Synthesis and application of chalcones to the preparation of heterocyclic structures

Article abstract of DOI:10.1134/S1070428013110080

Condensation of methyl N-(4-acetylphenyl)carbamate with aromatic aldehydes in basic and acid environment, and also with hetarylaldehydes in the presence of bases afforded chalcones with the carbamate function. Under the conditions of basic catalysis a nucleophilic substitution was observed of a methoxy group in the carbamate moiety of the chalcone for an ethoxy group. The reactions of the obtained chalcones with hydrazine hydrate, isonicotinic acid hydrazide, guanidine and hydroxylamine hydrochlorides, thiourea, and selenium dioxide furnished the corresponding derivatives of pyrazole, oxazole, pyrimidine, and selenadiazole. Pleiades Publishing, Ltd., 2013.

Full text of DOI:10.1134/S1070428013110080

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 11, pp. 1610−1616. © Pleiades Publishing, Ltd., 2013.
Original English Text © A.V. Velikorodov, V.A. Ionova, S.I. Temirbulatova, O.L. Titova, N.N. Stepkina, 2013, published in Zhurnal Organicheskoi Khimii, 2013,
Vol. 49, No. 11, pp. 1631−1637.
Synthesis and Application of Chalcones to the Preparation
of Heterocyclic Structures
A. V. Velikorodov, V. A. Ionova, S. I. Temirbulatova,
O. L. Titova, and N. N. Stepkina
Astrakhan State University, Astrakhan, 414000 Russia
e-mail: avelikorodov@mail.ru
Received February 21, 2013
Abstract—Condensation of methyl N-(4-acetylphenyl)carbamate with aromatic aldehydes in basic and acid
environment, and also with hetarylaldehydes in the presence of bases afforded chalcones with the carbamate
function. Under the conditions of basic catalysis a nucleophilic substitution was observed of a methoxy group in
the carbamate moiety of the chalcone for an ethoxy group. The reactions of the obtained chalcones with hydrazine
hydrate, isonicotinic acid hydrazide, guanidine and hydroxylamine hydrochlorides, thiourea, and selenium dioxide
furnished the corresponding derivatives of pyrazole, oxazole, pyrimidine, and selenadiazole.
DOI: 10.1134/S1070428013110080
Chalcones (trans-1,3-diaryl-2-propen-1-ones) are
key compounds in the synthesis of many biologically
important heterocycles, in particular, of benzothiazepines,
pyrazolines, pyrimidines, flavones, isoxazolines, etc. The
traditional methods of chalcones preparation involve the
use as catalysts of strong bases like alkali and alkaline
earth metals hydroxides [1–3], alkali metals alcoholates
[4], lithium bis(trimethylsilyl)amide [5]. The chalcones
synthesis also can be performed utilizing acid catalysts
(AlCl3, BF3 [6, 7], HCl [8], RuCl3 [9] etc.).
We explored condensation reactions of methyl N-(4-
acetylphenyl)carbamate (I) with 4-methoxy-, 3,4-dime-
thoxy-, 4-fluoro-, and 2-hydroxybenzaldehydes, furfural,
and 2-thiophenecarbaldehyde under the conditions of
basic and acidic catalysis. In the first case the reaction was
carried out in methanol in the presence of 10% methanol
solution of KOH.As an acid catalyst conc. HCl was used.
Claisen–Schmidt condensation of aromatic aldehydes
with ketone I under the conditions of the basic catalysis
resulted in methyl N-4-[(3-arylprop-2-enoyl)phenyl]car-
bamates II–V in 68–86% yields. At the condensation in
the presence of conc. HCl chalcone yields were 60–72%,
and a more careful purification of products was required.
Among α,β-unsaturated ketones and their deriva-
tives compounds were found exhibiting the cytotoxicity
with respect to various strains of cancer cells [10–12],
antimutagenic [13], antimicrobial [14], antiviral [15],
antiphlogistic [16], fungicidal [17], hepatoprotective [18],
and the other kinds of biological action. In this connection
the synthesis of new chalcones and nitrogen heterocyclic
compounds therefrom is an important task.
The structure of compounds II–V was confirmed by
IR and 1Н NMR spectra.
