Efficient catalytic conversion of pyridine N-oxides to pyridine with an oxorhenium(V) catalyst

Article abstract of DOI:10.1021/ol006595k

(Equation Presented) The compound CH₃Re(O)(SR)₂PPh₃, where (SR)₂ represents the dianion of 2-(mercaptomethyl)thiophenol, catalyzes the rapid and efficient transfer of an oxygen atom from a wide range of ring-substituted pyridine N-oxides to triphenylphosphine, yielding the pyridines in high yield.

Full text of DOI:10.1021/ol006595k

ORGANIC
LETTERS
2
000
Vol. 2, No. 22
525-3526
Efficient Catalytic Conversion of
Pyridine N-Oxides to Pyridine with an
Oxorhenium(V) Catalyst
3
Ying Wang and James H. Espenson*
Ames Laboratory and Department of Chemistry, Iowa State UniVersity,
Ames, Iowa 50011
espenson@ameslab.goV
Received September 14, 2000
ABSTRACT
3 2 3 2
The compound CH Re(O)(SR) PPh , where (SR) represents the dianion of 2-(mercaptomethyl)thiophenol, catalyzes the rapid and efficient
transfer of an oxygen atom from a wide range of ring-substituted pyridine N-oxides to triphenylphosphine, yielding the pyridines in high yield.
The selective deoxygenation of heteroaromatic N-oxides has
reactions occur rapidly. Typical conditions are as follows:
14 mM 4-picoline N-oxide and 14 mM PPh , with 42 µM 1
(0.3% mol/mol) in 0.7 mL of C in air. The reaction
received previous attention, being an important step in the
3
1,2
synthesis of heterocycles in many procedures. Various
methods have been developed,3 but many are limited by
side reactions or reduction of the ring substituents and may
require tedious procedures.3
6 6
D
-6
reached completion (100% conversion) within 1 min. The
other compounds in Table 1 also gave quantitative conver-
sions with 0.1-5% 1, within a few minutes (entries 1-6)
or hours (entries 7-15), when studied on this scale. The
system is tolerant of nitro and halide substituents, which can
-5,7,8
9
We have found that rhenium compound 1 catalyzes the
transfer of oxygen from numerous pyridine N-oxides to
triphenylphosphine. The synthesis of 1 has been reported
3
,12-14
cause problems in earlier procedures.
Even sterically
hindered compounds such as 2-picoline N-oxide and 2,6-
lutidine N-oxide gave 100% conversion, the latter more
slowly; on a larger (1 g) scale, however, 2-picoline was
formed in only 67% yield. Other amine oxides undergo this
conversion: both 6-methoxyquinoline N-oxide and tri-
methylamine N-oxide also gave high yields of product.
As a control, the reagents were mixed without 1; no
reaction was found for >10 h. Molecular oxygen is not
involved in the catalysis or stoichiometry, in that the same
reaction performed under argon gave virtually the same
result. The overall stoichiometry is simply
previously;10,11 only a small quantity is needed. One group
of reactions was carried out in benzene-d , where the
6
(
(
(
1) Ochiai, E. J. Org. Chem. 1953, 18, 354.
2) Rosenau, T.; Potthast, A.; Ebner, G.; Kosma, P. Synlett 1999, 6, 623.
3) Trost, B. M.; Fleming, L. ComprehensiVe Organic Synthesis; Per-
gamon Press: Oxford, 1991; Vol. 8, p 390.
cat. 1
4
-MeC H NO + PPh
84-MeC H N + Ph PO
(4) Konwar, D.; Boruah, R. C.; Sandhu, J. S. Synthesis 1990, 337-339.
(5) Sim, T. B.; Ahn, J. H.; Yoon, N. M. Synthesis 1996, 324-326.
(6) Nakagawa, H.; Higuchi, T.; Kikuchi, K.; Urano, Y.; Nagano, T. Chem.
5
4
3
5 4 3
Benzene was usually used as solvent, and in limited tests
toluene did as well. THF can be used, but it must be freshly
Pharm. Bull. 1998, 46, 1656-1657.
7) Ochiai, E. Aromatic Amine Oxides; Elsevier Publishing Co: Am-
sterdam, 1967; Chapter 5, p 184.
8) Katritzky, A. R.; Lagowski, J. M. Chemistry of the Heterocyclic
(
(
(10) Jacob, J.; Espenson, J. H. Chem. Commun. 1999, 1003-1004.
(11) Jacob, J.; Guzei, I. A.; Espenson, J. H. Inorg. Chem. 1999, 38,
1040-1041.
(12) Balicki, R. Synthesis 1989, 645-646.
(13) Kagami, H.; Motoki, S. J. Org. Chem. 1978, 43, 1267-1268.
N-Oxides (Organic Chemistry, a Series of Monographs); Academic Press:
London, New York, 1971; Chapter 3, p 170.
(
9) Rhenium, [2-(mercapto-κS)benzenemethanethiolato(2-)-κS]meth-
yloxo(triphenylphosphine).
1
0.1021/ol006595k CCC: $19.00 © 2000 American Chemical Society
Published on Web 10/03/2000

