Reactions of pyrazinium salts with phenols: From σh- adducts to SN H products and transformations into benzo[b]furans

Article abstract of DOI:10.1007/s11172-011-0144-5

The reaction of 5-(het)aryl-2,3-dicyano-1-ethylpyrazinium salts with phenol derivatives affords relatively stable dihydropyrazines, whereas the reactions of 6-(het)aryl-1,2,5-oxadiazolo[3,4-b]pyrazin-4-ium protic salts, depending on the phenol structure,

Full text of DOI:10.1007/s11172-011-0144-5

Russian Chemical Bulletin, International Edition, Vol. 60, No. 5, pp. 919—928, May, 2011
919
Reactions of pyrazinium salts with phenols: from σНꢀadducts
Н
to SN products and transformations into benzo[b]furans
E. V. Verbitskiy,a Yu. A. Kvashnin,a P. A. Slepukhin,a A. V. Kuchin,b G. L. Rusinov,a
O. N. Chupakhin,a and V. N. Charushina
аI. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
22 ul. S. Kovalevskoi, 620041 Ekaterinburg, Russian Federation.
Еꢀmail: Verbitsky@ios.uran.ru
bInstitute of Chemistry, Komi Research Center, Russian Academy of Sciences,
48 ul. Pervomaiskaya, 167982 Syktyvkar, Russian Federation.
Еꢀmail: Kutchinꢀav@chemi.komisc.ru
The reaction of 5ꢀ(het)arylꢀ2,3ꢀdicyanoꢀ1ꢀethylpyrazinium salts with phenol derivatives
affords relatively stable dihydropyrazines, whereas the reactions of 6ꢀ(het)arylꢀ1,2,5ꢀoxadiazoꢀ
lo[3,4ꢀb]pyrazinꢀ4ꢀium protic salts, depending on the phenol structure, result in products of
nucleophilic substitution of hydrogen or openꢀchain transformation products: benzo[b]furanꢀ
substituted derivatives. The crystallographic data on the spatial structure of all types of the
synthesized products were obtained.
Н
Key words: pyrazinium salts, phenols, 1,2ꢀdihydropyrazines, σ ꢀadducts, nucleophilic subꢀ
stitution of hydrogen (SNH).
Azinium salts are active heteroaromatic substrates
capable of chemical modifying under relatively mild condiꢀ
tions.1—12 Depending on the structure of the initial aziniꢀ
um salt, the nature of the attacking nucleophile, and reacꢀ
tion conditions, azinium salts can transform into σНꢀadꢀ
ducts and products of nucleophilic substitution of hydroꢀ
gen SNH or undergo deeper transformations (Scheme 1).
ucts of nucleophile addition to unsubstituted positions of
the heterocycle.
In the present work, we studied the possibility of using
substituted phenols as nucleophiles. It is known that the
phenol derivatives are efficient antioxidants. Among the
modern inhibitors of freeꢀradical oxidation of organic and
bioorganic substrates, antioxidants of the phenol type play
the leading role: stabilizers of plastics, rubbers, and caꢀ
outchoucs; the most part of food antioxidants and drugs
with antioxidant effect are also phenol compounds.13—24
It seemed interesting to study the possibility of direct crossꢀ
coupling of 1,4ꢀdiazinium systems with phenol derivatives
aimed at developing new types of compounds with antioxꢀ
idant activity.
Scheme 1
There are published data on the reactions of 1,2,4ꢀtriꢀ
azinium and 1,3ꢀdiazinium salts with resorcinol.25—28 Inꢀ
formation on the reactions of pyrazinium salts with pheꢀ
nol derivatives are almost absent, and only the single
example of the reaction of 2,3ꢀdichloroꢀ1ꢀethylpyraziniꢀ
um with resorcinol was described.29 In particular, it was
shown that protic salts of 3ꢀsubstituted 1,2,4ꢀtriazines 1
are transformed into benzofurotriazines 2, whereas the
reaction of azolopyrimidinium salts 3 with resorcinol is
completed by the formation of framework structures, deꢀ
rivatives of oxazocines 4 (Scheme 2).
X, Y = CH, N
EWG is electronꢀwithdrawing group, Nu is nucleophile
We have earlier carried out the series of works on studyꢀ
ing the properties of substituted pyrazinium salts.6—12 It
was shown that they are capable of reacting with various
types of nucleophiles under mild conditions to form prodꢀ
In this work, quaternary salts of 5ꢀ(het)arylꢀ2,3ꢀdiꢀ
cyanoꢀ1ꢀethylpyrazinium 5a,b and protic salts of 1,2,5ꢀ
oxadiazolo[3,4ꢀb]pyrazinium were chosen as substrates.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 898—906, May, 2011.
1066ꢀ5285/11/6005ꢀ919 © 2011 Springer Science+Business Media, Inc.

920
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
Verbitskiy et al.
Scheme 2
C(18)
C(19)
N(3)
C(4)
C(3)
C(17)
C(16)
N(4)
C(6)
C(20)
C(21)
C(5)
C(7)
C(2)
C(8)
O(2)
C(9)
C(1)
N(1)
C(14)
C(13)
O(3)
N(2)
C(10)
C(12)
O(1)
C(11)
C(15)
X, Y, Z = CH, N
Salts of 5ꢀ(het)arylꢀ2,3ꢀdicyanoꢀ1ꢀethylpyrazinium
Fig. 1. Xꢀray structure of compound 15a.
5a,b were shown to react easily with resorcinol (6), pyroꢀ
gallol (7), phloroglucinol (8) and its trimethyl ester (9),
and natural antioxidant sesamol (10) under mild
conditions (CH3CN, 20—25 °C), giving σНꢀadducts
11a,b—15a,b to the position С(6) (Scheme 3). The strucꢀ
tures of synthesized 1,2ꢀdihydropyrazines 11—15 were unꢀ
ambiguously confirmed by Xꢀray diffraction data (Fig. 1,
Tables 1 and 2).
According to the Xꢀray diffraction data, adducts 11а,
12а, 14а, and 15а crystallize in centrosymmetric space
groups of various crystallographic systems (see Table 1).
The general geometry of the dihydroazine fragments of
the obtained adducts is close to the geometry of the adꢀ
ducts studied earlier8—12 and is determined by the presꢀ
ence of the system of conjugated multiple bonds of the
cyano groups and dihydroazine cycle. Compounds 11а
and 12а are characterized by the transꢀorientation of the
polyhydroxyarene fragment and group N—Et relative to
the rootꢀmeanꢀsquare plane of dihydroazine; compounds
14а and 15а are characterized by cisꢀorientation. Stereꢀ
ometry of the molecular packing is determined by the presꢀ
ence of the system of intramolecular hydrogen bonds and
intermolecular hydrogen bonds (see Table 1) and a series
of shortened contacts. So, the crystals of compounds 11а
and 15а contain intermolecular hydrogen bonds
O—H...N≡С— joining the molecules into polymer chains
of similar geometry. The orientation of the chain of
molecules of compound 11а coincides with the translaꢀ
tion chain 0b, and the chains of compounds 15а lie on
the sliding refection planes. The most developed sysꢀ
tem of hydrogen bonds is observed in the packing of
compound 12а. It includes intramolecular hydrogen bonds
О—Н...О in the polyhydroxyaryl substituent and inꢀ
termolecular hydrogen bonds between the OH and СN
groups and the nitrogen atom of the dihydroazine cycle.
As a result, a packing as double chains of molecules paralꢀ
lel to the axis а—b is formed. The molecules of the chains
are brought together, and the shortened π—πꢀcontact (the
distance between the atoms С(15)...С(15) [–x, –y, 1 – z]
is 3.370 Å) is observed between the polyhydroxyaryl
fragments.
