m-Chloroperbenzoic Acid-2,2,6,6-Tetramethylpiperidine Hydrochloride

[937-14-4]  · C7H5ClO3  · m-Chloroperbenzoic Acid-2,2,6,6-Tetramethylpiperidine Hydrochloride  · (MW 172.57)

[935-22-8]  · C9H20ClN  · m-Chloroperbenzoic Acid-2,2,6,6-Tetramethylpiperidine Hydrochloride  · (MW 177.75)

(reagent for the oxidation of alcohols at rt;1 when used in combination with other oxidizing properties of m-CPBA this reagent can effect conversion of alkenic alcohols to epoxy ketones or secondary alcohols to esters or lactones2)

Solubility: sol CH2Cl2, CHCl3, diethyl ether, THF.

Form Supplied in: for m-CPBA, see m-Chloroperbenzoic Acid; 2,2,6,6-tetramethylpiperidin-1-oxyl is a red solid, mp 36-38 °C and is available commercially.

Preparative Method: 2,2,6,6-tetramethylpiperidine hydrochloride is prepared by passing dry HCl into a cold solution of 2,2,6,6-Tetramethylpiperidine in ether.

Oxidation of Alcohols.

Secondary alcohols are oxidized to ketones at room temperature by m-CPBA in the presence of catalytic (1-2%) quantities of 2,2,6,6-tetramethylpiperidine-1-oxyl, and HCl.1 The nitroxide can be conveniently generated in situ from 2,2,6,6-tetramethylpiperidine hydrochloride (1), which also provides the requisite HCl (eq 1). The reaction can be conducted in CH2Cl2, CHCl3, or ether solvents. In practice a slight excess of m-CPBA is used to offset its slow decomposition catalyzed by the nitroxide. Workup simply involves removal of the m-CPBA by filtration and/or extraction with base followed by removal of solvent. Yields of ketones are generally quite high (75-95%).

Primary alcohols are oxidized to aldehydes by this reagent, but further oxidation of the aldehydes to carboxylic acids by m-CPBA is sometimes observed. The oxidation is tolerant of any functional groups stable to m-CPBA and dilute mineral acid. Combining this oxidation procedure with other oxidizing properties of m-CPBA enables a range of unique transformations to be effected in a simple manner.

Preparation of Epoxy Ketones.

Epoxy ketones are conveniently prepared from alkenic alcohols in a one-pot procedure by epoxidation of the alkene using slightly more than 2 equiv of m-CPBA followed by addition of TMP.HCl to the reaction mixture to effect oxidation of the alcohol.2 The procedure is particularly advantageous for the preparation of sensitive epoxy ketones. For example, (2) is prepared in 86% yield from norbornenol by this procedure (eq 2), compared to a 31% yield obtained by the Dipyridine Chromium(VI) Oxide oxidation of the same substrate.3

Combining this procedure for preparing epoxy ketones from allylic alcohols with the hydrazine-induced Wharton rearrangement4 provides a convenient sequence for the transposition of allylic alcohols, as exemplified by the conversion of (3) to (4) (eq 3).

Preparation of Esters and Lactones from Secondary Alcohols.

Although under ordinary conditions the Baeyer-Villiger oxidation does not interfere with the peracid-mediated alcohol oxidation, under more forcing conditions the reactions can be coupled to afford esters and lactones directly from secondary alcohols.2 Phenyl-2-propanol was converted to benzyl acetate in 90% yield by this process (eq 4). To accomplish this two-step sequence, a large excess of m-CPBA (3.5-4.0 equiv) is required; even under these conditions yields vary, depending on the reactivity of the ketone product to the Baeyer-Villiger reaction. Use of more reactive peracids (such as trifluoroperacetic acid or permaleic acid) was ineffective as these were rapidly degraded by the nitroxide catalyst.

Related Oxidants.

The oxoammonium ion (5) is believed to be the species responsible for alcohol oxidation in this system, and several related methods for oxidizing alcohols involving generation of this intermediate from the nitroxide using chlorine,5 bromine,5 copper(II) salts,6 sodium hypochlorite,7 or electrochemically8 have been reported. Acid-catalyzed oxidation of alcohols by m-CPBA alone has also been reported.9

1. (a) Cella, J. A.; Kelley, J. A.; Kenehan, E. F. JOC 1975, 40, 1860. (b) Cella, J. A.; Kelley, J. A.; Kenehan, E. F. CC 1974, 943. (c) Ganem, B. JOC 1975, 40, 1998.
2. Cella, J. A.; McGrath, J. P.; Kelley, J. A.; ElSoukkary, O.; Hilpert, L. JOC 1977, 42, 2077.
3. Meinwald, J; Cadoff, B. C. JOC 1962 27, 1539.
4. Wharton, P. S.; Bohlen, D. H. JOC 1961, 26, 3615.
5. (a) Golubev, V. A.; Zhdanov, R. I.; Rozantsev, E. G. IZV 1970, 184. (b) ibid., 186.
6. (a) Semmelhack, M. F.; Schmid, C. R.; Cortes, D. A.; Chou, C. S. JACS 1984, 106, 3374. (b) Yamaguchi, M.; Takata, T.; Endo, T. JOC 1990, 55, 1490.
7. Anelli, P. L.; Biffi, C.; Montanari, F.; Quici, S. JOC 1987, 52, 2559.
8. Inokuchi, T.; Matsumoto, S.; Nisiyama, T.; Torii, S. SL 1990, 57.
9. (a) Cella, J. A.; McGrath, J. P.; Regen, S. L. TL 1975, 4115. (b) Kim, H. R.; Jung, J. H.; Kim, J. N.; Ryu, E. K. SC 1990, 20, 637.

James A. Cella

General Electric Company, Schenectady, NY, USA

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