Reactions of 2Н(4Н)-chromenes with dinucleophiles: one-step synthesis of 2-(1H-(bi)pyrazol-3-yl)- and 2-(1,4(5)-(benzo)diazepin-4-yl)phenols

Article abstract of DOI:10.1007/s10593-018-2367-y

[Figure not available: see fulltext.] Novel derivatives of 2-(1H-(bi)pyrazol-3-yl)phenols and 2-(1,4(5)-(benzo)diazepin-4-yl)phenols were obtained in the reaction of (4-amino-2H-chromen-2-ylidene)malondialdehyde and 4H-chromen-4-imines with 1,2-, 1,3-, and 1,4-dinucleophiles proceeding as a cascade reaction initiated by the Michael reaction.

Full text of DOI:10.1007/s10593-018-2367-y

DOI 10.1007/s10593-018-2367-y
Chemistry of Heterocyclic Compounds 2018, 54(9), 859–867
Reactions of 2Н(4Н)-chromenes with dinucleophiles:
one-step synthesis of 2-(1H-(bi)pyrazol-3-yl)-
and 2-(1,4(5)-(benzo)diazepin-4-yl)phenols
Serhii P. Zahorulko1, Svetlana А. Varenichenko1*, Oleg K. Farat2,
Aleksander V. Mazepa3, Sergiy I. Okovytyy4, Victor I. Markov1
1 Ukrainian State University of Chemical Technology,
8 Gagarina Ave., Dnipro 49005, Ukraine; е-mail: svetlanavarenichenko@gmail.com
2 Moscow M. V. Lomonosov State University,
1 Build. 3 Leninskie Gory, Moscow 119991, Russia; е-mail: faratok@mail.ru
3 A. V. Bogatsky Physico-Chemical Institute, National Academy of Sciences of Ukraine,
86 Lyustdorfskaya Road , Odessa 65080, Ukraine; е-mail: almazepa@rambler.ru
4 Oles Honchar Dnipro National University,
72 Gagarina Ave., Dnipro 49010, Ukraine; е-mail: sokovyty@icnanotox.org
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
2018, 54(9), 859–867
Submitted March 6, 2018
Accepted after revision September 27, 2018
Novel derivatives of 2-(1H-(bi)pyrazol-3-yl)phenols and 2-(1,4(5)-(benzo)diazepin-4-yl)phenols were obtained in the reaction of
(4-amino-2H-chromen-2-ylidene)malondialdehyde and 4H-chromen-4-imines with 1,2-, 1,3-, and 1,4-dinucleophiles proceeding as a
cascade reaction initiated by the Michael reaction.
Keywords: chromenes, dipyrazoles, dinucleophiles, rearrangement, Vilsmeier–Haack reagent.
Currently, one of the most rapidly developing areas of
modern organic chemistry is the transformation
(recyclization) reactions of heterocyclic systems. These
chemical transformations lead not only to the rapid
formation of complex molecules, but also provide the
possibility of their further modification. Chromene
derivatives are very promising starting model compounds
for the study of such transformations. Due to their high
reactivity, various heterocyclic compounds may be
formed.1 The presence of several electrophilic centers in
chromene derivatives makes it possible to study in detail
the recyclization reactions with various nucleophilic
reagents, resulting in o-hydroxyphenyl derivatives of
pyrazoles and oxazoles,2–6 pyrazines and quinoxalines,7 as
well as aminopyrimidines.8,9 o-Hydroxyphenyl group is of
interest as a structural fragment of a large number of
biologically active compounds,10–13 stabilizers of polymeric
materials,14,15 antioxidants, and analytical reagents for
complexation with transition metal ions.16
Earlier,17 we obtained from compounds 1a,b polyfunc-
tional diformyl derivatives of chromenes 2a,b (Scheme 1),
promising starting compounds for combinatorial chemistry
due to the large number of possible functionalization
options. They are also attractive due to their photophysical
properties: in the solid state, derivatives of (4-amino-
chromen-2-ylidene)malondialdehyde 2a,b fluoresce in the
red region of the spectrum with a Stokes shift of 47 and
67 nm (1230 and 1900 cm–1), respectively.18
0009-3122/18/54(9)-0859©2018 Springer Science+Business Media, LLC
859

Chemistry of Heterocyclic Compounds 2018, 54(9), 859–867
Scheme 1
In the reaction of compounds 2a,b with hydrazine
In the literature, only two examples of the preparation of
such dipyrazoles can been found: the reaction of 4H,4'H-
3,3-bischromene-4,4'-dione derivatives with hydrazine19
and the treatment of 3-(3-aryl-3-oxopropenyl)chromen-
4-ones with hydrazine with their subsequent oxidation to
dipyrazoles.20
We have proposed a possible route for this reaction
(Scheme 3). An analysis of the bond lengths of compound
2a17 shows a significant redistribution of the electron
density in the molecule from the amino group to the
malondialdehyde group. Thus, carbonyl bonds are
lengthened to 1.226(3)–1.241(3) Å compared to the
average C=O bond length in aldehydes of 1.192 Å and
the C(9)–N(1) bond, at 1.316(3)–1.320(3) Å, is slightly
shortened compared with the average value for C(sp2)–NH2
bonds (1.336 Å).21 Despite the significantly reduced
electrophilicity of the carbon atoms of the carbonyl groups
compared to the carbon atoms of an aldehyde group which
is not conjugated with an electron-donating substituent, in
the first stage, the cyclic intermediate A is formed, for
hydrate, the pyranyl ring is opened to form o-hydroxy-
phenyl derivatives, dipyrazoles 4a,b, in 48–50% yields
(Scheme 2).
Presumably, the reaction proceeds according to the
mechanism of nucleophilic addition at the C-2 atom of
chromenes 2a,b, and compounds 4a,b are formed as a
result of the subsequent 5-exo-trig cyclization. Compound
4a retains its ability to fluorescence in the solid state in the
yellow-green region of the spectrum.
Scheme 2
R
OH
R
CHO
CHO
O
N
NH2NH2·H2O
DMF, , 1 h
R
NH
R
NH2
2a,b
N NH
4a
b
R = H (48%)
R = i-Pr (50%)
Scheme 3
O–
O
CHO
CHO
R
R
N
N
R
R
O
N
O
NH
O
O
NH2NH2·H2O
R
R
R
R
N+
NH2
NH2
A
NH
H
H
3a,b
2a,b
H2NNH2
NH2
NH2
+NH2
O
HN
N
NH
R
R
R
NH2NH2·H2O
O
N
O
N
NH
NH
R
R
R
– NH
NH2
NH
B
R
NH2
NH
NH2
OH
R
R
N
N
O–
NH
OH
N
NH
N
NH
R
NH HN
NH2
R
R
NH2
NH2
R
OH
R
OH
N
R
N
NH
NH
– NH3
R
H2N
HN
NH
N NH
4a,b
860

Chemistry of Heterocyclic Compounds 2018, 54(9), 859–867
which prototropic tautomerism is possible. The presence of
nature of this reaction is very close to the recyclization of
an activated double bond in the chromene ring allows
intermediates 3a,b to be regarded as Michael acceptors. This
is followed by the addition of the hydrazine molecule at the
double bond with the formation of the unstable Michael
adduct B, which stabilizes by cleavage of the chromene ring
and subsequent cyclization to dipyrazoles 4a,b.
benzopyrans 2a,b.
