Aerobic copper/TEMPO-catalyzed oxidation of primary alcohols to aldehydes using a microbubble strategy to increase gas concentration in liquid phase reactions

Article abstract of DOI:10.1039/c0cc04377j

An efficient method for the synthesis of aldehydes was achieved by using air-microbubble techniques in aerobic copper/TEMPO-catalyzed oxidation of primary alcohols. Use of air-microbubbles to improve gas absorption into liquid phase is proven to be highly beneficial for gas/liquid phase reactions.

Full text of DOI:10.1039/c0cc04377j

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COMMUNICATION
Aerobic copper/TEMPO-catalyzed oxidation of primary alcohols to
aldehydes using a microbubble strategy to increase gas concentration
in liquid phase reactionsw
Nobuyuki Mase,* Tomoya Mizumori and Yuji Tatemoto
Received 13th October 2010, Accepted 1st December 2010
DOI: 10.1039/c0cc04377j
An efficient method for the synthesis of aldehydes was achieved
by using air-microbubble techniques in aerobic copper/TEMPO-
catalyzed oxidation of primary alcohols. Use of air-microbubbles
to improve gas absorption into liquid phase is proven to be highly
beneficial for gas/liquid phase reactions.
Gas/liquid phase reactions are fundamental reaction types in
material syntheses, where a number of gas molecules are
employed, for example, O2, O3, H2, NH3, CO2, F2, Cl2,
CH2QCH2 and CHRCH etc. The concentration of gas
Fig. 1 Gas/liquid phase reactions.
dissolved in liquid phase largely affects reactive properties, which
inherently depends on both pressure and temperature. Although
have been already commercially available. In cooperation with
high concentrations of gas dissolved in solvent can be achieved
Asupu Company Limited, stainless steel-components from a
when the reaction is performed under high partial pressure at low
small generator were replaced with Teflons (MA2-FS,
temperature, in general these conditions result in decreasing
pumping rate 120–150 mL minÀ1, Fig. 2, upper right).
reactivity. If high concentrations of dissolved gas can be achieved
Performance evaluations measuring dissolved oxygen levels
at ordinary temperatures and pressures, the utility of gas/liquid
in distilled water showed that the Teflons-microbubble
phase reactions is significantly improved.
generator rapidly supersaturated with respect to oxygen at
Recently, microbubbles have attracted attention in
an air-flow rate of 3 mL minÀ1 without stirring. The solution
numerous areas of study due to their characteristic features.1
of water saturated with oxygen appeared cloudy (Fig. 2,
For example, microbubbles exhibit excellent gas-dissolution
lower right). After stopping the air supply for 20 minutes, it
abilities because of larger gas/liquid interfacial areas, in
remained oversaturated for 40 minutes (Fig. 2). On the other
addition, a longer stagnation compared to conventional larger
hand, air bubbling at an air-flow of rate 3 mL minÀ1 using a
bubbles is monitored owing to their small buoyancy. These
conventional gas dispersion tube with a porous fritted glass tip
phenomena cause microbubbles gradually to decrease in size,
resulted in low saturation of oxygen in solution after
with eventual disappearance into the liquid phase.
60 minutes with vigorous stirring. This result is similar to
As detailed in this communication, we propose a novel
that without air bubbling. These outcomes indicate that a
experimental methodology for gas/liquid phase reactions using
Teflons-microbubble generator is an efficient instrument to
microbubbles (Fig. 1, right), instead of conventional methods
dissolve oxygen into distilled water.
(Fig. 1, left) involving vigorous stirring and/or high pressure to
increase the interfacial surface between gas and liquid.
Prior to starting this project,
a special microbubble
generator, which is resistant to corrosion with acids, bases,
and organic solvents, was required. Furthermore, a small
microbubble generator was desired for an academic laboratory
setting, though larger generators (pumping rate 4 10 L minÀ1
)
Department of Molecular Science, Faculty of Engineering,
Shizuoka University, 3-5-1 Johoku, Hamamatsu 432-8561, Japan.
E-mail: tnmase@ipc.shizuoka.ac.jp; Fax: +81 53-478-1196;
Tel: +81 53-478-1196
w Electronic supplementary information (ESI) available: Experimental
procedure. See DOI: 10.1039/c0cc04377j
Fig. 2 The microbubble generator and degree of oxygenation in
distilled water.
c
2086 Chem. Commun., 2011, 47, 2086–2088
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Table
alcohol (1a) to benzaldehyde (2a)
1
Aerobic copper/TEMPO-catalyzed oxidation of benzyl
Table 2 Aerobic copper/TEMPO-catalyzed oxidation of alcohols 1
to aldehydes 2
Entry
R
Time/h
Conversiona (%)
Product
Entry Ligand Base Bubbling (mL minÀ1
)
Conversiona (%)
1
2
3
4
5
6
7
H
2
2
4
4
4
4
4
93
98
92
73
85
89
91
2a
2b
2c
2d
2e
2f
i-Pr
MeO
HO
NO2
Cl
1
2
3
4
5
6
7
8
4a
4a
4b
4b
4b
4b
4b
4b
5a
5b
5a
5b
5b
5b
5b
5b
Microbubbling (3)
Microbubbling (3)
Microbubbling (3)
Microbubbling (3)
Microbubbling (3)b
Open (0)c
81
87
90
93
94
30
48
84
Br
2g
a
Bubbling (3)c
Determined by GC-analyses (column: GL Sciences TC-17).
