Efficient NO equivalent for activation of molecular oxygen and its applications in transition-metal-free catalytic aerobic alcohol oxidation

Article abstract of DOI:10.1021/jo0705824

(Chemical Equation Presented) tert-Butyl nitrite (TBN) was identified as an efficient NO equivalent for the activation of molecular oxygen. The unique property of TBN enabled TEMPO-catalyzed aerobic alcohol oxidation to be performed in high-volume efficiency. Up to a 16 000 turnover number was achieved in this transition-metal-free aerobic catalytic system. Under the optimal reaction conditions, various alcohols were converted into their corresponding carbonyl compounds with TEMPO/HBr/TBN as catalyst. The newly developed method was suitable for the oxidation of solid substrate alcohols with high melting point and/or low solubility under the help of minimum solvent to form a slurry.

Full text of DOI:10.1021/jo0705824

gold was also found to be the effective catalyst for aerobic
alcohol oxidation.6 Recently, the combinations of transition
metals and nitroxy free radicals (e.g., 2,2,6,6-tetramethyl-
piperidyl-1-oxy, TEMPO) have shown to be very efficient in
this transformation.7 Most of the research is seeking an effective
bridge, where transition metals play important roles between
molecular oxygen and alcohol substrates. However, our interests
are the molecular nitric oxide (NO) for its ability to activate
molecular oxygen, although it widely attracted attention because
of its unique biological activity and once was named “the
molecule of the year” in 1992 by the editors of the journal
Efficient NO Equivalent for Activation of
Molecular Oxygen and Its Applications in
Transition-Metal-Free Catalytic Aerobic Alcohol
Oxidation
Yi Xie, Weimin Mo, Dong Xu, Zhenlu Shen, Nan Sun,
Baoxiang Hu, and Xinquan Hu*
College of Chemical Engineering and Material Sciences,
Zhejiang UniVersity of Technology,
Hangzhou, 310014, People’s Republic of China
(3) For copper-catalyzed aerobic alcohol oxidation, see: (a) Marko, I.
E.; Giles, P. R.; Tsukazaki, M.; Brown, S. M.; Urch, C. J. Science 1996,
274, 2044. (b) Marko, I. E.; Giles, P. R.; Tsukazaki, M.; Chelle-Regnaut,
I.; Gautier, A.; Brown, S. M.; Urch, C. J. J. Org. Chem. 1999, 64, 2433.
(c) Marko, I. E.; Gautier, A.; Dumeunier, R.; Doda, K.; Philippart, F.;
Brown, S. M.; Urch, C. J. Angew. Chem., Int. Ed. 2004, 43, 1588.
(4) For palladium-catalyzed aerobic oxidation, see: (a) Peterson, K. P.;
Larock, R. C. J. Org. Chem. 1998, 63, 3185. (b) Nishimura, T.; Onoue, T.;
Ohe, K.; Uemura, S. J. Org. Chem. 1999, 64, 6750. (c) ten Brink, G.-J.;
Arends, I. W. C. E.; Sheldon, R. A. Science 2000, 287, 1636. (d) Stahl, S.
S.; Thorman, J. L.; Nelson, R. C.; Kozee, M. A. J. Am. Chem. Soc. 2001,
123, 7188. (e) ten Brink, G.-J.; Arends, I. W. C. E.; Sheldon, R. A. AdV.
Synth. Catal. 2002, 344, 355. (f) Steinhoff, B. A.; Fix, S. R.; Stahl, S. S. J.
Am. Chem. Soc. 2002, 124, 766. (g) Steinhoff, B. A.; Stahl, S. S. Org. Lett.
2002, 4, 4179. (h) Schultz, M. J.; Park, C. C.; Sigman, M. S. Chem.
Commun. 2002, 3034. (i) Uozumi, Y.; Nakao, R. Angew. Chem., Int. Ed.
2003, 42, 194. (j) Jensen, D. R.; Schultz, M. J.; Mueller, J. A.; Sigman, M.
