Positive halogens from halides and hydrogen peroxide with organotellurium catalysts

Article abstract of DOI:10.1021/ja953187g

The oxidations of sodium bromide, sodium chloride, and sodium iodide to positive halogen with hydrogen peroxide in two-phase systems of dichloromethane and pH 6 phosphate buffer were catalyzed by organotellurium catalysts 1-3. The positive halogens were trapped by cyclohexene for bromine and chlorine to give mixtures of the 1,2-dihalocyclohexane (4) and 2-halocyclohexanol (5). For the bromination (4a)/hydrobromination (5a) of cyclohexene, unoptimized turnover numbers of 1010 mol of product per mole of catalyst for 1, 960 for 2, and 820 for 3 were measured with 4a/5a ratios of 55:45, 53:47, and 52:48, respectively. In cyclohexane, the turnover number for 1 was 150 and the 4a/5a ratio was 68:32. In the uncatalyzed process and in the reaction of aqueous bromine with cyclohexene, the 4a/5a ratio is 55:45 in dichloromethane and 67:33 in cyclohexane. The relative rates of catalysis for equimolar amounts of 1-3 were nearly identical to the relative second-order rate constants for oxidation of the organotellurium compounds with hydrogen peroxide, which suggests that oxidation of the catalyst is the rate-determining step of the process. Stopped-flow studies indicated a rapid reaction (k = 22.5 ± 0.3 M^-1 s^-1 for iodide and 13.9 ± 0.5 M^-1 s^-1 for bromide) between halide and oxidized 3 to regenerate catalyst 3. Relative rates of catalysis with 0.1 mol % of 1-3 (relative to cyclohexene) were 4.6 for 1, 2.0 for 2, 1.0 for 3, and 0.11 for the control reaction with no catalyst at 296.1 ± 0.1 K. Oxidation of chloride with hydrogen peroxide with 1 as a catalyst was much slower but the unoptimized turnover number was 100 with a 4b/5b ratio of 7:93 (10:90 in the uncatalyzed process) in a two-phase cylohexane/aqueous system. Oxidized 3 reacts rapidly with both sodium chloride and sodium bromide to give products from oxidative addition of halogen to the catalyst. Stronger Te-Cl bonds relative to Te-Br bonds slow down the release of the Te(II) state of the catalyst. Positive iodine from catalysis with 1 was trapped by 4-pentenoic acid to give iodomethyl lactone 6.

Full text of DOI:10.1021/ja953187g

J. Am. Chem. Soc. 1996, 118, 313-318
313
Positive Halogens from Halides and Hydrogen Peroxide with
Organotellurium Catalysts
Michael R. Detty,*,† Feng Zhou,‡ and Alan E. Friedman§
Contribution from the Department of Medicinal Chemistry, School of Pharmacy, SUNY
at Buffalo, Amherst, New York 14260, Department of Chemistry, SUNY at Buffalo,
Amherst, New York 14260, and Johnson & Johnson Clinical Diagnostics, Inc.,
Rochester, New York 14650-2117
ReceiVed September 18, 1995X
Abstract: The oxidations of sodium bromide, sodium chloride, and sodium iodide to positive halogen with hydrogen
peroxide in two-phase systems of dichloromethane and pH 6 phosphate buffer were catalyzed by organotellurium
catalysts 1-3. The positive halogens were trapped by cyclohexene for bromine and chlorine to give mixtures of the
1,2-dihalocyclohexane (4) and 2-halocyclohexanol (5). For the bromination (4a)/hydrobromination (5a) of
cyclohexene, unoptimized turnover numbers of 1010 mol of product per mole of catalyst for 1, 960 for 2, and 820
for 3 were measured with 4a/5a ratios of 55:45, 53:47, and 52:48, respectively. In cyclohexane, the turnover number
for 1 was 150 and the 4a/5a ratio was 68:32. In the uncatalyzed process and in the reaction of aqueous bromine
with cyclohexene, the 4a/5a ratio is 55:45 in dichloromethane and 67:33 in cyclohexane. The relative rates of
catalysis for equimolar amounts of 1-3 were nearly identical to the relative second-order rate constants for oxidation
of the organotellurium compounds with hydrogen peroxide, which suggests that oxidation of the catalyst is the
rate-determining step of the process. Stopped-flow studies indicated a rapid reaction (k ) 22.5 ( 0.3 M-1 s-1 for
iodide and 13.9 ( 0.5 M-1 s-1 for bromide) between halide and oxidized 3 to regenerate catalyst 3. Relative rates
of catalysis with 0.1 mol % of 1-3 (relative to cyclohexene) were 4.6 for 1, 2.0 for 2, 1.0 for 3, and 0.11 for the
control reaction with no catalyst at 296.1 ( 0.1 K. Oxidation of chloride with hydrogen peroxide with 1 as a
catalyst was much slower but the unoptimized turnover number was 100 with a 4b/5b ratio of 7:93 (10:90 in the
uncatalyzed process) in a two-phase cylohexane/aqueous system. Oxidized 3 reacts rapidly with both sodium chloride
and sodium bromide to give products from oxidative addition of halogen to the catalyst. Stronger Te-Cl bonds
relative to Te-Br bonds slow down the release of the Te(II) state of the catalyst. Positive iodine from catalysis with
1 was trapped by 4-pentenoic acid to give iodomethyl lactone 6.