The condensation of compound I with furfural and
2-thiophenecarbaldehyde was carried out in the pres-
MeO2CHN
MeO2CHN
ArCHO
10% KOH_MeOH
Ar
Me
or HCl
O
II_V
O
I
Ar = 4-MeOC6H4 (II), 3,4-(MeO)2C6H3 (III), 4-FC6H4 (IV), 2-HOC6H4 (V).
1610

SYNTHESIS AND APPLICATION OF CHALCONES
1611
ence of 10% alcoholic solution at 35°С. As expected, the
obtained products were the corresponding chalcones VI–
VIII. It was also found, that the use of ethanol instead of
methanol solution was accompanied by the nucleophilic
substitution of the alkoxy group in the carbamate moiety
compound I with the final formation of ethyl N-4-[(3-
hetarylprop-2-enoyl)phenyl]carbamates VII, VIII. Under
similar conditions the condensation of 4-methoxybenz-
aldehyde with ketone I led to the formation of chalcone
IX having an ethoxycarbonylamino group.
RO2CHN
MeO2CHN
R'CHO
10% KOH,
ROH
R'
Me
O
VI_IX
O
I
The structure of chalcones VI–IX was confirmed by
IR and 1Н NMR spectra, and that of compound VIII, also
by the mass spectrum.
Aiming at further functionalization of compounds
obtained we examined some chemical reactions of methyl
N-4-{[3-(4-methoxy-phenyl)prop-2-enoyl]phenyl}
carbamate (II). The condensation of chalcone II with
isonicotinic acid hydrazide in glacial acetic acid and with
hydrazine hydrate in ethanol led to the formation of the
corresponding pyrazole derivatives X, XII.
NHCO2Me
NH2
MeO
N
N
N
N
O
MeO2CHN
HN
OMe
XI
CONHNH2
N
X
NH2
.
HCl
NH2
MeONa, MeOH
N
AcOH, Δ
MeO2CHN
OMe
O
II
H2NNH2
EtOH, Δ
.
HCl
NH2OH
Py
, Δ
O N
N NH
NHCO2M
e
e
MeO
MeO2CHN
OMe
XII
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013
XIII

VELIKORODOV et al.
1612
In the 1Н NMR spectrum of compound X the protons
stretching vibrations of the NH bonds in the carbamate
and amide groups at 3310 and 3240 cm–1.
of the methylene group and the proton linked to the ter-
tiary carbon atom of the pyrazole ring appear as doublets
of doublets at 3.15, 3.65, and 4.89 ppm, respectively.
In the 1Н NMR spectrum of compound XIV the signals
of protons Н5, Н6 of the heterocycle appear as doublets at
5.74 and 5.20 ppm respectively, and the signals of the NH
groups of the pyrimidine ring are observed at 8.67 ppm;
the latter indicates the prevailing existence of the tauto-
meric form containing the thioxo group.
1
In the Н NMR spectrum of pyrazole derivative XII
also doublets are observed in the region 3.21, 3.34, and
4.90 ppm corresponding to the protons of СН2 and СН
groups.
The condensation of chalcone II with guanidine
hydrochloride in methanol in the presence of sodium
methoxide and with hydroxylamine hydrochloride
in pyridine in the presence of a catalytic quantity of
piperidine provided derivatives of pyrimidine XI and
isoxazole XIII.
In the 1Н NMR spectrum of compound XI alongside
the other signals a singlet appears at δ 5.49 ppm cor-
responding to the two protons of the NH2 group at the
atom С2 of the pyrimidine. IR spectrum of this compound
contains absorption bands at 3340 and 3410 cm–1 belong-
ing to the stretching vibrations of NH and NH2 groups. In
the 1Н NMR spectrum of isoxazole derivative XIII the
singlet of the proton Н4 is observed at 6.68 ppm.
Derivatives of 1,2,3-selenadiazole play an important
part in solving many theoretical and practical а problems
of organic chemistry [19, 20] attracting much atten-
tion of the researchers to these compounds [21]. The
compound containing the selenadiazole ring exhibit an
aromatic character but are prone to the elimination of
molecules of nitrogen and selenium with ring opening
and the formation of both acyclic compounds and new
heterocycles [20, 22]. They are interesting objects for
the study of the mechanism of some reactions and for
the synthesis of many compounds possessing practically
valuable properties [23].
In [24] 4-aryl-5-(2-nitro-1-arylpropyl)-1,2,3-
selenadiazoles were obtained from 1,3-diaryl-2-(4-
nitropentylidene)-1-hydrazinecarboxamides.
