Regioselectivity in the amination of azines: Reaction of pyrazine derivatives with O-mesitylenesulfonylhydroxylamine

Article abstract of DOI:10.1134/S1070428011060108

Treatment of 2-X-substituted pyrazines [X = H, Me, Et, Pr, i-Pr, t-Bu, MeCH(OH), H₂N, AcNH] with O-mesitylenesulfonylhydroxylamine gave the corresponding 2-X- and 3-X-(1-amino)pyrazin-1-ium mesitylenesulfonates. 2-Alkylpyrazines (X = Me, Et, Pr, i-Pr) displayed a correlation between the logarithms of the concentration ratio of 2- and 3-substituted cations and substituent steric constants. Wider series of substituted pyrazines [X = H, Me, Et, Pr, i-Pr, MeCH(OH), H₂N, AcNH] conformed to a multiparameter correlation between the logarithms of the concentration ratio of 2- and 3-substituted cations, on the one hand, and substituent constants σ_I, σ_R^?, and E _s^?, on the other. The obtained data on the regioselectivity of amination of pyrazines were interpreted in terms of DFT/PBE/3Z quantum-chemical calculations. Pleiades Publishing, Ltd., 2011.

Full text of DOI:10.1134/S1070428011060108

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 6, pp. 889–896. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © G.I. Borodkin, A.Yu. Vorob’ev, M.M. Shakirov, V.G. Shubin, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47,
No. 6, pp. 872–879.
Regioselectivity in the Amination of Azines: Reaction of Pyrazine
Derivatives with O-Mesitylenesulfonylhydroxylamine*
G. I. Borodkina, b, A. Yu. Vorob’eva, b, M. M. Shakirova, and V. G. Shubina
a Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences,
pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia
e-mail: gibor@nioch.nsc.ru
b Novosibirsk State University, Novosibirsk, Russia
Received February 17, 2010
Abstract—Treatment of 2-X-substituted pyrazines [X = H, Me, Et, Pr, i-Pr, t-Bu, MeCH(OH), H2N, AcNH]
with O-mesitylenesulfonylhydroxylamine gave the corresponding 2-X- and 3-X-(1-amino)pyrazin-1-ium
mesitylenesulfonates. 2-Alkylpyrazines (X = Me, Et, Pr, i-Pr) displayed a correlation between the logarithms of
the concentration ratio of 2- and 3-substituted cations and substituent steric constants. Wider series of sub-
stituted pyrazines [X = H, Me, Et, Pr, i-Pr, MeCH(OH), H2N, AcNH] conformed to a multiparameter correla-
tion between the logarithms of the concentration ratio of 2- and 3-substituted cations, on the one hand, and
substituent constants σI, σRo, and Eso, on the other. The obtained data on the regioselectivity of amination of
pyrazines were interpreted in terms of DFT/PBE/3Z quantum-chemical calculations.
DOI: 10.1134/S1070428011060108
Salts derived from N-amino-substituted nitrogen-
containing heterocycles are widely used as reagents for
the amination of arenes [3] and for the preparation of
imines [4] and various heterocyclic and other com-
pounds [5–17]. Such salts having several nitrogen
atoms in the ring are also promising as energetic
materials [18–20]. Salts of N-amino cations are usually
prepared by direct amination of nitrogen-containing
heterocycles with various aminating agents; among the
latter, O-mesitylenesulfonylhydroxylamine (MSH) is
used most widely [11–13].
1,10-phenanthrolines with MSH and found that the
ratio of the resulting isomeric amino cations is deter-
mined by their relative stability [21]. The goal of the
present work was to reveal factors responsible for
regioselectivity in the amination of pyrazine deriva-
tives. The latter were selected as substrates, taking into
account that pyrazines are widely used in the synthesis
of N-amino derivatives [13]. In addition, unlike
1,10-phenanthroline derivatives listed above, the sub-
stituent in 2-X-pyrazines is contiguous to the reaction
center, and the nitrogen atoms are present in a single
ring, which could endow the amination process with
some specificity.
If a heteroaromatic compounds contains nitrogen
atoms with different environments, amination regio-
selectivity problem arises [13, 21]. We previously
studied reactions of 3-bromo-, 4-methyl-, and 5-nitro-
The reaction of 2-substituted pyrazines Ia–Ii with
MSH in methylene chloride resulted in the formation
Scheme 1.
N
N
N
N
X
MesSO3NH2, CH2Cl2
+
MesSO3
MesSO3
X
N
X
N
NH2
NH2
Ia–Ij
IIa–IIe, IIg–IIi
IIIa–IIIi
X = H (a), Me (b), Et (c), Pr (d), i-Pr (e), t-Bu (f), MeCH(OH) (g), H2N (h), AcNH (i), CN (j).
