Boc deprotection: practice and mechanism
TFA removes the Boc group completely: the tert-butyl cation (as isobutene) and CO₂ leave, and the free amine remains. Esters and peptide bonds survive.
Example
Strong acid protonates the carbamate; the tert-butyl group leaves as a stable cation (becoming isobutene). The remaining carbamic acid loses CO₂, leaving the free amine. Methyl esters and amides survive TFA.
Mechanism step by step
- 1
TFA protonates the carbonyl oxygen of the carbamate.
- 2
The O–tBu bond breaks and the stable tert-butyl cation leaves (it loses H⁺ and becomes isobutene).
- 3
The carbamic acid decarboxylates spontaneously: CO₂ escapes and the amine remains (as the TFA salt).
Practice tasks
Which product forms, which reagent is needed? After each answer you see the explanation.
Which main product forms?
Typical mistakes
- The carbamic acid (N–COOH) is unstable and loses CO₂ immediately. The free amine is the end product.
- The tert-butyl group does not move to the nitrogen. It leaves as a cation and becomes isobutene.
Often confused with: Acidic hydrolysis of amides and nitriles · Ester hydrolysis (saponification)
Frequently asked questions
Why is the tert-butyl group in particular acid-labile?
It leaves as a tertiary carbocation (SN1-like). A methyl or ethyl ester would not be cleaved this way, which is why those esters survive TFA.
What happens after deprotection?
The free amine can be coupled with the next Boc amino acid. The chain grows step by step (protect → couple → deprotect).
Why is the Boc group acid-labile?
After protonation the very stable tert-butyl cation forms; the remaining carbamic acid falls apart into CO₂ and the free amine.