Selective Photooxidation Reactions using Water-Soluble Anthraquinone Photocatalysts

Article abstract of DOI:10.1002/cctc.201700779

The aerobic organocatalytic oxidation of alcohols was achieved by using water-soluble sodium anthraquinone sulfonate. Under visible-light activation, this catalyst mediated the aerobic oxidation of alcohols to aldehydes and ketones. The photo-oxyfunctionalization of alkanes was also possible under these conditions.

Full text of DOI:10.1002/cctc.201700779

Accepted Article
Title: Selective photooxidation reactions using water soluble
anthraquinone photocatalysts
Authors: Wuyuan Zhang, Jenő Gacs, Isabel W.C.E. Arends, and Frank
Hollmann
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Selective photooxidation reactions using water soluble
anthraquinone photocatalysts
Wuyuan Zhang,* Jenő Gacs, Isabel W.C.E. Arends and Frank Hollmann*
Abstract: Aerobic organocatalyic oxidation of alcohols can be
achieved using water soluble sodium anthraquinone sulfonate.
Under visible light activation this catalyst mediates the aerobic
oxidation of alcohols to aldehydes and ketones. Photo-
oxyfunctionalization of alkanes is also possible under these
conditions.
formation rate (Figure S3).
The search for selective and benign oxidation protocols
represents a very active research area in organic chemistry.
Catalytic methods utilizing molecular oxygen or hydrogen
peroxide are preferred due to the availability of the terminal
oxidants,[1] their atom efficiency and the unproblematic side
products formed. Today, transition-metal catalyzed methods[2]
prevail but organocatalytic approaches are developing rapidly.[3]
A particularly interesting field is organophotocatalysis exploiting
Scheme 1. Schematic representation of the photocatalytic, SAS-mediated
oxidation of C-H bonds
4]
the unique reactivities of photoexcited organinc dyes[3a,
Benzophenones and anthraquinones are among these
promising photoredox catalysts. Upon light initiation, the
anthraquinone catalysts allow C-H bond or alcohol oxidation,
oxidative esterification and cleavage of cyclic acetals.[5]
As early as the 1960s water soluble sodium anthraquinone
sulfonate (SAS) has been reported as photocatalyst for the
oxidation of alcohols.[6] However, while its mode of action is fairly
understood today, synthetic applications are scarce.
Interestingly enough, SAS so far has only been evaluated as
catalyst for the oxidation of alcohols. Oxyfunctionalization of C-H
bonds was scarcely considered with SAS.
Inspired by recent contributions from Wolf[3d] and König[3e-h]
using flavin photocatalysts for light-driven organocatalytic
oxyfunctionalization reactions of alkyl benzenes, we decided to
evaluate the usefulness of SAS as photocatalyst for the
oxygenation of alkyl benzenes (Scheme 1).
A first experiment with homogeneously dissolved toluene
gave clean conversion of the starting material into benzaldehyde
(81% yield) with minor amounts of benzyl alcohol (5.6 %) and
benzoic acid (2.5 %) formed (Figure S1). The apparent gap in
mass balance is most likely attributed to the volatility of the
starting material and product under the reaction conditions. It is
worth mentioning here that in the absence of either the
photocatalyst (SAS) and/or light, no conversion of the starting
material was observed. Performing the reaction under (near)
anaerobic conditions resulted in a significantly reduced product
Encouraged by these results we advanced to higher
substrate loadings by adding toluene as organic phase to the
reaction mixture (Figure 1). The oxidation of toluene proceeded
almost linearly for more than two days accumulating more than
170 mM of benzaldehyde in the organic phase. The
concentration of benzyl alcohol steadily rose to approx. 7 mM
within the first
8 h and then remained constant at this
concentration throughout the experiment suggesting that the
second oxidation of benzyl alcohol to benzaldehyde was
significantly faster than the first step (toluene to benzyl alcohol).
Indeed, repeating the same experiment but using benzyl
alcohol as organic phase resulted in a dramatic rate acceleration
as compared to the oxidation of toluene (Figure 2). While in the
first case an average product formation rate of approx. 5.2 mM
h-1 was observed, this value was roughly one order of magnitude
higher in case of benzyl alcohol as starting material (49.5 mM h-
1). In this experiment approximately 24% conversion of the
benzyl alcohol was achieved within 80h. The only by-product
detected was benzoic acid (60 mM in the aqueous phase
corresponding to approximately 5% of the total product).
Qualitatively, this trend was also observed with all other starting
materials evaluated here (Tables 1&2). This ‘overoxidation
activity’ was pH-dependent showing higher rates at more
alkaline pH values. We attribute this to the formation of gem-
diols exhibiting abstractable H-atoms and the pH-dependent
hydratation equilibrium of benzaldehyde.[7] In any case, under
buffered conditions (pH 7) the overoxidation was practically
negligible (Figure S5). Using benzaldehyde as starting material
gave only minor conversion under otherwise identical conditions.
