A xerogel-sequestered selenoxide catalyst for brominations with hydrogen peroxide and sodium bromide in an aqueous environment

Article abstract of DOI:10.1021/jo801234e

(Chemical Equation Presented) 4-(Hydroxymethyl)phenyl benzyl selenoxide (4) sequestered in a halide-permeable, Class II xerogel formed from 10/90 (mol/mol) 3-aminopropyltriethoxysilane/tetraethoxysilane catalyzes the bromination of organic substrates (4-pentenoic acid, 3,5-dihydroxybenzoic acid, 1,3,5-trimethoxybenzene, N-phenylmorpholine, and N,N-dimethylaniline) with NaBr and H₂O₂. Catalyst performance (reaction rate) when sequestered within the halide-permeable xerogel is 23-fold greater in comparison to xerogel-free catalyst in solution. The catalyst is easily separated from the reaction mixture via filtration and the recovered catalyst can be reused without loss of activity through formation of the first 80 mol of product per mole of catalyst.

Full text of DOI:10.1021/jo801234e

SCHEME 1. Oxidation of Bromide with H2O2 and a
Selenoxide Catalyst
A Xerogel-Sequestered Selenoxide Catalyst for
Brominations with Hydrogen Peroxide and
Sodium Bromide in an Aqueous Environment
Stephanie M. Bennett, Ying Tang, Danielle McMaster,
Frank V. Bright, and Michael R. Detty*
SCHEME 2. Synthesis of Selenoxide Catalyst 4
Department of Chemistry, UniVersity at Buffalo, The State
UniVersity of New York, 627 Natural Sciences Complex,
North Campus, Buffalo, New York 14260-3000
mdetty@buffalo.edu
ReceiVed June 8, 2008
1.2-4 However, the catalyst is only recovered following time-
consuming extractive workup and chromatography. Recent studies
have shown that catalytic groups can be sequestered within xerogels
or bulk silica by “imprinting” to give spatially arranged functional-
ity on the nanoscale.5 The reactivity of the imprinted functionality
and the transport of reagents from bulk solution into pores can be
modified by end-capping hydrophilic and acidic silanol functionality
with various groups.6 Enhanced rates have been observed for the
sequestered catalysts relative to similar catalyst structures used as
homogeneous catalysts.7 Xerogel-sequestered selenoxide catalysts
offer an environmentally benign, porous solid platform for using
H2O2 as an oxidant and simultaneously provide simple filtration
as a means to isolate and recycle the catalyst.
4-(Hydroxymethyl)phenyl benzyl selenoxide (4) sequestered in
a halide-permeable, Class II xerogel formed from 10/90 (mol/
mol) 3-aminopropyltriethoxysilane/tetraethoxysilane catalyzes
the bromination of organic substrates (4-pentenoic acid, 3,5-
dihydroxybenzoic acid, 1,3,5-trimethoxybenzene, N-phenyl-
morpholine, and N,N-dimethylaniline) with NaBr and H2O2.
Catalyst performance (reaction rate) when sequestered within
the halide-permeable xerogel is 23-fold greater in comparison
to xerogel-free catalyst in solution. The catalyst is easily
separated from the reaction mixture via filtration and the
recovered catalyst can be reused without loss of activity through
formation of the first 80 mol of product per mole of catalyst.
Synthesis of the Selenoxide Catalyst. Aryl benzyl selenoxides
3
have excellent catalytic activity with H2O2 and avoid the com-
plication of selenoxide elimination8 by having no ꢀ-hydrogens.
Covalent attachment of the catalyst within the xerogel requires
suitable functionality (alcohol, amine) on the catalyst. A selenoxide
with benzyl alcohol functionality was prepared as shown in Scheme
2. 4-Bromobenzyl alcohol was protected as its TBS ether 1 by
using TBSCl and imidazole and 1 was then treated with 2.2 equiv
of t-BuLi. The resulting anion was then reacted with Se powder
and benzyl bromide to give selenide 2. The TBS protecting group
was removed with Bu4NF to give selenide 3, which was then
In a “green” future, synthetic transformations that minimize
the use of organic-based solvents and reagents will contribute
to a low-carbon-use economy. Water is a carbon-free solvent,
H2O2 is a carbon-free, inexpensive oxidant, and aqueous
oxidations with H2O2 have the potential to minimize solvent
waste and organic byproducts. The bromination of organic
substrates with NaBr and H2O2 is one such reaction.1 An easily
recovered and recycled catalyst for the activation of H2O2 would
further contribute to value-added organic transformations while
making the use of aqueous H2O2 more practical.
