Synthesis and Properties of 3-Substituted 2H-Chromen-2-ones

Article abstract of DOI:10.1134/S1070428020070015

Abstract: The condensation of salicylaldehyde with CH acids [p-methoxyacetoacetanilide, ethyl3-amino-3-sulfanylidenepropanoate, 3-amino-N-aryl-3-sulfanylidenepropanamides, and ethyl 2-(1,3-thiazol-2- and-4-yl)acetates] afforded 3-substituted chromen-2-one

Full text of DOI:10.1134/S1070428020070015

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2020, Vol. 56, No. 7, pp. 1123–1131. © Pleiades Publishing, Ltd., 2020.
Russian Text © The Author(s), 2020, published in Zhurnal Organicheskoi Khimii, 2020, Vol. 56, No. 7, pp. 993–1003.
Synthesis and Properties of 3-Substituted 2H-Chromen-2-ones
I. V. Dyachenkoa, V. D. Dyachenkoa, P. V. Dorovatovskyb,
V. N. Khrustalevc,d, and V. G. Nenaidenkoe,*
a Taras Shevchenko Lugansk National University, Lugansk, 91011 Ukraine
b “Kurchatov Institute” National Research Center, Moscow, 123182 Russia
c People’s Friendship University of Russia, Moscow, 117198 Russia
d Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, 119991 Russia
e Faculty of Chemistry, Moscow State University, Moscow, 119991 Russia
*e-mail: nenajdenko@gmail.com
Received April 5, 2020; revised April 7, 2020; accepted April 10, 2020
Abstract—The condensation of salicylaldehyde with CH acids [p-methoxyacetoacetanilide, ethyl 3-amino-3-
sulfanylidenepropanoate, 3-amino-N-aryl-3-sulfanylidenepropanamides, and ethyl 2-(1,3-thiazol-2- and -4-yl)
acetates] afforded 3-substituted chromen-2-ones. Some properties of the products were studied. The structures
of 3-[4-(4-chlorophenyl)-1,3-thiazol-2-yl]-2H-chromen-2-one, 2-oxo-2H-chromene-3-carboxamide, and
2-imino-N-(2-methoxyphenyl)-2H-chromene-3-carboxamide were determined by X-ray analysis.
Keywords: p-methoxyacetoacetanilide, ethyl 3-amino-3-sulfanylidenepropanoate, 3-amino-N-aryl-3-sulfanyli-
denepropanamide, ethyl 2-(1,3-thiazol-2-yl)acetate, 2H-chromen-2-one (coumarin), X-ray analysis
DOI: 10.1134/S1070428020070015
2H-Chromen-2-one (coumarin) derivatives exhibit
various biological activities, such as fungicidal [1],
antimicrobial [2, 3], and antitumor [4]. They are used
as intermediate products in the synthesis of highly
fluorescent dyes [5], anticoagulants [6], caspase ac-
tivators and apoptosis inducers [7], as well as acetyl-
cholinesterase inhibitors [8].
densations of salicylaldehyde (1) with some CH acids,
p-methoxyacetoacetanilide (2) and 3-amino-N-aryl-3-
sulfanylidenepropanamides 3 in ethanol at 20°C in the
presence of triethylamine. The reaction with CH acid 2
gave 2-hydroxy-N-(4-methoxyphenyl)-2-methyl-2H-
chromene-3-carboxamide 4. A probable intermediate in
this transformation is Knoevenagel condensation prod-
uct A which undergoes chemoselective intramolecular
cyclization to final structure 4 (Scheme 1).
In continuation of our studies on 2H-chromen-2-one
derivatives [9–11], in this work we performed con-
Scheme 1.
OMe
O
O
OMe
CHO
OH
O
O
Me
N
H
+
–H2O
Me
N
H
HO
1
2
A
OMe
O
N
H
OH
O
Me
4
1123

DYACHENKO et al.
1124
Scheme 2.
S
O
S
O
H2N
N
H
1
+
H2N
N
H
R
R
3a, 3b
HO
B
O
O
H2O, KOH
R = Me
N
H
Me
O
O
6
N
H
–H2S
O
R
O
NH
5a, 5b
Me(CH2)8I (7), KOH
N
R = OMe
OMe
O
NH
Me
( )5
8
3, 5, R = Me (a), OMe (b).
Scheme 3.