S. Angew. Chem., Int. Ed. 2003, 42, 3810. (k) Iwasawa, T.; Tokunaga, M.;
Obora, Y.; Tsuji, Y. J. Am. Chem. Soc. 2004, 126, 6554. (l) Mori, K.; Hara,
T.; Mizugaki, T.; Ebitani, K.; Kaneda, K. J. Am. Chem. Soc. 2004, 126,
10657. (m) Buffin, B. P.; Clarkson, J. P.; Belitz, N. L.; Kundu, A. J. Mol.
Catal. A: Chem. 2005, 225, 111. (n) Kwon, M. S.; Kim, N.; Park, C. M.;
Lee, J. S.; Kang, K. Y.; Park, J. Org. Lett. 2005, 7, 1077. (o) Hou, Z.;
Theyssen, N.; Brinkmann, A.; Leitner, W. Angew. Chem., Int. Ed. 2005,
44, 1346. (p) Schultz, M. J.; Hamilton, S. S.; Jensen, D. R.; Sigman, M. S.
J. Org. Chem. 2005, 70, 3343. (q) Steinhoff, B. A.; King, A. E.; Stahl, S.
S. J. Org. Chem. 2006, 71, 1861.
(5) For ruthenium-catalyzed aerobic oxidation, see: (a) Marko, I. E.;
Giles, P. R.; Tsukazaki, M.; Chelle-Regnaut, I.; Urch, C. J.; Brown, S. M.
J. Am. Chem. Soc. 1997, 119, 12661. (b) Csjernyik, G.; Ell, A. H.; Fadini,
L.; Pugin, B.; Backvall, J.-E. J. Org. Chem. 2002, 67, 1657. (c) Yamaguchi,
K.; Mizuno, N. Angew. Chem., Int. Ed. 2002, 41, 4538. (d) Musawir, M.;
Davey, P. N.; Kelly, G.; Kozhevnikov, I. V. Chem. Commun. 2003, 1414.
(e) Zhan, B.-Z.; White, M. A.; Sham, T.-K.; Pincock, J. A.; Doucet, R. J.;
Ramana, Rao, K. V.; Robertson, K. N.; Cameron, T. S. J. Am. Chem. Soc.
2003, 125, 2195. (f) Shimizu, H.; Onitsuka, S.; Egami, H.; Katsuki, T. J.
Am. Chem. Soc. 2005, 127, 5396. (g) Egami, H.; Onitsuka, S.; Katsuki, T.
Tetrahedron Lett. 2005, 46, 6049. (h) Kaneda, K.; Ebitani, K.; Mizugaki,
T.; Mori, K. Bull. Chem. Soc. Jpn. 2006, 79, 981.
xinquan@zjut.edu.cn
ReceiVed March 23, 2007
tert-Butyl nitrite (TBN) was identified as an efficient NO
equivalent for the activation of molecular oxygen. The unique
property of TBN enabled TEMPO-catalyzed aerobic alcohol
oxidation to be performed in high-volume efficiency. Up to
a 16 000 turnover number was achieved in this transition-
metal-free aerobic catalytic system. Under the optimal
reaction conditions, various alcohols were converted into
their corresponding carbonyl compounds with TEMPO/HBr/
TBN as catalyst. The newly developed method was suitable
for the oxidation of solid substrate alcohols with high melting
point and/or low solubility under the help of minimum
solvent to form a slurry.
Conversion from alcohols to the corresponding aldehydes or
ketones is one of the most fundamental transformations in
organic chemistry.1 For obvious reasons, many research efforts
have been directed at using molecular oxygen as the terminal
oxidant in recent years.2 In the past decade, chemists have
developed many efficient catalytic oxidation systems using
molecular oxygen as the terminal oxidant. Among the transition-
metal catalysts, copper,3 palladium,4 and ruthenium catalysts5
played the major roles in the aerobic alcohol oxidations, while
(6) Guan, B.; Xing, D.; Cai, G.; Wan, X.; Yu, N.; Fang, Z.; Yang, L.;
Shi, Z. J. Am. Chem. Soc. 2005, 127, 18004.