Scheme 3
Ar = Ph (a), thiophenꢀ3ꢀyl (b)
6, 11: R1 = R2 = R4 = R5 = H, R3 = OH
7, 12: R1 = R4 = R5 = H, R2 = R3 = OH
8, 13: R1 = R2 = R4 = H, R3 = R5 = OH
9, 14: R1 = Me, R2 = R4 = H, R3 = R5 = OMe

Reactions of pyrazinium salts with phenols
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
921
Table 1. Parameters of hydrogen bonds D—H...A in molecular packings according to the Xꢀray diffraction data
Comꢀ
pound
D—H
d(D—H)
d(H...A)
d(D...A)
D—H—A
/deg
A
Å
11a
12a
O(2)—H(2)
O(1)—H(1)
O(3)—H(3)
O(3)—H(3)
O(1)—H(1)
O(2)—H(2)
O(2)—H(2)
O(1)—H(1)
O(2)—H(2)
N(2)—H(2)
N(4)—H(4B)
N(4)—H(4A)
O(1S)—H(1S)
O(1S)—H(1S)
N(2)—H(2A)
0.82(3)
0.86(3)
0.96(3)
0.96(3)
0.87(3)
0.92(3)
0.92(3)
0.91(3)
0.75(3)
0.80(2)
0.84(3)
0.89(2)
0.91(3)
0.91(3)
0.860
1.92(3)
2.03(3)
2.14(3)
2.23(3)
2.03(3)
2.21(3)
2.29(3)
1.96(3)
2.45(3)
2.17(2)
2.24(3)
2.14(3)
2.03(3)
2.58(3)
2.297
2.736(3)
2.884(3)
3.025(3)
2.719(3)
2.895(3)
2.700(3)
3.093(3)
2.862(3)
2.969(2)
2.961(3)
3.065(3)
3.006(4)
2.880(3)
3.291(3)
3.065(7)
177(1)
174(1)
153(1)
110(1)
170(1)
113(1)
146(1)
174(1)
128(1)
169(2)
169(2)
163(2)
154(3)
135(2)
148.82
O(2S)
N(3) [x, y – 1, z]
N(4) [x – 1/2, y + 1/2, z]
O(2)
N(3) [–x + 1/2, –y – 1/2, –z + 1]
O(1)
N(2) [x, y + 1, z]
15a
36а
45а
N(3) [x + 1, –y + 1/2, z – 1/2]
N(2) [x, –y + 3/2, z + 1/2]
O(1S)
N(3) [–x + 3/2, y – 1/2, –z – 1/2]
O(1S)
N(1) [x, y – 1, z]
O(2) [x, y – 1, z]
N(4) [–x + 1/2, y + 1/2, –z – 1/2]
46а
Attempts to carry out similar reactions with unsubstiꢀ
tuted 2,3ꢀdicyanoꢀ1ꢀethylpyrazinium salt and with
5ꢀ(het)arylꢀ1,2,5ꢀoxadiazolo[3,4ꢀb]pyrazines 16a,b in the
presence of CF3COOH were unsuccessful, because they
resulted in complicated multicomponent mixtures (acꢀ
cording to the TLC data).
The products of the reactions of 5ꢀ(het)arylꢀ1,2,5ꢀoxaꢀ
diazolo[3,4ꢀb]pyrazines 16a,b (Scheme 4) with sterically
hindered phenols 18—20, their methyl esters 9 and 21, 23,
24, and 2ꢀnaphthol (25) and its methyl ester 22 depend on
the structure of reacting phenol.
In the reactions with 2,6ꢀdimethylꢀ (18), 2,6ꢀdiꢀtertꢀ
butylꢀ (19), and 2ꢀisobornylꢀ6ꢀmethylphenols (20), as well
as with dimethyl ester of resorcinol (21), trimethyl ester of
phloroglucine (9), and methyl ester of 2 naphthol (22),
1,2ꢀdihydropyrazines 26—31 are spontaneously oxidized
with air oxygen to the corresponding aromatic SNH prodꢀ
ucts 35—36a,b, 37а, and 38—40a.
At the same time, the reactions of 2,4ꢀdiꢀtertꢀbutylꢀ
phenol (23), 2ꢀisobornylꢀ4ꢀmethylphenol (24), and
naphthol (25) gave unexpected benzo[b]furan derivatives
as products: Nꢀ(2ꢀ(het)arylꢀ5,7ꢀdiꢀtertꢀbutylbenzofuranꢀ
3ꢀyl)furazanꢀ3,4ꢀdiamines 44a,b, Nꢀ(5ꢀisobornylꢀ7ꢀmeꢀ
thylꢀ2ꢀphenylbenzofuranꢀ3ꢀyl)furazanꢀ3,4ꢀdiamine 45a,
and Nꢀ(2ꢀ(het)arylnaphtho[2,1ꢀb]furanꢀ1ꢀyl)furazanꢀ3,4ꢀ
diamines 46a,b. Their formation can be explained by the
further transformations of 1,2ꢀdihydropyrazines 32—34a,b
formed at the first stage into the corresponding 1,2,3,4ꢀ
tetrahydropyrazines 41—43a,b, which are transformed, in
turn, into benzofuran derivatives 44—46 due to tetraꢀ
hydropyrazine ring opening (see Scheme 4). It is most
probable that the reactions of furazanopyrazinium protic
salts with polyphenols proceed through the intermediate
formation of Cꢀadducts 26—34 to the position C(5); howꢀ
ever, σНꢀadducts 26—34 are unstable and undergo further
transformations.
The differences in the behavior of the σНꢀadducts can
be explained by their structure. Phenols with the unsubstiꢀ
tuted orthoꢀposition to the OH group act as 1,3ꢀC,Оꢀdiꢀ
nucleophiles and produce the corresponding monoadducts
32—34, which undergo further transformations into more
stable benzofurans 41—43. In the case of phenols having
no free orthoꢀposition to the OH group or their methyl
esters. monoadducts are formed and their further stabiliꢀ
zation occurs due to the formation of aromatic furazanoꢀ
pyrazines 35—40.
As shown previously,8 Nꢀethyl salts of 2,3ꢀdicyanoꢀ
pyrazinium are characterized by comparatively stable
monoadducts and, hence, the reactions cease at the stage
of formation of 1,2ꢀdihydropyrazines 11—15.
H
The structures of SN product 36а and openꢀchain
compounds 45а and 46а were confirmed by the Xꢀray
diffraction data. The general views of the molecules
are presented in Figs 2 and 3. The main parameters
of structural experiments are listed in Table 2. Compound
36а crystallizes in the centrosymmetric space group of
orthorhombic crystal system. The phenyl and hydroxyꢀ
phenyl substituents of the azine cycle exhibit nonꢀcoplaꢀ
nar unfolding relative to the pyrazine cycle plane due to
the steric influence of the tertꢀbutyl groups. The molecular
packing is characterized by the intermolecular hydrogen
bonds between the OH group of the hydroxyphenyl subꢀ
stituent and the nitrogen atom of the azine cycle, due
to which the molecules are packed into polymer ribbons
extended along the axis 0с. In this case, shortened
π—πꢀcontacts (the distance С(4)...С(4) [–х, 1 – у, –z]
is 3.292(3) Å, which is 0.108 Å shorter than the sum of van
der Waals radii) appear between the 1,2,5ꢀoxadiazoꢀ

922
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
Verbitskiy et al.
Scheme 4
Ar = Ph (a), 3ꢀthienyl (b)
18, 26, 35: R1 = R2 = Me
19, 27, 36: R1 = R2 = But
20, 28, 37: R1 = Me, R2
=

Reactions of pyrazinium salts with phenols
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
923
and the oxadiazole fragment is unfolded at an angle of
69.5°. The molecules are packed into polymer spiral
ribbons arranged on the screw 2ꢀfold axis by intermolecuꢀ
lar hydrogen bonds of the N—H...N type (see Table 1).