The condensation of chalcone VI with thiourea in the
presence of sodium methoxide at boiling in methanol
was completed within 3 h and afforded methyl N-{4-[6-
(thiophen-2-yl)-2-thioxo-1,2,3,6-tetrahydro-pyrimidin-
4-yl]phenyl}carbamate (XIV) in 74% yield. Compound
XIV formed apparently through intermediates А, B.
We attempted to build up the 1,2,3-selenadiazole ring
from the semicarbazone of methyl N-{4-[2-(2-oxo-2,3-
dihydro-1Н-indol-3-yl)acetyl]-phenyl}carbamate (XV)
that in its turn was obtained by the reduction of methyl
N-{4-[2-(2-oxo-1,2-dihydro-3Н-indol-3-ylidene)acetyl]
phenyl}carbamate [25] with sodium dithionite in a water-
dioxane mixture [26].
IR spectrum of compound XIV contains absorption
bands of the thiocarbonyl group at 1163 cm–1 and of the
S
S
MeO2CHN
MeO2CHN
HN
NH2
S
H2N
NH2
MeOH, MeONa
OH
S
O
A
VI
NHCO2Me
H
S
S
N
MeO2CHN
N
NH2
S
HN
H2O
S
B
XIV
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013

SYNTHESIS AND APPLICATION OF CHALCONES
NHCO2Me
1613
N
Se
N
THF, Δ
SeO2,
NNHCONH2
O
O
NHCO2Me
N
N
H
H
XV
XVI
Semicarbazone XV was prepared by boiling equimolar
amounts of methyl N-{4-[2-(2-oxo-2,3-dihydro-1Н-
indol-3-yl)acetyl]phenyl}carbamate with semicarbazide
hydrochloride in ethanol for 5 h.
phenyl}carbamate (II). To a mixture of 1.93 g (0.01 mol)
of methyl N-(4-acetylphenyl)carbamate (I), 1.2 mL
(0.01 mol) of freshly distilled 4-methoxybenzaldehyde
in 50 mL of methanol at 35°С was added within 30 min
while stirring 3 mL of 10% methanol solution of
potassium hydroxide. The reaction mixture was stirred for
4 h at 35°С and left standing for 24 h at room temperature.
The reaction mixture was poured into 100 mL of ice
water and was acidified with diluted hydrochloric acid
(1 : 1). The separated precipitate was filtered off, dried
in air, and recrystallized from ethanol. Yield 2.4 g (78%),
light yellow crystals, mp 124–126°С. IR spectrum, ν,
cm–1: 3330 (NH), 1710, 1680 (С=O), 1610, 1585, 1565
(С=С, C=Carom). 1Н NMR spectrum, δ, ppm: 3.71 s (3Н,
NHCO2Me), 3.87 s (3H, OMe), 6.92 d (2Нarom, J 8.7 Hz),
The heating at 60°С of an equimolar mixture of
semicarbazone XV and powdered selenium dioxide in
anhydrous tetrahydrofuran results in heterocyclization
with the formation of 1,2,3-selenadiazole derivative XVI.
The structure of methyl N-{4-[5-(2-oxo-2,3-dihydro-
1Н-indol-3-yl)-1,2,3-selenadiazol-4-yl]phenyl}carba-
mate (XVI) was confirmed by IR, 1Н, 13С NMR spectra,
among them HMBC spectrum.
In the IR spectrum of compound XVI alongside with
the other bands an adsorption band is present in the
region 830 cm–1 related to the stretching vibrations of
the С–Se–N bond of the 1,2,3-selenadiazole ring [27]. In
7.24–7.28 m (2Нarom, 1Н, НС=СН), 7.44–7.54 m (2Нarom
,
1Н, НС=СН), 7.95 d (2Нarom, J 8.5 Hz), 9.58 br.s (1Н,
NH). Found, %: С 69.27; Н 5.35; N 4.37. C18H17NO4.
Calculated, %: С 69.45; Н 5.47; N 4.51.
1
the Н NMR spectrum the proton attached to С3 of the
indolinone fragment appears at 4.52 ppm. In the HMBC
spectrum a cross-peak was found originating from the
long-range proton-carbon coupling of this proton with
the quaternary atom С4 of the 1,2,3-selenadiazole ring
that in the 13С NMR spectrum gave rise to the signal at
δ 152.08 ppm.
