Synthesis of imidazo[4,5-e]benzo[1,2-c;3,4-c′]difuroxanes

Article abstract of DOI:10.1007/s11172-017-1880-y

A method for the synthesis of imidazo[4,5-e]benzo[1,2-c;3,4-c′]difuroxanes, potential nitric oxide donors, has been developed. The synthesized compounds were characterized by IR and NMR spectroscopy, high resolution mass spectrometry, and elemental analysis.

Full text of DOI:10.1007/s11172-017-1880-y

Russian Chemical Bulletin, International Edition, Vol. 66, No. 7, pp. 1250—1255, July, 2017
1250
Synthesis of imidazo[4,5ꢀe]benzo[1,2ꢀc;3,4ꢀc´]difuroxanes
V. L. Korolev,a,b V. V. Toporov,c N. L. Merkulova,a,b V. M. Danilenko,d V. P. Ivshin,c and Т. S. Pivinab
aI. M. Sechenov First Moscow State Medical University
Ministry of Healthcare of Russian Federation,
Build. 2, 8 ul. Trubetskaya, 119991 Moscow, Russian Federation.
Fax: +7 (499) 248 018. Eꢀmail: wlkor@mail.ru, fraumerk@gmail.com
bN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328. Eꢀmail: tsp@ioc.ac.ru
cMary State University,
1 pl. Lenina, 424000 YoshkarꢀOla, Russian Federation.
Fax: +7 (836 2) 64 1541
dHigh School in the SouthꢀEast,
Korp. 6, 32 ul. Zelenodolskaya, 109457 Moscow, Russian Federation.
Fax: +7 (495) 362 3440
A method for the synthesis of imidazo[4,5ꢀe]benzo[1,2ꢀc;3,4ꢀc´]difuroxanes, potential
nitric oxide donors, has been developed. The synthesized compounds were characterized by
IR and NMR spectroscopy, high resolution mass spectrometry, and elemental analysis.
Key words: 3.5ꢀdibromophenyleneꢀ1,2ꢀdiamine, carboxylic acids, acyl chlorides, benzꢀ
imidazoles, nitration, azidation, thermal cyclization, imidazo[4,5ꢀe]benzo[1,2ꢀc;3,4ꢀc´]ꢀ
difuroxanes.
Nitric oxide, being one of the universal regulators of
molytic,18 hypotensive18 effect and inhibit platelet aggreꢀ
gation.18—23
the functions of cellular metabolism, is involved, among
other things, in the regulation of the tone of blood vesꢀ
sels.1 The therapeutic effect of known vasodilators is due
to the processes of decomposition of these substances
in vivo with the release of NO.2,3 Compounds having in
the structure a furoxane ring can be considered as potenꢀ
tial nitric oxide donors.4—11 It has been found that, as
vasodilators, furoxanes are distinguished by the absence
of nitrate tolerance and the slow transformation, which
reduces the risk of hypotensive conditions, one of the
most serious problems of antihypertensive therapy.12 It
was also noted that furoxanes possess antiinflammatory13
and cytotoxic14 activity. Thus, it can be concluded that
compounds with a furoxane ring are promising objects for
the study in pharmaceutics. At the present time, the studꢀ
ies are carried out for both the linear heterocyclic assemꢀ
bles based on furoxanes and the fused systems. Among
the latter, a certain interest is caused by benzodifurꢀ
oxanes,15—17 compounds with two furoxane rings in the
structure.
An example of the synthesis of imidazo[4,5ꢀe]benzoꢀ
[1,2ꢀc;3,4ꢀc´]difuroxane from 4,7ꢀdiiodoꢀ5,6ꢀdinitrobenzꢀ
imidazole was described recently.24
In the present work, we consider a general approach
to the synthesis of imidazo[4,5ꢀe]benzo[1,2ꢀc;3,4ꢀc´]ꢀ
difuroxanes, representatives of a new class of NOꢀgenerꢀ
ating compounds.
Results and Discussion
The condensation of 3,5ꢀdibromophenyleneꢀ1,2ꢀdiꢀ
amine (1) with carboxylic acids leads to the correspondꢀ
ing benzimidazoles 2a—e. Compound 2f was obtained by
the reaction of 1 with valeroyl chloride in the presence of
pyridine (Scheme 1).
