Efficient Chemoselective Reduction of N-Oxides and Sulfoxides Using a Carbon-Supported Molybdenum-Dioxo Catalyst and Alcohol

Article abstract of DOI:10.1002/cctc.201900436

The chemoselective reduction of a wide range of N-oxides and sulfoxides with alcohols is achieved using a carbon-supported dioxo-molybdenum (Mo@C) catalyst. Of the 10 alcohols screened, benzyl alcohol exhibits the highest reduction efficiency. A variety of N-oxide and both aromatic and aliphatic sulfoxide substrates bearing halogens as well as additional reducible functionalities are efficiently and chemoselectively reduced with benzyl alcohol. Chemoselective N-oxide reduction is effected even in the presence of potentially competing sulfoxide moieties. In addition, the Mo@C catalyst is air- and moisture-stable, and is easily separated from the reaction mixture and then re-subjected to reaction conditions over multiple cycles without significant reactivity or selectivity degradation. The high stability and recyclability of the catalyst, paired with its low toxicity and use of earth-abundant elements makes it an environmentally friendly catalytic system.

Full text of DOI:10.1002/cctc.201900436

DOI: 10.1002/cctc.201900436
Full Papers
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Efficient Chemoselective Reduction of N-Oxides and
Sulfoxides Using a Carbon-Supported Molybdenum-Dioxo
Catalyst and Alcohol
[a]
[a]
[a, b]
[a]
Jiaqi Li, Shengsi Liu, Tracy L. Lohr,*
and Tobin J. Marks*
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The chemoselective reduction of a wide range of N-oxides and
sulfoxides with alcohols is achieved using a carbon-supported
dioxo-molybdenum (Mo@C) catalyst. Of the 10 alcohols
screened, benzyl alcohol exhibits the highest reduction effi-
ciency. A variety of N-oxide and both aromatic and aliphatic
sulfoxide substrates bearing halogens as well as additional
reducible functionalities are efficiently and chemoselectively
reduced with benzyl alcohol. Chemoselective N-oxide reduction
is effected even in the presence of potentially competing
sulfoxide moieties. In addition, the Mo@C catalyst is air- and
moisture-stable, and is easily separated from the reaction
mixture and then re-subjected to reaction conditions over
multiple cycles without significant reactivity or selectivity
degradation. The high stability and recyclability of the catalyst,
paired with its low toxicity and use of earth-abundant elements
makes it an environmentally friendly catalytic system.
Introduction
The chemoselective reduction of oxygenated compounds, such
as N-oxides and sulfoxides, is of great importance from both a
[1–3]
synthetic and biological standpoint.
The reduction of such
compounds has typically been carried out with low-valent
[
2,4]
[5–8]
metal ions or precious metal catalysts
in the presence of
[9]
an excess of sacrificial reducing agents such as metal hydrides,
hydrogen halides, organosulfur reagents, and phosphorus
containing reagents.
[10]
[11]
[12]
These sacrificial reducing agents are
often highly toxic, and are known to produce large quantities of
waste. Recent advances using high-valent transition metal
catalysts have been reported, in which metal ions are combined
Scheme 1. Various methods of Reducing N-Oxides and Sulfoxides.
[5,13]
[8,14,15]
[16]
with reducing agents such as PPh3,
silanes,
boranes,
Despite these
[
7,17]
or high pressures of H2 (Scheme 1, A).
advances in synthetic methodology, many of these systems still
require highly toxic additives, stoichiometric sacrificial reducing
agents, a rigorously air-/moisture-free environment, and harsh
reaction conditions that are not suitable for many functional-
ized substrates. Furthermore, the fundamental problem of
separating catalysts from the reaction mixture has not always
been addressed, and potential catalyst recyclability has also not
been thoroughly investigated. For these reasons, recent studies
have focused on the development of more sustainable and
environmentally friendly strategies.
[18,19]
Molybdenum-oxo based catalysts have attracted a consid-
erable attention due to their low toxicity, earth abundance, and
[20]
versatility in various reaction systems. One promising meth-
odology of interest to us involves the use of alcohols as a
greener reducing agent. The Sanz group has reported the use
[21]
of pinacol for the reduction of sulfoxides and heteroaromatic
[19]
[
a] J. Li, S. Liu, Dr. T. L. Lohr, Prof. Dr. T. J. Marks
Department of Chemistry
N-oxides using a homogeneous MoO Cl (DMF) catalyst. In
2 2 2
[22]
addition to pinacol, glycerol and mercaptopropyl-functional-
Northwestern University
[23]
ized silica gel have also proven effective in this methodology
for the reduction of sulfoxides.