water mixtures) proceeded nearly quantitatively with 0.1-
.5% 1. At this scale, reaction times were 0.3-7 h, dividing
into two groups as with smaller-scale reactions.
As it turns out, (n-Bu) NBr may be more than a phase-
transfer catalyst. Both it and pyridine are pronounced
accelerators (cocatalysts) as shown in Figure 1. Their role
0
Table 1. Oxygen Transfer from Pyridine N-Oxides to
Triphenylphosphine, Catalyzed by 1
4
RC5H4NO,
Py yield,c
%
entry
R )
scalea solventb
1
time/h
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
4-Me
4-Cl
4-MeO
2-Me
4-Ph
4-(CH2)3Ph
4-NO2
4-CN
2,6-Me2
2-Me, 4-NO2 1.0 g
2-OH
3-CH2OH
3-OH
3-C(O)NH2
3-COOH
1.0 g
1.0 g
1.0 g
1.0 g
1.0 g
1.0 g
1.0 g
1.0 g
1.0 g
AB
B
AB
AB
B
B
B
AB
B
B
AB
B
B
THF
THF
0.1%
0.1%
0.5%
0.1%
0.1%
0.1%
0.5%
0.5%
0.5%
0.5%
0.5%
0.1%
0.5%
0.5%
0.5%
0.7
3
3
0.3
0.3
0.3
6
6
7
5
3
100
94
93
67d
100
100
100
92
100
100
50
90
99
51
57
1
1
1
1
1
1
1.0 g
1.0 g
1.0 g
0.5 g
0.5 g
1
7
2
3
a
With 1.0 equiv of PPh3. b Solvents are 60 mL of benzene (B), 10%
water with benzene containing 5% (n-Bu)4NBr (AB), and tetrahydrofuran
c
under argon (THF). The solution was stirred throughout and monitored
3
1
intermittently by TLC and P NMR. After the reaction had finished, the
water layer was separated, the organic layer was dried over anhydrous
magnesium sulfate and evaporated to dryness; the residue was then taken
Figure 1. An experiment in benzene with 44.4 mM each of
2-methyl-4-nitropyridine N-oxide and Ph P containing 1.0 mM 1,
3
showing the decrease in the concentration of the pyridine oxide in
the catalyzed reaction and the further rate acceleration brought about
with 4.4 mM (n-Bu) NBr or 8.8 mM pyridine added.
4
d
up in C6D6 for determination of the Py yield. On a smaller scale, 100%
conversion of 2-picoline N-oxide was obtained.
distilled and the reaction run under argon, as a trace of
peroxide destroys the catalyst. Acetone gave adequate results,
but the reactions proceeded more slowly and in reduced yield.
In chloroform and acetonitrile, the reaction stopped at an
early stage.
To show the generality of this catalytic system and extend
its applicability to reactions carried out on a larger scale,
many pyridine oxides were studied on a scale of 1.0 g of
substrate and 1.0 equiv of phosphine in 60 mL of solvent.
Since several of the pyridine N-oxides are nearly insoluble
in benzene, in some cases 5 mL ofwater and 55 mL of
benzene were used as a two-phase medium. In such cases
is likely to be one of promoting ligand substitution reactions
1
5,16
of 1.
The mechanism of this interesting transformation
remains under investigation, but entry of PyO into the
coordination sphere of rhenium will certainly play a role;
release of pyridine may occur by a process we abbreviate as
follows: L
n
Re-OPy f L RedO + Py.
n
Acknowledgment. This research was supported by the
U.S. Department of Energy, Office of Basic Energy Sciences,
Division of Chemical Sciences, under Contract W-7405-Eng-
82. We are grateful to Professor J. Michl for helpful
discussions.
5
4
% of (n-Bu) NBr was added as a phase-transfer catalyst.
OL006595K
Table 1 presents 15 examples on this larger scale. Most of
the reactions run in ambient-temperature benzene (or benzene-
(
15) Jacob, J.; Lente, G.; Guzei, I. A.; Espenson, J. H. Inorg. Chem.
999, 38, 3762-3763.
16) Lente, G.; Jacob, J.; Guzei, I.; Espenson, J. H. Inorg. Chem. 2000,
39, 1311.
1
(
(14) Jousseaume, B.; Chanson, E. Synthesis 1987, 55-56.
3526
Org. Lett., Vol. 2, No. 22, 2000