My issue is the following: I am trying to protect D-(+)-gluconic acid
δ-lactone using TMCl, N-methylmorpholine (NMM) and THF as a solvent. However during the addition of TMSCl the lactone suffers a hydrolysis reaction before the reaction of protection takes place. In the reaction medium it was observed a huge steam of HCl during the adition of TMSCl, which yields a whithe solid in the reaction medium. I would like to know how prevents the hydrolysis product takes place and how reduce the steam of HCl form TMSCl.
Hi
If I am not wrong, the alcohol reacts with TMSCl to form the silyated alcohol and HCl as the byproduct which reacts with NMM to form the amine salt which should be the white solid.
By hydrolysis you mean cleavage of the lactone? How do you know the lactone has been cleaved?
What temperature are you doing the addition at? Lowering the temperature to 0oC during the addition of TMSCl can help slow the initial reaction and prevent overheating.
There are other silylating reagents which do not generate HCl but will require other conditions.
Hi Anderson,
At first I would check that the reaction mixture is surely water free. Next, I try a different solvent, like pyridine.
Finally, I change the reagent to TMS-imidazole (preferred) or hexamethyldisilazane-TMSCl. For the TMS-IMI no base is necessary, otherwise when you use pyridine (and e.g. TMSCl), no additional base is necessary.
Here is how to prepare TMS-IMI: L. Birkofer, A. Ritter, Angew. Chem. 77, 414 (1965 ).
Good luck,
Laszlo
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