2145 Sheridan Road, Evanston, Illinois 60208 (USA)
E-mail: tracy.lohr@shell.com
t-marks@northwestern.edu
Although the investigation of homogeneous dioxo-molyb-
denum(VI) catalyzed deoxygenation has yielded many advances
in recent years, the study of their heterogeneous counterparts
has received considerably less attention. Compared to homoge-
neous catalytic processes, heterogeneous catalysts offer several
advantages including higher thermal stability and
[b] Dr. T. L. Lohr
Current Address:
Shell Catalysts & Technologies
Shell Technology Center Houston
3333 Highway 6 South, Houston, Texas, 77082 (USA)
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/cctc.201900436
[24]
recyclability. Recent work from the Marks group has shown
that single-site dioxo-molybdenum species grafted on high
This manuscript is part of the Special Issue dedicated to the Women of
Catalysis.
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surface area activated carbon, Mo@C, is a highly active catalyst
95% conversion is achieved after 6 h. Decreasing the temper-
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[25]
[26]
for alcohol oxidation, transesterification, as well as reduc-
ature to 105°C achieves >99% conversion after 20 h (Table 1,
[27]
tive carbonyl coupling. Therefore, we reasoned that in the
presence of alcohols Mo@C might also be competent for
catalyzing reductions.
Entry 2–4). These milder reaction conditions still achieve full
conversion of the starting material, although slightly longer
reaction times are necessary.
In this report, we describe an ecofriendly heterogeneous
catalytic system for the chemoselective reduction of pyridine N-
oxides and sulfoxides (Scheme 1, B). This system operates under
mild conditions with an inexpensive single-site supported Mo
catalyst that is both air- and moisture-stable (Scheme 2).
A solvent screen was next conducted in order to compare
the effects of anisole, chlorobenzene, benzyl nitrile, and ο-
xylene. All solvents examined afford full conversion and
excellent yields in 3 h (Table 1). Additionally, solvent-free
conditions were investigated and a similar conversion to
product is observed. Note that because of the nature of the
activated charcoal used as the carbon support, strong adsorp-
tion of substrates and products is unavoidable under both
solvated and solvent-free conditions. Consultation of the
solvent selection guide developed by ACS Green Chemistry
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[28,29]
Institute and others,
paired with the superior substrate
solubility in anisole led us to pursue further investigations using
Scheme 2. Synthesis of Mo@C. For characterization details see ref. 26.
[29,30]
this ecofriendly solvent.
In order to better understand the electronic and steric
effects of the reducing agent, 10 alcohols were screened for
their efficiency (Table 2). Compared to benzyl alcohol, the
Results and Discussion
[a]
Table 2. Alcohol screening.
Optimization of Reaction Conditions
Initial experiments were carried out using pyridine N-oxide as a
model substrate (Table 1, Entry 1). In the presence of 2 mol%
Entry
1
Alcohol
t [h]
Conversion
R=H
R=CH
R=CF
3
3
6
>99%
98%
84%
3
[a]
Table 1. Solvent screening.
3
2
20
>99%
3
4
6
6
>99%
>99%
Entry
1
Solvent
t [h]
Conversion
3
20
6
>99%
<1%
95%
[
b]
2
3
4
R=H
R=CHO
R=NO
R=CH
6
6
6
6
>99%
>99%
>99%
>99%
[c]
d]
[
20
>99%
5
2
5
3
3
3
>99%
>99%
>99%
3
[
a]
Conditions: 1.0 mmol pyridine N-oxide, 1.25 mmol alcohol, 2 mol%
6
Mo@C, 1.0 mmol mesitylene, 2.0 mL anisole, 500 rpm, 120°C.