[a]
Dr. W. Zhang,* J. Gacs, Prof. I.W.C.E. Arends and Dr. F. Hollmann*
Department of Biotechnology
Delft University of Technology
Van der Maasweg 9
2629HZ Delft, The Netherlands
E-mail: W.Zhang-1@tudelft.nl; F.Hollmann@tudelft.nl
Supporting information for this article is given via a link at the end of
the document.
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Furthermore, performing the photochemical oxidation reactions
either in the presence of catalase (to dismutate any H2O2
formed) or in the presence of excess H2O2 under otherwise
identical conditions to the experiments outlined above, had no
significant influence on the time course of the reaction (Figure
S8). Therefore, we conclude that H2O2 is not involved in the
actual oxidation reaction.
The reaction rate correlated with the concentration of
photocatalyst applied (Figure 3). This correlation, however, was
not linear with the photocatalyst concentration. The turnover
frequency of SAS (as determined within the first 3 h of reaction)
decreased from 26.4 h-1, via 13.9 h-1 to 10.8 h-1 using 0.25 mM,
0.5 mM and 1 mM of SAS, respectively. Possibly, this may be
attributed to a decreasing transparency of the reaction medium
leading to a reduced photoexcitation of SAS. In fact, the rate of
the reaction directly correlated with the light intensity applied
(Figure S9), supporting this assumption. However, at present
time we also cannot fully rule out that O2 diffusion into the
reaction system may become overall rate limiting at high overall
conversion rates. Previously, we have observed similar effects in
case of photoenzymatic oxidation reactions.[8]
Figure 1. Representative time course of a photocatalytic oxidation of toluene
in a biphasic system. Conditions: toluene : water (c(SAS)aq = 1 mM) = 3:7,
ambient atmosphere, T = 30 °C,  > 400 nm. : benzaldehyde, : benzyl
alcohol. Values correspond to the concentration in the organic phase.
Figure 3. Time courses of benzaldehyde formation at different SAS
concentrations. The general conditions are described in Figure 1. c(SAS)aq
0.25 mM (), 0.5 mM (), 1 mM().
=
Figure 2. Time course of the photocatalytic oxidation of benzyl alcohol in a
biphasic system. Conditions: benzyl alcohol : water (c(SAS)aq=1 mM)=3:7,
ambient atmosphere, T=30 oC,
 > 400 nm. Values correspond to the
concentration in the organic phase.
Next, we set out to further characterize the novel
photocatalytic reaction system. As shown in Scheme 1, H2O2 is
expected as by-product of the aerobic oxidation reaction. Indeed
we observed the accumulation of H2O2 in the course of the
reaction (Figure S6); however, not in stoichiometric amounts.
Most likely this can be attributed to a competing H2O2-oxidation
activity of the photoexcited SAS (Figure S7). To exclude a
possible contribution of H2O2 oxidation reaction some control
experiments were performed. Performing the reaction in the
presence of H2O2 (100 mM) in the dark gave no conversion.
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8[c]
195
96
41.8
0.9
9
29.3+38.8 n.d.
12.6+16.6 0.5+0.7
10
94.3
n.d.
40.4
1.7
11
12
14.4
19.2
n.d.
n.d.
6.2
8.2
0.3
0.34
13[d]
14[d]
7.5/0.6[e]
n.d.
n.d.
3.2/0.4[e] 0.13/0.02[e]
5.1/3.1[e]
11.9/4.4[e]
0.21/0.1[e]
Figure 4. SAS recycling experiments. Conditions: toluene : water (c(SAS)aq =
1 mM)= 3:7, ambient atmosphere, T=30 °C,  > 400 nm. The organic phase
was replaced every 24 hours by fresh toluene and the reaction continued.
[a] Conditions: alkane : water (c(SAS)aq=1 mM) = 3:7, O2 atmosphere, T =
30 °C,  > 400 nm, reaction time: 24h. Values correspond to the concentration
in the organic phase; [b] selectivity is calculated based on the sum of products
aldehyde/ketone and intermediates alcohols; [c] c(SAS)aq= 2 mM, t=48h; [d]
minor amounts of side products were detected by GC (Fig. S16 and S17); [e]
the product concentration in water phase; n.d.= not determined. TON =
molProduct  molSAS-1; TOF = TON  24h-1.
We also investigated the stability of SAS under the reaction
conditions (transformation of toluene to benzaldehyde). As
shown in Figure 4, SAS could be re-used in consecutive batch
reactions but continuously lost its catalytic activity (as indicated
by the decreasing toluene oxidation rate). Approximately after
72h, SAS exhibited 50% of its initial activity (overall a TON of 71
was estimated for SAS). This loss in catalytic performance is
also accompanied by significant structural modifications as
judged by 1H NMR analysis (Figure S15). Probably, the aromatic
hydroxylation of SAS led to (photocatalytically) inactive species
and, eventually, resulted in structural decomposition of the
catalyst.[9] This is partially supported by the occurrence of
hydroxyl (OH) radicals in the course of the photocatalytic
reactions (Figure S16). It is, however, worth mentioning here
that significantly higher TON are possible e.g. with benzyl
alcohol as starting material (Table 2).
