I am a first-year chemistry graduate student and I am currently learning how to synthesize proteins. I have reached a stage in the process where I need to deprotect a carboxylic acid moiety protected by t-butyl using trifluoroacetic acid (TFA). I went online trying to find the mechanism for this step, but in terms of step-wise mechanism with electron movement arrows, the only thing I was able to find was this: Deprotection of t-butyl carboxylic acid using TFA

(Taken from here, no references therein)

While this looks legit, I am wondering about the t-butyl cation and its fate. My reaction is a bit simpler, and is presented below: Deprotection of t-butyl with TFA

And my question is: is this truly where the deprotection ends? Does the t-butyl cation remains in solution as pictured?

(I know that a t-butyl cation is considered to be relatively stable on account of it being a tertiary carbocation, but still I was not sure that it can remain in solution like that.)

  • 2
    $\begingroup$ Probably gives isobutene, depending on what solvent you're using $\endgroup$
    – Waylander
    Nov 19, 2017 at 16:31
  • $\begingroup$ The solvent is dichloromethane. What is its role? $\endgroup$
    – Don_S
    Nov 19, 2017 at 18:22
  • $\begingroup$ In which case DCM plays no part as it will not react with tBu+, other solvents may react with it e.g. toluene $\endgroup$
    – Waylander
    Nov 19, 2017 at 18:42
  • $\begingroup$ According to a post-doc colleague, step no. 4 IS the final state of the molecules in the solution (i.e. t-butyl can exist in the solution as a cation), but if water will be added to the solution, then the t-butyl cation will take an OH group and the TFA will become protonated. In case anyone was wondering... $\endgroup$
    – Don_S
    Nov 21, 2017 at 9:49
  • $\begingroup$ It is worth remembering that when you cleave a tBu ester, tBu+ can hang around and potentially react with e.g. electron-rich aromatics $\endgroup$
    – Waylander
    Nov 21, 2017 at 12:22

2 Answers 2


I realize this question is old but the mechanism is nicely described here (steps 1-3): http://www.umich.edu/~chemh215/W06HTML/SSG2/ssg6/main_files/Page346.htm

Briefly, the released t-butyl carbocation is subsequently deprotonated by the anionic TFA, resulting in the formation of 2-methyl-propene. This regenerates the protonated TFA that is needed to continue the reaction, and thus the TFA is catalytic (i.e. not consumed in the reaction).


The reaction is, in principle, catalytic in TFA. If t-butyltrifluoroacetate is the by-product, then the catalyst is consumed. If only isobutylene is formed, catalytic is OK. Using excess TFA covers all contingencies. In the initial step, protonation is more likely on the C=O oxygen. Higher electron density.


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