A rather unusual N—H...π contact is observed between
molecules of the ribbons between the secondary amino
group of the molecule and one of the rings of the naphꢀ
thalene system (the distance from the centroid
С(4)С(5)С(6)С(7)С(8)С(9) [x, –1 + y, z] to the atom
N(1) is 3.309(7) Å and that to the atom Н(1) is 2.40(6) Å;
contact angle 152(3)°, which is comparable with the hydroꢀ
gen bond parameters).
Thus, tandem reactions giving the products of 1,4ꢀdiꢀ
azine ring opening are discovered in the reactions of
pyrazinium salts with polyphenols along with the formaꢀ
tion of comparatively stable Cꢀadducts at the activated
С=N bond or the products of aromatic hydrogen nucleoꢀ
philic substitution. The reaction proceeds via one of the
possible routes depending on the nature and arrangement
of substituents in the phenol derivatives.
C(17)
C(25)
C(18)
C(19)
C(23)
C(16)
C(15)
C(24)
O(2)
C(13)
C(10)
C(14)
C(2)
C(9)
C(8)
N(2)
C(5)
C(6)
N(1)
C(21)
C(1)
C(7)
C(12)
C(3)
N(3)
O(1)
C(22)
C(4)
N(4)
C(20)
Fig. 2. General view of compound 36а in thermal ellipsoids of
50% probability according to the Xꢀray diffraction data.
lo[3,4ꢀb]pyrazine fragments of molecules of the adjaꢀ
cent chains.
Experimental
Compound 45а crystallizes in the centrosymmetric
space group of monoclinic crystal system as a solvate with
an EtOH molecule (Table 2). The phenyl substituent of
the benzofuran fragment is unfolded relative to its plane at
an angle of 13.0°, and the oxadiazole fragment is unfolded
at an angle of 73.2°. The molecular packing is characterꢀ
ized by the system of intermolecular hydrogen bonds inꢀ
volving the ОН group of EtOH, the NH2 group, and the
nitrogen atoms of the oxadiazole cycle (see Table 2), due
to which the molecules are packed into polymer ribbons
extended along the axis 0b.
The low quality of the crystal of compound 46а preꢀ
sented for Xꢀray diffraction analysis allows only rough
estimation of its structure to perform. Compound 46а crysꢀ
tallizes in the centrosymmetric space group of monoclinic
crystal system. The phenyl substituent of the benzofuran
cycle is unfolded relative to its plane at an angle of 14.5°,
Solvents and reagents were dried and purified according to
the literature procedures.30 The initial compounds 5a,b and 16a
were synthesized according to procedures described earlier.8,31
1Н NMR spectra were recorded on a Bruker DRXꢀ400 inꢀ
strument with a working frequency of 400 MHz using SiMe4 as
an internal standard. Elemental analysis was carried out on
a Perkin—Elmer PEꢀ2400 automated analyzer. Melting points
were determined on Boetius combined heating stages and no
corrections were applied. Flash chromatography was carried out
using silica gel Lancaster 0.040—0.063 mm (230—400 mesh).
The reaction course and purity of the products were moniꢀ
tored by TLC on the plates Sorbfil developing under UV irradiaꢀ
tion or I2 vapors.
The Xꢀray diffraction studies were carried out on an Xcaliꢀ
burꢀ3 Xꢀray diffractometer with a CCD detector using a stanꢀ
dard procedure (λMoꢀKα, graphite monochromator, ω scan
mode). The structures of all compounds were solved by a direct
method using the SHELXSꢀ97 program and refined using the
SHELXLꢀ97 program in the anisotropic (isotropic for hydrogen
atoms) approximation.32 No absorption correction was applied.
Selected parameters of structural experiments are listed in Table 2.
The results of Xꢀray diffraction studies* were deposited with the
Cambridge Crystallographic Data Centre as cif files (CCDC Nos
816 956 (compound 11а), 816 957 (compound 12а), 816 959
(compound 14а), 816 958 (compound 15а), 816 961 (compound
36а), 816 962 (compound 45а), and 816 960 (compound 46а).**
5ꢀ(3ꢀThienyl)ꢀ1,2,5ꢀOxadiazolo[3,4ꢀb]pyrazine (16b).
3,4ꢀDiaminofurazan (1 g, 10 mmol) and 3ꢀthienylglyoxal (1.4 g,
C(16)
C(15)
C(17)
C(16)
C(18)
C(21)
C(27)
C(25)
C(20)
C(23)
C(6)
C(11)
N(4)
N(2)
C(2)
C(1)
C(4)
C(3)
C(13)
C(14)
C(26)
C(22)
C(7)
C(9)
N(3)
N(1)
C(5)
* The Xꢀray diffraction results were obtained for seven comꢀ
pounds. However, only three significant figures are presented in
the article because of their resemblance and low information
content.
O(2)
C(10)
C(12)
C(24)
Fig. 3. General view of compound 45а according to the Xꢀray
diffraction data.
** These materials are available free of charge and can be reꢀ
quested at www.ccdc.cam.ac.uk/data_request/cif.

924
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
Verbitskiy et al.

Reactions of pyrazinium salts with phenols
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
925
10 mmol) were refluxed for 1 h in a mixture of EtOH (4 mL) and
glacial acetic CH3COOH (4 mL). At the end of the reaction, the
mixture was cooled down, and the precipitate that formed was
filtered off and washed with ethanol. The product was obtained
as a dark yellow crystalline powder. The yield was 68%, m.p.
166—168 °С. 1Н NMR (DMSOꢀd6), δ: 7.86 (dd, 1 Н, H(5″)ꢀ3ꢀ
thienyl, J = 5.2 Hz, J = 2.8 Hz); 8.01 (dd, 1 Н, H(4″)ꢀ3ꢀthienyl,
J = 5.2 Hz, J = 1.2 Hz); 9.05, 7.81 (both dd, 1 Н, H(2″)ꢀ3ꢀ
thienyl, J = 2.8 Hz, J = 1.2 Hz); 9.76 (s, 1 H, С6(H)). Found (%):
C, 47.15; Н, 2.03; N, 27.64. С8Н4N4ОS. Calculated (%):
C, 47.05; Н, 1.97; N, 27.44.
Synthesis of 6ꢀsubstituted 5ꢀ(het)arylꢀ1ꢀethylꢀ1,6ꢀdihydroꢀ
pyrazineꢀ2,3ꢀdicarbonitriles 11a,b—15a,b (general procedure).
A solution of salt 5а or 5b (1.2 mmol) and phenol derivative 6 or
7—10 (1 mmol) in anhydrous MeCN (5—7 mL) was stirred for
1 h at room temperature, the solvent was distilled in vacuo, and
the residue was chromatographed eluting with an ethyl aceꢀ
tate—hexane (1 : 1) mixture. If necessary, the obtained product
was additionally recrystallized from an EtOH—H2O (1 : 1) mixture.
6ꢀ(2,4ꢀDihydroxyphenyl)ꢀ1ꢀethylꢀ5ꢀphenylꢀ1,6ꢀdihydropyrꢀ
azineꢀ2,3ꢀdicarbonitrile (11a). Product 11a was obtained as an
orange crystalline powder. The yield was 95%, m.p. 198—201 °С
(decomp.).1Н NMR (CD3CN), δ: 1.20 (t, 3 Н, СН3, J = 7.2 Hz);
3.58 (dq, 1 Н, NCHA, J = 14.4 Hz, J = 7.2 Hz); 3.71 (dq, 1 Н,
NCHB, J = 14.4 Hz, J = 7.2 Hz); 6.19 (s, 1 Н, C(6)Н); 6.27 (dd,
1 Н, Сarom(Н(5´)), J = 8.5 Hz, J = 2.4 Hz); 6.40 (d, 1 Н,
Сarom(Н(3´)), J = 2.4 Hz); 6.84 (d, 1 Н, Сarom(Н(6´)), J = 8.5 Hz);
7.11 (s, 1 Н, ОН); 7.39—7.46 (m, 3 Н, Ph); 7.71 (s, 1 Н, ОН);
7.86—7.88 (m, 2 Н, Ph). Found (%): C, 67.57; Н, 4.99; N, 15.61.