(7) For transition metal assisted TEMPO-catalyzed aerobic alcohol
oxidations, see, (a) Semmelhack, F. M.; Schmidt, C. R.; Cortes, D. A.;
Chou, C. S. J. Am. Chem. Soc. 1984, 106, 3374. (b) Betzemeier, B.;
Cavazzini, M.; Quici, S.; Knochel, P. Tetrahedron Lett. 2000, 41, 4343.
(c) Cecchetto, A.; Fontana, F.; Minisci, F.; Recupero, F. Tetrahedron Lett.
2001, 42, 6651. (d) Dijksman, A.; Mmarino-Gonzalez, A.; i Payeras, A.
M.; Arends, I. W. C. E.; Sheldon, R. A. J. Am. Chem. Soc. 2001, 123,
6826. (e) Ben-Daniel, R.; Alsters, P.; Neumann, R. J. Org. Chem. 2001,
66, 8650. (f) Ansari, I. A.; Gree, R. Org. Lett. 2002, 4, 1507. (g) Gamez,
P.; Arends, I. W. C. E.; Reedijk, J.; Sheldon, R. A. Chem. Commun. 2003,
2414. (h) Minisci, F.; Recupero, F.; Pedulli, G. F.; Lucarini, M. J. Mol.
Catal. A: Chem. 2003, 204-205, 63. (i) Dijiksman, A.; Arends, I. W. C.
E.; Sheldon, R. A. Org. Biomol. Chem. 2003, 1, 3232. (j) Minisci, F.;
Recupero, F.; Cecchetto, A.; Gambarotti, C.; Punta, C.; Faletti, R.; Paganelli,
R.; Pedulli, G. F. Eur. J. Org. Chem. 2004, 109. (k) Wang, N.; Liu, R.;
Chen, J.; Liang, X. Chem. Commun. 2005, 5322. (l) Jiang, N,; Ragauskas,
A. J. Org. Lett. 2005, 7, 3689. (m) Valusamy, S.; Srinivasan, A.;
Punniyamurthy, T. Tetrahedron Lett. 2006, 47, 923. (n) Jiang, N.;
Ragauskas, A. J. J. Org. Chem. 2006, 71, 7087. (o) Shibuya, M.; Tomizawa,
M.; Suzuki, I.; Iwabuchi, Y. J. Am. Chem. Soc. 2006, 128, 8412.
(1) (a) Hudlicky, M. Oxidations in Organic Chemistry; American
Chemical Society: Washington D.C., 1990. (b) Larock, R. C. Comprehen-
siVe Organic Transformation, 2nd ed.; Wiley-VCH: New York, 1999; p
1197. (c) Sheldon, R. A.; Arends, I. W. C. E. In Modern Oxidation
Methods; Backvall, J.-E., Ed.; Wiley-VCH: Weinheim, 2004; p 83. (d)
Tojo, G.; Fernandez, M. In Oxidation of Alcohols to Aldehydes and
Ketones: A Guide to Current Common Practice; Tojo, G., Ed.; Springer:
New York, 2006.
(2) (a) de Nooy, A. E. J.; Besemer, A. C.; van Bekkum, H. Synthesis
1996, 1153. (b) Adam, W.; Saha-Moller, C. R.; Ganeshpure, P. A.
Chem. ReV. 2001, 101, 3499. (c) Sheldon, R. A.; Arends, I. W. C. E.; ten
Brink, G.-J.; Dijksman, A. Acc. Chem. Res. 2002, 35, 774. (d) Stahl,
S. S. Angew. Chem., Int. Ed. 2004, 43, 3400. (e) Sheldon, R. A.;
Arends, I. W. C. E. J. Mol. Catal. A: Chem. 2006, 251, 200. (f)
Lenoir, D. Angew. Chem., Int. Ed. 2006, 45, 3206 and references cited
therein.
