Technical Library

Outline

1. Hexamethyldisilazane, SIH6110.0, SIH6110.1, in trimethylsilylation of alcohols.
One equivalent of the alcohol to be silylated is mixed with 0.5 equivalents of HMDS, SIH6110.0, SIH6110.1, in an inert solvent or without solvent. Warming the reaction to 40 – 50 °C or adding a drop of TMSCl, SIT8510.0, can significantly accelerate the rate of reaction. The reaction is allowed to continue until no further evidence of the evolution of ammonia is observed. For primary and secondary alcohols the reaction is rapid and nearly quantitative. For tertiary alcohols the reaction will be slower.

2. Trimethylchlorosilane, SIT8510.0, SIT8510.1, in trimethylsilylation of alcohols.
One equivalent of the alcohol, 1.1 equivalents of pyridine or triethylamine are mixed in an inert solvent and one equivalent of trimethylchlorosilane, SIT8510.0or SIT8510.1, is added. The amine can also be used as the reaction solvent. The reaction can be followed any of the standard techniques including thin layer and gas chromatography. The reaction is quite fast with primary and secondary alcohols and slower with tertiary alcohols. The trimethylsilylation of amides and amines can be accomplished by a modification of this procedure wherein the reaction mixture is heated to reflux for 16 h.

3. Trimethylbromosilane, SIT8430.0, or Trimethyliodosilane, SIT8564.0 in the trimethylsilylation of alcohols.
One equivalent of the alcohol, 1.1 equivalents of a suitable amine base are mixed in an inert solvent and 1 equivalent of the trimethylbromosilane, SIT8430.0, or trimethyliodosilane, SIT8564.0, is added. Both of these reagents are more reactive than the corresponding trimethylchlorosilane.

4. Trimethyliodosilane, SIT8564.0, and Hexamethyldisilazane, SIH6110.0, combination in the trimethylsilylation of hindered alcohols.
One equivalent of the alcohol and 2.2 equivalents of trimethyliodosilane, SIT8564.0, along with 1.1 equivalents of hexamethyldisilazane, SIH6110.0, are mixed in pyridine and the reaction stirred at room temperature.

5. Trimethylsilyltrifluoromethanesulfonate, SIT8620.0, or Trimethylsilyl Cyanide, SIT8585.1 in the trimethylsilylation of alcohols.
Trimethylsilylation with these very reactive organosilanes is carried out by the simple mixing of the alcohol and the silane in an inert solvent and allowing the reaction to occur, usually at room temperature. CAUTION: the reagent trimethylsilyl cyanide generates hydrogen cyanide as a by-product.

6. Allyltrimethylsilane, SIA0555.0, in the trimethylsilylation of carboxylic acids.
One equivalent of the acid is dissolved in carbon tetrachloride (other solvents such as dichloromethane can probably be used as well) and 1.1 equivalents of allyltrimethylsilane, SIA0555.0, are added. To this reaction mixture is added about three drops of triflic acid. The reaction is very fast being complete when the evolution of propylene gas ceases.

7. Triethylchlorosilane, SIT8250.0, tert-butyldimethylchlorosilane, SIB1935.0, tert-butyldiphenylchlorosilane, SIB1968.0, Triisopropylchlorosilane, SIT8384.0, or Thexyldimethylchlorosilane, SIT7906.0 in the silylation of alcohols.
One equivalent of the alcohol is dissolved in DMF along with 1.1 equivalents of the chlorosilane and 2.2 equivalents of imidazole or 2,6-lutidine are added. The reaction is normally heated to about 40 °C for 10 to 20 h.

8. Tert-butyldimethylsilylation of an alcohol in dichloromethane.
The tert-butyldimethylsilylation of an alcohol has been carried out by treating 0.89 equivalents of tertbutyldimethylchlorosilane, SIB1935.0, in dichloromethane with 0.91 equivalents of the alcohol, 1.19 equivalents of triethylamine, and 0.036 equivalents of 4-dimethylaminopyridine at room temperature for several hours.

9. Triisopropylsilyltrifluoromethanesulfonate, SIT8620.0, in the TIPS silylation of alcohols.
One equivalent of the alcohol is reacted with 1.1 equivalents of triisopropylsilyltrifluoromethanesulfonate, SIT8620.0, in dichloromethane with 2.2 equivalents of 2,6-lutidine as catalyst. The reaction can be carried out as low as -78 °C in less than 5 h depending on the structure of the alcohol.

10. Tert-butyldimethylsilyltrifluoromethanesulfonate, SIB1967.0, in the TBS silylation of alcohols.
One equivalent of the alcohol is treated with tert-butyldimethylsiyltrifluoromethanesulfonate, SIB1967.0, as a 1 M solution in 50:50 mixture by volume of dichloromethane and pyridine. Additional SIB1967.0 may have to be added to finish the reaction for the lower reactive alcohols.

11. Di-tert-butylsilylbis(trifluoromethanesulfonate), SID3345.0, in the silylation of diols.
One equivalent of the diol is reacted at room temperature with 1.2 equivalents of di-tert-butylsilylbis(trifluorometha nesulfonate), SID3345.0, and 3 equivalents of 2,6-lutidine in chloroform. 1,3-Diols and 1,4-diols are, in general, more reactive than 1,2-diols.

