Self-neutralizing in situ acidic CO2/H2O system for aerobic oxidation of alcohols catalyzed by TEMPO functionalized imidazolium Salt/NaNO2

Article abstract of DOI:10.1021/jo902292t

(Chemical Equation Presented) A reversible in situ acidic catalytic system comprising recyclable TEMPO functionalized imidazolium salt ([Imim-TEMPO][Cl])/ NaNO₂/CO₂/H₂O was developed for selective transformation of a series of aliphatic, allylic, heterocyclic, and benzylic alcohols to the respective carbonyl compounds. Notably, the system avoids any conventional acid and can eliminate unwanted byproducts, facilitate reaction, ease separation of the catalyst and product, and also provide a safe environment for oxidation involving oxygen gas.

Full text of DOI:10.1021/jo902292t

pubs.acs.org/joc
reaction of CO2 with water to form carbonic acid is well-
Self-Neutralizing in Situ Acidic CO2/H2O System for
Aerobic Oxidation of Alcohols Catalyzed by
TEMPO Functionalized Imidazolium Salt/NaNO2
known, resulting in low pH values of about 3. This provides
in situ formation of the acid catalyst. Indeed, self-neutralizing
in situ acid catalysis from CO2 has shown great applications,3-5
e.g., decarboxylation, diazotization, and cyclization, with
profound advantages for both green chemistry and improved
economics. Particularly, the CO2/H2O system provides in
situ acid formation for catalysis which can be readily neu-
tralized by the removal of CO2. In other words, the acid
formation is reversible upon the removal of CO2. Thus
carbonic acid offers simple neutralization and does not
require any waste disposal.
Cheng-Xia Miao, Liang-Nian He,* Jing-Lun Wang, and
Fang Wu
State Key Laboratory and Institute of Elemento-Organic
Chemistry, Nankai University, Tianjin 300071, China
heln@nankai.edu.cn
Received October 27, 2009
The selective oxidation of primary and secondary alcohols
into the corresponding aldehydes and ketones is undoubt-
edly one of the most important and challenging transforma-
tions in organic chemistry.6 Recently, utilization of the stable
nitroxyl radical 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)
in combination with oxygen as terminal oxidant for oxida-
tion of alcohols3 appears very appealing in view of catalytic
efficacy and green chemistry. Liang and Hu have made a
great breakthrough in this respect. First, they developed
a three-component transition metal-free catalyst system,
including TEMPO/Br2/NaNO2,7 which would be considered
to go through a three-sequence-cycle with a two-electron-
transfer mechanism. In the system, bromine would offer
bromide ion as well as create acid, which causes NaNO2 to
release NO and NO2. Continuing their own work, a NaNO2-
based catalyst system comprising TEMPO/1, 3-dibromo-
A reversible in situ acidic catalytic system comprising
recyclable TEMPO functionalized imidazolium salt
([Imim-TEMPO][Cl])/NaNO2/CO2/H2O was developed
for selective transformation of a series of aliphatic, allylic,
heterocyclic, and benzylic alcohols to the respective carbonyl
compounds. Notably, the system avoids any conven-
tional acid and can eliminate unwanted byproducts,
facilitate reaction, ease separation of the catalyst
and product, and also provide a safe environment for
oxidation involving oxygen gas.
9
5,5-dimethylhydantoin/NaNO2,8 or TEMPO/HCl/NaNO2
was reported, in which acid conditions are essential either by
initial input or being created in situ. On the other hand,
Karimi10 also developed a heterogeneous catalyst system
consisting of the SBA-15 supported TEMPO/Bu4NBr/
NaNO2 to recover the supported TEMPO in CH3CO2H.
Accordingly, the acidic condition is essential to the TEMPO-
catalyzed oxidation of alcohols when simple, inexpensive,
and biodegradable NaNO2 is used as the activator of oxygen.
