Catalytic hydrogenation of substituted pyridines with PtO2 catalyst

Article abstract of DOI:10.14233/ajchem.2015.19127

The challenging methodology for the hydrogenation of substituted pyridines with mild reducing catalyst PtO₂ in glacial acetic acid as a protic solvent using clean hydrogen under 50 to 70 bar atmospheric pressure leads to the synthesis of piperidine derivatives is reported. All the hydrogenated compounds were characterized by ¹H NMR and ESI-MS.

Full text of DOI:10.14233/ajchem.2015.19127

Asian Journal of Chemistry; Vol. 27, No. 12 (2015), 4358-4360
A
SIAN
J
OURNAL OF HEMISTRY
C
http://dx.doi.org/10.14233/ajchem.2015.19127
Catalytic Hydrogenation of Substituted Pyridines with PtO2 Catalyst
1
2
1,*
REDDYMASU SREENIVASULU , KALLURI VENKATA SRI RANGANATH and RUDRARAJU RAMESH RAJU
1Department of Chemistry, Acharya Nagarjuna University, Nagarjuna Nagar-522 510, India
2Department of Chemistry, Guru Ghasidas Viswavidyalaya (Central University), Bilasapur-495 009, India
*Corresponding author: Fax: +91 863 2293292; E-mail: rrraju1@gmail.com
Received: 24 February 2015;
Accepted: 13 April 2015;
Published online: 29 August 2015;
AJC-17471
The challenging methodology for the hydrogenation of substituted pyridines with mild reducing catalyst PtO2 in glacial acetic acid as a
protic solvent using clean hydrogen under 50 to 70 bar atmospheric pressure leads to the synthesis of piperidine derivatives is reported.
All the hydrogenated compounds were characterized by 1H NMR and ESI-MS.
Keywords: Piperidines, Hydrogenation, PtO2, Substituted pyridines.
cis-Piperidine derivatives were also synthesized by the catalytic
INTRODUCTION
hydrogenation of certain pyridine derivatives with acidified
PtO2 catalyst25,26
.
The most powerful catalytic hydrogenation was one of
the ways to produce a wide array of important compounds in
large quantities using inexpensive and clean hydrogen gas
without forming any waste. The hydrogenation of nitrogen
containing heterocyclic compounds has been investigated by
different catalysts such as palladium, nickel, rhodium, ruthenium
and platinum. The hydrogenation of substituted pyridines is
of particular interest to scientists1-8 as the resulting functiona-
lized piperidines are most important intermediates in the
Due to the aromatic nature of pyridine nucleus, the
hydrogenation of these heterocyclic moieties often requires
the elevated temperatures in combination with significant
hydrogen pressures and the survey of literature reveals that
most of the pyridine derivatives was not satisfactorily reduced
with mild reducing catalyst PtO2 at high temperatures. In
this paper we reported one methodology to the synthesis of
piperidine derivatives from the catalytic hydrogenation of
pyridine substrates with mild reducing catalyst PtO2 at room
temperatures only. The catalytic hydrogenation of substituted
pyridines by the absorption of three moles of clean hydrogen
with PtO2 as catalyst under 50 to 70 bar atmospheric pressure in
glacial acetic acid at room temperature then afforded piperidine
derivatives (Fig. 1).
synthesis of both natural products and pharmaceuticals9-12
.
Mono substituted piperidine derivatives were synthesized by
the catalytic hydrogenation of the corresponding pyridines with
ruthenium dioxide catalyst at high temperatures and larger
atmospheric pressures13. Further the lower atmospheric
pressures favour the catalytic hydrogenation of pyridines with
rhodium on carbon catalyst14. The catalytic hydrogenation of
pyridines with aryl substituent’s leads to the selective reduction
of the heterocyclic ring was desired15,16 under acidic conditions.
The synthesis of pinacol derivative of pyridines has been
achieved by the coupling of selective hydrogenated acetyl
pyridines with adams catalyst, PtO217. Partial catalytic hydro-
genation of catechol, 4-phenyl pyridine, 4-(3-phenyl propyl)
pyridine and N,N-alkyl amino pyridines had done with the
mild reducing catalyst PtO218-20.N-substituted pyridinium salts
undergo catalytic hydrogenation with PtO2 afforded piperidine
derivatives21. The unexpected product piperidine hydrochloride
was also obtained by the catalytic hydrogenation of nicotinic
acid, 3-hydroxy pyridine hydrochloride, 3-pyridyl diphenyl
R
R
R
2
1
2
PtO2/3H2
50 - 70 bar pressure
AcOH
N
R
N
H
1
Fig. 1. Catalytic hydrogenation of substituted pyridines with PtO2 catalyst
EXPERIMENTAL
All the starting materials and reagent (PtO2) were
purchased from Sigma Aldrich and TCI companies. Solvents
were purchased from Merck and used without further
purification. The Progress of the reactions were monitored by
thin layer chromatography (TLC) with ninhydrin charring.
acetate hydro chloride and 2-methoxy pyridine with PtO222-24
.