* For preliminary communications, see [1, 2].
889

BORODKIN et al.
890
Scheme 2.
N
NH2
N
O
N
N
N
MesSO3
Me
–H3O+, –MesSO3
N
N
N
N
Me
H
NH2
NH2
IIi
IV
A
Table 1. 1H NMR spectra of N-aminopyrazinium salts II and III in DMSO-d6 at 25°C
Chemical shifts δ,a ppm (J, Hz)
Cation
b
no.
X
–
2-H
3-H
5-H
6-H
NH2
IIa
IIb
8.74 d.d.d
(J = 4.0, 1.6, 1.0) (J = 4.0, 1.0)
9.14 d.d
9.14 d.d
(J = 4.0, 1.0)
8.74 d.d.d
(J = 4.0, 1.6, 1.0)
9.60
9.08
9.51
9.60
2.67 d.d.d (3H, J = 0.8, 0.8, 0.4)
–
9.13 q.d
(J = 0.8, 0.7)
8.97 d.q
(J = 4.0, 0.8)
8.80 d.d.q
(J = 4.0, 0.7, 0.4)
IIIb 2.60 d.d.d (3H, J = 0.7, 0.7, 0.7)
8.71 d.q.d
(J = 1.5, 0.7, 0.7)
–
9.01 d.q.d
(J = 3.9, 0.7, 0.7) (J = 3.9, 1.5, 0.7)
8.62 d.d.q
IIc
1.30 t (3H, J = 7.4),
3.05 q.d.d.d (2H, J = 7.4, 0.8,
0.7, 0.4)
–
9.08 t.d
(J = 0.8, 0.8)
8.98 d.t
(J = 4.0, 0.7)
8.84 d.d.t
(J = 4.0, 0.8, 0.4)
IIIc 1.24 t (3H, J = 7.6),
8.78 d.d.t
–
9.03 d.d
(J = 3.9, 0.9)
8.66 d.d.t
(J = 3.9, 1.6, 0.6)
9.60
9.60
2.87 q.d.d (2H, J = 7.6, 0.6, 0.5) (J = 1.6, 0.9, 0.5)
IId
0.95 t (3H, J = 7.4),
1.71 t.q (2H, J = 7.8, 7.4),
3.01 t (2H, J = 7.8)
–
9.08 d
(J = 0.8)
8.98 d
(J = 4.0)
8.85 d.d
(J = 4.0, 0.8)
IIId 0.88 t (3H, J = 7.4),
1.66 t.q (2H, J = 7.6, 7.4),
2.80 t (2H, J = 7.6)
IIec 1.32 d (6H, J = 6.8),
3.64 sept (1H, J = 6.8)
8.80 d.d
(J = 1.6,
0.9)
–
9.04 d.d
(J = 3.9, 0.9)
8.68 d.d
(J = 3.9, 1.6)
9.10
–
9.19
–
8.99 d
(J = 4.0)
8.81 d
(J = 4.0)
9.50
9.50
9.50
9.10
IIIe 1.23 d (6H, J = 6.9),
3.16 sept (1H, J = 6.9)
8.83 d.d
(J = 1.5, 0.9)
9.05 d.d
(J = 3.9, 0.9)
8.67 d.d
(J = 3.9, 1.5)
IIIf 1.35 s (9H)
8.82 d.d
(J = 1.5, 0.9)
–
9.10 d.d
(J = 3.8, 0.9)
8.63 d.d
(J = 3.8, 1.5)
IIg
1.55 d (3H, J = 6.6),
5.34 q.d.d (1H, J = 6.6, 0.6, 0.6),
5.2 br.s (1H)
–
9.22 d.d
(J = 0.8, 0.6)
9.05 d.d
(J = 4.0, 0.6)
8.81 d.d
(J = 4.0,
0.8)
IIIg 1.44 d (3H, J = 6.6),
8.80 d.d.d
–
9.04 d.d
8.66 d.d.d
9.60
4.91 q.d.d (1H, J = 6.6, 0.8, 0.8), (J = 1.7, 0.9, 0.8)
(J = 3.9, 0.9)
(J = 3.9, 1.7, 0.8)
5.2 br.s (1H)
IIh
8.84 br.s (2H)
–
8.61 d
(J = 1.0)
7.90 d
(J = 4.4)
8.07 d.d
(J = 4.4, 1.0)
7.14
9.00
9.60
IIIh 7.68 br.s (2H)
7.84 d.d
(J = 1.5, 0.9)
–
7.80 d.d
(J = 3.8, 1.5)
8.37 d.d
(J = 3.8, 0.9)
IIIi
2.20 s (3H),
9.42 d.d
–
8.83 d.d
8.43 d.d
11.6 br.s (1H)
(J = 1.5, 0.9)
(J = 3.9, 0.9)
(J = 3.9, 1.5)
a
b
c
The chemical shifts were measured relative to the residual solvent signal (DMSO, δ 2.50 ppm).