The nitration of compounds 2a—f with a mixture of
o
concentrated HNO3 and H2SO4 at 90—95 C gave the
corresponding dinitroderivatives 3a—f (Scheme 2).
Treatment of compounds 3a—f with NaN3 in DMF
at room temperature led to the formation of the correꢀ
sponding diazido derivatives 4a—f (Scheme 3).
Because of a potentially high sensitivity to mechaniꢀ
cal impacts, compounds 4a—f after the azidation reacꢀ
tion were precipitated from DMF with water and subjectꢀ
From the multitude of annulated systems with a furꢀ
oxane ring, a relatively new type based on imidazo[4,5ꢀe]ꢀ
benzo[1,2ꢀc;3,4ꢀc´]difuroxane requires special attention.
Imidazo[4,5ꢀe]benzo[1,2ꢀc;3,4ꢀc´]difuroxane derivatives
are nitric oxide generators,18 possess vasodilator,18 spasꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1250—1255, July, 2017.
1066ꢀ5285/17/6607ꢀ1250 © 2017 Springer Science+Business Media, Inc.

Imidazo[4,5ꢀe]benzo[1,2ꢀc;3,4ꢀc´]difuroxans
Russ. Chem. Bull., Int. Ed., Vol. 66, No. 7, July, 2017
1251
Scheme 1
Scheme 5
R = H (a), Me (b), Et (c), Pr (d), Pri (e), Bu (f)
Scheme 2
Scheme 3
stabilities of tautomers 5´a—5´´´´ a in the gas phase and in
DMSO (Table 1).
The computational results given in Table 1 indicate
that tautomer 5´´a has the lowest thermodynamic stabiliꢀ
ty in the gas phase and in solution of DMSO in comꢀ
parison with other tautomers. However, the comparative
thermodynamic preference of different tautomers of
compound 5a was found to be very insignificant, namely,
near the limit of the permissible error of calculation
(~0.5 kcal mol–1).33
ed to thermal cyclization without preliminary purificaꢀ
tion and drying.
The tautomerism of compound 5a in solution of
DMSOꢀd6 at room temperature was confirmed by the
presence in the H NMR spectrum a triple set of signals
Compounds 5a—f were obtained by heating diazido
derivatives 4a—f in glacial AcOH at 100 oC (Scheme 4).
1
for the C—H proton of the imidazole ring: δ 8.35 s, 8.40 s,
8.45 s in the ratio of 1 : 0.25 : 0.13 (Table 2). An evidence
of tautomerism of compounds 5a—f was the appearance
in their 13C NMR spectra of additional signals for
the carbon atoms of the aromatic ring bonded to the
Nꢀoxide nitrogen atom (5a—d) and the oxazole nitrogen
atom (5c); the imidazole carbon atom C(2) (5e); the
carbon atom of the alkyl substituent CH2—C= (5f) (see
Table 2).
Scheme 4
Compounds 5a—f are yellowish crystalline substancꢀ
es, insoluble in water, but soluble in acetone and ethyl
acetate. The compounds decompose upon heating withꢀ
out melting; they can be purified by recrystallization from
ethanol or acetic acid. Compounds 5a—f can give comꢀ
plexes with solvents. Thus, for example, compound 5a
forms 2 : 1 complex with acetic acid, which decomposes
upon heating in water.
The furoxane ring in the molecule of benzofuroxane
derivatives possesses an ability to tautomerize to the secꢀ
ond form containing an Nꢀoxide group on the other side
of the ring.17,25,26 This isomerization is reversible, and in
solutions both tautomers exist in equilibrium. Compounds
5a—f theoretically can exist in four tautomeric forms
5´a—f—5´´´´ a—f (Scheme 5).
