Solvent-free, visible-light photocatalytic alcohol oxidations applying an organic photocatalyst

Article abstract of DOI:10.3762/bjoc.12.229

A method for the solvent-free photocatalytic conversion of solid and liquid substrates was developed, using a novel rod mill apparatus. In this setup, thin liquid films are realized which is crucial for an effective photocatalytic conversion due to the low penetration depth of light in heterogeneous systems. Several benzylic alcohols were oxidized with riboflavin tetraacetate as photocatalyst under blue light irradiation of the reaction mixture. The corresponding carbonyl compounds were obtained in moderate to good yields.

Full text of DOI:10.3762/bjoc.12.229

Solvent-free, visible-light photocatalytic alcohol oxidations
applying an organic photocatalyst
Martin Obst and Burkhard König*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2016, 12, 2358–2363.
Institute of Organic Chemistry, University of Regensburg,
Universitätsstraße 31, 93040 Regensburg, Germany
doi:10.3762/bjoc.12.229
Received: 01 September 2016
Accepted: 27 October 2016
Published: 09 November 2016
Email:
Burkhard König* - burkhard.koenig@chemie.uni-regenburg.de
*
Corresponding author
Associate Editor: C. Stephenson
Keywords:
© 2016 Obst and König; licensee Beilstein-Institut.
License and terms: see end of document.
benzylic alcohol; oxidation; photocatalysis; solvent free; visible light
Abstract
A method for the solvent-free photocatalytic conversion of solid and liquid substrates was developed, using a novel rod mill appa-
ratus. In this setup, thin liquid films are realized which is crucial for an effective photocatalytic conversion due to the low penetra-
tion depth of light in heterogeneous systems. Several benzylic alcohols were oxidized with riboflavin tetraacetate as photocatalyst
under blue light irradiation of the reaction mixture. The corresponding carbonyl compounds were obtained in moderate to good
yields.
Introduction
According to a classification made by Wilhelm Ostwald, one of process more environmentally friendly and sustainable. Further-
the pioneers in the field of physical chemistry and Nobel Prize more, quantitative yields can be achieved, avoiding work-up
laureate 1909, chemistry can be divided into the four sub-disci- and laborious purification [2]. Moreover, solubility problems,
plines thermochemistry, electrochemistry, photochemistry, and like insolubility of one reactant or the different polarity of two
mechanochemistry, depending on the kind of energy involved reactants, are solved. Examples for mechanochemical synthe-
in a chemical process [1]. Among these, mechanochemistry is ses include stoichiometric reactions such as the Knoevenagel
nowadays a well-established method for the solvent-free condensation and the Wittig reaction, but also reactions cata-
conversion of solid reactants. The reaction is driven by mechan- lyzed by metal catalysts, like the Sonogashira coupling and the
ical energy, which is for instance realized by grinding in ball Suzuki coupling [1].
mills or pestle and mortar. Obviously, this method possesses
several advantages compared to reactions, which are performed Photocatalysis, as a part of Ostwald’s sub-discipline photo-
in solution: toxic solvents and wastes are avoided, making the chemistry, is a rather new field of great academic interest.
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Namely, visible-light photocatalysis applying an organic, redox- In this work, we focus on benzylic alcohols as substrates since
active catalyst allows mild and efficient transformations. By their oxidation to the corresponding carbonyl compounds can be
exciting the photocatalyst, which then exchanges electrons with simply performed in acetonitrile/water mixtures. Thus, they are
the substrate, light energy is converted into chemical energy [3]. suitable model substrates for the investigation of our solvent-
This approach avoids expensive reagents and harsh reaction free principle.
conditions, which are improvements compared to conventional
processes. Considering that, we envisaged combining photo- In mechanochemistry, reactions are performed by grinding the
catalysis with mechanochemistry, thereby making use of the reaction mixture in ball mills, such as the vibrational ball mill or
advantages of both disciplines. In such an approach, solid sub- the planetary ball mill, or with a pestle and mortar. In prelimi-
strates would be grinded under visible light irradiation. In nary studies, we tested a vibrational ball mill for photocatalytic
contrast to mechanochemistry, the process would be driven by oxidations with riboflavin tetraacetate, using a transparent
light energy and not by mechanical energy, but profit from the milling chamber. However, this reactor proved to be unsuitable:
absence of toxic solvents, high concentrations of the substrate, the solid reaction mixture prevented light to reach the photocat-
and easy work-up. Furthermore, undesired effects of the sol- alyst, both by attachment of small amounts of solid to the inner
vent like hydrogen-atom transfer or the formation of byprod- side and shielding within the milling chamber. The low penetra-
ucts could be excluded.
tion depth of light led us to the conclusion that thin interfaces of
reactants, combined with continuous grinding, are necessary.