Broadened singlet (2H).
Some coupling constants were not determined because of low signal intensity.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 6 2011

REGIOSELECTIVITY IN THE AMINATION OF AZINES:
891
Table 2. 13C NMR spectra of N-aminopyrazinium salts II and III in DMSO-d6 at 25°C
Chemical shifts δC,a ppm (JCH, Hz)
Cation
no.
substituent X
–
C2
C3
C5
C6
IIa
127.8 (197.3)
140.2
150.0 (195.2)
151.0 (194.0)
159.7
150.0 (195.2)
146.6 (195.0)
148.8 (194.0)
146.8 (195.2)
149.1 (194.0)
146.8 (195.4)
127.8 (197.3)
128.2 (196.5)
125.2 (198.2)
128.5 (196.0)
125.5 (197.6)
128.7b
IIb
IIIb
IIc
15.4 (131.9)
21.8 (129.6)
126.9 (198.8)
143.7
27.8 (127.7), 13.2 (128.9)
28.5(129.7), 12.1 (127.6)
149.6 (192.7)
164.1
IIIc
IId
126.5 (194.6)
142.6
13.4 (127.5), 22.0 (127.4), 36.5
(127.5)
150.3 (193.1)
IIId
13.3 (125.6), 21.2 (128.2), 36.9
(129.5)
126.7 (194.7)
163.0
149.1 (194.2)
125.5 (197.9)
IIIec
IIIf
IIg
21.1 (127.7), 33.9 (130.9)
28.6 (127.2), 37.3
125.7 (194.2)
125.3 (197.5)
143.9
167.4
149.0 (194.2)
148.6 (192.5)
147.6 (191)
125.5 (197.8)
124.7 (194.3)
128.6 (196.7)
125.8 (197.7)
130.6 (193.6)
116.2 (199)
169.4
19.5 (128.9), 62.7 (148.2)
22.8 (128.0), 67.5 (145.4)
148.0 (191)
166.9
IIIg
IIh
124.4 (197.0)
147.1
148.6 (194.7)
130.4 (194.6)
148.3 (194)
141.3 (195.8)
165.5
IIIh
IIIi
114.0 (202)
118.3 (201.6)
23.8 (129.0), 170.6
164.1
148.1 (194.5)
123.0 (199.0)
a
b
c
The chemical shifts were measured relative to the solvent signal (DMSO-d6, δC 39.50 ppm).
The coupling constant was not determined due to superposition of other signals.
The data for cation IIe are not given because of its low concentration.
of isomeric cations IIa–IIe, IIg, IIh and IIIb–IIIi
(Scheme 1). No amination of pyrazine-2-carbonitrile
(Ij) was observed, whereas in the reaction with 2-tert-
butylpyrazine (If) only one isomeric cation IIIf was
formed. We failed to identify cation IIi, for it under-
went intramolecular cyclization to 2-methyl[1,2,4]tri-
azolo[1,5-a]pyrazine (IV) (Scheme 2).
The structure of N-aminopyrazinium salts II and III
1
was determined by H and 13C NMR spectroscopy
(Tables 1, 2), and the structure of IIa, IIh, and IIIi was
additionally proved by X-ray analysis [22]. Signals in
the NMR spectra were assigned using various correla-
1
tion techniques, H-2D NOESY and two-dimensional
1
1H–1H and H–13C COSY. NOESY experiments
Table 3. Concentration ratios of isomeric N-aminopyrazinium ions II and III, substituent constants σI, Es, Es°, σR°, and F, and
calculated energy barriers for the amination process (E≠calc
)
X
log([II]/[III])a
σI [24] σR° [25, 26]
Es [25]
Es° b
F [27]
E≠calc,c kJ/mol ΔE≠calc, kJ/mol
H
–0.0
0.00
–0.01–
–0.01–
–0.01–
0.01
–0.00
–0.10
–0.10
–0.11
–0.12
–0.08
–0.47
–0.41
1.24
0.00
0.25
0.00
–0.28–
0.00
0.73
0.52
2.12
0.64
–
62.8
00.00
0–0.38–
00.84
Me
Et
–0.173±0.003
–0.498±0.017
–0.478±0.012
–1.020±0.055
–0.479±0.003
–0.406±0.015
–0.473±0.019
57.3 (57.7)
59.3 (58.5)
63.3 (58.4)
72.0 (58.6)
73.3 (64.2)
–0.07–
–0.36–
–0.47–
0.09
d0.00d
d–0.75d– –0.95–
–0.27–
–0.56–
–0.87–
–0.44–
0.00
Pr
01.17
i-Pr
13.43
MeCH(OH)
NH2
0.04
09.08
0.17
36.3 (54.1)
–17.87–
e
e
AcNH
0.28
–
a
b
c
d
e
Average values from 5–8 measurements by 1H NMR.