10.1021/jo0705824 CCC: $37.00 © 2007 American Chemical Society
Published on Web 04/21/2007
4288
J. Org. Chem. 2007, 72, 4288-4291

TABLE 1. Catalytic Aerobic Oxidation of Benzyl Alcohola
TEMPO
(mol %)
HBr
(mol %)
TBN (IAMN)
(mol %)
time
(h)
conv
(%)
select
(%)
entry
TONb
1
2
3
4
5
6
7
8
9
1 (1)
4 (5)
4 (5)
4 (5)
4 (5)
4
1 (1)
0.4 (0.5)
0.1 (0.1)
0.4 (0.5)
0.1 (0.1)
4 (5)
4 (5)
4 (5)
4 (5)
4
1 (1)
0.4 (0.5)
0.4 (0.5)
0.1 (0.1)
0.1 (0.1)
1 (1)
1 (1)
1 (1)
2.5 (7)
24
1 (1)
4 (1.5)
4 (2)
10 (6)
10 (6)
100 (100)
100 (100)
100 (100)
100 (99.5)
16.1
99.9 (100)
100 (100)
100 (100)
15.0 (21)
55.6 (96)
99.7 (100)
99.9 (100)
99.7 (100)
100 (100)
100
100 (100)
100 (98)
100 (99)
99.8 (100)
100 (100)
100
200
0.5 (0.5)
0.1 (0.1)
0.01 (0.02)
0.001
0.1 (0.1)
0.1 (0.1)
0.1 (0.1)
0.1 (0.1)
0.1 (0.1)
1000
10 000
16 100
1000
1000
1000
150
10
550
a Aerobic oxidation conditions were as follows: benzyl alcohol (10.8 g, 100 mmol), 1 mL of water, initial 0.6 MPa oxygen pressure, 80 °C (oil bath
temperature). End point of the reaction with complete conversion was judged by the barometer. Conversions and selectivity were based on the gas
chromatography with area normalization. Data in parentheses were obtained with IAMN as NO equivalent. b TON ) turnover number.
Science.8 We have previously reported a triple-component
catalytic oxidation system to enable the efficient use of O2 as
the terminal oxidant, with NaNO2 as an NO equivalent under
acidic condition playing the pivotal role of activating molecular
oxygen. This novel oxidation pathway has been applied to
various alcohol substrates,9 and extended to the application of
total degradation of environmental pollutants such as 2,4,6-
trichlorophenol (TCP).10 Very recently, the utility of the NO-
mediated oxidation mechanism has been applied to other fields
including methane oxidation.11 However, efficiency gaps still
exist between these catalytic aerobic oxidation systems and the
leading catalytic oxidation processes, such as Anelli oxidation,1d,2f
from the economic and throughput point of view.
Further examination of our catalytic system led us to identify
that the weakest link within the three catalytic cycles is the
oxidation of Br- by an NO source, which resulted in a narrow
tunable ranges of the catalyst molar ratios. Though the catalytic
cycle can be revived by addition of catalytic amount of Br2, a
more robust system is clearly desirable. One to overcome this
inherent limitation is to develop a more efficient NO source.
Toward this end, we considered organic nitrites, typically, tert-
butyl nitrite (TBN) and iso-amyl nitrite (IAMN), which have
been frequently used as the reagents for nonaqueous nitrozation
and diazotization, as an alternative NO source for their property
of thermal instability.8 In this paper, we report a new and more
robust triple-component catalyst system, TEMPO/HBr/TBN,
which provides a robust and economic catalytic oxidation of
various alcohols to their corresponding aldehydes and ketones
with a high turnover number (TON; eq 1).
