Chromatography Forum

Our lab finally got an LCMS, a Q-TOF, and Q-TOF's always give me noisy TIC's and never really clean peaks. Anyway...I've found a bit of my substrate + TBDMS after finally checking literature and seeing that TBDMS protected groups seem to generally yield [M-57] ions.

That aside, I noticed what I THINK is a major peak that would correlate to the loss of the TBDMS protecting group, and am wondering if the 0.1%FA in the mobile phases is enough to cleave the group as soon as it's injected. That would explain why my yield looks terrible, but I'm unsure if it would happen that fast since the actual deprotection step runs overnight in FA.

I think most of the literature you might have seen regarding TBDMS is relevant to GC-MS. That's where TBSMS is used for derivatization.

If you look at the sort of acid concentrations and hydrolysis times used for deprotecting groups deliberately, they are much harsher than 0.1% formic acid for a few minutes, so I'd be dubious that it's being cleaved. If your product is small, and completely protected, it may be hard to ionise and possibly volatile (dried off almost as efficiently as solvent!), in which case it may be harder to detect in LC-MS.

I've seen silylations that include trifluouroacetic acid in the reaction mix. Formic acid not sure. However the water will start to hydrolyze the esters. Whether they will survive long enough to get to the MS I can't say.

Random thought - are any of these reactions (and others that might affect analysis) affected by HPLC or UHPLC pressures ? I would guess not since it is all liquid phase.

CH

TBDMS ethers should be totally stable to 0.1% formic acid. The removal of these groups from an alcohol with just acid requires vigorous conditions. So much so that an F- source is typically employed to get rid of them with any efficiency