1H, 13C and 15N NMR spectral and theoretical studies of some methyl and alkylamino derivatives of 4-halopyridine N-oxides

Article abstract of DOI:10.1016/j.molstruc.2005.01.065

Nine new and three earlier known 4-halogen (Cl and Br) substituted pyridine N-oxides have been prepared and their ¹H, ¹³C and ¹⁵N NMR chemical shifts assigned based on PFG ¹H, X (X=¹³C and ¹⁵N) HMQC and HMBC experiments as well as the comparison with our earlier results for substituted pyridine N-oxide derivatives. The ¹⁵N resonances of the pyridine nitrogen are 27-40 ppm more shielded in 4-halo-2-alkylamino-6-methyl-5-nitropyridine N-oxide than in parent 4-halopyridine N-oxide. According to quantum chemical ab initio HF/6-311G** calculations the amino tautomer of 4-chloro-2- methylamino-6-methyl-5-nitropyridine N-oxide is more stable than its imino form. Using B3LYP/6-311G** optimized structures both ¹³C and ¹⁵N shifts were calculated by density functional B3LYP/6-311G ** CSGT methods for the amino and imino tautomers as well as for the dimeric structure for 4-chloro-2-methylamino-6-methyl-5-nitropyridine N-oxide. The ¹⁵N NMR and DFT calculations suggest the prevailing of the dimeric amino form for one congener, which is further supported by ESI-TOF MS data.

Full text of DOI:10.1016/j.molstruc.2005.01.065

Journal of Molecular Structure 783 (2006) 73–78
www.elsevier.com/locate/molstruc
13
15
1H, C and N NMR spectral and theoretical studies of some methyl
and alkylamino derivatives of 4-halopyridine N-oxides
a,
K. Laihia , A. Puszko , J. Linnanto , E. Kolehmainen
b
a
a
*
aDepartment of Chemistry, University of Jyvaskyla¨, P.O. Box 35, Jyvaskyla¨ FIN-40014, Finland
bDepartment of Bioorganic Chemistry, University of Economics, Wrocław 53-345, Poland
Received 10 September 2004; revised 17 January 2005; accepted 17 January 2005
Available online 22 September 2005
Abstract
Nine new and three earlier known 4-halogen (Cl and Br) substituted pyridine N-oxides have been prepared and their 1H, 13C and 15N NMR
chemical shifts assigned based on PFG 1H, X (XZ13C and 15N) HMQC and HMBC experiments as well as the comparison with our earlier
results for substituted pyridine N-oxide derivatives. The 15N resonances of the pyridine nitrogen are 27–40 ppm more shielded in 4-halo-2-
alkylamino-6-methyl-5-nitropyridine N-oxide than in parent 4-halopyridine N-oxide. According to quantum chemical ab initio HF/
6-311G** calculations the amino tautomer of 4-chloro-2-methylamino-6-methyl-5-nitropyridine N-oxide is more stable than its imino form.
Using B3LYP/6-311G** optimized structures both 13C and 15N shifts were calculated by density functional B3LYP/6-311G** CSGT
methods for the amino and imino tautomers as well as for the dimeric structure for 4-chloro-2-methylamino-6-methyl-5-nitropyridine
N-oxide. The 15N NMR and DFT calculations suggest the prevailing of the dimeric amino form for one congener, which is further supported
by ESI-TOF MS data.
q 2005 Elsevier B.V. All rights reserved.
Keywords: 1H, 13C, 15N NMR; Chemical shifts; 4-Halogen pyridine N-oxides; Quantum chemical ab initio HF/6-311G**; Density functional B3LYP/6-311G**
structure optimization and theoretical B3LYP/6-311G** CSGT calculation; ESI-TOF mass spectrometry
1. Introduction
pyridine N-oxide derivatives have been the subject of 15N
NMR studies, but not, however, 4-halopyridine N-oxides
and their derivatives [1,4,5,8,9]. It is known that N-oxide
group is characterized by so called ‘push–pull’ property.
The strong electron-withdrawing effects of 4-substituents
perturb this situation and can be observed in the 15N NMR
chemical shifts, which are sensitive to the position of the
substituents in the pyridine N-oxide ring [1].