Hydrogen peroxide is both a powerful oxidant from a
thermodynamic perspective and an environmentally friendly
oxidant yielding oxygen and water upon decomposition. Many
reactions of H2O2, which are favored thermodynamically, are
limited by the kinetics of reaction. Two such reactions are the
oxidations of bromide to bromine/hypobromous acid and
chloride to chlorine/hypochlorous acid with H2O2, which are
slow at ambient temperature and neutral pH.1 In nature, halide
oxidations with peroxide are conducted by the haloperoxidase
enzymes.2 Chloroperoxidase3 and bromoperoxidase2 enzymes
and model systems that mimic their activity4,5 use a transition
metal (heme-bound iron for chloroperoxidase, non-heme vana-
dium for bromoperoxidase)2c to activate H2O2 for the oxidation
of halide to halogen or hypohalous acid. Model studies have
shown that chloride,6 bromide,2,5 and iodide7 can be oxidized
by such catalysis and that the metal undergoes sequential one-
electron steps. These biomimetic reactions are important to
chemistry in general in that they perform many desired chemical
transformations such as epoxidations and halogenations in an
environmentally acceptable way. However, adaption of enzy-
matic processes to commercial application is limited by the
availability and the chemical and physical constraints of the
enzyme.
We report here preparative and mechanistic studies on new
main-group organometallic catalysts for the oxidation of halides
with hydrogen peroxide in which two-electron redox processes
at tellurium mimic the haloperoxidase enzymes but avoid one-
electron pathways. Organotellurium compounds 1-38-10 (Chart
1) were found to catalyze the formation of positive halogens as
† Department of Medicinal Chemistry.
‡ Department of Chemistry.
§ Johnson & Johnson Clinical Diagnostics, Inc.
X Abstract published in AdVance ACS Abstracts, January 1, 1996.
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Am. Chem. Soc. 1994, 116, 9333-9334. (c) Jacobsen, E. N.; Zhang, W.;
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(5) (a) Andersson, M.; Conte, V.; Di Furia, F.; Moro, S. Tetrahedron
Lett. 1995, 36, 2675-2678. (b) Clague, M. J.; Butler, A. J. Am. Chem.
Soc. 1995, 117, 3475-3484. (c) Meister, G. E.; Butler, A. Inorg. Chem.
1994, 33, 3269-3275. (d) Colpas, G. J.; Hamstra, B. J.; Kampf, J. W.;
Pecoraro, V. L. J. Am. Chem. Soc. 1994, 116, 3627-3628. (e) Reynolds,
M. S.; Morcandi, S. J.; Raebiger, J. W.; Miliccin, S. P.; Smith, S. P. E.
Inorg. Chem. 1994, 33, 4977-4984. (f) Espenson, J. H.; Pestovsky, O.;
Huston, P.; Staudt, S. J. Am. Chem. Soc. 1994, 116, 2869-2877. (g) Ma,
R.; Bakac, A.; Espenson, J. H. Inorg. Chem. 1992, 31, 1925-1930. (h) de
la Rosa, R. I.; Clague, M. J.; Butler, A. J. Am. Chem. Soc. 1992, 114, 760-
761.
(6) Soedjak, H. S.; Butler, A. Inorg. Chem. 1990, 29, 5015-5017.
(7) (a) Secco, F. Inorg. Chem. 1980, 19, 2722-2725. (b) Arias, C.; Mata,
F.; Perez-Benito, J. F. Can. J. Chem. 1990, 68, 1499-1503.
(8) For the preparation of 1: Detty, M. R.; Friedman, A. E.; McMillan,
M. Organometallics, 1995, 14, 1442-1449.
0002-7863/96/1518-0313$12.00/0 © 1996 American Chemical Society

314 J. Am. Chem. Soc., Vol. 118, No. 2, 1996
Detty et al.
Table 1. Product Ratios and Turnover Numbers for the Oxidation of Sodium Chloride and Sodium Bromide by Hydrogen Peroxide with
Organotellurium Catalysts 1-3
k(H2O2),a
halide
salt
mol of (4/5)/
mol of catalyst
catalyst
none
L mol-1 s-1
solvent
CH2Cl2
cyclohexane
cyclohexane
CH2Cl2
cyclohexane
cyclohexane
CH2Cl2
krel(cat)b
4/5 ratio
NaBr
NaBr
NaCl
NaBr
NaBr
NaCl
NaBr
NaBr
0.11
0.02
56:44 (4a/5a)
67:33 (4a/5a)
10:90 (4b/5b)
55:45 (4a/5a)
68:32 (4a/5a)
7:93 (4b/5b)
53:47 (4a/5a)
52:48 (4a/5a)
1
17.1 ( 0.3
4.6
0.6
1010
150
100c
960
2
3
8.94 ( 0.05
2.74 ( 0.03
2.0
1.0
CH2Cl2
820
a Second-order rate constant for oxidation of diorgano telluride at 298.0 ( 0.1 K with H2O2. b Relative rates of product formation at 296.1 K
with no catalyst (controls) or with 0.1 mol % catalyst 1-3 (relative to cyclohexene). c At reflux.