We used the density functional theory (DFT) with the
exchangeꢀcorrelation functional B3LYP27—30 in the
valenceꢀsplit basis 6ꢀ311++G(d,p)31,32 to calculate for
compound 5a (as an example) the relative thermodynamic
In conclusion, we have developed a general method
for the synthesis of imidazo[4,5ꢀe]benzo[1,2ꢀc;3,4ꢀc´]ꢀ
difuroxanes by the condensation of 3,5ꢀdibromoꢀ
phenyleneꢀ1,2ꢀdiamine with carboxylic acids or their

1252
Russ. Chem. Bull., Int. Ed., Vol. 66, No. 7, July, 2017
Korolev et al.
Table 1. Relative thermodynamic stabilities of tautomers of imidazo[4,5ꢀe]benzo[1,2ꢀc;3,4ꢀc´]ꢀ
difuroxane (5a) in the gas phase and in DMSO calculated by DFT B3LYP/6ꢀ311++G(d,p)
Compound
Gas phase
(Е + ZPE)
DMSO
(ЕDMSO + ZPE)
RTS *
/kcal mol–1
RTS*
/kcal mol–1
/at.u.
/at.u.
5´а
5″а
5´´´а
5´´´´а
–897.186886
–897.184042
–897.185713
–897.186042
0
–897.207080
–897.205472
–897.205662
–897.207285
0.1
1.1
1.0
0
1.8
0.7
0.5
* Relative thermodynamic stabilities (RTS) of tautomers were calculated in the gas phase using
the following formula [(E + ZPE)х – (E + ZPE)у]•627.5 kcal mol–1 (see Ref. 34) (E is the total
energy, ZPE is the correction for the zeroꢀpoint energy of vibrations, x is the data for compound
5´a, у is the data for all other compounds), in DMSO using the following formula [(EDMSO
+
+ ZPE)х – (EDMSO + ZPE)у]•627.5 kcal mol–1 (EDMSO is the total energy in the solvent, ZPE is
the correction for the zeroꢀpoint energy of vibrations, x is the data for compoundя 5´´´´a, у is
the data for all other compounds).
Table 2. Spectral characteristics of the synthesized compounds
Compound
IR, ν/cm–1
NMR (δ, J/Hz)
1Н
13С
2a
3160, 1615, 1556, 1547, 1486, 1387, 1343,
1314, 1280, 1197, 1142, 987, 936, 822, 806,
753, 703, 625, 588, 469
3400, 2921, 2850, 1619, 1539, 1517, 1393,
1335, 1297, 1257, 1234, 1183, 1071, 1019,
958, 833, 757, 742, 660, 581, 570, 513
7.54 (s, 1 H, CH);
7.80 (s, 1 H, CH);
8.36 (s, 1 H, C(2)H)
2.50 (s, Me);**
7.45 (s, 1 H, CH);
7.64 (s, 1 H, CH);
12.75 (s, 1 H, NH)
110.5, 114.2, 116.3, 126.4, 137.7,
138.5 (—C=); 144.0 (N—CH=N)
2b*
14.7 (CH3); 113.5, 125.8 (—C=);
153.9 (C—CH3)
2c*
2d*
3437, 2973, 2929, 1619, 1571, 1541, 1454,
1424, 1411, 1315, 1292, 1265, 1245, 1185,
1076, 1059, 1030, 949, 839
1.29 (t, 3 H, Me, 3J = 7.62);
2.84 (q, 2 H, CH2, 3J = 7.62);
7.43 (s, 1 H, CH);
7.64 (s, 1 H, CH);
12.74 (s, 1 H, NH)
0.92 (t, 3 H, Me, 3J = 7.35);
1.78 (m, 2 H, CH2);
2.80 (t, 2 H, CH2, 3J = 7.35);
