σh-Adducts of N-alkylpyrazinium and quinoxalinium salts with nucleophiles. the 1H and 13C NMR spectra and the crystal structures of P-adducts

Article abstract of DOI:10.1007/s11172-009-0027-1

The previously unknown addition products of P-nucleophiles to 5-aryl- and 5-hetaryl- 2,3-dicyano-1-ethylpyrazinium salts and to 5-aryl- and 5-hetaryl-14nethylquinoxalinium salts were synthesized. The three-dimensional structures of the P- σ^H-ad

Full text of DOI:10.1007/s11172-009-0027-1

Russian Chemical Bulletin, International Edition, Vol. 58, No. 1, pp. 176—181, January, 2009
176
H
σ ꢀAdducts of Nꢀalkylpyrazinium and quinoxalinium salts with nucleophiles.
The 1H and 13C NMR spectra and the crystal structures of Pꢀadducts*
E. V. Verbitskiy, M. V. Berezin, P. A. Slepukhin, G. L. Rusinov, and V. N. Charushin
I. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
22/20 ul. S. Kovalevskoi, 620041 Ekaterinburg, Russian Federation.
Fax: +7 (343 2) 74 1189. Еꢀmail: rusinov@ios.uran.ru
The previously unknown addition products of Pꢀnucleophiles to 5ꢀarylꢀ and 5ꢀhetarylꢀ
2,3ꢀdicyanoꢀ1ꢀethylpyrazinium salts and to 5ꢀarylꢀ and 5ꢀhetarylꢀ1ꢀmethylquinoxalinium
H
salts were synthesized. The threeꢀdimensional structures of the Pꢀσ ꢀadducts of the 1,4ꢀdiazine
series were established by Xꢀray diffraction.
Key words: 5ꢀarylꢀ and 5ꢀhetarylꢀ2,3ꢀdicyanoꢀ1ꢀethylpyrazinium salts, 3ꢀarylꢀ and
H
3ꢀhetarylꢀ1ꢀmethylquinoxalinium salts, diethyl phosphonate, diphenyl phosphonate, σ ꢀadducts
with Pꢀnucleophiles.
Pyrazines1—4 and quinoxalines5—8 are of interest for
medical chemistry, form a skeleton of numerous natural
compounds and antibiotics, and exhibit antitumor, antiꢀ
tuberculosis, and other activities.9—11 In recent years, the
development of new methods for the synthesis and modiꢀ
fications of diazines, including methods based on the
direct nucleophilic attack on the unsubstituted carbon
atom of the azine ring, has attracted great attention.12—19
It is known that Nꢀalkylpyrazinium and quinoxalinium
salts are prone to the monoꢀ and diaddition of Oꢀ, Cꢀ,
Nꢀ, and Sꢀnucleophiles, as well as to annulation of fiveꢀ
or sixꢀmembered heterocycles in reactions with a wide
range of dinucleophiles.12—14 Primary σHꢀadducts, which
are generated via the nucleophilic attack on the α position
with respect to the cationic center, were comprehensively
substituent in the β position with respect to the quaterꢀ
nary cationic group would block the secondary addition
with the result that the β attack will be the only reaction
pathway.
Actually, the reactions of salts 1a,b and 2a,b with
phosphonates 3a,b proceed under mild conditions (20 °C,
CH3CN). It should be noted that bases are not required
for the initiation of the reactions of the pyrazinium salts.
The structures of Pꢀadducts 4a,b, 5a,b, and 6a,b
were confirmed by NMR spectroscopy. The structures of
products 4a,b (Figs 1 and 2, respectively) were established
also by Xꢀray diffraction.
Product 4a crystallizes in the space group P21/c and
was obtained as yellow monoclinic single crystals. The
pyrazine ring adopts a pseudoenvelope conformation.