match the activity of substrates with the different solvents.9 The
question is the lower volume efficiency if the developed
methodology is to be applied in the practical scale, because
solvent or water significantly dilutes the effective volume. Only
if the volume efficiency was greatly improved could the
developed aerobic oxidation of alcohols be considered to
compete with the convenient catalytic oxidation using cheap
catalyst and stoichiometric oxidants. After careful studies of
the transition-metal-free catalytic cycles, two aspects could be
adjusted. One is cutting down the dosage of the catalyst system
for economic reasons and the other is to minimize the solvent
to increase the volume efficiency. Many experiments data
showed that a new modified catalyst system, TEMPO/HBr/
IAMN could meet the above requirement. Our initial efforts
focused on the application of IAMN because of its widespread
use. We chose neat benzyl alcohol (0.1 mol scale) as the
substrate to pursue the best combination of the catalyst system
for the new aerobic oxidations. It did work well in the aerobic
oxidation, where partial results were listed in the parentheses
of Table 1, and showed very good results. Unfortunately, iso-
amyl alcohol resulted from the decomposition of IAMN, which
probably participated in the oxidation in some cases and
complicated the purification. On the contrary, the decomposed
byproduct of TBN is tert-butyl alcohol, which cannot be
oxidized in most cases and does not affect most potential
applications of carbonyl compounds. Thus, we turned our
attention to the use of TBN as the new NO source. As seen
from Table 1, the results showed that the newly modified triple-
component catalyst system, TEMPO/HBr/TBN, greatly im-
proves the catalytic efficiency and can tolerate a high degree
of variations on catalyst loading. For example, with TEMPO
ranging from 1 to 0.1 mol %, together with both 4 mol % of
HBr and TBN, the model substrate, benzyl alcohol, could be
totally oxidized into benzaldehyde within 1 h.
Our previous studies demonstrated that each catalytic cycle
in the transition-metal-free oxidation system can be adjusted to
By further decreasing the amount of TEMPO to 0.01 mol
%, the reaction was complete within 2.5 h with a TON up to
10 000 (entry 5). To the best of our knowledge, this is the
highest TON for the homogeneous catalytic aerobic alcohol
oxidation to date. Trying to reduce the amount of TEMPO to
10 ppm resulted in 16% conversion after 24 h (entry 6). The
loading effects of the other two cocatalysts were also investi-
gated in the presence of 0.1 mol % of TEMPO as catalyst. For
example, a full conversion was obtained with 0.4 mol % of
TBN, while the dosage of HBr was flexible (entries 7 and 8).
However, the oxidation with 0.4 mol % of HBr, together with
0.1 mol % of TBN showed extremely low conversion (entry
9), even with prolonged reaction time. Interestingly, when both
(8) Wang, P. G.; Cai, T. B.; Taniguchi, N. Nitric Oxide Donors: for
Pharmaceutical and Biological Application; Wang, P. G., Cai, T. B.,
Taniguchi, N., Eds.; Wiley-VCH: Weinheim, 2005.
(9) (a) Liu, R.; Liang, X.; Dong, C.; Hu, X. J. Am. Chem. Soc. 2004,
126, 4112. (b) Liu, R.; Dong, C.; Liang, X.; Wang, X.; Hu, X. J. Org.
Chem. 2005, 70, 729.
(10) Liang, X.; Fu, D.; Liu, R.; Zhang, Q.; Zhang, T. Y.; Hu, X. Angew.
Chem., Int. Ed. 2005, 44, 5520.
(11) (a) Mu, R. Z.; Liu, Z. Q.; Yang, Z. J.; Liu, Z. G.; Wu, L. M.; Liu,
Z. L. AdV. Synth. Catal. 2005, 347, 1333. (b) Wang, N.; Liu, R.; Chen, J.;
Liang, X. Chem. Commun. 2005, 5322. (c) Herrerias, C. I.; Zhang, T. Y.;
Li, C.-J. Tetrahedron Lett. 2006, 47, 13. (d) Zhang, G.; Liu, R.; Xu, Q.;
Ma, L.; Liang, X. AdV. Synth. Catal. 2006, 348, 862. (f) An, Z. J.; Pan, X.
L.; Liu, X. M.; Han, X. W.; Bao, X. H. J. Am. Chem. Soc. 2006, 128,
16028.