Compounds III, VI–IX were obtained similarly.
Methyl N-4-{[3-(3,4-dimethoxyphenyl)prop-2-
enoyl]phenyl}carbamate (III) was obtained from
1.93 g (0.01 mol) of ketone I, 1.66 g (0.01 mol) of
3,4-dimethoxybenzaldehyde. Yield 2.9 g (86%), yel-
low crystals, mp 178–180°С (ethanol). IR spectrum, ν,
cm–1: 3330 (NH), 1710, 1680 (С=O), 1615, 1585, 1575
EXPERIMENTAL
1
1Н, HMBC NMR spectra were registered on a spec-
trometer Bruker DRX-500 (500.13 MHz). 13С NMR
spectra were obtained on a spectrometer Bruker WM-400
(100 MHz) at complete decoupling from protons, solvent
DMSO-d6. IR spectra were recorded on a Fourier spec-
trophotometer InfraLUM FT-02 in the range 4000–400
cm–1 from pellets with KBr. The purity of compounds
synthesized was checked by TLC on Silufol UV-254
plates, development in iodine vapor.
(С=С, C=Carom). Н NMR spectrum, δ, ppm: 3.71 s
(3Н, NHCO2Me), 3.86 s (6H, 2OMe), 6.84 d (1Нarom
,
J 8.0 Hz), 7.02 s (1Н, Нarom), 7.07 s (1Н, Нarom), 7.20–
7.30 m (2Нarom, 2Н, НС=СН), 7.97 d (2Нarom, J 8.5 Hz),
9.56 br.s (1Н, NH). Found, %: С 66.73; Н 5.57; N 4.00.
C19H19NO5. Calculated, %: С 66.86; Н 5.57; N 4.11.
Methyl N-4-{[3-(thiophen-2-yl)prop-2-enoyl]-
phenyl}carbamate (VI) was obtained from 1.93 g
(0.01 mol) of compound I, 0.92 mL (0.01 mol) of
thiophene-2-carbaldehyde. Yield 2.15 g (75%), light yel-
Methyl N-4-{[3-(4-methoxyphenyl)prop-2-enoyl]
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013

VELIKORODOV et al.
1614
low crystals, mp 159–160°С (ethanol). IR spectrum, ν,
cm–1: 3325 (NH), 1710, 1690 (С=O), 1610, 1580, 1570
(С=С, C=Carom). 1Н NMR spectrum, δ, ppm: 3.71 s (3Н,
NHCO2Me), 6.85 d (1Нthienyl, J 5.1 Hz), 6.96–6.98 m
(1Нthienyl, 1Н, НС=СН), 7.19 d (1Нthienyl, J 5.0 Hz), 7.25 d
(2Нarom, J 8.6 Hz), 7.91 d (1Н, НС=СН, J 15.6 Hz),
7.97 d (2Нarom, J 8.6 Hz), 9.58 br.s (1Н, NH). Found, %:
С 62.54; Н 4.46; N 4.74. C15H13NO3S. Calculated, %:
С 62.72; Н 4.53; N 4.88.
(2Нarom, J 8.5 Hz), 7.90 d (1Н, НС=СН, J 15.0 Hz),
7.97 d (2Нarom, J 8.5 Hz), 9.56 br.s (1Н, NH). Found,
%: С 66.37; Н 4.68; N 5.04. C15H13NO4. Calculated, %:
С 66.42; Н 4.80; N 5.17.
Ethyl N-4-{[3-(furan-2-yl)prop-2-enoyl]phenyl}
carbamate (VIII) was obtained from 1.93 g (0.01 mol)
of compound I and 0.83 mL (0.01 mol) of furfural in
50 mLof ethanol in the presence of 3% ethanol solution of
KOH. Yield 2.3 g (79%), yellow crystals, mp 141–142°С
(ethanol). IR spectrum, ν, cm–1: 3328 (NH), 1715, 1690
Methyl N-4-{[3-(4-fluorophenyl)prop-2-enoyl]-
phenyl}carbamate (IV). A slurry of 0.96 g (4.97 mmol)
of methyl N-(4-acetylphenyl)carbamate (I), 0.53 mL
(4.97 mmol) of 4-fluorobenzaldehyde in 5 mL of conc.
