O-acetyl salicylic acid

Here is the reaction scheme for the synthesis of O-acetyl salicylic acid (13.f) from salicylic acid (13.e). What is the atom economy for this reaction ... 

Acetic anhydride is often used to prepare acetate esters from alcohols and AT-substituted acetamides from amines. For example, aspirin (acetyl-salicylic acid) is prepared commercially by the acetylation of o-hydroxy-benzoic acid (salicylic acid) with acetic anhydride. Acetaminophen, a drug used in over-the-counter analgesics such as Tylenol, is prepared by reaction of p-hydroxyaniline with acetic anhydride. Note that the more nucleophilic -NH2 group reacts, rather than the less nucleophilic -OH group. 

CONVERSION OF ACID ANHYDRIDES INTO ESTERS Acetic anhydride is often used to prepare acetate esters from alcohols. For example, aspirin (acetyl-salicylic acid) is prepared commercially by the acetylation of o-hydroxy-benzoic acid (salicylic acid) with acetic anhydride. 

Dissolve 10 g. of salicylic acid (o-hydroxybenzoic acid) in 7 ml. of dry pyridine contained in a too ml. conical flask. Then without delay (since this solution if allowed to stand tends to become a semi-solid mass) run in 7 5 ml. (8 3 g.) of acetyl chloride, adding about i ml. of the chloride at a time, and shaking the mixture continuously during the addition. The heat of the reaction causes the temperature of the mixture to rise rapidly ... 

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 ... 

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... 

The biosynthetic pathway for salicylic acid is not clear. At present, at least two pathways have been proposed. Each branches from phenyl-propanoid biosynthesis after phenylalanine has been converted to trans-cinnamic acid by phenylalanine ammonium lyase (PAL). In one scheme (Pathway 1 Fig. 4), tram-cinnamic acid would be converted to 2-hydroxy cinnamic acid (or 2-coumaric acid) by a cinnamate 2-hydroxylase. This compound could then be converted to salicylic acid via -oxidation possibly through an acetyl coenzyme A (CoA) intermediate. Alternatively, tram-cinnamic acid could be oxidized to benzoic acid and then hydrox-ylated via a postulated o-hydroxylase activity. The details of this pathway, particularly in tobacco and cucumber, deserve further study. 

Salbutamol is made from aspirin, itself simply the acetate ester of the natural product salicylic acid, by a series of substitution reactions. The first is a Friedel-Crafts acylation (an electrophilic substitution) in which aspirin itself is the acylating agent it is an isomerization in which the acetyl group gets transferred from O to C. Acylation occurs para to the electron-donating alkoxy substituent, and gives this ketone. 

Unfortunately, high-dosage chronic toxicity tests in rats and dogs resulted in gastrointestinal lesions and papillary necrosis. Clinical tests ceased. Reexamination of close analogs of flufenisal led to the selection of the 5-(2,4-difluorophenyl) derivative of salicylic acid—diflunisal. The additional fluorine atom may have compensated for loss of potency attributable to the lack of the O-acetyl group, which in turn probably accounts for... 

Acetaminosalol. 2 - li ytiroxybenzoic acid 4-(acet ylaminotphenyl ester p-aeetamidophenyl salicylate acetyl -aminophenyl salicylate acetyl -p-aminosalol p-aceiylamino-phenol salicylic acid ester phenetsal Salophen Fhenosal. C SH 3N04 mol wt 271.26. C 66.41%, H 4.83%, N 5.16%, O... 

Salicylacetatc, CMH20N2O6, a -carhoxy-o anhie acid compound with antipyrirteT l yrosat Crystals mp 149-15B, Bitter acid taste. Sparingly soluble in water soluble in ale. Noie Not to be confused with antipyrine acetyl salicylate,... 

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

A comparison of the molecular structures of salicylic acid and acetylsalicylic acid informs us that the difference between these two molecules is the presence of an 0-H group in the salicylic acid and an acetyl O-COCHs group in the acetylsalicylic acid. The crucial differences in the spectra will manifest themselves in the 0-H stretching and C=0 stretching regions of each spectrum. 

For less acidic alcohols, nucleophilic participation is ineffective because of the low tendency for such alcohols to function as leaving groups. The tetrahedral intermediate formed by intramolecular addition simply returns to starting material because the carboxylate is a much better leaving roup than the alkoxide. In contrast to aspirin itself, acetyl salicylates with electron-withdrawing groups (o- and p-nitro analogs) hydrolyze via the nucleophilic catalysis mechanism. ... 

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). 

---