J. Org. Chem, Vol. 72, No. 11, 2007 4289

TABLE 2. Catalytic Aerobic Oxidation to Various Alcoholsa
a Aerobic oxidations were carried out with 0.1 mol of alcohol substrate at 80 °C (oil bath temperature) under initial oxygen (0.6 MPa). Conversions for
all substrates were over 99.5%. All yields are for pure, isolated products. b Cat. ) TEMPO/HBr/TBN. c 6.0 mL of acetic acid was added. d With 20 mL of
acetonitrile. e With 10 mL of 1,2-dichloroethane. f The GC area ratio of 1-octanal/1-octyl 1-octanoate is 54/45; distillation yield of pure 1-octanal. g With 40
mL of acetonitrile and 6 mL of acetic acid.
HBr and TBN were decreased to 0.1 mol %, a moderate
conversion level was maintained (entry 10). Based on our
previous proposed cascade mechanism,9 we reckoned that the
high ratio of HBr to NO did not favor for the equilibrium in
the oxidation HBr to Br2, and the excess HBr could accelerate
the decomposition of TEMP-OH, thus inhibiting the reaction.
A wide range of primary and secondary alcohols have been
tested under the optimized conditions (0.1 mol of alcohol
substrate, 0.1 mol % of TEMPO, 0.4 mol % HBr, 0.4 mol % of
TBN, 0.6 MPa of initial oxygen, 1.0 mL of water, 80 °C) and
the results are summarized in Table 2. All benzylic alcohols,
with either electron-donating or electron-withdrawing substit-
uents, can be oxidized into their corresponding aldehydes in
high isolated yields within 4 h (entries 2-7 in Table 2). The
hetero-aromatic analogs showed low activity under this condi-
tion, but with a higher catalyst loading, the complete oxidation
could also be achieved. In the presence of acetonitrile and with
a higher ratio of TBN/HBr, 2-thiophene methanol was oxidized
into 2-thiophene carboxaldehyde in a 95.5% yield (entry 8).
Less HBr can significantly reduce the bromination impurity at
4290 J. Org. Chem., Vol. 72, No. 11, 2007

the 5-position of the thiophene ring. As usual, the oxidation of
3-pyridine methanol was driven to completion with the help of
equal mole amount of acetic acid to keep the system under weak
acidic conditions (entry 9). Interestingly, with the strong ability
to activate molecular oxygen, the new aerobic catalytic system
with TBN could efficiently oxidize those substrates with high
melting points and/or low solubility. Under the assistance of
20 mL of acetonitrile to form a slurry, p-nitro benzylic alcohol
was totally oxidized with 0.5 mol % of TEMPO, 2 mol % of
HBr, and 2 mol % of TBN. Pure p-nitro benzaldehyde was
isolated by a simple filtration in high yield (entry 10). The neat
R-methyl benzyl alcohols were converted to their corresponding
acetophenones in high yields in the presence of 0.1 mol % of
TEMPO and 4 mol % of both cocatalysts (entries 11-13). In
the presence of 1,2-dichloroethane, secondary aliphatic alcohol,
2-octanol for an example, could also be oxidized into 2-octanone
in high yield (entry 14). For primary aliphatic alcohol substrate,
1-octanol for an example, high conversion with a moderate
selectivity can be achieved. Pure 1-octanal can be separated via
distillation in 40% yield (entry 15). As an example for the
potential application of this newly developed method of aerobic
oxidation of alcohol to aldehyde, it was successfully applied
in the oxidation of the highly functionalized 4-amino-2-
methylthio-pyrimidine-5-methanol to its corresponding aldehyde
in a 0.1 mol scale (entry 16). The obtained aldehyde is a useful
pharmaceutical intermediate.12 For the large-scale preparation
of this compound, this method is superior to all the reported
ones.12b,13
Experimental Section
Procedure of Oxidation of 4-Nitrobenzyl Alcohol (Entry 10
in Table 2): To a teflon-line 316L stainless steel autoclave (300
mL) was added 15.31 g (100 mmol) of 4-nitro benzyl alcohol, 78.0
mg (0.5 mmol, 0.5 mol %) of TEMPO, 350 mg (2.0 mmol, 2 mol
%) of 48% HBr, 210 mg (2.0 mmol, 2 mol %) of TBN, and 20 mL
of acetonitrile (the minimum volume to form a slurry at room
temperature). Then the autoclave was closed and charged with
oxygen to 0.6 MPa. The autoclave was put into an oil bath that
was preheated to 80 °C. Six h later, the barometer dropped to 0.2
MPa, which indicated that the reaction was finished. The autoclave
was taken out of the heating bath, cooled to room temperature,
and carefully depressurized. A sampling was taken from the slurry,
the sample was diluted with CH2Cl2, and conversion and selectivity
was detected by GC without any purification. GC results showed
the reaction was complete. The slurry was diluted with 20 mL of
water, filtered, washed with water (10 mL × 2), and dried to yield
14.65 g (97.0%) as a pale yellow solid: mp 105-107 °C; 1H NMR
(CDCl3) δ 8.10 (m, 2H), 8.42 (m, 2H), 10.18 (s, 1H); GC purity
(area) >99%.