Calculated by the equation Es° = Es – 0.33(3 – nH) + 0.13nC [27].
Activation barriers for the amination with formation of 3-substituted isomer are given in parentheses.
Calculated in terms of the isostericity concept [27].
Transition state leading to cation IIi was not found.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 6 2011

BORODKIN et al.
892
3-H, 5-H
may be due to significant contribution of canonical
structure A. In most cases, signals from endocyclic
carbon atoms remote from the N+–NH2 fragment ap-
peared in a weaker field than those neighboring to that
fragment. Presumably, this is the result of polarization
of the C–C bonds toward electron-withdrawing
N+–NH2 group. The coupling constants JHH were deter-
mined by comparing the calculated and experimental
spectra. As an example, Fig. 1 shows the calculated
1
and experimental H NMR spectra of cation IIa in the
(b)
aromatic region. Fairly large absolute values of the
direct coupling constants 1JC1H (191–202 Hz) should be
noted. Analogous values of JCH were observed previ-
ously for N-methylpyrazinium [23].
(a)
9.16
9.15
9.14
9.13
δ, ppm
2-H, 6-H
The concentration ratio of isomeric cations II and
1
III was determined on the basis of the H NMR
spectra. It strongly depends on the substituent nature
(Table 3) and is kinetically controlled. This follows
1
from the fact that the H NMR spectra of IIh and IIIi
remained unchanged after heating for 4 h at 100°C in
1
DMSO. Likewise, according to the H NMR data,
heating of a solution of 1-aminopyrazinium salt in
DMSO in the presence of 5 equiv of pyridine or
mesitylene did not result in amino group transfer to
pyridine or mesitylene molecule.
(b)
(a)
8.76
8.75
8.74
8.73
δ, ppm
Taking into account vicinity of the reaction center
to the X substituent in 2-X-pyrazines, the isomer ratio
may be presumed to be determined by both electronic
and steric effects of the substituent. The difference in
the inductive effects of alkyl groups in positions 2 and
3 of the pyrazine ring is likely to be insignificant, as
follows from the existence of a correlation between the
logarithms of the concentration ratio of cations II and
III and steric constants of alkyl substituents (Table 3,
Fig. 2).**
1
Fig. 1. (a) Experimental and (b) calculated H NMR spectra
of cation IIa.
revealed nuclear Overhauser effects for spatially close
protons in the NH2 group and 2-H (6-H). The 2-H and
C2 signals in the H and 13C NMR spectra of cation
1
IIIh were observed in a relatively strong field, which
log([II]/[III])
H
0.0
–0.2
–0.4
–0.6
–0.8
–1.0
–1.2
log([II]/[III]) = (0.84±0.15)Es° – (0.19±0.07);
r = 0.96, s = 0.13, n = 5;
(1)
Me
log([II]/[III]) = –(0.41±0.03)F – (0.18±0.04);
r = 0.99, s = 0.06, n = 5.
(2)
Pr
Et
In the general case, electronic effect of a substituent
should be taken into consideration together with its
steric effect. In fact, a broader series of substituents
[X = H, Me, Et, Pr, i-Pr, MeCH(OH), H2N, AcNH]
gave rise to a multiparaameter correlation between the
logarithms of the concentration ratio of N-aminopyr-
i-Pr
–0.5
0.0
0.5
1.0
1.5
2.0
2.5
F
** The concentration of isomeric cation IIf, calculated by Eqs. (1)
and (2), is 1 and 2%, respectively, which is consistent with the
experimental data.
Fig. 2. Plot of log[(II)/(III)] versus substituent steric con-
stants F.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 6 2011

REGIOSELECTIVITY IN THE AMINATION OF AZINES:
893
azinium cations and substituent constants σI, σR°, and
Es° (Table 3).
Application of the internal reaction coordinate (IRC)
procedure resulted in direct transition from the
activated complex to the product or initial compound.
