tertbutylocarbonyl

tert-butylocarbonyl, commonly known as the Boc group, is a protecting group used to mask amine functionalities in organic synthesis. It consists of a carbamate moiety with a tert-butyl group, giving the tert-butoxycarbonyl structure attached to the nitrogen: R-NH-CO-O-tBu. The Boc group is introduced by treating the amine with di-tert-butyl dicarbonate (Boc2O) in the presence of a base such as DIPEA or DMAP, forming the Boc-protected amine R-NH-CO-O-tBu. The group is valued for its stability to bases and many coupling conditions used in peptide synthesis, while being readily removable under acidic conditions.

Deprotection is typically achieved with strong acids such as trifluoroacetic acid (TFA) in dichloromethane, or HCl in dioxane, often at room temperature. Removal of Boc generates carbon dioxide and tert-butyl cation, which is captured by scavengers to form byproducts like tert-butyl alcohol or isobutene, leaving behind the free amine as its salt in acidic media. Alternative deprotection methods include more aggressive acid treatments or heating in the presence of solvents, and scavengers are commonly included to minimize side reactions.

In peptide synthesis, the Boc strategy is often contrasted with Fmoc, a base-labile protecting group. Boc remains one of the oldest and most widely used amine protections, particularly in solid-phase peptide synthesis, though Fmoc now dominates some workflows due to milder deprotection conditions.

See also: Fmoc, Cbz, di-tert-butyl dicarbonate.