Sol-gel entrapped pyridinium hydrobromide perbromide as a recyclable bromination agent: Its application to a one-pot bromination and dehydrobromination process

Article abstract of DOI:10.1002/ejoc.200500982

Silica sol-gel encaged pyridinium hydrobromide perbromide can be used for clean, odorless bromination of a variety of substrates, including alkenes, ketones, and arenes. The used heterogenized bromination reagent can be recharged with bromine and recycled. In the presence of sol-gel entrapped 1,5,7-triazabicyclo[4.4.0]dec-5-ene, dibromides are dehydrobrominated to give vinyl monobromides and/or alkynes. Encapsulation of the pyridinium derivative and the guanidine base within separate sol-gel matrices enables the use of both opposing reagents in one-pot reactions without their mutual destroying each other. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

Full text of DOI:10.1002/ejoc.200500982

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200500982
Sol-Gel Entrapped Pyridinium Hydrobromide Perbromide as a Recyclable
Bromination Agent: Its Application to a One-Pot Bromination and
Dehydrobromination Process
Yevgenia Levin,[a] Khalil Hamza,[a] Raed Abu-Reziq,[b] and Jochanan Blum*[a]
Keywords: Bromination / Dehydrobromination / Guanidine base / One-pot reaction / Silica sol-gel
Silica sol-gel encaged pyridinium hydrobromide perbromide
can be used for clean, odorless bromination of a variety of
substrates, including alkenes, ketones, and arenes. The used
heterogenized bromination reagent can be recharged with
bromine and recycled. In the presence of sol-gel entrapped
Encapsulation of the pyridinium derivative and the guani-
dine base within separate sol-gel matrices enables the use
of both opposing reagents in one-pot reactions without their
mutual destroying each other.
1,5,7-triazabicyclo[4.4.0]dec-5-ene, dibromides are dehy- (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
drobrominated to give vinyl monobromides and/or alkynes.
Germany, 2006)
rivative of the strong base 1,5,7-triazabicyclo[4.4.0]dec-5-
ene[8] that under homogeneous conditions inactivates com-
pletely the bromination reagent.
Introduction
In the course of our studies on the application of sol-
gel technology to catalytic one-pot processes with opposing
chemicals,[1] we have demonstrated that by entrapment of
each of the reaction components within a separate ceramic
matrix it is possible to carry out such catalyses without the
mutual destruction of the reacting species. We were able to
Results and Discussion
The silica sol-gel entrapped bromination reagent was pre-
perform (i) rhodium-, ruthenium-, and mixed-metal-cata- pared as described in the Exp. Sect. by treatment of com-
lyzed hydrogenations and hydroformylations in the presence mercially available 2-[2-(trimethoxysilyl)ethyl]pyridine with
of catalyst poisons and inhibitors,[2] (ii) simultaneous acid- concentrated hydrobromic acid and bromine followed by
and base-promoted processes,[3] (iii) catalyses with oxidants hydrolysis and co-condensation with tetramethoxysilane
and reductants,[4] enzymatic reactions in the presence of en- (TMOS), as shown in Scheme 1.
zyme-destroying organometallics,[5] and (iv) combination of
The heterogenized pyridinium hydrobromide perbromide
the catalytic Heck coupling with interfering photochemis- (PHPB@s.g.) formed after drying over P2O5 under reduced
try.[6] We have now extended our research to include a cou- pressure, proved to act between 50 and 65 °C as a versatile
ple of opposing reactions which do not involve catalysts bromination reagent. Examples given in Table 1 indicate
namely bromination and dehydrobromination. The bromi- that the reagent adds bromine to alkenes to form dibro-
nation reagent of choice was a silylated modification of the mides, it turns ketones into α-bromo ketones, brominates
well-known pyridinium hydrobromide perbromide[7] and as toluene to give benzyl bromide and converts phenol to ring-