Vol. 27, No. 12 (2015)
Catalytic Hydrogenation of Substituted Pyridines with PtO2 Catalyst 4359
TABLE-1
CATALYTIC HYDROGENATION OF SUBSTITUTED PYRIDINE DERIVATIVES UNDER VARIOUS CONDITIONS
Entry
Catalyst
Solvent
Time (h)
Temp. (°C)
Pressure (bar)
Yield (%)
1
2
3
4
5
6
7
8
9*
PtO2
PtO2
PtO2
PtO2
PtO2
PtO2
PtO2
PtO2
PtO2
THF
MeOH
EtOH
12
12
16
16
16
16
18
10
6-10
50
60
70
50
60
70
50
60
rt
50-70
50-70
50-70
50-70
50-70
50-70
50-70
50-70
50-70
–
–
–
–
–
–
10
THF/conc. HCl (0.1 equiv.)
MeOH/conc. HCl (0.1 equiv.)
EtOH/conc. HCl (0.1 equiv.)
THF/AcOH (0.1 equiv.)
MeOH/AcOH (0.1 equiv.)
Glacial AcOH
15
above 50
*9th entry is the optimization condition.
1H NMR spectra were recorded on Bruker 300 MHz spectro-
meter with tetra methyl silane was internal standard. All the
chemical shift values are reported in δ units. Mass spectra were
performed on direct inlet system or LC by MSD trap SL.
General protocol for the catalytic hydrogenation of
substituted pyridines with PtO2: Stirred solution of
substituted pyridines (1.0 g) in acetic acid (5 mL) was treated
with 5 mol % catalytic amount of PtO2 under H2 gas pressure.
After 6-10 h, it was quenched with NaHCO3 then it was extracted
with ethyl acetate (3 × 20 mL), filtered through celite and
dried on Na2SO4. The solvent was evaporated under reduced
to gave residue. Further the purification of residue was done
by column chromatography (Silica gel, 60-120 mesh, 5 %
EtOAc in pet. ether) to furnish the substituted piperidine deri-
vatives. All the synthesized compounds are colourless liquids.
mixture to enhance the activity of catalyst. At this condition
the progress of reaction appears to a small extent, but not
significantly. Further the significant progress of the reaction
would achieved in better yields with glacial acetic acid was
used as a protic solvent. Here the optimized results were given
in Table-1.
The catalytic hydrogenation of 2-methoxy pyridine and
2-chloro pyridine in absolute methanolic hydrochloride with
PtO2 then 2-methoxy piperidine and 2-chloro piperidines were
almost susceptible products, but they cannot be detected in
the reduction product. Apparently the unexpected product
piperidine was obtained. The expected products such as
methoxy piperidine and chloro piperidine derivatives were
obtained by the catalytic hydrogenation of 2-methoxy pyridine
TABLE-2
Spectral data of piperidine compounds
CATALYTIC HYDROGENATION OF SUBSTITUTED
PYRIDINE DERIVATIVES UNDER ACETIC ACID AS
A PROTIC SOLVENT AT ROOM TEMPERATURE
2-Bromopiperidine: 1H NMR (CDCl3, 300 MHz): δ 1.52-
1.79 (m, 4H), 2.08-2.37 (m, 3H), 2.73-2.85 (m, 2H), 4.72 (t, J
= 6.3 Hz, 1H). ESI-MS: m/z = 164 (100 %) (M++H), 166 (98 %).
2-Fluoropiperidine: 1H NMR (CDCl3, 300 MHz): δ 1.42-
1.57 (m, 4H), 1.61-1.78 (m, 2H), 2.69-2.78 (m, 2H), 4.03 (br.s,
1H), 4.89 (m, 1H). ESI-MS: m/z = 104 (M++1).
Time
(h)
Yield
(%)
Entry
Reactant
Product
1
6
6
4
8
53
51
68
54
N
H
Br
2-Methylpiperidine: 1H NMR (CDCl3, 300 MHz): δ 1.09
(d, J = 6.1 Hz, 3H), 1.52-1.94 (m, 6H), 2.09 (br.s, 1H), 2.89-
2.68 (m, 3H). ESI-MS: m/z = 100 (M++1).
N
N
Br
2
3
4
1
N
H
F
CH3
O
2-Methoxypiperidine: H NMR (CDCl3, 300 MHz): δ
F
1.56-1.78 (m, 6H), 2.61-2.84 (m, 3H), 3.19 (s, 3H), 3.94 (t, J
= 7.3 Hz, 1H). ESI-MS: m/z = 116 (M++1).
3-Phenylpiperidine: 1H NMR (CDCl3, 300 MHz): δ 1.56-
1.86 (m, 4H), 2.56-2.78 (m, 3H), 3.11 (dd, J = 5.2, 7.1 Hz,
2H), 7.11-7.21 (m, 5H). ESI-MS: m/z = 162 (M++1).
3-Methylpiperidine: 1H NMR (CDCl3, 300 MHz): δ 1.02
(d, J = 6.3 Hz, 3H), 1.43-1.66 (m, 5H), 1.94 (br.s, 1H), 2.37-
2.58 (m, 2H), 2.73-2.87 (m, 2H). ESI-MS: m/z = 100 (M++1).
N
N
CH3
H
N
H
N
O
1
2-Chloro-3-(trifluoromethyl)piperidine: H NMR
(CDCl3, 300 MHz): δ 1.51-1.79 (m, 4H), 2.05-2.38 (m, 1H),
2.74 (t, J = 5.8 Hz, 2H), 4.51 (br.s, 1H), 4.94 (d, J = 9.1 Hz,
1H).ESI-MS: m/z = 188 (M++1).
5
8
55
N
N
H
CH3
CH3
RESULTS AND DISCUSSION
6
7
6
62
58
N
To optimize the reaction conditions, we had investigated
the catalytic hydrogenation of substituted pyridine derivatives
with platinum oxide in different solvents like tetrahydrofuran,
methanol and ethanol, but this hydrogenation was not preceded.
After a small quantity of acetic acid was added to the reaction
N
N
H
CF3
Cl
CF3
Cl
10
N
H

