Aerobic oxidation of methylpyridines to pyridinecarboxylic acids catalyzed by N-hydroxyphthalimide

Article abstract of DOI:10.1021/op000061h

Selective aerobic oxidation of methylpyridines to pyridinecarboxylic acids was successfully achieved by the use of a radical catalyst, N-hydroxyphthalimide (NHPI), in the presence of Co(II) and/or Mn(II) salts. The oxidation of 3-methylpyridine by NHPI combined with Co(OAc)₂ under O₂ (1 atm) in AcOH at 100 °C gave 3-pyridinecarboxylic acid (76percent). The reaction was found to be enhanced by addition of a small amount of Mn(OAc)₂ to the catalytic system. The reaction with 20 atm of air, catalyzed by NHPI-Co(OAc)₂-Mn(OAc)₂ at 150 °C for 1 h, gave 3-pyridinecarboxylic acid (85percent). 4-Methylpyridine was much less easily oxidized than 3-methylpyridine. The co-oxidation of 3-methylpyridine and 4-methylpyridine by NHPI-Co(OAc)₂-Mn(OAc)₂ at 150 °C for 5 h gave results that were better than those obtained from individual oxidations, forming 3-pyridinecarboxylic acid (93percent) and 4-pyridinecarboxylic acid (70percent). The NHPI-catalyzed oxidation of methylpyridines would provide an attractive direct method which has long been desired in the chemical industry for the manufacturing of pyridinecarboxylic acids.

Full text of DOI:10.1021/op000061h

Organic Process Research & Development 2000, 4, 505−508
Aerobic Oxidation of Methylpyridines to Pyridinecarboxylic Acids Catalyzed by
N-Hydroxyphthalimide
Akihiro Shibamoto, Satoshi Sakaguchi, and Yasutaka Ishii*
Department of Applied Chemistry, Faculty of Engineering & High Technology Research Center, Kansai UniVersity,
Suita, Osaka 564-8680, Japan
Abstract:
Aerobic oxidation of methylpyridines is thought to be a
straightforward approach to pyridinecarboxylic acids and to
provide a practical method from the environmental and
economic viewpoints. However, there has been little infor-
mation on the aerobic oxidation of these substrates so far.4
According to the patent literature, these oxidations occur
under severe reaction conditions in the presence of cobalt
and manganese ions with highly corrosive promoters such
Selective aerobic oxidation of methylpyridines to pyridinecar-
boxylic acids was successfully achieved by the use of a radical
catalyst, N-hydroxyphthalimide (NHPI), in the presence of
Co(II) and/or Mn(II) salts. The oxidation of 3-methylpyridine
by NHPI combined with Co(OAc) under O (1 atm) in AcOH
2 2
at 100 °C gave 3-pyridinecarboxylic acid (76%). The reaction
was found to be enhanced by addition of a small amount of
Mn(OAc)
air, catalyzed by NHPI-Co(OAc)
-6
5
2
to the catalytic system. The reaction with 20 atm of
-Mn(OAc) at 150 °C for 1
as bromide salts. Recently, the autoxidation of methylpyr-
2
2
idines has been reported to be accelerated by the addition of
5
b
h, gave 3-pyridinecarboxylic acid (85%). 4-Methylpyridine was
much less easily oxidized than 3-methylpyridine. The co-
oxidation of 3-methylpyridine and 4-methylpyridine by NHPI-
lithium chloride as the promoter. It is very important to
carry out the aerobic oxidation without any corrosive halide
ions as promoters, since the oxidation in the absence of halide
ions did not call for the employment of a reactor made of
Co(OAc)
better than those obtained from individual oxidations, forming
-pyridinecarboxylic acid (93%) and 4-pyridinecarboxylic acid
70%). The NHPI-catalyzed oxidation of methylpyridines would
2
-Mn(OAc)
2
at 150 °C for 5 h gave results that were
6
titanium alloy. Therefore, it is very attractive to develop an
3
(
efficient catalytic method for the production of pyridinecar-
boxylic acids from methylpyridines by aerobic oxidation
under mild conditions.
provide an attractive direct method which has long been desired
in the chemical industry for the manufacturing of pyridinecar-
boxylic acids.
