BOC Protection and Deprotection
The BOC (tert-butoxycarbonyl) group is used to protect amines in synthetic reactions.
Di-tert-butyl dicarbonate, BOC2O (also known as di-tert-butyl pyrocarbonate or BOC anhydride), triethylamine (TEA), and tetrahydrofuran (THF) are commonly used to add the BOC group. The amine attacks a carbonyl site of BOC2O, creating a t-butyl carbonate leaving group that breaks down to carbon dioxide gas and t-butoxide. The base then abstracts a proton from the positively charged amine.
Trifluoroacetic acid (TFA) and dichloromethane (DCM) are commonly used to remove the BOC group. The protected amine is first protonated by TFA, triggering the production of a t-butyl cation and carbamic acid, which is decarboxylated to yield the amine.
Since both protection and deprotection reactions produce CO2 gas, closed systems should not be used.
1. Jia, X., Huang, Q, Li, J., Li, S., Yang, Q. Environmentally benign N-Boc protection under solvent-and catalyst-free conditions. Synlett 2007, 5, 0806-0808.
- The BOC group can also be added without the use of a solvent. 
- One way to selectively protect primary amines in polyamines is to use t-BuOCO2Ph in CH2Cl2, or DMF. 
- ZnBr2 in CH2Cl2 selectively cleaves secondary N-BOC groups, leaving primary N-BOC groups untouched. 
- Montmorillonite K10 clay in ClCH2CH2Cl selectively cleaves aromatic N-BOC groups, leaving aliphatic N-BOC amines intact. 
2. Pittelkow, M., Lewinsky, R., Christensen, J.B. Selective synthesis of carbamate protected polyamines using alkyl phenyl carbonates. Synthesis 2002, 15, 2195-2202.
3. Nigama, S. C., Mann, A., Taddei, M., Wermutha, C-G. Selective removal of the tert-butoxycarbonyl group from secondary amines: ZnBr2 as the deprotecting reagent. Synth. Commun. 1989, 19(18), 3139-3142.
4. Shaikh, N. S., Gajare, A. S., Deshpande, V. H., Bedekar, A. V. A mild procedure for the clay catalyzed selective removal of the tert-butoxycarbonyl protecting group from aromatic amines. Tetrahedron Lett. 2000, 41(3), 385-387.
- Reagents: BOC2O, Base (TEA), THF
- Reactant: 1° or 2°Amine
- Product: N-BOC Protected Amine
- Type of Reaction: Nucleophilic Acyl Substitution
- Bond Formation: N-BOC group
- Reagents: Strong Organic Acid (TFA, p-Toluenesulfonic Acid), DCM
- Reactant: N-BOC Protected Amine
- Product: 1° or 2°Amine