Specificity of 15N NMR chemical shifts to the nature of substituents and tautomerism in substituted pyridine N-oxides
Aniela Puszko
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Katri Laihia
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Erkki Kolehmainen
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Zofia Talik
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Z. Talik: Deceased.
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K. Laihia E. Kolehmainen Department of Chemistry, University of Jyvaskyla
, FI-40014 Jyvaskyla,
Finland
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A. Puszko (&) Z. Talik Department of Bioorganic Chemistry, Faculty of Industry and Economics, University of Economics
, 53-345 Wrocaw,
Poland
1H, 13C, and 15N NMR chemical shifts have been measured for 2-aminopyridine N-oxide (1), its eleven derivatives (2-10, 13, 14), and 3-Cl and 3-Br substituted 4-nitropyridine N-oxides (11, 12). d(15N) of pyridine ring nitrogen in 2-acetylaminopyridine N-oxides are 5.9-11.5 ppm deshielded from those in 2-aminopyridine N-oxides. When amino and acetylamino substituents are in 4-position, d(15N) of ring nitrogen is 21.3 ppm deshielded in the acetylated derivative. The strong resonance interaction between 2-amino and 5-nitro groups reflects in the decrease of amino nitrogen shielding about 5.3-17.9 ppm. Also, 1H and 13C NMR spectral data are in agreement with 15N NMR results reflected as deshielded amino protons and carbons C-2 and C-5. The pyridine nitrogen chemical shift in all amino- and acetylamino derivatives vary between -101.2 and -126.7 ppm, which has been connected with the tautomeric balance in our earlier studies.
Introduction
15N isotope is the most sensitive NMR nucleus to the effect
of a substituent introduced to pyridine N-oxide (2- and
4-amino, 2- and 4-acetylamino, methyl group in different
positions together with 2-amino and/or 2-acetylamino,
5-nitro with 2-amino, 4-nitro together with 3-chloro and
3-bromo e.g.). Pyridine N-oxides possess an NO-moiety, a
dual resonance functionality, that can act as both a
p-electron donor and a p-electron acceptor [1]. Acceptors
in the ring decrease and donors increase the shielding of
15N. A linear relationship has been observed between the
substituent chemical shifts of 15N and 13C for the related
substituted benzenes.
Only few research reports on 15N and 14N NMR studies of
aminopyridine N-oxides are found in the literature [25]. In
this paper, we present our studies regarding the possible
tautomerism in amino and acetylaminopyridine N-oxides
because this problem has not yet been unambiguously
solved. Another interest lies in the 5-nitro-substituted
compounds (10, 13, 14), where the electron lone pair of amino
moiety is involved in the p-electron conjugation with the
aromatic ring the nitro group acting as an electron acceptor.
Recently, 2-amino-5-nitropyridine derivatives have been
shown to be very interesting owing to their promising
nonlinear optical properties as these molecules possess high
hyperpolarizability and highly delocalised p-electron
system for reason that acceptor and donor group are situated in
para-position to each other [6].
Experimental
2-Aminopyridine N-oxide and its 3- and 5-methyl
derivatives were obtained by protecting the primary amino group
by acetylation during the oxidation of ring nitrogen.
Otherwise, oxidation would have transformed
aminopyridines into nitropyridines [715]. In hydrolysis, acetylamino
derivatives of pyridine N-oxide gave the corresponding
amino compounds [7]. 2-Amino- and
2-acetylaminopyridine N-oxides as well as their 3-, 4-, 5-, and 6-methyl
derivatives are reported in literature [8, 9], but their
synthesis were greatly improved [14] compared to the earlier
reported methods [813].
The modified synthesis of 2-acetylaminopyridine N-oxides
(2, 4) and 4-, 5-, and
6-methyl-(2-acetylaminopyridine-Noxides) (7, 8, 9) [810, 13] has been presented previously
[14]. By modification of methods by Brown and Adam
et al. [9, 10], a remarkable shortening in reaction time (9 to
2 h) was achieved by substituting acetic acid by acetic
anhydride in the reaction.
The syntheses of 2-amino- (1), 4-amino- (3),
2-amino-3methyl- (5), 2-amino-5-methylpyridine N-oxide (6) have
also been reported earlier [16]. These compounds were
obtained by hydrolysis of the corresponding
acetylaminopyridine N-oxides [13]. By Herzs hydrolysis method [13]
with 50 % H2SO4 instead of 10 % NaOH decreases, the
reaction time varied from 5 to 1 h [9, 10].
The syntheses of 2-amino-5-nitro- (10),
2-amino-5nitro-3-methyl- (13) and 2-amino-5-nitro-6-methylpyridine
N-oxides (14) have been presented previously [16, 17].
These compounds were obtained in rearrangement reaction
of the corresponding nitraminopyridine N-oxides [16, 17].
3-Chloro- (11) and 3-bromo-4-nitropyridine N-oxides
(12) were prepared by oxidation of 3-chloro- and
3-bromopyridine by 30 % H2O2 in the presence of acetic
anhydride followed by nitration of the crude products after
the excess acid was removed [18]. The modification of this
synthesis in comparison with earlier applied methods [7]
consists an improvement of N-oxidation (using acetic
anhydride instead of acetic acid) and separation of final
product from reaction mixture (using 25 % NH4OH and
NH4HCO3 instead of NaOH) giving the pure product due
to low temperature during the neutralization proces (...truncated)