The deviations of the N(1), N(2), C(1), C(2), and C(3)
atoms from the mean plane are at most 0.075 Å, whereas
the sp3ꢀhybridized C(4) atom deviates from this plane by
0.560 Å (see Fig. 1). The bond lengths in the conjugation
system of the pyrazine ring C(3)=N(2)—C(2)=C(1)—N(1)
differ substantially from the standard C—C, C=C, C—N,
and C=N bond lengths and vary from 1.291(3) Å to
1.382(3) Å (Table 1). One ethoxy group of the diethoxyꢀ
phosphoryl fragment is thermally disordered in the site 2
with occupancies of 0.5. The P—C bond length (1.836(2) Å)
is close to the standard value. The overall geometry of the
dialkylphosphoryl substituent in the adduct is similar to
that observed for a series of dihydrobenzoazines prepared
earlier.23,24 The molecular packing consists of layers. The
interlayer interactions are characterized by the absence
of shortened contacts, whereas shortened intermolecular
π—π contacts between the cyano groups (the transformaꢀ
tion –х, –y, 1 – z; the interaction length is ~3.3 Å), the
1
characterized by H and 13C NMR spectroscopy.20 The
synthesis of 1,2ꢀdihydroꢀ and 1,4ꢀtetrahydropyrazines
by the addition of Oꢀ and Cꢀnucleophiles to 1ꢀalkylꢀ
2,3ꢀdicyanopyrazinium salts was also documented.21,22
Data on the involvement of Pꢀnucleophiles in the reacꢀ
tions with 1,4ꢀdiazines are lacking, although examples of
the addition of Pꢀnucleophiles to πꢀdeficient nitroarenes12
and azines23—26 were reported. The structures of the
Pꢀadducts of isoquinoline,23 phthalazine,24 and 4,7ꢀpheꢀ
nanthroline25,26 were established by Xꢀray diffraction.
The aim of the present study was to synthesize relaꢀ
tively stable addition products of diethyl and diphenyl
phosphonates to 1,4ꢀdiazinium salts, such as 5ꢀarylꢀsubꢀ
stituted 2,3ꢀdicyanoꢀ1ꢀethylpyrazinium tetrafluoroborates
1a,b and 3ꢀarylꢀ1ꢀmethylquinoxalinium iodides 2a,b
(Scheme 1). It was expected that the presence of an aryl
* Dedicated to Academician A. I. Konovalov on his 75th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 176—181, January, 2009.
1066ꢀ5285/09/5801ꢀ0176 © 2009 Springer Science+Business Media, Inc.

Addition of Pꢀnucleophiles to diazinium salts
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
177
Scheme 1
C(11)
C(16)
C(12)
C(10)
N(3)
C(5)
C(13)
N(2)
C(15)
C(14)
O(3)
C(3)
C(4)
C(2)
C(1)
O(1)
P(1)
C(6)
N(4)
N(1)
O(2)
C(17)
C(7)
C(18)
C(8)
Fig. 1. Geometry of molecule 4a in the crystal structure.
C(12)
C(14)
C(11)
O(3)
N(4)
C(10)
C(13)
N(1)
P(1)
C(1)
C(4)
O(1)
C(3)
O(2)
C(2)
C(9)
C(6)
S(1)
C(15)
C(16)
Comꢀ
pound
1a
1b
2a
2b
3a
3b
Ar
R
Comꢀ
pound
4a
4b
5a
5b
6a
6b
Ar
R
N(2)
C(8)
C(5)
N(3)
Ph
3ꢀthienyl
3ꢀNO2C6H4
3ꢀthienyl
—
—
—
—
—
Et
Ph
Ph
3ꢀthienyl
Ph
3ꢀthienyl
3ꢀNO2C6H4
3ꢀthienyl
Et
Et
Ph
Ph
—
—
C(7)
—
Fig. 2. Geometry of molecule 4b in the crystal structure.
Table 1. Selected bond lengths in compounds 4a and 4b based on
Xꢀray diffraction data
polar P(1)—O(1)...H—Csp (4) contacts (x, 0.5 – y, –0.5 + z;
3
~2.3 Å), the shortened Caр—H...N contacts (~2.6 Å, with
the CN group and the N(2) atom), and some other conꢀ
tacts are present within the layers.
Bond
d/Å
The main structural characteristics of compound 4b
(the crystal system, the space group, the unit cell paramꢀ
eters, the bond lengths, the molecular conformation, and
the packing mode) are, on the whole, similar to those
determined for the structure of 4a.
4а
4b
C(1)—N(1)
C(2)—C(1)
N(2)—C(2)
С(3)—N(2)
С(3)—С(4)
N(1)—C(4)
С(4)—Р(1)
P(1)—O(1)
1.359(3)
1.352(3)
1.381(3)
1.291(3)
1.538(3)
1.464(3)
1.836(3)
1.4681(16)
1.353(2)
1.360(2)
1.389(2)
1.2949(19)
1.521(2)
1.459(2)
The NMR data for σHꢀadducts of 1,4ꢀdiazinium
salts with Pꢀnucleophiles are lacking in the literature. A
1
comparative analysis of the H and 13C NMR spectra of
1.8271(15)
1.4585(11)
the Pꢀadducts, the spectra of the Oꢀ and CꢀσHꢀadducts
of 5ꢀarylꢀ and 5ꢀhetarylꢀ2,3ꢀdicyanoꢀ1ꢀethylpyrazinium
salts prepared previously,22 and the spectra of the already
known Oꢀadducts of pyrazinium and quinoxalinium salts20
showed that the chemical shifts of the sp3ꢀhybridized carꢀ
bon atom and the attached proton are in good agreement
with the theory27 and available data.20 Thus, the more
electronegative is the fragment bound to the sp3ꢀcarbon

178
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
Verbitskiy et al.
