One-pot sequences of reactions with sol-gel entrapped opposing reagents. Oxidations and catalytic reductions

Article abstract of DOI:10.1039/b208043p

An oxidant and a reducing catalyst are placed in a single pot without destroying each other, but are still capable of carrying out useful reactions, simultaneously. The oxidant, pyridinium dichromate, and an H₂-reduction catalyst, RhCl[P(C₆H₅)₃]₃, were entrapped in separate sol-gel matrices, and with these entrapped reagent and catalyst, three different flow-chart sequences of one-pot redox reactions were carried out - up to four reactions in one pot - without their mutual destruction and with no need for separation steps.

Full text of DOI:10.1039/b208043p

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One-pot sequences of reactions with sol-gel entrapped opposing
reagents. Oxidations and catalytic reductions
Faina Gelman, Jochanan Blum* and David Avnir*
Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
E-mail: david@chem.ch.huji.ac.il, jblum@chem.ch.huji.ac.il; Fax: +972 2 652 0099
L e t t e r
Received (in Montpellier, France) 14th August 2002, Accepted 12th November 2002
First published as an Advance Article on the web 12th December 2002
introduced by direct physical entrapment; the inorganic matrix
is very stable both to oxidizing and reducing conditions; SiO2
sol-gel materials do not swell; they are characterized by very
high surface areas and yet at the same time provide excellent
dopant protection by their full isolation from another sol-gel
entrapped reagent.
An oxidant and a reducing catalyst are placed in a single pot
without destroying each other, but are still capable of carrying
out useful reactions, simultaneously. The oxidant, pyridinium
dichromate, and an H2-reduction catalyst, RhCl[P(C6H5)3]3 ,
were entrapped in separate sol-gel matrices, and with these
entrapped reagent and catalyst, three different flow-chart
sequences of one-pot redox reactions were carried out—up to
four reactions in one pot—without their mutual destruction and
with no need for separation steps.
One specific system we studied (Scheme 1) was composed of
SiO2 sol-gel entrapped pyridinium dichromate16 as an oxidant
(PyCr@sol-gel), and hydrogen as a reductant, the activity of
which was catalyzed by entrapped RhCl[P(C6H5)3]3 (Cat@
sol-gel)17). The two precursors, benzyl alcohol, 1 (to be oxi-
dized to benzaldehyde 2), and nitrobenzene, 3 (to be reduced
to aniline 4), and the granules of PyCr@sol-gel and of Cat@
sol-gel were dissolved/dispersed in 1,2-dichloroethane in a
hydrogen-purged (atmospheric pressure) autoclave. Since the
reduction product of nitrobenzene, 3, namely aniline, 4, is
prone to oxidation by PyCr@sol-gel, pressurizing the auto-
clave with hydrogen was delayed for 1 h, during which PyCr@
sol-gel selectively oxidized the alcohol to benzaldehyde, 2. The
pressure of the hydrogen was then increased to 13 atm and the
reduction of nitrobenzene to aniline was carried out for 6 h.
(The reduction is negligible with the 1 atm hydrogen present
during the oxidation stage). After being formed the aniline
was trapped by the aldehyde in a spontaneous condensation
reaction to form the Schiff base 5 (thus avoiding aniline oxida-
tion) in 91% yield. Formed as well was 9% of the further reduc-
tion product of 5, namely N-benzylaniline, 6. Its yield can be
increased if desired by extension of the reaction time: after
an additional 10 h reaction time the yield of 6 increased to
23%. Thus, the use of two different sol-gel entrapped reagents
allowed one to carry out four reactions in the same reaction
flask without any separation of intermediate products. When
non-entrapped RhCl[P(C6H5)3]3 was used in the presence of
the entrapped oxidant, only benzaldehyde, 2, was formed.