HCl was stirred for 8 h at room temperature, the reaction
mixture was transferred into 50 mL of ice water, the
acid was neutralized with sodium acetate, the separated
precipitate was filtered off, washed on the filter with
water (25 ml), dried in air, and twice recrystallized from
ethanol. Yield 1.07 g (72%), light yellow crystals, mp
120–121°С (ethanol). IR spectrum, ν, cm–1: 3330 (NH),
1710, 1680 (С=O), 1615, 1580, 1575 (С=С, C=Carom).
1Н NMR spectrum, δ, ppm: 3.71 s (3Н, NHCO2Me),
1
(С=O), 1610, 1580, 1575 (С=С, C=Carom). Н NMR
spectrum, δ, ppm: 1.27 t (3Н, ОСН2СН3, J 7.0 Hz), 4.19 q
(2Н, ОСН2СН3, J 7.0 Hz), 6.82 d (1Нfuryl, J 5.0 Hz),
6.94–6.97 m (1Нfuryl, 1Н, НС=СН), 7.17 d (1Нfuryl
,
J 5.0 Hz), 7.28 d (2Нarom, J 8.5 Hz), 7.90 d (1Н, НС=СН,
J 15.0 Hz), 7.97 d (2Нarom, J 8.5 Hz), 9.57 br.s (1Н, NH).
Mass spectrum, m/z (Irel, %): 286 (20) [M + 1]+, 285 (100)
[M]+, 271 (50), 256 (10), 231 (24), 217 (16), 211 (22),
203 (8), 198 (4), 192 (42), 184 (34), 178 (30), 164 (26),
156 (16), 146 (60), 128 (22), 121 (36), 115 (6), 92 (20),
77 (12), 65 (66), 59 (6), 39 (36). Found, %: С 67.31;
Н 5.18; N 4.78. C16H15NO4. Calculated, %: С 67.37;
Н 5.26; N 4.91. M 285.
7.24–7.40 m (6Нarom, 2Н, НС=СН), 7.97 d (2Нarom
,
J 8.5 Hz), 9.56 br.s (1Н, NH). Found, %: С 68.24; Н 4.59;
N 4.57. C17H14FNO3. Calculated, %: С 68.23; Н 4.68;
N 4.68.
Ethyl N-4-{[3-(4-methoxyphenyl)prop-2-enoyl]
phenyl}carbamate (IX) was obtained from 1.93 g
(0.01 mol) of ketone I and 1.2 mL (0.01 mol) of 4-me-
thoxybenzaldehyde in 50 mL of ethanol in he presence
of 3% ethanol solution of KOH. Yield 2.2 g (68%), yel-
low crystals, mp 129–132°С (ethanol). IR spectrum, ν,
cm–1: 3330 (NH), 1710, 1680 (С=O), 1615, 1575, 1570
Methyl N-4-{[3-(2-hydroxyphenyl)prop-2-enoyl]-
phenyl}carbamate (V) was similarly obtained from
0.96 g (4.97 mmol) of compound I and 0.52 mL
(4.97 mmol) of salicylaldehyde. Yield 0.88 g (60%),
yellow crystals, mp 98–100°С (ethanol). IR spectrum, ν,
cm–1: 3330, 3265 (NH, ОН), 1710, 1680 (С=O), 1615,
1580, 1575 (С=С, C=Carom). 1Н NMR spectrum, δ, ppm:
3.71 s (3Н, NHCO2Me), 6.65 d (1Нarom, J 8.1 Hz), 7.13 t
(1Нarom, J 8.1 Hz), 7.28 d (2Нarom, J 8.5 Hz), 7.36 d
(1Нarom, J 8.1 Hz), 7.49 d (1Н, НС=СН, J 14.0 Hz), 7.65 t
(1Нarom, J 8.1 Hz), 7.98 d (2Нarom, J 8.5 Hz), 8.24 d (1Н,
НС=СН, J 14.0 Hz), 9.55 br.s (1Н, NH), 10.15 s (1Н,
ОН). Found, %: С 68.53; Н 4.94; N 4.65. C17H15NO4.
Calculated, %: С 68.69; Н 5.05; N 4.71.