For liquid substrates, some examples for photocatalytic, sol- Based on these considerations, we constructed a rod mill,
vent-free conversions are reported, such as the oxidation of consisting of a test tube which contains the reaction mixture, a
benzyl alcohol to benzaldehyde [4] and the oxidation of glass rod, which is fixed to a stirrer, and an LED frame with
benzenes to phenols [5]. Another field of solvent-free photo- 5 LEDs (λ = 455 nm). Figure 1 shows a schematic representa-
catalysis is the application of heterogeneous, semiconducting tion and photographs. Before reaction, the solid substrate and
photocatalysts, often based on titanium dioxide and other metal photocatalyst are gently homogenized with a spatula, followed
oxides [6-8]. However, to the best of our knowledge, no by grinding with pestle and mortar. The reaction mixture is then
solvent-free visible-light driven transformation of a solid filled into the test tube. Subsequently, the rotating glass rod is
substrate applying an organic photocatalyst has been reported pressed into the test tube, which leads to vertical migration of
yet.
the reaction mixture and the formation of a film between the
inner wall of the test tube and the glass rod. The reaction is
In this work, we present a novel milling apparatus, which we carried out by rotation and irradiation with the LEDs from the
developed especially for the conversion of solid substrates. outside.
Applying this apparatus, the solvent-free oxidation of various
benzylic alcohols to their corresponding carbonyl compounds We started our investigations with the oxidation of 4,4’-
using riboflavin tetraacetate as photocatalyst under blue light ir- dimethoxybenzhydrol (1a) to 4,4’-dimethoxybenzophenone
radiation was performed. Furthermore, the oxidation of a liquid (1b), applying 10% RFTA (Scheme 1).
benzylic alcohol is presented as well.
In this initial trial, the product could be obtained in 72% yield.
Results and Discussion
For our investigations on solvent-free photocatalytic conver-
Subsequently, we varied the amount of RFTA (Table 1).
sions, we chose riboflavin tetraacetate (RFTA) as photocatalyst. Lowering the catalyst concentration from 10% to 5% does not
RFTA and flavin derivatives in general are well-known blue- significantly influence the yield (entry 2, Table 1, yield in aver-
light absorbing photocatalysts, which can oxidize a variety of age of four trials). Even a further decrease to 2% (entry 3,
substrates under aerobic conditions with oxygen as terminal Table 1) causes no essential decline. However, at a RFTA con-
oxidant. Flavins were studied extensively for the oxidation of centration of 1% (entry 4, Table 1), the isolated yield was only
alcohols, amines, methylbenzenes, styrenes, and phenylacetic 61%; very low catalyst concentrations are problematic due to
acids [9-12]. Some derivatives were also immobilized on silica inactivation of a certain portion of the catalyst, which might be
gel and applied in the oxidation of benzyl alcohols [13]. due to burning.
Furthermore, it was shown that the oxidation power of RFTA
can be increased by coordination to scandium triflate [14]. No product was formed in the dark (entry 5, Table 1) and only
Recently, the E/Z-isomerization of olefins with riboflavin as traces were obtained without photocatalyst (entry 6, Table 1).
catalyst was reported [15], which was also used for cyclization However, in this control reaction, melting of the substrate was
to form coumarins [16].
observed. All reaction mixtures containing RFTA appeared
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Beilstein J. Org. Chem. 2016, 12, 2358–2363.
Figure 1: Rod mill, schematic (left) and photographs (middle and right).
Scheme 1: Oxidation of 4,4’-dimethoxybenzhydrol (1a) to 4,4’-dimethoxybenzophenone (1b).
showing that the oxidation of the substrate is not only due to
heating. For further investigation, the reaction was performed
within a continuous water cooling (entry 8, Table 1). In this
setup, no product was formed. Therefore, the heating effect of
the blue light was found to be necessary to perform the reaction:
melting of the substrate leads to mobility of the substrate and
catalyst molecules, ensuring the occurrence of the catalytic
cycle. When the rotation was switched off after the formation of
the solid film (2 min), followed by LED irradiation (entry 9,
Table 1), the product was obtained in similar yield compared to
the reactions performed under grinding (entry 2, Table 1), indi-
cating that the grinding does not contribute to the essential
heating. Hence, light irradiation fulfils a double function: the
excitation of the photocatalyst and melting of the substrate, in-
ducing mobility of the molecules. As mentioned above, the
Table 1: Conditions and yields for the oxidation of 4,4’-dimethoxy-
benzhydrol (1a).