Chart 1
Scheme 1
Figure 1. Initial rates of formation of 4a (filled symbols) and 5a (open
symbols) (as measured by GC) for the oxidation of bromide with
hydrogen peroxide catalyzed by 0.010 mmol (0.1 mol % relative to
cyclohexene, 0.01 mol % relative to H2O2) 1-3 in a two-phase system
of 0.5 M cyclohexene in CH2Cl2 (20 mL) and H2O2 (3.0 M) and NaBr
(2.0 M) in pH 6.0 phosphate buffer (32.5 mL aqueous volume) at 296.6
( 0.1 K with stirring at a constant rate. The rates of product formation
for catalyzed (1-3) and uncatalyzed (control) reactions are in arbitrary
units and were measured by GC response relative to an internal standard
of 1.0 mg/mL of diphenyl ether.
exhibited in the bromination/bromohydration and chlorination/
chlorohydration of cyclohexene and the iodolactonization of
4-pentenoic acid with H2O2 and the corresponding halide salt
(Scheme 1). These catalysts were chosen for their solubility
in both water and organic solvents for evaluation of two-phase
reaction systems. In addition, compound 3 displays huge
spectral changes between the Te(II) state [λmax(H2O) 810 nm
suggest that the same oxidizing species are formed in both the
catalyzed and uncatalyzed reactions with NaBr/H2O2 and with
aqueous bromine.
The second-order rate constants for the oxidation of 1-3 with
H2O2 at 298.0 ( 0.1 K were determined under pseudo-first-
order conditions and are compiled in Table 1. The relative rates
(ꢀ ) 150 000)] and the H2O2-oxidized states [λmax(H2O) 510
of formation of 4a/5a with catalysts 1-3 are remarkably
nm (ꢀ ) 50 000)],10 which allows facile monitoring of the
mirrored by the rates of oxidation of 1-3 with H2O2. The
kinetics of changes in the oxidation state at the catalyst.
relatiVe initial rates of catalysis in Figure 1 under the conditions
described above are 1.0 for 3, 2.0 for 2, and 4.6 for 1 while the
Results and Discussion
relatiVe second-order rate constants for H2O2 oxidation of the
catalysts to the corresponding telluroxides (Table 1) are 1.0 for
3, 3.3 for 2, and 6.2 for 1. These relatiVe rates are consistent
with the rate-determing step of the catalytic process being the
oxidation of the telluride.
Preparative Studies. The oxidation of bromide with hy-
drogen peroxide was followed by the initial rate of formation
of 4a and 5a in a two-phase system of 0.5 M cyclohexene in
CH2Cl2 for the organic phase and an aqueous phase of H2O2
(3.0 M) and NaBr (2.0 M) in pH 6.0 phosphate buffer at 296.6
( 0.1 K. The control experiments were then compared to
catalyzed reactions at 296.6 ( 0.1 K in which 0.010 mmol of
1-3 were added (0.1 mol % relative to cyclohexene, 0.01 mol
% relative to H2O2) as shown in Figure 1. The stirring rate
was held constant for all runs. The 4a/5a ratios were nearly
identical in both catalyzed and uncatalyzed reactions (Table 1)
and to the 55:45 4a/5a ratio produced by the addition of
cyclohexene to bromine in the aqueous pH 6 buffer. These data
The turnover numbers for these catalysts were obtained from
preparative runs with a large excess of cyclohexene and H2O2
relative to catalyst. A two-phase system of 50 mL of 0.5 M
cyclohexene in CH2Cl2, 50 mL of 2.0 M NaBr in pH 6
phosphate buffer, and 12.5 mL of 50% H2O2 (3.0 M H2O2
overall) with 0.010 mmol of catalyst was stirred at ambient
temperature. When the reaction began to slow (as monitored
by GC), a second 12.5-mL aliquot of H2O2 was added. When
reaction began to slow again, the product mixtures were isolated,
yields corrected for the uncatalyzed process, and 4a/5a ratios
and turnover numbers calculated (Table 1). The unoptimized
turnoVer numbers listed in Table 1 are in the range 820-1010
mol of product/mol of catalyst.
(9) For the preparation of 2: Ley, S. V.; Meerholz, C. A.; Barton, D. H.
R. Tetrahedron 1981, 37, Suppl. No. 1, 213-223.
(10) For the preparation of 3: Detty, M. R.; Merkel, P. B. J. Am. Chem.
Soc. 1990, 112, 3845-3855.

PositiVe Halogens from Halides and H2O2
J. Am. Chem. Soc., Vol. 118, No. 2, 1996 315
Scheme 2
Figure 2. Iodolactonization of 4-pentenoic acid (10 mmol) to give 6
(as measured by GC) with NaI (65 mmol) and H2O2 (100 mmol) in a
two-phase system of 20 mL of CH2Cl2 and 32.5 mL of pH 6 phosphate
buffer catalyzed by 0.010 mmol (0.1 mol % relative to cyclohexene,
0.01 mol % relative to H2O2) of 1. The rates of product formation for
catalyzed (1) and uncatalyzed (Control) reactions are in arbitrary units
and were measured by GC response relative to an internal standard of
1.0 mg/mL of diphenyl ether.
philic attack of halide at a halide ligand to produce halogen
while regenerating the diorganotelluride catalyst. Reactions
related to these mechanistic possibilities have been proposed
for the oxidation of thiols to disulfides with Te(IV) derivatives.11
In the presence of a large excess of H2O2, the formation of
higher oxidation states of tellurium is possible as is catalysis
via peroxo Te(IV) derivatives.12 In order to eliminate such
possibilities, the chemistry of oxidized telluropyrylium dye 3
was examined under conditions where no excess H2O2 is present.