(2) Drake, M. D.; Bright, F. V.; Detty, M. R. J. Am. Chem. Soc. 2003, 125,
12558.
(3) Goodman, M. A.; Detty, M. R. Organometallics 2004, 23, 3016.
(4) Goodman, M. A.; Detty, M. R. Syn. Lett. 2006, 1100.
(5) (a) Katz, A.; Davis, M. E. Nature 2000, 403, 286. (b) Notestine, J.; Katz,
A. Chem. Eur. J. 2006, 12, 3954.
(6) (a) Bass, J. D.; Katz, A. Chem. Mater. 2003, 15, 2757. (b) Bass, J. D.;
Anderson, S. L.; Katz, A. Angew. Chem., Int. Ed. 2003, 42, 5219. (c) Bass,
J. D.; Solovyov, A.; Pascall, A. J.; Katz, A. J. Am. Chem. Soc. 2006, 126, 3737.
(7) Notestein, J. M.; Solovyov, A.; Andrini, L. R.; Requejo, F. G.; Katz, A.;
Iglesia, E. J. Am. Chem. Soc. 2007, 129, 15585.
Selenoxides are excellent catalysts for a variety of oxidations
with H2O2 including bromination with NaBr as shown in Scheme
(8) (a) Walter, R.; Roy, J. J. Org. Chem. 1970, 36, 2561. (b) Jones, D. N.;
Mundy, D.; Whitehouse, R. D. J. Chem. Soc., Chem. Commun. 1970, 86. (c)
Sharpless, K. B.; Young, M. W.; Lauer, R. F. Tetrahedron Lett. 1973, 1979. (d)
Reich, H. J.; Reich, I. L.; Renga, J. M. J. Am. Chem. Soc. 1973, 95, 5813.
* To whom correspondence may be sent. Phone:(716)-645-6800 × 2200. Fax:
(716)-645-6963.
(1) Mohammed, A.; Liebhafsky, H. A. J. Am. Chem. Soc. 1934, 56, 1680.
10.1021/jo801234e CCC: $40.75
Published on Web 08/01/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 6849–6852 6849

FIGURE 1. (A) Moles of brominated products 5 and 6 per mole of 4 as a function of time for 5 mol % 4 sequestered in APTES/TEOS (filled
circles), sequestered in C3TriMOS/TMOS (filled triangles), and dissolved in D2O (open circles) with 0.38 M H2O2 and 1.4 M NaBr at 301.5 ( 0.4
K. Lines represent first-order fits of the data. (B) Rate dependence on H2O2 concentration for the APTES/TEOS-sequestered 4 catalyzed reactions
at 301.5 ( 0.4 K.
SCHEME 3. Bromination Products of 4-Pentenoic Acid
oxidized to selenoxide 4 with N-chlorosuccinimide in MeOH/
CH2Cl2 followed by hydrolysis with aqueous NaOH.9
Sequestered Catalysts. As described in the Supporting Infor-
mation, halide permeability was determined in a series of xerogels
by investigating the I- quenching of sequestered tris(4,7′-diphenyl-
1,10′-phenanathroline)ruthenium(II) chloride. A xerogel based on
10/90 (mol/mol) 3-aminopropyltriethoxysilane/tetraethoxysilane
xerogel (APTES/TEOS) was permeable to halide ions and had
catalyzed process and (6.7 ( 0.3) × 10-7 s-1 (R2 ) 0.98) for
mechanical properties suitable for use as a powdered support for
catalyst 4. A second xerogel based on 50/50 (mol/mol) n-
the catalyst-free APTES/TEOS control. The uncatalyzed, xe-
rogel-free bromination of 4-pentenoic acid under identical
propyltrimethoxysilane/tetramethoxysilane (C3TriMOS/TMOS) was
much less permeable to halides (Supporting Information) and was
used as a control. Monoliths of both APTES/TEOS and C3TriMOS/
TMOS with and without 0.015 mM 4 were prepared and crushed
into a fine powder by using a mortar and pestle (particle diameter
) 30-90 µm). Theoretically, each gram of APTES/TEOS
contained 0.057 g (1.9 × 10-4 mol) of selenoxide 4 while each
gram of C3TriMOS/TMOS contained 0.037 g (1.3 × 10-4 mol).