Entry
RFTA (%)
Yield (%)
1
2
3
4
10
5
72
74
2
69
1
61
5
a
10
–
0
6
traces
traces
traces
78
7b
5
8
c
5
9d
5
aIn the dark; bin the dark at 85 °C; cwith cooling; dno rotation.
solid. The fact that the substrate was molten without RFTA reaction mixtures containing RFTA appeared solid. Possibly,
leads to the conclusion that the blue light irradiation was small droplets of molten substrate were formed; due to the pres-
heating the substrate and temperatures higher than its melting ence of RFTA, no homogeneous liquid phase was observed. In
point (67–70 °C) occurred. The temperatures of the reaction mechanochemistry, the formation of hot spots by friction
mixtures were measured using an IR thermometer. Though, heating with high local temperatures and the existence of liquid
values not higher than 42 °C were obtained. This could be ex- eutectic states are believed to be responsible for chemical trans-
plained by the fact that the IR thermometer records only the sur- formations [1]. In contrast, in our rod mill apparatus, heating is
face temperature of the test tube; the temperature within the not induced by mechanical but by electromagnetic energy input,
reaction mixture might be above this value. When the reaction realized by blue light irradiation. Furthermore, the heat
mixture was heated to 85 °C in the dark, melting was observed input is not the primary cause for the reaction, but its prerequi-
(
entry 7, Table 1) and only traces of product were formed, site.
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Beilstein J. Org. Chem. 2016, 12, 2358–2363.
Subsequently, the scope of the benzylic alcohol oxidation was
investigated, applying 5% of RFTA. Four solid alcohols were
oxidized to their corresponding ketones or aldehydes, including
fluorenol (9-hydroxyfluoren), benzhydrol, benzilic acid, and
3
,4,5-triethoxybenzyl alcohol (2a–5a). Scheme 2 shows the
products and isolated yields, which are in the range from 37%
to 72%. In contrast to 4,4’-dimethoxybenzhydrol, a liquid paste
was observed in all cases, indicating melting of the substrate or
the product, which maintains mobility. The oxidation of
benzilic acid and benzhydrol was also performed using an LED
Scheme 3: Oxidation of 4-methoxyphenyl methyl carbinol (6a) to
4-methoxyacetophenone (6b).
setup containing only 4 LEDs instead of 5 LEDs like in the side product formation (see Experimental). In general terms,
frame rod mill. Here, the obtained yields were significantly this shows the potential of the method for an efficient synthesis
lower (36% and 30% vs 55% and 50%). This shows that the with direct product formation, facilitating work-up. However,
amount of energy reaching the reaction mixture plays a crucial the isolated yield was only 64% (average of two trials), indicat-
role.
ing loss in the column purification process and decomposition
of a part of the product in the reaction mixture.
Conclusion
We have developed a method for the solvent-free photocatalyt-
ic conversion of solid and liquid substrates using a novel rod
mill apparatus. The applicability of the rod mill was shown for
the oxidation of benzylic alcohols with riboflavin tetraacetate as
photocatalyst under blue light irradiation; the products were iso-
lated in moderate to good yields. In case of the solid benzyl
alcohols, the reactions were found to proceed via the molten
state of the substrates or products, which enables mobility of the
substrate and catalyst molecules and the occurrence of the cata-
lytic cycle. Thus, light fulfils the double function of both the ex-
citation of the photocatalyst and heating of the reaction mixture.
To summarize, the new combination of photocatalysis and
mechanochemistry, realized in a simple rod mill apparatus is an
alternative to conventional reaction setups. It may provide
advantages for the conversion of starting materials or catalysts
with no or low solubility in the same solvent and reactions
benefitting from high substrate concentrations.
Experimental
Materials and methods
NMR spectra were recorded on a Bruker Avance 300.
4
9
,4’-Dimethoxybenzhydrol was purchased from Alfa Aesar,
-hydroxyfluoren, benzhydrol, and 3,4,5-triethoxybenzalde-
hyde from Sigma-Aldrich, benzilic acid from Merck Schuchardt
and 4-methoxyphenyl methyl carbinol from Fluorochem.
Riboflavin tetraacetate was synthesized from riboflavin (Acros
Scheme 2: Scope for benzylic alcohol oxidation and obtained yields.