Bubbling (15)c
a
Determined by GC-analyses (column: GL Sciences TC-17).
c
O2-microbubbles were used instead of air-microbubbles. These
b
reactions were carried out with vigorous stirring.
Encouraged by these basic results, we started to investigate
novel microbubble strategies for gas/liquid phase reactions.
The aerobic copper/2,2,6,6-tetramethylpiperidine N-oxyl
(TEMPO)-catalyzed oxidation of primary alcohols (20 mmol)
to aldehydes developed by the Sheldon group was chosen as a
model reaction, Table 1.2–4 First attempts under Sheldon’s
Scheme 1 Competition experiments.
conversion to the aldehyde 2a was observed using standard air-
bubbling and stirring conditions. Therefore, primary alcohols were
selectively oxidized in the presence of secondary alcohols in the
microbubble oxidation system with excellent conversion.
condition with microbubbling (air-flow rate: 3 mL minÀ1
)
afforded the desired benzaldehyde (2a) in 81% conversion
without formation of carboxylic acid (3a) (entry 1). The
catalytic activity was improved by the addition of 2,2-bipyr-
idine (4b) and MeONa (5b), in which conversion to the
aldehyde increased to 93% at 30 1C (entries 1–4). Air was
replaced by O2-microbubbles in the oxidation of alcohol 1a, a
similar result was observed (entry 4 vs. 5). On the other hand,
poor conversion of alcohol 1a to aldehyde 2a (30%) was
observed under open conditions after 2 hours of vigorous
stirring (entry 6). In addition, air bubbling (air-flow rate:
3 mL minÀ1) using a conventional gas dispersion tube fitted
with a porous fritted glass tip resulted in 48% conversion
We next examined microbubble oxidation using aliphatic
alcohols as substrates. The allylic alcohol geraniol (8) was an
excellent substrate giving geranial (9) in 99% conversion with
high regioselectivity ((E) : (Z) = 99 : 1) with a short reaction
time (1 h). Standard work-up and reduced-pressure distillation
afforded geranial (9) in 84% yield and 97% purity as
determined by GC analysis. In contrast, oxidation with
conventional air-bubbling techniques resulted in only 73%
conversion (Scheme 2). The cyclic monoterpene allyl alcohol
myrtenol (10) was also oxidized to myrtenal (11) in 99%
conversion under the same microbubble conditions
(Scheme 2). These exceptional results show the broad potential
(entry 7). Even when the air-flow rate was up to 15 mL minÀ1
,
conversion was lower than that of the microbubbling
procedure (entry 4 vs. 8). Condensers must be attached to
the reaction vessel when reactions are performed at high gas-
flow rates such as 15 mL minÀ1, whereas microbubbling
procedures do not require similar engineering controls.
The scope of this class of microbubble oxidation was
examined with a series of benzyl alcohol derivatives 1 under
the optimized conditions and the results are summarized in
Table 2. Aromatic aldehydes 2 were obtained in good to
excellent yields within 4 hours at 30 1C. Overoxidation from
aldehyde to carboxylic acid was not observed.
The microbubble oxidation system displayed a preference
for primary versus secondary alcohols (10 mmol each) according
to intermolecular competition experiments (Scheme 1).5
Corresponding benzaldehyde (2a) and acetophenone (7) were
obtained in 99% and 3% conversion, respectively, after 30 minutes
under optimized air-microbubbling conditions. As expected, poor
Scheme 2 Aerobic copper/TEMPO-catalyzed oxidation of aliphatic
alcohols with the microbubble procedure.
c
This journal is The Royal Society of Chemistry 2011
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molecular oxygen (Scheme 4).4c In both Schemes 3 and 4
molecular oxygen (O2) is the key to oxidation to form reactive
species, hence high concentrations of dissolved O2 should
significantly affect the reaction efficiency.
In summary, we have developed a novel experimental
methodology by using microbubbles for gas/liquid phase
reactions in organic synthesis. The exact role of microbubbles
remains unclear;7 however, our strategy showed an improved
efficiency on the aerobic copper/TEMPO-catalyzed oxidation
of primary alcohols to aldehydes. Further studies focusing on
the full scope of this unique microbubble system are currently
under investigation and will be reported in due course.8
In addition, since this new microbubble-system could be
potentially used for any gas/liquid phase reactions at least in
principle, we believe that this study is an important contribution
to all gas/liquid phase reactions including not only the present
aerobic oxidation but also hydrogenation, ozonation, reductive
amination, halogenation, etc. under environmentally-friendly
protocols and are currently under investigation.
We gratefully acknowledge Dr D. D. Steiner for a scientific
discussion. Thanks to Shiono Koryo Kaisha, Ltd. for a
generous gift of alcohols and aldehydes. This study was
supported in part by a Grant-in-Aid for Exploratory Research
from the Japan Society for the Promotion of Science.