7.49 (s, 1 H, CH);
1.4 (CH3); 22.1 (CH2CH3);
1113.6, 124.8, 127.1 (—C=);
158.7 (C—CH2)
3400, 2956, 2871, 1619, 1570, 1537, 1470,
1411, 1359, 1321, 1298, 1260, 1236, 1183,
1071, 1012, 960, 836, 806, 758, 733, 662, 582
13.7 (CH3); 21.0 (CH2CH3);
30.4 (CH2CH2CH3);
113.7, 121.0, 125.8 (—C=)
7.63 (s, 1H, CH);
12.71 (s, 1 H, NH)
2e*
3450, 2969, 2926, 1615, 1568, 1533, 1461,
1410, 1392, 1338, 1307, 1287, 1233, 1184,
1070, 1006, 956, 839, 759, 728, 659, 610, 583
1.34 (d, 6 H, Me, 3J = 7.35);
3.18 (m, 1 H, CH);
7.51 (s, 1 H, CH);
21.2 (CH3); 28.5 (CH);
113.6, 115.4, 126.0, 138.5 (—C=);
162.3 (C—CH)
7.62 (s, 1 H, CH);
12.71 (s, 1 H, NH)
2f
3318, 2960, 2929, 2858, 1611, 1568, 1474,
1410, 1320, 1288, 1255, 1225, 1191, 1071,
958, 846, 768, 739, 684, 583
0.92 (t, 3 H, Me, 3J = 7.04);
1.37 (m, 2 H, CH2Me);
1.79 (m, 2 H, CH2CH2Me);
2.95 (t, 2 H, CH2 (CH2)2Me,
3J = 7.50); 7.40 (s, 1 H, CH);
7.73 (s, 1 H, CH)
13.5 (CH3); 21.7 (CH2CH3);
27.1 (CH2CH2CH3);
29.2 (CH2(CH2)2CH3);
115.7, 118.2, 124.5, 128.1,
132.8, 135.6 (—C=);
157.3(=C—CH2)
3a*
3131, 1613, 1549, 1479, 1385, 1339, 1315,
1278, 1196, 1127, 939, 805, 752, 701, 628
3370, 1615, 1561, 1546, 1518, 1448, 1384,
1360, 1335, 1302, 1276, 1196, 906, 818,
766, 660
8.79 (s, CH)
149.1 (CH)
3b
2.50 (s, Me)**
15.0 (CH3); 99.3, 104.7, 132.6,
135.7, 140.6; 146.2 (—C=);
160.4 (=C—CH3)
(to be continued)

Imidazo[4,5ꢀe]benzo[1,2ꢀc;3,4ꢀc´]difuroxans
Table 2 (continued)
Russ. Chem. Bull., Int. Ed., Vol. 66, No. 7, July, 2017
1253
Compound
IR, ν/cm–1
NMR (δ, J/Hz)
1Н
13С
3c*
3430, 2991, 2945, 1614, 1553, 1538, 1513,
1457, 1400, 1379, 1359, 1340, 1315, 1299,
1208, 1187, 1076, 991, 905, 823, 806
1.32 (t, 3 H, Me, 3J = 7.54);
2.93 (q, 2 H, CH2, 3J = 7.56);
13.65 (br.s, 1 H, NH)
11.7 (CH3); 22.0 (CH2CH3);
164.4 (=C—CH2)
3d
3450, 2966, 1618, 1553, 1405, 1356, 1303,
1206, 1092, 992, 807, 716
0.95 (t, 3 H, Me, 3J = 6.99);
1.81 (m, 2 H, CH2);
2.91 (t, 2 H, CH2, 3J = 7.35);
13.67 (br.s, 1 H, NH)
13.6 (CH3); 20.9 (CH2CH3);
30.3 (CH2CH2CH3);
99.1, 104.5, 132.3, 135.5, 140.5,
145.9 (—C=); 163.4 (=C—CH2)
3e
3f
3449, 2974, 2934, 1619, 1551, 1537, 1462,
1421, 1358, 1310, 1209, 1094, 991, 806, 716
1.36 (d, 6 H, Me, 3J = 7.32)
3.31 (m, 1 H, CH);
13.80 (br.s, 1 H, NH)
0.91 (t, 3 H, Me, 3J = 7.32);
21.0 (CH3); 28.6 (CH); 99.0,
104.8, 132.2, 135.8, 140.1,
145.9 (—C=); 168.0 (=C—CH2)
3450, 2958, 2930, 2860, 1615, 1552, 1403,
1355, 1300, 1221, 907, 808
13.6 (CH3); 21.8 (CH2CH3);
28.2 (CH2CH2CH3);