4360 Sreenivasulu et al.
Asian J. Chem.
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and 2-chloro-3-trifluoro methyl pyridines with PtO2 in glacial
acetic under 50 bar atmospheric pressure at room temperature
from 6-8 h. Further the hydrogenation of 2-methyl pyridine
and 3-methyl pyridine with PtO2 in glacial acetic acid under
70 bar atmospheric pressure afforded the corresponding 2-
methyl and 3-methyl piperidine derivatives from 4-6 h. Under
similar experimental conditions, the catalytic hydrogenation
of 2-bromo and 2-fluoro pyridines gave the 2-bromo and 2-
fluoro piperidine derivatives with 50 bar atmospheric pressure
at 6 h. A similar protocol was applied for 3-phenyl pyridine
with 60 bar atmospheric pressure yielded the 3-phenyl
piperidine at 8 h (Table-2).
Conclusion
In conclusion, the catalytic hydrogenation of pyridine
derivatives with PtO2 catalyst still remains challenging methodo-
logy. The decreasing poisonous character of pyridine deriva-
tives and enhancing the catalytic activity towards PtO2 catalyst
then the selection of glacial acetic acid was suitable protic
solvent. Further our research work should be concentrated on
the catalytic hydrogenation of indoles and pyrroles by the mild
reducing catalyst PtO2.
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ACKNOWLEDGEMENTS
The authors are thankful to Department of Science &
Technology, New Delhi, India for financial assistance in the
form ofYoung Scientist major research project F. No. SR/FT/
CS-095/2009.
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