Although much progress has been made, toxic, highly vola-
tile, corrosive conventional acids, such as HCl, HBr, or
CH3CO2H, are commonly used in the literature and the
Recently, carbon dioxide as either an abundant and cheap
carbon resource or a nontoxic reaction medium has attracted
great attention and gradually has become an active area of
research.1 Particularly, CO2 appears to be an ideal solvent
for use in oxidation, because CO2 as a reaction medium could
not only eliminate byproducts originating from solvents but
also provide a safe reaction environment with excellent mass
and heat transfer for aerobic oxidations.2
(4) Reviews on self-neutralizing in situ acid catalysts from CO2: (a) Hallett,
J. P.; Pollet, P.; Liotta, C. L.; Eckert, C. A. Acc. Chem. Res. 2008, 41 (3), 458.
(b) Eckert, C. A.; Liotta, C. L.; Bush, D.; Brown, J. S.; Hallett, J. P. J. Phys.
Chem. B 2004, 108, 18108.
(5) In situ acidic CO2/H2O system, see: (a) Toews, K. L.; Shroll, R. M.;
Wai, C. M.; Smartt, N. G. Anal. Chem. 1995, 67, 4040. (b) Roosen, C.;
Ansorge-Schumacher, M.; Mang, T.; Leitner, W.; Greiner, L. Green Chem.
2007, 9, 455. (c) Holmes, J. D.; Ziegler, K. J.; Audriani, M.; Lee, C. T. J.;
Bhargava, P. A.; Steytler, D. C.; Johnston, K. P. J. Phys. Chem. B 1999, 103,
5703.
(6) Hudlicky, M. Oxidations in Organic Chemistry, American Chemical
Society: Washington, DC, 1990.
(7) Liu, R. H.; Liang, X. M.; Dong, C. Y.; Hu, X. Q. J. Am. Chem. Soc.
2004, 126, 4112.
(8) Liu, R. H.; Dong, C. Y.; Liang, X. M.; Wang, X. J.; Hu, X. Q. J. Org.
Chem. 2005, 70, 729.
(9) He, X. J.; Shen, Z. L.; Mo, W. M.; Sun, N.; Hu, B. X.; Hu, X. Q. Adv.
Synth. Catal. 2009, 351, 89.
On the other hand, acids are the most common industrial
catalysts but have the disadvantage of requiring postreaction
neutralization and salt disposal. In this context, the reversible
(1) (a) Sakakura, T.; Choi, J.-C.; Yasuda, H. Chem. Rev. 2007, 107 (6),
2365. (b) Aresta, M.; Dibenedetto, A. Dalton Trans. 2007, 2975. (c) Musie,
G.; Wei, M.; Subramaniam, B.; Bush, D. H. Coord. Chem. Rev. 2001,
219-221, 789.
(2) Recent reviews on CO2 as reaction medium in oxidation: (a) Jessop,
P. G.; Ikariya, T.; Noyori, R. Chem. Rev. 1999, 99, 475. (b) Baiker, A. Chem.
Rev. 1999, 99, 453. (c) Seki, T.; Baiker, A. Chem. Rev. 2009, 109 (6), 2409.
(3) Typical examples for utilizing the acidity of the CO2/H2O system:
(a) Hunter, S. E.; Ehrenberger, C. E.; Savage, P. E. J. Org. Chem. 2006, 71,
6229. (b) Rayner, C. M. Org. Process Res. Dev. 2007, 11, 121. (c) Tundo, P.;
Loris, A.; Selva, M. Green Chem. 2007, 9, 777. (d) Yamaguchi, A.; Hiyoshi,
N.; Sato, O.; Bando, K. K.; Shirai, M. Green Chem. 2009, 11, 48. (e) Cheng,
H. Y.; Meng, X. C.; Liu, R. X.; Hao, Y. F.; Yu, Y. C.; Cai, S. X.; Zhao, F. Y.
Green Chem. 2009, 11, 1227.