In recent years, we have developed a novel catalytic
aerobic oxidation system of a variety of hydrocarbons using
7
N-hydroxyphthalimide (NHPI) as the key catalyst. Thus,
alkanes such as isobutane, cyclohexane, and toluene could
be efficiently oxidized with molecular oxygen by NHPI
combined with Co(OAc) under mild conditions to give
2
Introduction
Pyridinecarboxylic acids derived from methylpyridines are
important intermediates as pharmaceutical materials. In
particular, 3-pyridinecarboxylic acid, which is used as a
oxygen-containing compounds such as alcohols, ketones, and
8
carboxylic acids. In this paper, we report the NHPI-catalyzed
aerobic oxidation of methylpyridines, which are difficult to
selectively oxidize by conventional autoxidation.
3
precursor of vitamin B , has been manufactured in large
1
scale. Two basic methods are employed for the synthesis
of pyridinecarboxylic acids: one method is based on the
hydrolysis of pyridinecarboxamides derived from pyridine-
carbonitriles, and the other is the oxidation of alkylpyridines
Results and Discussion
1. Oxidation of 3-Methylpyridine. Representative results
for the oxidation of 3-methylpyridine (1) with molecular
oxygen (1 atm) catalyzed by NHPI combined with a small
amount of a transition metal ion in acetic acid at 100 °C are
given in Table 1.
2
by air, nitric acid, selenium dioxide, etc. The ammoxidation
of methylpyridines forms pyridinecarbonitriles, which are
subsequently hydrolyzed to pyridinecarboxylic acids through
3
pyridinecarboxamides. 3-Pyridinecarboxylic acid has been
(4) Hoelderich, W. F. Appl. Catal. A: General, 2000, 194-195, 487.
commercially manufactured by nitric acid oxidation of
(5) Roy, A. N.; Guha, D. K.; Bhattacharyya, D. Indian Chem. Eng. 1982, 24,
46 and references therein. (b) Mukhopadhyay, S.; Chandalia. S. B. Org.
Process Res. DeV. 1999, 3, 227. (c) Hashimoto, T.; Nakamura, K.;
Takagawa, M. Jpn Kokai Tokkyo 92, 02, 772, 1997; Chem. Abstr. 1997,
127, 176350.
-ethyl-2-methylpyridine.2
a
5
(1) Davis, D. D. In Ullmann’s Encyclopedia of Industrial Chemistry, 5th ed.;
Gerhartz, W. Ed.; VCH: Weinheim, 1985; Vol. A27, p 587.
(6) Inoue, H. T. Jpn. Kokai 76, 29, 483, 1976; Chem. Abstr. 1976, 85, 94233.
(7) Ishi, Y.; Nakayama, K.; Takeno, M.; Sakaguti, S.; Iwahama, T.; Nisiyama,
Y. J. Org. Chem. 1995, 60, 3934.
(
2) Davis, D. D. In Ullmann’s Encyclopedia of Industrial Chemistry, 5th ed.;
Gerhartz, W. Ed.; VCH: Weinheim, 1985; Vol. A27, p 584 (b) Steckhan,
E.; Azzem, M, A. Heterocycles 1990, 31, 1959. (c) Teubner, H.; Schmidt,
M.; Teubner, H.; Tiyze, H.; Schmind, M.; Schick, H. Chem. Abstr. 1988,
(8) Ishii, Y.; Iwahama, T.; Sakaguchi, S.; Nakayama, K.; Nishiyama. J. Org.
Chem. 1996, 61, 4520. (b) Iwahama, T.; Shoujo, K.; Sakaguchi, S.; Ishii,
Y. Org. Process Res. DeV. 1998, 2, 255. (c) Iwahama, T.; Sakaguchi, S.;
Nishiyama, Y.; Ishii, Y. Tetrahedron Lett. 1995, 38, 6923. (d) Ishii, Y.;
Kato, S.; Iwahama, T.; Sakaguchi, S. Tetrahedron Lett. 1996, 37, 4993. (e)
Sakaguchi, S.; Kato, S.; Iwahama, T.; Ishii, Y. Bull. Chem. Soc. Jpn. 1998,
71, 1237. (f) Yoshino, Y.; Hayashi, Y.; Iwahama, T.; Sakaguchi., S.; Ishii,
Y. J. Org. Chem. 1997, 62, 6810.
1
08, 150322. (d) Paraskewas, P. Synthesis 1974, 11, 819. (e) Beletskaya, I.