Scheme 5
R
OH
a R = H, Ar = Ph
NH2NH2·H2O
b R = H, Ar = 4-O2NC6H4
c R = i-Pr, Ar = Ph
EtOH
1H NMR spectra of compounds 4a,b contain the
characteristic singlet signals of the protons of NH groups in
the 13.07–13.33 ppm range and the signal of the proton of
the hydroxyl group in the 10.98–11.20 ppm range. In the
13С NMR spectra of compounds 4a,b, the signals of the
carbon atoms of the pyrazole rings as well as the carbon
atom bonded to the OH group are recorded. Vibrations of
the OH and NH groups in the IR spectrum of compound 4a
correspond to intense absorption bands at 3418 and 2292–
3252 cm–1.
N
6a–d
R
, 3–4 h
32–74%
NH
d R = i-Pr, Ar = 4-O2NC6H4
7a–d
Ar
To establish the most preferred localization of NH
protons in dipyrazoles 4a,b and pyrazoles 7a–d, we
investigated the tautomeric properties of compounds 4a,
7a,b (Fig. 1) by quantum-chemical calculations using the
MP2/6-311+G(d,p) approximation (Table 1).
A characteristic feature of the structure of compounds
4a, 7a,b is the nonplanar mutual arrangement of rings,
which is consistent with the X-ray diffraction data of
similar compounds.24,25 The dihedral angle between
pyrazole rings (as well as pyrazole and phenyl (nitroaryl))
varies within 38.4–52.0° for N(2)–H tautomers and 25.2–
30.3° for N(1)–H forms. The dihedral angle between the
phenol and pyrazole rings is significantly smaller (15.9–
21.0°), which can be explained by the formation of
O–H···N or O···H–N hydrogen bonds with a length of 1.82–
1.83 Å and 2.11 Å, respectively. The high strength of the
O–H···N bond increases the stability of the N(2)–H
tautomers for all studied compounds. The position of the
proton in the second pyrazole ring of compound 4a has
practically no effect on the energy of the compound. It
should be noted that, unlike pyrazoles 4a, 7a, for which the
occupancy of the N(2)–H forms exceeds 99%, there is a
significant occupancy of the tautomeric N(1)–H form
(20%) in the case of nitroaryl derivative 7b. This is due to
the electron-withdrawing effect of the nitro group, as a
result of which the basicity of the N(1) atom in the N(2)–H
tautomer decreases (and, as a result, the energy of the O–H···N
hydrogen bond decreases), and the acidity of the N(1)-H group
increases in the corresponding tautomer, which leads to an
increase in the energy of the O···H–N hydrogen bond as
compared to compounds 4a and 7a. This is experimentally
In order to expand the number of examples of an effective
method for the synthesis of pyrazole derivatives, we obtained
new model compounds, imines 6a–e (Scheme 4), which
possess an activated double bond. Despite the availability
of literature data on the recyclization of chromones by the
action of nucleophilic reagents, it is necessary to emphasize
the lack of information on the reactivity of 4H-chromen-
4-imines under these conditions. Considering the different
electronegativity of oxygen and nitrogen atoms, it was
necessary to establish whether the replacement of the C=O
group in the chromone ring by the C=NH group in the
chromene ring would influence the course of the reaction.
Synthesis of imine derivatives 6b–e illustrates the
general nature of the new multistage cascade reaction,
namely, rearrangement of geminal 1,3-benzoxazines 5b–e
by the action of the Vilsmeier–Haack reagent, which has
previously been described in one example.17 Compounds
5a–e were prepared according to a published method.23
The characteristic signal of the 3-CH proton of
chromene products 6a–e appears at 6.91–7.45 ppm.
Scheme 4
1
confirmed by the H NMR spectrum of compound 7b,
where, unlike the spectra of compounds 4a and 7a, the
signals of the protons of the OH and NH groups are not
observed due to deuterium exchange with the solvent.
We found that when benzopyran 2a reacts with
o-phenylenediamine under the conditions of acid catalysis,
benzodiazepine 8 is formed (Scheme 6). Unlike the parent
compound, fluorescence is not observed for compound 8.
The expected substituted (1H-pyrazol-3-yl)phenols 7a–d
(Scheme 5) were obtained in the reaction of imines 6a–d
with hydrazine hydrate. The structure of compounds 7a–d,
confirmed by a collection of spectral data, suggests that the
Figure 1. Structures of compounds 4a, 7a,b.
861

Chemistry of Heterocyclic Compounds 2018, 54(9), 859–867
Table 1. Quantum-chemical data of the localization of the proton of the NH group in dipyrazole 4a and pyrazoles 7a,b
Compound
Parameter
4a
ΔGrel, kJ/mol
Occupancy, %
α*, deg
0.00
55.95
20.2
0.63
43.38
19.8
12.75
0.32
15.9
12.56
0.35
20.0
β**, deg
48.9
52.0
30.3
27.5
Hydrogen bond length, Å
1.820
1.820
2.110
2.110
7a
7b
ΔGrel, kJ/mol
Occupancy, %
α*, deg
0.00
99.74
19.0
14.71
0.00
3.43
0.26
19.7
79.97
21.0
20.03
20.2
γ***, deg
40.9
29.3
38.4
25.2
Hydrogen bond length, Å
1.820
2.110
1.830
2.110
* The angle between hydroxyphenyl and pyrazole rings.
** The angle between pyrazole rings.
*** The angle between pyrazole and phenyl (nitroaryl) rings.
compound 9b are linked by weak intermolecular hydrogen
bonds of the C–H···π type. The seven-membered ring of the
heterocycle is in the "bath" conformation. The C(1), C(6), and
C(8) atoms deviate from the RMS plane of the rest of the
heterocyclic ring atoms by 0.55 Å in molecule A and by 0.63
and 0.77 Å in molecule B. The p-nitrophenyl and o-hydroxyl-
phenyl substituents are somewhat noncoplanar with the
endocyclic double bonds N(1)=C(9) and N(2)=C(7) (torsion
angles N(1)–C(9)–C(16)–C(21) equal 15(1)° in molecule A
and 9(1)° in molecule B; angles N(2)–C(7)–C(10)–C(11) equal
2(1)° in molecule A and 4(1)° in molecule B), which is a
consequence of significant steric repulsion between atoms of
the aromatic rings and atoms of the heterocyclic ring (shortened
intramolecular contacts H(21a)···N (1a) 2.45 Å, H(17a)···C(8a)
2.73 Å, H(17a)···H(8ab) 2.07 Å, H(8ab )···C(17a) 2.65 Å,
H(15a)···C(8a) 2.66 Å, H(8ab)···C(15a) 2.61 Å, H (8ab)···H(15a)
2.02 Å in molecule A and H(21b)···N(1b) 2.44 Å,
H(17b)···C(8b) 2.73 Å, H(17b)···H(8bb) 2.06 Å, H(8bb)···C (17b)
2.63 Å, H(15b)···C(8b) 2.68 Å, H(8bb)···C(15b) 2.62 Å,
H(8bb)···H(15b) 2.03 Å in molecule B with the sum of van der
Scheme 6
In the reaction with 1,4-dinucleophiles, o-phenylene-
diamine and ethylenediamine, imines 6a,b,d form recycli-
zation products o-hydroxyphenylbenzodiazepines 9a,b,d
and 10b,d (Scheme 7). The reaction was carried out by
heating under reflux in DMF for 1–3 h; when AcOH was
present in catalytic amounts, the product yields somewhat
increased. Benzodiazepine 9a exhibits the ability to
fluorescence in the solid state in the yellow-green region of
the spectrum.