1
(С=С, C=Carom). Н NMR spectrum, δ, ppm: 1.23 t
(3Н, ОСН2СН3, J 7.0 Hz), 3.87 s (3Н, ОСН3), 4.08 q
(2Н, ОСН2СН3, J 7.0 Hz), 6.92 d (2Нarom, J 8.7 Hz),
7.24–7.32 m (2Нarom, 1Н, НС=СН), 7.42 d (1Н, НС=СН,
J 16.0 Hz), 7.51 d (2Нarom, J 8.7 Hz), 7.96 d (2Нarom
,
J 8.5 Hz), 9.89 br.s (1Н, NH). Found, %: С 70.09; Н 5.98;
N 4.22. C19H19NO4. Calculated, %: С 70.15; Н 5.85;
N 4.31.
Methyl N-{4-[2-isonicotinoyl-3-(4-methoxyphenyl)-
4,5-dihydro-1Н-pyrazol-5-yl]phenyl}-carbamate (X).
A mixture of 1.55 g (5 mmol) of chalcone II, 0.69 g
(5 mmol) of isonicotinic acid hydrazide in 25 mL of gla-
cial АсОН was boiled for 48 h, the excess of the solvent
was removed at a reduced pressure, the residue was trans-
ferred into 50 mL of ice water, the separated precipitate
was filtered off, washed on the filter with water (20 ml),
dried in air, and recrystallized from ethanol. Yield 1.6 g
(75%), colorless crystals, mp 84–86°С. IR spectrum, ν,
Methyl N-4-{[3-(furan-2-yl)prop-2-enoyl]phenyl}
carbamate (VII) was obtained from 1.93 g (0.01 mol) of
ketone I and 0.83 mL (0.01 mol) of furfural. Yield 2.1 g
(78%), yellow crystals, mp 151–153°С (ethanol). IR spec-
trum, ν, cm–1: 3330 (NH), 1710, 1690 (С=O), 1610, 1585,
1570 (С=С, C=Carom). 1Н NMR spectrum, δ, ppm: 3.71 s
(3Н, NHCO2Me), 6.82 d (1Нfuryl, J 5.0 Hz), 6.94–6.97 m
(1Нfuryl, 1Н, НС=СН), 7.17 d (1Нfuryl, J 5.0 Hz), 7.28 d
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013

SYNTHESIS AND APPLICATION OF CHALCONES
1615
cm–1: 3310 (NH), 1710, 1695 (С=O), 1615, 1575, 1565
(С=С, C=Carom). Н NMR spectrum, δ, ppm: 3.15 d.d
of chalcone II and 0.35 g (5 mmol) of hydroxylamine hy-
drochloride in 20 mLof pyridine was boiled for 5 h in the
presence of 0.2 mLof piperidine. On cooling the reaction
mixture was poured into 250 mL of ice water, the bases
were neutralized with conc. HCl, the separated precipitate
was filtered off, washed on the filter with water (50 ml),
dried in air, and recrystallized from ethanol. Yield 1.33 g
(82%), colorless crystals, mp 153–154°С. IR spectrum, ν,
cm–1: 3310 (NH), 1720 (С=O), 1610, 1575, 1565 (С=С,
C=Carom), 1595 (C=N). 1Н NMR spectrum, δ, ppm: 3.71 s
(3Н, NHCO2Me), 3.80 s (3Н, ОMe), 6.68 s (1Н, Н4),
7.08 d (2Нarom, J 8.6 Hz), 7.14 d (2Нarom, J 8.5 Hz), 7.20 d
(2Нarom, J 8.5 Hz), 8.02 d (2Нarom, J 8.6 Hz), 9.59 br.s (1Н,
NH). Found, %: С 66.61; Н 5.01; N 8.59. C18H16N2O4.
Calculated, %: С 66.67; Н 4.94; N 8.64.
1
(1Н, СН2, J 8.4, 8.4 Hz), 3.61 s (3Н, ОСН3), 3.65 d.d
(1Н, СН2, J 10.5, 10.5 Hz), 3.71 s (3Н, NHCO2Me), 4.89
d.d (1Н, СН, J 8.4, 8.8 Hz), 6.72 d (2Нarom, J 8.4 Hz),
6.94 d (2Нarom, J 8.5 Hz), 7.43 d (1Нarom, J 8.5 Hz), 7.55 d
(1Нarom, J 8.5 Hz), 7.81 d (2Нarom, J 8.4 Hz), 8.10 d
(2НPy, J 5.1 Hz), 8.98 d (2НPy, J 5.1 Hz), 9.61 br.s (1Н,
NH). Found, %: С 66.92; Н 5.14; N 12.88. C24H22N4O4.