This was achieved via the self-sensitized, photochemical genera-
tion of singlet oxygen with 3. Dye 3 is oxidized under these
conditions to the same product from oxidation of 3 with H2O2.10
Dye 3 [λmax(H2O) 810 nm (ꢀ ) 150 000)] and oxidized dye 3
[λmax(H2O) 510 nm (ꢀ ) 50 000)] have distinctly different
absorption spectra allowing unequivocal observation of changes
in oxidation state.
Stopped-Flow Experiments. The reaction of oxidized dye
3 with sodium halide salts was followed by stopped-flow
spectroscopy. In reactions with NaI, the reduction of oxidized
dye 3 to regenerate catalyst 3 was the first process observed as
shown in Figure 3 for the reaction of 2 × 10-5 M oxidized 3
with 0.25 M NaI at 310.0 ( 0.1 K. A kinetic trace of this
process at 670 nm is shown in Figure 4 with an observed
pseudo-first-order rate constant of 5.26 ( 0.03 s-1 at pH 6.8.
A plot of the pseudo-first-order rate constants as a function of
iodide concentration (Figure 5) gave a second-order rate constant
of 22.5 ( 0.3 M-1 s-1 for reaction with iodide.
Cyclohexane as an environmentally more acceptable solvent
than CH2Cl2 can be utilized in the two-phase procedure
described above. Reaction is somewhat slower at ambient
temperature, but the turnover number for 1 after two aliquots
of H2O2 is 150 mol of product/mol of catalyst and the product
ratios again are nearly identical in the catalyzed and uncatalyzed
reactions (Table 1).
Chloride is also oxidized by H2O2 with diorganotelluride
catalysis but the process is slower. A two-phase mixture of
0.03 mmol of 1 and 10 mmol of cyclohexene in 20 mL of
cyclohexane, 20 mL of 2.0 M NCl in pH 6 phosphate buffer,
and 12.5 mL of 50% H2O2 (5.5 M H2O2 overall) was heated at
reflux for 2 h. A second 12.5-mL aliquot of H2O2 was added
and the reaction mixture was stirred an additional 3 h at reflux.
The product mixture was isolated, yield corrected for the
negligible uncatalyzed process, and the 4b/5b ratio and unop-
timized turnover number of 100 calculated (Table 1).
The oxidation of NaI with H2O2 to give HOI/I2 is also
catalyzed by the addition of a diorganotelluride catalyst. The
rate of iodolactonization of 4-pentenoic acid (10 mmol) to give
6 (Scheme 1) with NaI (65 mmol) and H2O2 (100 mmol) in a
two-phase system of 20 mL of CH2Cl2 and 32.5 mL of pH 6
phosphate buffer (Scheme 1) was more than doubled by the
addition of 0.01 mmol of catalyst 1 (0.1 mol % relative to
4-pentenoic acid, 0.01 mol % relative to H2O2) to the reaction
mixture (Figure 2). The ease of oxidation of iodide by H2O2
renders less dramatic the catalytic efficiency of 1 in this process.
The use of sodium fluoride under the conditions described
for the oxidation of sodium chloride in the presence of
cyclohexene did not lead to appreciable yields of 1,2-difluoro-
cyclohexane or 2-fluorocyclohexanol with 0.1 mol % of catalyst
1 or 3.
Mechanistic Studies. One possible mechanistic route for
the catalytic role of diorganotellurides is shown in Scheme 2.
Based on the similarity of relative rates of catalysis with relative
rates of oxidation of catalyst by H2O2, we assume the initial
step is oxidation of the diorgano telluride to the hydroxy (for
1) or dihydroxy (for 2 and 3) Te(IV) derivative. Subsequent
nucleophilic attack by halide at ligated hydroxide oxygen would
give diorganotelluride and hypohalous acid. Alternatively,
addition of halide to a telluroxide intermediate might lead to
an R2Te(OH)X intermediate, which then loses hypohalous acid
via either reductive elimination of hypohalous acid or nucleo-
In the bromide reaction at pH 6.8, the addition of bromide
gave a new Te(IV) product with only small changes from the
absorption spectra of oxidized 3 and a low conversion to reduced
catalyst 3. The rate of appearance of catalyst 3 at 810 nm is
shown in the kinetic trace of Figure 6 (0.1 M NaBr, kobs
)
1.09 ( 0.5 M-1 s-1 at 310.0 ( 0.1 K) with a second-order rate
constant of 13.9 ( 0.5 M-1 s-1 from the concentration studies.
The formation of a new Te(IV) product appears to be a
consequence of rapid oxidative addition of bromine to the
Te(II) state of catalyst 3 regenerated from oxidized 3 as
demonstrated in the two-phase experiments described below.
(11) (a) Engman, L.; Stern, D.; Pelcman, M.; Andersson, C. M. J. Org.