P.; Grinfel’d, A. A.; Artamkina, G. A. Tetrahedron Lett. 1984, 25, 4989.
f) Mukhopadhyay, S.; Chandalia, S. B. Org. Process Res. DeV. 1999, 3,
55.
3) Beschke, H.; Friedrich, H.; Mueller, K. P.; Schreyer, G. Chem. Abstr. 1977,
6, 43576. (b) Gaddis, J. L.; Spencer, H. G. Chem. Abstr. 1980, 93, 79696.
(
4
(
8
1
0.1021/op000061h CCC: $19.00 © 2000 American Chemical Society and The Royal Society of Chemistry
Vol. 4, No. 6, 2000 / Organic Process Research & Development
•
505
Published on Web 09/28/2000

Table 1. Effect of transition metal salt on aerobic oxidation
Table 3. Effect of Mn(OAc)
2
on aerobic oxidation of 1 by
of 3-methylpyridine (1) by NHPIa
NHPI-Co(OAc)
a
2
yield (%)
Co(OAc)
(mol %)
2
Mn(OAc)
(mol %)
2
run
conv (%)
2
3
1
2
3
4
5
6
7
8
9
1.5
1.5
1.0
1.0
0.5
0.5
0.1
0.1
0.1
0.5
82
80
67
77
60
78
5
48
72
65
76
74
63
2
1
1
1
1
1
0.1
0.1
0.1
yield (%)
72 (70)c
run
metal
conv (%)
2
3
53
73
4
1
2
3
4
5
6
7
8
no reaction
Co(acac)
Co(acac)
Mn(OAc)
Cu(OAc)
VO(acac)
Fe(acac)
Ni(OAc)
2
2
60
46
3
5
2
8
3
53
43
trace
2
1
1
0.1
0.5
0.1
41
1
2
2
65
b
62 (57)c
2
10
2
a
2
1 (2 mmol) was allowed to react with O
2
(1 atm) in the presence of NHPI
2
in acetic acid (7 mL) at 100 °C for 15
(
10 mol %), Co(OAc)
2
, and Mn(OAc)
3
1
b
h. The reaction was carried out using 1 (10 mmol) in acetic acid (35 mL).
2
c
Isolated yield.
a
1
2
(2 mmol) was allowed to react with O (1atm) in the presence of NHPI
(
10 mol %) and a transition metal (0.5 mol %) in acetic acid (7 mL) at 100 °C
for 15 h.
among the aerobic oxidations examined earlier. The oxidation
of 1 by the addition of Co(OAc)
(10 mol %) gave almost the same result as that obtained for
the addition of the 1.5 mol % of Co(OAc)
2
(2 mol %) to the NHPI
Table 2. Effect of quantity of Co(OAc)
2
on aerobic oxidation
of 1 by NHPIa
2
.
It has long been known that a combined system of Co
and Mn ions is effective for the autoxidation of hydrocar-
yield (%)
run
Co(OAc)
2
(mol %)
conv (%)
2
3
1
0
bons. Thus, the influence of the Mn ion on the oxidation
of 1 by the NHPI-Co(OAc) was examined (Table 3).
There was slight effect of Mn(OAc) on the oxidation of
by the NHPI (10 mol %)-Co(OAc) (1.5 mol %) system
runs 1 and 2), but a remarkable enhancement was observed
when Mn(OAc) was added to the NHPI (10 mol %)-Co-
(OAc) (0.1-0.5 mol %) systems (runs 6 and 8). Interest-
ingly, the addition of 0.5 mol % of Mn(OAc) to the NHPI
10 mol %)-Co(OAc) (0.1 mol %) system gave 2 in 65%
2
1
2
3
4
5
0.1
0.5
1.0
1.5
2.0
5
60
67
82
87
4
<1
1
1
1
1
53
63
76
77
2
1
(
2
2
a
1
(2 mmol) was allowed to react with O
2
(1 atm) in the presence of NHPI
in acetic acid (7 mL) at 100 °C for 15 h.
2
(
10 mol %) and Co(OAc)
2
2
(
2
yield at 72% conversion of 1 (run 9). A larger-scale
experiment was also run. The oxidation of 10 mmol of 2
under the same reaction conditions as those used for run 6
gave 2 in 62% yield (run 10).