С20Н16N4O2•0.67 H2O. Calculated (%): C, 67.42; Н, 4.89;
N, 15.73.
6ꢀ(2,4ꢀDihydroxyphenyl)ꢀ1ꢀethylꢀ5ꢀ(3ꢀthienyl)ꢀ1,6ꢀdihydroꢀ
pyrazineꢀ2,3ꢀdicarbonitrile (11b) was obtained as a yellow crysꢀ
talline powder. The yield was 95%, m.p. 180—182 °С (decomp.).
1Н NMR (CD3CN), δ: 1.19 (t, 3 Н, СН3, J = 7.2); 3.53 (dq, 1 Н,
NCHA, J = 14.4 Hz, J = 7.2 Hz); 3.59 (dq, 1 Н, NCHB, J = 14.4 Hz,
J = 7.2 Hz); 6.07 (s, 1 Н, C(6)Н); 6.30 (dd, 1 Н, Сarom(Н(5´)),
J = 8.5 Hz, J = 2.4 Hz); 6.38 (d, 1 Н, Сarom(Н(3´)), J = 2.4 Hz);
6.91 (d, 1 Н, Сarom(Н(6´)), J = 8.5 Hz); 7.12 (s, 1 Н, ОН); 7.27
(dd, 1 Н, H(5″)ꢀ3ꢀthienyl, J = 5.2 Hz, J = 2.8 Hz); 7.58 (dd, 1 Н,
H(4″)ꢀ3ꢀthienyl, J = 5.2 Hz, J = 1.3 Hz); 7.71 (s, 1 Н, ОН); 7.87
(dd, 1 Н, H(2″)ꢀ3ꢀthienyl, J = 2.8 Hz, J = 1.3 Hz). Found (%):
C, 61.36; Н, 4.06; N, 15.79. С18Н14N4О2S. Calculated (%):
C, 61.70; Н, 4.03; N, 15.99.
6ꢀ(2,3,4ꢀDihydroxyphenyl)ꢀ1ꢀethylꢀ5ꢀphenylꢀ1,6ꢀdihydroꢀ
pyrazineꢀ2,3ꢀdicarbonitrile (12a) was obtained as a yellow crysꢀ
talline powder. The yield was 60%, m.p. 205—207 °С (decomp.).
1Н NMR (CD3CN), δ: 1.21 (t, 3 Н, СН3, J = 7.2 Hz); 3.59 (dq,
1 Н, NCHA, J = 14.4 Hz, J = 7.2 Hz); 3.72 (dq, 1 Н, NCHB,
J = 14.4 Hz, J = 7.2 Hz); 6.20 (s, 1 Н, C(6)Н); 6.35 (d, 1 Н,
Сarom(Н(6´)), J = 8.5 Hz); 6.45 (d, 1 Н, Сarom(Н(5´)), J = 8.5 Hz);
6.91 (br.s, 3 Н, ОН); 7.38—7.45 (m, 3 Н, Ph); 7.86—7.88
(m, 2 Н, Ph). Found (%): C, 66.65; Н, 4.46; N, 15.61.
С20Н16N4O3. Calculated (%): C, 66.66; Н, 4.48; N, 15.55.
6ꢀ(2,3,4ꢀDihydroxyphenyl)ꢀ1ꢀethylꢀ5ꢀ(3ꢀthienyl)ꢀ1,6ꢀdiꢀ
hydropyrazineꢀ2,3ꢀdicarbonitrile (12b) was obtained as a yellow
crystalline powder. The yield was 62%, m.p. 224—226 °С (deꢀ
comp.). 1Н NMR (CD3CN), δ: 1.19 (t, 3 Н, СН3, J = 7.2 Hz);
3.55 (dq, 1 Н, NCHA, J = 14.4 Hz, J = 7.2 Hz); 3.62 (dq, 1 Н,
NCHB, J = 14.4 Hz, J = 7.2 Hz); 6.08 (s, 1 Н, C(6)Н); 6.37
(d, 1 Н, Сarom(Н(6´)), J = 8.5 Hz); 6.52 (d, 1 Н, Сarom(Н(5´)),
J = 8.5 Hz); 7.02 (br.s, 3 Н, ОН); 7.41 (dd, 1 Н, H(5″)ꢀ3ꢀ
thienyl, J = 5.2 Hz, J = 2.8 Hz); 7.58 (dd, 1 Н, H(4″)ꢀ3ꢀthienyl,
J = 5.2 Hz, J = 1.3 Hz); 7.87 (dd, 1 Н, H(2″)ꢀ3ꢀthienyl, J = 2.8 Hz,
J = 1.3 Hz). Found (%): C, 58.76; Н, 3.70; N, 15.04.
С18Н14N4О3S. Calculated (%): C, 59.01; Н, 3.85; N, 15.29.
1ꢀEthylꢀ5ꢀphenylꢀ6ꢀ(2,4,6ꢀtrihydroxyphenyl)ꢀ1,6ꢀdihydroꢀ
pyrazineꢀ2,3ꢀdicarbonitrile (13a) was obtained as a dark yellow
crystalline powder. The yield was 67%, m.p. 200—201 °С (deꢀ
comp.). 1Н NMR (CD3CN), δ: 1.16 (t, 3 Н, СН3, J = 7.2 Hz);
3.33 (dq, 2 Н, NCH2, J = 14.4 Hz, J = 7.2 Hz); 5.89 (s, 2 Н,
Сarom(Н(3´)), Сarom(Н(5´))); 6.46 (s, 1 Н, C(6)Н); 7.00 (s, 1 Н,
Сarom(4´)ОН); 7.32—7.39 (m, 3 Н, Ph); 7.50 (s, 2 Н,
Сarom(2´)ОН, Сarom(6´)ОН); 7.89—7.91 (m, 2 Н, Ph). Found (%):
C, 66.56; Н, 4.37; N, 15.44. С20Н16N4O3. Calculated (%):
C, 66.66; Н, 4.48; N, 15.55.
1ꢀEthylꢀ5ꢀ(3ꢀthienyl)ꢀ6ꢀ(2,4,6ꢀtrihydroxyphenyl)ꢀ1,6ꢀdiꢀ
hydropyrazineꢀ2,3ꢀdicarbonitrile (13b) was obtained as an orꢀ
ange crystalline powder. The yield was 95%, m.p. 198—201 °С
(decomp.). 1Н NMR (CD3CN), δ: 1.14 (t, 3 Н, СН3, J = 7.3 Hz);
3.31 (dq, 2 Н, NCH2, J = 14.6 Hz, J = 7.3 Hz); 5.92 (s, 2 Н,
Сarom(Н(3´)), Сarom(Н(5´))); 6.34 (s, 1 Н, C(6)Н); 7.03 (s, 1 Н,
Сarom(4´)ОН); 7.34 (dd, 1 Н, H(5″)ꢀ3ꢀthienyl, J = 5.1 Hz,
J = 2.8 Hz); 7.55—7.56 (m, 3 Н, H(4″)ꢀ3ꢀthienyl, Сarom(2´)ОН,
Сarom(6´)ОН); 7.93 (dd, 1 Н, H(2″)ꢀ3ꢀthienyl, J = 2.8 Hz,
J = 1.2 Hz). Found (%): C, 57.50; Н, 3.96; N, 14.61.