Table 1. photocatalytic oxidation of some C-H bonds.[a]
To further explore the scope of the photocatalytic oxidation
reaction, a range of activated and non-activated alkanes and
alcohols were evaluated (Tables 1&2). Again, oxidation of
alcohols was significantly faster yielding up to 10 times more
product as compared to the corresponding alkanes. Also,
activated C-H bonds (e.g. benzylic or allylic ones) yielded higher
product concentrations.
[Product] Selectivity TON
mM
TOF
h-1
Entry Substrate Product
[%][b]
Table 2. photocatalytic oxidation of some alcohols.[a]
1
2
37.1
25.2
3.7
1.5
1.0
0.2
0.4
0.3
86.6
89.4
58.8
8.6
80
3
4
5
69.5
76
[Product]
mM
TON
TOF
h-1
Entry
1
Substrate
Product
9.2
21.4
14.5
424
17.7
1.6
989
6.2
n.d.
2
3
37.5
87.5
6
7
7.3
0.3
0.6
17
n.d.
142
5.9
330
14.7
34.3
80.7
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4
101
4.2
235
179/15.7 [c]
359/63.6 [c]
5
6
76.8/11.0[c] 3.2/0.5[c]
154/44.5[c] 6.4/1.9[c]
7
188
7.8
2.7
440
307
8[b]
65.7
9
177
220
412
514
7.4
9.2
10
11
12
13
11.8
30.0
19.0
27.5
69.9
44.3
0.5
1.3
0.8
[a] Conditions: alcohol : water (c(SAS)aq=1 mM) = 3:7, O2 atmosphere, T =
30 °C,  > 400 nm, reaction time: 24h. Values correspond to the concentration in
the organic phase; [b] c(SAS)aq= 2 mM was used, t=48h; [c] the product
concentration in water phase. n.d.= not determined. TON = molProduct  molSAS
TOF = TON  24h-1.
-1
;
It should be noted that the conversions of the experiments
shown in Table 2 are generally below 20%, which can be
attributed to the low catalyst loading (S:C < 4000 mol mol-1).
Comparative experiments at more favorable S:C ratios (approx.
50:1 mol mol-1) gave full conversion within 2 days (Figure S25).
Wells and coworkers[6a, 6b] suggested H-atom abstraction to
Scheme 2. Plausible elementary steps involved in the photochemical alcohol
oxidation using SAS (sodium anthraquinone sulfonate).[4a, 4b, 6a, 6b]
be the overall rate-limiting step followed by
a series of
deprotonation and secondary electron transfer steps.
Accordingly, an increasing substitution pattern as well as
electron-donating substituents should increase the overall
reaction rate. The results shown in Tables 1&2 however do not
allow for such a conclusion. Most probably this can be assigned
to the biphasic character of the reaction mixtures used. As a
consequence the aqueous concentrations of the different
starting materials may differ significantly due to their different
partitioning coefficients. Hence the different in situ
concentrations of the reagents in the aqueous (SAS-containing)
phase may influence the oxidation rate to a similar extent as
their oxidizability and thereby lead to the somewhat confusing
correlation. In addition, the oxidation of aliphatic alcohols, as
expected, is much slower compared to that of aromatic and
allylic alcohols (Table 2, Entries 11-13).
Overall, we have demonstrated that simple and
commercially available sodium anthraquinone sulfonate can be
used
as
photocatalyst
for
the
selective
oxidation/oxyfunctionalization of a range of (non-)activated C-H
bonds in alkanes and alkanols. Particularly, selective oxidation
of alcohols appears to be a promising method for photocatalytic,
metal-free oxidation using molecular oxygen as oxidant.
Preliminary experiments in our laboratory also indicate that this
reaction can be extended to amines and other functionalities.
Future studies will concentrate on exploring the functional group
preference of the present photocatalyst as well as further
optimization of this reaction based on more in-depth
understanding of the catalytic mechanism.
For anthraquinone a H-atom-abstraction mechanism from
the starting material to the photoexcited (triplet) catalyst has
been established.[4a, 4b] This radical mechanism most likely also
applies to the SAS-catalyzed reaction reported here (Scheme 2).
Nevertheless, further studies clarifying the catalytic mechanism
in more detail are currently underway in our laboratory.
Acknowledgements
Financial support by the European Research Council (ERC
Consolidator Grant No. 648026) is gratefully acknowledged. The
authors thank Prof. Fred Hagen (Delft University of Technology)
for EPR measurements, Dr. S. Schmidt (Delft University of
Technology) for GC analysis and M. van Schie (Delft University
of Technology) for the characterization of light source.
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Keywords: photocatalysis • oxidation • oxyfunctionalization •
anthraquinone catalyst
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Water soluble sodium anthraquinone
sulfonate is used as an organo-
photocatalyst for the aerobic oxidation
of alkanes and alcohols.
Wuyuan Zhang,* Jenő Gacs, Isabel
W.C.E. Arends and Frank Hollmann*
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Selective photooxidation reactions
using water soluble anthraquinone
photocatalysts
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Author(s), Corresponding Author(s)*
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