O
S
O
O
S
O
EtO
NH2
H2O
NH2
1
+
–EtOH, –H2S
H2N
OEt
O
HO
9
C
10
Salicylaldehyde (1) reacted with CH acids 3a and
3b under similar conditions to produce N-aryl-2-imino-
2H-chromene-3-carboxamides 5a and 5b. Presumably,
initial Knoevenagel condensation is followed by intra-
molecular heterocyclization of the condensation prod-
uct (B) with elimination of hydrogen sulfide, yielding
iminochromene 5 (Scheme 2). Treatment of 5a with
aqueous potassium hydroxide gave 2-oxo-N-(4-methyl-
phenyl)-2H-chromene-3-carboxamide (6) as a result of
hydrolysis of the imino group. The alkylation of 5b
with nonyl iodide (7) in DMF at 20°C in the presence
of KOH regioselectively involved the amide nitrogen
atom to afford 2-imino-N-(2-methoxyphenyl)-N-nonyl-
C14
O2
C9
C15
C10
C13
C12
C5
C4
C3
C6
C4A
N2
C11
C7
C8A
1
C2
2H-chromene-3-carboxamide (8). The H NMR
spectrum of 8 showed no NH proton signal (see
Experimental).
N1
O3
C8
O1
C16
Fig. 1. Structure of the molecule of 2-imino-N-(2-methoxy-
phenyl)-2H-chromene-3-carboxamide (5b) according to the
X-ray diffraction data. Non-hydrogen atoms are shown as
50% anisotropic thermal displacement ellipsoids. Intramolec-
ular hydrogen bond is shown with a dashed line.
The structure of 2-imino-N-(2-methoxyphenyl)-2H-
chromene-3-carboxamide (5b) was studied by X-ray
analysis. The 2-imino-2H-chromene-3-carboxamide
fragment of molecule 5b is almost planar (the mean-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 7 2020

SYNTHESIS AND PROPERTIES OF 3-SUBSTITUTED 2H-CHROMEN-2-ONES
1125
square deviation of atoms from the average plane is
0.040 Å); the planar structure is stabilized by both
extended conjugated bond system and fairly strong
intramolecular hydrogen bond between the amide NH
proton and nitrogen atom of the imino group (Fig. 1,
Table 1). The methoxy group is coplanar to the benzene
ring [torsion angle C12C11O3C16 –2.28(17)°], and the
methoxyphenyl substituent is turned through an angle
of 18.31(5)° with respect to the plane of the main
fragment. The observed geometry of molecule 5b is
also stabilized by the intramolecular hydrogen bond
N–H···O (Fig. 1, Table 1). Molecules 5b in crystal are
stacked along the b crystallographic axis and are
arranged by an angle of ~53° with respect to the (010)
plane (Fig. 2). No short intermolecular contacts were
found in the crystal structure of 5b.
a
c
0
b
By condensation of salicylaldehyde (1) with ethyl
3-amino-3-sulfanylidenepropanoate (9) in ethanol at
20°C in the presence of aqueous potassium hydroxide
we obtained 2-oxo-2H-chromene-3-carboxamide 10.
The reaction is likely to involve initial formation of
Knoevenagel condensation product C which undergoes
chemoselective cyclization at the ester group
(Scheme 3). The reaction was accompanied by hy-
drolysis of the thioamide group to amide. It should be
noted that analogous condensation in the presence of
morpholine instead of KOH lead to the formation of
2-oxo-2H-chromene-3-carbothioamide [9].
Fig. 2. Crystal packing of 2-imino-N-(2-methoxyphenyl)-
2H-chromene-3-carboxamide (5b).
O3
C5
C4
C9
C4A
C6
C3
N1
The structure of compound 10 was proved by X-ray
analysis. It crystallized in monoclinic crystal system,
space group P21/n, with three crystallographically
independent molecules in a unit cell. All crystallo-
graphically independent molecules of 10 have similar
structures and are virtually planar (the mean-square
deviations of atoms from the average planes are 0.034,
0.042, and 0.040 Å); the planar structure is stabilized
by both extended conjugated bond system and fairly
strong intramolecular hydrogen bond N–H···O (Fig. 3,
Table 1). Two of the three crystallographically inde-
pendent molecules 10 are linked to form an H-bonded
dimer through intermolecular hydrogen bonds
N–H···O (Fig. 4, Table 1). The third molecule also
forms a similar hydrogen-bonded dimer through inter-
molecular hydrogen bond N–H···O with a symmet-
rically equivalent molecule; i.e., unlike the former
dimer, the latter is centrosymmetric (Fig. 4, Table 1).
The hydrogen-bonded dimers are stacked along the
c crystallographic axis. Dimers within the stacks are
oriented parallel to the (0 1 2) i (0 –1 2) planes (Fig. 4).
C7
C8A
C2
C8
O2
O1
Fig. 3. Structure of the molecule of 2-oxo-2H-chromene-3-
carboxamide (10) according to the X-ray diffraction data.