С18Н14N4О3S•0.5Н2О. Calculated (%): C, 57.59; Н, 4.03;
N, 14.92.
1ꢀEthylꢀ5ꢀphenylꢀ6ꢀ(2,4,6ꢀtrimethoxyphenyl)ꢀ1,6ꢀdihydroꢀ
pyrazineꢀ2,3ꢀdicarbonitrile (14a). was obtained as an orange crysꢀ
talline powder. The yield was 79%, m.p. 192—195 °С. 1Н NMR
(CD3CN), δ: 1.14 (t, 3 Н, СН3, J = 7.2 Hz); 3.27 (dq, 1 Н,
NCHA, J = 14.4 Hz, J = 7.2 Hz); 3.36 (dq, 1 Н, NCHB, J = 14.4 Hz,
J = 7.2 Hz); 3.76 (s, 3 Н, Сarom(4´)ОСН3); 3.87 (s, 6 Н,
Сarom(2´)ОСН3, Сarom(6´)ОСН3); 6.20 (s, 2 Н, Сarom(Н(3´)),
Сarom(Н(5´))); 6.58 (s, 1 Н, C(6)Н); 7.32—7.38 (m, 3 Н, Ph);
7.82—7.85 (m, 2 Н, Ph). Found (%): C, 68.68; Н, 5.57; N, 13.82.
С23Н22N4O3. Calculated (%): C, 68.64; Н, 5.51; N, 13.92.
1ꢀEthylꢀ5ꢀ(3ꢀthienyl)ꢀ6ꢀ(2,4,6ꢀtrimethoxyphenyl)ꢀ1,6ꢀdiꢀ
hydropyrazineꢀ2,3ꢀdicarbonitrile (14b) was obtained as a dark
yellow crystalline powder. The yield was 70%, m.p. 206—207 °С.
1Н NMR (CD3CN), δ: 1.12 (t, 3 Н, СН3, J = 7.2 Hz); 3.23 (dq,
1 Н, NCHA, J = 14.4 Hz, J = 7.2 Hz); 3.32 (dq, 1 Н, NCHB,
J = 14.4 Hz, J = 7.2 Hz); 3.78 (s, 3 Н, Сarom(4´)ОСН3); 3.88 (s, 6 Н,
Сarom(2´)ОСН3, Сarom(6´)ОСН3); 6.23 (s, 2 Н, Сarom(Н(3´)),
Сarom(Н(5´))); 6.46 (s, 1 Н, C(6)Н); 7.34 (dd, 1 Н, H(5″)ꢀ3ꢀ
thienyl, J = 5.2, J = 2.8 Hz); 7.52 (dd, 1 Н, H(4″)ꢀ3ꢀthienyl,
J = 5.2 Hz, J = 1.3 Hz); 7.81 (dd, 1 Н, H(2″)ꢀ3ꢀthienyl,
J = 2.8 Hz, J = 1.2 Hz). Found (%): C, 61.54; Н, 4.77; N, 13.81.
С21Н20N4О3S. Calculated (%): C, 61.75; Н, 4.94; N, 13.72.
1ꢀEthylꢀ6ꢀ(6ꢀhydroxybenzo[1,3]dioxolꢀ5ꢀyl)ꢀ5ꢀphenylꢀ1,6ꢀ
dihydropyrazineꢀ2,3ꢀdicarbonitrile (15a) was obtained as a dark
yellow crystalline powder. The yield was 51%, m.p. 216—217 °С.
1Н NMR (CDCl3), δ: 1.26 (t, 3 Н, СН3, J = 7.1 Hz); 3.70 (dq, 2 Н,
NCH2, J = 14.2 Hz, J = 7.1 Hz); 5.38 (br.s, 1 Н, Сarom(6´)ОН);
5.88 (br.s, 1 Н, Сarom(2´)НA); 5.91 (br.s, 1 Н, Сarom(2´)НB);
6.16 (s, 1 Н, C(6)Н); 6.42, 6.45 (two s, 2 Н, Сarom(Н(4´)),
Сarom(Н(7´))); 7.36—7.44 (m, 3 Н, Ph); 7.88—7.90 (m, 2 Н,
Ph). Found (%): C, 67.64; Н, 4.09; N, 15.08. С21Н16N4O3.
Calculated (%): C, 67.73; Н, 4.33; N, 15.05.
1ꢀEthylꢀ6ꢀ(6ꢀhydroxybenzo[1,3]dioxolꢀ5ꢀyl)ꢀ5ꢀ(3ꢀthienyl)ꢀ
1,6ꢀdihydropyrazineꢀ2,3ꢀdicarbonitrile (15b) was obtained as

926
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
Verbitskiy et al.
a yellow crystalline powder. The yield was 72%, m.p. 185—187 °С.
1Н NMR (CDCl3), δ: 1.27 (t, 3 Н, СН3, J = 7.2 Hz); 3.63 (dq, 2 Н,
NCH2, J = 14.2 Hz, J = 7.1 Hz); 5.74 (br.s, 1 Н, Сarom(6´)ОН);
5.89 (br.s, 1 Н, Сarom(2´)НA); 5.91 (br.s, 1 Н, Сarom(2´)НB);
6.08 (s, 1 Н, C(6)Н); 6.43, 6.51 (both s, 2 Н, Сarom(Н(4´)),
Сarom(Н(7´))); 7.30 (dd, 1 Н, H(5″)ꢀ3ꢀthienyl, J = 5.2 Hz,
J = 2.8 Hz); 7.66 (br.d, 1 Н, H(4″)ꢀ3ꢀthienyl, J = 5.2 Hz); 7.80
(br.d, 1 Н, H(2″)ꢀ3ꢀthienyl, J =1.2). Found (%): C, 60.14;
Н, 3.97; N, 15.00. С19Н14N4О3S. Calculated (%): C, 60.31;
Н, 3.73; N, 14.81.
Synthesis of 2,6ꢀdisubstituted 4ꢀ(6ꢀ(het)arylꢀ1,2,5ꢀoxadiꢀ
azolo[3,4ꢀb]pyrazinꢀ5ꢀyl)phenols 35a,b, 36a,b, and 37a (general
procedure). 2,6ꢀDisubstituted phenol (1 mmol) dissolved in triꢀ
fluoroacetic acid (2 mL) was added with stirring to a solution of
6ꢀ(het)arylfurazano[3,4ꢀb]pyrazine (1 mmol) in trifluoroacetic
acid (2 mL). The reaction mixture was stored from 15 min to 2 h
(TLC monitoring) and diluted with water. The precipitate that
formed was filtered off, washed with water several times, and
recrystallized from ethanol. In the case of products 35a and 36b,
the mixture was separated by chromatography eluting with an
ethyl acetate—hexane (1 : 2) mixture.
2,6ꢀDimethylꢀ4ꢀ(6ꢀphenylꢀ1,2,5ꢀoxadiazolo[3,4ꢀb]pyrazinꢀ
5ꢀyl)phenol (35a). Product 35a was obtained as a yellowꢀorange
crystalline powder. The yield was 55%, m.p. 207—208 °С (deꢀ
comp.). 1Н NMR (DMSOꢀd6), δ: 2.05 (s, 6 Н, CH3); 7.05 (s, 2 H,
Ar); 7.40—7.52 (m, 5 H, Ar); 9.02 (s, 1 H, OH). Found (%):
C, 67.77; Н, 4.55; N, 17.52. С18Н14N4О2. Calculated (%):
C, 67.91; Н, 4.43; N, 17.6.
2,6ꢀDimethylꢀ4ꢀ[6ꢀ(3ꢀthienyl)ꢀ1,2,5ꢀoxadiazolo[3,4ꢀb]pyrꢀ
azinꢀ5ꢀyl]phenol (35b) was obtained as a yellowꢀorange crystalꢀ
line powder. The yield was 41%, m.p. 201—203 °С (decomp.).