It is very important to utilize air instead of dioxygen in
industrial processes. Thus, the oxidation of 1 by NHPI (10
The oxidation of 1 in the presence of NHPI (10 mol %)
and Co(OAc) (0.5 mol %) produced 3-pyridinecarboxylic
acid (2), along with a small amount of 3-pyridinecarboal-
dehyde (3). However, the oxidation of 1 in the absence of
2
Co(OAc)
2
under these conditions did not lead to any
was also
oxidation products at all. Although Co(acac)
2
mol %)-Co(OAc)
2
2
(0.5 mol %)-Mn(OAc) (0.1 mol %)
effective for the oxidation of 1 (run 3), transition metal salts
other than Co salts did not accelerate the oxidation of 1 (runs
under 20 atm of air in several solvents at varying reaction
temperatures was examined (Table 4).
4-8). In a previous paper, we revealed the role of a Co(II)
The oxidation of 1 in acetic acid at 150 °C for 5 h afforded
ion in the NHPI-catalyzed oxidation of alkanes with molec-
ular oxygen and showed that the Co(II) species reacts with
2
in 89% yield (91% conversion). Almost the same result
was obtained in the oxidation at 140 °C, but the yield of 2
decreased to 69% (73% conversion) when the reaction
temperature was lowered to 120 °C. 2 was obtained in 77%
yield (81% conversion) in the oxidation, even at 100 °C,
although the reaction must be prolonged to 15 h (run 5).
Oxidation was difficult at 80 °C. Among the solvents
examined, acetic acid was the best. Reactions in benzonitrile
and in acetonitrile afforded 2 in moderate yields, 42% and
dioxygen to generate a cobalt-oxygen complex, such as L
2
-
•
CoOO and L
2
CoOOCoL
2
, which assist the abstraction of
the hydrogen atom from the hydroxyimide group in the NHPI
to form phthalimide N-oxyl (PINO) radical.8
f,9
The effect of the quantity of Co(OAc)
oxidation of 1 with O by NHPI was examined (Table 2).
The yield of 2 increased as the quantity of the Co(OAc)
added to the NHPI was increased. The oxidation of 1 by
addition of 1.5 mol % of Co(OAc) to the NHPI (10 mol
) afforded 2 in satisfactory yield (76%) at 82% conversion
of 1. To our best knowledge, this is the first successful
oxidation of 1 to 2 by O (1 atm) under the mildest conditions
2
on the present
2
2
4
0%, respectively (runs 8 and 9). However, the addition of
2
a small amount of acetic acid to the reaction system led to
a slightly higher yield of 2 (run 10).
%
2
(
10) Shigeyasu, T.; Kurokawa, A.; Ozaki, S. Nippon Kagaku Kaishi 1985, 2,
07. (b) Kamiya, Y.; Nakajima, T.; Sakoda, K. Bull. Chem. Soc. Jpn. 1966,
39, 2211. (c) Kamiya, Y.; Kotake, M. Bull. Chem. Soc. Jpn. 1973, 46, 2780.
2
(9) Golden, D. M. Annu. ReV. Phys. Chem. 1982, 33, 493.
5
06 Vol. 4, No. 6, 2000 / Organic Process Research & Development
•

Table 4. Oxidation of 1 with air by
Table 5. Oxidation of 4-methylpyridine (4) with air by
NHPI-Co(OAc)
2
-Mn(OAc)
2
catalyst at varying
NHPI-Co(OAc)
2 2
-Mn(OAc) catalyst under various
temperaturesa
conditionsa
yield (%)
run
solvent
temp (°C)
conv (%)
2
3
1
2
3
4
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
PhCN
MeCN
MeCN
150
140
120
100
100
100
80
150
150
150
91
90
73
40
81
66
10
45
53
60
89
86
69
35
77
60
8
42
40
50
trace
1
1
1
1
trace
1
1
NHPI
Co(Ac)
2
Mn(OAc)
(mol %)
2
yield (%),
b
run (mol %) (mol %)
conv (%)
5
5
b,c
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
10
10
10
10
10
10
15
20
10
10
0.5
0.5
0.1
25
3
22
2
0.5
0.5
1
1
1
1
0.5
0.5
no reaction
d
1
2
1
1
0.5
1
1
1
1
46
52
15
62
67
18
43
44
46
10
56
60
15
39
a
b
1
(2 mmol) was allowed to react with 20 atm of air in the presence of
NHPI (10 mol %), Co(OAc) (0.5 mol %), and Mn(OAc) (0.1 mol %) at 150
2
2
b
c
°
C in solvent (7 mL) for 5 h. The reaction was carried out for 15 h. The
d
reaction was carried out with 5 atm of air. AcOH (2 mmol) was added.
c
c,d
1
a
4
(2 mmol) was allowed to react with 20 atm of air in the presence of
b
NHPI, Co(OAc) , and Mn(OAc) in AcOH (7 mL) at 150 °C for 5 h. The
2
2
c
reaction was carried out at 120 °C. The reaction was carried out in MeCN (7
d
mL). AcOH (2 mmol) was added.