atom, the larger are the downfield shifts. For instance,
in the series of Oꢀ, Cꢀ, and Pꢀadducts (Table 2), the
chemical shifts of Csp3—H groups in the NMR spectra of
the Oꢀadducts are observed at the lowest field, whereas
the corresponding chemical shifts for the Pꢀadducts are
observed at the highest field, which is consistent with the
changes in the electronegativity in the series O > C ≈ P.28
Unlike the 1H NMR spectra of the Oꢀ and Cꢀadducts,
the spectra of the Pꢀadducts are characterized by a comꢀ
plex multiplet structure of the signals for the methylene
protons of the NEt group due not only to their nonꢀ
equivalence but also to the spinꢀspin coupling constants
with the phosphorus atom. This is also responsible for the
fact that the singlet of the hydrogen atom at C(2) characꢀ
teristic of Oꢀ and Cꢀadducts appears as a doublet in the
spectra of the Pꢀadducts. The 13C NMR spectra show
doubling of the signals giving rise to the corresponding
doublets with the firstꢀ to fourthꢀorder coupling constants
(see the Experimental section).
Earlier,29 we have studied the LC/MSꢀchromatoꢀ
graphic behavior of the Oꢀ and Cꢀadducts of 2,3ꢀdicyanoꢀ
1ꢀethylpyrazinium. The optimal conditions for LC/MS
experiments were found. The positiveꢀion atmospheric
pressure chemical ionization (APCI) is a method
of choice. Under these conditions, the Oꢀadducts of
2,3ꢀdicyanopyrazinium salts with water and alcohols
(7 and 8) were shown to eliminate the alkoxy group due to
thermal decomposition in the ion source (200—450 °C);
however, attempts to detect the molecular ion failed
(Scheme 2). The Oꢀadducts of quinoxalinium salts
1
H
Table 2. Proton and sp3ꢀcarbon chemical shifts in the H and 13C NMR spectra of the σ ꢀadducts prepared by the addition of Oꢀ,
Cꢀ, and Pꢀnucleophiles to 1ꢀalkylꢀ1,4ꢀdiazinium salts
Compound
Substituents
Solvent
δ
Ar
R
С(sp3)—Н
6.24
С(sp3)
73.28
Ph
H
DMSOꢀd6—1Н
CD3CN—13С
DMSOꢀd6
Ph
Ph
Me
Et
6.41
6.12
—
79.88
CD3CN
3ꢀNO2—С6Н4
3ꢀNO2—С6Н4
H
Me
DMSOꢀd6
CDCl3—1Н
DMSOꢀd6—13С
6.01
5.98
74.09
74.19
Ph
Me
Me
Me
DMSOꢀd6
CDCl3
5.85
5.76
5.65
—
—
53.83
4ꢀF—С6Н4
3ꢀThienyl
CD3CN—1Н
CDCl3—13С
CDCl3
Ph
OEt
OEt
OEt
5.78* (5.76)
5.74* (5.71)
5.66* (5.63)
—
—
—
4ꢀF—С6Н4
3ꢀThienyl
CDCl3
CD3CN
Ph
3ꢀThienyl
—
—
DMSOꢀd6
DMSOꢀd6
6.59
6.46
—
50.64
Ph
3ꢀThienyl
Ph
Et
Et
Ph
Ph
CDCl3
CDCl3
CDCl3
CDCl3
5.17
4.97
5.57
5.37
53.07
54.29
53.60
—
3ꢀThienyl
3ꢀNO2—С6Н4
3ꢀThienyl
Et
Et
DMSOꢀd6
DMSOꢀd6
5.77
5.41
—
—
* The major diastereomer.22

Addition of Pꢀnucleophiles to diazinium salts
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
179
Scheme 2
measured in CH3CN on a Shimadzu LCMSꢀ2010 quadrupole
LCꢀmass spectrometer equipped with a Supelco LCꢀ18 column
(4.6×250 mm) at a scan rate of 0.25 mL min–1. The atmospheric
pressure chemical ionization (APCI) or electrospray ionization
(ESI) was used; the working voltage was 4.5 kV; nitrogen was
used as the carrier gas; the flow rate was 2.5 L min–1. The
elemental analysis was carried out on an automated Perkin Elmer
PEꢀ2400 analyzer. The melting points were determined on
combined Boetius stages and are uncorrected. The flash chroꢀ
matography was performed with the use of silica gel Lancaster
0.040—0.063 mm (230—400 mesh).