Procedure of Oxidation of 4-Amino-2-methylthio-pyrimidine-
5-methanol (Entry 16 in Table 2): A similar operating proce-
dure was used for aerobic oxidation of 4-nitrobenzyl alcohol. A
total of 16.40 g (96 mmol) of 4-amino-2-methylthio-pyrimidine-
5-methanol, 0.30 g (1.92 mmol, 2 mol %) of TEMPO, 1.34 g (7.68
mmol, 8 mol %) of 48% HBr, 0.79 g (7.68 mmol, 8 mol %) of
TBN, 6 mL of acetic acid, 40 mL of acetonitrile (the minimum
volume to form a slurry at room temperature), and 0.6 MPa of
oxygen were heated to 80 °C for 6 h. After carefully depressurizing
the autoclave, the slurry was diluted with 40 mL of water and then
filtered. The solid was washed with aqueous acetonitrile (1:1, v/v,
20 mL × 2) and dried to yield 13.30 g (81.8%) as a yellow solid:
In conclusion, we have identified tert-butyl nitrite as an
efficient NO equivalent for the activation of molecular oxygen
and have applied this to a highly volume efficient and
economically competitive, transition-metal-free catalytic aerobic
alcohol oxidation process. Under the optimal reaction conditions,
various alcohols can be converted to their corresponding
aldehydes and ketones in high yields. The newly developed
process also exhibited a high potential for the oxidations, as
solid alcohols were demonstrated to be oxidizable with the help
of minimum amount of solvent.
1
mp 178-180 °C; H NMR (DMSO-d6) δ 2.50 (s, 3H), 8.02 (b,
1H), 8.22 (b, 1H), 8.56 (s, 1H), 9.77 (s, 1H); 13C NMR (DMSO-
d6) δ 13.6, 109.2, 160.1, 163.6, 175.8, 191.8; HPLC purity (area)
>99%.
Acknowledgment. This work was supported by the start-
up grant of Zhejiang University of Technology and the Natural
Science Foundation of Zhejiang Province (Y406419). The
authors thank Dr. Tony Y. Zhang at Eli Lilly and Company for
his helpful discussion.
Supporting Information Available: Complete ref 12a, detailed
experimental procedures, GC diagrams for all substrates and
products, and NMR spectra for selected products. This material is
available free of charge via the Internet at http://pubs.acs.org.
(12) (a) Toogood, P.; et al. J. Med. Chem. 2000, 43, 4606. (b) Thompson,
A. M.; Delaney, A. M.; Hamby, J. M.; Schroeder, M. C.; Spoon, T. A.;
Crean, S. M.; Showalter, H. D. H.; Denny, W. A. J. Med. Chem. 2005, 48,
4628.
(13) Okuda, T.; Price, C. C. J. Org. Chem. 1958, 23, 1738.
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