Table 6. Co-oxidation of 3-methylpyridine (1) and
4
-methylpyridine (4) with air by
NHPI-Co(OAc) -Mn(OAc)
2
2
catalysta
conv (%)
yield (%)
run
1 (mmol)
4 (mmol)
1
4
2
5
1
2
3
1
1
95
89
90
45
75
75
61
61
15
41
93
87
88
43
72
70
56
58
13
38
0.67
1.33
1
1.33
0.67
1
b
4
c
Figure 1. Time dependence curves for the oxiation of 1 to 2
5
1
1
under 20 atm of air by NHPI (10 mol %)-Co(OAc)
) or NHPI (10 mol %)-Co(OAc) (0.5 mol %)-Mn(OAc)
0.1 mol %) in AcOH (7 mL) at 150 °C.
2
(0.5 mol
a
A mixture of 1 and 4 was allowed to react with 20 atm of air in the presence
(0.5 mol %), and Mn(OAc) (0.1 mol %) in
%
(
2
2
of NHPI (10 mol %), Co(OAc)
AcOH (7 mL) at 150 °C for 5 h. The reaction was carried out at 120 °C. The
reaction was carried out in the absence of Mn(OAc)
2
2
b
c
2
.
Figure 1 shows the time dependence curves for the
oxidation of 1 to 2 under 20 atm of air by both NHPI-Co-
When the NHPI (10 mol %)-Co(OAc)
Mn(OAc) (1 mol %) system was employed as the catalyst,
was obtained in 46% yield at 52% conversion (run 5).
Oxidation using 20 mol % of NHPI under these conditions
afforded 5 in 60% yield (67% conversion). Oxidation of 4
using acetonitrile as a solvent resulted in low conversion
2
(1.0 mol %)-
(
OAc)
This indicates that the oxidation of 1 by the NHPI-Co-
OAc) -Mn(OAc) system took place very fast and was
2
and NHPI-Co(OAc)
2
2
-Mn(OAc) systems at 150 °C.
2
5
(
2
2
complete within about 1 h. On the other hand, the time taken
to complete the oxidation by the NHPI-Co(OAc) system
2
was about 3 h. Unfortunately, the effect of the Mn ion on
the rate enhancement in this oxidation is difficult to explain
at the present time.
(
18%) (run 9). However, it is interesting to note that the
addition of a small amount of acetic acid to the reaction
system led to considerable improvements in the conversion
of 4 and the yield of 5 (run 10).
To promote the oxidation of 4, the co-oxidation of 4 and
1 was carried out under several reaction conditions (Table
6).
2. Oxidation of 4-Methylpyridine. Table 5 shows the
results of oxidation of 4-methylpyridine (4) under 20 atm
of air by the NHPI-Co(OAc)
2
2
-Mn(OAc) system under
various conditions.
In contrast to the oxidation of 1 by the NHPI-Co(OAc)
Mn(OAc) system, where 2 was formed in good yield (89%)
Table 4, run 1), 4-methylpyridine 4 was oxidized with some
difficulty under these conditions to form 4-pyridinecarboxylic
acid (5) in moderate yield (22%) (run 1). However, the same
2
-
The co-oxidation of 1 and 4 gave results that were better
than those obtained from the individual oxidations of 1 and
4. For instance, a 1:1 mixture of 1 and 4, oxidized under 20
atm of air by the same catalytic system that was employed
for the oxidation of 1 (run 1 in Table 5) at 150 °C for 5 h,
gave 2 and 5 in 93% and 70% yields, respectively (run 1).
The co-oxidation of a 1:2 mixture of 1 and 4 afforded 2
2
(
oxidation by the NHPI-Co(OAc)
2
system in the absence of
Mn(OAc) led to 5 in only 2% yield (run 2).