7
[
a]
reduction was found to proceed more slowly in the presence of
electron poor or sterically hindered alcohols. It is worth high-
lighting that when furfuryl alcohol is used as the reducing
agent, the reduction of pyridine N-oxide is achieved at a
comparable rate as benzylic alcohols (>99% in 6 h, Table 2,
Entry 5). The introduction of functional groups to furfuryl
alcohol did not affect the reaction rate as illustrated in Table 2
Entry 5. Considering the wide availability of biomass-derived
Conditions: 1.0 mmol pyridine N-oxide, 1.25 mmol benzyl alcohol,
2
mol% Mo@C, 1.0 mmol mesitylene, 2.0 mL solvent, 500 rpm, 120°C. [b]
Carbon support alone. [c] 1 mol% Mo@C. [d] 105°C.
Mo@C, the reaction of 1 equiv. of pyridine N-oxide with a slight
excess of benzyl alcohol in anisole affords complete conversion
of the starting material to pyridine within 3 h at 120°C. As
expected, no significant conversion takes place in the absence
of Mo (carbon only) when pyridine N-oxide is subjected to
identical reaction conditions. An investigation of temperature
as well as catalyst loading effects were also conducted using
the same conditions as Table 1 entry 1. With 1 mol% Mo@C,
[31]
furfuryl alcohol, this result further demonstrates the great
potential of our system as a green chemical process.
Most of the alcohols are stoichiometrically converted to the
corresponding aldehydes (Table S1 and Table S2 Entry 1–3,
>90% selectivity) except for 3-methyl-2-buten-1-ol, furfuryl
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alcohol, and 5-methylfurfuryl alcohol (Table S2, Entry 4 and 5).
For 3-methyl-2-buten-1-ol (Table S2, Entry 4), 3-methyl-2-bute-
nal is the only product detected by H-NMR and GC-MS and
[a]
Table 3. Scope of N-oxide substrate reduction.
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accounts for 67% of the consumed alcohol. The negative mass
balance may reflect strong adsorption of the aldehyde on the
surface of the activated carbon. For furfuryl alcohol and 5-
methylfurfuryl alcohol (Table S2, Entry 5), aldehydes (65–69%
selectivity), dehydrated ethers (4–5% selectivity), and trace
amounts of 2-methylfuran or 2,5-dimethylfuran (2% selectivity)
were observed. The furan derivatives may be due to the low
stability of the corresponding aldehydes and alcohols, which
Entry
Substrate
t [h]
Conversion (Yield)
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5
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6
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6
3
>99% (85%)
[c]
[c]
>99% (86%) (75%)
>99% (96%)
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[32]
>99% (93%) (78%)
92% (81%)
are known to undergo deoxygenation.
Again, incomplete
mass balance is observed in these two cases and may reflect
[33]
strong adsorption of the aldehydes on the activated carbon.
6
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3
6
>99% (95%)
>99% (92%)
Substrate Functional Group Tolerance
[
c]
With optimal reaction conditions in hand, benzyl alcohol as
reducing agent, anisole as solvent, 2 mol% Mo at 120°C, the
reduction of a representative selection of pyridine N-oxides was
examined. These results are detailed below (Table 3).
Excellent conversion of N-oxide substrates and high
selectivity towards the corresponding reduced products are
observed regardless of the electronic nature of their substitu-
ents (Table 3, Entries 1–8). Additionally, reductions of various
quinolone and isoquinoline N-oxides also proceed efficiently
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95% (86%) (71%)
>99% (92%)
10
6
88% (77%)
[c]
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12
6
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>99% (90%) (84%)
[
b]
[c]
>99% (89%)
(Table 3, Entries 11–13). Moreover, the introduction of sterically
demanding groups in close proximity to the N-oxide function-
ality do not have any major detrimental effect on the outcome
of the reaction, as illustrated by the reactions of 2-methyl and
[
c]
13
3
96% (85%) (79%)
2
,6-dimethyl pyridine N-oxide (Table 3, Entries 9–10). Note that
[a]
Conditions unless otherwise specified: 1.0 mmol of substrate, 2 mol% of
the catalyst retains excellent chemoselectivity towards NÀ O
moieties in the presence of halogens and additional reducible
functionalities such carbonyls and cyano groups (Table 3,
Entries 2–3, 6–7). The broad substrate tolerance of the present
catalytic system offers an attractive alternative to chemo-
selectively reduce pyridine and its derivatives, which is known
Mo (59 mg of 3.23 wt% Mo@C), 1.25 mmol benzyl alcohol, 1.0 mmol
mesitylene (internal standard), 2.0 mL anisole, 500 rpm, 120°C. Conver-
1
sions and yields were determined by H NMR spectroscopy using
13
mesitylene as internal standard; products also confirmed by C NMR
spectroscopy and GC-MS. During the reaction, the chemical shift of the N-
oxides in the H NMR spectra change slightly, but the integration is not
influenced. For a more detailed analysis, see SI.
reaction. Isolated yield.
