating acetylsalicylic acid possess chain structures formed through intermolecular esterification. He assigned the dimeric and tetrameric formulas... 

This example will illustrate the quantitative analysis of aspirin (acetylsalicylic acid), phenacetin and caffeine in a mixture. The structures of these three are shown in Fig. 4.4a. 

Figure 9.1.3 The molecular structure of aspirin or acetylsalicylic acid.

Figure 13.4.4 The molecular structure of aspirin, acetylsalicylic acid.

Draw the structural formula of acetylsalicylic acid shown on p. 78 and highlight the types of interactions that may be formed between it and a protein receptor. 

You find them in citrus fruits (citric acid), vinegar (acetic acid), aspirin (acetylsalicylic acid), and numerous other natural and synthetic compounds, as well on numerous organic exams. In this chapter you explore the structure, synthesis, and reactions of these acids and acids like them. 

The formulas of salicylic acid, salol, and acetylsalicylic acid are given below to show the structural modifications that turned an unsatisfactory product into a much better product. 

The active principle was shown to be salicin by Buchner in 1828 but the bitter taste and damage to the gastric mucosa limited its use. Piria isolated salicylic acid from salicin in 1838. In 1859, Kolbe discovered the structure and synthesis of salicylic acid and in 1897 acetylsalicylic acid was synthesized by Hoffmann. Two years later, in 1899, acetylsalecylic acid, the first nonsteroidal antiinflammatory drug was registered under the name Aspirin (Fig. 2). 

Acetylsalicylic acid, a common pain reliever, is composed of two fragments resembling structures from the above list of compounds. These fragments are illustrated below and relate to salicylic acid and acetyl chloride. 

Small differences in the structure of the molecules result in changes in the elution volumes. Note the difference that shortening the side chain from propyl to methyl has on the elution volume of the paraben. Even such a minor difference is sufficient to permit the separation of these two compounds. The same effect can be observed if aspirin (acetylsalicylic acid) is hydrolyzed to salicylic acid. Reduction in molecular size increases the elution volume. 

Figure 12.15. Increased leukotriene formation as an indirect consequence of cyclooxygenase inhibition by, e g., acetylsalicylic acid (ASS a), and structure of the 5-Lox/Cox-2 dual inhibitor tepoxalin (b).

Since salicylic acid has both an alcohol functional group and a carboxylic acid functional group, it can undergo two different esterification reactions depending on which functional group reacts. For example, when treated with ethanoic acid (acetic acid), salicylic acid behaves as an alcohol and the ester produced is acetylsalicylic acid (aspirin). On the other hand, when reacted with methanol, salicylic acid behaves as an acid and the ester methyl salicylate (oil of wintergreen) is produced. Methyl salicylate is also an analgesic and part of the formulation of many liniments for sore muscles. What are the structures of acetylsalicylic acid and methyl salicylate ... 

Recall from Chapter 2 that aspirin (acetylsalicylic acid) is a synthetic carboxylic acid, similar in structure to salicin, a naturally occurring compound isolated from willow bark, and salicylic add, found in meadowsweet. 

With reference to the structures of acetylsalicylic acid (aspirin, Chapter 2 opening molecule) and acetaminophen (the active ingredient in Tylenol), explain each statement (a) Acetaminophen tablets can be stored in the medicine cabinet for years, but aspirin slowly decomposes over time (b) Children s Tylenol can be sold as a liquid (acetaminophen dissolved in water), but aspirin cannot. 

Another active principle soon extracted from plants was salicylic acid. Salicin, extracted from the willow tree, has been launched in 1876 by a Scottish physician, Thomas John McLogan It was in extensive competition with Cinchona bark and quinine and never became a very popular treatment for fever or rheumatic symptoms. The Italian chemist Raffaele Piria, after having isolated salicylalde-hyde (1839) in Spireae species, prepared salicylic acid from salicin in Dumas laboratory in the Sorbonne, Paris. This acid was easier to use and was an ideal step before future syntheses. Its structure was closely related to benzoic acid, an effective preservative useful as an intestinal antiseptic for instance in typhoid fever. Acetylsalicylic acid has been first synthesized by Charles Frederic Gerhardt in 1853 and then, in a purer form, by Johann Kraut (1869). Acetylsalicylic acid synthesis with carbolic acid and carbon dioxide was improved by Hermann Kolbe in1874, but in fact nobody noticed its pharmacological interest. 

Modeling In what ways are the structures of salicylic acid and acetylsalicylic acid (aspirin) alike In what ways are they different ... 

A relatively nonpolar molecule, acetylsalicylic acid has the ability to penetrate membrane barriers that are also made up of nonpolar molecules. However, inside the membrane are many small water pockets, and when an acetylsalicylic acid molecule enters such a pocket, it ionizes into and acetylsalicylate ions. These ionic species become trapped in the interior regions of the membrane. The continued buildup of ions in this fashion weakens the structure of the membrane and eventually causes bleeding. Approximately 2 ml of blood are usually lost for every aspirin tablet taken, an amount not generally considered harmful. However, the action of aspirin can result in severe bleeding in some individuals. It is interesting to note that the presence of alcohol makes acetylsalicylic acid even more soluble in the membrane, and so further promotes the bleeding. 

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