Azidotrimethylsilane1

Me3SiN3

[4648-54-8]  · C3H9N3Si  · Azidotrimethylsilane  · (MW 115.21)

(azidation of organic halides, acetals, and esters; a- and b-siloxy azides from carbonyl compounds and epoxides; preparation of heterocyclic compounds; effective substitute for hydrazoic acid)

Alternate Names: trimethylsilyl azide; TMSA.

Physical Data: bp 95-96 °C; n20D 1.416; d 0.868 g cm-3; fp 23 °C; IR nmax 2100 cm-1; 1H NMR (CDCl3) d = 0.22.

Solubility: sol most organic solvents.

Form Supplied in: colorless liquid.

Preparative Methods: several methods for the synthesis of this azide have been reported.1 The procedure involving aluminum chloride is not recommended, since an explosive product is formed.2 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.

Handling, Storage, and Precautions: the azide, which decomposes at 500 °C,1b is more stable thermally than most organic azides and can be stored in a refrigerator for more than one year. It is moisture sensitive, and should be handled with care since it reacts rapidly with water to release toxic hydrazoic acid. Handle in a fume hood.

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).3 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).4

Acyl halides react with TMSA to give trimethylsilyl halides and the corresponding isocyanates in a range of 83-98% yields, which are rearranged from the acyl azides via the Curtius degradation (eq 2).5 However, a reaction of aroyl chlorides with TMSA in the presence of Zinc Iodide at 0 °C gives the corresponding azides in 85-96% yields (eq 3).6

The azide reacts with orthoesters at reflux temperature and acetals in the presence of SnCl4 at -78 °C to give the corresponding azides in 40-70% yields (eq 4).7

a-Siloxy Azides.

TMSA reacts with carbonyl compounds to give a-siloxy azides in the presence of Zinc Chloride or Tin(II) Chloride. With aldehydes, a-siloxy azides are obtained in 70-80% yields,8,9 but the yields of these compounds are very low with most ketones.9 Carbonyl compounds including ketones are stepwisely or directly converted into gem-diazides (30-80%), tetrazoles (40-100%), and nitriles (60-100%), depending on the reaction conditions.9 The reaction sequences are summarized in Scheme 1.

b-Siloxy Azides.

The azide reacts with epoxides in the presence of zinc chloride,8b titanium and vanadium complexes,10 zinc tartrate,11 and Aluminum Isopropoxide12 to give b-siloxy azides in 80-100% yields (eq 5), which are precursors of b-amino alcohols. With cyclohexene oxide, the trans isomer is formed exclusively, regardless of the catalyst used.8b,10 However, the regio- and chemoselectivity of the reactions of other epoxides depend upon the catalyst.10-12

Application of this procedure for the regio- and stereoselective synthesis of vinyl azides in the presence of Boron Trifluoride Etherate complex is summarized in eq 6.13

o-Siloxy Isocyanates.

Acyclic anhydrides react with TMSA in a manner similar to acid halides to give equal amounts of trimethylsilyl esters and isocyanates (eq 7).5b,14 Similarly, cyclic anhydrides react with the azide to give o-trimethylsiloxycarbonyl alk(en)yl isocyanates (eq 8)14a,15 which are further transformed into 1,3-oxazine-2,6-dione derivatives (70-90%).14b

[3 + 2] Cycloaddition.

TMSA, like other alkyl azides, reacts with alkynes and C-hetero multiple bonds to give [3 + 2] cycloaddition products, triazoles and tetrazoles.1 For example, the reaction of TMSA with 2-butyne gives 4,5-dimethyl-2-trimethylsilyl-1,2,3-triazole in 78-87% yields (eq 9),16 and TMSA and cyanoferrocene react to give 5-ferrocenyl-2-trimethylsilyltetrazole in 75% yield (eq 10).17

Lead and Phenyliodoso Azides.

When Lead(IV) Acetate and phenyliodoso derivatives are used as a catalyst for azidation of alkenic and aromatic compounds (eq 11),1,18 lead azides and phenyliodoso azides are formed as intermediates.

Miscellaneous.

A combination of the azide and triflic acid is a highly efficient electrophilic aromatic amination reagent system.19

Related Reagents.

Hydrazoic Acid; Sodium Azide; Tri-n-butyltin Azide.


1. (a) Weber, W. P. Silicon Reagents for Organic Synthesis; Springer: New York, 1983; p 40 and references cited therein; (b) Peterson, Jr. W. R. Rev. Silicon, Germanium, Tin, Lead Compounds 1974, 1, 193.
2. West, R.; Zigler, S. Chem. Eng. News 1984, 62 (34), 4.
3. Nishiyama, K.; Karigomi, H. CL 1982, 1477.
4. Prakash, G. K. S.; Stephenson, M. A.; Shih, J. G.; Olah, G. A. JOC 1986, 51, 3215.
5. (a) Kricheldorf, H. R. S 1972, 551; (b) Washburne, S. S.; Peterson, Jr., W. R. SC 1972, 2, 227.
6. Prakash, G. K. S.; Iyer, P. S.; Arvanaghi, M.; Olah, G. A. JOC 1983, 48, 3358.
7. (a) Hartmann, W.; Heine, H.-G. TL 1979, 513; (b) Kirchmeyer, S.; Mertens, A.; Olah, G. A. S 1983, 500; (c) Moriarty, R. M.; Hou, K.-C. S 1984, 683.
8. (a) Birkofer, L.; Müller, F.; Kaiser, W. TL 1967, 2781; (b) Birkofer, L.; Kaiser, W. LA 1975, 266.
9. (a) Nishiyama, K.; Watanabe, A. CL 1984, 455. (b) Nishiyama, K.; Oba, M.; Wantanabe, A. T 1987, 43, 693. (c) Nishiyama, K.; Yamaguchi, T. S 1988, 106.
10. Blandy, C.; Choukroun, R.; Gervais, D. TL 1983, 24, 4189.
11. Yamashita, H. CL 1987, 525.
12. Emziane, M.; Lhoste, P.; Sinou, D. S 1988, 541.
13. Tomoda, S.; Matsumoto, Y.; Takeuchi, Y.; Nomura, Y. BCJ 1986, 59, 3283.
14. (a) Washburne, S. S.; Peterson, Jr., W. R.; Berman, D. A. JOC 1972, 37, 1738; (b) Kricheldorf, H. R. CB 1972, 105, 3958.
15. Kricheldorf, H. R.; Regel, W. CB 1973, 106, 3753.
16. Birkofer, L.; Wegner, P. CB 1966, 99, 2512.
17. Washburne, S. S.; Peterson, Jr. W. R. JOM 1970, 21, 427.
18. (a) Zbiral, E.; Kischa, K. TL 1969, 1167; (b) Ehrenfreund, J.; Zbiral, E. T 1972, 28, 1697.
19. Olah, G. A.; Ernst, T. D. JOC 1989, 54, 1204.

Kozaburo Nishiyama

Tokai University, Shizuoka, Japan



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