Atomic absorption analysis of Se content was consistent with the
theoretical values.
conditions gave kobs of (4.8 ( 0.3) × 10-7 s-1
.
In D2O as Solvent. The bromination of 4-pentenoic acid was
1
also followed by H NMR spectroscopy in D2O at pH/D 6 with
suppression of the HOD/H2O signal. As shown in Figure 1A,
bromination of 4-pentenoic acid (0.13 M) with 5 mol % APTES/
TEOS-sequestered 4, 0.38 M H2O2, and 1.4 M NaBr followed
excellent pseudo-first-order behavior [k ) (1.38 ( 0.03) × 10-4
s-1, R2 ) 0.99, Table 1] and the reactions went to completion (20
mol of product per mole of catalyst). A first-order dependence on
H2O2 was observed over the range of 0.19-0.75 M with a second-
order rate constant of 3.8 × 10-4 M-1 s-1 with respect to H2O2
concentration (Figure 1B). Bromination appeared to be independent
of Br- concentration at the concentrations (0.7 to 2.8 M NaBr)
employed in these studies (Table 1).
The bromination of 4-pentenoic acid using 5 mol %
C3TriMOS/TMOS-sequestered 4 or for xerogel-free 4 dissolved
in buffered D2O is also shown in Figure 1A. Bromination was
nearly 10-fold slower [k ) (1.48 ( 0.03) × 10-5 s-1, Table 1]
with C3TriMOS/TMOS-sequestered 4 relative to APTES/TEOS-
sequestered 4. Bromination with 5 mol % 4 dissolved in D2O
gave kobs of (6.06 ( 0.04) × 10-6 s-1 while the catalyst-free
APTES/TEOS powder as a control reaction was much slower
with kobs of (5.45 ( 0.09) × 10-7 s-1 (Table 1).
The importance of covalent attachment of the catalyst was
demonstrated by preparing monoliths of APTES/TEOS containing
0.015 M benzyl phenyl selenoxide.3 Ether extraction of the crushed
powder removed >90% of the selenoxide catalyst from the xerogel.
Kinetic Studies of the Bromination of 4-Pentenoic Acid
with NaBr/H2O2 and APTES/TEOS-Sequestered 4. Bromi-
nation of 4-pentenoic acid with 1.4 M NaBr and 0.38 M H2O2
at pH 6 with 5 mol % APTES/TEOS-sequestered 4 at 296 ( 1
K gives 4,5-dibromopentanoic acid (5) and bromolactone 6 as
shown in Scheme 3.10 At pH 6, 5 is converted to 6 upon
1
standing. The H NMR chemical shifts of the olefinic protons
of 4-pentenoic acid are distinct from the bromomethine proton
of 5 and the lactone methine proton of 6 (Figure S11, Supporting
Information), allowing product ratios to be determined as a
function of time. As shown in Figure S12 (Supporting Informa-
tion), pseudo-first-order behavior was observed with rate
constants, kobs, of (8.9 ( 0.1) × 10-5 s-1 (R2 ) 0.99) for the
The bromination of 4-pentenoic acid with 5 mol % C3TriMOS/
TMOS-sequestered 4 or for xerogel-free 4 dissolved in buffered
D2O is also shown in Figure 1A. Bromination was nearly 10-
fold slower [k ) (1.48 ( 0.03) × 10-5 s-1, Table 1] with 5
mol % C3TriMOS/TMOS-sequestered 4. Bromination of 4-pen-
tenoic acid with 5 mol % 4 dissolved in D2O gave kobs of (6.06
( 0.04) × 10-6 s-1 while bromination in the presence of
catalyst-free APTES/TEOS powder was much slower with kobs
of (5.45 ( 0.09) × 10-7 s-1 (Table 1).
(9) Detty, M. R. J. Org. Chem. 1980, 45, 274.
(10) (a) Francavilla, C.; Bright, F. V.; Detty, M. R. Org. Lett. 1999, 1, 1043.
(b) Francavilla, C.; Drake, M. D.; Bright, F. V.; Detty, M. R. J. Am. Chem. Soc.