The reaction progress was monitored and the purity of the
reaction products was checked by TLC on Sorbfil plates; spots
were visualized with UV light or I2 vapor.
The Xꢀray diffraction study was carried out on an automated
Xcaliburꢀ3 diffractometer equipped with a CCD detector at
295(2) К (λMoꢀKα, graphite monochromator, ωꢀscanning
technique). The Xꢀray data for compound 4a were collected
from a piece of a yellow plateꢀlike single crystal of dimensions
0.43×0.23×0.11 mm; for compound 4b, from a piece of a yellow
prismatic single crystal of dimensions 0.51×0.38×0.25 mm. The
absorption corrections were not applied. The structures were
solved by direct methods using the SHELXSꢀ97 program
package and refined with anisotropic (isotropic for hydrogen
atoms) displacement parameters with the use of the SHELXLꢀ97
program package.31,32 The hydrogen atoms were refined using a
riding model with fixed thermal parameters. The principal Xꢀray
diffraction data collection and refinement statistics are given
in Table 3. The results of the Xꢀray diffraction study were
deposited with the Cambridge Structural Database (deposition
numbers CCDC 714995 and 714996 for compounds 4a and 4b,
respectively).*
Synthesis of (3ꢀarylꢀ and 3ꢀhetarylꢀ5,6ꢀdicyanoꢀ1ꢀethylꢀ1,2ꢀ
dihydropyrazinꢀ2ꢀyl)phosphonic acid esters (general procedure).
A mixture of salt 1a or 1b (1 mmol) and diethyl (3a) or diphenyl
phosphonate (3b) (1 mmol) in CH3CN (5 mL) was stirred for
1 h. The solvent was distilled off in vacuo, and the residue was
separated on silica gel using elution with a 1 : 2 ethyl acetate—
benzene mixture.
Comꢀ
pound
7a
7b
7c
8a
8b
8c
X
R
Comꢀ
pound
9a
X
R
H
H
H
F
F
F
H
Me
Et
H
Me
Et
H
H
F
F
—
—
Me
OEt
Me
OEt
H
9b
10a
10b
11a
11b
Me
Diethyl (5,6ꢀdicyanoꢀ1ꢀethylꢀ3ꢀphenylꢀ1,2ꢀdihydropyrazinꢀ
2ꢀyl)phosphonate (4a). Yellowꢀorange crystalline powder,
m.p. 138—140 °C. The yield was 66%. Found (%): C, 57.97;
H, 5.41; N, 14.96. C18H21N4O3P. Calculated (%): C, 58.06;
behave analogously. In the case of Cꢀadducts 9 and 10,
only the expected ions corresponding to the protonated
form of the starting adduct were detected (see Scheme 2).
A different behavior is observed for the Pꢀadducts of
pyrazinium salts 4 and 5, which give primarily ions correꢀ
sponding to deprotonation, the molecular ion, and its
protonated form.
Hence, we showed that 2,3ꢀdicyanoꢀ1ꢀethylpyraziꢀ
nium and 1ꢀmethylquinoxalinium salts react with phosꢀ
phorus(V) derivatives to form stable Pꢀadducts, which were
characterized by H and 13C NMR spectroscopy and
1
H, 5.69; N, 15.05. H NMR (CDCl3), δ: 1.21 (t, 3 H, CH3,
J = 7.0 Hz); 1.26 (t, 3 H, CH3, J = 7.2 Hz); 1.33 (t, 3 H, CH3,
J = 7.1 Hz); 3.64 (m, 1 H, NCH); 3.74 (m, 1 H, NCH);
4.00—4.16 (m, 4 H, OCH2); 5.17 (d, 1 H, H(2), J = 14.2 Hz);
7.45—7.53 (m, 3 H, Ar); 7.97—7.99 (m, 2 H, Ar). 13C NMR
(CDCl3), δ: 14.33 (s, NCH2CH3); 16.21 (d, OCH2CH3,
3J = 5.8 Hz); 16.39 (d, OCH2CH3, 3J = 5.5 Hz); 49.39 (s,
NCH2); 53.07 (d, C(2), 1J = 162.1 Hz); 63.62 (d, OCH2,
2J = 7.4 Hz); 63.80 (d, OCH2, 2J = 7.6 Hz); 111.01 (s, CN
(C(5)); 112.20 (d, CN (C(6)), 4J = 2.0 Hz); 115.65 (d, C(5),
4J = 2.5 Hz); 118.67 (d, C(6), 3J = 3.2 Hz); 128.43 (d, Co—Ph,
4J = 9.3 Hz); 128.85 (s, Cm—Ph); 132.12 (s, Cp—Ph); 133.55 (d,
Cipso—Ph, 3J = 2.9 Hz); 143.59 (d, C(3), 2J = 4.1 Hz). 31P NMR
(162 MHz, CDCl3), δ: 15.27 (P(O)(OEt)2). LC/MS, m/z (I (%)):
372 [M – H]+ (100), 373 [M]+ (23), 374 [M + H]+ (3).
