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 SN2 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.
Lab Tips:
- 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]
1. White, E. H., Maskill, H., Woodcock, D. J. Schroeder, M.A. Carbonium ions formed in the triazene method of deamination. Tetrahedron Lett. 1969, 1713.
2. White, E. H., Scherrer, H. The triazene method for the deamination of aliphatic amines. Tetrahedron Lett. 1961, 758.
3. Wuts, P. G. M. (2014). Greene’s Protective Groups in Organic Synthesis (5th ed.). Hoboken, New Jersey: John Wiley & Sons.
Protection
- Reactant: Carboxylic Acid, Diazomethane
- Product: Ester
- Type of Reaction: SN2
- 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
Top Citations
Related Reactions
Related Compounds
Protection
- Diazomethane (CAS 334-88-3)
Deprotection