1
[
b]
Preparative scale
[c]
[3]
to be a challenging task.
In previous reports of N-oxide reduction, particularly those
using strong reducing agents, concurrent reduction of sulfoxide
moieties is frequently observed, such as with PhSiH /MoO Cl ,
3
2
2
H /MoO Cl , and the Fe/CO /H O system reported by the
2
2
2
2
2
[14,17,34]
Romao, Royo, and He groups respectively.
Given the
chemo-selective nature of our catalyst described above, we
were intrigued to explore whether the heterogeneous Mo@C
system can differentiate between N-oxide and sulfoxide reduc-
tion within the same reaction flask (Scheme 3). Interestingly,
when a one pot competition reaction between pyridine N-oxide
and methyl phenyl sulfoxide is conducted using a slight excess
of benzyl alcohol, monitoring of the reaction mixture shows
that the sulfoxide remains intact until complete conversion of
pyridine N-oxide is achieved. Following the complete reduction
of the N-oxide, thioether is detected as the only product from
the sulfoxide reduction (Figure 1A). A similar experiment under
benzyl alcohol starved conditions also confirms that Mo@C
does not concurrently reduce both N-oxide and sulfoxide
Scheme 3. Sulfoxide-N-oxide competition reactions.
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[
a]
Table 4. Scope of sulfoxide substrate reduction.
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Entry
1
Substrate
t [h]
Conversion (Yield)
96% (96%)
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87% (87%)
[
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[c]
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85% (72%)
96% (96%)
[
b]
[c]
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95% (80%)
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94% (89%)
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90% (90%)
90% (90%)
8
Figure 1. Sulfoxide and N-oxide competition reactions. Conversion of N-
oxide (blue), methyl phenyl sulfoxide (red), and benzyl alcohol (gray) over
time under alcohol sufficient (A) and starved (B) conditions at 120°C.
[
a]
Conditions unless otherwise specified: 1.0 mmol of substrate, 2 mol% of
Mo (59 mg of 3.23 wt% Mo@C), 1.25 mmol benzyl alcohol, 1.0 mmol
1
Conversions were determined by H NMR integration against mesitylene as
internal standard.
mesitylene (internal standard), 2.0 mL anisole, 500 rpm, 135°C. Conver-
1
sions and yields were determined by H NMR spectroscopy using
1
3
mesitylene as internal standard; products also confirmed by C NMR
[b]
[c]
spectroscopy and GC-MS. Preparative scale reaction. Isolated yield.
(Figure 1B), as only N-oxide reduction products are observed
under these conditions. Similar selectivity results are observed
at 135°C (SI, Scheme S1 and Figure S2).
Upon comparing the elemental analyses of both spent and
fresh catalyst the Mo loading remains essentially unchanged
(3.2 wt.% fresh versus 3.1 wt.% spent). Additionally, ICP analysis
of the reaction solution reveals that only trace amounts of Mo
(<13 ppm) leach from the supported catalyst into the reaction
solution under typical reaction conditions. The trace amount of
Mo in solution was determined to be catalytically insignificant
via hot filtration experiments also conducted under optimized
reaction conditions (Figure S1). Furthermore, recycling experi-
ments show that the catalyst can be used 4 times without any
significant decline in activity or selectivity (Figure 2A and B).
The surface Mo of the spent catalyst was next characterized by
XPS (Figure 2C) and PXRD (Figure 2D). No variation in the Mo
binding energy is observed between the spent and fresh
catalyst, indicating that the nature of the surface bound Mo
species remains unchanged. The Mo 3d5/2 peak is found to be
With these catalytic N-oxide results in hand, we next
extended the scope of this catalytic reduction protocol to
sulfoxides. An initial investigation was done with methyl phenyl
sulfoxide. After optimizing reaction conditions, 96% conversion
in 3 h at 135°C was achieved (Table 4, Entry 1). Next, the survey
was expanded to other aliphatic and aromatic sulfoxides. In
general, the Mo@C catalyst achieves excellent conversion to the
corresponding thioether (Table 4, Entry 2–8) and retains the
chemoselectivity over halogens, carbonyls, cyano groups, and
CÀ C multiple bonds that was previously observed in the
reduction of N-oxides (Table S3). These results show that Mo@C
with alcohol serves as a broad and environmentally friendly
system for chemoselective reduction.