1
Xꢀray diffraction.
Experimental
The solvents and reagents were dried and purified according
to known procedures.30 The NMR spectra were recorded on a
Bruker DRXꢀ400 spectrometer (400 MHz for H, 100 MHz for
13C, and 162 MHz for 31P) with SiMe4 as the internal standard.
The negativeꢀ and positiveꢀion electrospray LC/MS were
1
* These data can be obtained, free of charge, on application to the
Cambridge Crystallographic Data Centre, www.ccdc.cam.ac.uk/
datarequest/sif.

180
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
Verbitskiy et al.
Table 3. Principal Xꢀray diffraction data collection and refineꢀ
ment statistics for compounds 4a,b
C26H21N4O3P•1/6C6H6 (PhH). Calculated (%): C, 66.98;
H, 4.58; N, 11.57. H NMR (CDCl3), δ: 1.31 (t, 3 H, CH3,
1
J = 7.2 Hz); 3.64 (m, 1 H, NCH); 3.80 (m, 1 H, NCH); 5.57 (d,
1 H, H(2), J = 13.4 Hz); 6.80—7.52 (m, 13 H, Ar); 8.03—8.06
(m, 2 H, Ar). 13C NMR (CDCl3), δ: 14.40 (s, NCH2CH3);
49.69 (s, NCH2); 53.60 (d, C(2), 1J = 162.6 Hz); 110.75 (s, CN
(C(5)), 5J = 1.0 Hz); 112.69 (d, CN (C(6)), 4J = 2.2 Hz); 115.21
(d, C(5), 4J = 2.7 Hz); 118.70 (d, C(6), 3J = 3.5 Hz); 119.70
(d, Ph, J = 4.6 Hz); 119.77 (d, Ph, J = 4.5 Hz); 125.86 (d, Ph,
J = 6.7 Hz); 128.40 (s, Ph); 129.08 (s, Ph); 130.05 (d, Co—Ph,
4J = 10.9 Hz); 132.42 (s, Ph); 133.39 (d, Cipso—Ph, 3J = 3.1 Hz);
143.05 (d, C(3), 2J = 4.6 Hz); 149.48 (d, Ph, J = 3.1 Hz); 149.58
(d, Ph, J = 2.6 Hz). 31P NMR (162 MHz, CDCl3), δ: 7.40
(P(O)(OPh)2). LC/MS, m/z (I (%)): 467 [M – H]+ (100), 468
[M]+ (36), 469 [M + H]+ (6).
Diphenyl [5,6ꢀdicyanoꢀ1ꢀethylꢀ3ꢀ(3ꢀthienyl)ꢀ1,2ꢀdihydroꢀ
pyrazinꢀ2ꢀyl]phosphonate (5b). Yellow powder, m.p. 111—113 °C.
The yield was 32%. Found (%): C, 61.07; H, 4.22; N, 11.67.
C24H19N4O3SP. Calculated (%): C, 60.75; H, 4.04; N, 11.81.
1H NMR (CDCl3), δ: 1.31 (t, 3 H, CH3, J = 7.2 Hz); 3.62 (m, 1 H,
NCH); 3.80 (m, 1 H, NCH); 5.37 (d, 1 H, H(2), J = 12.8 Hz);
6.96—7.34 (m, 10 H, Ar); 7.42 (dd, 1 H, H(5″), J = 5.2 Hz,
J = 2.8 Hz); 7.71 (dd, 1 H, H(4″), J = 5.2 Hz, J = 1.2 Hz); 7.97
(dd, 1 H, H(2″), J = 2.8 Hz, J = 1.2 Hz). 31P NMR (162 MHz,
CDCl3), δ: 7.20 (P(O)(OPh)2). LC/MS, m/z (I (%)): 473
[M – H]+ (100), 474 [M]+ (37), 475 [M + H]+ (10).
