J . Org. Chem. 1999, 64, 1191-1196
1191
Br om id e Ion s a n d Meth yltr ioxor h en iu m a s Coca ta lysts for
Hyd r ogen P er oxid e Oxid a tion s a n d Br om in a tion s
J ames H. Espenson,* Zuolin Zhu, and Timothy H. Zauche
Ames Laboratory and Department of Chemistry, Iowa State University, Ames, Iowa 50011
Received August 24, 1998
Oxidation of alcohols by hydrogen peroxide is negligible; even when catalyzed by methyltrioxorhe-
nium (MTO), the process requires a long reaction time. The addition of a catalytic quantity of
bromide ions, as HBr or NaBr, greatly enhances the rate. Some of the reactions were carried out
on a larger scale in glacial acetic acid, and others at kinetic concentrations. The data establish
that Br2 is the active oxidizing agent in the system, because the catalytic rates under suitable
circumstances match those for the independently measured Br2 reaction with alcohol (benzyl alcohol,
in particular). At much lower levels of MTO, however, Br2 formation plays a role in the kinetics.
Certain other reluctant transformations are conveniently carried out with the MTO/H2O2/Br-
combination: aldehydes to methyl esters; 1,3-dioxolanes to glycol monoesters; and ethers (with
cleavage) to ketones (mostly), but in fair yield only. When Br- was used in stoichiometric quantity,
certain bromination reactions occur. Thus, phenyl acetylenes (PhC2R, R ) H, Me, Ph) are converted
to dibromoalkenes that are entirely or largely formed as the trans isomer, and phenols are
brominated. The latter reaction shows the preference para > ortho > meta. Kinetic studies of benzyl
alcohol oxidation with MTO/H2O2/Br- were carried out in aqueous solution. With sufficient (normal)
levels of MTO, the rate constant for the formation of benzaldehyde agreed with the independently
determined value for Br2 + PhCH2OH, k ) 4.3 × 10-3 L mol-1 s-1 at 25.0 °C; for sec-phenethyl
alcohol, k ) (9.8 ( 0.4) × 10-3 L mol-1 s-1. Bromine is formed from the known oxidation of Br-
with H2O2, catalyzed by MTO. This reaction results in BrO-/HOBr, which is then rapidly converted
to Br2. However, with substantially lower concentrations of MTO, the buildup of benzaldehyde is
ca. 4-fold slower, reflecting the diminished rate of Br- oxidation.
In tr od u ction
ing agents for Br- are the two peroxorhenium species A,
CH3Re(O)2(η2-O2), and B, CH3Re(O)(η2-O2)2(H2O).
Reactions of hydrogen peroxide for which MTO is an
efficient catalyst are nearly always those in which one
oxygen atom can be added immediately to the substrate.1-3
A rare exception is alcohol oxidation, which occurs quite
slowly even with MTO present.4,5 Alcohols show an
appreciable C-H/C-D kinetic isotope effect, which is one
reason to suggest a mechanism involving C-H activation
and, in particular, hydride abstraction.5
The oxidation of organic compounds by hypohalite salts
or halogens is an important method in organic syn-
thesis.12-15 Halogenation reactions are widely used in the
synthesis of flame retardants, pharmaceuticals, agro-
chemicals, and specialty chemicals.16 Because they are
high-risk oxidants, it is useful to develop catalytic routes
that minimize the introduction of halogens and the
production of halogenated wastes.17 The development of
regiospecific reactions is one area needing investigation.
Alcohols were one target for oxidations, in that the
reactions without bromide ions are so sluggish despite
the acceleration provided by MTO. We also sought to
discover the conditions under which alcohols would be
oxidized, to evaluate bromide vs chloride as cocatalyst,
and to examine the oxidations of 1,3-dioxolanes and
ethers. In a separate aspect of this research, we set out
Because MTO catalyzes the peroxide oxidation of bro-
mide to hypobromite,6 we chose to examine whether Br-
would promote hydrogen peroxide oxidations that occur
by hydride ion abstraction. Catalytic functionalization of
organic compounds by mimicking metalloenzymes is one
of the important methods for mild and highly selective
syntheses.7 Haloperoxidases are enzymes that catalyze
the oxidation of halide ions by hydrogen peroxide.8 Cer-
tain of their reactions have been mimicked by ammonium
metavanadate.9-11 In the case of MTO, the active oxidiz-
(10) Conte, V.; Furia, F. D.; Moro, S. Tetrahedron Lett. 1994, 35,
7429.
(11) Conte, V.; Furia, F. D.; Moro, S.; Rabbollini, S. J . Mol. Catal.
1996, 113, 175.
(12) Stevens, R. V.; Chapman, K. T.; Weller, H. N. J . Org. Chem.
1980, 45, 2030.
(13) Katritzky, A. R.; Meth-Cohn, O.; Rees, C. W. In Comprehensive
Organic Functional Group Transformations; Pergamon Press: New
York, 1995; Vol. 5.
(14) Larock, R. C. Comprehensive Organic Transformations; VCH
Publishers, Inc.: New York, 1989.
(15) Palou, J . Chem. Soc. Rev. 1994, 357-361.
(16) Taylor, R. Electrophilic Aromatic Substitution; J ohn Wiley &
Sons: New York, 1990.
(17) Nelson, D. W.; Gypser, A.; Ho, P. T.; Kolb, H. C.; Kondo, T.;
Kwong, H.-L.; McGrath, D. V.; Rubin, A. E.; Norrby, P.-O.; Gable, K.
P.; Sharpless, K. B. J . Am. Chem. Soc. 1997, 119, 1840.
(1) Espenson, J . H.; Abu-Omar, M. M. Adv. Chem. Ser. 1997, 253,
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(2) Herrmann, W. A.; Ku¨hn, F. E. Acc. Chem. Res. 1997, 30, 169-
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(3) Gable, K. P. Adv. Organomet. Chem. 1997, 41, 127-161.
(4) Murray, R. W.; Iyanar, K.; Chen, J .; Wearing, J . T. Tetrahedron
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(5) Zauche, T. H.; Espenson, J . H. Inorg. Chem., 1998, 37, 6827.
(6) Espenson, J . H.; Pestovsky, O.; Huston, P.; Staudt, S. J . Am.
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(7) Barton, D. H. R.; Doller, D. Acc. Chem. Res. 1992, 25, 504-512.
(8) Butler, A.; Walker, J . V. Chem. Rev. 1993, 93, 1937-1944.
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10.1021/jo9817164 CCC: $18.00 © 1999 American Chemical Society
Published on Web 01/22/1999