1Н NMR (DMSOꢀd6), δ: 2.13 (s, 6 Н, CH3); 7.14—7.16 (m, 3 H,
H(4″)ꢀ3ꢀthienyl, Сarom(Н(3´)), Сarom(Н(5´))С); 7.58 (dd, 1 Н,
H(5″)ꢀ3ꢀthienyl, J = 5.2 Hz, J = 2.8 Hz); 7.77 (dd, 1 Н, H(2″)ꢀ
3ꢀthienyl, J = 2.8 Hz, J = 1.2 Hz); 9.02 (s, 1 H, OH). Found (%):
C, 59.54; Н, 3.55; N, 17.52. С16Н12N4О2S. Calculated (%):
C, 59.25; Н, 3.73; N, 17.27.
1 H, OH). Found (%): C, 73.74; Н, 6.59; N, 12.55. С27Н28N4О2.
Calculated (%): C, 73.61; Н, 6.41; N, 12.72.
Synthesis of 5ꢀarylꢀ6ꢀphenylꢀ1,2,5ꢀoxadiazolo[3,4ꢀb]pyrꢀ
azines 38a, 39a, and 40a (general procedure). A solution of methꢀ
oxylated resorcinol, phloroglucine, or 2ꢀnaphthol (1 mol) in benꢀ
zene (2—3 mL) was added to a solution of 6ꢀphenylfurazanoꢀ
[3,4ꢀb]pyrazine (1 mmol) in anhydrous benzene (3 mL). Several
droplets of boron trifluoride etherate were added to the obtained
mixture, and the resulting solution was left to stay for 2—3 h.
The reaction mixture was concentrated by evaporation, washed
with a solution of sodium hydrocarbonate, and recrystallized
from isopropyl alcohol.
5ꢀ(2,4ꢀDimethoxyphenyl)ꢀ6ꢀphenylꢀ1,2,5ꢀoxadiazolo[3,4ꢀb]ꢀ
pyrazine (38a). Product 38a was obtained as a yellow crystalline
powder. The yield was 62%, m.p. 128—130 °С. 1Н NMR
(DMSOꢀd6), δ: 3,09 (s, 3 Н, ОСН3); 3.81 (s, 3 Н, ОСН3); 6.38
(br.s, 1 Н, Сarom(Н(3´)); 6.78 (br.d, 1 H, Сarom(Н(5´)), J = 8.0 Hz);
7.33—7.45 (m, 5 H, Ph); 7.64 (br.d, 1 H, Сarom(Н(6´)), J = 8.0 Hz).
Found (%): C, 64.5; Н, 4.16; N, 17.01. С18Н14N4О3. Calculatꢀ
ed (%): C, 64.66; Н, 4.22; N, 16.76.
6ꢀPhenylꢀ5ꢀ(2,4,6ꢀtrimethoxyphenyl)ꢀ1,2,5ꢀoxadiazolo[3,4ꢀb]ꢀ
pyrazine (39a) was obtained as a yellow crystalline powder.
The yield was 60%, m.p. 133—136 °С. 1Н NMR (DMSOꢀd6), δ:
3.33 (s, 6 Н, Сarom(2´)ОСН3, Сarom(6´)ОСН3); 3.79 (s, 3 Н,
Сarom(4´)ОСН3); 6.23 (s, 2 Н, Сarom(Н(3´)), Сarom(Н(5´)));
7.34—7.48 (m, 5 H, Ph). Found (%): C, 62.81; Н, 4.36; N, 15.41.
С19Н16N4О4. Calculated (%): C, 62.63; Н, 4.43; N, 15.38.
5ꢀ(2ꢀMethoxynaphthalenꢀ1ꢀyl)ꢀ6ꢀphenylꢀ1,2,5ꢀoxadiazoꢀ
lo[3,4ꢀb]pyrazine (40a) was obtained as an orangeꢀred crystalꢀ
line powder. The yield was 52%, m.p. 228—230 °С. 1Н NMR
(DMSOꢀd6), δ: 3.37 (s, 3 Н, ОСН3); 7.19—7.26 (m, 2 Н, Ph);
7.28—7.32 (m, 3 H, Ph); 7.35—7.38 (m, 1 H, naphthyl);
7.46—7.49 (m, 1 H, naphthyl); 7.54—7.58 (m, 1 H, naphthyl);
7.97—7.99 (m, 1 H, naphthyl); 8.08—8.1 (m, 2 H, naphthyl).
Found (%): C, 71.34; Н, 3.91; N, 15.82. С21Н14N4О2. Calculatꢀ
ed (%): C, 71.18; Н, 3.98; N, 15.81.
Synthesis of Nꢀ[5,7ꢀdiꢀtertꢀbutylꢀ2ꢀ(het)arylbenzofuranꢀ3ꢀ
yl]furazanꢀ3,4ꢀdiamines 44a,b (general procedure). 2,4ꢀDiꢀtertꢀ
butylphenol (206 mg, 1 mmol) dissolved in trifluoroacetic acid
(2 mL) was added with stirring to a solution of 6ꢀ(het)arylꢀ
furazano[3,4ꢀb]pyrazine (1 mmol) in trifluoroacetic acid (2 mL).
The reaction mixture was stored for 1 h and then diluted with
water. The precipitate that formed was filtered off, washed with
water several times, and recrystallized from ethanol.
2,6ꢀDiꢀtertꢀbutylꢀ4ꢀ(6ꢀphenylꢀ1,2,5ꢀoxadiazolo[3,4ꢀb]pyrꢀ
azinꢀ5ꢀyl)phenol (36a) was obtained as an orange crystalline
powder. The yield was 75%, m.p. 220—222 °С. 1Н NMR
(DMSOꢀd6), δ: 1.23 (s, 18 Н, But); 7.32 (s, 2 H, Ar); 7.43—7.51
(m, 5 H, Ar); 7.62 (s, 1 H, OH). Found (%): C, 71.25; Н, 6.43;
N, 13.8. С24Н26N4О2. Calculated (%): C, 71.62; Н, 6.51;
N, 13.92.
2,6ꢀDiꢀtertꢀbutylꢀ4ꢀ[6ꢀ(3ꢀthienyl)ꢀ1,2,5ꢀoxadiazolo[3,4ꢀb]ꢀ
pyrazinꢀ5ꢀyl]phenol (36b) was obtained as a yellowꢀorange crysꢀ
talline powder. The yield was 68%, m.p. 192—194 °С (decomp.).
1Н NMR (DMSOꢀd6), δ: 1.31 (s, 18 Н, But); 7.00 (dd, 1 Н,
H(4″)ꢀ3ꢀthienyl, J = 5.2 Hz, J = 1.2 Hz); 7.38 (s, 2 H, Ar); 7.59
(dd, 1 Н, H(5″)ꢀ3ꢀthienyl, J = 5.0 Hz, J = 2.8 Hz); 7.7 (s, 1 H,
OH); 7.80 (dd, 1 Н, H(2″)ꢀ3ꢀthienyl, J = 2.8 Hz, J = 1.2 Hz).
Found (%): C, 64.50; Н, 5.99; N, 13.8. С22Н24N4О2S. Calculatꢀ
ed (%): C, 64.68; Н, 5.92; N, 13,71.
Nꢀ(5,7ꢀDiꢀtertꢀbutylꢀ2ꢀphenylbenzofuranꢀ3ꢀyl)furazanꢀ3,4ꢀ
diamine (44a). Product 44a was obtained as a colorless powder.