Calculated, %: С 66.98; Н 5.12; N 13.02.
Methyl N-{4-[2-amino-6-(4-methoxyphenyl)pyrim-
idin-4-yl]phenyl}carbamate (XI). In 25 mLof methanol
was dissolved 0.12 g (5 mmol) of sodium, 0.48 g (5 mmol)
of guanidine hydrochloride was added, and the mixture
was boiled for 1 h, then 1.55 g (5 mmol) of chalcone
II was added, and the reaction mixture was boiled for
5 h. On cooling it was poured into 50 mL of ice water,
the separated precipitate was filtered off, washed on the
filter with water (10 ml), dried in air, and recrystallized
from ethanol. Yield 1.38 g (79%), light yellow crystals,
mp 110–112°С. IR spectrum, ν, cm–1: 3340, 3410 (NH,
NH2), 1720 (С=O), 1620, 1575, 1565 (С=С, C=Carom).
1Н NMR spectrum, δ, ppm: 3.71 s (3Н, NHCO2Me),
Methyl N-{4-[6-(thiophen-2-yl)-2-thioxo-1,2,3,6-
tetrahydropyrimidin-4-yl]phenyl}carbamate (XIV).
To 1.44 g (5 mmol) of chalcone VI and 0.46 g (6 mmol)
of thiourea in 5 mL of methanol was added 0.324 g
(6 mmol) of sodium methoxide prepared by dissolv-
ing 0.138 g (6 mmol) of sodium in 3 mL of anhydrous
methanol. The mixture was boiled for 3 h, cooled, the
base was neutralized with 5% acetic acid, the separated
precipitate was filtered off, washed on the filter with
water, dried in air, and recrystallized from mixture ethyl
acetate–petroleum ether, 1 : 3. Yield 1.28 g (74%), col-
orless crystals, mp 187–189°С. IR spectrum, ν, cm–1:
3240, 3310 (NH), 1720 (С=O), 1610, 1575, 1565 (С=С,
C=Carom), 1163 (C=S). 1Н NMR spectrum, δ, ppm: 3.71 s
(3Н, NHCO2Me), 5.20 d (1Н, Н6, J 4.4 Hz), 5.74 d (1Н,
Н5, J 4.4 Hz), 7.08 d (1Нarom, J 3.8 Hz), 7.28 t (1Н,
3.79 s (3H, OCH3), 5.49 s (2Н, NH2), 7.02 d (2Нarom
,
J 8.6 Hz), 7.08 d (2Нarom, J 8.5 Hz), 7.62 s (1Нarom),
8.05 d (2Нarom, J 8.6 Hz), 8.19 d (2Нarom, J 8.5 Hz),
9.54 br.s (1Н, NH). Found, %: С 65.17; Н 5.08; N 15.87.
C19H18N4O3. Calculated, %: С 65.14; Н 5.14; N 16.00.
Methyl N-{4-[5-(4-methoxyphenyl)-4,5-dihydro-
1Н-pyrazol-3-yl]phenyl}carbamate (XII). A mixture
of 1.55 g (5 mmol) of chalcone II and 0.18 g (5.5 mmol)
of 99% hydrazine hydrate in 10 mLof anhydrous ethanol
was boiled for 1 h, the reaction mixture was cooled, the
crystals were filtered off, washed on the filter with 10 mL
of cooled ethanol, 5 mL of ethyl ether, and recrystal-
lized from ethanol. Yield 1.5 g (94%), colorless crystals,
mp 164–166°С. IR spectrum, ν, cm–1: 3300–3330 (NH),
1715 (С=O), 1620, 1575, 1565 (С=С, C=Carom), 1586
(C=N). 1Н NMR spectrum, δ, ppm: 3.21 d.d (1Н, СН2,
J 8.4, 8.4 Hz), 3.34 d.d (1Н, СН2, J 10.5, 10.5 Hz), 3.71 s
(3Н, NHCO2Me), 3.79 s (3Н, ОMe), 4.90 d.d (1Н, СН,
J 8.4, 8.9 Hz), 6.72–6.76 m (3Н, 2Нarom, NH), 7.22 d
Нarom, J 4.5 Hz), 7.56–7.63 m (3Н, Нarom), 7.82 d (2Нarom,
J 7.9 Hz), 8.67 br.s (2Н, 2NH), 9.59 br.s (1Н, NHCO2Me).