15N NMR spectral data have been already used 25 years
ago in studying the substituent effects and the magnitude of
the back donation of the N-oxide group in monosubstituted
pyridine N-oxides [1]. Steric effects were reported in a 15
N
NMR study of 3-methyl-4-nitro- and 2,6-dimethylpyridine
N-oxide and the effects of peri-substituents in the 15N NMR
study of quinoline N-oxide and 8-hydroxyquinoline N-oxide
[1]. Only scarce data existed about 15N NMR spectroscopy
of multisubstituted pyridine N-oxides. Recently, however,
there has been a great progress in the spectroscopic
investigation of multisubstituted pyridine N-oxide deriva-
tives due to novel successful synthesis of alkylamino-,
nitramino and nitropyridine N-oxides [2–7]. Various
4-Halogen pyridine N-oxides and their derivatives were
synthesized from the corresponding nitro compounds. Using
acetyl halide the nitro group could be substituted with
halogen, chlorine and bromine.
In a previous paper, it described the synthesis of
2-alkylamino-3-methyl- and 2-alkylamino-5-methyl-
4-nitropyridine N-oxides and their low temperature nitration
products, e.g. 2-alkylnitramino-3-methyl- and 2-alkylnitra-
mino-5-methyl-4-nitropyridine N-oxides [3]. However,
when the 6-methyl derivatives (2-alkylamino-6-methyl-4-
nitropyridine N-oxides) were nitrated, they gave 4,5-
dinitroderivative instead of a 2-nitramino derivative. From
these compounds, the four new 4-halogen derivatives were
synthesized possessing three very different nitrogen atoms
*
Corresponding author. Tel.: C358 14 260 2655; fax: C358 14 260
2501.
E-mail address: laihia@cc.jyu.fi (K. Laihia).
0022-2860/$ - see front matter q 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2005.01.065

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K. Laihia et al. / Journal of Molecular Structure 783 (2006) 73–78
in the molecule [3,5]. These multisubstituted derivatives are
worth to study due to their complex substituent interactions.
Further, it is interesting to understand more from the amino/
imino tautomer balance, which we have studied earlier with
2-alkyl- and 2-nitramino pyridine N-oxides [5]. In some of
those compounds, theoretical calculations proved that the
solution in a 5 mm sample tube at 30 8C on a Bruker Avance
DRX 500 spectrometer working at 500.13 and 125.77 MHz,
respectively.
In 1H NMR experiments, the number of data points was
64 K giving a spectral resolution of 0.05 Hz, the number of
scans was eight and the flip angle 308. An exponential
window function of the spectral resolution was used prior to
imino tautomer is energetically more favorable, but the 15
N
1
spectral data did not support the calculated result. That is
why more study was needed to elucidate this controversy.
To our knowledge there exist no earlier systematic
spectral studies for multisubstituted methyl derivatives of
4-halopyridine N-oxides.
FT. The H NMR chemical shifts are referenced to the
signal of residual DMSO-d5 (dZ2.50 ppm from TMS).
In 13C experiments, the number of data points was 32 K
giving a spectral resolution of 0.5 Hz, the number of scans
was 64 and flip angle 308. A composite pulse decoupling,
Waltz-16, was used to remove proton couplings. An
exponential window function of the spectral resolution
was used prior to FT. The 13C NMR chemical shifts are
referenced to the centre peak of the solvent DMSO-d6
(dZ39.50 ppm from TMS).
2. Experimental
2.1. Synthesis
The number of data points in 1H, 13C HMQC and HMBC
measurements were 1024 (f2)!256 (f1). This matrix was
zero filled to 2048!512 and apodized by a shifted sine bell
window function analogue both axes prior to FT.
Compounds 4-chloro- (1), 4-chloro-3,5-dimethyl- (3)
and 4-bromo- (7) pyridine N-oxides were synthesized as
described in the literature [19]. Syntheses of compounds
4-chloro-2,3-dimethyl- (2), 4-chloro-2,3,6-trimethyl- (4), 4-
bromo-2,3-dimethyl- (8), 4-bromo-3,5-dimethyl- (9) and
4-bromo-2,3,6-trimethyl (10) pyridine N-oxides were per-
formed as followed: 20 ml acetyl halide (chloride or
bromide) was added dropwise to a 0.01 M solution of the
corresponding 4-nitropyridine N-oxide (2,3-dimethyl-, 3,5-
dimethyl-, 2,3,6-trimethyl-4-nitropyridine N-oxide) in
30 ml of chloroform. The reaction mixture was refluxed
for 1 h. The solvent was evaporated, water added, basified
by K2CO3, extracted by chloroform and dried by mag-
nesium sulphate. After distillation of solvent the residue was
recrystallized from acetone. The yields and melting points
(in parentheses) were: 2, 87% (55 8C), 4, 95% (132 8C), 8,
93% (63 8C), 9, 89% (199 8C) and 10, 71% (126 8C).
