Acetic anhydride with salicylic acid

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 ... 

Thus, the reaction of an alcohol with an anhydride is a useful method for synthesizing esters. Aspirin is synthesized on an industrial scale by reacting acetic anhydride with salicylic acid ... 

The reaction of acetic anhydride with salicylic acid (o-hydroxybenzoic acid) is used to synthesize aspirin. In this reaction, the phenolic hydroxyl group is acetylated (converted to its acetate ester). 

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 liquor. Other methods of preparing aspirin, which are not of commercial significance, involve acetyl chloride and salicylic acid, salicylic acid and acetic anhydride with sulfuric acid as the catalyst, reaction of salicylic acid and ketene, and the reaction of sodium salicylate with acetyl chloride or acetic anhydride. 

Mechanism I was ruled out by an isotopic labeling experiment. The mixed anhydride of salicylic acid and acetic acid is an intermediate if nucleophilic catalysis occurs by mechanism 1. This molecule is known to hydrolyze in water with about 25% incorporation of solvent water into the salicylic acid. 

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. 

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. 

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. 

The commercial process for the production of aspirin (or acetylsalicylic acid) involves a one-pot acylation reaction. Acetic anhydride reacts with salicylic acid in the presence of a small amount of sulfuric acid to produce acetylsalicylic acid and acetic acid. 

Acetylation. A comparative student experiment with salicylic acid and acetic anhydride demonstrates that common acetylation catalysts fall into the following order of relative effectiveness coned. H2SO4 > boron trifluoride etherate > pyridine > sodium acetate. Although it is a relatively weak catalyst, sodium acetate is completely nondestructive and can be employed in much larger than truly catalytic amounts. An example is the acetylation of furylcarbinol. A mixture of the reactants and solvent benzene was heated on the steam bath with stirring to prevent caking... 

The first step in the industrial synthesis of aspirin is known as the Kolbe-Schmitt carboxylation reaction. In this step, the phenolate ion reacts with carbon dioxide under pressure to form salicylic acid. Reaction of salicylic acid with acetic anhydride forms acetylsalicylic acid (aspirin). 

Aspirin can be made in the laboratory by reacting acetic anhydride (C4H5O3) with salicylic acid (C7Hg03) to form aspirin (C9Hg04) and acetic acid (C2H4O2). The balanced equation is... 

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 ... 

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. 

Coumarin was first produced synthetically by Perkin. He made it by heating salicylic aldehyde, CgH (OH)i(COH), acetic anhydride, and sodium acetate. The whole solidifies to a crystalline mass, from which, on treatment with water, an oil separates containing coumarin and aceto-coumaric acid. This acid on heating is decomposed into acetic acid and coumarin, so that the product of distillation is principally coumarin. Perkin s synthesis proceeds according to the following equation —... 

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. 

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... 

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 ... 

Method of Preparation Add 0.5 mL of H2SO4 to a mixture of 5 g of salicylic acid and 5 mL acetic anhydride in a 100 mL flask. Continue stirring and heat on water bath for 15 min, keeping the temperature between 50°C and 60°C. Pour the mixture in about 80 mL of ice cold water, filter and crystallize with a mixture of equal volumes of acetic acid and water. 

Scenario A student prepared ASA starting with 2.00 g of salicylic acid and 5.00 mL of acetic anhydride (density = 1.08 g mL-1). After the product was dried, it weighed 1.90 grams. The student then hydrolyzed the ASA with sodium hydroxide and heated the mixture to produce the salicylate dianion ... 

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. 

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

Esters of the phenolic hydroxyl are obtained easily by the Schotten-Baumann reaction. The reaction in many cases involves 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 salicylic acid with acetic anhydride to produce acetylsalicylic acid [50-78-2] (aspirin). 

Production. Coumarin is currently produced by Perkin synthesis from salicyl-aldehyde. In the presence of sodium acetate, salicylaldehyde reacts with acetic anhydride to produce coumarin and acetic acid. The reaction is carried out in the liquid phase at elevated temperature. 

A number of 5//-l,4-benzodioxepin-ones and -diones have been prepared (72HC(26)319, p. 339). The reaction of the sodium salt of salicylic acid with 2-chloroethanol gave (269) (75BSF(2)277) and treatment of the methyl ester of 2-acetyl-6-chloro-3,5-dimethoxyphenoxyacetic acid with 3M hydrochloric acid gave (270). The dione (271) was prepared by heating 2-carboxy-5,6-dimethoxyphenoxyacetic acid in acetic anhydride and (272) was prepared from chloroacetylsalicylic acid. 

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