Oxidation of tertiary nitrogen compounds to N-oxides by molecular oxygen-aldehyde system in the absence of metal catalyst

Article abstract of DOI:10.1081/SCC-100000196

A variety of tertiary nitrogen compounds have been oxidized to corresponding N-oxides in near quantitative yields by molecular oxygen/2-methylpropanal system in the absence of metal catalyst.

Full text of DOI:10.1081/SCC-100000196

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OXIDATION OF TERTIARY NITROGEN COMPOUNDS
TO N-OXIDES BY MOLECULAR OXYGEN-ALDEHYDE
SYSTEM IN THE ABSENCE OF METAL CATALYST
a
a
a
b
a
Rajendra S. Dongre , T. Venkateshwar Rao , B. K. Sharma , Bir Sain & V. K. Bhatia
a
Indian Institute of Petroleum , Dehradun, 248 005, India
b
Indian Institute of Petroleum , Dehradun, 248 005, India
Published online: 16 Aug 2006.
To cite this article: Rajendra S. Dongre , T. Venkateshwar Rao , B. K. Sharma , Bir Sain & V. K. Bhatia (2001) OXIDATION
OF TERTIARY NITROGEN COMPOUNDS TO N-OXIDES BY MOLECULAR OXYGEN-ALDEHYDE SYSTEM IN THE ABSENCE OF METAL
CATALYST, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
31:2, 167-172, DOI: 10.1081/SCC-100000196
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SYNTHETIC COMMUNICATIONS, 31(2), 167–172 (2001)
OXIDATION OF TERTIARY NITROGEN
COMPOUNDS TO N-OXIDES BY
MOLECULAR OXYGEN-ALDEHYDE
SYSTEM IN THE ABSENCE
OF METAL CATALYST
Rajendra S. Dongre, T. Venkateshwar Rao,
∗
B. K. Sharma, Bir Sain, and V. K. Bhatia
Indian Institute of Petroleum, Dehradun-248 005, India
ABSTRACT
A variety of tertiary nitrogen compounds have been oxidized
to corresponding N-oxides in near quantitative yields by molecular
oxygen/2-methylpropanal system in the absence of metal catalyst.
Oxidation of tertiary nitrogen compounds is an important synthetic transfor-
mation as the N-oxides find wider application as oxidants (1–7), offer functional
group manipulation, structural modification possibilities (8–10), and can activate
the nitrogen-containing ring towards both electrophilic and nucleophilic attack
(
11). A variety of oxidants—m-chloroperoxybenzoic acid (MCPBA) (12), acetic
acid and hydrogen peroxide (12–15), magnesium monoperphthalate (MMPP) (16),
dioxiranes (17,18), Caro’s acid (H2SO5) (19), 2-sulfonyloxaziridines (20), ∝-
azohydroperoxides (21), and peroxytrifluroacetic acid (22)—have been used for
carrying out this transformation.
∗
To whom correspondence should be addressed.
167
Copyright ꢀC 2001 by Marcel Dekker, Inc.
www.dekker.com

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DONGRE ET AL.
Scheme 1.
Recently the oxidation of tertiary nitrogen compounds with hydrogen perox-
ide using methyltrioxorhenium (MTO) (23), manganese porphyrin (24), and flavin
25) as catalysts has been reported in pursuit of the development of eco-friendly
(
synthetic methodologies. Molecular oxygen is an attractive oxidant from both an
environmental and an economic point of view, and there has been great interest
in the development of oxidation methodologies using molecular oxygen-aldehyde
system with or without transition metal complexes as catalysts (26). The molecular
oxygen-aldehyde system without any catalyst has been reported to be a most effec-
tive oxidant for epoxidation of olefins (27), Baeyer-Villiger oxidation of ketones
(
28), oxidation of secondary alcohols (29), and sulphides (30).
In continuation of our studies with molecular oxygen as a primary oxidant
30–33), herein we report for the first time, a simple and convenient method for the
(
oxidation of tertiary-nitrogen compounds (1) to N-oxides (2) in near quantitative
yields with molecular oxygen/2-methylpropanal system in the absence of metal
catalyst (Scheme 1).
Awidevarietyoftertiarynitrogencompounds(pyridinesandtertiaryamines)
was oxidized to N-oxides in near quantitative yields (Table 1).
The protocol developed consists of simply bubbling molecular oxygen in a
solution of 2-methylporpanal in 1,2-dichloroethane for 1 h, followed by the addi-
tion of tertiary nitrogen compound, and further bubbling oxygen until completion
of the reaction (via TLC). It was observed that 3.5 mmoles of 2-methylpropanal per
mmole of tertiary nitrogen compound are required for the oxidation to N-oxide in
a reasonable time of 10–24 h. Pyridines, in general, were found to be less reactive
than tertiary amines.
In the oxidation with molecular oxygen-aldehyde system without any cata-
lyst, while alphatic aldehydes like isobutyraldehyde, cyclohexanecarboxaldehyde
showed high reactivities for epoxidation of olefins (27) and oxidation of sulphides
(30), aromatic aldehydes like benzaldehyde proved to be more effective for the
Baeyar-Villiger oxidation of ketones (28) and secondary alcohols oxidation (29).
With a view to determine the relative efficiency of various aldehydes, we stud-
ied the oxidation of pyridine with a series of aldehydes (alphatic, aromatic, and
heterocyclic). These results are presented in Table 2 and clearly show that the
aliphatic aldehydes isobutyraldehyde and cyclohexanecarboxaldehyde are most
effective among those studied for oxidation of pyridine to the pyridine N-oxides
under these conditions.

