Synthesis of 3-(N-arylcarbamoyl)chromones from 2-hydroxyarylaminoenones and isocyanates

Article abstract of DOI:10.1007/s11172-019-2423-5

A new method for the synthesis of 2-unsubstituted and 2-substituted 3-(N-arylcarbamoyl)-chromones by the reaction of 3-dimethylamino-1-(2-hydroxyaryl)prop-2-en-1-ones with arylisocyanates has been proposed.

Full text of DOI:10.1007/s11172-019-2423-5

Russian Chemical Bulletin, International Edition, Vol. 68, No. 1, pp. 104—109, January, 2019
104
Synthesis of 3-(N-arylcarbamoyl)chromones from
2-hydroxyarylaminoenones and isocyanates
K. A. Myannik, I. S. Semenova, V. N. Yarovenko, and M. M. Krayushkin
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
E-mail: mkray@ioc.ac.ru
A new method for the synthesis of 2-unsubstituted and 2-substituted 3-(N-arylcarbamoyl)-
chromones by the reaction of 3-dimethylamino-1-(2-hydroxyaryl)prop-2-en-1-ones with
arylisocyanates has been proposed.
Key words: heterocyclic compounds, chromones, enaminones, amides, isocyanates.
Chromones containing carbamoyl groups are of
to the corresponding acids, and subsequent reaction
with amines.6—8 The disadvantages of this method in-
clude the multistage process, as well as the limitation
associated with the difficulties of using substances with
substituents that are sensitive to oxidizing agents. We
also note that using this method it was not possible to
obtain 3-carbamoylchromones containing substituents
in position 2.
considerable interest. Much attention is paid, in par-
ticular, to the synthesis and study of the biological activ-
ity of 3-carbamoylchromones. They are being studied
as antioxidants and ligands of adenosine receptor that
regulate a number of important biological functions and
are useful for treating various diseases, such as cancer
and cardiovascular diseases.1,2 It was also established
that they are of interest as promising monoamineoxidase
inhibitors, which are used in the treatment of a number
of diseases, for example, Alzheimer´s and Parkinson´s
diseases.3—5 Thus, the synthetic and practical potential
of these benzopyrans stimulates the development of new
convenient methods for their preparation.
Earlier,9 we have shown that thiocarbamoylchrom-
ones can be formed by the interaction of β-benzo-
enaminone compounds with isothiocyanates.
In this work, we investigated the reaction of enami-
none 1 with isocyanates. It could be assumed that
heterocyclization will occur after the addition of the
isocyanate to the enaminone, and subsequent elimina-
tion of the amine will lead to the formation of 3-carb-
amoylchromones 2 (Scheme 1).
The most common approach to the synthesis of
3-carbamoylchromones involves the conversion of hydr-
oxyacetophenones to formylchromones, their oxidation
Scheme 1
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 0104—0109, January, 2019.
1066-5285/19/6801-0104 © 2019 Springer Science+Business Media, Inc.