The non-destructive co-existence of this oxidation-reduction
pair and its utilization for one-pot reactions was further
We report a new development of our sol-gel methodology for
the non-destructive co-existence of sol-gel entrapped reagents
and catalysts and their use in one-pot multistep syntheses.1–3
In our previous studies we demonstrated the synthetic use of
the one-pot co-existence of acids and bases,2 of catalysts with
acids and bases,1,3b and even of an enzyme in the presence of
destructive catalysts,3a all of which were entrapped, separately,
in SiO2-type porous sol-gel matrices but added together to
one and the same reaction pot. Examples of such one-pot
simultaneous or consecutive reactions carried out under these
conditions include the use of the hydrogenation catalyst RhCl-
[P(C6H5)3]3 and a diamine (which poisons this catalyst under
homogeneous conditions) for the preparation of ethylbenzene
from iodoethylbenzene1 and the one-pot acid-catalyzed pina-
col–pinacolone rearrangement followed by base-catalyzed con-
densation with malononitrile.2 To further generalize this
methodology we report here its application for another key
family of incompatible reactions, namely oxidations and cata-
lytic reductions. Furthermore, we report here also an increase
in the number of reactions we have been able to carry out by
this one-pot methodology from two in our previous reports,
to four.
Despite the inherent advantages of one-pot sequences of
reactions, namely saving separation and purification steps, cut-
ting down on the use of solvents and reagents and increasing
yields by eliminating the need to separate intermediate pro-
ducts, one-pot reactions with opposing reagents are rare4
and limited, to the best of our knowledge, to a few polymer-
bound reagents (reduction/oxidation5–8 and acid/base reac-
tions9–11). It seems that the rarity of the one-pot approach
has been due to cumbersom synthetic procedures for the pre-
paration of derivatized polymers, to auto- and mutual destruc-
tion of the organic polymeric support by the bound reagents,12
and to swelling in organic solvents, which increases local visc-
osity and opens the polymer network to further mutual
destruction of the opposing active moieties. A discussion of
these difficulties can be found in chapters 1 and 13 of ref. 12;
see also refs. 13–15. Sol-gel matrices are devoid of these diffi-
culties: straightforward covalent bonding can be used but
is not always needed as reactive functionalization can be
Scheme 1
DOI: 10.1039/b208043p
New J. Chem., 2003, 27, 205–207
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proven with two additional sequences. These additional
sequences also demonstrate the possibility of employing var-
ious flow charts in this one-pot method. Thus, whereas in
Scheme 1 the flow chart is of parallel reactions that form pro-
ducts that react with each other, our next sequence (Scheme 2)
is a flow-chart that leads from a starting material to a product
in two parallel routes: cinnamyl alcohol (3-phenylpropenol), 7,
dissolved in 1,2-dichloroethane was converted into 3-phenyl-
propionaldehyde, 10, as the result of the double bond reduc-
tion by H2/Cat@sol-gel and the oxidation of the alcohol
moiety by the PyCr@sol-gel. After 18 h at 60 ꢀC and 13 atm
H2 , 32% of 10 was obtained, along with some residual poly-
meric material. The reaction proceeds both via the aldehyde
8 (3-phenylprop-2-enal) and via the reduced alcohol (3-phenyl-
propanol, 9), as was evident from NMR follow-up.
while H2/Cat@sol-gel is mild enough not to reduce the carbo-
nyls of 10 and 13.
Beyond the proof-of-concept reported here, work towards
faster reaction rates and higher yields is still needed. An
approach towards these goals that proved useful in other sol-
gel studies has been to reduce the size of the material, that is
to work with micro- and nanaoparticles. In any event, taking
into account our earlier reports on other one-pot incompatible
systems,1–3 we believe that evidence has been now accumulated
that the sol-gel methodology is a convenient approach for het-
erogenizing a wide range of opposing chemicals for multistep
one-pot syntheses.