Taking into account asymmetry of transition states,
four different orientations of the reagent with respect
to the substituent in the pyrazine ring were considered
[X = Me, Et, Pr, i-Pr, MeCH(OH), NH2, CN, Cl,
MeO]. In all transition states found for 2-X-pyrazines,
the interacting atoms N1, N(NH2), and oxygen atom in
the SO3NH2 group lie almost in one straight line
(∠NNO 173–176°; Figs. 3, 4), which is typical of SN2
reactions [31, 32]. The X substituent does not affect
the N1–N(NH2) and O(SO3)–N(NH2) bond lengths to
a considerable extent. All transition states are charac-
terized by formation of hydrogen bond between hydro-
gen atom in the amino group and oxygen atom in the
log([II]/[III]) = –(0.24±0.08) + (0.87±0.98)σI
– (1.03±0.60)σR° + (0.94±0.11)Es°;
r = 0.98, s = 0.12, n = 8.
(3)
With a view to predict regioselectivity in the
amination of substituted pyrazines we performed
DFT/PBE/3z quantum-chemical calculations [28–30].
Transition states on the potential energy surface were
identified by the presence of at least one imaginary
frequency in the corresponding Hessian matrix, and the
vibrational vector conformed to motion of the NH2
group from the oxygen atom in the SO3NH2 group to
the nitrogen atom in the pyrazine ring (Figs. 3, 4).
1.916
1.919
1.936
1.914
1.929
1.908
1.909
1.916
1.923
1.949
1.905
1.907
2-Me
3-Me
2-Et
3-Et
1.936
1.915
1.920
1.922
1.920
1.923
1.938
1.925
1.909
1.908
1.910
1.902
2-Pr
3-Pr
2-i-Pr
3-i-Pr
Fig. 3. Structures of transition states for the amination of 2-X-substituted pyrazines with O-mesitylenesulfonylhydroxylamine
(X = Me, Et, Pr, i-Pr).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 6 2011

BORODKIN et al.
894
1.895
1.931
1.913
1.939
1.913
1.961
1.915
1.924
1.933
1.942
1.889
1.913
2-MeCH(OH)
3-MeCH(OH)
2-NH2
3-NH2
1.872
1.984
2.383
1.922
1.913
1.926
1.838
1.871
2.759
1.958
1.872
1.940
1.874
1.914
2-MeO
3-MeO
2-Cl
3-Cl
1.901
1.923
1.918
3-AcNH
Fig. 4. Structures of transition states for the amination of 2-X-substituted pyrazines with O-mesitylenesulfonylhydroxylamine
[X = MeCH(OH), H2N, MeO, Cl, AcNH].
for 2-chloro- and 2-methoxypyrazines (X = Cl, MeO),
which is consistent with the experimental data [22].
The difference in the calculated energies of activation
for the formation of 2- and 3-substituted isomers is
fairly large (13.4 and 20.9 kJ/mol, respectively). This
may be due to unfavorable effect of unshared electron
pairs on the chlorine or oxygen atom (in the methoxy
group) which are not involved in n,π-conjugation with
electron pairs on the oxygen atom in the OSO2Mes
group in the transition state corresponding to amina-
tion of 2-X-pyrazines at the N1 atom. The calculated
energy barriers to the amination of 2-cyanopyrazine at
the nitrogen atoms in positions 1 and 4 (E≠calc = 77.0
MesSO3 group. Table 3 contains minimal energy bar-
riers to the amination process.
Comparison of the log([II]/[III]) values with the
calculated differences in the energies of activation
for the formation of 2- and 3-substituted N-aminopyr-
azinium salts (ΔE≠, Table 3) led to the following cor-
relation:
log([II]/[III]) = –(0.28±0.08) – (0.042±0.009)ΔE≠calc; (4)
r = 0.91, s = 0.21, n = 7.
The calculations predicted formation of only one
isomer, namely 3-substituted 1-aminopyrazinium ion,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 6 2011

REGIOSELECTIVITY IN THE AMINATION OF AZINES:
895
and 79.5 kJ/mol, respectively) are much higher than
those found for the other examined pyrazines (Table 3);
this is consistent with our failure to obtain amination
product from pyrazine Ij (X = CN).
N-(Pyrazin-2-yl)acetamide (Ii) was synthesized as
described in [39]. Colorless crystals, mp 132–133°C
1
[40]. H NMR spectrum (DMSO-d6, 200 MHz), δ,
ppm: 2.16 s (3H), 8.12 d.d (1H, J = 2.5, 1.5 Hz),
8.20 d.d (1H, J = 2.5, 0.9 Hz), 8.88 br.s (1H), 9.41 d.d
(1H, J = 1.5, 0.9 Hz) (cf. [41, 42]).