2
32.6 eV with a spin orbit splitting of 3.1 eV. These results are in
[
26]
Catalyst Recyclability
good agreement with previously reported XPS data
support our hypothesis of the existence of a Mo(VI) dioxo
species.
and
As noted above, homogeneous analogues of Mo@C have been
reported to affect operationally similar reduction reactions. In
order to ensure that the present system is indeed catalyzed by
a heterogeneous Mo-dioxo species rather than leached homo-
geneous molecular Mo species, a number of control experi-
ments were conducted.
Preliminary Empirical Rate Law Investigation
A preliminary investigation of the empirical rate law for the
Mo@C catalyzed reduction was conducted using pyridine N-
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2
5%. Again, because of the highly porous nature of the
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activated carbon support there is potential for the substrates
and products to competitively adsorb on the catalyst surface
(SI). This makes an accurate rate law challenging to deduce.
Nevertheless, under the present conditions the overall rate for
N-oxide reduction is found to be zero-order in pyridine N-oxide
concentration, first-order in benzyl alcohol concentration, and
fractional order in Mo content (Figure S3). However, for
sulfoxide reduction, the overall rate is found to be zero-order in
methyl phenyl sulfoxide concentration, and fractional order in
both benzyl alcohol and Mo content (Figure S4). While detailed
interpretation is frequently not straightforward in heteroge-
neous systems where the reaction occurs at the liquid-solid
interface, the measured reaction orders suggest that both
alcohol and Mo may be involved in the turnover-limiting step.
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Deoxygenation by H produced from direct alcohol oxidation
can be excluded since no deoxygenated products are observed
under 50 psi of H in the absence of alcohol (see Experimental).
2
2
Conclusions
We report a heterogeneous Mo@C catalyst demonstrating both
high activity and selectivity in the reduction of N-oxides and
sulfoxides when paired with alcohol reducing agents. The high
functional group tolerance has been demonstrated by the
chemoselective reduction of challenging substrates bearing
C=C, C�C, C�N, C=O, halides, and S=O functional groups. The
ease with which sterically hindered substrates undergo reduc-
tion is also noteworthy. The high stability, wide availability,
recyclability, and low toxicity of the Mo@C catalyst and the
reducing agents further support this system as an ecofriendly
and robust catalytic system. We envision that the operational
simplicity of this protocol allows for its use by not only
experienced heterogeneous catalytic chemists, but also chem-
ists that do not typically utilize heterogeneous catalysis.
Experimental Section
General Considerations
Activated carbon (06-0100, Lot#2562087) was purchased from
Strem Chemicals. The reagents 3-acetylpyridine N-oxide, 4-chlor-
opyridine N-oxide, 4-(dimethylamino)pyridine N-oxide hydrate, 2,5-
lutidine N-oxide, 4-methoxypyridine N-oxide, 2-methylpyridine N-
oxide, 4-nitropyridine N-oxide, 4-chlorophenyl sulfoxide, dibenzyl
sulfoxide, and tetramethylene sulfoxide were purchased from TCI
America. All other starting materials and solvents were purchased
from Sigma-Aldrich. All chemicals were used as received and
without further purification unless otherwise noted. Mo@C was
prepared and fully characterized previously by this laboratory from
Figure 2. Recycling experiments illustrating conversion and selectivity from
pyridine N-oxide to pyridine (A) and methyl phenyl sulfoxide to methyl
phenyl sulfide (B) using the recycled Mo@C catalyst. Mo(3d5/2) XPS spectra
of Mo@C before (black) and after (red and blue) reactions (C). PXRD spectra
of carbon support (red) and Mo@C before (black) and after (blue and green)
reactions(D).