(10) Karimi, B.; Biglari, A.; Clark, J. H.; Budarin, V. Angew. Chem., Int.
Ed. 2007, 46, 7210.
(11) Miao, C.-X.; He, L.-N.; Wang, J.-Q.; Wang, J.-L. Adv. Synth. Catal.
2009, 351, 2209.
DOI: 10.1021/jo902292t
r
Published on Web 12/07/2009
J. Org. Chem. 2010, 75, 257–260 257
2009 American Chemical Society

Miao et al.
JOCNote
TABLE 1. Aerobic Oxidation of Benzyl Alcohola
entry
Po2/MPa
Pco2 þ Po2/MPa
T/K
VH O/mL
t/h
conv/ %b
yield b of aldehyde/%
2
1
2
1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
4
373
373
373
373
373
373
353
333
303
373
373
373
373
373
373
373
373
373
373
373
373
373
0
2
2
2
2
2
2
2
2
24
2
2
2
2
2
2
2
2
2
5
3
1
0.5
4
3
2
1
0.4
3
1
4
4
3
4
4
4
4
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.2
0.2
0.2
0.2
0.5
0.05
0.2
0.2
0.2
3c
4d
5
6
7
8
9
73
41
11
45
66
52
93
37
97
0
93
92
40
56
52
34
20
73
41
10
44
66
52
93
37
97
0
93
92
40
56
51
34
19
10
11
12
13
14
15e
16 f
17g
18
19
20h
21i
22j
2
7
11
15
11
11
11
11
11
11
11
11
11
2
2
12
2
aUnless otherwise noted, all the experiments were run with benzyl alcohol (0.2 mL, 1.93 mmol), NaNO2 (6.7 mg, 5 mol %), and [Imim-TEMPO][Cl]
(31.9 mg, 5 mol %). bDetermined by GC. cWithout [Imim-TEMPO][Cl]. dWithout NaNO2. eThe second run after entry 14, only benzyl alcohol were
replenished. fThe third run after entry 14, NaNO2 and benzyl alcohol were replenished. gThe fourth run after entry 14, NaNO2 and benzyl alcohol were
replenished. h[Imim-TEMPO][Cl] (1 mol %). i[Imim-TEMPO][Cl] (0.5 mol %). jTEMPO instead of [Imim-TEMPO][Cl].
quantity of water was further evaluated under 11 MPa of
total pressure and 373 K (entries 12, 14, 18, and 19).
An almost quantitative result was obtained in the presence
of 0.2 mL of water (entry 14). It is also worth mentioning that
the reaction could go smoothly even with 0.5 mol % of
[Imim-TEMPO][Cl] (entry 21).
SCHEME 1. Aerobic Oxidation of Alcohols Catalyzed by
NaNO2/[Imim-TEMPO][Cl]/CO2/H2O
Another practical feature of the designed catalyst system is
the facile separation from the reaction mixture. Moreover,
the remaining [Imim-TEMPO][Cl] in the aqueous phase
could be recovered. In each cycle, the catalysts were dissolved
in water, and the product could be extracted by diethyl ether
(see the Supporting Information). Fortunately, [Imim-
TEMPO][Cl] could be reused at least three times with slight
loss of activity as anticipated (entries 14, 16, and 17). In
addition, NaNO2 should be replenished for the subsequent
run (entry 15).
To examine the utility and generality of this methodology
for the oxidation of alcohols, we applied the present catalyst
system to a variety of alcohols as shown in Table 2.