Chem. 1994, 59, 1973-1979. (b) Detty, M. R.; Friedman, A. E.; Oseroff,
A. R. J. Org. Chem. 1994, 59, 8245-8250.
(12) One reviewer raised the concern that species like R2Te(OOH)OH
and/or R2Te(OOH)Br might form in the presence of a huge excess of H2O2.
Polarization of the O-O bond in these intermediates could facilitate
nucleophilic attack of halide on the hydroperoxide group releasing HOX
and a Te(IV) species, which would be the actual catalytic species. While
such species would be novel and are quite intriguing, we have no
experimental evidence for such peroxo species, but we cannot rigorously
exclude their presence.

316 J. Am. Chem. Soc., Vol. 118, No. 2, 1996
Detty et al.
Figure 3. Spectral changes for the reaction of 2 × 10-5 M oxidized
3 with 0.5 M NaI at pH 6.8 and 310.0 ( 0.1 K as observed by stopped-
flow spectroscopy. Traces from the arrows are at 0.025, 0.062, 0.125,
0.187, 0.25, 0.375, 0.5, 0.625, 0.75, and 1.00 s after mixing.
Figure 6. A kinetic trace and first-order curve fitting for the reaction
of 2 × 10-5 M oxidized 3 with 0.1 M NaBr at pH 6.8 and 310.0 ( 0.1
K observed at 810 nm. The observed pseudo-first-order rate constant
is 1.09 ( 0.05 s-1
.
Chart 2
of NaBr to the stirred mixture of Figure 7b gave an immediate
loss of color in the aqueous layer and a purple color in the
organic phase [Figure 7c, λmax(CH2Cl2) 563 nm]. The absorp-
tion spectrum of the product in the organic phase is identical to
that of 7 (Chart 2) in CH2Cl2.13,14 The addition of cyclohexene
to the mixture of Figure 7c regenerated the spectra of Figure
3a with stirring. No other intermediates related to 3 were
detected under these conditions. GC analysis of the concen-
trated organic phase showed the presence of the 55:45 4a/5a
mixture. In the absence of a substrate such as cyclohexene,
product 7 (as the bromide/tribromide salt) would form via the
oxidative addition of bromine to 3 from the following equilib-
rium:
Figure 4. A kinetic trace and first-order curve fitting for the reaction
of 2 × 10-5 M oxidized 3 with 0.5 M NaI at pH 6.8 and 310.0 ( 0.1
K observed at 670 nm. The observed pseudo-first-order rate constant
is 5.26 ( 0.03 s-1
.
The absorption spectrum of 7 in water [λmax(H2O) 520 nm
(ꢀ ) 50 000)] is nearly identical to that of oxidized 3. However,
the addition of CH2Cl2 to aqueous 7 gives a purple organic phase
[λmax(CH2Cl2) 563 nm (ꢀ ) 55 000)]. The similarity of the
absorption spectra of 7 and oxidized 3 in aqueous solution is
not that surprising. However, their solubilities in organic
solvents are markedly different.10,13,14
Repetition of the photochemical experiment with catalyst 3
with 0.1 M cyclohexene in the organic phase gave formation
of the 55:45 4a/5a mixture. Spectroscopically, catalyst 3 and
dibromide 7 were detected in the organic layer while both
reduced and oxidized 3 were detected in the aqueous layer in
early stages of the reaction. These data implicate the Te(II)-
Te(IV) shuttle in the photochemical catalytic cycle for bromi-
nation, not a higher oxidation state tellurium intermediate. It
should also be noted that a control photochemical reaction (no
catalyst) gave no detectable formation of either 4a or 5a.
No suitable spectral changes for stopped-flow spectroscopy
in aqueous solution were observed upon addition of NaCl to
Figure 5. A plot of the pseudo-first-order rate constants measured at
iodide concentrations of 0.25, 0.1, and 0.05 M at pH 6.8 vs iodide
concentration. The slope of the least-squares fit gave a second-order
rate constant of 22.5 ( 0.3 M-1 s-1 for reaction with iodide.
Two-Phase Mechanistic Experiments. A two-phase mix-
ture of a 1.0 × 10-5 M CH2Cl2 solution of 3 was stirred with
an equal volume of pH 6.0 phosphate buffer (50 mL). After
equilibration, the absorption spectra of the organic and aqueous
phases showed the dye to be mostly in the organic phase (Figure
7a). Irradiation of the mixture gave oxidized 3 (Figure 7b),
which has minimal solubility in the organic phase. The addition
(13) Detty, M. R.; Luss, H. R. Organometallics 1986, 5, 2250-2257.
(14) Detty, M. R.; Frade, T. M. Organometallics 1993, 12, 2496-2504.

PositiVe Halogens from Halides and H2O2
J. Am. Chem. Soc., Vol. 118, No. 2, 1996 317
Scheme 3
to the corresponding halogen with H2O2. Preparative studies
in two-phase systems indicate high turnover numbers for these
catalysts. Furthermore, in aerated systems with catalysts such
as 3, the photochemical, self-sensitized generation of singlet
oxygen from catalyst may obviate the need for any added
oxidant (other than oxygen) for halogenation reactions with this
catalyst.