Found, %: С 55.60; Н 4.27; N 11.99. C16H15N3O2S2.
Calculated, %: С 55.65; Н 4.35; N 12.17.
Semicarbazone of methyl N-{4-[2-(2-oxo-2,3-
dihydro-1Н-indol-3-yl)acetyl]phenyl}carbamate
(XV).Amixture of 1.62 g (5 mmol) of methyl N-{4-[2-(2-
oxo-2,3-dihydro-1Н-indol-3-yl)acetyl]phenyl}carbamate
[26], 0.56 g (5 mmol) of semicarbazide hydrochloride,
and 0.41 g (5 mmol) of anhydrous sodium acetate in
15 mL of methanol was boiled for 5 h, the reaction
mixture was poured on crushed ice, the separated pre-
cipitate was filtered off, washed with water, dried in air,
and recrystallized from ethanol. Yield 1.8 g (89%), light
yellow crystals, mp 209–210°С. IR spectrum, ν, cm–1:
3230, 3310 (NH), 1720, 1710 (С=O), 1620, 1580, 1565
(С=С, C=Carom). Found, %: С 59.82; Н 5.02; N 18.19.
(1Нarom, J 8.7 Hz), 7.30–7.33 m (3Нarom), 7.72 d (2Нarom
,
J 8.2 Hz), 9.68 br.s (1Н, NH). Found, %: С 66.22; Н 5.76;
N 12.85. C18H19N3O3. Calculated, %: С 66.46; Н 5.85;
N 12.92.
Methyl N-{4-[5-(4-methoxyphenyl)isoxazol-3-yl]
phenyl}carbamate (XIII).Amixture of 1.55 g (5 mmol)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 11 2013

VELIKORODOV et al.
1616
vol. 62, p. 2385.
C19H19N5O4. Calculated, %: С 59.84; Н 4.99; N 18.37.
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Org. Commun., 2010, vol. 3, p. 57.
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Toxicol. Lett., 2010, 196, p. 213.
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Indian J. Chem., 2009, vol. 48B, p. 1144.
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Astrakhan, 2011, p. 148.
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Methyl N-{4-[5-(2-oxo-2,3-dihydro-1Н-indol- 3-yl)-
1,2,3-selenadiazol-4-yl]phenyl}carbamate (XVI). A
mixture of 0.38 g (1 mmol) of semicarbazone XV and
0.56 g (5 mmol) of powdered selenium dioxide in 15 mL
of anhydrous tetrahydrofuran was heated at 60°С while
vigorously stirring for 2 h. The precipitate was filtered
off, the filtrate was poured on 50 g of crushed ice, the
reaction product was extracted with chloroform (3 ×
10 ml), the combined organic solutions were dried with
sodium sulfate, chloroform was removed, and the residue
was purified by column chromatography on silica gel
(60–120 mesh), eluent petroleum ether–ethyl acetate, 3 :
1, and recrystallized from ethanol. Yield 0.19 g (47%),
yellow crystals, mp 115–117°С. IR spectrum, ν, cm–1:
3330–3400 (NH), 1710, 1680 (C=O), 1620, 1575, 1560
1
(С=С, C=Carom), 830 (C–Se–N). Н NMR spectrum,
δ, ppm: 3.70 s (3Н, NHCO2Me), 4.52 s (1Н, Н3), 6.95 d
(2Нarom, J 8.5 Hz), 7.21–7.32 m (2Нarom), 7.48 d (1Нarom
J 7.8 Hz), 7.58 d (1Нarom, J 8.0 Hz), 7.81 d (2Нarom
,
,
J 8.5 Hz), 9.54 br.s (1Н, NHCO2Me), 10.35 br.s (1Н,
NHCO). 13С, δ, ppm: 51.32 (СН), 52.60 (ОMе), 108.78,
117.85, 121.13, 124.30, 125.12, 127.08, 128.19, 131.86,
135.74, 146.30 (Сarom), 146.14 (C5), 152.08 (C4), 154.84
(NHCO2Me), 168.15 (NHCO). Found, %: С 52.24;
Н 3.29; N 13.29. C18H14N4O3Se. Calculated, %: С 52.30;
Н 3.39; N 13.56.
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