Synthesis of 4-chloro-2-methylamino-6-methyl-5-nitro-
(5), 4-chloro-2-ethylamino-6-methyl-5-nitro- (6), 4-bromo-
2-methylamino-6-methyl-5-nitro- (11) and 4-bromo-2-ethy
lamino-6-methyl-5-nitro- (12) pyridine N-oxides were
performed as followed. The mixture of 2-alkylamino (methyl
or ethyl) -4,5-dinitropyridine N-oxide (2 g) and a solution of
the corresponding acetyl halide (chloride or bromide) in
acetonitrile (2 g of acetyl halide in 8 g of acetonitrile) was
heated on water bath for 30 min. Then the reaction mixture
was evaporated to 1/2 volume, 10 ml of water was added,
basified by K2CO3, extracted with diethyl ether and dried
with magnesium sulphate. After distilling-off the ether, the
crude product was chromatographed on aluminia and then
recrystallized from acetone. The yields and melting points
(in parentheses) were: 5, 54% (174 8C), 6, 33% (121 8C), 11,
44% (176 8C) and 12, 29% (138 8C).
1
In PFG H, 15N HMBC experiments a 50 ms delay was
used for evolution of long-range couplings. The number of
data points were 1024 (f2)!512/450 ppm (f1Z15N). This
matrix was zero filled to 1024!1024 and apodized by a
shifted sine bell window function along both axes prior to
FT. 15N NMR chemical shifts are referenced to the signal of
an external CH3NO2 (dZ0.0 ppm).
2.3. Mass spectroscopy
Electrospray mass spectrometric measurements were
performed for compound 5, using LCT time of flight (TOF)
mass spectrometer with electrospray ionization (ESI;
Micromass LCT). The spectrometer utilized two hexapole
RF lenses to transfer ions from the source to the orthogonal
acceleration TOF mass analyzer. Ions emerging from the
analyzer were detected by a dual microchannel plate
detector and ion counting system. Controlling the LCT as
well as acquiring and processing the data were performed
with MassLynx NT software system. In each experiment, a
flow rate of 20 ml/min was used for the sample solution and
the sample droplets were dried with nitrogen gas. The
potentials of 15–20 and 4 V for the sample and extraction
cones were applied. RF lens was set as a potential of 366 V
and the potential in the capillary at 4100 V. The desolvation
temperature was set at 120 8C and the source temperature at
80 8C.
3. Results and discussion
2.2. NMR spectroscopy
The structures of the studied pyridine N-oxides are
1
1
1
The H, 13C and PFG [20] H,13C HMQC [21,22] and
HMBC [23] spectra were recorded for 0.5 M DMSO-d6
presented in Fig. 1. The 15N, 13C and H NMR chemical
shifts of compounds 1–12 are presented in Tables 1–3.

K. Laihia et al. / Journal of Molecular Structure 783 (2006) 73–78
75
between K88.5 and K129.5 ppm. The very shielded values
for 5, 6, 11 and 12 (K129.5 to K128.4 ppm) can be
explained by the structures where hydrogen bond between
an amino proton and an oxygen atom of N-oxide group is
possible. The hydrogen bond between two molecules
N–H–N diminishes the electron density of the ring nitrogen.
In our earlier study of pyridine N-oxides [5] d(15Nring
)
varied between K92.7 and K93.0 ppm in three derivatives,
where only the amino form was possible. In five other
studied derivatives with 2-alkylamino substituent, the
d(15Nring) varied between K112.8 and K120.9 ppm. In all
these compounds, the imino tautomer as well as the
hydrogen bond between two amino tautomers were
possible.
3.2. 15N NMR shifts of Namino
d(15Namino) values for 5, 6, 11 and 12 vary from K307.5
to K290.5 ppm and are close to the values earlier measured
for 2-alkylamino-4-nitro- and 2-alkylamino-4,5-dinitropyr-
idine N-oxides, where, based on calculations, the imino
tautomer is energetically somewhat more favourable [5].
These shift values are, however, typical for amino nitrogen.
Deprotonation of alkylamino group by the formation of
N-hydroxypyridinium ion should strongly deshield the
amino nitrogen with an increase of double bond character
in the C(2)aNCH3 bond [10]. In our earlier study of
pyridine N-oxide derivatives [5], d(15Namino) varied
between K305.0 and K313.0 ppm in three derivatives,
where only the amino form was possible. In five other
Fig. 1. Structures of compounds 1–12.