Mechanistically, the initial step in the reaction is oxidation
of the organotellurium compounds to the corresponding tel-
luroxide or dihydroxy Te(IV) derivatives as shown in Scheme
2. Subsequent nucleophilic attack by halide at ligated hydroxide
oxygen would give diorganotelluride and hypohalous acid.
Alternatively, addition of halide to a telluroxide intermediate
might lead to an R2Te(OH)X intermediate, which then under-
goes reductive elimination of HOX or loses halogen via
nucleophilic attack of halide at a halide ligand, regenerating
the diorganotelluride. These fates for the oxidized species are
illustrated in Scheme 3.
It should also be noted that no other intermediates were
detected in the time course of the mechanistic and preparative
studies. No oxirane intermediates were detected, which mini-
mizes the possibility of epoxidation followed by nucleophilic
opening with halide. The chemistry observed at high H2O2
concentrations and the chemistry observed under conditions of
no excess H2O2 are identical, which argues against the involve-
ment of species like R2Te(OOH)OH and/or R2Te(OOH)Br.12
The stopped-flow experiments indicate that the initial reaction
detected upon mixing involves reduction of Te(IV) to Te(II)
consistent with nucleophilic attack of halide at a hydroxide
ligand. However, if hydration-dehydration of the telluroxide
intermediate and subsequent halide additions were sufficiently
fast (kobs g 100 s-1) and if the absorption spectra of all Te(IV)
intermediates were similar in H2O, then these processes would
be transparent to detection prior to a change in oxidation state.16
Figure 7. Intermediates formed in the use of catalyst 3 in two-phase
systems for the oxidation of sodium bromide with oxidized catalyst 3.
(a) Absorption spectra of aqueous pH 6 phosphate buffer and CH2Cl2
following equilibration of 1.0 × 10-5 M 3 in CH2Cl2 with the aqueous
phase. (b) Distribution of oxidized 3 between aqueous and organic
phases following irradiation of the mixture of (a) with a 60-W tungsten
bulb. (c) Chromophores in aqueous and organic phases following
addition of 0.50 g of NaBr (5 mmol, 0.1 M in the aqueous layer) to
the mixture of (b).
Experimental Section
General Methods. Solvents (cyclohexane, dichloromethane), cy-
clohexene, 4-pentenoic acid, sodium chloride, sodium bromide, sodium
iodide, and hydrogen peroxide (30% and 50% solutions) were used as
received from Aldrich Chemical Co. Two-phase reaction mixtures were
mechanically stirred at a constant rate for kinetic runs. Preparative
reactions were stirred magnetically. Concentration in Vacuo was
performed on a Bu¨chi rotary evaporator. Nuclear magnetic resonance
spectra were recorded on a Varian Gemini-300 instrument with residual
solvent signal as internal standard: CDCl3 (δ 7.26). UV-visible-near
IR spectra were recorded on a Perkin-Elmer Lambda 12 spectropho-
tometer equipped with a circulating constant-temperature bath for the
sample holder. Gas chromatography was performed on a Shimadzu
GC-14A instrument with a 15 m × 0.53 mm ID Rtx-5 column
(Crossbonded 95% dimethyl-5% diphenyl polysiloxane) from Restek
Corp., 110 Benner Circle, Bellefonte, PA.
Catalyst 1 was prepared according to ref 8. Catalyst 2 was prepared
according to ref 9. Hydrolysis of the bis methyl ester with NaOH in
aqueous MeOH gave 2 as a white crystalline solid that precipitated
from the reaction mixture. Catalyst 3 was prepared according to ref
10. trans-1,2-Dihalocyclohexanes 4a [m/z 244 (C6H1081Br2)] and 4b
[m/z 152 (C6H1035Cl2)] were prepared by bromination and chlorination,
respectively, of cyclohexene in CH2Cl2. trans-2-Halocyclohexanols 5a
[m/z 180 (C6H1181BrO)] and 5b [m/z 134 (C6H1135ClO)] were prepared
oxidized 3. However, in the two-phase system, the addition of
NaCl to oxidized dye 3 gave chlorine oxidative addition product
8 (λmax 548 nm in CH2Cl2)14 in the time frame of mixing.
However, the addition of cyclohexene to the mixture containing
8 does not lead to regeneration of the starting catalyst 3 with
the formation of 4b and 5b in the time frame of the bromide
experiments above. Studies of the thermal reductive elimination
of halogen from 7 and 8 have shown that the Te-Cl bond is
stronger than the Te-Br bond.14,15 The poorer catalysis
observed in the chloride reactions may be due to competitive
formation of chlorine oxidative-addition products, which only
slowly regenerate the Te(II) state of the catalyst.
Conclusions
Organotellurium compounds 1-3 are useful catalysts for the
oxidation of aqueous solutions of chloride, bromide, and iodide
(16) Glutathione thiol substitution for hydroxide at Te(IV) in ref 11b is
sufficiently fast (k g 5 × 106 M-1 s-1) to mask such a reaction in the
current studies.
(15) Detty, M. R.; Fleming, J. C. AdV. Mater. 1994, 6, 48-51.

