p-Nitrobenzyl p-Toluenesulfonate1

[4450-68-4]  · C14H13NO5S  · p-Nitrobenzyl p-Toluenesulfonate  · (MW 307.35)

(conversion of a carboxylate anion into the p-nitrobenzyl ester, principally for use as a protecting group1,2)

Physical Data: mp 103-104 °C.

Solubility: sol most organic solvents.

Form Supplied in: not commercially available.

Preparative Methods: by reaction of (a) p-Toluenesulfonyl Chloride with p-nitrobenzyl alcohol3 for 30 min in dry pyridine at -10 °C; or (b) dry Silver(I) p-Toluenesulfonate with p-nitrobenzyl bromide in refluxing dry CHCl3 for 24 h in the dark.2

Purification: recrystallize from 2-propanol-petroleum ether,2 ligroin,3 or anhydrous ethyl ether.4

Handling, Storage, and Precautions: mutagenic in the Ames Salmonella plate incorporation assay (using strain TA100);5 should be treated as a potential carcinogen; can induce skin sensitization in guinea pigs.6 Can be kept for long periods without apparent decomposition.3

p-Nitrobenzyl p-toluenesulfonate (PNB-OTs) is used as a reagent for protecting carboxylic acids. Formation of the ester involves conversion of the acid to a carboxylate salt (e.g. to the sodium salt using NaOMe in methanol,2 or to the Et3NH+ salt using Et3N7), followed by reaction with PNB-OTs in Me2CO2,7 or Me2CO-DMF (2:1).2,8 The PNB esters are stable to HBr/HOAc at room temperature (permitting cleavage of N-Cbz groups) and are readily cleaved by catalytic hydrogenation2 (or NaOH/aq acetone8); the conditions of protection and deprotection minimize racemization of amino acids and peptides. In the example in eq 1, the protection-deprotection sequence was used9 to avoid formation of a lactone along with the diacetate.

PNB-OTs has also been used as a UV labeling agent for detecting monocarboxylic acids in HPLC analyses.10

1. Fieser, L. F.; Fieser, M. FF 1967, 1, 736.
2. Theodoropoulos, D.; Tsangaris, J. JOC 1964, 29, 2272.
3. Kochi, J. K.; Hammond, G. S. JACS 1953, 75, 3443.
4. Dietze, P.; Jencks, W. P. JACS 1989, 111, 5880.
5. Ball, J. C.; Foxall-VanAken, S.; Jensen, T. E. Mutat. Res. 1984, 138, 145.
6. Roberts, D. W.; Goodwin, B. F. J.; Williams, D. L.; Jones, K.; Johnson, A. W.; Alderson, J. C. E. Food Chem. Toxicol. 1983, 21, 811.
7. Stavropoulos, G.; Theodoropoulos, D. JHC 1977, 14, 1139.
8. Jacobs, P. M.; Sneath, R. L., Jr.; Soloway, A. H.; Dey, A. S. JPS 1976, 65, 604.
9. Starratt, A. N. Chem. Phys. Lipids 1976, 16, 215.
10. Funazo, K.; Tanaka, M.; Yasaka, Y.; Takigawa, H.; Shono, T. J. Chromatogr. 1989, 481, 211.

James F. King

The University of Western Ontario, London, Ontario, Canada

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