The structure of compound 9b was proven by X-ray
structural analysis (Fig. 2). In the solid state, the molecules of
Scheme 7
862

Chemistry of Heterocyclic Compounds 2018, 54(9), 859–867
with 1,2-, 1,3-, and 1,4-dinucleophiles is presented in this
work. Replacing the C=O group with the C=NH group in
the chromene ring reduces the reactivity with respect to
dinucleophilic reagents compared to chromones, but the
reaction proceeds in a similar way. This recyclization can
be widely used in the synthesis of o-hydroxyphenyl
derivatives of heterocyclic compounds.
Experimental
IR spectra were registered on a PerkinElmer One FT-IR
spectrometer in KBr pellets. 1H and 13C NMR spectra were
acquired on a Bruker Avance II 400 spectrometer (400 and
100 MHz, respectively) in DMSO-d6 or DMSO-d6–
CF3CO2D, 10:1 (compounds 8, 9a,b), with TMS as internal
standard. Mass spectra (FAB ionization) were registered on a
VG-7070 spectrometer. Ion desorption from m-nitrobenzyl
alcohol was done by a beam of argon atoms with an energy
of 8 keV. Mass spectra (EI ionization, 70 eV) for
compounds 4a and 8 were recorded on a Varian 1200L
apparatus with direct sample injection at 250°C ionization
chamber temperature. Elemental analysis was performed
on a LECO CHN-900 Elemental analyzer. Melting points
were determined on an Electrothermal 9100 Digital
apparatus. Monitoring of the reaction progress and
assessment of the purity of synthesized compounds was
done by TLC on Silica gel 60 F254 (Merck) plates, eluent
CHCl3−i-PrOH, 10:1, visualization in the iodine chamber.
Compounds 2а and 6а were synthesized following a
published method.17
Figure 2. Molecular structure of compound 9b with atoms
represented as thermal vibration ellipsoids with 50% probability.
The intramolecular hydrogen bonds OH···N are denoted by dashed
lines.
Waals radii26 H···N 2.67 Å, H···C 2.87 Å, H···H 2.34 Å). It
can be assumed that the weaker rotation of the o-hydroxy-
phenyl substituent is due to the formation of an intramolecular
O(1)–H···N(2) hydrogen bond (H···N 1.84 Å, angle O–H···N
144° in molecule A and H···N 1.84 Å, angle O–H···N 146° in
molecule B).
A notable feature of the spectral data of diazepins 9a,b is
the predominance of the diimine (3H) form in the presence
of a couple of drops of CF3CO2H, while for compound 9d,
the enamine (1H) form is observed in DMSO-d6.
As a result of the reaction of imine 6b with the
1,3-dinucleophile guanidine, aminopyrimidine 11 was
obtained in good yield (Scheme 8). The reaction was
carried out by refluxing in MeOH in the presence of an
equimolar amount of MeONa, since guanidine was used as
the hydrochloride.
Synthesis of bipyrazoles 4a,b (General method).
Dialdehyde 2a,b (1.2 g, 5.6 mmol) was dissolved in DMF
(10 ml). Hydrazine hydrate (0.54 ml, 11.1 mmol) was added
to the solution, and the mixture heated under reflux for 1 h.
After cooling, the solution was poured into H2O (20 ml),
the formed precipitate was filtered off and recrystallized
from methanol.
1
In the H NMR spectrum of aminopyrimidine 11, the
signal of the OH group proton is at 13.75 ppm. The
characteristic signal of the pyrimidine ring has a chemical
shift of 7.96 ppm, and the signals of the amino group
protons are at 6.94 ppm. The vibrations of the amino group
in the IR spectrum correspond to an intense absorption
band at 3358 cm–1. At 3428 cm–1, the absorption band of
the OH group can be found. In the 13C NMR spectrum, the
characteristic signals of the carbon atoms of the chromene
and pyrimidine rings resonate in the downfield region of
the spectrum.
2-(1'H,2H-3,4'-Bipyrazol-5-yl)phenol (4а). Yield
0.61
g (48%), light-yellow powder, mp 260–261°C.
IR spectrum, ν, cm–1: 3418 (OH), 3252 (NH), 2922 (NH).
1H NMR spectrum, δ, ppm: 13.33 (1Н, s, NH); 13.13 (1Н,
s, NH); 10.98 (1Н, s, ОН); 8.16 (1Н, br. s, Н Ar); 7.92 (1Н,
br. s, Н Ar); 7.70–7.68 (1Н, m, Н Ar); 7.17–7.15 (1Н, m,
Н Ar); 7.00 (1Н, s, Н Ar); 6.89–6.87 (2H, m, H Ar).
13C NMR spectrum, δ, ppm: 155.3; 151.1; 136.9; 136.5;
128.7; 126.5; 119.1; 118.3; 117.6; 116.3; 110.2; 98.4. Mass
spectrum, m/z (Irel, %): 226 [M]+ (100). Found, %: C 63.76;
H 4.58; N 24.67. C12H10N4O. Calculated, %: C 63.71;
H 4.46; N 24.76.
To conclude, an effective one-step method for the
synthesis of previously unknown 2-(1H-(bi)pyrazol-3-yl)-
phenols,
2-(1,4(5)-(benzo)diazepin-4-yl)phenols,
and
pyrimidin-4-ylphenol by the reaction of 2H(4H)-chromenes
Scheme 8
2-(1'H,2H-3,4'-Bipyrazol-5-yl)-4,6-diisopropylphenol
(4b). Yield 0.86 g (50%), light-beige powder, mp 254–255°C.
1H NMR spectrum, δ, ppm: 13.26 (1Н, s, NH); 13.07 (1Н,
s, NH); 11.20 (1Н, s, ОН); 8.17 (1Н, s, Н Ar); 7.95 (1Н, s,
Н Ar); 7.36 (1Н, s, Н Ar); 7.01–6.98 (2Н, m, Н Ar); 3.28–
3.26 (1Н, m, СН(CH3)2); 2.86–2.85 (1Н, m, СН(CH3)2);
1.22–1.20 (12Н, m, CH3). 13C NMR spectrum, δ, ppm:
152.1; 150.9; 138.6; 136.9; 134.8; 126.3; 123.5; 121.4
(2C); 115.9; 110.4; 98.3; 33.2; 26.7; 24.5; 22.7. Mass
spectrum, m/z (Irel, %): 311 [M+Н]+ (100). Found, %:
OH
NH·HCl
N
NH2
H2N
NH2
N
MeONa
6b
MeOH, , 3–3.5 h
80%
NO2
11
863

Chemistry of Heterocyclic Compounds 2018, 54(9), 859–867
C 69.58; H 7.09; N 18.12. C18H22N4O. Calculated, %:
C 69.65; H 7.14; N 18.05.
mp 216–218°C. IR spectrum, ν, cm–1: 3181 (NH), 3075
1
(CH Ar), 2912 (CH), 1679 (C=O). H NMR spectrum,
3
Synthesis of 1,3-benzoxazines 5a–e (General method).
A solution of the corresponding salicylamide (10 mmol),
ketone (12 mmol), and p-TsOH (5 mmol) in PhMe (70 ml)
was heated under reflux for 4–6 h with azeotropic removal
of water using the Deen–Stark adaptor. The reaction
mixture was cooled to 10°С and stirred at this temperature
for 1 h. The formed precipitate was filtered off, washed with
PhMe (10 ml) followed by i-PrOH (10 ml), and dried at 50°С.