318 J. Am. Chem. Soc., Vol. 118, No. 2, 1996
Detty et al.
by ring-opening of cyclohexene oxide (Aldrich Chemical Co.) with
aqueous HBr and HCl, respectively. The 2-oxo-4-(iodomethyl)-
tetrahydrofuran (6) was prepared by the addition of iodine to a
dichloromethane solution of 4-pentenoic acid containing 1.2 equiv of
pyridine: 1H NMR (CDCl3) δ 4.52 (m, 1 H), 3.39 (ABX, 1 H), 3.27
(ABX, 1 H), 2.35-2.7 (m, 3 H), 1.96 (m, 1 H); IR (film, NaCl) 1776
cm-1; m/z 226.5 (C5H7O2I).
dilution) were followed spectrophotometrically at 298.0 ( 0.1 K to
completion. The pseudo-first-order rate constants were plotted as a
function of [H2O2] with the slope of the resulting lines giving the
second-order rate constants compiled in Table 1 for 1-3, respectively.
Mechanistic Studies. Spectroscopic Studies with Catalyst 3 in
Two-Phase Systems. (a) Bromide Oxidation. A 1.0 × 10-5 M CH2-
Cl2 solution of 3 (50 mL) was stirred with an equal volume of pH 6.0
phosphate buffer (50 mL). After equilibration, the absorption spectra
of the organic and aqueous phases showed the dye to be mostly in the
Kinetic Comparisons. (a) Bromide Oxidations. In typical experi-
ments, 0.010 mmol of catalyst 1-3 was added to a two-phase system
of 0.5 M substrate [0.820 g (0.0100 mol) of cyclohexene] in CH2Cl2
(20 mL) for the organic phase and an aqueous phase of H2O2 (12.5
mL of a 30% solution) and NaBr (6.63 g, 0.065 mol) in pH 6.0
phosphate buffer (20 mL) at 296.6 ( 0.1 K. The trans-1,2-dibro-
mocyclohexane (4a) and trans-2-bromocyclohexanol (5a) produced in
this reaction were identified by GC-mass spectroscopy with comparison
to authentic samples for retention time. Relative response factors were
measured for standard 5.0 × 10-3 M solutions of 4a and 5a. Diphenyl
ether (1 mg/mL) was added to the starting solution of cyclohexene as
an internal standard for the GC measurements. The organic phase was
sampled periodically by gas chromatography (GC) and the relative rates
of appearance of 4a and 5a for each catalyst are illustrated in Figure
1. These relative rates of appearance of 4a and 5a are compared to
the appearance of 4a and 5a in control reactions in which no catalyst
is added. The ratio of products 4a/5a for each catalyst is compiled in
Table 1.
organic phase [Figure 3a, λmax(CH2Cl2) 830 nm, ꢀ ) 330 000; λmax
-
(H2O) 810 nm (ꢀ ) 150 000)].10 Irradiation of the mixture with a 60-W
tungsten bulb held 10 cm from the Pyrex reaction flask gave oxidized
3 [Figure 3b, λmax(H2O) 510 nm (ꢀ ) 50 000)].10 The addition of 0.50
g of NaBr (5 mmol, 0.1 M in the aqueous layer) to the stirred mixture
of Figure 3b gave an immediate loss of color in the aqueous layer and
a purple color in the organic phase [Figure 3c, λmax(CH2Cl2) 563 nm
(ꢀ ) 55 000)]. The addition of 0.41 g (5.0 mmol, 0.1 M in the organic
phase) of cyclohexene to the mixture of Figure 3c regenerated the
spectra of Figure 3a with stirring.
The reaction was repeated and the organic phase was separated, dried
over MgSO4, and concentrated in Vacuo. The field desorption mass
spectrum of the purple product mixture gave a weak parent ion cluster
with m/z 813 (C29H4381Br2130Te2) and a strong (M+ - Br) cluster,
consistent with the dibromotelluropyryanyl telluropyrylium cation of
structure 7.
(b) Chloride Oxidation. The procedure described above was
repeated except that 0.29 g (5 mmol) of NaCl was added in place of
NaBr. The product formed in the organic phase displayed λmax(CH2-
Cl2) 548 nm (ꢀ ) 53 000). Nearly identical chemistry is observed upon
the addition of NaCl rather than NaBr to oxidized dye 3. The chlorine
oxidative addition product 8 (λmax 548 nm in CH2Cl2)15 is formed in
the time frame of mixing. However, the addition of cyclohexene to
the mixture containing 8 does not lead to regeneration of the starting
catalyst 3 (with the formation of 4b and 5b) in the time frame of the
bromide experiments above. The organic phase was separated, dried
over MgSO4, and concentrated in Vacuo. The field desorption mass
spectrum of the purple product mixture gave a parent ion cluster with
m/z 661 (C29H4335Cl2130Te2), consistent with the dichlorotelluropyranyl
telluropyrylium cation of structure 8.
Stopped-Flow Experiments. All stopped-flow experiments were
performed on a Sequential DX17 MV Stopped-Flow Spectrometer
(Applied Photophysics, Leatherhead, UK). All experiments incorpo-
rated the instrument in stopped-flow mode only. The sample handling
unit was fitted with two drive syringes that are mounted inside a
thermostated-bath compartment, which allowed for constant temperature
experimentation at 310.0 ( 0.1 K. The optical-detection cell was set
up in the 10-mm path length. First- and second-order curve fitting
and rate constants used a Marquardt algorithm17 based on the routine
Curfit.18 Absorption spectra at indicated time points were calculated
through software provided by Applied Photophysics. This consisted
of slicing the appropriate time points across a series of kinetic traces
(at different wavelengths) and then splining the points of a specific
time group.