Furthermore, the suitability of the rod mill for the conversion of Organics) according to a procedure reported in the literature
liquid substrates was tested. 4-Methoxyphenyl methyl carbinol [17].
was oxidized applying 5% of RFTA (Scheme 3).
Technical data of the rod mill apparatus: 4 LEDs (455 nm,
The crude 1H NMR spectrum recorded after the reaction shows 700 mA) on a square aluminium frame (inner diameter 35 mm)
a quantitative conversion of the staring material and no visible and one LED below the test tube were used. The distance of
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Beilstein J. Org. Chem. 2016, 12, 2358–2363.
each LED to the test tube was 10 mm. The diameter of the used for reaction. Yield: 72%. 1H NMR (300 MHz, CDCl3)
glass rod was 8 mm and the inner diameter of the test tube was 7.66 (d, 2H, CH), 7.54–7.47 (m, 4H, CH), 7.30 (m, 2H, CH);
9
mm.
EIMS m/z: 180.0579 [M]+.
Synthesis
Benzophenone (3b)
General procedure: The substrate and riboflavin tetraacetate
were weighed into a mortar in stoichiometric amounts and
gently homogenized with a spatula, followed by grinding with a
pestle and mortar. The reaction mixture was filled into the rod
mill test tube and the mass was determined. Subsequently, the
rotating glass rod was pressed into the test tube, forming a film 3b from 3a: Diphenylmethanol (73.3 mg, 0.40 mmol) and
between the test tube and the glass rod. The reaction was carried RFTA (10.9 mg, 0.020 mmol) were weighed and 74.0 mg of the
out by rotation of the glass rod (80 rpm) and parallel irradiation mixture was used for reaction. Yield: 50%. 1H NMR
with the 455 nm LEDs for 24 hours. After the reaction, the (300 MHz, CDCl3) 7.83–7.79 (m, 2H, CH), 7.62–7.57
product was isolated by flash column chromatography (gradient (m, 2H, CH), 7.51–7.46 (m, 4H, CH); EIMS m/z: 182.0730
of ethyl acetate in petroleum ether).
[M]+.
4,4’-Dimethoxybenzophenone (1b)
3b from 4a: Benzylic acid (91.3 mg, 0.40 mmol) and RFTA
(
10.9 mg, 0.020 mmol) were weighed and 89.2 mg of the mix-
ture was used for reaction. Yield: 55%.
3,4,5-Triethoxybenzaldehyde (5b)
1
H NMR (300 MHz, CDCl3) 7.79 (m, 4H, CH), 6.96 (m, 4H,
CH), 3.88 (s, 6H, CH3); EIMS m/z: 242.0924 [M]+.
9-Fluorenone (2b)
3
,4,5-Triethoxybenzyl alcohol (96.1 mg, 0.40 mmol) and RFTA
10.9 mg, 0.020 mmol) were weighed and 82.3 mg of the mix-
ture was used for reaction. Yield: 37%. 1H NMR (300 MHz,
(
9
0
-Hydroxyfluorene (82.0 mg, 0.45 mmol) and RFTA (12.3 mg, CDCl3) 9.82 (s, 1H, CHO), 7.08 (s, 1H, CH), 4.17–4.09 (m, 6H,
.023 mmol) were weighed and 70.6 mg of the mixture was CH2), 1.45 (t, 6H, CH3), 1.36 (t, 3H, CH3).
Table 2: Amounts of 4,4’-dimethoxybenzhydrol (1a) and riboflavin tetraacetate (RFTA) and yields for the oxidation to 4,4’-dimethoxybenzo-
phenone (1b).
Entrya
Amount, weighed (mg/mmol)
(trial)
Total mass for reaction (mg)
Yield (%)
1a
RFTA
1
2
85.5/0.35
85.5/0.35
19.1/0.035
9.5/0.018
–
1
2
3
4
–
–
–
77.2
76.7
76.3
81.4
83.2
83.5
76.6
81.9
72
70
79
70
76
69
61
78
3
4
9
97.7/0.4
97.7/0.4
85.5/0.35
4.4/0.008
2.2/0.004
9.5/0.018
aIn Table 1.
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4-Methoxyacetophenone (6b)
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Figure 2: 1H NMR (crude) of 4-methoxyacetophenone 6b.
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Supporting Information
Supporting Information File 1
Video showing the rod mill apparatus and the procedure of
loading and reaction.
(
http://www.beilstein-journals.org/bjoc)
The definitive version of this article is the electronic one
which can be found at:
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-12-229-S1.mp4]
doi:10.3762/bjoc.12.229
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