(dme)Mo(=O) Cl
(dme=1,2-dimethoxyethane) and activated
2
2
[26]
carbon.
oxide and methyl phenyl sulfoxide as model substrates
Analytical Measurements
1
respectively. The reaction was monitored via H NMR using
1
13
H and C NMR spectra were recorded at Integrated Molecular
mesitylene as an internal standard. The initial reaction rates at
different concentrations were measured at conversions below
Structure Education and Research Center (IMSERC) at Northwestern
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University with a 500 MHz Bruker Avance III HD system equipped
with a TXO Prodigy probe, a 400 MHz Bruker Avance III HD Nanobay
system equipped with SampleXpress autosampler, or a 500 MHz
Preparative Scale Reduction
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On a preparative scale, isoquinoline N-oxide (1.161 g, 8 mmol) was
subjected to the catalytic reduction conditions with benzyl alcohol
at 120°C with 2 mol% Mo metal loading. After 6 h, the reaction
mixture was cooled to room temperature, treated with 1M aqueous
HCl solution, washed with DCM, neutralized with 1M aqueous
NaOH solution, and then extracted with DCM. Isoquinoline was
recovered as yellow oil in 89% isolated yield after removal of
solvent in vacuo. Similar reduction procedures were performed
with p-tolyl sulfoxide (1.152 g, 5 mmol) and 4-chlorophenyl
sulfoxide (1.356 g, 5 mmol) at 135°C. After 20 h, the reaction
mixtures were cooled to room temperature, filtered through a silica
bed, placed under vacuum to remove solvent, and further purified
by column chromatography. The corresponding sulfides were
recovered as white solids in 72% and 80% isolated yields
1
13
Varian Inova-500 spectrometer. Chemical shifts (δ) for H and
C
are referenced to TMS. Mesitylene was used as an internal standard
unless otherwise noted. GC/MS analyses were recorded at IMSERC
at Northwestern University with an Agilent 7890 GC-TOF equipped
with a 30 meter DB-5 column. An initial temperature of 75°C was
held for 2 min before applying a ramp rate of 20°C/min up to
300°C. The temperature was then held at 300°C for an additional
10 min. ICP analysis of the catalyst Mo metal loading was
performed by Galbraith Labs (Knoxville, TN). ICP analysis of the
reaction solution was recorded at Quantitative Bio-element Imaging
Center (QBIC) at Northwestern University with a Thermo iCAP 7600
Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-
OES). Powder X-ray diffraction (PXRD) experiments were carried out
in the J. B. Cohen facility at Northwestern University using a Rigaku
Ultima diffractometer.
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respectively after removal of solvent in vacuo, with H-NMR spectra
[
2,36]
(agreeing with the literature ) presented in the Supporting
Information.
Catalytic Reduction
Catalyst Recycling
In a typical experiment, pyridine N-oxide (0.095 g, 1.0 mmol,
After the initial reaction, the reaction mixture was filtered using a
Buchner funnel and the Mo@C catalyst was then collected and
washed with anisole (3×3 mL) and hexanes (2×3 mL). The catalyst
was then allowed to air dry. The recyclability test was then
performed for reduction of pyridine N-oxide and methyl phenyl
sulfoxide under the same conditions detailed above. Four sequen-
tial catalytic runs were performed.
1
.0 equiv) or methyl phenyl sulfoxide (0.140 g, 1.0 mmol, 1.0 equiv),
benzyl alcohol (0.135 g, 1.25 mmol, 1.25 equiv), mesitylene
0.14 mL, 1.0 mmol, 1.0 equiv), anisole (2.0 mL), Mo@C (0.059 g,
mol% Mo) and a magnetic stir bar were added to a single neck
Schlenk flask in air. A reflux condenser was attached with a port to
house N . The solution was degassed then placed under N . While
(
2
2
2
stirring at 500 rpm, the flask was lowered into an oil bath at 120°C.
Samples were periodically collected and analyzed via NMR spectro-
scopy to monitor the course of the reaction. Conversion and
1
Hot filtration Procedure
selectivity were calculated by H NMR spectroscopy through
integration against the internal standard. All reported products area
Mo@C (0.594 g), anisole (2.0 mL), mesitylene (1.4 mL), benzyl
alcohol (0.135 g), and a magnetic stir bar were added to a single
neck Schlenk flask equipped with a reflux condenser. The solution
was degassed, heated to 120°C under nitrogen for 1 h, then filtered
1
13
known compounds and were compared to published H/ C NMR
values when possible and verified by GC/MS when appropriate.
into another flask while still hot via cannula filter. After cooling to
rt, pyridine N-oxide (0.095 g, 1.0 mmol) was added to the flask and
heated to 120°C for 3 h. The solution remained colorless, and no
Product Purification for N-Oxides
After the reaction, the reaction mixture was cooled to room
temperature and the crude mixture was treated with 1 M aqueous
HCl solution (5 mL). During extraction, the catalyst remained in the
organic layer, which was discarded. The aqueous layer was washed
with DCM (5×1 mL), neutralized with 1M aqueous NaOH solution
(6 mL), and extracted with DCM (3×2 mL). The combined organic
1
benzaldehyde or pyridine peaks were observed in the H NMR
spectrum.