Scheme 3 Sheldon’s proposed oxidation mechanism.
Notes and references
1 (a) E. Stride and M. Edirisinghe, Soft Matter, 2008, 4, 2350–2359;
(b) Y.-z. Hu, J.-a. Zhu, Y.-g. Jiang and B. Hu, Adv. Ther., 2009, 26,
425–434; (c) I. Lentacker, S. S. C. De and N. N. Sanders,
Soft Matter, 2009, 5, 2161–2170.
2 P. Gamez, I. W. C. E. Arends, R. A. Sheldon and J. Reedijk,
Adv. Synth. Catal., 2004, 346, 805.
Scheme 4 Koskinen’s proposed binuclear copper(II) complex.
3 Reviews: (a) R. A. Sheldon and I. W. C. E. Arends, Adv. Synth.
Catal., 2004, 346, 1051; (b) R. Ciriminna and M. Pagliaro,
Org. Process Res. Dev., 2009, 14, 245.
4 Recent aerobic TEMPO-catalyzed oxidation of primary alcohols to
aldehydes: (a) W. Yin, C. Chu, Q. Lu, J. Tao, X. Liang and R. Liu,
Adv. Synth. Catal., 2010, 352, 113; (b) C.-X. Miao, L.-N. He,
J.-L. Wang and F. Wu, J. Org. Chem., 2010, 75, 257; (c) E. T.
T. Kumpulainen and A. M. P. Koskinen, Chem.–Eur. J., 2009, 15,
10901; (d) P. J. Figiel, A. Sibaouih, J. U. Ahmad, M. Nieger,
of our microbubble strategy in aerobic oxidation of primary
alcohols.
Aerobic copper/TEMPO-catalyzed oxidation of unmodified
aliphatic primary alcohols has great utility in organic synthesis
due to their low reactivity,4 oxidation of 1-octanol carried out
by both microbubbling and conventional air-bubbling
procedure furnished 1-octanal in almost the same conversion
(72% and 74%, respectively) after a prolonged reaction time
(12 h).6 This is an undesirable result for us, but it suggests that
air- and/or O2-microbubble techniques do not accelerate the
rate-determining step but have more effect on the regeneration
steps of TEMPO from TEMPOH. The Sheldon group has
proposed the mechanism of aerobic copper/TEMPO-oxidations
as shown in Scheme 3.2 Hydrogen abstraction from the
a-carbon atom by TEMPO (C to D in Scheme 3) is the rate-
determining step (RDS); therefore, oxidation of an unmodified
aliphatic primary alcohol is expected to be much slower than
that of benzylic and allylic alcohols. Consequently, the highly
oxygenated water present due to air-microbubbling has almost
no effect on the rate-determining step. However, it probably
accelerates regeneration of TEMPO from TEMPOH during
the proposed catalytic cycle in Scheme 3.
M. T. Raisanen, M. Leskela and T. Repo, Adv. Synth. Catal.,
¨
¨
¨
2009, 351, 2625; (e) G. Yang, W. Zhu, P. Zhang, H. Xue,
W. Wang, J. Tian and M. Song, Adv. Synth. Catal., 2008, 350,
542; (f) X. Wang, R. Liu, Y. Jin and X. Liang, Chem.–Eur. J., 2008,
14, 2679–2685; (g) N. Jiang and A. J. Ragauskas, ChemSusChem,
2008, 1, 823; (h) Y. Xie, W. Mo, D. Xu, Z. Shen, N. Sun, B. Hu and
X. Hu, J. Org. Chem., 2007, 72, 4288–4291; (i) S. Mannam,
S. K. Alamsetti and G. Sekar, Adv. Synth. Catal., 2007, 349,
2253–2258; (j) B. Karimi, A. Biglari, J. H. Clark and V. Budarin,
Angew. Chem., Int. Ed., 2007, 46, 7210; (k) C. W. Y. Chung and
P. H. Toy, J. Comb. Chem., 2007, 9, 115–120.
5 Acetophenone (7) was obtained in 13% conversion after 2 h using
the microbubble system in oxidation of the secondary alcohol
(air-flow rate 3 mL minÀ1).
6 These reactions were carried out using CuBr2 (10 mol%), ligand 4b
(10 mol%), TEMPO (12.5 mol%) and base 5b (10 mol%) in
CH3CN/H2O (2 : 1) for 12 h.
7 A local ‘‘hot spot’’ theory is probably another possibility; however,
positive effect was not reported in the study of decomposition of
perfluorooctanoic acid. M. Takahashi, K. Chiba and P. Li, J. Phys.
Chem. B, 2007, 111, 1343.
8 Preliminary results were discussed at the 2010 summer symposium
of the Japanese Society for Process Chemistry, 1P-32 on July 15,
2010.
In addition, the Koskinen group suggested a different
reaction species, a binuclear copper(II) complex G, which is
derived from a monomeric species F in the presence of
c
2088 Chem. Commun., 2011, 47, 2086–2088
This journal is The Royal Society of Chemistry 2011