3.1. 15N NMR shifts of Nring
d(15Nring) values are sensitive to the nature of the ring
substituents in the pyridine N-oxide as can be seen in
Table 1. In pyridine N-oxide d(15Nring)ZK86.8 ppm [10].
So, the 4-chloro substituent increases the shielding 1.7 ppm.
This effect is still increased by methyl ring substituents from
3.2 (3) to 6.8 ppm (4). In 4-bromopyridine N-oxide (5)
d(15Nring)ZK101.2 ppm, is much more shielded than in the
4-chloro derivative, which is in agreement with the
diamagnetic effect of bromine. Generally, d(15Nring) varies
derivatives with 2-alkylamino substituent, the d(15Namino
)
varied between K285.2 and K321.9 ppm. It means that,
because the shielding around amino nitrogen stays very
similar in both 2-alkyl- and 2-dialkylamino pyridine N-
oxides, these derivatives exist rather as dimer structures
than as their imino tautomers.
3.3. 15N NMR shifts of Nnitro
Table 1
15N NMR data of compounds 1–12 in 0.5 M DMSO-d6 solution at 30 8C,
ppm
The 15N chemical shifts of NO2 group in compounds
6, 11 and 12 vary from K14.8 to K12.5 ppm, being
K9.8 ppm for nitrobenzene [10]. On passing from 2-
alkylamino-6-methyl-4,5-dinitro- to 4-halo-2-alkylamino-
6-methyl-5-nitropyridine N-oxides the shielding of 5-nitro
Compounda Kd (15N) (ppm)
1J(N,H)
(Hz)
Nring
Namino
Arnitro
1
88.5
92.1
group, K18.1 ppm [5], in the 4,5-dinitro derivative,
15
2
decreases several ppm’s. The very shielded
value can be explained by twisting of 5-nitro group by the
N
shift
nitro
3
90.0
4
93.6
5
129.2
129.5
101.2
91.2
306.2
290.5
96
95
vicinal nitro group.
6
14.8
7
3.4. 13C NMR shifts
8
9
89.1
The assignment of 13C NMR chemical shifts for
compounds 1–12 (in Table 2), are based on literature data,
substituent induced chemical shifts [11–14] as well as
homo- and hetero-nuclear 2D chemical shift correlation
measurements. The substituent induced chemical shifts of
10
11
12
93.0
128.4
128.9
307.5
292.3
12.5
12.8
97
94
The 15NMR chemical shift of pyridine N-oxide is K86.8 ppm and that
of pyridine is K63.2 ppm (from Ref [5]).
a

76
K. Laihia et al. / Journal of Molecular Structure 783 (2006) 73–78
Table 2
13C NMR chemical shifts for compounds 1–12, ppm from TMS, in 0.5 M DMSO-d6 solution at 30 8C
Compound
d (13C)/ppm
C-2
C-3
C-4
C-5
C-6
2-CH3
3-CH3
5-CH3
6-CH3
1
139.97
148.75
137.39
148.36
151.83
150.92
140.09
148.70
136.94
148.16
151.71
150.81
126.60
132.52
134.24
129.50
101.70
101.96
129.49
134.35
136.26
131.16
104.61
104.63
129.28
129.33
130.73
128.34
122.85
122.96
116.88
119.86
123.09
118.77
110.83
110.92
126.60
123.22
134.24
122.93
135.00
134.94
129.49
126.30
136.26
125.90
137.07
137.02
139.97
137.08
137.39
146.14
142.39
142.54
140.09
137.15
136.94
146.18
142.02
142.17
–
–
–
–
2
14.35
16.32
16.68
16.07
–
–
–
3
–
16.68
–
4
14.79
–
17.33
14.28
14.35
–
5a
6b
7
–
–
–
–
–
–
–
–
8
14.58
19.39
19.60
19.10
–
–
–
9
–
19.60
–
10
11c
12d
14.96
–
–
–
17.24
14.22
14.29
–
–
–
a
NHCH3Z28.53 ppm.
NHCH2Z36.24 ppm, NHCH2CH3Z13.98 ppm.
NHCH3Z28.51 ppm.
b
c
d
NHCH2Z36.19 ppm, NHCH2CH3Z14.00 ppm.
2-CH3, 3-CH3, 2-NHCH3 and 4-NO2 were found for
pyridine N-oxide [11,12] and 5-NO2 for benzene [15].
