1. Write the reaction involved in the synthesis of Aspirin.

Acetylation, a type of nucleophilic acyl substitution is a reaction employed in the synthesis of aspirin. It involves acid- catalyzed reaction of an acetyl group (-COCH3) with a hydroxyl group (-OH) of an alcohol and phenol producing a functional group, ester. In the experiment, acetic anhydride is the source of the acetyl group which is a carboxylic acid derivative. Salicylic acid on the other hand, is the source of the hydroxyl group which is an aromatic compound. Carboxylic acid is the acid catalyst used in the process.

The synthesis of aspirin involves acetylation, the acid catalyzed reaction of acetyl ( COCH3) group with a hydroxyl (OH) group of an alcohol and phenol, yielding an ester. Acetylation is a type of nucleophilic acyl substituion, and it is also closely related to esterification (the difference being that esterification involves a carboxyl group, not acetyl). In this experiment, the source of the acetyl group is acetic anhydride, a carboxylic acid derivative; the source of the hydroxyl group is salicyclic acid, an aromatic compound; and the acid catalyst is carboxylic acid.

3. Explain why in the recrystallization of Aspirin the water should not be heated above 80C.
The water should not be heated at a temperature above 80C in the recrystallizaion of aspirin in order to avoid the hydrolysis of ester which will reverse the reaction, producing carboxylic acid as a reactant instead of ester as a product.

The recrystallization of aspirin in water must not exceed a temperature of 80C in order to prevent hydrolysis of the ester, which will reverse the reaction, yielding reactant (carboxylic acid) instead of product (ester).

4. Explain the results obtained when Aspirin and salicyclic acid were treated with FeCl3.
A purple or violet coloration was observed when FeCl3 reacted to phenol which indicates a positive result. If the synthesized product gives a purple or violet color with FeCl3 solution, this means that not all of the salicylic acid has been used up.

Ferric chloride reacts with phenol to give a purple solution. Since salicylic acid has a phenol group, it is expected to give a positive result, that is, become purple. If the synthesized product gives a purple color with ferric chloride solution, it means that not all of the salicylic acid has been consumed.

APPLICATIONS: Phenol must first be reacted with NaOH, yielding salt and water. The salt is reacted with salicylic acid to produce phenyl salicylate, or salol, and NaOH. Aspirin is more acidic than salol because of the stability of its conjugate base and its COOH functional group. Aspirin will be hydrolyzed easily because it is acidic. Aspirin (acety salicylic acid) is a stronger acid than salol, because aspirin contains the carboxylic acid functional group (pKa ~3) and salol contains a phenol (pKa ~10) Aspirin is hydrolysed easier since the leaving group (LG) is acetate (pKa of conjugate acid is ~5). The LG for salol would be phenol (pKa ~10). The more stable the LG the better it is at leaving and the easier the ester is to hydrolyse. Incidentally the same reasoning can be used to explain acid strength above, resonance stability of carboxylate

ASPIRIN Aspirin is in a group of drugs called salicylates. It works by reducing substances in the body that cause pain, fever, and inflammation. It is used to treat mild to moderate pain, and also to reduce fever or inflammation. It is sometimes used to treat or prevent heart attacks, strokes, and angina. Aspirin should be used for cardiovascular conditions only under the supervision of a doctor. SYNTHESIS OF ASPIRIN Can be prepared by the esterification of the phenolic hydroxyl group of salicylic acid with the acetyl group from acetic anhydride or acetyl chloride. It involves primarily of 3 parts HOW TO MAKE ASPIRIN S Synthesize I Isolate P Purify SYNTHESIS The synthesis involves the reaction of salicylic acid and acetic anhydride in the presence of a catalyst, phosphoric acid, H3PO4. The synthesis of aspirin is classified as an esterification reaction. Salicylic acid is treated with acetic anhydride, an acid derivative, causing a chemical reaction that turns salicylic acid's hydroxyl group into an ester group. This process yields aspirin and acetic acid, which is considered a byproduct of this reaction. Small amounts of sulfuric acid (and occasionally phosphoric acid) are almost always used as a catalyst. WHY THE NEED FOR ACIDIC CATALYST? The minute amount of acid is needed to produce hydronium ions in the solution(both by dissociation and by water dissociation and this is why it is considered a catalyst because it is not consumed) The hydronium ions acts as the electrophile which attacks the acid anhydride which in turns attacks the salycilic acid. ISOLATION Once the aspirin is prepared it must be isolated from the reaction solution and purified. The aspirin is insoluble in cold water, and can be isolated by filtering the chilled reaction solution.

The aspirin is insoluble in cold water, and can be isolated by filtering the chilled reaction solution. Purification is necessary to remove any unreacted salicylic acid and acetic anhydride, as well as the acetic acid product and phosphoric acid. Acetic anhydride is caused to decompose by the addition of water once the formation of aspirin is complete:

ESTIMATION OF PURITY The melting point of a compound can be used to identify it and also to estimate its purity. Generally an impure compound will exhibit a melting point which is lower than that of the pure compound. Recrystallization Salicylic acid is only slightly soluble in water and is not completely removed in the washing step. The impure aspirin is dissolved in warm ethanol. The solution is then cooled slowly, and the aspirin crystallizes out of solution leaving the salicylic acid and other impurities behind. Explain why in the crystallization of aspirin, the water should not be heated above 80C Excess acetic anhydride present along with the aspirin decomposes upon heating. The reaction is exothermic and hot vapor and spattering of the solution may occur. Aspirin may degrade to form back into acetic anhydride and salicylic acid Explain the results obtained when aspirin and salicylic acid were treated with FeCl3 solution. The addition of ferric chloride to salicylic acid produces a specific color caused by the reaction of salicylic acid with aqueous ferric (Fe(H2O)6+3) ion. The oxygen atoms of the acid group COOH, and of the -OH group on the salicylic acid together can form a complex with Fe(H2O)6+3. That complex has an intense violet color. In aspirin, the OH group of salicylic acid has been replaced by a O-COCH group which prevents the second bond from being formed. The resulting complex with aspirin shows only a slight yellow color, not very different from that of Fe(H2O)6+3 itself. Another pharmaceutical product derived from salicylic acid is salol (phenyl salicylate), the phenyl ester of salicylic acid. Since phenol cannot be esterified by direct interaction with salicylic acid, some indirect method must be used. Write equations for a sequence that might be used to prepare salol from phenol and salicylic acid. Aspirin and salol are both acidic substances. Which is the stronger acid? Which would be more easily hydrolyzed in an alkaline medium? Why?