One of the three crystallographically independent molecules
is shown. Non-hydrogen atoms are shown as 50% anisotropic
thermal displacement ellipsoids. Intramolecular hydrogen
bond is shown with a dashed line.
a
c
0
b
Fig. 4. Crystal packing of 2-oxo-2H-chromene-3-carbox-
amide (10). Intra- and intermolecular hydrogen bonds are
shown with dashed lines.
Likewise, the reaction of salicylaldehyde (1) with
ethyl 2-[2-(pyridin-3-yl)-1,3-thiazol-4-yl]acetate (11)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 7 2020

DYACHENKO et al.
1126
Scheme 4.
4"
5"
S
5'
4'
2'
3"
4
S
6"
O
3
N
N
1
+
2"
2
N
EtO
N
O
O
11
13
5'
S
4'
4
2'
R
O
S
3
N
R
1
+
2
N
EtO
O
O
12a–12c
14a–14c
12, 14, R = Bu (a), 4-ClC6H4 (b), cyclopropyl (c).
and ethyl 2-(4-R-1,3-thiazol-2-yl)acetates 12a–12c in
ethanol at 20°C in the presence of potassium hydroxide
led to the formation of 3-thiazolyl-2H-chromen-2-ones
13 and 14a–14c, respectively. These compounds are
convenient intermediate products for the construction
of ring assemblies [12, 13] (Scheme 4).
[3.2747(17) Å; –x, 1/2 + y, 1/2 – z] and S1···O1
[3.2842(14) Å; 1 – x, 1/2 + y, 3/2 – z] to form a three-
dimensional framework (Fig. 6).
EXPERIMENTAL
The unit cell parameters and X-ray reflection in-
tensities for compounds 5b, 10, and 14b were measured
on a BELOK synchrotron station at the Kurchatov
Institute National Research Center using a Rayonix
SX165 CCD two-coordinate detector (temperature
100 K, λ 0.96990 Å, φ-scanning with a step of 1.0°).
The data were processed by iMOSFLM program in-
cluded in CCP4 package [14]. A correction for absorp-
tion of X-rays was applied using SCALA program
[15]. The principal crystallographic data and structure
refinement parameters are collected in Table 2. The
structures were solved by the direct method and were
The structure of 3-[4-(4'-chlorophenyl)-1,3-thiazol-
2-yl]-2H-chromen-2-one (14b) was determined by
X-ray analysis. The chromene fragment of molecule
14b is planar within 0.042 Å (Fig. 5). The thiazole and
chlorophenyl rings are turned through dihedral angles
of 10.10(9) and 8.34(8)°, respectively, in opposite
directions relative to the chromene fragment, presum-
ably for steric reasons. Molecules 14b in crystal are
stacked along the a crystallographic axis. Molecules in
different stacks are linked to each other through weak
intermolecular non-covalent interactions Cl1···N1
Table 1. Hydrogen bonds in structures 5b and 10
D–H···A
d(D–H), Å
d(H···A), Å
d(D···A), Å
Angle DHA, deg
Compound 5b
N2–H2···O3
N2–H2···N1
0.938(15)
0.938(15)
2.253(14)
1.915(15)
2.6404(14)
2.7097(15)
103.9(10)
141.1(12)
Compound 10
N1–H1A···O6
N1–H1B···O2
N2–H2A···O3
N2–H2B···O5
N3–H3B···O8
N3–H3A···O9 a
0.88
0.88
0.88
0.88
0.88
0.88
2.03
1.98
1.97
2.11
2.03
2.02
2.908(8)
2.697(8)
2.852(9)
2.783(8)
2.729(9)
2.898(8)
173.6
137.2
175.8
133.1
135.0
173.6
a Symmetry operation: –x + 1, –y + 1, –z + 2.
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SYNTHESIS AND PROPERTIES OF 3-SUBSTITUTED 2H-CHROMEN-2-ONES
1127
Cl1
C14
C15
C16
C13
a
C12
C17
c
0
C10
N1
C9
C4
C5
C11
b
C4A
C6
C3
S1
C2
C8A
C7
C8
O2
O1
Fig. 5. Structure of the molecule of 3-[4-(4-chlorophenyl)-
1,3-thiazol-2-yl]-2H-chromen-2-one (14b) according to the
X-ray diffraction data. Non-hydrogen atoms are shown as
50% anisotropic thermal displacement ellipsoids.