Competition Experiment for Reduction of Sulfoxides and
N-Oxides
layers were dried over anhydrous Na SO , filtered, and the solvent
2
4
was evaporated under reduced pressure. The1 corresponding
Pyridine N-oxide (0.095 g, 1.0 mmol, 1 equiv), methyl phenyl
sulfoxide (0.140 g, 1.0 mmol, 1.0 equiv), benzyl alcohol (0.140 g,
pyridines were obtained in pure form with H-NMR spectra
[35,36]
(agreeing with the literature
) presented in the Supporting
1
.3 mmol, 1.3 equiv, or 0.081 g, 0.75 mmol, 0.75 equiv), mesitylene
Information.
(0.14 mL, 1.0 mmol), anisole (2.0 mL), Mo@C (0.059 g, 2 mol% Mo)
and a magnetic stir bar were added to a single neck Schlenk flask in
air. A reflux condenser was attached with a port to house N . The
solution was degassed and then placed under N . While stirring at
2
Product Purification of Sulfoxides
2
5
00 rpm, the flask was lowered into an oil bath at 120°C. Samples
After the reaction, the reaction mixture was cooled to room
temperature and the crude mixture was filtered through a silica
bed to remove the catalyst and washed with hexanes (3×5 mL).
Then the collected filtrate was placed under vacuum to remove
hexanes and anisole at room temperature and the crude product
further purified by column chromatography using hexanes as the
eluent. The solvent was evaporated under vacuum. The purified
product is slightly air-sensitive and was stored under inert
atmosphere. The corresponding sulfides were obtained in pure
were periodically collected and analyzed via NMR spectroscopy to
monitor the course of the reaction. Conversion and selectivity were
1
calculated by H NMR through integration against the internal
standard.
Control Experiments Using H as a Reductant
2
Pyridine N-oxide (0.095 g, 1.0 mmol, 1.0 equiv), mesitylene (0.14 mL,
1.0 mmol), anisole (2.0 mL), Mo@C (0.059 g, 2 mol% Mo) and a
magnetic stir bar were added to a round bottom heavy wall
pressure vessel in air. The solution was degassed and then placed
1
[2]
form with H-NMR spectra (agreeing with the literature ) presented
in the Supporting Information.
under 50 psi H (g). While stirring at 500 rpm, the flask was lowered
2
ChemCatChem 2019, 11, 1–9
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Full Papers
into an oil bath at 120°C and heated for 3 h. Samples were
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magnetic stir bar were added to a round bottom heavy wall
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Acknowledgements
This work is supported by the U.S. Department of Energy, Office of
Science, Office of Basic Energy Sciences under Award Number DOE
DE-FG02-03ER15457 to the Institute for Catalysis in Energy
Processes (ICEP) at Northwestern University (J.L., S.L.). This work
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support from the NSF CHE-1048773, NSF CHE-9871268; Soft and
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[
[
Conflict of Interest
The authors declare no conflict of interest.
[
[
[
[
Keywords: Chemoselective · N-oxide and Sulfoxide Reduction ·
Carbon-supported Dioxo-Molybdenum
·
Environmentally
Friendly · Heterogeneous Catalysis
ChemCatChem 2019, 11, 1–9
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(
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FULL PAPERS
J. Li, S. Liu, Dr. T. L. Lohr*,
Prof. Dr. T. J. Marks*
1 – 9
Efficient Chemoselective
Reduction of N-Oxides and Sulfox-
ides Using a Carbon-Supported
Molybdenum-Dioxo Catalyst and
Alcohol
Mo@C makes it: The chemoselective
reduction of a wide range of N-oxides
and sulfoxides with alcohols using a
carbon-supported dioxo-molybdenum
catalyst is reported. The high stability,
earth abundance, and recyclability of
the catalyst, paired with its low
toxicity represents an environmentally
friendly catalytic system.
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