Methyl-Ester Protection and Deprotection

Carboxylic acids can be protected by conversion to a methyl ester using diazomethane. The diazomethane abstracts a proton to make a carboxylate, which undergoes an S_N2 reaction with the methyldiazonium ion, releasing nitrogen gas to form the ester.

The carboxylic acid is regenerated when hydroxide attacks the carbonyl to release methoxide.

• The main drawback to methyl-ester protection is the toxicity of diazomethane. One possible alternative is to use alkyltriazene instead ^[1], which is readily prepared from primary amines and aryldiazonium salts. ^[2]
• The carboxylic acid can also be regenerated under acidic conditions (pH < 1). ^[3]

Protection

• Reactant: Carboxylic Acid, Diazomethane
• Product: Ester
• Type of Reaction: S_N2
• Bond Formation: O=C-O-Me

Deprotection

• Reagents: Base (Alkali Metal Hydroxides, Carbonates), Aqueous/Organic Solvent Mixture (H₂O, MeOH, THF, Dioxane)
• Reactant: Ester
• Product: Carboxylic Acid
• Type of Reaction: Ester Hydrolysis
• Bond Formation: O=C-OH

Mechanism

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Related Reactions

Related Compounds

Protection

Deprotection