2
Vol. 4, No. 6, 2000 / Organic Process Research & Development
•
507

Experimental Section
General. The starting materials, 3- and 4-methylpyridines
(1 and 4), and catalysts were commercially available and
used without purification. GC analysis was performed with
a flame ionization detector using a 0.2-mm × 30-m capillary
column (OV-17). LC was performed with a UV detector (254
nm) using a 4.6-mm × 270-mm column chromatography
1
13
(
Mightysil RP-18, Kanto Chem. Co Ltd). H and C NMR
spectra were measured at 270 and 67.5 MHz, respectively,
in DMSO-d with Me Si as the internal standard. Infrared
IR) spectra were measured using NaCl or KBr pellets. GC-
6
4
(
MS spectra were obtained at an ionization energy of 70 eV.
The yields of products were estimated from the peak areas
on the basis of the internal standard technique by the use of
GC or LC.
A Typical Procedure for the Oxidation of 3-Methyl-
2
pyridine (1) or 4-Methylpyridine (4) under O (1 atm).
Figure 2. Time dependence curves for the oxiation of a 1:1
mixture of 1 and 4 with 20 atm of air in AcOH (7 mL) by NHPI
(
10 mol %)-CO(OAc)
2
2
(0.5 mol %)-Mn(OAc) (0.1 mol %)
at 150 °C.
To a solution of NHPI (10 mol %) and transition metals in
acetic acid (7 mL) in a pear-shaped flask was added 1 or 4
(2 mmol). The flask was equipped with a balloon filled with
(87%) and 5 (56%) (run 2). The result of the oxidation of a
2:1 mixture of 1 and 4 was almost the same as that of the
2
O (1 atm). The mixture was stirred at 100 °C for 15 h. After
oxidation of the 1:2 mixture (run 3). The co-oxidation of 1
and 4 at 120 °C led to 2 (43%) and 5 (13%) (run 4). As
shown in run 2 in Table 5, it was difficult to oxidize 4 by
the reaction, the solvent was removed under reduced pressure
to afford a brown solid. To remove NHPI, metal salts, and
side products, the resulting solids obtained by the oxidation
of 1 or 4 were dissolved in a small amount of methanol or
DMSO, respectively, and the solution was refluxed. The
solution was cooled in an ice bath, and excess acetonitrile
was added to give a pure white solid, 3-pyridinecarboxylic
acid (2) or 4-pyridinecarboxylic acid (5).
the NHPI-Co(OAc)
the co-oxidation of 1 and 4, 4 was oxidized by the NHPI-
Co(OAc) system to give 5 in 38% yield (run 5).
2 2
in the absence of Mn(OAc) , but, in
2
From the time dependence of the co-oxidation of 1 and 4
Figure 2), it was found that the oxidation of 1 to 2 was
(
All products were identified by comparison of their
spectral data with those of authentic samples.
complete in 2 h, but the oxidation of 4 proceeded much more
slowly than that of 1 and was terminated at about 70% yield.
The oxidation of 4 was considerably accelerated in the
presence of 1. This shows that radical intermediates such as
A Typical Procedure for the Oxidation of 1 or 4 under
Air (20 atm). 1 or 4 (2 mmol), NHPI (10 mol %), Co(OAc)
2
•
•
(0.5 mol %), and Mn(OAc) (0.1 mol %) in AcOH (7 mL)
2
2 2
3-ArCH OO and 3-ArCH O (where Ar is a pyridinyl
were placed in a 50-mL Teflon-coated autoclave, and 20 atm
of air was charged. The workup was performed by the
procedure described above.
moiety) generated from 1 serve as chain-transfer agents to
•
facilitate the generation of a radical species such as 4-ArCH
2
from 4. Therefore, when 1 was consumed in the co-oxidation
of 1 and 4, the oxidation of 4 did not proceed easily, as
shown in Figure 2.
In summary, we have found an effective catalytic method
for the direct aerobic oxidation of methylpyridines to
pyridinecarboxylic acids. Further elaboration of this method
would provide a direct route to pyridinecarboxylic acids from
methylpyridines.
Acknowledgment
This work was partly supported by Research for the Future
program JSPS.
Received for review June 7, 2000.
OP000061H
508
•
Vol. 4, No. 6, 2000 / Organic Process Research & Development