Thus our results showed that the regioselectivity in
the amination of 2-substituted pyrazines is determined
by both electronic and steric effects of the substituent.
2-Methyl-1,2,4-triazolo[1,5-a]pyrazine (IV). Yel-
1
low crystals, mp 130–132°C [43, 44]. H NMR spec-
EXPERIMENTAL
trum (200 MHz, CDCl3), δ, ppm: 2.62 (3H), 9.14 d
(1H, J = 2 Hz), 8.42 d.d (1H, J = 4.4, 2 Hz), 8.08 d
(1H, J = 4.4 Hz) (cf. [44]).
1
The H and 13C NMR spectra were recorded on
Bruker AC-200, DRX-500, and AV-600 instruments at
room temperature from solutions in DMSO-d6 and
CDCl3 using the residual proton and carbon signals of
the solvent as reference (DMSO-d5, δ 2.50 ppm;
DMSO-d6, δC 39.50 ppm; CHCl3, δ 7.24 ppm). Quan-
tum-chemical calculations in terms of the density func-
tional theory (DFT) using PBE functional [28] were
performed with the aid of PRIRODA program
[3z basis set; (11s6p2d)/(6s3p2d) and (5s1p)/(3s1p) for
C, O, N, and S atoms and hydrogen atoms, respec-
tively] [29, 30]. Critical points on the potential energy
surface were identified by calculating the correspond-
General procedure for the amination of substi-
tuted pyrazines. Pyrazine Ia–Ij, ~0.5 mmol, was
dissolved in 0.5 ml of methylene chloride, the solution
was cooled to 0°C, and a solution of ~0.75 mmol of
O-mesitylenesulfonylhydroxylamine in 1 ml of
methylene chloride (preliminarily dried over sodium
sulfate) was added dropwise under stirring. The mix-
ture was stirred for 30 min at 0°C, allowed to warm up
to room temperature, kept for 3 h, and diluted with
5 ml of diethyl ether. The precipitate was filtered off,
washed with diethyl ether, and dried under reduced
pressure. The overall yield of isomeric 2- and 3-substi-
tuted 1-aminopyrazinium salts II and III was 50–90%.
1
ing Hessian matrix [33]. The H NMR spectra were
calculated using Spinworks 2.5 program.
The following reagents and solvents were used:
pyrazine (99%), 2-methylpyrazine (99%), pyrazin-2-
carbonitrile (97%), pyrazin-2-amine (98%), 1-(pyra-
zin-2-yl)ethanone (99%) (Lancaster); 2-ethylpyrazine
(98%), 2-propylpyrazine (>98%), isovaleric acid
(99%), mesitylene (>98%) (Acros Organics); distilled
isobutyric and pivalic acids of pure grade, DMSO-d6
and CDCl3 containing 99% of deuterium, and O-mesit-
ylenesulfonylhydroxylamine [11]. Methylene chloride
was purified according to the procedure described in
[34] by washing with a saturated solution of sodium
carbonate, followed by heating with activated charcoal
under reflux, drying, and distillation over CaCl2.
Evaluation of the kinetic stability of substituted
1-aminopyrazinium mesitylenesulfonates and of
the possibility for NH2 group transfer to bases.
A ~0.1 M solution of 1-aminopyrazinium salt IIh or
IIIi in DMSO was heated for 4 h at 100°C, and NMR
spectra of the solution were recorded. Mesitylene or
pyridine, 5 equiv, was added to a ~0.1 M solution of
N-aminopyrazinium salt IIa, the mixture was heated
for 3 h at 90°C, and its NMR spectra were recorded.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 09-03-00116-a) and by the Chemistry and Mate-
rials Science Department of the Russian Academy of
Sciences (project no. 5.1.4).
1-(Pyrazin-2-yl)ethanol (Ig) was synthesized by
1
reduction of 2-acetylpyrazine [35]. H NMR spectrum
(CDCl3, 200 MHz), δ, ppm: 1.54 d (3H, J = 7.0 Hz),
3.60 br.s, 4.97 q (1H, J = 7.0 Hz), 8.48 m (2H), 8.65 m
(1H) (cf. [36]).
REFERENCES
1. Vorob’ev, A.Yu., Andreev, R.V., Borodkin, G.I., Gati-
lov, Yu.V., and Shubin, V.G., Abstracts of Papers,
IX Nauchnaya shkola–konferentsiya po organicheskoi
khimii (IXth Scientific School–Conf. on Organic Chem-
istry), Moscow, 2006, p. 112.