2001, 123, 57.
(11) (a) Dave, B. C.; Soyez, H.; Miller, J. M.; Dunn, B.; Valentine, J. S.;
Zink, J. I. Chem. Mater. 1995, 7, 1431. (b) Avnir, D. Acc. Chem. Res. 1995, 28,
328. (c) Ingersoll, C. M.; Bright, F. V. CHEMTECH 1997, 27, 26.
(12) Jaber, N.; Gelman, D.; Schumann, H.; Dechert, S.; Blum, J. Eur. J.
Org. Chem. 2002, 1628.
(13) Fischer, A.; Henderson, G. N. Can. J. Chem. 1983, 61, 1045.
(14) (a) Effenberger, F.; Steinbach, A.; Epple, G.; Hanauer, J. Chem. Ber. 1983,
116, 3539. (b) Cheng, Y.; Zhan, Y.-H.; Meth-Cohn, O. Synthesis 2002, 1, 34.
Preparative Bromination of Organic Substrates with
Xerogel-Sequestered Catalyst 4. Bromination of 4-pentenoic
acid was complete within 15 h at ambient temperature with 1.4 M
NaBr, 0.25 M H2O2 (2 equiv), and 5 mol % APTES/TEOS-
6850 J. Org. Chem. Vol. 73, No. 17, 2008

TABLE 1. Rate Constants for the Bromination of 4-Pentenoic Acid with Various Concentrations of H2O2 and NaBr in the Presence or
Absence of 5 mol % Selenoxide 4 (Relative to 4-Pentenoic Acid) Sequestered in 10/90 APTES/TEOS or 50/50 C3TriMOS/TMOS or Dissolved in
D2O
a
catalyst/xerogel combination
[H2O2], M
[NaBr], M
kobs
,
s-1
krel
APTES/TEOS-
sequestered 4
0.19
0.38
0.38
0.38
0.75
0.38
0.38
0.38
1.4
1.4
2.8
0.7
1.4
1.4
1.4
1.4
(3.81 ( 0.22) × 10-5
(1.38 ( 0.03) × 10-4
(1.13 ( 0.02) × 10-4
(1.23 ( 0.03) × 10-4
(2.53 ( 0.26) × 10-4
(6.06 ( 0.04) × 10-6
(1.48 ( 0.18) × 10-5
(5.45 ( 0.09) × 10-7
6.3
23
19
22
42
1
2.4
0.09
5 mol % 4 in D2O
C3TriMOS/TMOS- sequestered 4
APTES/TEOS (no 4)
a Average of duplicate runs at 301.5 ( 0.4 K.
TABLE 2. Bromination of Organic Substrates with 1.4 M NaBr,
0.25 M H2O2 with and without 5 mol % Selenoxide 4 (Relative to
4-Pentenoic Acid) Sequestered in 10/90 APTES/TEOS in pH 6
Phosphate Buffer (Entry 1) or 1/1 (v/v) Dioxane/pH 6 Phosphate
Buffer (Entries 2-4)
dibrominated product. Bromination of N-phenylmorpholine was
complete after 24 h to give a 97:3 mixture of N-(4-bromophe-
nyl)morpholine (9) and the 2-isomer as the minor component
in 89% isolated yield for the two products.
As a control reaction, the preparative brominations were also
conducted with an equivalent weight of catalyst-free xerogel.
After 24 h, <1% bromination was observed with 3,5-dihy-
droxybenzoic acid and approximately 8% bromination was
observed with 1,3,5-trimethoxybenzene and N-phenylmorpholine
(Table 2).
Recycling APTES/TEOS-Sequestered 4. The APTES/
TEOS-sequestered 4 from the bromination of 4-pentenoic acid
was recovered by filtration, washed with water and ether, dried,
and recycled. Complete conversion of 4-pentenoic acid to
bromolactone 6 was observed after 24 h for three additional
runs with the same catalyst (total of 80 mol of product per mole
of 4) with 6 isolated in 86% yield (average of four runs, each
run in duplicate). When the catalyst was used for a fifth time,
only 69% conversion to bromolactone 6 was observed after 24 h.
However, the selenium content [(1.4 ( 0.3)% Se by atomic
absorption analysis] was essentially unchanged from that of the
virgin catalyst [(1.5 ( 0.3)% Se].