the hydrodebromination agent, we chose a glycidylated de- brominated phenols. The addition of bromine to the double
Scheme 1.
bond of 4-methylstyrene takes place in preference to the
substitution of a methyl hydrogen atom (see Entry 3), and
the bromination of the CH3 group of toluene is preferred
Fax: +972-2-6513832
[a] Department of Organic Chemistry, The Hebrew University,
Jerusalem 91904, Israel
E-mail: jblum@chem.ch.huji.ac.il
to the ring bromination (Entry 7). Only in the case of the
phenol, the ring is affected at the ortho and para positions
(Entry 8). It is also notable that, unlike the bromination of
[b] Centre for Catalysis, Research and Innovation, University of
Ottawa,
10 Marie Curie, Ottawa, Ontario K1N 6N5, Canada
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Sol-Gel Entrapped Pyridinium Hydrobromide Perbromide
SHORT COMMUNICATION
Table 1. Bromination of various substrates by sol-gel entrapped py- the isomeric stilbenes by non-heterogenized pyridinium hy-
ridinium hydrobromide perbromide.[a]
drobromide perbromide that transforms the (Z) and (E)
compounds to dl- and meso-dibromides, respectively,[9] the
entrapped reagent converts both stilbenes solely into the
meso product. This phenomenon may be associated with
the ability of the silica-bound reagent to reversibly intercon-
vert the isomeric stilbenes.
Upon completion of the reaction, the used heterogenized
pyridinium residue can be recharged with bromine and re-
cycled. When the bromination reagent, that had been used
in the experiments of Table 1 (6 mmol), was washed with
CH2Cl2 (3×10 mL) and sonicated followed by treatment
with Br2 and removal of the excessive halogen, the bromina-
tion ability of the reagent was renewed. For example, the
recycled PHPB@s.g., that was used under the conditions of
Table 1 for the bromination of cyclohexene, afforded in the
second, third and fourth runs of 7 h, 91, 92, and 88% of
1,2-dibromocyclohexane, respectively. Likewise, we bromi-
nated toluene with used and recharged agent and obtained
in the first four cycles of 7 h, 75, 74, 77, and 74% of benzyl
bromide.
Some of the bromination products (e.g., the dibromides)
could be dehydrobrominated by strong bases. Under homo-
geneous conditions, this operation could be carried out only
after completion of the bromination process and isolation
of the dibromides. A one-pot combined reaction is not pos-
sible because strong bases destroy the bromination reagent.
This shortcoming could be overcome by entrapment of the
base within a silica sol-gel matrix. The strong guanidine
base 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) was modi-
fied with (3-glycidoxypropyl)trimethoxysilane, hydrolyzed
and co-condensed with TMOS as shown in Scheme 2.[2b]
Application of the entrapped base TBD@s.g., does not
destroy the heterogenized reagent, PHPB@s.g., and permits
to carry out the bromination and hydrobromination in one
pot. Representative results are summarized in Table 2. Vinyl
bromides and/or acetylenes are formed in the first place
during the dehydrobromination. It seems however, that the
unsaturated products are re-brominated. Elimination of
HBr may form an olefin with a different stereochemistry
[a] Reaction conditions (except for Entry 8): 1.5 mmol of substrate
than the starting alkene. Indeed, the bromination of (Z)-
stilbene (Table 2, Entry 3) forms during a reaction period
of 15 h at 65 °C 47% of (E)-stilbene [only 2% of the (Z)
isomer remains]. Likewise, (E)-stilbene affords under the
same conditions 13% of (Z)- together with 20% of “un-
changed” (E)-stilbene. Thus, unlike under homogeneous
in n-hexane (10 mL) was stirred under N2 at 65 °C with 3 mmol of
PHPB@s.g. In Entry 8, 2.25 mmol of the bromination reagent was
used. [b] Average of at least 2 experiments that did not differ by
more than 3%. Analyses of the reaction mixtures indicated only
the presence of the bromination products and the unreacted sub-
strates. [c] If the reagent was not dried completely, the product was
contaminated with varying amounts of 2-bromocyclohexanol.