2-tert-Butylpyrazine (If) was synthesized as de-
scribed in [37]. 1H NMR spectrum (CDCl3, 200 MHz),
δ, ppm: 1.38 s (9H), 8.36 d (1H, J = 2.5 Hz), 8.48 d.d
(1H, J = 2.5, 1.6 Hz), 8.64 d (1H, J = 1.6 Hz) (cf. [38]).
2. Borodkin, G.I., Vorob’ev, A.Yu., Shakirov, M.M., and
2-Isopropylpyrazine (Ie) was synthesized in a sim-
ilar way. H NMR spectrum (CDCl3, 200 MHz), δ,
1
Shubin, V.G., Tetrahedron Lett., 2009, vol. 50, p. 6779.
ppm: 1.32 d (6H, J = 7.0 Hz), 3.08 sept (1H, J =
3. Borodkin, G.I. and Shubin, V.G., Russ. J. Org. Chem.,
7.0 Hz), 8.36 m (1H), 8.46 m (2H) (cf. [38]).
2005, vol. 41, p. 473.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 6 2011

BORODKIN et al.
896
4. Sadykov, A.S., Kurbatov, Yu.V., and Zalyalieva, S.V.,
22. Andreev, R.V., Borodkin, G.I., Vorob’ev, A.Yu., Gati-
lov, Yu.V., and Shubin, V.G., Russ. J. Org. Chem., 2008,
vol. 44, p. 292.
N-Iminy piridinovykh osnovanii (N-Imines Derived
from Pyridine Bases), Tashkent: FAN, 1982.
23. Newmark, R.A., Tucker, A., and Hardy, L.C., Magn.
Reson. Chem., 1996, vol. 34, p. 728.
5. Katritzky, A.R., Ballesteros, P., and Tomas, A.T.,
J. Chem. Soc., Perkin Trans. 1, 1981, p. 1495.
24. Charton, M., Progress in Physical Organic Chemistry,
Taft, R.W., Ed., New York: Wiley, 1981, vol. 13, p. 119.
25. Exner, O., Correlation Analysis in Chemistry. Recent
Advances, Chapman, N.B. and Shorter, J., Eds., New
York: Plenum, 1978, p. 439.
26. Grindley, T.B., Johnson, K.F., Katritzky, A.R.,
Keogh, H.J., Thirkettle, C., Brownlee, R.T.C., Mun-
day, J.A., and Topsom, R.D., J. Chem. Soc., Perkin
Trans. 2, 1974, p. 276.
27. Pal’m, V.A., Osnovy kolichestvennoi teorii organiche-
skikh reaktsii (Principles of the Quantitative Theory of
Organic Reactions), Leningrad: Khimiya, 1977, pp. 226,
319.
6. Andreev, R.V. and Borodkin, G.I., Materialy konferentsii
“Organicheskii sintez v novom stoletii” (Proc. Conf.
“Organic Synthesis in the New Century”), St. Peters-
burg, 2002, p. 64.
7. Billert, T., Beckert, R., Döring, M., Wuckelt, J.,
Fehling, P., and Görls, H., J. Heterocycl. Chem., 2001,
vol. 38, p. 205.
8. Abe, N., Odagiri, K., Otani, M., Fujinaga, E., Fujii, H.,
and Kakehi, A., J. Chem. Soc., Perkin Trans. 1, 1999,
p. 1339.
9. Yao, G., Haque, S., Sha, L., Kumaravel, G., Wang, J.,
Engler, T.M., Whalley, E.T., Conlon, P.R., Chang, H.,
Kiesman, W.F., and Petter, R., Bioorg. Med. Chem. Lett.,
2005, vol. 15, p. 511.
28. Perdew, J.P., Burke, K., and Ernzerhof, M., Phys. Rev.
Lett., 1996, vol. 77, p. 3865.
29. Laikov, D.N., Chem. Phys. Lett., 1997, vol. 281, p. 151.
30. Laikov, D.N. and Ustynyuk, Yu.A., Izv. Ross. Akad.
Nauk, Ser. Khim., 2005, p. 804.
10. Vinogradova, O.V., Kryshtalyuk, O.V., Rudnev, M.I.,
Pozharskii, A.F., and Kuz’menko, V.V., Khim. Getero-
tsikl. Soedin., 1994, p. 1364.
11. Tamura, Y., Minamikawa, J., and Ikeda, M., Synthesis,
31. Vayner, G., Houk, K.N., Jorgensen, W.L., and Brau-
man, J.I., J. Am. Chem. Soc., 2004, vol. 126, p. 9054.