Obviously, all primary benzylic alcohols were converted into
their corresponding aldehydes in high yields with excellent
selectivity (entries 1-7). It was found that electronic proper-
ties and steric hindrance of the substituents on the benzene
rings have a negligible influence on the reactivity in the cases
of primary benzylic alcohols. Whereas the reactivity of the
secondary benzylic alcohols was affected by R substituent
groups probably due to the steric hindrance, moderate yields
were attained by prolonging the reaction time (entries 8
and 9). Notably, a type of heterocyclic alcohol (such as
2-furfurylmethanol), being less active in many reported
systems, worked well in the NaNO2/[Imim-TEMPO][Cl]/
CO2/H2O system. Furthermore, the present protocol was
also applicable to the oxidation of allylic alcohol such as
cinnamyl alcohol, which is sensitive to acid during the
aerobic oxidation. Moderate yield of cinnamaldehyde was
obtained with ca. 5% of benzyl aldehyde under 3 MPa of
CO2 (entry 11).
inherent disadvantages related to the workup procedure are
unavoidable.
In our previous work,11 recyclable acidic imidazolium
salts were developed to replace those conventional acids
used in the TEMPO-catalyzed oxidation of alcohols.
We herein would like to apply the self-neutralizing acids
that form in situ in the CO2/H2O system to an aerobic
oxidation of alcohols catalyzed by [Imim-TEMPO][Cl]/
NaNO2 (Scheme 1) in order to avoid the tedious synthe-
sis of the above recyclable acid. Improved reaction with
facilitated separation of the catalyst and products were
achieved.
The exploratory experiments were started by testing this
protocol and screening the reaction conditions with benzyl
alcohol as the model substrate (Table 1). Oxygen, CO2,
water, NaNO2, and [Imim-TEMPO][Cl] were essential to
the aerobic oxidation of benzyl alcohol (Table 1, entries
1-5). Preliminary results indicate that the reaction tempera-
ture has a significant effect on the oxidation. Good catalytic
performance was shown at 373 K (entry 6). Subsequently, the
partial pressure of CO2 was examined. Delightedly, the
presence of CO2 was found to enhance the oxidation (entry
2 vs. 10). In the range of 1-14 MPa, the appropriate CO2
pressure could be 10 MPa, at which excellent yield and
selectivity were attained (entry 12).
As the TEMPO-catalyzed oxidation of alcohols with
NaNO2 to activate dioxygen would be a pH-dependent
reaction and the pH of the CO2/H2O system at a given
temperature and pressure is constant,5 the effect of the
258 J. Org. Chem. Vol. 75, No. 1, 2010

Miao et al.
JOCNote
TABLE 2. Catalytic Aerobic Oxidation of Various Alcoholsa
SCHEME 2. The Proposed Mechanism for the in Situ Acid
Catalysis
primary aliphatic alcohols, the longer the chain, the better
the activity (entries 12-15). As expected, the formation of
alkylcarbonic acid in the system (Scheme 2, b) could compete
with the oxidation of the alcohol. The reaction rate of
forming alkylcarbonic acid could presumably be affected
by the chain length and the steric hindrance,4 being in good
accordance with the experimental findings. In addition, the
primary aliphatic alcohols with branched chain or secondary
aliphatic alcohol gave poor results possibly owing to the
steric effect (entries 15 and 16).
Interestingly, the designed oxidation system proved to be
chemoselective. An equimolar mixture of primary and sec-
ondary alcohols was used in the system. 1-Hexadecanol or
4-methoxybenzyl alcohol was converted to the corresponding
aldehydes while secondary alcohols recovered completely
(entries 17 and 18).
On the basis of the experimental results, a possible mechan-
ism for the transition metal-free aerobic oxidation of alcohols
in the CO2/H2O system was proposed as shown in Scheme 2.
The designed system was completed by a two- or three-
sequence cycle with a two-electron-transfer process. Intrinsi-
cally, the combination of CO2 with water leads to the forma-
tion and dissociation of carbonic acid, resulting in low pH
values of about 3 (Scheme 2, cycle I).3,5 This provides in situ
acid formation of catalysts to release nitric oxide from the
NO2-. TEMPO instead of [Imim-TEMPO][Cl] could also
promote the reaction; however, the low solubility of TEMPO
likely leads to poor catalytic activity (entry 22, Table 1). In
other words, cycle II, as depicted in Scheme 2, is not required
for the catalytic cycle to proceed. In this regard, TEMPO
derivatives and NO2 could indirectly or directly react to
generate the Imim-TEMPO cation (I, III). Subsequently,
Imim-TEMPO cation oxidizes the alcohol to the correspond-
ing carbonyl compound (III). Moreover, possible formation of
alkylcarbonic acid especially for the aliphatic alcohols could
have an adverse effect on the reaction (Table 2, entries 12-15).