The solid was mixed with 5% aqueous NaOH, filtered, and
recrystallized from MeOH.
δ, ppm (J, Hz): 9.47 (1Н, s, NH); 7.61 (1Н, d, J = 7.3,
3
Н Ar); 7.50 (2Н, d, J = 8.3, Н-3,5 Ar); 7.43 (1Н, t,
3J = 7.8, Н Ar); 7.38 (2Н, d, J = 8.3, Н-2,6 Ar); 7.05 (1Н, d,
3
3J = 7.8, Н Ar); 6.97 (1Н, t, J = 7.3, Н Ar); 1.77 (1H, s,
CH3). 13C NMR spectrum, δ, ppm: 161.7; 155.5; 143.2;
134.5; 131.2; 127.8; 127.0; 122.0; 121.4; 117.9; 117.1; 88.9;
29.9. Mass spectrum, m/z (Irel, %): 318 [М(81Br)+Н]+ (94),
320 [М(79Br)+Н]+ (100). Found, %: C 56.74; H 3.86; N 4.33.
C15H12BrNO2. Calculated, %: C 56.63; H 3.80; N 4.40.
Synthesis of imines 6a–e (General method). The
Vilsmeier–Haack reagent was prepared by mixing POCl3
(0.9 ml, 9.6 mmol) and DMF (2.3 ml, 30 mmol) in ice bath.
The corresponding oxazine 5a–e (5 mmol) was added to
the prepared reagent solution. The reaction mixture was
heated in water bath at 80°С for 1 h, then cooled to 10°С,
and 15% aqueous NaClO4 (10 ml) added. The precipitate of the
corresponding salt was filtered, dried, and purified by boiling
with PhMe. The prepared perchlorate was dissolved in
MeOH (5 ml) and treated with 15% aqueous NaOH
(1.5 ml). The mixture was boiled for a few minutes, then
cooled to room temperature, and diluted with H2O (3–4 ml).
The precipitate was filtered off, washed with H2O, and the
prepared imines 6a–e purified by recrystallization from
MeCN.
2-Methyl-2-phenyl-2,3-dihydro-4Н-1,3-benzoxazin-4-one
(5a). Yield 2.19 g (92%), white powder, mp 229–230°C
(mp 227–228°C27). Spectral characteristics match litera-
ture data.27
2-Methyl-2-(4-nitrophenyl)-2,3-dihydro-4Н-1,3-benz-
oxazin-4-one (5b). Yield 1.85 g (65%), white powder,
mp 195–197°C. IR spectrum, ν, cm–1: 3184 (NH), 3075
1
(CH Ar), 1680 (C=O). H NMR spectrum, δ, ppm (J, Hz):
3
9.58 (1Н, s, NH); 8.15 (2Н, d, J = 8.8, Н-3,5 Ar); 7.71
(2Н, d, 3J = 8.8, Н-2,6 Ar); 7.61 (1Н, d, 3J = 7.7, Н-5); 7.44
(1Н, t, 3J = 8.0, Н-7); 7.10 (1Н, d, 3J = 8.0, Н-8); 6.98 (1Н,
3
t, J = 7.3, Н-6); 1.81 (3H, s, CH3). 13C NMR spectrum,
δ, ppm: 161.6; 155.5; 151.1; 147.3; 134.8; 127.2; 127.1;
123.7; 122.4; 117.9; 117.3; 88.9; 29.6. Mass spectrum, m/z
(Irel, %): 285 [M+Н]+ (100). Found, %: C 63.43; H 4.34;
N 9.79. C15H12N2O4. Calculated, %: C 63.38; H 4.26; N 9.85.
2-Methyl-2-phenyl-6,8-di(propan-2-yl)-2,3-dihydro-
4Н-1,3-benzoxazin-4-one (5с). Yield 2.43 g (75%), white
powder, mp 205–207°C. IR spectrum, ν, cm–1: 3174 (NH),
3060 (CH Ar), 2965 (CH), 1679 (C=O). 1H NMR
spectrum, δ, ppm (J, Hz): 9.27 (1Н, s, NH); 7.45–7.43 (2Н,
m, Н Ph); 7.34–7.31 (3Н, m, Н Ph); 7.22–7.20 (2Н, m,
Н-5,7); 3.40 (1Н, sept, 3J = 6.8, СН(СН3)2); 2.76 (1Н, sept,
3J = 6.8, СН(СН3)2); 1.80 (3Н, s, СН3); 1.20 (6Н, d,
2-Phenyl-4Н-chromen-4-imine (6a). Yield 0.86 g (78%),
white powder, mp 70–72°С (mp 68–70°С17). Spectral
characteristics match literature data.17
2-(4-Nitrophenyl)-4Н-chromen-4-imine (6b). Yield
0.72 g (54%), yellow powder, mp 203–205°C. IR spectrum,
ν, cm–1: 3079 (CH Ar), 1524 (as NO2), 1345 (sym NO2).
1H NMR spectrum, δ, ppm: 8.33–8.31 (4Н, m, Н Ar); 8.23–
8.22 (1Н, m, NH); 8.06–8.04 (1Н, m, Н Ar); 7.85–7.83
(1Н, m, Н Ar); 7.77–7.76 (1Н, m, Н Ar); 7.50–7.48 (1Н,
m, Н Ar); 7.14 (1Н, s, 3-СН). 13C NMR spectrum, δ, ppm:
159.8; 159.3; 155.3; 148.7; 136.7; 134.1; 127.3; 125.3;
124.4; 123.5; 118.1; 108.8. Mass spectrum, m/z (Irel, %):
267 [M+Н]+ (100). Found, %: C 67.76; H 3.69; N 10.59.
C15H10N2O3. Calculated, %: C 67.67; H 3.79; N 10.52.
6,8-Diisopropyl-2-phenyl-4Н-chromen-4-imine (6с).
Yield 1.04 g (68%), yellow powder, mp 210–212°C.
3
3J = 6.8, СН(СН3)2); 1.10 (6Н, d, J = 6.8, СН(СН3)2).
13C NMR spectrum, δ, ppm: 162.4; 150.5; 143.9; 141.2;
135.8; 129.3; 128.2; 128.1; 125.3; 121.4; 117.4; 88.8; 32.7;
30.3; 25.5; 23.8; 23.4; 22.6. Mass spectrum, m/z (Irel, %):
324 [M+Н]+ (100). Found, %: C 77.84; H 7.86; N 4.27.
C21H25NO2. Calculated, %: C 77.98; H 7.79; N 4.33.