1.36 (m, 2 H, CH2Me);
1.76 (m, 2 H, CH2CH2Me);
2.90 (m, 2 H, CH2(CH2)2Me)
29.5 (CH2(CH2)2CH3); 99.2, 104.7,
132.3, 135.7, 140.3, 145.9 (—C=);
163.6 (=C—CH2)
5a
3130, 1654, 1607, 1563, 1534, 1498, 1461,
1416, 1391, 1262, 1064, 997, 965, 887, 811,
772, 656, 641, 456
8.35 s; 8.40 s; 8.45 s (СН)
d for the mixture of four
isomers in the ratio
1 : 0.25 : 0.13
101.4, 103.7, 105.2, 106.3
(C=N(O)O,
=C—N=C, =C—NH—C);
141.4, 143.8, 145.7 (CH и C=NO)
5b*
5c
3021, 2888, 1653, 1575, 1561, 1522, 1472,
1450, 1383, 1286, 1227, 1114, 1069, 1023,
894, 870, 828, 816, 773, 750, 715, 659
2.55 (s, Ме);
14.20 (br.s, 1 Н, NН)
14.0 (CH3); 100.7, 103.1, 104.6
(C=N(O)O,
=C—N=C, =C—NH—C); 140.9,
143.2 (C=NO); 153.7 (C—CH3)
2852, 1650, 1608, 1564, 1541, 1520, 1469,
1450, 1392, 1367, 1269, 1232, 1070, 1034,
998, 968, 925, 813, 771, 750
1.29 (t, 3 H, Me, 3J = 7.70);
2.80 (q, 2 H, CH2, 3J = 7.70);
14.15 (br.s, 1 Н, NH)
12.2 (CH3); 21.8 (CH2);
101.0, 103.3, 104.8, 105.9
(C=N(O)O,
=C—N=C, =C—NH—C);
141.1, 143.5, 144.7, 145.2
(C=NO); 158.6 (C—CH2)
5d*
3430, 2961, 2873, 1676, 1649, 1604, 1562,
1537, 1510, 1446, 1407, 1332, 1259, 1067,
1015, 996, 969, 923, 817, 769, 650
0.96 (t, 3 Н, Me, 3J = 6.99);
1.76 (m, 2 Н, CH2);
2.75 (q, 2 Н, CH2, 3J = 7.35);
14.19 (br.s, 1 Н, NH)
13.6 (CH3); 21.0 (CH2CH3);
30.1 (CH2CH2СH3);
100.9; 103.2; 104.8 (C=N(O)O,
=C—N=C, =C—NH—C);
141.0, 143.4 (C=NO);
157.6 (=C—CH2)
5e*
5f*
3430, 2972, 1649, 1606, 1560, 1518, 1448,
1384, 1236, 1092, 1063, 997, 967, 924, 806,
769, 741, 648
1.36 (d, 6 Н, Me, 3J = 6.62);
3.20 (m, 1 Н, СН);
14.19 (br.s, 1 Н, NH)
21.1 (CH3); 28.4 (CH);
101.1, 103.4 (C=N(O)O,
=C—N=C, =C—NH—C);
141.2 (C=NO); 162.1, 162.3, 162.4
(C—CH)
3448, 2956, 2874, 1681, 1647, 1607, 1557,
1519, 1450, 1393, 1266, 1096, 1065, 1024,
997, 971, 924, 811, 770, 651, 650
0.94 (t, 3 Н, Ме, 3J = 7.35);
1.36 (m, 2 Н, СН2);
1.73 (m, 2 Н, СН2);
2.82 (t, 2 Н, СН2, 3J = 7.35);
14.23 (br.s, 1 Н, NH)
13.6 (CH3); 21.7 (CH2CH3);
27.8 (CH2—CH2—CH3);
29.5, 29.7, 29.8 (CH2—C=);
103.4 (C=N(O)O);
141.2 (C=NO);157.6 (C—CH3)
* Low intensity and broadening of signals in the 13C NMR spectra of compounds 2b,c,d,f, 3a,c, and 5b,d,e,f lead to a decrease in the
number of signals for aromatic carbon atoms.
** Overlapped with the signal of the solvent DMSOꢀd6.
chlorides, nitration of 4,6ꢀdibromobenzimidazoles,
azidation of 4,6ꢀdibromoꢀ5,7ꢀdinitrobenzimidazoles,
and thermal cyclization of 4,6ꢀdiazidoꢀ5,7ꢀdinitrobenzꢀ
imidazoles.
