[14691-89-5]  · C11H21N2O2  · 4-Acetamido-2,2,6,6-tetramethyl-1-piperidinyloxyl  · (MW 213.30)

(reagent and catalyst for selective oxidation of alcohols2)

Alternate Names: 4-acetamido-TEMPO; 4-acetylamino-TEMPO.

Physical Data: mp 146-147 °C,2 147.5 °C.3

Solubility: nearly insol hexane, ether; sol ethanol, acetone, acetonitrile, methylene chloride; slightly sol water, from which it can be recrystallized.

Form Supplied in: red or pink solid, commercially available.

Preparative Method: can be easily prepared in high yield from 4-amino-2,2,6,6-tetramethylpiperidine.2

Handling, Storage, and Precautions: completely stable and nonhygroscopic.

Oxidation of Alcohols.

4-Acetamido-TEMPO is a representative of the nitroxide radicals (1) which have been used as reagents or catalysts for the oxidation of organic compounds.1 Several nitroxide radicals have been converted to the corresponding oxoammonium salts (2) and used as stoichiometric oxidizing reagents.1 Nitroxide radicals have also been used as catalysts in the the presence of a secondary, stoichiometric oxidant (see 2,2,6,6-Tetramethylpiperidin-1-oxyl).1

4-Acetamido-TEMPO (3) is not, itself, a reagent for the oxidation of alcohols. Rather, it serves as a convenient precursor for the in situ preparation of an oxoammonium salt (4), which is the true oxidant. The oxoammonium salt (4) is the product of the acid-catalyzed disproportionation of (3) to (4) and (5) in the presence of p-Toluenesulfonic Acid (eq 1) and is a highly selective reagent for alcohol oxidation (eq 2).1 The reactions are carried out in methylene chloride in which TsOH.H2O is essentially insoluble. The only products of the reaction are the desired carbonyl compound product (7) and the hydroxylamine salt (5), which is completely insoluble in methylene chloride. Product isolation simply involves the filtration of (5) and the evaporation of methylene chloride. Compound (5) can be converted back to the nitroxide radical (3) in quantitative yield.2

The reaction has been used for the oxidation of a variety of alcohols with excellent yields of isolated products.2 Primary alcohols are converted to the corresponding aldehydes, and no over-oxidation is observed. Secondary alcohols react as well as primary alcohols and provide the corresponding ketones. The mildness of this reaction has been demonstrated by the oxidations of nerol (8) and geraniol (9) to the corresponding cis-citral (10) and trans-citral (11).

Oxidation with this reagent does not take place when there is an oxygen or nitrogen in the b-position to the alcohol being oxidized and does not take place with 1,2-diols or sugars. Amines,1,4 thiols,5 phenols,6 indoles,7 benzyl ethers,1 and ketones (very slow)1 react with oxoammonium salts and may interfere with alcohol oxidation. However, sulfides, most ethers, amides, esters, and double bonds do not react with oxoammonium salts and should not interfere.1

A number of other oxoammonium salts have been described in the literature.1 In addition, TEMPO-type nitroxide radicals have been used as specific catalysts for the oxidation of alcohols using one or several secondary, stoichiometric oxidants.1,8 Neither 4-acetamido-TEMPO nor any of its derivatives have been used in this manner, but they should function satisfactorily.

1. Bobbitt, J. M.; Flores, M. C. L. H 1988, 27, 509 (general review on oxoammonium salts, but they are called nitrosonium salts in the title).
2. Ma, Z.; Bobbitt, J. M. JOC 1991, 56, 6110.
3. Rozantsev, E. G.; Kokhanov, Y. V. BAU 1966, 8, 1422.
4. Hunter, D. H.; Racok, J. S.; Rey, A. W.; Ponce, Y. Z. JOC 1988, 53, 1278.
5. Kashiwagi, Y.; Ohsawa, A.; Osa, T.; Ma, Z.; Bobbitt, J. M. CL 1991, 581.
6. Bobbitt, J. M.; Ma, Z. H 1992, 33, 641.
7. Bobbitt, J. M.; Guttermuth, M. C. F.; Ma, Z.; Tang, H. H 1990, 30, 1131.
8. (a) Anelli, P. L.; Montanari, F.; Quici, S. OS 1990, 69, 212. (b) Inokuchi, T.; Matsumoto, S.; Torii, S. JOC 1991, 56, 2416. (c) Leanna, M. R.; Sowin, T. J.; Morton, H. E. TL 1992, 33, 5029.

James M. Bobbitt & Zhenkun Ma

University of Connecticut, Storrs, CT, USA

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