1
2-Methyl-2-(4-nitrophenyl)-6,8-di(propan-2-yl)-2,3-di-
hydro-4Н-1,3-benzoxazin-4-one (5d). Yield 2.94 g (80%),
beige powder, mp 218–220°C. IR spectrum, ν, cm–1: 3184
(NH), 3078 (CH Ar), 2961 (CH), 1679 (C=O), 1524 (as NO2),
IR spectrum, ν, cm–1: 3170 (NH), 2968 (CH). H NMR
spectrum, δ, ppm (J, Hz): 10.46 (1Н, s, NH); 8.22 (1Н, s,
Н-7); 8.11–8.10 (2Н, m, Н Ph); 7.90 (1Н, s, Н-5); 7.72–
7.70 (3Н, m, Н Ph); 7.45 (1Н, s, 3-СН); 3.73 (1H, sept,
1
3
1348 (sym NO2). H NMR spectrum, δ, ppm (J, Hz): 9.53
3J = 6.8, CH(CH3)2); 3.09 (1H, sept, J = 6.8, CH(CH3)2);
3
3
(1Н, s, NH); 8.20 (2Н, d, J = 8.3, Н-3,5 Ar); 7.70 (2Н, d,
J = 8.7, Н-2,6 Ar); 7.34 (1Н, s, Н-7); 7.25 (1Н, s, Н-5);
3.24 (1Н, sept, 3J = 6.8, СН(СН3)2); 2.76 (1Н, sept, 3J = 6.8,
1.39 (6H, d, J = 6.8, CH(CH3)2); 1.30 (6H, d, J = 6.8,
CH(CH3)2). 13C NMR spectrum, δ, ppm: 163.7; 161.2;
150.4; 147.7; 138.4; 133.3; 132.9; 129.8; 129.6; 126.8;
118.4; 113.8; 98.9; 33.6; 27.0; 23.7; 22.4. Mass spectrum,
m/z (Irel, %): 306 [M+Н]+ (100). Found, %: C 82.67;
H 7.50; N 4.65. C21H23NO. Calculated, %: C 82.58; H 7.59;
N 4.59.
3
СН(СН3)2); 1.82 (3Н, s, СН3); 1.18 (6Н, d, J = 6.8,
3
СН(СН3)2); 1.07 (6Н, d, J = 6.8, СН(СН3)2). 13C NMR
spectrum, δ, ppm: 162.1; 151.1; 150.2; 147.3; 141.7; 135.9;
129.5; 126.8; 123.6; 121.6; 117.3; 88.5; 32.7; 29.7; 25.5;
23.7; 22.5. Mass spectrum, m/z (Irel, %): 369 [M+Н]+ (100).
Found, %: C 68.37; H 6.46; N 7.67. C21H24N2O4
Calculated, %: C 68.46; H 6.57; N 7.60.
6,8-Diisopropyl-2-(4-nitrophenyl)-4Н-chromen-4-imine
(6d). Yield 0.82 g (47%), light-brown powder, mp 214–
216°C. IR spectrum, ν, cm–1: 3272 (NH), 2924–2961 (CH),
1521 (as NO2), 1344 (sym NO2). 1H NMR spectrum,
δ, ppm (J, Hz): signal of the NH group proton not observed
2-(4-Bromophenyl)-2-methyl-2,3-dihydro-4Н-1,3-benz-
oxazin-4-one (5e). Yield 1.27 g (40%), white powder,
864

Chemistry of Heterocyclic Compounds 2018, 54(9), 859–867
due to deuterium exchange with solvent; 8.35 (1Н, d,
Н Ph); 7.41–7.39 (2Н, m, Н Ph); 6.99 (1Н, s, Н Ph); 3.33–
3.32 (1Н, m, CН(CH3)2, signal overlaps with Н2О signal);
2.86 (1Н, sept, 3J = 6.8, CН(CH3)2); 1.22 (12Н, d, 3J = 6.8,
2CН(CH3)2). 13C NMR spectrum, δ, ppm: 152.4; 150.8;
143.0; 138.6; 134.7; 128.9; 128.7; 128.5; 125.4; 123.5;
121.4; 115.7; 99.4; 33.1; 26.6; 24.3; 22.5. Mass spectrum,
m/z (Irel, %): 321 [M+Н]+ (100). Found, %: C 78.65;
H 7.62; N 8.81. C21H24N2O. Calculated, %: C 78.71;
H 7.55; N 8.74.
J = 8.3, Н-3,5 Ar); 8.13 (1Н, d, J = 8.3, Н-2,6 Ar); 7.87
(1Н, s, Н-7); 7.41 (1Н, s, Н-5); 7.03 (1Н, s, 3-СН); 3.57
3
3
(1H, sept, J = 6.8, CH(CH3)2); 2.97 (1H, sept, J = 6.8,
3
CH(CH3)2); 1.32 (6H, d, J = 6.8, CH(CH3)2); 1.25 (6H, d,
3J = 6.8, CH(CH3)2). 13C NMR spectrum, δ, ppm: 158.7; 151.4;
148.3; 147.9; 144.7; 138.0; 136.6; 127.4; 126.2; 123.9; 120.5;
118.3; 107.3; 33.2; 26.8; 23.8; 22.5. Mass spectrum, m/z
(Irel, %): 351 [M+Н]+ (100). Found, %: C 71.92; H 6.39;
N 7.90. C21H22N2O3. Calculated, %: C 71.98; H 6.33; N 7.99.
2-(4-Bromophenyl)-4Н-chromen-4-imine (6е). Yield
0.58 g (39%), yellow powder, mp 125–127°C. IR spect-
rum, ν, cm–1: 3181 (NH), 3079 (CH Ar). 1H NMR
spectrum, δ, ppm: 8.16–8.14 (1Н, m, H Ar); 7.88–7.86 (2Н,
m, Н-3,5 Ar); 7.76–7.74 (2Н, m, Н-2,6 Ar); 7.63–7.61 (1Н,
m, Н Ar); 7.52–7.50 (1Н, m, Н Ar); 7.38–7.36 (1Н, m,
Н Ar); 6.91 (1Н, s, 3-СН). 13C NMR spectrum, δ, ppm: 158.4;
153.3; 152.8; 132.4; 131.9; 130.9; 127.3; 124.9; 124.1;
124.0; 120.9; 117.9; 105.3. Mass spectrum, m/z (Irel, %): 302
[М(81Br)+Н]+ (96), 300 [М (79Br)+Н]+ (100). Found, %:
C 60.16; H 3.49; N 4.59. C15H10BrNO. Calculated, %:
C 60.02; H 3.36; N 4.67.
2,4-Diisopropyl-6-[5-(4-nitrophenyl)-1Н-pyrazol-3-yl]-
phenol (7d). Yield 0.98 g (67%), white powder, mp 198–
1
200°C. H NMR spectrum, δ, ppm: 14.00 (1H, s, NH);
10.96 (1H, s, OH); 8.37–8.35 (2Н, m, Н-3,5 Ar); 8.14–8.12
(2Н, m, Н-2,6 Ar); 7.68 (1Н, s, Н-3); 7.49 (1Н, s, Н-5); 7.01
(1Н, s, Н pyrazole); 3.33 (1Н, m, CН(CH3)2, signal
overlaps with Н2О signal); 2.86–2.84 (1Н, m, CН(CH3)2);
1.22–1.20 (12 Н, m, CН(CH3)2). 13C NMR spectrum, δ, ppm:
150.4; 146.7; 138.9; 135.0; 126.2; 124.3; 123.8; 121.6;
115.5; 101.9; 33.0; 26.5; 24.2; 22.6. Mass spectrum, m/z
(Irel, %): 366 [M+Н]+ (85), 365[M]+ (100). Found, %:
C 69.07; H 6.29; N 11.43. C21H23N3O3. Calculated, %:
C 69.02; H 6.34; N 11.50.
Synthesis of pyrazoles 7a–d (General method).
Hydrazine hydrate (0.8 ml, 16 mmol) was added dropwise
to a solution of the corresponding imine 6a–d (4 mmol) in
absolute EtOH (10 ml). The reaction mixture was heated
under reflux for 3–4 h. The solution after cooling was
poured into H2O (20 ml), the formed precipitate was
filtered off, washed with H2O, and pyrazoles 7a–d
recrystallized from MeCN.