Fig. 6. Crystal packing of 3-[4-(4-chlorophenyl)-1,3-thiazol-
2-yl]-2H-chromen-2-one (14b). Non-covalent intermolecular
interactions Cl···N and S···O are shown with dashed lines.
refined against F2 by the full-matrix least-squares
method in anisotropic approximation for non-hydrogen
atoms. Hydrogen atoms of the amino and imino groups
of 5b were localized by the difference Fourier syn-
theses and were refined in isotropic approximation
with fixed thermal displacement parameters [Uiso(H) =
1.2Ueq(N)]. Hydrogen atoms of the amino group of 10
were localized by the difference Fourier syntheses and
were refined with fixed positional (riding model) and
isotropic thermal displacement parameters [Uiso(H) =
1.2Ueq(N)]. The positions of the other hydrogen atoms
for all compounds were calculated geometrically and
were refined according to the riding model with fixed
positional parameters and isotropic thermal displace-
ment parameters [Uiso(H) = 1.5Ueq(C) for methyl
groups Uiso(H) = 1.2Ueq(C) for other hydrogens]. All
calculations were performed using SHELXTL software
package [16]. The tabulated coordinates of atoms, bond
lengths, bond and torsion angles, and anisotropic
displacement parameters for compounds 5b, 10, and
14b were deposited to the Cambridge Crystallographic
Data Centre [CCDC entry nos. 1877233 (5b), 1877234
(10), and 1877235 (14b)].
5b, 6, and 14b were obtained on an Orbitrap Elite high-
resolution mass spectrometer; samples were dissolved
in 1 mL of DMSO, and the solutions were diluted 100-
fold with 1% HCOOH in MeCN and introduced into
the electrospray ionization source at a flow rate of
40 μL/min using a syringe pump; ion source gas supply
was turned off; capillary voltage 3.5 kV, capillary
temperature 275°C; positive and negative ion detection,
Orbitrap resolution 480 000; internal calibrants
[2DMSO + H]+ ion (m/z 157.03515) for positive ions
and dodecyl sulfate anion (m/z 265.14789) for negative
ions. The mass spectra of the other compounds (elec-
tron impact, 70 eV) were recorded using an Agilent
1100 Series liquid chromatograph coupled with
an Agilent LC/MSD LS mass-selective detector
(samples were introduced in acetic acid). Elemental
analysis was performed with a Perkin Elmer CHN
analyzer. The melting points were measured on
a Kofler hot stage. The progress of reactions was
monitored, and the purity of the isolated compounds
was checked, by TLC on Silufol UV-254 plates using
acetone–hexane (3:5) as eluent; spots were visualized
by treatment with iodine vapor and under UV light.
The IR spectra were recorded on an IKS-40 spec-
trometer from samples dispersed in mineral oil. The
1H and 13C NMR spectra were measured on a Varian
VXR–400 spectrometer at 399.97 and 100 MHz,
respectively, using DMSO-d6 as solvent and tetra-
methylsilane as internal standard. The mass spectra of
2-Hydroxy-N-(2-methoxyphenyl)-2-methyl-2H-
chromene-3-carboxamide (4). A mixture of 1.1 mL
(10 mmol) of salicylaldehyde (1), 2.1 g (10 mmol) of
p-methoxyacetoacetanilide (2), and 0.1 mL of triethyl-
amine in 50 mL of ethanol was stirred at 20°C for 4 h
and was then left to stand for 3 days. The precipitate
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DYACHENKO et al.
1128
Table 2. Crystallographic data for compounds 5b, 10, and 14b
Parameter
5b
10
14b
Formula
C17H14N2O3
294.30
C10H7NO3
189.17
C18H10ClNO2S
339.78
Molecular weight
Single crystal dimensions, mm
0.15×0.15×0.15
Monoclinic
C2/c
0.10×0.15×0.25
Monoclinic
P21/n
0.10×0.10×0.30
Monoclinic
P21/c
Crystal system
Space group
a, Å
14.680(3)
11.455(2)
17.415(4)
107.86(3)
2787.4(11)
8
12.700(3)
14.290(3)
14.330(3)
105.43(3)
2506.9(10)
12
8.3300(17)
12.384(3)
14.622(3)
102.12(3)
1474.8(6)
4
b, Å
c, Å
β, deg
V, Å3
Z
d
calc, g/cm3
1.403
1.504
1.530
F(000)
1232
1176
696
μ, mm–1
0.206
0.242
0.965
2θmax, deg
76.84
66.00
76.92
Total number of reflections
Number of independent reflections (Rint)
Number of reflections with I > 2σ(I)
Number of variables
23895
8182
22410
2917 (0.062)
2511
3543 (0.114)
805
3006 (0.092)
2524
207
176
209
R1, wR2 [reflections with I > 2σ(I)]
R1; wR2 (all independent reflections)
Goodness of fit with respect to F2
Extinction coefficient
0.046; 0.123
0.053; 0.129
1.075
0.075; 0.153
0.243; 0.256
0.747
0.044; 0.055
0.108; 0.116
1.049
0.0045(4)
0.960; 0.960
0.0007(1)
0.930; 0.970
0.0111(11)
0.740; 0.900
Tmin; Tmax
was filtered off and washed with ethanol and hexane.