Parameter
4а
4b
Molecular formula
Molecular weight
Т/K
Crystal system
Space group
a/Å
b/Å
c/Å
C18H21N4O3P
372.36
295(2)
Monoclinic
P21/с
9.9595(9)
17.518(3)
11.374(2)
90.00
101.208(11)
90.00
1946.5(5)
4
1.271
C16H19N4O3PS
378.38
295(2)
Monoclinic
P21/с
9.6360(13)
17.8265(17)
11.1595(12)
90.00
100.462(10)
90.00
1885.1(4)
4
1.333
α/deg
β/deg
γ/deg
V/Å3
Z
dcalc
μ/мм–1
Scan range, θ/deg
Number of measured
reflections (Rint
Number of reflections
with I > 2σ
Number of refined
parameters
0.166
0.279
26.37 > θ > 2.75 32.52 > θ > 2.81
3833 (0.0890)
5916 (0.0340)
)
1375
2198
260
235
Synthesis of diethyl (3ꢀarylꢀ and 3ꢀhetarylꢀ1ꢀmethylꢀ
1,2ꢀdihydroquinoxalinꢀ2ꢀyl)phosphonates. A mixture of salt 2a
or 2b (1 mmol), diethyl phosphonate 3a (1 mmol), and NEt3
(1.1 mmol) in CH3CN (5 mL) was stirred for 1.5 h. The solvent
was distilled off in vacuo, and the residue was separated on silica
gel using elution with a 1 : 2 ethyl acetate—benzene mixture.
Diethyl [1ꢀmethylꢀ3ꢀ(3ꢀnitrophenyl)ꢀ1,2ꢀdihydroquinoxalinꢀ
2ꢀyl]phosphonate (6a). Yellow powder, m.p. 64—66 °C (decomp.).
The yield was 34%. Found (%): C, 56.41; H, 5.62; N, 10.50.
C19H22N3O5P. Calculated (%): C, 56.57; H, 5.50; N, 10.42.
1H NMR (DMSOꢀd6), δ: 0.89 (t, 3 H, CH3, J = 7.0 Hz); 0.95
(t, 3 H, CH3, J = 7.0 Hz); 3.09 (s, 3 H, CH3); 3.60—3.83 (m,
4 H, 2 OCH2); 5.77 (d, 1 H, H(2), J = 12.4 Hz); 6.74—6.80 (m,
2 H, Ar); 7.16—7.18 (m, 1 H, Ar); 7.29—7.31 (m, 1 H, Ar);
7.78—7.82 (m, 1 H, Ar); 8.34—8.36 (m, 1 H, Ar); 8.51—8.53
(m, 1 H, Ar); 8.90—8.91 (m, 1 H, Ar).
S
0.857
0.0497
0.0575
0.1972
0.996
0.0411
0.0832
0.1428
R1 (based on I > 2σ(I))
wR2 (based on I > 2σ(I))
R1 (based on all
reflections)
wR2 (based on all
reflections)
0.0698
0.0895
Residual electron density 0.176/–0.257
0.227/–0.414
/e Å–3, max/min
Diethyl [5,6ꢀdicyanoꢀ1ꢀethylꢀ3ꢀ(3ꢀthienyl)ꢀ1,2ꢀdihydroꢀ
pyrazinꢀ2ꢀyl]phosphonate (4b). Darkꢀyellow crystalline powder,
m.p. 136—138 °C. The yield was 69%. Found (%): C, 50.21;
H, 4.81; N, 14.48. C16H19N4O3SP•0.2H2O. Calculated (%):
C, 50.31; H, 5.12; N, 14.67. 1H NMR (CDCl3), δ: 1.24 (t, 3 H,
CH3, J = 7.2 Hz); 1.26 (t, 3 H, CH3, J = 7.3 Hz); 1.34 (t, 3 H,
CH3, J = 7.1 Hz); 3.56 (m, 1 H, NCH); 3.73 (m, 1 H, NCH);
4.03—4.16 (m, 4 H, OCH2); 4.97 (d, 1 H, H(2), J = 13.6 Hz);
7.38 (dd, 1 H, H(5″), J = 5.2 Hz, J = 2.9 Hz); 7.66 (dd, 1 H,
H(4″), J = 5.2 Hz, J = 1.3 Hz); 7.91 (dd, 1 H, H(2″), J = 2.8 Hz,