When C-4 is substituted with chlorine, the ipso carbon
resonance changes from 126.1 [15] to 129.28 ppm. In its
methylated derivatives 2–4 C-4 is 2.2–4.6 ppm
more deshielded. Introducing three substituents 2-NHCH3,
5-NO2 (in ortho position the nitro group has a shielding
effect) and 6-CH3 into 4-chloropyridine N-oxide increases
the shielding in C-4, 129.28 (1) to 122.85 (5) ppm and
decreases it in C-2, 139.97 (1) to 151.83 ppm (5). These
changes in shielding can be explained with a structure with a
hydrogen bond between the oxygen and the alkylamino
group, which drifts the electrons only in one direction, from
C-4 to ring nitrogen.
effect’ of bromine. The shielding effect of 4-bromine on ipso
carbon is observed also in the methylated derivatives
(8–10). In 2-alkylamino substituted derivatives 11 and 12
C-4 is, however, most shielded, while the C-2 chemical
shifts are most deshielded (11 ppm) compared to the
chemical shifts of 4-bromopyridine N-oxide (7). This
situation is similar to the situation in the 2-alkylamino
substituted 4-chlorine compounds 5 and 6. Similar C-2 shift
values occur in the spectra of 2-methylamino-4-nitro-
(151.24 ppm) and 2-methylamino-6-methyl-4,5-dinitropyr-
idine N-oxides (152.02 ppm), which exist mainly in their
imino forms [5].
In order to deepen our understanding on the possible
amino/imino prototropic tautomerism of 5, 6, 11 and 12, we
can study the changes of carbon chemical shifts from 2-
methylamino- [12] to 2-methylamino-6-methyl-4,5-dinitro-
pyridine N-oxide [5]. When the N-oxide group is involved
When pyridine N-oxide is changed into 4-bromopyridine
N-oxide, the change in the ipso carbon resonance is from
126.1 [15] to 116.88 ppm (7), because of the ‘heavy atom
Table 3
1H NMR chemical shifts of compounds 1–12, ppm from residual DMSO-d5 in 0.5 M DMSO-d6 solutions at 30 8C
Compound
d (1H) (ppm)
H-2
H-3
H-5
H-6
2-CH3
3-CH3
5-CH3
6-CH3
NCH3
1
8.21
–
7.52
–
7.52
7.39
–
8.21
8.14
8.16
–
–
–
–
–
–
2
2.40
–
2.33
2.24
2.29
–
–
–
–
3
8.16
–
–
2.24
–
–
4
–
7.49
–
2.40
–
–
2.31
2.44
2.44
–
–
5a
6b
7
–
6.99
7.09
7.73
–
–
–
2.93
–
–
–
–
–
–
–
8.24
–
7.73
7.51
–
8.24
8.05
8.13
–
–
–
–
–
8
2.42
–
2.36
2.26
2.30
–
–
–
–
9
8.13
–
–
2.26
–
–
–
10
11c
12d
–
7.60
–
2.41
–
2.30
2.43
2.43
–
–
7.07
7.18
–
–
2.93
–
–
–
–
–
–
–
a
NHZ8.15 ppm.
NHZ8.13 ppm, NHCH2Z3.39 ppm, NHCH2CH3Z1.16 ppm.
NHZ8.07 ppm.
b
c
d
NHZ8.05 ppm, NHCH2Z3.38 ppm, NHCH2CH3Z1.15 ppm.

K. Laihia et al. / Journal of Molecular Structure 783 (2006) 73–78
77
Table 4
in hydrogen bonding, a structure is expected to become less
effective in contributing to the resonance hybrid of pyridine
N-oxide and thus decrease the electron density on C-2 and
C-4. In the case of N-hydroxy pyridinium ion two different
mechanism with opposite effect on the 13C chemical shifts
are operative for the C-2 atoms [1].
Density functional B3LYP optimized structures and B3LYP/6-311G**
calculated 13C NMR chemical shifts for 4, 5 and dimeric 5 structures
Structure C-2
C-3
C-4
C-5
C-6 2-CH3 3-CH3 6-CH3
4a
4b
5a
5b
5c
5d
148.4 129.5 128.3 122.9 146.1 14.79 16.07 17.33
152.0 130.7 137.8 121.8 149.7 15.12 16.32 18.15
151.8 101.7 122.9 135.0 142.4 –
151.2 96.05 132.9 135.6 146.8 –
144.9 101.9 145.7 127.3 142.9 –
151.2 98.76 136.1 134.8 147.6 –
–
–
–
–
14.28
14.79
13.78
15.00
The shielding of C-2 for four 4-halo-2-alkylamino-6-
methyl-5-nitropyridine N-oxides 5, 6, 11 and 12, stay fairly
constant and independent on the nature of the ring
substituents (Table 2).
a
Experimental data.
b
c
d
Calculated data for the amino form.