In summary, we developed a self-neutralizing in situ acidic
catalyst system from CO2 comprised of a recyclable TEMPO
functionalized imidazolium salt/NaNO2/CO2/H2O for the
selective oxidation of a series of aliphatic, allylic, heterocyc-
lic, and benzylic alcohols to the respective carbonyl com-
pounds. The present protocol offers simple neutralization,
which does not require any waste disposal with advantages of
improved reaction, facilitated separation of the catalyst and
products, and safe operation for aerobic oxidation.
aReaction conditions: alcohol (1.93 mmol), [Imim-TEMPO][Cl]
(31.9 mg, 5 mol %), NaNO2 (6.7 mg, 5 mol %), VH O = 0.2 mL,
2
PO = 1 MPa, PO þ PCO = 11 MPa, T = 373 K. bDetermined by GC,
2
2
2
and data in parentheses refer to isolated yields. cVH O = 0.05 mL, PO
=
2
2
1 MPa, PO þ PCO = 4 MPa, and 5% of benzyl aldehyde was obtained.
Experimental Section
2
2
Several aliphatic alcohols were further examined to extend
the substrate scope for this methodology. In the cases of
Representative Procedure for the Aerobic Oxidation of Alco-
hol. A mixture of substrate (1.93 mmol), [Imim-TEMPO][Cl]
J. Org. Chem. Vol. 75, No. 1, 2010 259

Miao et al.
JOCNote
(31.9 mg, 5 mol %), NaNO2 (6.7 mg, 5 mol %), and 0.20 mL of
water was placed in a 25 mL autoclave equipped with an inner
glass tube. CO2 (2 MPa) and O2 (1 MPa) were introduced into
the autoclave and the system was heated to the reaction tem-
perature. Then the final pressure was adjusted to the desired
pressure at the reaction temperature by introducing the correct
amount of CO2. The mixture was stirred continuously for
the desired reaction time. After cooling, products were then
extracted by diethyl ether and analyzed by gas chromatograph
(Shimadzu GC-2014) equipped with a capillary column (RTX-5
30 m ꢀ 0.25 μm) using a flame ionization detector by comparing
retention times of authentic samples. The residue was purified
by column chromatography on silica gel (200-300 mesh, eluting
with 20:1 petroleum ether/ethyl acetate) to afford the desired
product. The isolated products were further identified with
NMR spectra (Bruker-300 MHz, 400 MHz), which are consis-
tent with those reported in the literature.7-9
fluids, are potentially hazardous and must only be carried out
by using the appropriate equipment and under rigorous safety
precautions. In particular, oxygen is introduced into the sub-
strate-loaded reactor after CO2. Moreover, the oxygen content
should not exceed 14 vol % when CO2 is used as a reaction
medium.
Acknowledgment. We are grateful to the National Natur-
al Science Foundation of China (Nos. 20421202, 20672054,
and 20872073), the 111 project (B06005), and the Committee
of Science and Technology of Tianjin for financial support.
Supporting Information Available: General experimental
methods, synthetic procedure of [Imim-TEMPO][Cl], charac-
terization of [Imim-TEMPO][Cl], and the isolated product
and GC diagrams for substrates and products. This material
is available free of charge via the Internet at http://pubs.
acs.org.
Safety Warning. Experiments with large amounts of com-
pressed gases, especially molecular oxygen and supercritical
260 J. Org. Chem. Vol. 75, No. 1, 2010