Hi Vivek,

If you told that what functional group you going to silylate- then it will be easy to give suggestions. If it is hydroxyl, amino or carboxyl group then you can use only BSTFA at 70oC for hallf an hour. There is no requirement of any base. If you see the mechanism of silylation by BSTFA then it will be clear why there is no requirement of any base.

Hi Vivek,

Not sure what you are trying to achieve with your project/ samples.

If for metabolomics, then N- incorporation post "methoxyamination" is normal too. Is that what you are referring to ?

Also, pyridine enhances/ base of the reaction, or else, you can use BSTFA without it too, though the reaction would be extremely slow/ non-reproducible/ inconsistent results among batches.

Also, if you look at Sigma-Milipore site on the different derivatization reagents: https://www.sigmaaldrich.com/analytical-chromatography/analytical-reagents/derivatization-reagents/silylation.html and see the 2nd one, BSA for example another derivatizing reagent, has other alternatives to use other than Pyridine. Same is true for MSTFA/ BSTFA as well, and pyridine is a choice and not a must.

As Buddhadeb Chandra correctly points out are you looking for a specific functional group to be derivatized or doing more complex sample preparation (profiling of diverse chemical classes(or single class) or omics- metabolomics scale work?).

And John R Carney nicely points out to susceptibility of columns to silylation reagents and pyridine, esp. fro WAX like columns, but have been rendered harmless/ safe for xP-5MS type columns which we routinely used in the metabolomis arena for years now. True was the same concerns for DMSO with LC-MS columns but they have all developed chemistries to not let a great loss of column efficiency with pyridine/ silylation n GCMS columns and DMSO/DMF in LC-MS columns!

Good luck with your work and keep posted!

Thanks,

Biswa

Thank you, everyone, for your kind suggestions! I forgot to mention that I am trying to derivatize hydroxyl groups. It looks like avoiding pyridine (at the cost of potentially lower reproducibility) is the best choice. Also, I realized that it will take a few trial and errors to get to the right derivatization strategy. I will continue experimenting and will keep posting so that someone in the future may benefit from it.

Thanks!

Vivek