The yield was 68%, m.p. 226—228 °С (decomp.). 1Н NMR
(DMSOꢀd6), δ: 1.32 (s, 9 H, But); 1.54 (s, 9 H, But); 5.15 (br.s,
2 H, NH2); 7.25 (d, 1 H, Сarom(Н(4´)), J = 1.6 Hz); 7.28 (d, 1 H,
Сarom(Н(6´)), J = 1.6 Hz); 7.38—7.42 (m, 2 H, Ph); 7.51—7.55
(m, 1 H, Ph); 7.85—7.88 (m, 2 H, Ph); 8.25 (s, 1 H, NH).
Found (%): C, 70.16; Н, 6.97; N, 13.50. С24Н28N4О2. Calculatꢀ
ed (%): C, 71.26; Н, 6.98; N, 13.85.
2ꢀMethylꢀ4ꢀ(6ꢀphenylꢀ1,2,5ꢀoxadiazolo[3,4ꢀb]pyrazinꢀ5ꢀ
yl)ꢀ6ꢀ(1,7,7ꢀtrimethylbicyclo[2.2.1]heptanꢀ2ꢀyl)phenol (37a) was
obtained as an orange crystalline powder. The yield was 47%,
Nꢀ[5,7ꢀDiꢀtertꢀbutylꢀ2ꢀ(3ꢀthienyl)benzofuranꢀ3ꢀyl]furazanꢀ
3,4ꢀdiamine (44b) was obtained as a colorless powder. The yield
was 71%, m.p. 247—250 °С (decomp.). Н NMR (DMSOꢀd6),
1
1
m.p. 231 °С (decomp.). Н NMR (DMSOꢀd6), δ: 0.42 (s, 3 Н,
δ: 1.32 (s, 9 H, But); 1.53 (s, 9 H, But); 6.15 (br.s, 2 H, NH2);
7.23 (d, 1 H, Сarom(Н(4´)), J = 1.6 Hz); 7.25 (d, 1 H, Сarom(Н(6´)),
J = 1.6 Hz); 7.51 (dd, 1 Н, H(4″)ꢀ3ꢀthienyl, J = 5.2 Hz,
J = 1.3 Hz); 7.72—7.75 (m, 1 H, H(5″)ꢀ3ꢀthienyl); 7.89 (dd, 1 Н,
H(2″)ꢀ3ꢀthienyl, J = 2.8 Hz, J = 1.2 Hz); 8.16 (s, 1 H, NH).
СН3); 0.60 (s, 3 Н, СН3); 0.71 (s, 3 Н, СН3); 1.21—1.27 (m, 2 H,
Alk); 1.4—1.54 (m, 3 H, Alk); 1.64—1.76 (m, 2 H, Alk); 2.2
(s, 3 Н, СН3); 3.15 (t, 1 H, J = 8.4 Hz); 7.03 (d, 1 H, Ar, J = 2.0 Hz);
7.32 (d, 1 H, Ar, J = 2.0 Hz); 7.37—7.48 (m, 5 H, Ph); 8.85 (br.s,

Reactions of pyrazinium salts with phenols
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
927
Found (%): C, 64.16; Н, 6.97; N, 13.50. С22Н26N4О2S. Calcuꢀ
lated (%): C, 64.36; Н, 6.38; N, 13.65.
2. J. A. Joule, K. Mills, Heterocyclic Chemistry, Blackwell Sciꢀ
ence Limited, Oxford, 2000.
Nꢀ3ꢀ[5ꢀMethylꢀ7ꢀ(1,7,7ꢀtrimethylbicyclo[2.2.1]heptanꢀ2ꢀ
yl)ꢀ2ꢀphenylbenzofuranꢀ3ꢀyl]ꢀ1,2,5ꢀoxadiazoloꢀ3,4ꢀdiamine (45а).
2ꢀIsobornylꢀ4ꢀmethylphenol (24) (244 mg, 1 mmol) dissolved in
CF3COOH (2 mL) was added with stirring to a solution of
6ꢀphenylfurazano[3,4ꢀb]pyrazine (198 mg, 1 mmol) in CF3COOH
(2 mL). The reaction mixture was stored for 1 h and then diluted
with water. The precipitate that formed was filtered off, washed
with water several times, and recrystallized from ethanol. Prodꢀ
uct 45а was obtained as a colorless crystalline powder. The yield
was 326 mg (74%), m.p. 214 °С (decomp.). 1Н NMR (DMSOꢀd6),
δ: 0.72 (s, 3 Н, СН3); 0.85 (s, 3 Н, СН3); 0.93 (s, 3 Н, СН3);
1.39—1.45 (m, 1 H); 1.59—1.75 (m, 3 H, Alk); 2.37 (s, 3 Н,
СН3); 2.41—2.44 (m, 1 H, Alk); 3.41—3.52 (m, 3 H, Alk); 6.14
(br.s, 2 H, NH2); 7.02 (br.s, 1 H, Ar); 7.14 (br.s, 1 H, Ar);
7.38—7.42 (m, 1 H, Ph); 7.51—7.55 (m, 2 H, Ph); 7.88—7.91
(m, 2 H, Ph); 8.28 (br.s, 1 H, NH). Found (%): C, 73.02;
Н, 6.39; N, 12.45. С27Н28N4О2. Calculated (%): C, 73.28;
H, 6.83; N, 12.66.
Synthesis of Nꢀ(2ꢀ(het)arylnaphtho[2,1ꢀb]furanꢀ1ꢀyl)furꢀ
azanꢀ3,4ꢀdiamines 46a,b (general procedure). 2ꢀNaphthol (144 mg,
1 mmol) dissolved in CF3COOH (2 mL) was added with stirring
to a solution of 6ꢀ(het)arylfurazano[3,4ꢀb]pyrazine (1 mmol) in
CF3COOH (2 mL). The reaction mixture was stored for 1 h and then
diluted with water. The precipitate that formed was filtered off,
washed with water several times, and recrystallized from ethanol.
Nꢀ(2ꢀPhenylnaphtho[2,1ꢀb]furanꢀ1ꢀyl)furazanꢀ3,4ꢀdiamine
(46a). Product 46a was obtained as a colorless crystalline powder.
The yield was 78%, m.p. 253—255 °С. 1Н NMR (DMSOꢀd6), δ:
6.09 (s, 2 H, NH2); 7.41—7.45 (m, 1 H, Ar); 7.51—7.58 (m, 4 H,
Ar); 7.86—7.95 (m, 4 H, Ar); 8.07 (d, 1 H, Ar, J = 7.6 Hz); 8.16
(d, 1 H, Ar, J = 7.6 Hz); 8.58 (s, 1 H, NH). Found (%): C, 70.38;
Н, 4.17; N, 16.45. С20Н14N4О2. Calculated (%): C, 70.17;
Н, 4.12; N, 16.37.
3. O. N. Chupakhin, G. L. Rusinov, D. G. Beresnev, S. Sh.
Bashirov, M. G. P. M. S. Neves, Zh. A. S. Kavaleiro, Izv.
Akad. Nauk, Ser. Khim., 2004, 155 [Russ. Chem. Bull.,
Int. Ed., 2004, 53, 160].
4. N. A. Itsikson, D. G. Beresnev, G. L. Rusinov, O. N. Chupaꢀ
khin, ARKIVOC, 2004, XII, 6.
5. G. L. Rusinov, P. A. Slepukhin, V. N. Charushin, O. N.
Chupakhin, Mendeleev Commun., 2001, 11, 78.
6. G. L. Rusinov, P. A. Slepukhin, V. N. Charushin, O. A.
Dyachenko, O. N. Kazheva, A. N. Chekhlov, E. V. Verꢀ
bitsky, M. I. Kodess, O. N. Chupakhin, Mendeleev Comꢀ
mun., 2006, 16, 26.