32. Martínez, A.G., Vilar, E.T., Barcina, J.O., and
Cerero, S.M., J. Org. Chem., 2005, vol. 70, p. 10238.
1977, p. 1.
12. Tamura, Y. and Ikeda, M., Advances in Heterocyclic
Chemistry, Katritzky, A.R. and Boulton, A.J., London:
Academic, 1981, vol. 29, p. 71.
33. Minkin, V.I., Simkin, B.Ya., and Minyaev, R.M., Kvan-
tovaya khimiya organicheskikh soedinenii. Mekhanizmy
reaktsii (Quantum Chemistry of Organic Compounds.
Reaction Mechanisms), Moscow: Khimiya, 1986, p. 10.
13. Ivanov, A.Yu. and Lobanov, P.S., Sovremennye prob-
lemy organicheskoi khimii, Potekhin, A.A. and Kosti-
kov, R.R., Eds., St. Petersburg: Sankt-Peterb. Gos.
Univ., 1998, no. 12, p. 79.
34. Gordon, A.J. and Ford, R.A., The Chemist’s Com-
panion, New York: Wiley, 1972. Translated under the
title Sputnik khimika, Moscow: Mir, 1976, p. 127.
35. Fernholz, E., Schloeder, D., Liu, K.K.C., Brad-
shaw, C.W., Huang, H., Janda, K., Lerner, R.A., and
Wong, C.-H., J. Org. Chem., 1992, vol. 57, p. 4756.
14. Martínez, V., Burgos, C., Alvarez-Builla, J., Fernán-
dez, G., Domingo, A., García-Nieto, R., Gago, F., Man-
zanares, I., Cuevas, C., and Vaquero, J.J., J. Med.
Chem., 2004, vol. 47, p. 1136.
15. Dowling, J.E., Vessels, J.T., Haque, S., Chang, H.X.,
van Vloten, K., Kumaravel, G., Engber, T., Jin, X.,
Phadke, D., Wang, J., Ayyub, E., and Petter, R.C.,
Bioorg. Med. Chem. Lett., 2005, vol. 15, p. 4809.
36. Plé, N., Turck, A., Couture, K., and Quéguiner, G.,
J. Org. Chem., 1995, vol. 60, p. 3781.
37. Fontana, F., Minisci, F., Nogueira Barbosa, M.C., and
Vismara, E., Tetrahedron, 1990, vol. 46, p. 2525.
38. Rizzi, G.P., J. Org. Chem., 1974, vol. 39, p. 3598.
39. Sudha, L.V., Manogaran, S., and Sathyanarayana, D.N.,
J. Mol. Struct., 1985, vol. 129, p. 137.
40. Hall, S.A. and Spoerri, P.E., J. Am. Chem. Soc., 1940,
vol. 62, p. 664.
41. Brown, R.F.C., Radom, L., Sternhell, S., and Rae, I.D.,
Can. J. Chem., 1968, vol. 46, p. 2577.
16. Filák, L., Riedl, Z., Egyed, O., Czugler, M.,
Hoang, C.N., Schantl, J.G., and Hajós, G., Tetrahedron,
2008, vol. 64, p. 1101.
17. Cunha, S., Rodrigues, M.T., Silva, C.C., Napoli-
tano, H.B., Vencato, I., and Lariucci, C., Tetrahedron,
2005, vol. 61, p. 10536.
18. Olah, G.A., Sassaman, M.B., Zuanic, M., Rao, C.B.,
Prakash, G.K.S., Gilardi, R., Flippen-Anderson, J., and
George, C., J. Org. Chem., 1992, vol. 57, p. 1585.
19. Xue, H., Gao, Y., Twamley, B., and Shreeve, J.M.,
Chem. Mater., 2005, vol. 17, p. 191.
20. Wang, R., Gao, H., Ye, C., Twamley, B., and
42. Syrova, G.P., Sheinker, Yu.N., Musatova, I.S., and
Elina, A.S., Khim. Geterotsikl. Soedin., 1972, p. 266.
43. Tamura, Y., Kim, J.-H., and Ikeda, M., J. Heterocycl.
Chem., 1975, vol. 12, p. 107.
Shreeve, J.M., Inorg. Chem., 2007, vol. 46, p. 932.
21. Andreev, R.V., Borodkin, G.I., Shakirov, M.M., and
44. Okamoto, T., Torigoe, Y., Sato, M., and Isogai, Y.,
Shubin, V.G., Russ. J. Org. Chem., 2004, vol. 40, p. 1379.
Chem. Pharm. Bull., 1968, vol. 16, p. 1154.
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