Yield 2.1 g (68%), yellow tube-like crystals, mp 131–
132°C (from EtOH). IR spectrum, ν, cm–1: 3010–3435
(O–H, N–H), 1658 (C=O). 1H NMR spectrum, δ, ppm:
1.79 c (3H, Me), 3.75 s (3H, MeO), 6.95–7.01 m (4H,
Harom, 4-H), 7.18-7.24 m (2H, Harom, OH), 7.30 t (1H,
precipitate was filtered off and washed with ethanol
and hexane. Yield 2.1 g (77%), yellow cotton-like
material, mp 202–204°C (from BuOH). IR spectrum, ν,
cm–1: 3300 (N–H), 1668 (C=O). 1H NMR spectrum, δ,
ppm: 2.34 s (3H, Me), 7.02 t (1H, Harom, J = 6.9 Hz),
7.11–7.30 m (4H, Harom), 7.57 t (1H, Harom, J = 7.4 Hz),
7.78 d (1H, Harom, J = 7.1 Hz), 8.24 d (1H, Harom, J =
7.7 Hz), 8.58 s (1H, 4-H), 9.13 br.s (1H, =NH),
12.53 br.s (1H, CONH). Mass spectrum: m/z 279.0
(Irel 100%) [M + 1]+. Found, %: C 73.25; H 4.93;
N 9.91. C17H14N2O2. Calculated, %: C 73.37; H 5.07;
N 10.07. M 278.3.
Harom, J = 6.5 Hz), 7.37 d (1H, Harom, J = 7.5 Hz),
7.61 d (2H, Harom, J = 7.2 Hz), 9.94 br.s (1H, NH).
13C NMR spectrum, δC, ppm: 26.4, 26.9, 55.2, 97.6,
113.9 (2C), 119.4, 121.1, 121.4 (2C), 128.1, 128.4,
131.9, 132.2, 152.3, 155.7, 164.0, 195.8. Mass spec-
trum: m/z 310.0 (Irel 100%) [M – 1]+. Found, %:
C 69.31; H 5.35; N 4.40. C18H17NO4. Calculated, %:
C 69.44; H 5.50; N 4.50. M 311.3.
2-Imino-N-(2-methoxyphenyl)-2H-chromene-3-
carboxamide (5b) was synthesized in a similar way
using 2.3 g (10 mmol) of 3-amino-N-(2-methoxy-
phenyl)-3-sulfanylidenepropanamide (3b). Yield 2.4 g
(82%), yellow crystals, mp 161–163°C (from BuOH).
IR spectrum, ν, cm–1: 3330 (N–H), 1662 (C=O).
1H NMR spectrum, δ, ppm: 3.84 s (3H, MeO), 6.91 t
(1H, Harom, J = 7.2 Hz), 7.01–7.12 m (2H, Harom), 7.19–
2-Imino-N-(2-methylphenyl)-2H-chromene-3-
carboxamide (5a). A mixture of 1.1 mL (10 mmol) of
aldehyde 1, 2.1 g (10 mmol) of 3-amino-N-(2-methyl-
phenyl)-3-sulfanylidenepropanamide (3a), and 0.1 mL
of triethylamine in 70 mL of ethanol was stirred at
20°C for 5 h and was then left to stand for 2 days. The
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SYNTHESIS AND PROPERTIES OF 3-SUBSTITUTED 2H-CHROMEN-2-ONES
1129
7.28 m (2H, Harom), 7.54 t (1H, Harom, J = 7.2 Hz),
7.76 d (1H, Harom, J = 7.6 Hz), 8.42 d (1H, Harom, J =
7.2 Hz), 8.52 br.s (1H, =NH), 9.13 s (1H, 4-H),
12.79 br.s (1H, CONH). 13C NMR spectrum, δC, ppm:
56.4, 111.5, 115.4, 119.0, 120.4, 120.9, 121.1, 124.5,
124.6, 128.3, 130.5, 133.6, 142.0, 149.4, 154.0, 155.7,
160.0. Found: m/z 295.1078 [M + H]+. C17H14NO3.
Calculated: M + H 295.1004.