Experimental
Melting points were determined on a Boetius microscope
heating stage. Electrospray ionization high resolution mass

1254
Russ. Chem. Bull., Int. Ed., Vol. 66, No. 7, July, 2017
Korolev et al.
spectra (ESIꢀMS) were recorded on a Q Exactive in a positive
ion mode; capillary potential 3500 V, range of scanning masses
90—900 Da. 1H and 13C NMR spectra were recorded on
a Bruker AMꢀ300; 1H and 13C NMR chemical shift were meaꢀ
(2 mL) was refluxed for 2 h and cooled to 20 °C. Then, a 10%
aqueous solution of NaOH was added to make the reaction
mixture weakly basic, a precipitate formed was collected by
filtration, washed with water, dried, and recrystallized from
a mixture of EtOH—H2O. Characteristics of compounds 2a—e
are summarized in Tables 2 and 3.
sured relative to the signal of solvent (DMSOꢀd6, δ 2.5;
H
δ
C 39.5). IR spectra were recorded on a Vector 22 spectrometer
in KBr pellets.
Quantum chemical calculations were carried out by DFT
Synthesis of 2ꢀbutylꢀ4,6ꢀdibromobenzimidazole (2f). A mixꢀ
ture of compound 1 (1.7 g, 6.39 mmol) and valeroyl chloride
(2.0 g, 16.53 mmol) in pyridine (4 mL) was refluxed for 2 h,
cooled to 50 °C, and poured into water (15 mL), a precipitate
formed was collected by filtration, washed with water, dried,
and recrystallized from a mixture of EtOH—H2O. Characterisꢀ
tics of compound 2f are summarized in Tables 2 and 3.
Synthesis of 2ꢀRꢀ4,6ꢀdibromoꢀ5,7ꢀdinitrobenzimidazoles
B3LYP in the basis 6ꢀ311++G(d,p) using the GAUSSIAN 09
software35 with full optimization of geometrical parameters of
structure without any restriction of the symmetry. After optiꢀ
mization of geometry, the frequencies of normal vibration of
these compounds were calculated. The absence of imaginary
values of frequency in the vibrational spectrum indicated that
the optimized structures correspond to the minima on the poꢀ
tential energy surface (PES), rather than to the transition states.
Synthesis of 2ꢀRꢀ4,6ꢀdibromobenzimidazoles (2a—e) (genꢀ
eral procedure). A solution of 1 (1.0 g, 3.76 mmol) in RCOOH
(3a—f) (general procedure). Nitric acid (1 mL, d = 1.50 g cm–3
)
was added dropwise to compounds 2a—f (3.62 mmol) in H2SO4
(7 mL) (d = 1.84 g cm–3) at 0—5 °C with stirring. The temperꢀ
ature was increased to 90—95 °C and the mixture was stirred for
Table 3. Physicochemical characteristics of synthesized compounds
Comꢀ
pound
Yield
(%)
M.p./°С
Found
Calculated
Molecular
formula
m/z [M + H]+
found
calculated
(%)
N
С
Н
Br
2а
2b
2c
2d
2e
2f
95
81
78
85
80
83
90
86
75
70
53
37
80
40
70
70
80
72
230—232
(Ref. 36: 223—225)
216—218
(Ref. 36: 212—215)
179—181
30.53
30.43
33.26
33.10
35.56
35.53
37.81
37.74
37.79
37.74
39.80
39.76
23.02
22.95
25.45
25.26
27.44
27.41
29.53
29.41
29.43
29.41
31.34
31.27
35.94
35.90
38.56
38.71
41.23
41.22
43.55
43.48
43.58
43.48
45.61
45.52
1.48
1.45
2.15
2.07
2.65
2.63
3.17
3.14
3.16
3.14
3.64
3.61
0.41
0.55
1.18
1.05
1.54
1.52
2.01