Summary and Discussion. We have developed a recyclable
catalyst for bromination of organic substrates with NaBr and
H2O2 based on xerogel-sequestered selenoxide 4. When used
at 5 mol % catalyst, the APTES/TEOS-sequestered catalyst can
be recovered by filtration and recycled without apparent loss
of activity through 80 mol of product per mole of catalyst. The
xerogel-sequestered catalyst works well in water and aqueous
dioxane as solvents. The system appears to be first order in H2O2
and independent of Br- at the concentrations employed here.
a No starting material detected at this point. b Average of duplicate
runs.
sequestered 4 (relative to 4-pentenoic acid at 0.125 M) to give
bromolactone 6 in (87 ( 1)% isolated yield (average of duplicate
runs) after a total reaction time of 24 h (entry 1, Table 2). The
APTES/TEOS-sequestered 4 was separated via filtration from the
reaction mixture. Control reactions in the presence of catalyst-free
APTES/TEOS gave approximately 5% conversion to products after
24 h.
Brominations of 3,5-dihydroxybenzoic acid (entry 2), 1,3,5-
trimethoxybenzene (entry 3), and N-phenylmorpholine (entry
4) were also examined with 5 mol % 4 sequestered in APTES/
TEOS as summarized in Table 2. These substrates were less
soluble in phosphate buffer and a 1/1 mixture of dioxane and
pH 6 phosphate buffer was used as solvent in these reactions.
Bromination of 3,5-dihydroxybenzoic acid was complete after
19 h to give a 94:6 mixture of two products from which
2-bromo-3,5-dihydroxybenzoic acid (7) was isolated in 89%
yield. The 4-bromo isomer was the minor product. Bromination
of 1,3,5-trimethoxybenzene was complete after 24 h to give a
98:2 mixture of 2-bromo-1,3,5-trimethoxybenzene (8) as the
major product, isolated in 96% yield, and trace amounts of the
The relative rate of bromination of pentenoic acid with the
APTES/TEOS-sequestered selenoxide 4 was 23× faster in com-
parison to the homogeneous reaction with 4 dissolved in D2O. This
difference is even more remarkable when one considers that only
a fraction of the total catalytic sites are likely accessible within
the xerogel matrix in comparison to 100% in bulk solution.11 There
is precedent for reactions with silica-sequestered catalysts being
faster relative to homogeneous catalysis with soluble analogues of
the same catalyst.7 Local concentrations of reagents within the
xerogel pores would be higher in comparison to bulk solution
leading to faster reaction rates. The enhanced rate of catalysis
observed with APTES/TEOS-sequestered 4 is another example of
active-site/surface cooperativity5b and is the first example of this
in an aqueous environment with use of either organically modified
xerogels or imprinted silica.
The importance of hydrogen-bond donors and acceptors in the
xerogel support can be gleaned from catalysis with the C3TriMOS/
TMOS-sequestered 4. In this material the surface is more hydro-
J. Org. Chem. Vol. 73, No. 17, 2008 6851

mL, 4 h each), and dried. The combined ether washes were
concentrated to give <0.010 g of residue, suggesting >95% of 4
was sequestered. Theoretically, each gram of xerogel contains 0.057
g (1.9 × 10-4 mol) of selenoxide 4. Atomic absorption analysis
indicated (1.5 ( 0.3)% Se in the powdered xerogel. (Calcd for
1.9 × 10-4 mol of Se per g: 1.5%.)
phobic from the n-propyl groups and lacks the amino functionality
of the APTES. This xerogel is also much less permeable to halides
(Figure S8, Supporting Information), which suggests that catalysis,
if any, will come from catalytic sites at the surface and near-surface
pores and not from deeper pores within the xerogel bulk. The
consequence is that catalysis with the APTES/TEOS-sequestered
4 is nearly 10× faster than catalysis with C3TriMOS/TMOS-
sequestered 4.
The catalyst, while effective, has a somewhat limited lifetime.
The catalyst is not leaching from the xerogel during reaction based
on selenium content. Solution studies have shown that aryl benzyl
selenoxides remain intact at the completion of reaction.3,4 The local
concentrations of reagents within the xerogel pores may be
sufficiently high that the benzyl carbon of the catalyst becomes a
site for nucleophilic attack with loss of the selenoxide functionality
and loss of catalytic activity. Diaryl selenoxides with appropriate
reactivity may be more robust catalysts for sequestering in xerogels
in future studies.