2-Oxo-2H-chromene-3-carboxamide (10). A mix-
ture of 1.1 mL (10 mmol) of aldehyde 1, 1.5 g
(10 mmol) of ethyl 3-amino-3-sulfanylidenepropanoate
(9), and 5.6 mL(10 mmol) of 10% aqueous potassium
hydroxide in 25 mL of DMF was stirred at 20°C for 5 h
and was then left to stand for 2 days. The mixture was
diluted with an equal volume of water, and the precip-
itate was filtered off and washed with water, ethanol,
and hexane. Yield 1.3 g (68%), yellow needles fluor-
escing under UV light, mp 268–270°C (from AcOH).
IR spectrum, ν, cm–1: 3389, 3149, 3056 (N–H), 1716
2-Oxo-N-(2-methylphenyl)-2H-chromene-3-
carboxamide (6). Compound 5a, 2.8 g (10 mmol), was
dissolved in 25 mL of DMF, 5.6 mL (10 mmol) of
10% aqueous potassium hydroxide was added with
stirring at 20°C, and the mixture was stirred for 4 h and
left to stand for 2 days. The mixture was diluted with
an equal volume of water, and the precipitate was
filtered off and washed in succession with water,
ethanol, and hexane. Yield 2.1 g (75%), yellow cotton-
like material, mp 215–216°C (from BuOH). IR spec-
trum, ν, cm–1: 3300 (N–H), 1713 (C2=O), 1658
(3-C=O). 1H NMR spectrum, δ, ppm: 2.32 s (3H, Me),
7.07 t (1H, Harom, J = 7.4 Hz), 7.21 t (1H, Harom, J =
8.0 Hz), 7.25 d (1H, Harom, J = 7.6 Hz), 7.46 t (1H,
Harom, J = 7.6 Hz), 7.51 d (1H, Harom, J = 8.3 Hz),
7.75 t (1H, Harom, J = 8.3 Hz), 7.99 d (1H, Harom, J =
7.8 Hz), 8.08 d (1H, Harom, J = 8.0 Hz), 8.98 s (1H,
4-H), 10.53 br.s (1H, NH). 13C NMR spectrum, δC,
ppm: 17.9, 110.0, 116.6, 119.0, 119.6, 122.1, 125.1,
125.7, 126.8, 128.9, 130.8, 134.8, 136.6, 148.6, 154.4,
159.8, 161.6. Found: m/z 280.0988 [M + H]+.
C17H13NO3. Calculated: M + H 280.0895.
1
(C2=O), 1678 (3-C=O). H NMR spectrum, δ, ppm:
7.38 t (1H, Harom, J = 7.4 Hz), 7.44 d (1H, Harom, J =
8.4 Hz), 7.63–7.75 m (2H, Harom, NH2), 7.91 d (1H,
H
arom, J = 7.8 Hz), 7.98 br.s (1H, NH2), 8.81 s (1H,
4-H). 13C NMR spectrum, δC, ppm: 116.5, 118.9,
119.9, 125.5, 130.6, 134.4, 148.1, 154.5, 160.7, 162.9.
Mass spectrum: m/z 190.1 (Irel 100%): [M + 1]+.
Found, %: C 63.32; H 3.64; N 7.35. C10H7NO3. Cal-
culated, %: C 63.49; H 3.73; N 7.40. M 189.2.
3-Thiazolyl-2H-chromen-2-ones 13 and 14a–14c
(general procedure). Aldehyde 1, 1.1 mL (10 mmol),
was dissolved in 30 mL of DMF, 10 mmol of CH acid
11 or 12a–12c and 5.6 mL (10 mmol) of 10% aqueous
potassium hydroxide were added at 20°C, and the
mixture was stirred for 5 h and left to stand for 24 h.
The mixture was diluted with an equal volume of
water, and the precipitate was filtered off and washed
with water, ethanol, and hexane.
3-[2-(Pyridin-3-yl)-1,3-thiazol-4-yl]-2H-chromen-
2-one (13). Yield 2.5 g (80%), light yellow powder
fluorescing under UV light, mp 172–174°C (from
2-Imino-N-(2-methoxyphenyl)-N-nonyl-2H-
chromene-3-carboxamide (8). A mixture of 3.0 g
(10 mmol) of chromene 5b, 5.6 mL (10 mmol) of
10% aqueous potassium hydroxide, and 1.2 mL
(10 mmol) of nonyl iodide (7) in 30 mL of DMF was
stirred at 20°C for 5 h and was then left to stand for
24 h. The mixture was diluted with an equal volume of
water, and the precipitate was filtered off and washed
with water, ethanol, and hexane. Yield 3.0 g (71%),
bright yellow finely crystalline powder, mp 98–99°C
(from EtOH). IR spectrum, ν, cm–1: 3300 (N–H), 1665
(C=O). 1H NMR spectrum, δ, ppm: 0.81 t (3H, Me, J =
6.8 Hz), 1.13–1.52 m (12H, CH2), 1.73–1.82 m (2H,
CH2), 3.89 s (3H, MeO), 4.06 t (2H, NCH2, J =
6.4 Hz), 6.92 t (1H, Harom, J = 7.6 Hz), 6.95–7.19 m
(4H, Harom), 7.51 t (1H, Harom, J = 7.6 Hz), 8.03–
8.06 m (1H, Harom), 8.14 d (1H, Harom, J = 8.0 Hz),
8.66 s (1H, 4-H), 8.94 br.s (1H, NH). Mass spectrum:
m/z 421.2 (Irel 100%): [M + 1]+. Found, %: C 74.11;
H 7.55; N 6.50. C26H32N2O3. Calculated, %: C 74.26;
H 7.67; N 6.66. M 420.6.
