P-toluenesulfonic acid is a commonly used acid catalyst in organic synthesis. It is neutralized with sodium hydroxide to prepare sodium p-toluenesulfonate, and then reacted with phosphorus pentachloride to prepare p-toluenesulfonyl chloride. The latter is used in nucleophilic substitution reactions and also as a protecting group for alcoholic hydroxyl groups.

p-CH3C6H4SO3Na + PCl5 → p-CH3C6H4SO2Cl

P-toluenesulfonic acid can be mixed with dehydrating agent phosphorus pentoxide to generate p-toluenesulfonic anhydride.
P-toluenesulfonic acid is also used to catalyze the esterification and transesterification of dihydropyran protecting groups on alcohols, carboxylic acids; make aldehydes form acetals; as catalysts for hydrolyzing proteins and glycoproteins; and can be used to synthesize dihydropyrimidines The Biginelli reaction and the metal nitrate are selectively nitrated in the ortho position of the phenolic hydroxyl group in phenol and substituted phenol.

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