J = 1.3 Hz). 13C NMR (CDCl3), δ: 14.18 (d, NCH2CH3,
4J = 7.2 Hz); 16.24 (d, OCH2CH3, 3J = 5.8 Hz); 16.39 (d,
OCH2CH3, 3J = 5.6 Hz); 49.27 (s, NCH2); 54.29 (d, C(2),
1J = 162.2 Hz); 63.63 (d, OCH2, 2J = 7.4 Hz); 63.83 (d, OCH2,
2J = 7.6 Hz); 111.06 (s, CN (C(5)); 112.03 (d, CN (C(6)),
4J = 1.9 Hz); 115.68 (d, C(5), 4J = 2.4 Hz); 118.30 (d, C(6),
3J = 3.3); 126.96 (s, C(4″)—thienyl); 127.26 (s, C(5″)—thienyl);
Diethyl [1ꢀmethylꢀ3ꢀ(3ꢀthienyl)ꢀ1,2ꢀdihydroquinoxalinꢀ
2ꢀyl]phosphonate (6b). Yellow oil. The yield was 39%. Found (%):
56.09; H, 5.74; N, 7.45. C17H21N2O3SP. Calculated (%):
1
C, 56.03; H, 5.81; N, 7.69. H NMR (DMSOꢀd6), δ: 0.93 (m,
6 H, CH3); 3.05 (s, 3 H, CH3); 3.53—3.78 (m, 4 H, 2 OCH2);
5.41 (d, 1 H, H(2), J = 11.7 Hz); 6.69—6.76 (m, 2 H, Ar);
7.09—7.19 (m, 2 H, Ar); 7.60—7.71 (m, 2 H, Ar); 8.21 (dd, 1 H,
H(2″), J = 2.8 Hz, J = 1.1 Hz).
1ꢀMethylꢀ3ꢀ(3ꢀnitrophenyl)ꢀ1,2ꢀdihydroquinoxalinꢀ2ꢀol (11a).
A mixture of salt 1b (100 mg, 0.254 mmol) and Na2CO3 (32 mg,
0.304 mmol) in H2O (3 mL) was stirred for 1 h. The precipitate
that formed was recrystallized from acetonitrile. A yellow powder
with m.p. 116—118 °C was obtained. The yield was 67 mg (93%).
Found (%): C, 63.48; H, 4.54; N, 14.62. C15H13N3O3. Calcuꢀ
lated (%): C, 63.60; H, 4.63; N, 14.83. 1H NMR (DMSOꢀd6), δ:
3.19 (s, 3 H, NCH3); 6.01 (s, 1 H, Het—H); 6.51 (s, 1 H, Het—OH);
6.88—6.92 (m, 2 H, Ar); 7.27—7.30 (m, 1 H, Ar); 7.40—7.44
(m, 1 H, Ar); 7.49—7.50 (m, 1 H, Ar); 8.31—8.33 (m, 1 H, Ar);
8.47—8.49 (m, 1 H, Ar); 8.84—8.85 (m, 1 H, Ar). 13C NMR
3
130.06 (s, C(2″)—thienyl); 137.88 (d, C(3″)—thienyl, J = 2.8 Hz);
139.69 (d, C(3), 2J = 3.7 Hz). 31P NMR (162 MHz, CDCl3), δ:
15.04 (P(O)(OEt)2). LC/MS, m/z (I (%)): 377 [M – H]+ (100),
378 [M]+ (21), 379 [M + H]+ (8).
Diphenyl (5,6ꢀdicyanoꢀ1ꢀethylꢀ3ꢀphenylꢀ1,2ꢀdihydropyrazinꢀ
2ꢀyl)phosphonate (5a). Yellow powder, m.p. 114—116 °C. The
yield was 45%. Found (%): C, 67.22; H, 4.49; N, 11.43.

Addition of Pꢀnucleophiles to diazinium salts
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 1, January, 2009
181
(DMSOꢀd6), δ: 34.89 (s, NCH3); 74.09 (s, Csp3); 112.00 (s, Ar);
117.99 (s, Ar); 121.26 (s, Ar); 124.36 (s, Ar); 128.15 (s,
Ar); 129.28 (s, Ar); 130.175 (s, Ar); 132.23 (s, Ar); 133.05
(s, Ar); 136.18 (s, Ar); 138.04 (s, Ar); 148.18 (s, Ar); 151.44 (s,
Ar). LS/MS, m/z (I (%)): 266 [M – OH]+ (100).
