[22737-37-7]  · C6H19NOSi2  · N,O-Bis(trimethylsilyl)hydroxylamine  · (MW 177.39)

(protected hydroxylamine synthon for the formation of isocyanates,6 hydroxamic acids,6 N-phosphinoylhydroxylamines,12 and oximes13)

Physical Data: bp 137-139 °C, 78-80 °C/100 mmHg; d 0.830 g cm-3; flash point 28 °C.

Solubility: sol THF, ether, pentane, CH2Cl2.

Form Supplied in: liquid; widely available, but expensive.

Analysis of Reagent Purity: 1H NMR (benzene-d6) d 0.16 (s, 9, NSiMe3), 0.25 (s, 9, OSiMe3), 4.6 (br s, 1, NH).1-3

Preparative Methods: can be prepared in 69% yield by treating dry Hydroxylamine with 2 equiv Chlorotrimethylsilane and 2 equiv Triethylamine.3 A safer preparation, which avoids the use of the explosive solid, hydroxylamine, uses the reaction of hydroxylamine hydrochloride with excess Hexamethyldisilazane (71-75% yield).1,2 Alternatively, neutralization of hydroxylamine hydrochloride with ethylenediamine followed by addition of chlorotrimethylsilane can be used.4

Handling, Storage, and Precautions: flammable, corrosive liquid; hydrolyzed by moist air. Avoid inhalation and prevent contact with skin and eyes. The reagent should be stored under argon at 0-4 °C. Use in a fume hood.

Nucleophilic Reactions.

N,O-Bis(trimethylsilyl)hydroxylamine is a protected, lipophilic form of hydroxylamine. It reacts with a variety of electrophiles predominantly by attack on the nitrogen nucleophilic center. Reaction with acid chlorides (1 equiv) in the presence of triethylamine gives N,O-bis(trimethylsilyl)hydroxamic acids by N-acylation.6 A related reagent, tris(trimethylsilyl)hydroxylamine, gives the same product in high yields, also by N-acylation.5,6 Hydrolysis gives the free hydroxamic acids, whereas thermal fragmentation affords isocyanates (eq 1).6

Excess Acetyl Chloride (and presumably other acyl chlorides) reacts with N,O-bis(trimethylsilyl)hydroxylamine to give O-acetyl acetohydroxamate in 88% yield after hydrolytic workup.7 Isocyanates react exothermically with N,O-bis(trimethylsilyl)hydroxylamine to give N,O-bis(trimethylsilyl)-N-hydroxyureas in high yields.8 Carboxylation of N,O-bis(trimethylsilyl)hydroxylamine with Carbon Dioxide in THF followed by silylation gives a tris(trimethylsilyl) derivative of N-hydroxycarbamic acid.9 This intermediate rearranges in high yield to afford an N-trimethylsilyloxy isocyanate (eq 2).10

Reaction of N,O-bis(trimethylsilyl)hydroxylamine with Diketene affords the explosive N,O-bis(trimethylsilyl) derivative of acetoacetylhydroxamic acid. Deprotection and cyclization gives an isoxazole (eq 3) whose dianion serves as a useful b-keto amide synthon.11

Phosphorus analogs of hydroxamic acids, prepared from phosphinic chlorides and N,O-bis(trimethylsilyl)hydroxylamine, tend to be unstable. The stable O-sulfonyl derivatives of the phosphinoylhydroxylamines undergo base-induced, Lossen-type rearrangement to phosphonamidates by aryl group migration from P to N (eq 4).12

Deprotonation of N,O-bis(trimethylsilyl)hydroxylamine with n-Butyllithium or Potassium Hydride at low temperature yields the nitrogen centered anion N,O-bis(trimethylsilyl)hydroxylamide.6,13 At higher temperatures the oxyanion N,N-bis(trimethylsilyl)hydroxylamide is formed by rearrangement.1,14 Each reacts with acyl chlorides chemospecifically by N-acylation and O-acylation, respectively. The oxyanion also reacts with silyl halides,1a methyl iodide,1 and sulfonyl chlorides14 chemospecifically on oxygen. In a Peterson-type one-pot reaction, oximes and oxime derivatives can be prepared effectively from the N-anion of N,O-bis(trimethylsilyl)hydroxylamine and an aldehyde or ketone (eq 5).13 Oximes of sterically hindered ketones can be formed in high yields by this procedure.

1. (a) West, R.; Boudjouk, P. JACS 1973, 95, 3987. (b) West, R.; Boudjouk, P.; Matuszko, A. JACS 1969, 91, 5184.
2. Chang, Y. H.; Chiu, F.-T.; Zon, G. JOC 1981, 46, 342.
3. Wannagat, U.; Smrekar, O. M 1969, 100, 750 (CA 1969, 71, 22 148x).
4. Bottaro, J. C.; Bedford, C. D.; Dodge, A. SC 1985, 15, 1333.
5. Ando, W.; Tsumake, H. SC 1983, 13, 1053.
6. King, F. D.; Pike, S.; Walton, D. R. M. CC 1978, 351.
7. Kozyukov, V. P.; Feoktistov, A. E.; Mironov, V. F. JGU 1988, 58, 1154.
8. Muzovskaya, E. V.; Kozyukov, Vik. P.; Mironov, V. F.; Kozyukov, V. P. JGU 1989, 59, 349.
9. Mironov, V. F.; Sheludyakov, V. D.; Kirilin, A. D. JGU 1979, 49, 817.
10. Sheludyakov, V. D.; Gusev, A. I.; Dmitrieva, A. B.; Los', M. G.; Kirilin, A. D. JGU 1983, 53, 2051.
11. Oster, T. A.; Harris, T. M. JOC 1983, 48, 4307.
12. (a) Harger, M. J. P.; Shimmin, P. A. TL 1991, 32, 4769. (b) Fawcett, J.; Harger, M. J. P.; Sreedharan-Menon, R. CC 1992, 227. (c) Harger, M. J. P.; Shimmin, P. A. T 1992, 48, 7539.
13. Hoffman, R. V.; Buntain, G. A. S 1987, 831.
14. King, F. D.; Walton, D. R. M. S 1975, 788.

M. Catherine Johnson & Robert V. Hoffman

New Mexico State University, Las Cruces, NM, USA

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