12. Tert-butyldiphenylchlorosilane, SIB1968.0, in the TBDPS silylation of primary amines.
One equivalent of the primary amine is reacted with tert-butyldiphenylchlorosilane, SIB1968.0, and 1.5 equivalents of triethylamine in acetonitrile at room temperature for 1 to 3 h. Secondary amines do not silylate under these conditions.

13. 1,2-Bis(chlorodimethylsilyl)ethane, SIB1042.0, in the silylation of primary amines.
One equivalent of the primary amine is reacted with 1 equivalent of the 1,2-bis(chlorodimethylsilyl)ethane, SIB1042.0, and 2 equivalents of triethylamine in dichloromethane at room temperature for 2 to 3 h. A convenient way to isolate the product is to filter, concentrate, add pentane, filter again and concentrate to provide the product in high purity without further purification.

14. 1,1,3,3-Tetraisopropyl-1,3-dichlorodisiloxane, SIT7273.0, in the silylation of nucleosides.
One equivalent of the nucleoside is reacted with the silane, SIT7273.0, and 4.4 equivalents of imidazole in DMF at room temperature. The yields are typically 80%.

15. 1,2-Bis(dimethylsilyl)benzene, SIB1084.0, in the silylation of primary amines.
One equivalent of the amine is reacted with SIB1084.0 and a catalytic amount of Wilkinson’s catalyst, tris(triphenylphosphine) rhodium (I) chloride, in toluene.

16. Trimethylsilylethanol, SIT8589.2, in the protection of carboxylic acids.
One equivalent of the acid is reacted with trimethylsilylethanol, SIT8589.2, one equivalent of dicyclohexylcarbodiimide, in ethyl acetate with a catalytic amount of DMAP added. A typical reaction time is about 12 h at room temperature.

17. Triisopropylchlorosilane, SIT8384.0, in the trimethylsilylation of alcohols.
One equivalent of the acid is reacted with triisopropylchlorosilane, SIT8384.0, and 1.4 equivalents of triethylamine in dichloromethane for 1 h at -35 °C and then 15 h at room temperature.

18. Triisopropylsilyltrifluoromethanesulfonate, SIT8387.0, as precursor to triisopropylsilylcarbamate, Tsoc, protecting group.
The amine is reacted with carbon dioxide in the presence of triethylamine at -78 °C for 30 to 60 minutes. This mixture is then treated with triisopropylsilyltrifluoromethanesulfonate, SIT8387.0, at room temperature. The reaction mixture can be washed with water without hydrolysis of the protecting group.

19. Formation of acetonides of diols with Isopropenoxytrimethylsilane, SII6460.0.
One equivalent of the diol is mixed with isopropoxytrimethylsilane, SII6460.0, in an inert solvent (THF, ether, toluene) and 1 to 2 drops of concentrated HCl or trimethylchlorosilane are added. The reaction is complete in less than 30 minutes.

20. Dimethylaminotrimethylsilane or diethylaminotrimethylsilane in the trimethylsilylation of alcohols.
One equivalent of the alcohol or amine is reacted with the aminotrimethylsilane and dimethylamine (or diethylamine) is removed by distillation as the reaction proceeds. These reagents are particularly useful in the silylation of amines. HMDS, SIH6110.0, is preferred for the trimethylsilylation of alcohols.

21. Trimethylsilylimidazole, TMSI, SIT8590.0, in the silylation of alcohols.
Trimethylsilylimidazole, SIT8590.0, is a very reactive silylating agent, especially for alcohols. It is typically reacted with an equivalent amount of the alcohol in the presence or absence of an acid catalyst.

22. N,O-Bis(trimethylsilyl)acetamide, SIB1846.0, trimethylsilylation of alcohols.
One equivalent of the alcohol is reacted with 0.5 equivalents of N,O-bis(trimethylsilyl)acetamide, SIB1846.0, in an inert solvent. The reaction proceeds faster with a small amount of trimethylchlorosilane, SIT8510.0, as catalyst.

23. N,O-Bis(trimethylsilyl)trifluoroacetamide, SIB1876.0, trimethylsilylation of alcohols.
One equivalent of the alcohol is reacted with 0.5 equivalents of N,O-bis(trimethylsilyl)trifluoroacetamide, BSTFA, SIB1876.0, in an inert solvent with or without trimethylchlorosilane, SIT8510.0, catalysis. This has the advantage ofproducing the liquid byproduct, trifluoroacetamide, which is oftentimes easier to remove than the solid acetamide from SIB1846.0 or the diphenylurea from SIB1878.0.

24. N,N-Bis(trimethylsilyl)urea, BSU, SIB1878.0, in the trimethylsilylation of alcohols.
Two equivalents of the solid trimethylsilylating agent are reacted with one equivalent of the alcohol in an inert solvent. The solid, insoluble diphenylurea produced is readily removed by filtration and the product purified.