13. V. N. Charushin, O. N. Chupakhin, Mendeleev Commun.,
2007, 17, 249.
14. V. N. Charushin, O. N. Chupakhin, Pure Appl. Chem., 2004,
76, 1621.
15. A. V. Gulevskaya, A. F. Pozharskii, Adv. Heterocycl. Chem.,
2007, 93, 57.
16. D. V. Besedin, A. V. Gulevskaya, A. F. Pozharskii, Chem.
Heterocycl. Compd., 2000, 36, 10, 1213.
17. A. V. Gulevskaya, A. F. Pozharskii, Chem. Heterocycl.
Compd., 2001, 37, 12, 1461.
18. A. V. Gulevskaya, D. V. Besedin, A. F. Pozharskii, Z. A.
Starikova, Tetrahedron Lett., 2001, 42, 5981.
19. A. V. Gulevskaya, O. V. Serduke, A. F. Pozharskii, D. V.
Besedin, Tetrahedron, 2003, 59, 7669.
20. O. N. Chupakhin, V. N. Charushin, A. R. Chernyshev, Prog.
Nucl. Magn. Res. Spectr., 1988, 20, 95.
2ꢀMethoxyꢀ1ꢀmethylꢀ3ꢀ(3ꢀnitrophenyl)ꢀ1,2ꢀdihydroquinoxaꢀ
line (11b). A mixture of salt 1b (100 mg, 0.254 mmol) and NEt3
(42 μl, 0.304 mmol) in methanol (3 mL) was stirred for 1 h. The
precipitate that formed was recrystallized from acetonitrile.
A yellow powder with m.p. 103—104 °C was obtained. The yield
was 67 mg (85%). Found (%): C, 64.32; H, 4.85; N, 14.19.
C16H15N3O3. Calculated (%): C, 64.64; H, 5.09; N, 14.13.
1H NMR (CDCl3), δ 2.95 (s, 3 H, NCH3); 3.34 (s, 3 H, OCH3);
5.98 (s, 1 H, Het—H); 6.90—7.00 (m, 2 H, Ar); 7.32—7.34 (m,
1 H, Ar); 7.60—7.67 (m, 2 H, Ar and Het); 8.28—8.30 (m, 1 H,
Het); 8.47—8.49 (m, 1 H, Het); 8.95—8.97 (m, 1 H, Het).
13C NMR (DMSOꢀd6), δ: 34.93 (s, NCH3); 74.19 (s, Csp3);
112.12 (s, Ar); 118.12 (s, Ar); 121.38 (s, Ar); 124.45 (s, Ar);
128.18 (s, Ar); 129.36 (s, Ar); 130.18 (s, Ar); 132.35 (s,
Ar); 133.25 (s, Ar); 136.27 (s, Ar); 138.15 (s, Ar); 148.23 (s, Ar);
151.52 (s, Ar). LC/MS, m/z (I (%)): 266 [M – OCH3]+ (100).
21. P. A. Slepukhin, N. N. Mochul´skaya, L. P. Sidorova, G. L.
Rusinov, M. A. Ezhikova, M. I. Kodess, O. N. Kazheva,
A. N. Chekhlov, O. A. D´yachenko, V. N. Charushin, Izv.
Akad. Nauk, Ser. Khim., 2005, 2132 [Russ. Chem. Bull., Int.
Ed., 2005, 54, 2197].
22. E. V. Verbitskiy, G. L. Rusinov, P. A. Slepukhin, A. N.
Grishakov, M. A. Ezhikova, M. I. Kodess, V. N. Charushin,
Zh. Org. Khim., 2008, 44, 305 [Russ. J. Org. Chem. (Engl.
Transl.), 2008, 44].
23. M. Haase,W. Günther, H. Görls, E. Anders, Synthesis, 1999,
2071.
This study was financially supported by the Russian
Foundation for Basic Research (Project Nos 07ꢀ03ꢀ12112ꢀofi,
07ꢀ03ꢀ96113ꢀr_ural_a, and 07ꢀ03ꢀ96123ꢀr_ural_a) and
the Council on Grants of the President of the Russian Federaꢀ
tion (Program for State Support of Leading Scientific
Schools of the Russian Federation, Grant NShꢀ3758.2008.3).
24. I. Takeuchi, Y. Hamada, Y. Kurono, T. Yashiro, Chem.
Pharm. Bull., 1990, 38, 1504.
25. I. Takeuchi, Y. Shibata, Y. Hamada, M. Kido, Heterocycles,
1986, 24, 647.
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Received July 7, 2008;
in revised form November 11, 2008