1.96
1.98
1.96
2.43
2.37
0.75
0.85
1.43
1.61
2.31
2.29
2.96
2.90
2.98
2.90
3.52
3.45
10.23
10.14
19.22
19.66
19.22
19.21
18.83
18.81
18.85
18.81
18.51
18.43
15.21
15.30
14.53
14.74
14.22
14.21
13.82
13.73
13.75
13.73
13.31
13.27
35.80
35.90
33.69
33.87
32.06
32.06
30.48
30.43
30.52
30.43
29.04
28.97
58.05
57.97
55.23
55.17
52.68
52.63
50.33
50.31
50.38
50.31
48.34
48.19
43.85
43.72
42.26
42.11
40.85
40.61
39.30
39.22
39.41
39.22
38.04
37.91
—
C7H4Br2N2
C8H6Br2N2
276.8790
276.8794
290.8942
290.8950
304.9099
304.9107
318.9256
318.9263
318.9255
318.9263
332.9414
332.9420
366.8488
366.8495
380.8643
380.8652
394.8799
394.8808
408.8957
408.8965
408.8958
408.8965
422.9114
422.9121
235.0206
235.0210
249.0360
249.0367
263.0517
263.0523
277.0673
277.0680
277.0674
277.0680
291.0830
291.08367
C9H8Br2N2
225—227
226—228
C10H10Br2N2
C10H10Br2N2
C11H12Br2N2
C7H2Br2N4O4
C8H4Br2N4O4
C9H6Br2N4O4
C10H8Br2N4O4
C10H8Br2N4O4
C11H10Br2N4O4
C7H2N6O4
181—183
3a
3b
3c
3d
3e
3f
303—305
306—308
287—289
272—274
275—277
254—256
5a
5b
5c
5d
5e
5f
220 (decomp.)
190 (decomp.)
211 (decomp.)
200 (decomp.)
195 (decomp.)
195 (decomp.)
—
—
—
—
—
C8H4N6O4
C9H6N6O4
C10H8N6O4
C10H8N6O4
C11H10N6O4

Imidazo[4,5ꢀe]benzo[1,2ꢀc;3,4ꢀc´]difuroxans
Russ. Chem. Bull., Int. Ed., Vol. 66, No. 7, July, 2017
1255
3 h, cooled to 20 °C, and poured onto ice. A precipitate formed
was collected by filtration, washed with water, and dried. Charꢀ
acteristics of compounds 3a—f are summarized in Tables 2 and 3.
Synthesis of 2ꢀRꢀimidazo[4,5ꢀe]benzo[1,2ꢀc;3,4ꢀc´]difurꢀ
oxanes 5a—f (general procedure). A mixture of compounds 3a—f
(2.63 mmol) and NaN3 (0.45 g, 6.92 mmol) in DMF (5 mL)
was stirred at 20 °C until the starting compound disappeared
(TLC monitoring). After addition of water (100 mL), a precipꢀ
itate formed (4a—f) was collected by filtration, transferred into
AcOH (3 mL), heated for 2 h at 100 °C, and cooled to 20 °C.
A precipitate formed was collected by filtration, washed with
water, heated in water (10 mL) for 0.5 h at 100 °C, cooled to
20 °C, filtered, and dried. Characteristics of compounds 5a—f
are summarized in Tables 2 and 3.
Toporov, V. M. Danilenko, N. V. Pyatakova, I. S. Severiꢀ
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19. (a) A. A. Alekseyev, Ph. D. Thesis (Pharm.), I. M. Sechenꢀ
ov First Moscow State Medical University, Moscow, 2015,
152 pp. (in Russian).
20. Pat. RF No. 2502739; Byul. Izobret. [Invention Bull.], 2013,
5, 7 (in Russian).
21. A. A. Alekseyev, M. I. Brylev, V. L. Korolev, D. S. Lotorev,
A. Yu. Lizunov, L. A. Pavlova, V. P. Ivshin, O. Yu. Domaꢀ
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22. Pat RF No. 2549355; Byul. Izobret. [Invention Bull.], 2015, 12,
7 (in Russian).
23. Pat RF No. 2550223; Byul. Izobret. [Invention Bull.], 2014, 13,
9 (in Russian).
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Received February 15, 2017;
in revised form April 13, 2017