Stock Solutions for Kinetics Experiments. K2HPO4 (1.75 g,
10.0 mmol) and KH2PO4 (4.80 g, 35.2 mmol) were dissolved in 200
mL of distilled H2O or D2O to give pH 6.0 ( 0.2 buffer (0.23 M in
phosphate). 4-Pentenoic acid (2.56 g, 2.56 mmol) and NaBr (28.6 g,
0.28 mol) were added and the mixture was stirred until they dissolved.
Benzoic acid (0.61 g, 0.5 mmol) was added to the D2O stock.
Kinetic Studies of the Bromination of 4-Pentenoic Acid.
APTES-TEOS-sequestered 4 [0.65 g, 0.037 g (1.3 × 10-4 mol) of
selenoxide 4] or selenoxide-free APTES-TEOS (0.65 g) was added to 20
mL of stock pH 6 phosphate buffer. H2O2 (8.8 M, 0.81 mL, 7.5 mmol)
was added via micropipette in one portion. Small aliquots of the reaction
mixture (0.5 mL) were quenched with sodium bisulfite, acidified with
10% HCl, and extracted with CDCl3 (1.0 mL). The progress of bromi-
nation was determined by 1H NMR spectroscopy by integration of the
olefinic proton at C4 of 4-pentenoic acid (δ 5.82) with the methine protons
of 5 (δ 4.75) and 6 (δ 4.25). Rates of bromination, kobs, are based on the
average of duplicate runs, which agreed within 10%.
Experimental Section
Preparation of the TBS Ether 1.10 Imidazole (4.73 g, 69.5 mmol),
TBSCl (10.5 g, 69.5 mmol), and 4-bromobenzyl alcohol (10.0 g,
53.5 mmol) were stirred 15 h in CH2Cl2 (100 mL). Aqueous workup
and extraction with CH2Cl2 (3 × 25 mL) gave 15.7 g (98%) of 1
as a colorless oil following SiO2 chromatography eluting with
CH2Cl2.
Preparation of Selenide 2. Silyl ether 1 (9.63 g, 32.0 mmol) in
anhydrous THF (200 mL) was treated sequentially with t-BuLi (1.7 M
solution, 41 mL, 70 mmol) at -78 °C, Se powder (2.52 g, 32.0 mmol) at
room temperature until Se was consumed, and benzyl bromide (6.01 g,
32.0 mmol) at -78 °C. The mixture was stirred 15 h at ambient
temperature followed by an aqueous workup and extraction with ether (3
× 30 mL) to give 10.5 g (84%) of selenide 2 as an orange oil following
SiO2 chromatography eluting with hexanes (Rf 0.4).
Preparation of 4-(Hydroxymethyl)phenyl Benzyl Selenide
(3). A mixture of Bu4NF (1 M in THF, 77 mmol) and silyl ether 2
(15.0 g, 38.3 mmol) was stirred 2 h at room temperature in anhydrous
THF (150 mL). Saturated NH4Cl (200 mL) was added and products
were extracted with EtOAc (3 × 40 mL) to give 8.52 g (80%) of
selenide 3 as a white solid, mp 76-78 °C, following SiO2 chroma-
tography eluting with CH2Cl2 (Rf 0.4).
Preparation of Selenoxide 4. N-Chlorosuccinimide (1.40 g, 10.5
mmol) and selenide 3 (2.42 g, 8.7 mmol) in 20 mL of 1/1 (v/v)
MeOH/CH2Cl2 were stirred for 0.5 h at 0 °C.9 The reaction mixture
was diluted with CH2Cl2 (20 mL) and 10% aq NaOH (20 mL)
followed by stirring for 5 min. The organic layer was separated,
dried over MgSO4, and concentrated to a yellow oil, which was
crystallized form CH2Cl2/hexanes to give selenoxide 4 (2.15 g, 94%)
as a white solid: mp 126-126.5 °C. Anal. Calcd for C14H14O2Se:
C, 57.35; H, 4.81. Found: C, 57.26; H, 4.95.
