Azidotrimethylsilane

Azidotrimethylsilane (TMSN3) is a clear colorless to slightly yellow liquid. It shows very slow decomposition at high temperatures. It is a very commonly used azide source and has been used in the synthesis of aminotriazole ligands. Azidotrimethylsilane can be easily synthesised by adding chlorotrimethylsilane dropwise to a stirred solution of NaN3 in diethylene glycol dimethyl ether.

Trimethylsilyl azide is used as an azidonation reagent for amines, amides, aldehydes and ketones. It is involved in the preparation of alfa- and beta-siloxy azides from carbonyl compounds and epoxides. It is also used in the preparation of heterocyclic compounds and also acts as an effective substitute for hydrazoic acid. Further, it is used in the Oseltamivir total synthesis.

Many applications of TMSA in organic synthesis have been reported but only representative examples are described herein.Substitution Reactions. Benzyl,allyl,and substituted alkyl halides are converted to the corresponding azides in 60–100% yields via reactions with TMSA under neutral conditions in a nonaqueous solvent (eq 1).By using tin(IV) chloride as a catalyst, secondary and tertiary cyclic and polycyclic halides are similarly transformed into the corresponding azides in 50–92% yields (eq 1).

Azidotrimethylsilane may be synthesised by reacting trimethylchlorosilane with sodium azide in hexamethylphosphoramidic triamide. several methods for the synthesis of this azide have been reported.The procedure involving aluminum chloride is not recommended, since an explosive product is formed.Azidotrimethylsilane is now commercially available, and a representative synthetic procedure is as follows. A mixture of sodium azide and chlorotrimethylsilane is refluxed in di-n-butyl ether for 2 days and the azide is safely distilled directly from the reaction vessel. Purer compound (99% content) is obtained by redistillation of the product. Several improved conditions have been reported for the preparation of this azide.In these procedures, trimethylsilyl chloride is reacted with sodium azide either neat or in a high boiling point solvent, such as a mixture of silicone oil and polyethylene glycol. Distillation of the crude product usually provides trimethylsilyl azide (TMSA) in high purity (97.9%) and yield (97%).

Distil the azide through a Vigreux column (p 11) in a N2 atmosphere maintaining the oil bath temperature thermostat at 135-140o . Check the purity by 1H NMR [CHCl3, : single peak at 13cps from Me4Si]. Likely impurities are siloxane hydrolysis products. The azide is thermally stable even at 200o when it decomposes slowly without explosive violence. All the same, it is advisable to carry out the distillation behind a thick safety screen in a fumehood because unforseen EXPLOSIVE azides may be formed on long standing. [Birkofer & Wagner Org Synth Coll Vol VI 1030 1988.]

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