Silylating agents alcohol groups

A large number of silylating agents exist for the introduction of the trimethylsilyl group onto a variety of alcohols. In general, the sterically least hindered alcohols are the most readily silylated, but these are also the most labile to hydrolysis with either acid or base. Trimethylsilylation is used extensively for derivatization of... 

To remove the water, which is formed on dimerization of trimethylsilanol, at least one additional equivalent of a silylating agent such as HMDS [boiling point = 126°C] must be used. Excess HMDS can then react with trimethylsilanol or water to give hexamethyidisiloxane and ammonia, but will also reconvert any hydrolyzed hydroxy-N-heterocycle into the corresponding activated 0-silylated intermediates. Thus, sufficient HMDS should be used to silylate the hydroxy-N-heterocycle and all the alcoholic, phenolic, or other acidic hydroxy groups present in the heterocyclic or amine moiety. It should also be used to convert trimethylsilanol and water (or intruded humidity) from the reaction into hexamethyidisiloxane and ammonia (Eqs. 1-3). 

Hexamethyldisilazane (HMDS) is one of the most common silylating agents and readily silylates alcohols, acids, amines, thiols, phenols, hydroxamic acids, amides, thioamides, sulfonamides, phosphoric amides, phosphites, hydrazines, and enolizable ketones. It works best in the presence of a catalyst such as X..NH...Y, where at least one of the groups X or Y is electron-withdraw-... 

Depending on the type of silylating agent, in the case of unsaturated alcohols either the double (or triple) bond or the hydroxyl group is silylated398. For instance, if 2,3-dihydroxy-2,3-dimethylhept-6-en-4-yne (718) is treated with triethylsilane, then C-silylation to 719 occurs, whereas the combination Me3SiCl/pyridine leads to O-silylation (720) (equation 365)400. 

Many of the biologically important -phenylalkyl-amines and also indolylalkylamines contain alcoholic and/or phenolic hydroxyls. For a separation by GC, these polar groups must be derivatized. This can be done by silylation. We use a one-step method [49], Both reagents, carbon disulfide and the silylating agent (usually trimethylsilylimidazole), are added to a solution of the amine in a polar solvent such as dimethylforma-mide or pyridine. A two-step procedure has also been described [56, 57]. The free bases are dissolved in ethyl acetate and treated with carbon disulfide, the solution is evaporated to dryness, and mustard oil is dissolved in pyridine and silylated at 100 °C. If the reaction time is sufficiently long, this procedure also silylates the indole nitrogen. Trifluoroacetylation has also been used to block the hydroxyls of the mustard oils [60]. 

---