[58632-95-4]  · C13H14N2O3  · 2-(t-Butoxycarbonyloxyimino)-2-phenylacetonitrile  · (MW 246.27)

(reagent for protection of amino acids as t-butyl carbamates1-3 and for protection of alcohols as t-butyl carbonates4)

Alternate Name: Boc-ON.

Physical Data: mp 87-89 °C.

Solubility: very sol ethyl acetate, ether, benzene, chloroform, dioxane and acetone; sol methanol, 2-propanol, and t-butanol; insol petroleum ether and water.

Form Supplied in: solid.

Handling, Storage, and Precautions: contact with the reagent may cause irritation. The toxicological properties of the reagent have not been thoroughly investigated. The reagent should be stored in a brown bottle at -20 °C to prolong shelf life. After several weeks at rt the reagent undergoes gradual decomposition with evolution of CO2.

Amine Protection.

The reagent, informally referred to as Boc-ON, has been widely employed for the protection of amines as their t-butoxycarbonyl (Boc) derivatives. The original description of Boc-ON reports its utility for the N-protection of a-amino acids (eq 1),1 and this use is still the major application.5

The reaction is generally carried out using 1.1 equiv of Boc-ON and 1.5 equiv of Triethylamine in either 50% aqueous dioxane or 50% aqueous acetone. Boc derivatives are obtained in high yields after 4-5 h at 20 °C or 1 h at 45 °C. The oxime byproduct (eq 1) can be easily and completely removed from the reaction mixture by extraction with ether, ethyl acetate, or benzene. To secure high purity and high yield, distillation of the dioxane or acetone prior to extraction of the oxime byproduct is recommended, though direct extraction may be feasible in most cases. Yields for various amino acids range from good to virtually quantitative (Table 1).

Boc-ON offers a distinct advantage over t-Boc azide which can require reaction temperatures of 50-60 °C.6 In addition, t-Boc azide is thermally unstable and decomposes with apparent detonation at temperatures above 80 °C. Boc-ON is comparable to Di-t-butyl Dicarbonate in terms of reaction times, yields, convenience, availability, and work-up procedure.7

Boc-ON has also been employed for the protection of secondary amines (eqs 2 and 3).8,9

The reagent will selectively protect the amino group in the presence of alcohols and phenols as well as carboxylic acids. Examples include the Boc protection of a kanamycin A derivative (eq 4)10 and of the glycopeptide antibiotic A41030A (eq 5).11

In the case of diamino acids, such as ornithine or lysine, Boc-ON has been used to effect selective protection of NW at pH 11 (eqs 6 and 7).12,13

This selective protection has also been accomplished with copper-chelated diamino acids (eq 8).14

Alcohol Protection.

Boc-ON has also been employed to protect alcohols as their t-butyl carbonates.4,15,16 For this application the alcohol must first be deprotonated to its alkoxide conjugate base (eqs 9 and 10).

Related Reagents.

N-(t-Butoxycarbonyloxy)phthalimide; N-(t-Butoxycarbonyloxy)succinimide; t-Butyl Azidoformate; Di-t-butyl Dicarbonate.

1. Itoh, M.; Hagiwara, D.; Kamiya, T. TL 1975, 49, 4393.
2. Itoh, M.; Hagiwara, D.; Kamiya, T. BCJ 1977, 50, 718.
3. Itoh, M.; Hagiwara, D.; Kamiya, T. OS 1980, 59, 95.
4. Barlett, P. A.; Meadows, J. D.; Ottow, E. JACS 1984, 106, 5304.
5. FF 1977, 6, 91.
6. OS 1977, 57, 122.
7. Persio, G.; Piani, S.; De Castiglione, R. Int. J. Peptide Protein Res. 1983, 21, 227.
8. Galardy, R. E. B 1987, 21, 5777.
9. Vaurecka, M.; Hesse, M. HCA 1989, 72, 847.
10. Matsuda, K.; Yasuda, N.; Tsutsumi, H.; Takaya, T. J. Antibiot. 1985, 38, 1719.
11. Hunt, A. H.; Dorman, D. E.; Debono, M.; Molloy, R. M. JOC 1985, 50, 2031.
12. Heimer, E. P.; Wang, C.-T.; Lambros, T. J.; Felix, A. M. OPP 1983, 15, 379.
13. Bigge, C. F.; Hays, S. J.; Novak, P. M.; Drummond, J. T.; Johnson, G.; Bobovski, T. P. TL 1989, 30, 5193.
14. Rosowsky, A.; Freisham, J. H.; Moran, R. G.; Solan, V. C.; Bader, H.; Wright, J. E.; Radike-Smith, M. JMC 1986, 29, 655.
15. Bartlett, P. A.; Meadows, J. D.; Brown, E. G.; Morimoto, A.; Jernstedt, K. K. JOC 1982, 47, 4013.
16. Martin, S. F.; Zinke, P. W. JOC 1991, 56, 6600.

Michael S. Wolfe

National Institutes of Health, Bethesda, MD, USA

Jeffrey Aubé

University of Kansas, Lawrence, KS, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.