2-(3H-1,5-Benzodiazepin-3-ylidene)-2H-chromen-
4-amine (8). Dialdehyde 2a (1 g, 4.65 mmol) and
о-phenylenediamine (1 g, 9.26 mmol) were dissolved in
DMF (15 ml), and a few drops of AcOH added. The reaction
mixture was heated under reflux for 30 min, whereupon
colored precipitate formed. The precipitated benzodiazepine
was filtered off and recrystallized from DMF. Yield 1.20 g
(90%), red powder, mp >300°C. 1H NMR spectrum, δ, ppm:
9.60 (2Н, br. s, NH2); 8.64 (2Н, s, 2СН=N); 8.14–8.12
(1Н, m, H Ar); 7.89–7.87 (2Н, m, H Ar); 7.47–7.45 (3H,
m, H Ar); 7.11–7.09 (2Н, m, H Ar); 6.95 (1H, s, 3-СН).
Mass spectrum, m/z (Irel, %): 287 [М]+ (1), 44 (100).
Found, %: C 75.37; H 4.53; N 14.57. C18H13N3O.
Calculated, %: C 75.25; H 4.56; N 14.63.
2-(4-Phenyl-1Н-pyrazol-3-yl)phenol (7а). Yield 0.30 g
(32%), light-yellow powder, mp 114–116°C (mp 120–122°С28).
1H NMR spectrum, δ, ppm: 13.67 (1Н, br. s, NH); 10.95
(1Н, br. s, ОН); 7.84–7.77 (4Н, m, Н Ar); 7.47–7.19 (4Н,
m, Н Ar); 6.97–6.91 (3Н, m, Н Ar, H pyrazole). 13C NMR
spectrum, δ, ppm: 155.2; 151.2; 143.2; 129.9; 128.9; 126.9;
125.3; 125.0; 119.2; 116.9; 116.4; 99.9. Mass spectrum, m/z
(Irel, %): 237 [M+Н]+ (100). Found, %: C 76.14; H 5.08;
N 11.95. C15H12N2O. Calculated, %: C 76.25; H 5.12; N 11.86.
13C NMR spectrum for compound 8 could not be
recorded due to low solubility in DMSO-d6, CF3CO2D,
СDCl3.
2-[5-(4-Nitrophenyl)-1Н-pyrazol-3-yl]phenol
(7b).
Synthesis of 1,5-benzodiazepines 9a,b,d (General
procedure). Method I. A solution of the corresponding imine
6a,b,d (1.5 mmol) and о-phenylenediamine (1.85 mmol) in
DMF (3 ml) was heated under reflux for 2 h. After cooling
to room temperature, a precipitate formed, which was
filtered off and recrystallized.
Method II. AcOH (0.1 ml) was added to a solution of
imine 6a,b,d (4.42 mmol) and o-penylenediamine
(9.7 mmol) in DMF (5 ml). The reaction mixture was
heated under reflux for 1–1.5 h and kept at room
temperature for 12 h. The formed precipitate was filtered
off and recrystallized.
2-(4-Phenyl-1H-1,5-benzodiazepin-2-yl)phenol (9a).
Yield 0.28 g (60%, method I), 1.03 g (75%, method II),
yellow powder, mp 186–188°C (mp 108–110°C26). 1H NMR
spectrum, δ, ppm: 8.19–8.12 (4Н, m, Н Ar); 7.58–7.56
(2Н, m, Н Ar); 7.51–7.48 (3Н, m, Н Ar); 7.43–7.38 (2Н,
m, Н Ar); 6.91–6.89 (2Н, m, Н Ar). 13C NMR spectrum,
δ, ppm: 161.5; 159.2; 155.1; 141.1; 136.7; 135.7; 133.8;
131.2; 129.6; 128.7 128.6; 127.5; 126.3; 125.8; 118.7;
Yield 0.71 g (63%), yellow powder, mp 218–220°C (mp 230–
232°С29). IR spectrum, ν, cm–1: 3350 (OH), 3187 (NH),
1521 (as NO2), 1334 (sym NO2). 1H NMR spectrum, δ, ppm
(J, Hz): signals of the NH and OH group protons not
observed due to deuterium exchange with solvent; 8.29 (2Н,
d, 3J = 8.3, Н-3,5 Ar); 8.11 (2Н, d, J = 8.3, Н-2,6 Ar); 7.71
(1Н, d, 3J = 6.8, Н Ar); 7.38 (1Н, s, Н pyrazole); 7.20 (1Н,
t, 3J = 7.8, Н Ar); 6.99 (1Н, d, 3J = 7.8, Н Ar); 6.91 (1Н, t,
3J = 6.8, Н Ar). 13C NMR spectrum, δ, ppm: 154.4; 150.8;
146.3; 129.3; 129.2; 127.3; 125.8; 124.1; 119.3; 116.4;
116.1; 102.4. Mass spectrum, m/z (Irel, %): 282 [M+Н]+
(100). Found, %: C 64.17; H 3.87; N 14.89. C15H11N3O3.
Calculated, %: C 64.05; H 3.94; N 14.94.
2,4-Diisopropyl-6-(5-phenyl-1Н-pyrazol-3-yl)phenol
(7с). Yield 0.95 g (74%), white powder, mp 190–192°C.
IR spectrum, ν, cm–1: 3367 (OH), 3347 (NH), 2954 (CH).
1H NMR spectrum, δ, ppm (J, Hz): signals of the NH and
OH group protons not observed due to deuterium exchange
with solvent; 7.88 (2Н, d, J = 8.3, Н-5,7); 7.50–7.48 (3Н, m,
865

Chemistry of Heterocyclic Compounds 2018, 54(9), 859–867
117.6; 33.0. Mass spectrum, m/z (Irel, %): 313 [M+Н]+
2,4-Diisopropyl-6-[5-(4-nitrophenyl)-2,3-dihydro-1H-1,4-
diazepin-7-yl]phenol (10d). Yield 0.27 g (45%, method I),
1.04 g (60%, method II), red crystals, mp 120–122°C. 1H NMR
spectrum, δ, ppm (J, Hz): 8.31 (2Н, d, 3J = 8.7, Н-3,5 Ar); 7.89
(2Н, d, 3J = 8.7, Н-2,6 Ar); 7.26 (1Н, s, Н-5 Ar); 6.99 (1Н, s,
Н-3 Ar); 5.65 (1Н, s, Н Ar); 3.92–3.90 (2Н, m, CH2); 3.56–
3.54 (2Н, m, CH2); 2.76–2.74 (1H, m, CH(CH3)2); 2.50 (1H,
m, CH(CH3)2, signal overlaps with DMSO-d6 signal); 1.15–
1.12 (12H, m, 2CH(CH3)2)). 13C NMR spectrum, δ, ppm:
168.4; 163.3; 154.9; 148.0; 145.0; 137.4; 132.9; 128.9; 125.8;
123.6; 121.9; 116.1; 88.5; 50.9; 49.0; 26.4; 25.6; 24.3; 22.5. Mass
spectrum, m/z (Irel, %): 394 [M+Н]+ (100). Found, %: C 70.33;
H 6.78; N 10.76. C23H27N3O3. Calculated, %: C 70.21; H 6.92;
N 10.68.
(100). Found, %: C 80.97; H 5.29; N 8.63. C21H16N2O.