7. E. V. Verbitskiy, G. L. Rusinov, P. A. Slepukhin, A. I.
Matern, Yu. N. Shvachko, D. V. Starichenko, V. N. Chaꢀ
rushin, O. N. Chupakhin, Izv. Akad. Nauk, Ser. Khim., 2006,
2035 [Russ. Chem. Bull., Int. Ed., 2006, 55, 2114].
8. E. V. Verbitskiy, G. L. Rusinov, P. A. Slepukhin, A. N. Griꢀ
shakov, M. A. Ezhikova, M. I. Kodess, V. N. Charushin,
Zh. Org. Khim., 2008, 44, 305 [Russ. J. Org. Chem. (Engl. Transl.),
2008, 44].
9. E. V. Verbitskiy, M. V. Berezin, P. A. Slepukhin, G. L. Rusiꢀ
nov, V. N. Charushin, Izv. Akad. Nauk, Ser. Khim., 2009,
176 [Russ. Chem. Bull., Int. Ed., 2009, 58, 176].
10. G. L. Rusinov, E. V. Verbitskiy, P. A. Slepukhin, O. N.
Zabelina, M. I. Kodess, M. A. Ezhikova, V. N. Charushin,
O. N. Chupakhin, Heterocycles, 2009, 78, 2315.
11. G. L. Rusinov, E. V. Verbitsky, P. A. Slepukhin, O. N. Zaꢀ
belina, I. N. Ganebnykh, V. N. Kalinin, V. A. Ol´shevskaya,
V. N. Charushin, Mendeleev Commun., 2009, 19, 243.
12. E. V. Verbitskiy, P. A. Slepukhin, M. A. Ezhikova, M. I.
Kodess, G. L. Rusinov, V. N. Charushin, Izv. Akad. Nauk,
Ser. Khim., 2009, 1255 [Russ. Chem. Bull., Int. Ed., 2009,
58, 1291].
Nꢀ[2ꢀ(3ꢀThienyl)naphtho[2,1ꢀb]furanꢀ1ꢀyl]furazanꢀ3,4ꢀdiꢀ
amine (46b) was obtained as a colorless crystalline powder. The
yield was 71%, m.p. 238—239 °С. 1Н NMR (DMSOꢀd6), δ: 6.25
(s, 2 H, NH2); 7.51—7.58 (m, 2 H, naphthyl); 7.61 (dd, 1 Н,
H(4″)ꢀ3ꢀthienyl, J = 5.2 Hz, J = 1.2 Hz); 7.77 (dd, 1 Н, H(5″)ꢀ
3ꢀthienyl, J = 5.2 Hz, J = 2.8 Hz); 7.84 (d, 1 H, naphthyl,
J = 8.0 Hz); 7.90 (d, 1 H, naphthyl, J = 8.0 Hz); 8.03 (dd, 1 Н,
H(2″)ꢀ3ꢀthienyl, J = 2.8 Hz, J = 1.2 Hz); 8.05 (m, 1 H, naphthꢀ
yl); 8.16 (m, 1 H, naphthyl); 8.51 (s, 1 H, NH). Found (%):
C, 62.15; Н, 3.17; N, 16.35. С18Н12N4О2S. Calculated (%):
C, 62.06; Н, 3.47; N, 16.08.
13. Z. Rappoport, The Chemistry of Phenols, John Wiley & Sons,
Ltd., 2003, 1658 pp.
14. J. M. Herdan, M. Giurginca, Polymer Degradation and Stabiꢀ
lity, 1993, 41, 157.
15. G. R. Lapin, C. E. Tholstup, C. A. Kelly, in Advances in
Chemistry, 1968, 85, Ch. 12, 155.
16. E. G. Jones, L. M. Balster, Energy Fuels, 2000, 14, 640.
17. M. A. de Sousa, S. N. Santiago, A. A. S. Lopes, S. E. Mazzetꢀ
to, Energy Fuels, 2010, 24, 3285.
18. Z. Hodzis, H. Pasalis, A. Memisevis, M. Srabvis, M. Saletoꢀ
vis, M. Poljakovis, Eur. J. Sci. Res., 2009, 28, 471.
19. G. W. Burton, T. Doba, E. J. Gabe, L. Hughes, F. L. Lee,
L. Prasad, K. U. Ingold, J. Am. Chem. Soc., 1985, 107, 7053.
20. Y. Aizawa, T. Kanai, K. Hasegawa, T. Yamaguchi, Y. Iiꢀ
zuka, T. Iwaoka, T. Yoshioka, J. Med. Chem., 1990, 33, 1491.
21. K. Tamura, Y. Kato, A. Ishikawa, Y. Kato, M. Himori,
M. Yoshida, Y. Takashima, T. Suzuki, Y. Kawabe, O. Cynꢀ
shi, T. Kodama, E. Niki, M. Shimizu, J. Med. Chem., 2003,
46, 3083.
22. C. Q. Meng, P. K. Somers, L. K. Hoong, X. S. Zheng, Z. Ye,
K. J. Worsencroft, J. E. Simpson, M. R. Hotema, M. D.
Weingarten, M. L. MacDonald, R. R. Hill, E. M. Marino,
K.ꢀL. Suen, J. Luchoomun, C. Kunsch, L. K. Landers,
D. Stefanopoulos, R. B. Howard, C. L. Sundell, U. Saxena,
M. A. Wasserman, J. A. Sikorski, J. Med. Chem., 2004,
47, 6420.
This work was financially supported by the Russian
Academy of Sciences (Program of the Ural Branch of the
Russian Academy of Sciences Nos 09ꢀPꢀ3ꢀ1015 and
09ꢀTꢀ3ꢀ1022), the Ministry of Education and Science of
the Russian Federation, and the Russian Foundation for
Basic Research (Project Nos 09ꢀ03ꢀ12242ꢀofi_m and
VNShꢀ65261.2010.3).
References
1. O. N. Chupakhin, V. N. Charushin, H. C. van der Plas,
Nucleophilic Aromatic Substitution of Hydrogen, Academic
Press, San Diego, New York, 1994, 376 pp.

928
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 5, May, 2011
Verbitskiy et al.
23. D. Boskou, Trends in Food Science & Technology, 2006,
17, 505.
Ser. Khim., 1999, 1573 [Russ. Chem. Bull. (Engl. Transl.),
1999, 48, 1553].
24. E. Haslam, J. Nat. Prod., 1996, 59, 205.
25. O. N. Chupakhin, D. G. Beresnev, Vestnik RFFI, 2002,
3, 31.aaa
29. P. A. Slepukhin, Ph. D. (Chem.) Thesis, Institute of Organic
Synthesis, Ural Branch of the Russian Academy of Sciences,
Yekaterinburg, 2005, 149 pp. (in Russian).
26. G. L. Rusinov, D. G. Beresnev, O. N. Chupakhin, Zh. Org.
Khim., 1998, 34, 450 [Russ. J. Org. Chem. (Engl. Transl.),
1998, 34].
30. L. Tietze, T. Eicher, Reactionen und Synthesen im organishꢀ
chemiscen Praktikum und Forschunglaboratorium, Georg
Thieme Verlag, Stuttgart—New York, 1991.
27. E. V. Bartashevich, V. A. Potemkin, D. G. Beresnev, G. L.
Rusinov, O. N. Chupakhin, Zh. Obshch. Khim., 2003, 73,
862 [Russ. J. Gen. Chem. (Engl. Transl.), 2003, 73].
28. E. V. Bartashevich, P. V. Plekhanov, G. L. Rusinov, V. A.
Potemkin, A. V. Belik, O. N. Chupakhin, Izv. Akad. Nauk,
31. N. Satio, J. Adachi, J. Org. Chem., 1978, 43, 341.
32. G. M. Sheldrick, Acta Cryst., 2008, A64, 112.
Received January 20, 2011;
in revised form March 14, 2011