Experimental
The third system (Scheme 3) provides the most elementary
flow-chart, namely of two consecutive steps: 1-(4-nitrophenyl-
ethanol), 11, dissolved in 1,2-dichloroethane was converted
by the same pair of reactive sol-gel materials (16 h, 70 ꢀC, 21
atm H2) to 42% of 4-aminoacetophenone, 138 (along with
some 4-aminostyrene and 4-aminoethylbenzene). To avoid
possible oxidation of the amino group the same routine as in
Scheme 1 was employed: first the conversion of 11 to 12 was
affected, and after 2 h hydrogen was injected, converting
12 to 13. A similar one-pot reaction with the non-entrapped
catalyst RhCl[P(C6H5)3]3 resulted in the oxidation of 11 to
4-nitroacetophenone, without any reduction products.
Finally, it should be noted that in designing one-pot flow-
charts of redox reactions, one should consider the possibility
that the final products might be further reduced or oxidized.
Thus, the selection of the reagents should be tailored to the
desired product. For instance, in our case, PyCr@sol-gel is
mild enough to avoid oxidation of the nitrogen in 6 or 13,
Procedure for preparation of sol-gel entrapped pyridinium
dichromate (PyCr@sol-gel)
A mixture of 3.7 g (24.3 mmol) tetramethoxysilane (TMOS),
1.3 g (5.7 mmol) of 2-(trimethoxysilylethyl)pyridine (Gelest)
and 10 ml of methanol was stirred for 10 min. Then 2.2 ml
of water was added and the solution stirred at 40 ꢀC until gela-
tion occurred (within a few hours). The gel was kept at 40 ꢀC
for 3 days and then dried at that temperature for 40 h. The
resulting material was stirred with 20 ml of an aqueous solu-
tion of 0.6 g (6 mmol) of CrO3 for 4 h and then washed with
water portions until the water was colorless. The material
was then dried under vacuum (1 mm) at room temperature
for 20 h. The weight of the final material was 3.0 g.
Procedure for preparation of sol-gel entrapped
RhCl[P(C6H5)3]3 (Cat@sol-gel)17
A mixture of 18 mg (1.95 Â 10À2 mmol) of chlorotris(triphenyl-
phosphine)rhodium, 3.2 ml of peroxide-free THF, 0.4 ml
degassed water and 1.0 ml (6.8 mmol) TMOS was stirred under
Ar atmosphere until a clear solution was obtained, and then
allowed to stand at room temperature until the solution gelled
(2 days). The gel was dried under a vacuum of 0.1 mm Hg,
washed and sonicated for 1 h with 30 ml dichlomethane and
dried again under 0.1 mm vacuum until constant weight was
achieved. The Rh content in the CH2Cl2 washings was deter-
mined by atomic absorption analysis and was found to be less
than 1 ppm.
Procedure for the one-pot reaction
Following Scheme 1, a mini autoclave was charged with a solu-
tion of equimolar amounts of benzyl alcohol (0.16 g, 1.45
mmol) and nitrobenzene (0.2 g, 1.45 mmol) dissolved in 6 ml
of 1,2-dichloroethane. After addition of 1.5 g of a sol-gel
matrix containing 3 mmol of entrapped pyridinium dichro-
mate and 1.3 g of a sol-gel matrix containing 1.95 Â 10À2 mmol
of RhCl[P(C6H5)3]3 , the autoclave was purged three times with
hydrogen and heated in a thermostated oil bath to 70 ꢀC. After
1 h the autoclave was pressurized to 13 atm H2 and heated at
70 ꢀC for an additional 6 h. The reaction was then stopped and
the mixture cooled to room temperature. The sol-gel matrices
were filtered out and the products, all known compounds
(Scheme 1), were characterized and analyzed by NMR,
GC-MS and GC. The transformations of cinnamyl alcohol
(Scheme 2) and 4-nitrobenzyl alcohol (Scheme 3) were carried
out by similar procedures; the products are all known.
Scheme 2
Acknowledgements
We thank the Ministry of Science, Arts and Sport for support-
ing this project under the special Tashtiot project, as well as the
Israel Science Foundation (grant # 143/00-12) for financial aid.
Scheme 3
206
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