Kinetic Studies in Buffered D2O. Selenoxide 4 (0.018 g,
6.1 × 10-5 mol), APTES/TEOS-sequestered 4 (0.32 g, 6.1 × 10-5
mol of 4), C3TriMOS/TMOS-sequestered 4 (0.50 g, 6.5 × 10-5 mol
of 4), or catalyst-free APTES/TEOS (0.32 g) was added to 10 mL of
stock phosphate-buffered D2O. H2O2 (8.8 M, 0.405 mL, 3.8 mmol;
0.81 mL, 7.5 mmol; or 0.203 mL, 1.9 mmol) was added in one portion
via micropipette. One milliliter aliquots of the reaction mixture were
1
removed, filtered through a cotton plug, and analyzed by H NMR
spectroscopy by integration of the olefinic proton at C4 of 4-pentenoic
acid and the methine protons of 5 (δ 4.75) and 6 (δ 4.25). The aliquot
was returned to the reaction vessel immediately after acquisition of
1H NMR spectral data. The benzoic acid doublet at δ 7.94 was used
as an internal standard. Rates of bromination, kobs, are compiled in
Table 1 and are based on the average of duplicate runs.
General Procedure for the Bromination of Organic Sub-
strates. Hydrogen peroxide (0.56 mL, 30% by wt, 8.8 M, 5.0 mmol)
was added dropwise to a mixture of NaBr (2.86 g, 28.0 mmol),
substrate (2.50 mmol), and 5 mol % APTES/TEOS-sequestered 4 [0.65
g containing 0.037 g (1.3 × 10-4 mol) of selenoxide 4] in 20 mL of
a 1:1 (v/v) mixture of pH 6 phosphate buffer (0.23 M in phosphate)
and dioxane. After 19 or 24 h (Table 2), the catalyst was removed via
filtration, and products were extracted with EtOAc (3 × 20 mL). The
combined organic extracts were washed with 5% sodium bisulfite (10
mL) and brine (10 mL), dried over MgSO4, and concentrated. Products
were purified by SiO2 chromatography eluted with EtOAc/hexanes to
give 0.530 g (91%) of 2-bromo-3,5-dihydroxybenzoic acid (7),12 0.562
g (96%) of 1-bromo-2,4,6-trimethoxybenzene (8), mp 93.5-95.0 °C
(lit.13 mp 98-99 °C), or 0.545 g (90%) of N-(4-bromophenyl)mor-
pholine (9), mp 112-115 °C (lit.14 mp 114.5-115.5 °C).
Preparation of the Sol APTES/TEOS. Sol TEOS: TEOS (12.5
g, 60.1 mmol), water (2.16 mL), EtOH (13.6 mL), and 60 µL of
0.1 N HCl sealed in a glass vial were stirred at room temperature
for 6 h. Sol APTES: APTES (2.544 g, 11.49 mmol), 6.67 N HCl
(2.00 g), and EtOH (10.56 mL) sealed in a glass vial were sonicated
at room temperature for 40 min. Sol APTES/TEOS: Sol APTES
(5.000 mL, 3.83 mmol of APTES) and Sol TEOS (16.77 mL, 33.54
mmol of TEOS) were sonicated at room temperature for 20 min to
give 20 mL of Sol APTES/TEOS.
APTES/TEOS-Sequestered 4. Sol APTES/TEOS (20.00 mL)
and 4 (0.176 g, 0.58 mmol) in a glass vial were sonicated at room
temperature for 1 h, allowed to gel for 1 week covered, and then
placed uncovered under vacuum at room temperature for 1 week.
The resulting xerogel (3.09 g) was ground into a fine powder
(mortar and pestle), stirred with several portions of ether (3 × 100
Acknowledgment. We thank the Office of Naval Research
(Grant No. N00014021-0836) and the U.S. Department of Energy
(Grant No. DE-FG02-90ER14143) for support of this work.
Supporting Information Available: General experimental
statement; xerogel permeability studies; spectral characterization
1
of compounds 1-4 and 6-9; H and 13C NMR spectra for
compounds 3 and 4; 1H NMR spectrum of a mixture of
4-pentenoic acid, 5, and 6; and kinetics plots of the bromination
of 4-pentenoic acid with catalyst-doped and undoped APTES/
TEOS. This material is available free of charge via the Internet
at http://pubs.acs.org.
JO801234E
6852 J. Org. Chem. Vol. 73, No. 17, 2008