1
BuOH). IR spectrum: ν 1712 cm–1 (C=O). H NMR
spectrum, δ, ppm: 7.40 t (1H, Harom, J = 8.0 Hz), 7.46 d
(1H, Harom, J = 8.4 Hz), 7.56–7.62 m (1H, Harom),
7.66 t (1H, Harom, J = 8.0 Hz), 7.93 d (1H, Harom, J =
8.4 Hz), 8.37–8.43 m (1H, Harom), 8.52 s (1H, 2″-H),
8.71 d (1H, 6″-H, J = 4.9 Hz), 9.00 s (1H, 5′-H), 9.28 s
(1H, 4-H). 13C NMR spectrum, δC, ppm: 116.0, 119.2,
120.1, 121.0, 124.3, 125.0, 128.7, 129.2, 132.3, 134.0,
140.3, 147.3, 148.5, 151.3, 152.7, 159.0, 163.8. Mass
spectrum: m/z 307.0 (Irel 100%): [M + 1]+. Found, %:
C 66.51; H 3.18; N 8.96. C17H10N2O2S. Calculated, %:
C 66.65; H 3.29; N 9.14. M 306.4.
3-(4-Butyl-1,3-thiazol-2-yl)-2H-chromen-2-one
(14a). Yield 2.3 g (80%), yellow plates fluorescing
under UV light, mp 112–114°C (from AcOH). IR spec-
1
trum: ν 1715 cm–1 (C=O). H NMR spectrum, δ, ppm:
0.90 t (3H, Me, J = 7.4 Hz), 1.16–1.48 m (2H, CH2),
1.62–1.71 m (2H, CH2), 2.76 t (2H, CH2, J = 7.4 Hz),
7.40 t (1H, Harom, J = 7.8 Hz), 7.45 s (1H, 5′-H), 7.48 d
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 7 2020

DYACHENKO et al.
1130
3. Abdelhamid, A.O. and Al-Atoom, A.A., Phosphorus,
Sulfur Silicon Relat. Elem., 2005, vol. 180, p. 1629.
https://doi.org/10.1080/104265090885048
4. Trkovnik, M., Ivezich, Z., and Polak, L., RU Patent
Appl. no. 97111207/04, 1999; Ref. Zh., Khim., 2000,
no. 00.02-19O.178P.
(1H, Harom, J = 8.0 Hz), 7.65 t (1H, Harom, J = 8.0 Hz),
7.99 d (1H, Harom, J = 7.8 Hz), 8.91 s (1H, 4-H).
13C NMR spectrum, δC, ppm: 14.0, 22.1, 30.6, 31.0,
116.4, 117.4, 119.3, 119.7, 125.5, 130.2, 133.0, 139.3,
153.0, 157.5, 157.7, 160.4. Mass spectrum: m/z 286.0
(Irel 100%) [M + 1]+. Found, %: C 67.22; H 5.20;
N 4.85. C16H15NO2S. Calculated, %: C 67.34; H 5.30;
N 4.91. M 285.4.
5. Luo, X., Song, J., Cheng, L., and Huang, D., Sci. China,
Ser. B: Chem., 2001, vol. 44, p. 532.
https://doi.org/10.1007/BF02880684
3-[4-(4-Chlorophenyl)-1,3-thiazol-2-yl]-2H-
chromen-2-one (14b). Yield 2.7 g (78%), mp 208–
210°C (from BuOH); published data [9]: mp 208–
212°C. 13C NMR spectrum, δC, ppm: 116.7, 118.6,
119.4, 119.8, 125.7, 128.3 (2C), 129.3 (2C), 130.3,
133.1, 133.3, 133.5, 140.2, 153.4, 153.6, 159.1, 159.8.
Found: m/z 340.0197 [M + H]+. C18H10ClNO2S. Cal-
culated: M + H 340.0121.