Calculated, %: C 80.75; H 5.16; N 8.97.
2-[2-(4-Nitrophenyl)-1H-1,5-benzodiazepin-4-yl]-
phenol (9b). Yield 0.25 g (47%, method I), 1.26 g (80%,
method II), yellow crystals, mp 260–262°C (mp 123–125°C30).
IR spectrum, ν, cm–1: 3358 (OH), 1551 (as NO2), 1344
(sym NO2). 1H NMR spectrum, δ, ppm (J, Hz): 8.43 (2Н, d,
3J = 8.3, Н-3,5 Ar); 8.30 (2Н, d, 3J = 8.3, Н-2,6 Ar); 8.14–8.12
(1Н, m, Н Ar); 7.61–7.59 (2Н, m, Н Ar); 7.49–7.47 (2Н,
m, Н Ar); 7.41–7.39 (1Н, m, Ar); 6.93–6.91 (2Н, m, Н Ar).
13C NMR spectrum, δ, ppm: 175.1; 171.3; 156.9; 150.5;
141.1; 137.3; 135.8; 134.7; 130.3; 129.8; 125.6; 123.9; 121.7;
119.7; 117.5; 111.1; signal of the carbon of the CH2 overlaps
with DMSO-d6 signal. Mass spectrum, m/z (Irel, %): 358
[M+Н]+ (100). Found, %: C 70.67; H 4.29; N 11.53.
C21H15N3O3. Calculated, %: C 70.58; H 4.23; N 11.76.
2,4-Diisopropyl-6-[2-(4-nitrophenyl)-1H-1,5-benzodi-
azepin-4-yl]phenol (9d). Yield 0.27 g (41%, method I), 1.46 g
2-[2-Amino-6-(4-nitrophenyl)pyrimidin-4-yl]phenol (11).
A solution of imine 6b (3.4 mmol) and guanidine
hydrochloride (6.8 mmol) in MeOH (10 ml) was added to
alcohol solution of MeONa (6.8 mmol), and the mixture
was heated under reflux for 3–3.5 h. The reaction mixture
was cooled to room temperature and poured into ice water
(20 ml). The precipitate was filtered off, dried, and
recrystallized from MeOH. Yield 0.84 g (80%), light-
yellow powder, mp 260–262°C. IR spectrum, ν, cm–1:
3428 (OH), 3358 (NH2), 1551 (as NO2), 1344 (sym NO2).
1H NMR spectrum, δ, ppm (J, Hz): 13.75 (1H, s, OH); 8.50
1
(75%, method II), red powder, mp 205–207°C. H NMR
3
spectrum, δ, ppm (J, Hz): 8.33 (2Н, d, J = 8.3, Н-3,5 Ar);
8.07 (1Н, s, Н-5 Ar); 7.99 (2Н, d, 3J = 8.3, Н-2,6 Ar); 7.47
(1Н, s, Н-7 Ar); 6.87–6.85 (1Н, m, Н Ar); 6.81–6.79 (1Н,
m, Н Ar); 6.76–6.70 (2Н, m, Н Ar); 6.60– 6.58 (1Н, m,
Н Ar); 4.66 (1H, s, CH); 3.62–3.60 (1Н, m, CН(CH3)2);
3
3
3.04–3.02 (1Н, m, CН(CH3)2); 1.34 (6Н, d, J = 6.8,
(2Н, d, 3J = 8.3, Н-3,5 Ar); 8.37 (2Н, d, J = 8.3, Н-2,6 Ar);
3
CН(CH3)2); 1.27 (6Н, d, J = 6.8, CН(CH3)2). 13C NMR
8.26–8.24 (1H, m, H Ar); 7.96 (1Н, s, Н Py); 7.39–7.36
(3Н, m, Н Ar); 6.49 (2Н, s, NН2). 13C NMR spectrum,
δ, ppm: 165.8; 162.8; 161.3; 160.3; 148.6; 142.9; 132.8;
128.3; 128.1; 123.6; 118.8; 118.0; 117.3; 101.0. Mass
spectrum, m/z (Irel, %): 309 [M+Н]+ (96), 308 [M]+ (100).
Found, %: C 62.27; H 3.99; N 18.28. C16H12N4O3.
Calculated, %: C 62.33; H 3.92; N 18.17.
spectrum, δ, ppm: 154.2; 150.7; 149.1; 148.2; 145.2; 140.7;
138.1; 136.7; 135.4; 127.4; 126.6; 124.3; 124.2; 121.7;
119.2; 118.8; 116.2; 114.5; 99.7; 33.3; 26.8; 23.9; 22.6. Mass
spectrum, m/z (Irel, %): 442 [M+Н]+ (81), 441 [M]+ (100).
Found, %: C 73.37; H 6.29; N 9.43. C27H27N3O3.
Calculated, %: C 73.45; H 6.16; N 9.52.
Synthesis of 1,4-diazepines 10b,d (General procedure).
Method I. Imine 6b,d (1.5 mmol) was dissolved in DMF
(5 ml), and ethylenediamine (7.5 mmol) added. The
reaction mixture was heated under reflux for 3 h. Then it
was cooled to room temperature, poured into Н2О (20 ml),
and kept for 12 h. The precipitate was filtered off and
purified by recrystallization from MeCN.
X-ray structural analysis of compound 9b was
performed on an X-calibur diffractometer (MoKα beam,
ССD detector, graphite monochromator, ω-scan, 2θmax
50°). Crystals are rhombic (C21H15N3O3, M 357.36) at 20°С:
a 19.476(4), b 4.8402(7), c 35.120(4) Å; V 3310.6(9) Å3;
Z 8; spatial symmetry group Рna21; dcalc 1.434 g/cm3,
µ(MoKα) 0.098 mm–1, F(000) 1488. A total of 18304
reflections were collected (5778 of which were independent,
Method II. AcOH (0.5 ml) was added to a solution of
imine 6b,d (4.42 mmol) and ethylenediamine (7.5 mmol) in
DMF (5 ml), and the solution was heated under reflux for 1.5–
2 h. The reaction mixture was poured into H2O (25 ml), the
precipitate was filtered off and recrystallized from MeCN.
2-[7-(4-Nitrophenyl)-2,3-dihydro-1H-1,4-diazepin-5-yl]-
phenol (10b). Yield 0.15 g (32%, method I), 0.95 g (70%,
method II), red crystals, mp 223–225°C. IR spectrum,
ν, cm–1: 3220 (OH), 3082 (NH), 1594 (as NO2), 1341 (sym
R
int 0.110). The structure was solved with the direct method
using the SHELXTL program set.31,32 H atom positions
were found from difference electron density synthesis and
were refined according to the ''rider'' model with
Uiso = 1.2Ueq of a non-hydrogen atom bonded with the
hydrogen atom. Positions of the hydrogen atoms of the
hydroxyl groups were refined in the isotropic approximation.
The structure was refined against F2 by the least-squares
technique in the full-matrix anisotropic approximation for
non-hydrogen atoms up to wR2 0.227 over 5758 reflections
(R1 0.083 over 2791 reflections with F > 4σ(F), S 0.940).
Crystallographic data was deposited at the Cambridge
Crystallographic Data Center (deposit CCDC 1856644).