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OXIDATION OF TERTIARY NITROGEN COMPOUNDS
169
Table 1. Oxidation of Tertiary Nitrogen Compounds to N-Oxides
a
Entry Tertiary Nitrogen Compound Reaction Time (h) N-Oxide Yield (%)
1
2
20
17
76
85
3
4
17
24
92
76
5
18
84
6
7
15
24
87
88
8
9
0
22
10
12
84
87
90
1
a
Isolated yield.
Aldehyde/tertiary nitrogen compound mole ratio = 3.5.
b
In conclusion, 2-methylpropanal-molecular oxygen provides a simple, ef-
ficient, convenient, and eco-friendly system for the oxidation of tertiary nitrogen
compounds to N-oxides under mild conditions. This methodology avoids the direct
use of hazardous peracids, which are difficult to handle and transport.
EXPERIMENTAL
A typical procedure for the oxidation of tertiary nitrogen compound to
N-oxide is as follows: Molecular oxygen was bubbled into the solution of 2-
methylpropanal (3.18 mL, 35 mmol) in 1,2-dichloroethane (30 mL) in a 50-mL,
◦
two-necked, round-bottom flask for 1 h at ambient temperature (30 C). The flask
◦
was fitted with well-cooled (10 C) condensor to minimize the aldehyde losses.
Pyridine (0.81 mL, 10 mmol) was then added while oxygen was kept bubbling and
the reaction mixture stirred with a magnetic stirrer. The reaction was monitored

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DONGRE ET AL.
Table 2. Efficiency of Different Aldehydes in the Oxidation of Pyridine by Molecular
Oxygen Aldehyde System (Aldehyde/Pyridine Mole Ratio = 3.5)
Conversion to Pyridine
†
Aldehyde
Reaction Time (h)
N-Oxide (%)
Isobutyraldehyde
n-Butyraldehyde
n-Heptaldehyde
Cyclohexanecarboxaldehyde
Benzaldehyde
m-Anisaldehyde
p-Tolualdehyde
p-Nitrobenzaldehyde
20
22
24
21
24
24
24
24
24
100
100
75
100
10
4
8
—
5
2
-Furaldehyde
†
Conversion was determined by HPLC using C18 Bondapack reverse phase column
(4.6 mm × 250 mm, 10µ), methanol as eluant (0.5 mL/min).
by TLC (SiO2 gel). At the end of the reaction (20 h), the reaction mixture was
washed successively with aqueous sodium metabisulphite, 5% aqueous sodium
carbonate and brine, dried (Na2SO4), followed by removal of the solvent under
reduced pressure. The residue thus obtained was purified by passing it through a
basic alumina column using chloroform, methanol (3:1) as eluent and recrystal-
lized from acetone, hexane (1:1) to obtain pyridine N-oxide as light yellow crystals
(
0.72 g, 76%). Similarly, other N-oxides were prepared, and their reaction time and
yields obtained are shown in Table 2. The products were identified by comparing
their physical and spectral data with those of authentic compounds reported in the
literature.
For comparing the efficiency of various aldehydes, experiments were sim-
ilarly conducted for a maximum of 24 h and the residue obtained after passing
through the basic alumina column was analyzed by HPLC using C18 Banda-
pack reverse phase column (4.6 mm × 250 mm, 10µ) methanol (0.5 mL/min) as
eluent.
ACKNOWLEDGMENTS
We are thankful to the Director, IIP, for his kind permission to publish these
results. Rajendra S. Dongre is thankful to CSIR, New Delhi, for the award of a
research fellowship.