6. Carter, D.C., US Patent no. 7179838, 2007; Ref. Zh.,
Khim., 2007, no. 07.24-19O.92P.
7. Cai, S.X., Zhang, H., Kemnitzer, W.E., Jiang, S.,
Drewe, J., and Storer, R., US Patent no. 6900325, 2005;
Ref. Zh., Khim., 2006, no. 06.06-19O.133P.
8. Brühlmann, C., Ooms, F., Carrupt, P.-A., Testa, B.,
Catto, M., Leonetti, F., Altomare, C., and Carotti, A.,
J. Med. Chem., 2001, vol. 44, p. 3195.
https://doi.org/10.1021/jm010894d
3-(4-Cyclopropyl-1,3-thiazol-2-yl)-2H-chromen-
2-one (14c). Yield 1.9 g (70%), yellow crystals,
mp 168–170°C (from AcOH). IR spectrum:
ν 1712 cm–1 (C=O). 1H NMR spectrum, δ, ppm: 0.81–
1.02 m (4H, CH2), 2.18–2.24 m (1H, 4′-CH), 7.43 t
(1H, Harom, J = 7.4 Hz), 7.45 s (1H, 5′-H), 7.47 d (1H,
9. Dyachenko, V.D. and Pugach, Yu.Yu., Russ. J. Gen.
Chem., 2012, vol. 82, p. 921.
https://doi.org/10.1134/s1070363212050209
10. Dyachenko, V.D., Chernega, A.N., and Dyachenko, S.V.,
Russ. J. Gen. Chem., 2012, vol. 82, p. 720.
https://doi.org/10.1134/s1070363212040184
11. Dyachenko, V.D. and Pugach, Yu.Yu., Russ. J. Gen.
Chem., 2013, vol. 83, p. 979.
H
arom, J = 7.4 Hz), 7.68 t (1H, Harom, J = 8.4 Hz),
7.98 d (1H, Harom, J = 7.8 Hz), 8.88 s (1H, 4-H).
13C NMR spectrum, δC, ppm: 8.4 (2C), 12.0, 115.3,
116.2, 119.0, 119.5, 125.2, 129.8, 132.8, 138.8, 152.9,
157.6, 158.8, 159.3. Mass spectrum: m/z 270.2
(Irel 100%) [M + 1]+. Found, %: C 66.59; H 3.97;
N 5.06. C15H11NO2S. Calculated, %: C 66.70; H 4.12;
N 5.20. M 269.3.
https://doi.org/10.1134/S1070363213050162
12. Antipin, I.S., Kazymova, M.A., Kuznetsov, M.A.,
Vasilyev, A.V., Ishchenko, M.A., Kiryushkin, A.A.,
Kuznetsova, L.M., Makarenko, S.V., Ostrovskii, V.A.,
Petrov, M.L., Solod, O.V., Trishin, Yu.G., Yakovlev, I.P.,
Nenaidenko, V.G., Beloglazkina, E.K., Beletskaya, I.P.,
Ustynyuk, Yu.A., Solov’ev, P.A., Ivanov, I.V.,
Malina, E.V., Sivova, N.V., Negrebetskii, V.V.,
Baukov, Yu.I., Pozharskaya, N.A., Traven’, V.F.,
Shchekotikhin, A.E., Varlamov, A.V., Borisova, T.N.,
Lesina, Yu.A., Krasnokutskaya, E.A., Rogozhni-
kov, S.I.,Shurov, S.N., Kustova, T.P., Klyuev, M.V.,
Khelevina, O.G., Stuzhin, P.A., Fedorov, A.Yu.,
Gushchin, A.V., Dodonov, V.A., Kolobov, A.V.,
Plakhtinskii, V.V., Orlov, V.Yu., Kriven’ko, A.P.,
Fedotova, O.V., Pchelintseva, N.V., Charushin, V.N.,
Chupakhin, O.N., Klimochkin, Yu.N., Klimochki-
na, A.Yu., Kuryatnikov, V.N., Malinovskaya, Yu.A.,
Levina, A.S., Zhuravlev, O.E., Voronchikhina, L.I.,
Fisyuk, A.S., Aksenov, A.V., Aksenov, N.A., and
Aksenova, I.V., Russ. J. Org. Chem., 2017, vol. 53,
p. 1275.
FUNDING
This study was financially supported by the “5–100”
Program for increasing the rating of the People’s Friendship
University of Russia. The X-ray diffraction studies were
performed on the unique research setup “Kurchatov
Synchrotron Radiation Source” supported by the Ministry of
Science and Higher Education of the Russian Federation
(project ID RFMEFI61917X0007).
CONFLICT OF INTEREST
The authors declare no conflict of interest.
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