A solution of 4 × 10-5 M dye 3 in pH 6.8 buffer (pH-adjusted 0.02
M N,N′-piperidine bis(2-ethanesulfonate) disodium salt) was irradiated
with a 60 W tungsten bulb held 10 cm from the Pyrex reaction flask
to give oxidized 3. The resulting solution served as the stock solution
for the stopped-flow experiments. Sodium bromide (0.5, 0.2, and 0.1
M) and sodium iodide (0.5, 0.2, and 0.1 M) solutions at appropriate
molarity were prepared in the pH 6.8 buffer system. A halide stock
solution and the oxidized 3 stock solution were mixed at equal volumes
in the stopped-flow instrument. The pseudo-first-order rate constants
were plotted as a function of [halide] with the slope of the resulting
lines giving second-order rate constants of 13.9 ( 0.5 for reaction with
bromide and 22.5 ( 0.3 for reaction with iodide.
(b) Iodide Reactions. In typical experiments, 0.010 mmol of
catalyst 1-3 was added to a two-phase system of 0.5 M substrate [1.00
g (0.0100 mol) of 4-pentenoic acid] in CH2Cl2 (20 mL) for the organic
phase and an aqueous phase of H2O2 (12.5 mL of a 30% solution) and
NaI (9.75 g, 0.065 mole) in pH 6.0 phosphate buffer (20 mL) at 296.6
( 0.1 K. The 2-oxo-4-(iodomethyl)tetrahydrofuran (6) produced in
this reaction was identified by GC-mass spectroscopy with comparison
to an authentic sample of 6 for retention time. Diphenyl ether (1 mg/
mL) was added to the starting solution of 4-pentenoic acid as an internal
standard for the GC measurements. The organic phase was sampled
periodically by gas chromatography (GC) and the relative rates of
appearance of 6 in catalyzed and control (no catalyst) reactions are
illustrated in Figure 2.
Preparative Reactions. (a) Bromide Reactions in Dichlo-
romethane. In typical experiments, 0.010 mmol of catalyst 1-3 was
added to a two-phase system of 0.5 M substrate [2.05 g (0.0250 mole)
cyclohexene] in CH2Cl2 (50 mL) for the organic phase and an aqueous
phase of H2O2 (12.5 mL of a 50% solution) and NaBr (10.2 g, 0.100
mol) in pH 6.0 phosphate buffer (50 mL) were stirred at ambient
temperature. The reactions were sampled periodically by GC. When
the rate of appearance of products began to plateau, a second 12.5-mL
aliquot of 50% H2O2 was added (approximately 2 h). When reaction
began to slow again after 2 h, the organic phase was separated, washed
with water and brine, dried over MgSO4, and concentrated in vacuo.
Bulb-to-bulb transfers at 1 Torr to remove traces of volatiles gave 2.15
( 0.04 g of the bromination product mixture for 1, 2.03 ( 0.05 g for
2, and 1.74 ( 0.04 g for 3 after correcting for the uncatalyzed process
(0.044 ( 0.005 g of product mixture). The yields cited are the average
of duplicate runs. Product ratios as determined by GC are compiled
in Table 1. For the control reaction, the second 12.5-mL aliquot of
50% H2O2 was added 2 h after addition of the first. Turnover numbers
are compiled in Table 1 and are based on 0.010 mmol of catalyst.
(b) Bromide Reactions in Cyclohexane. The procedure described
above was repeated with catalyst 1 (0.0034 g, 0.010 mmol) with
cyclohexane replacing dichloromethane as solvent. The second aliquot
of H2O2 was added after 4 h. The products were isolated 4 h following
the second addition of H2O2. Following workup, 0.34 ( 0.01 g of a
68:32 mixture of 4a:5a was isolated.
(c) Chloride Reactions in Cyclohexane. The procedure described
above was repeated with catalyst 1 (0.0102 g, 0.030 mmol) with
cyclohexane as solvent and NaCl (5.80 g, 0.100 mol) replacing NaBr.
The two-phase mixture was heated at reflux. The second aliquot of
H2O2 was added after 2 h. The products were isolated 2 h following
the second addition of H2O2. Following workup, 0.42 ( 0.01 g of a
7:93 mixture of 4b:5b was isolated.
Acknowledgment. The authors thank Mr. Jeff Washo
(SUNY Buffalo) for the preparation and characterization of the
authentic sample 6.
JA953187G
Oxidation of Catalysts with H2O2. The oxidations of 1-3 (5 ×
(17) Marquardt, D. W. J. Soc. Ind. Appl. Math. 1963, 11, 431.
(18) Curfit is found in: Bevington, P. R. Data Reduction and Error
Analysis for the Physical Sciences; McGraw-Hill: New York, 1969.
10-5 M for 1 and 2; 2 × 10-5 M for 3) with 5.0 × 10-3, 2.5 × 10-3
,
and 1.0 × 10-3 M H2O2 in pH 6.0 phosphate buffer (prepared by serial