1
NO2). H NMR spectrum, δ, ppm (J, Hz): 8.30 (2Н, d,
3
3J = 8.7, Н-3,5 Ar); 7.92 (2Н, d, J = 8.7, Н-2,6 Ar); 7.64
(1Н, d, 3J = 8.7, Н Ar); 7.11 (1Н, t, 3J = 7.8, Н Ar); 6.61 (1Н,
d, 3J = 7.8, Н Ar); 6.46 (1Н, t, 3J = 7.8, Н Ar); 5.67 (1H, s,
H Ar), 3.91–3.89 (2Н, m, CH2); 3.59–3.57 (2Н, m, CH2).
13C NMR spectrum, δ, ppm: 169.0; 168.1; 155.8; 148.3;
144.9; 132.2; 129.1; 127.8; 123.7; 120.6; 117.3; 113.7;
87.8; 50.4; 49.0. Mass spectrum, m/z (Irel, %): 310 [M+Н]+
(100). Found, %: C 66.11; H 4.78; N 13.63. C17H15N3O3.
Calculated, %: C 66.01; H 4.89; N 13.58.
1
The Supporting information file containing IR, H, 13C
NMR, and mass spectra of the synthesized compounds is
available at the journal website at http://link.springer.com/
journal/10593.
866

Chemistry of Heterocyclic Compounds 2018, 54(9), 859–867
13. Mutai, P.; Pavadai, E.; Wild, I.; Ngwane, A.; Baker, B.;
This work was financially supported by the Ministry of
Education and Science of Ukraine under the state budget
theme No. 0115U003159 ''New synthetic methods for the
design of nitrogen- and sulfur-containing biologically
active compounds''.
Chibale, K. Bioorg. Med. Chem. Lett. 2015, 25, 2510.
14. Catalan, J.; Fabero, F.; Claramunt, R. M.; Santa Maria, M. D.;
Foces-Foces, M. C.; Cano, F. H.; Martinez-Ripoll, M.;
Elguero, J.; Sastre, R. J. Am. Chem. Soc. 1992, 114, 5039.
15. Catalan, J.; Fabero F.; Guijarro, M. S.; Claramunt, R. M.;
Santa Maria, M. D.; Foces-Foces, M. C.; Cano, F. H.; Elguero, J.;
Sastre, R. J. Am. Chem. Soc. 1990, 112, 747.
References
16. Ahmad, R.; Ahmad, N.; Zia-U1-Haq, M.; Wahid, A. J. Chem.
Soc. Pak. 1996, 18, 38.
1. Gaspar, A.; Matos, M. J.; Garrido, J.; Uriarte, E.; Borges, F.
Chem. Rev. 2014, 114, 4960.
17. Farat, O. K.; Markov, V. I.; Varenichenko, S. А.;
Dotsenko, V. V.; Mazepa, A. V. Tetrahedron 2015, 71, 5554.
18. Farat, O. K.; Farat, S. A.; Ananyev, I. V.; Okovytyy, S. I.;
Tatarets, A. L.; Markov, V. I. Tetrahedron 2017, 73, 7159.
19. Eiden, F.; Prielipp L. Arch. Pharm. 1977, 310, 109.
20. Levai, A.; Silva, A. M. S.; Pinto, D. C. G. A.; Cavaleiro, J. A. S.;
Alkorta, I.; Elguero, J.; Jeko, J. Eur. J. Org. Chem. 2004, 4672.
21. Burgi, H.-B.; Dunitz, J. D. In Structure Correlation; VCH:
Weinheim, 1994, Vol. 2, p. 741.
22. Pretsch, E. Structure Determination of Organic Compounds.
Tables of Spectral Data [Russian translation]; Pretsch, E.;
Bühlmann, P.; Affolter, C., Ed.; Mir: Moscow, 2006, p. 438.
23. Kondo, K.; Seki, M.; Kuroda, T.; Yamanaka, T.; Iwasaki, T.
J. Org. Chem. 1997, 62, 2877.
24. Zhang, Z.-T.; Xu, F.-F.; Gao, M.-X.; Qiu, L. J. Comb. Chem.
2009, 11, 880.
25. Zhang, Z.-T.; Tan, D.-J.; Xue, D. Helv. Chim. Acta 2007, 90,
2096.
26. Zefirov, Yu. V. Kristallografiya 1997, 42(5), 936.
27. (a) Gammill, R. B. J. Org. Chem. 1981, 46, 3340. (b) Horrom, B.
W.; Zaugg, H. E. J. Am. Chem. Soc. 1950, 72, 721.
2. Chagarovsky, A. O.; Budynina, E. M.; Ivanova, O. A.;
Rybakov, V. B.; Trushkov, I. V.; Melnikov, M. Ya. Org.
Biomol. Chem. 2016, 14, 2905.
3. Sosnovskikh, V. Ya.; Irgashev, R. A.; Levchenko, A. A.
Tetrahedron 2008, 64, 6607.
4. Gabbutt, C. D.; Hargrove, T. F. L.; Heron, B. M.; Jones, D.;
Poyner, C.; Yildiz, E.; Horton, P. N.; Hursthouse, M. B.
Tetrahedron 2006, 62, 10945.
5. Silva, V. L. M.; Silva, A. M. S.; Pinto, D. C. G. A.; Cavaleiro, J. A.
S.; Elguero, J. Tetrahedron Lett. 2007, 48, 3859.
6. Lozinski, O. A.; Shokol, T. V.; Zubatyuk, R. I.; Shishkin, O. V.;
Khilya, V. P. Chem. Heterocycl. Compd. 2018, 54, 96. [Khim.
Geterotsikl. Soedin. 2018, 54, 96.]
7. Irgashev, R. A.; Safrygin, A. V.; Ezhikova, M. A.; Kodess, M. I.;
Röschenthaler, G.-V.; Sosnovskikh, V. Y. Tetrahedron 2015,
71, 1822.
8. Popova, Y. V.; Sakhnenko, D. V.; Arbuzova, I. V.; Osyanin, V. A.;
Osipov, D. V.; Klimochkin, Y. N. Chem. Heterocycl. Compd.
2016, 52, 803. [Khim. Geterotsikl. Soedin. 2016, 52, 803.]
9. Osyanin, V. A.; Popova, Y. V.; Osipov, D. V.; Klimochkin, Y. N.
Chem. Heterocycl. Compd. 2016, 52, 809. [Khim. Geterotsikl.
Soedin. 2016, 52, 809.]
10. Durrant, J. D.; Carlson, K. E.; Martin, T. A.; Offutt, T. L.;
Mayne, C. G.; Katzenellenbogen, J. A.; Amaro, R. E.
J. Chem. Inf. Model. 2015, 55, 1953.
28. Ingle, V. N.; Padwad, M. J. Indian Chem. Soc. 1999, 76, 161.
29. Ingle, V. N. J. Indian Chem. Soc. 1988, 65, 852.
30. Nagaraja, N. G.; Vaidya, V. P.; Rai, K. S.; Mahadevan, K. M.
Phosphorus, Sulfur Silicon Relat. Elem. 2006, 181, 2797.
31. Sheldrick, G. M. Acta Crystallogr., Sect. A: Found.
Crystallogr. 2008, A64, 112.
11. Rosowsky, A.; Forsch, R. A.; Sibley, C. H.; Inderlied, C. B.;
Queener, S. F. J. Med. Chem. 2004, 47, 1475.
12. Bepary, S.; Youn, I. K.; Lim, H.-J.; Lee, G. H. Bull. Korean
Chem. Soc. 2013, 9, 2829.
32. Sheldrick G. M. Acta Crystallogr., Sect. C: Struct. Chem.
2015, C71, 3.
867