Acetic anhydride Aspirin

Acetylation. Boil i g. of salicylic acid with 4 ml. of an acetic anhydride-acetic acid mixture (equal volumes) under reflux for 10 minutes. Pour into water. Filter off the aspirin (p. 111), wash with water and recrystallise from aqueous acetic acid (1 1) m.p. l36 ... 

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 ... 

Esters of the phenohc hydroxyl are obtained easily by the Schotten-Baumaim reaction. The reaction ia many cases iavolves an acid chloride as the acylating agent. However, acylation is achieved more commonly by reaction with an acid anhydride. The single most important commercial reaction of this type is the acetylation of sahcyhc acid with acetic anhydride to produce acetylsahcyhc acid [50-78-2] (aspirin). 

Manufacture. Aspirin [50-78-2] is manufactured by the acetylation of sahcyhc acid with acetic anhydride (eq. 9) (37,38). 

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. 

However, this method is appHed only when esterification cannot be effected by the usual acid—alcohol reaction because of the higher cost of the anhydrides. The production of cellulose acetate (see Fibers, cellulose esters), phenyl acetate (used in acetaminophen production), and aspirin (acetylsahcyhc acid) (see Salicylic acid) are examples of the large-scale use of acetic anhydride. The speed of acylation is greatiy increased by the use of catalysts (68) such as sulfuric acid, perchloric acid, trifluoroacetic acid, phosphoms pentoxide, 2inc chloride, ferric chloride, sodium acetate, and tertiary amines, eg, 4-dimethylaminopyridine. 

Aspirin (sahcyhc acid, acetic anhydride) B L None 90 1 >ih [7] 89... 

Acetic anhydride is mainly used to make acetic esters and acetyl salicylic acid (aspirin). 

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. 

Add 2.0 g of salicylic acid, 5.0 mL of acetic anhydride, and 5 drops of 85% H3P04 to a 50-mL Erlenmeyer flask. Heat in a water bath at 75°C for 15 minutes. Add cautiously 20 mL of water and transfer to an ice bath at 0°C. Scratch the inside of the flask with a stirring rod to initiate crystallization. Separate aspirin from the solid-liquid mixture by filtering through a Buchner funnel 10 cm in diameter. 

Aspirin, C9H804, is prepared by reacting salicylic acid QHQ with acetic anhydride, C4He03> in die reaction... 

A student is told to prepare 45.0 g of aspirin. She is also told to use a 55.0% excess of acetic anhydride and to expect to get an 85.0% yield in the reaction. How many grams of each reactant should she use ... 

Aspirin (shown here as acetylsalicylic acid, Ka = 3.2 X 10 4) is a product of the reaction of salicylic acid with acetic anhydride. Calculate the ratio of the concentrations... 

C04-0014. Aspirin is produced by treating salicylic acid with acetic anhydride ... 

Suppose a chemist started with 152 g of salicylic acid and 86.8 g of acetic anhydride and produced 133 g of aspirin. What is the yield of this reaction ... 

Essentially, all methods of synthesis are variations of the reaction of acetylchloride, acetic anhydride or ketene11 with salicylic acid using a variety of catalysts such as pyridine12 or sulfuric acid13 and reaction conditions (c.f. 14). The preparation of aspirin labeled with a i4c iaj-,eie(j acetyl group has also been reported.15 Efforts to improve the commercial processes continue to the present day. 

However, the driving force in this reaction is not large, so one usually ends up with an equilibrium mixture of water, salicylic acid, ASA and acetic acid. A better approach to produce ASA (aspirin) is to react acetic anhydride with salicylic acid in the presence of phosphoric or sulfuric acid acting as a catalyst ... 

Acetylium tetrailuoroborate, 4 144t N-Acetyl-p-aminophenol (acetaminophen), acetic anhydride used in production of, 1 158. See also Acetaminophen Acetyl perchlorate, 1 157 Acetylsalicylic acid (aspirin), 22 17-21 acetic anhydride used in production of, 1 158... 

The analgesic aspirin, acetylsalicylic acid, is an ester, hi this compound, the alcohol part is actually a phenol, salicylic acid. Aspirin is synthesized from salicylic acid by treatment with acetic anhydride. 

Uses. Organic chemical syntheses conversion of higher acids into their anhydrides for acetylation in the manufacture of cellulose acetate and aspirin... 

Acid anhydrides are between acid chlorides and carboxylic acids in reactivity, so this reaction is more effective than the reaction with a carboxylic acid but less efficient than the reaction with an acid chloride. Half of the acid anhydride goes into forming the ester, while the other half becomes a carboxylic acid. Figure 12-23 illustrates this reaction, using salicylic acid as the alcohol and acetic anhydride as the acid anhydride to form aspirin, an ester. 

Forming an ester (aspirin) by the reaction of an alcohol (salicylic acid) with an acid anhydride (acetic anhydride). 

Aspirin Aspirin, acetylsalicylic acid (3.2.2), is synthesized by the acetylation of salicylic acid (3.2.1) nsing acetic anhydride or acetyl chloride [60-63]. 

Acetic anhydride is one of the most important esters. The major market for acetic anhydride is in the production of cellulose acetate Other important uses Include production of cellulosic plastics, vinyl acetate, and aspirin. Acetic anhydride is u mature commercial product enjoying a stable price situation and steady growth... 

Bose et alm have demonstrated the synthesis of aspirin from salicylic acid and acetic anhydride using commercial microwave reactors (Scheme 9.6). Without optimising the conditions, high purity aspirin was obtained in greater than 80% yield (500-800 g scale). 

PROBLEM 3.8 Aspirin is prepared by reaction of salicylic acid (C7H15O3) with acetic anhydride (C4Hg03) according to the following equation ... 

How many grams of acetic anhydride are needed to react with 4.50 g of salicylic acid How many grams of aspirin will result How many grams of acetic acid are formed as a by-product ... 

C6H5OH + C02 - H0C6H4C02H Salicylic acid reacts easily with acetic anhydride to give aspirin. 

In this process, a 500-gallon glass-lined reactor is needed to heat the salicylic acid and acetic anhydride for 2 to 3 hours. The mixture is transferred to a crystallizing kettle and cooled to 3°C. Centrifuging and drying of the crystals yields the bulk aspirin. The excess solution is stored and the acetic acid is recovered to make more acetic anhydride. 

To form aspirin, the salicylic acid is refluxed with acetic anhydride in toluene at 88 to 92°C for 20 hours. The reaction mixture is then cooled in aluminum cooling tanks, and the acetylsalicylic acid precipitates as large crystals that are separated by filtration or by centrifugation, washed, and dried. 

This experiment will acquaint you with a simple synthetic problem in the preparation of aspirin. The preparative method uses acetic anhydride and an acid catalyst, like sulfuric or phosphoric acid, to speed up the reaction with salicylic acid. 

Take 2.0 g of salicylic acid and place it in a 125-mL Erlenmeyer flask. Use this quantity of salicylic acid to calculate the theoretical or expected yield of aspirin (1). Carefully add 3 mL of acetic anhydride to the flask and, while swirling, add 3 drops of... 

Remove the Erlenmeyer flask from the bath and let it cool to approximately room temperature. Then, slowly pour the solution into a 150-mL beaker containing 20 mL of ice water, mix thoroughly, and place the beaker in an ice bath. The water destroys any unreacted acetic anhydride and will cause the insoluble aspirin to precipitate from solution. 

---