Calculated data for the imino form.
Calculated data for the amino dimer.
1
3.5. Variable temperature H NMR measurement
1
The VT H NMR runs of 5 was performed in CDCl3
solution. Even at K50 8C, there was no change in the
couplings between NH and aminomethyl protons and no
additional signals appeared in that low temperature
supporting the predominance of the amino tautomer.
Table 5
Density functional B3LYP optimized and B3LYP/6-311G** calculated 15
N
NMR chemical shifts of 4, 5 and dimeric 5 structures
Structure
Nring
K93.6
Namino
Arnitro
4a
4b
5a
5b
5c
5d
–
–
–
4. Calculations
K78.19
K129.2
–
K306.5
K314.69
K204.72
K303.84
–
K118.42
K166.24
K126.14
K7.82
K12.12
K8.54
Full geometry optimizations for a comparison with the
conformational and structural properties were performed
with the GAUSSIAN 98 series of programs at the ab initio
HF/6-311G** level of theory [16,17] for compound 5. The
energies of the tautomers were as follow: 5 (amino)Z
K1117.11461633 a.u., 5 (imino)ZK1117.10803565 a.u.
These results prove that in 5 the amino tautomer is
17.4 kJ/mol more stable than the imino form.
a
Experimental data.
b
c
d
Calculated data for the amino form.
Calculated data for the imino form.
Calculated data for the amino dimer.
of amino predicts that 5 exists almost entirely as amino
form while the same comparison of pyridine shifts predicts
that there is ca. 1/3 contribution of imino form present.
Only the dimeric amino form gives satisfactory agreement
between the experimental and calculated chemical shifts
for both types of nitrogens.
The observed 13C NMR chemical shift values do not
support as straightforwardly the dimeric structure. Some
great differences in calculated and observed 13C shift values
can, however, be explained taking into account for solvent
effects.
Using UHF/6-311G** and B3LYP/6-311G** optimized
structures both 13C and 15N chemical shifts were calculated
by ab initio UHF/6-311-G** and density functional
B3LYP/6-311G** CSGT methods for the amino forms of
4 and 5, the imino tautomer of compound 5 and the dimeric
amino tautomer of 5 (see Fig. 2) [16–18]. The B3LYP /
6-311G** optimized structures and B3LYP/6-311G**
CSGT calculated 15N and 13C chemical shift values gave
better results and the calculated values were closer to the
observed ones. The theoretical values have been presented
in Tables 4 and 5. A comparison between the calculated
and experimental 15N shift values support the dimeric
amino structure for 5, as it matches best with the observed
ones (Fig. 3). If there is a fast (in NMR time scale) amino/
imino tautomeric equilibrium in 5 both pyridine and amino
15N chemical shifts should predict the same contribution
for both forms. This is not true, because a comparison of
the experimental value with the calculated one in case
Fig. 2. Compound 4 and amino/imino tautomeric equilibrium of
compound 5.
Fig. 3. The dimer of amino tautomer of compound 5.

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K. Laihia et al. / Journal of Molecular Structure 783 (2006) 73–78
[4] K. Laihia, E. Kolehmainen, R. Kauppinen, J. Lorenc, A. Puszko,
5. Mass spectrometry
Spectrochim. Acta, Part A 58 (2002) 1425.
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6. Conclusions
The 15N NMR chemical shifts appear to be the most
reliable tool for examining the effect of substituents on the
possible amino/imino tautomeric equilibrium in methyl and
alkylamino derivatives of 4-halopyridine N-oxides Further,
the 15N chemical shift assignment is straightforward
because pyridine, amino and nitro moieties have separate
ranges of 15N resonances. 15N NMR and sophisticated DFT
calculations suggest that 4-halo-2-alkylamino-6-methyl-
5-nitropyridine N-oxide (5) exists predominantly as dimeric
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Acknowledgements
The authors are grateful to Special laboratory technicians
¨
Reijo Kauppinen and Mirja Lahtipera for the measurements
of the NMR and mass spectra.
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