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OXIDATION OF TERTIARY NITROGEN COMPOUNDS
REFERENCES
171
1.
Van Rheenen, V.; Cha, D.Y.; Hartley, W.M. Org. Synth. Coll. Vol. 1988, 6,
42.
3
2.
3.
4.
5.
6.
Schroder, M. Chem. Rev. 1980, 80, 87.
Ahrgren, L.; Sutin, L. Org. Proc. Res. Dev. 1997, 1, 425.
Ley, S.V.; Norman, J.; Griffith, W.P., Marsden, S.P. Synthesis 1994, 639.
Franzen, V.; Otto, S. Chem. Ber. 1961, 94, 1360.
Suzuki, S.; Onishi, T.; Fujita, Y.; Misawa, H.; Otera, J. Bull. Chem. Soc. Jpn.
986, 59, 3287.
1
7.
8.
9.
Godfrey, A.G.; Ganem, B. Tetrahedr. Lett. 1990, 31, 4825.
Cope, A.C.; Ciganek, E. Org. Synth. Coll. Vol. 1963, 4, 612.
Cope, A.C.; Trumbull, E.R. Org. React 1960, 11, 317.
1
1
0. Ullmann’s Encyclopedia of Industrial Chemistry, 5th Ed; VCH: Germany;
993, A22, 399.
1. Katritzky A.R.; Lagowski, X. Chemistry of the Heterocyclic N-oxides;
Academic Press: New York, 1971.
1
12. Albini, P. Heterocyclic N-Oxides; CRC Press: Boca Raton, FL, 1991, 31–41.
13. Boekelheide, V.; Linn, W.J. J. Am. Chem. Soc. 1954, 76, 1286.
14. Taylor, E.C., Jr.; Crovetti, A.J. Org. Synth. Coll. Vol. 1963, 4, 704.
15. Mosher, H.S.; Turner, L.; Carlsmith, A. Org. Synth. Coll. Vol. 1963, 4, 828.
16. Brougham, P.; Cooper, M.S.; Cummerson, D.A.; Heaney, H.; Thompson, N.
Synthesis 1987, 1015.
1
1
1
2
2
2
2
7. Murray, R.W.; Jeyaraman, R. J. Org. Chem. 1985, 50, 2847.
8. Ferrer, M.; Sanchez-Baeza, F.; Messeguer, A. Tetrahedron 1997, 53, 15877.
9. Robke, J.G.; Behrman, E.J. J. Chem. Res (s) 1993, 412.
0. Zajac, W.W., Jr.; Walters, T.R., Darcy, M.G. J. Org. Chem. 1988, 53, 5856.
1. Baumstark, A.L.; Dotrong, M.; Vasquez, P.C. Tetrahedr. Lett. 1987, 29, 1963.
2. Chivers, G.E.; Suschitzky, H. J. Chem. Soc., Chem. Commun. 1971, 28.
3. Coperet, C.; Adolfsson, H.; Khuong, Tinh-Alfredo, V.; Yudin, A.K.;
Sharpless, K.B. J. Org. Chem. 1998, 63, 1740.
2
2
2
4. Thellend, A.; Battioni, P.; Sanderson, W.; Mansuy, D. Synthesis 1997, 1387.
5. Bergstad, K.; Backvall, Jan-E. J. Org. Chem. 1998, 63, 6650.
6. For a review on oxidations using molecular oxygen-aldehyde system, see
Mukaiyama, T.; Yamada, T. Bull. Chem. Soc. Jpn. 1995, 68, 17.
7. Kaneda, K.; Haruna, S.; Imanaka, T.; Hamamoto, M.; Nishiyama, Y.; Ishii,
Y. Tetrahedr. Lett. 1992, 33, 6827.
2
2
8. Kaneda, K.; Ueno, S.; Imanaka, T.; Shimotsuma, E.; Nishiyama, Y.; Ishii, Y.
J. Org. Chem. 1994, 59, 2915.
2
3
9. Choudary, B.M.; Sudha, Y. Synth. Commun. 1996, 26, 1651.
0. VenkateshwarRao, T.;Sain, B.;Kumar, K.;Murthy, P.S.;PrasadaRao, T.S.R.;
Joshi, G.C. Synth. Commun. 1998, 28, 319.

ORDER
REPRINTS
1
3
3
3
72
DONGRE ET AL.
1. Sain, B.; Murthy, P.S.; Venkateshwar Rao, T.; Prasada Rao, T.S.R.; Joshi,
G.C. Tetrahedr. Lett. 1994, 35, 5083.
2. Venkateshwar Rao, T.; Sain, B.; Murthy, P.S.; Prasada Rao, T.S.R.; Jain,
A.K.; Joshi, G.C. J. Chem. Res (s) 1997, 300.
3. Venkateshwar Rao, T.; Sain, B.; Murthy, P.S.N.; Joshi, G.C.; Prasada Rao,
T.S.R. Stud. Surf. Sci. Catal. 1998, 113, 921.
Accepted October 19, 1999

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