Scheme 2.
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Y. Levin, K. Hamza, R. Abu-Reziq, J. Blum
SHORT COMMUNICATION
Table 2. One-pot bromination and hydrodebromination of some unsaturated compounds.[a]
[a] Reaction conditions: 1.5 mmol of substrate in 30 mL of n-hexane was stirred under N2 at 65 °C (50 °C in Entry 2), with 3 mmol of
PHPB@s.g. and 3 mmol of DBN@s.g. [b] The yields refer to isolated products. They are the average of at least 2 experiments that did
not differ by more than 3%. Analyses of the reaction mixtures indicated only the presence of the products listed in the table und the
unreacted substrates.
Then CH2Cl2 (15 mL) was added and the agitated system cooled
to 0 °C. Bromine (9 mmol) was added and the agitation at that
temperature was continued for 3 h. The liquid was decanted and
the ceramic residue dried at 1 Torr for 12 h, sonciated in n-hexane
(3×10 mL) and redried at 1 Torr for 5 h before reapplication in a
second run.
conditions, the sol-gel entrapped base can enhance (indi-
rectly) also the bromination process.
Experimental Section
Preparation of Sol-Gel Entrapped Pyridinium Hydrobromide Perbro-
mide (PHPB@s.g.): To a solution of 2-[2-(trimethoxysilyl)ethyl]-
pyridine (6 mmol, ABCR GmbH) in n-hexane (2.5 mL) was added
with stirring 48% hydrobromic acid (7 mmol). After 10 min, ele-
mental bromine (6 mmol) was added and the stirring was continued
at 0 °C for 2 h. The mixture was then treated with tetramethoxysi-
lane (5 mL, 33.9 mmol) and triply distilled water (4 mL,
222 mmol). Within a period of 12–16 h at room temperature, the
mixture turned into a gel which was left to age for 24 h and dried
with P2O5 at 1 Torr for another 24 h. The orange ceramic material
was then sonicated in boiling n-hexane (3×10 mL), redried at room
temperature at 1 Torr for 5 h to give 2.8 g of the entrapped bromi-
nation reagent.
One-Pot Bromination and Dehydrobromination Processes: A mix-
ture of the unsaturated substrate (1.5 mmol), the heterogenized
bromination agent, PHPB@s.g. (3 mmol), the sol-gel entrapped
base, DBN@s.g. (3 mmol, prepared by a modification of the pub-
lished procedure, in which TMOS was used instead of tetraethoxy-
silane[2b]) and n-hexane (30 mL) was agitated at 65 °C for a period
of 12–15 h. The ceramic material was filtered off, the filtrate was
concentrated and separated by column chromatography on silica
gel. The identity of the resulting compounds was determined by
comparing the retention times of the gas chromatograms and the
IR, NMR and mass spectra with those of authentic samples.
General Procedure for the Bromination Process: Typically, a solution
of the substrate (3 mmol) and the heterogenized bromination rea-
gent (PHPB@s.g., 6 mmol) in n-hexane (20 mL) was stirred at
65 °C for 6 h. The ceramic material was filtered off and the filtrate
concentrated, chromatographed on silica gel and worked up in the
usual manner. The resulting products were separated either by GC
or HPLC and their NMR and mass spectra compared with those
of authentic samples.
Acknowledgments
We gratefully acknowledge the support of this study by the Israel
Science Foundation through Grant No. 177/03.
[1] See: S. J. Broadwater, S. L. Roth, K. E. Price, M. Kobaslija,
D. T. McQuade, Org. Biol. Chem. 2005, 3, 2899–2906.
[2] a) F. Gelman, J. Blum, D. Avnir, J. Am. Chem. Soc. 2000, 122,
11999–12000; b) F. Gelman, J. Blum, H. Schumann, D. Avnir,
J. Sol-Gel Sci. Technol. 2003, 26, 43–46.
Recharging of the Bromination Reagent: The filtered used bromina-
tion reagent was sonicated in warm (30 °C) CH2Cl2 (3×10 mL).
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Eur. J. Org. Chem. 2006, 1396–1399

Sol-Gel Entrapped Pyridinium Hydrobromide Perbromide
SHORT COMMUNICATION
[3] F. Gelman, J. Blum, D. Avnir, Angew. Chem. Int. Ed. 2001, 40, [8] a) R. Schwesinger, J. Willaredt, H. Schlemper, M. Keller, D.
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Published Online: February 3, 2006
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