Synthesis of 3-(N-arylcarbamoyl)chromones
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 1, January, 2019
105
Table 1. Influence of solvents, temperature (T), and
reaction duration (t) on yields of carboxamide 2f
It is known that β-enaminones, combining in their
molecule the ambident nucleophilicity of enamines with
the ambident electrophilicity of enones, are widely used
in the synthesis of various heterocyclic compounds.
β-Enaminones, obtained by reacting the corresponding
hydroxyacetophenones with dimethylformamide di-
acetal, have been used, for example, in the synthesis of
halogen, mercapto, and acetyl derivatives of chromone
with substituents in position 3.10—12 However, nothing
is known on application of β-enaminones in the syn-
thesis of 3-carbamoylchromones and their derivatives
substituted in position 2. We investigated the interaction
of β-benzoenaminone 1 containing primary, second-
ary, and tertiary amino groups with isocyanates. It is
known13,14 that, depending on the nature of the amino
group, β-enaminones can be in the form of Z- or
E-isomers. The β-enaminones 1 with a tertiary amino
group show in 1H NMR spectrum signals of vinyl proton
at 9 and 5 ppm with the coupling constants of 12.1 Hz,
and the signal of the OH group is shifted to the weak
field region (δ 11) due to the formation of a hydrogen
bond with the keto group. This is also confirmed by the
data of IR spectra, where there is a broad vibration band
of the hydroxyl group in the region of 3000 cm–1. On
this basis, the β-enaminones can be attributed to the
configuration of the E-s-Z isomer (Scheme 2).
Solvent
T/C
t/h
Yield (%)
DMF
120
110
110
110
101
184
120
8
8
8
8
1
1
2
50
65
65
32
—
—
60
DMF
Тоluene
Nitromethane
1,2-Dichloroethane
1,4-Dioxane
Without solvent
and toluene, the carboxamides are obtained at room
temperature keeping for a long time, and at 110—120 С
for 8 h. The best yields were observed in DMF and
toluene.
With an increase in the process temperature in DMF,
the yield of the target product decreased, possibly due
to the decomposition of the reactants and reaction
products (Table 1).
The effect of basic and acid catalysts on the process
was also investigated. It turned out that with the use of
acetic or p-toluenesulfonic acid, only the cyclization of
the starting enaminone into unsubstituted chromone 3
occurs (Scheme 3).
Scheme 3
Scheme 2
Potassium carbonate, triethylamine or Hünig´s base
had no significant effect on the process.
Electron-withdrawing substituents in isocyanates
promote the reaction, electron-donating groups reduce the
yields of 3-carbamoylchromones, while the influence of sub-
stituents in β-enaminones on the process is not detected.
It turned out that the structure of the amine fragment
in β-enaminone has virtually no effect on the yields of
chromones 2 or on the rate of the process, which makes
it possible to use the most accessible enaminones with
dimethylamine group in the synthesis of 3-carbamoyl-
chromones. The method allowed to obtain a wide range
of 3-carbamoylchromones containing various substitu-
ents (Scheme 4).
Along with the nature of the amino group, we inves-
tigated the effect of solvents, temperature, duration of
the reaction, as well as substituents in substrates and
reagents on the yields of carboxamides. Reactions were
carried out in an inert atmosphere with a twofold excess
of isocyanate to bind the amine released during the
reaction. It turned out that solvents play a significant
role in this process. Conducting the reaction in aceto-
nitrile, dichloroethane, N-methylpyrrolidone and vary-
ing the temperature did not lead to the formation of
carboxamides. At the same time, in DMF, nitromethane,
It is important to emphasize that the proposed ap-
proach can be used to obtain 3-carbamoylchromones with
substituents in position 2. This requires the presence of
a corresponding group in the ketoenamine moiety, which

106
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 1, January, 2019
Myannik et al.
Scheme 4
Thus, the interaction of o-hydroxyarylenaminones
containing amino groups in the β-enaminone moiety
with isocyanates has been investigated. This resulted in
a method for producing various 3-carbamoylchromones
with and without a substituent in position 2.
Experimental
2
a
b
c
d
e
f
R
H
6-Me
H
R´
Ph
Ph
2
k
l
m
n
o
p
q
r
R
H
6-Br
6-Br
6-Br
R´
NMR spectra were recorded in deuterated solvents using
a Bruker Avance 300 spectrometer (300.13 (1Н) and 75.77 MHz
1-Naphthyl
Ph
3-ClC6H4
1-Naphthyl
3-ClC6H4
1-Naphthyl
Ph
3-ClC6H4
1-Naphthyl
Ph
(
13С)). High-resolution mass spectra (HRMS) were obtained by
4-MeOC6H4
3-MeOC6H4
Ph
2,4-Cl2C6H3
4-CF3C6H4
Ph
spray ionization (ESI) in acetonitrile using a Bruker MicroTOF
spectrometer. Elemental analysis was performed on an auto-
matic analyzer Eurovector EA 3000.
H
6,7-Cl2
6-Me
6-Me
Benzo[h]
Benzo[h]
Benzo[h]
8H-[1,3]di-
oxolo[4,5-g]
H
g
h
i
H
7-MeO
H
Synthesis of chromone-3-carboxamides 2 (general procedure).
Mixture of β-enaminone 1 (1 mmol) and corresponding iso-
cyanate (2.2 mmol) was heated in a minimal amount of DMF
(1 mL) or toluene (3 mL) at 110 C. After heating for 1—8 h (TLC
control) and subsequent cooling, a white precipitate appeared,
which was filtered, washed with ethanol and diethyl ether, and
dried in air. If enaminone remained in the precipitate, the mix-
ture was recrystallized from ethanol.
3-ClC6H4
4-ClC6H4
s
t
j
H
can be introduced, for example, by reacting benzylamine
with benzopyrans15 4 in ethanol (Scheme 5).
4-Oxo-N-phenyl-4H-chromen-3-carboxamide (2a). White
crystals, yield 0.35 g (65%), m.p. 214—215 C (see Ref. 16: m.p.
214—216 C). 1H NMR (DMSO-d6), δ: 7.13 (t, 1 Н, HAr´
,
Scheme 5
J = 7.0 Hz); 7.39 (t, 2 Н, HAr´, J = 7.4 Hz); 7.62—7.73 (m, 3 Н, HAr);
7.82 (d, 1 Н, HAr, J = 8.3 Hz); 7.94 (t, 1 Н, HAr, J = 7.4 Hz);
8.25 (d, 1 Н, H(4), J = 7.8 Hz); 9.17 (s, 1 Н, H(2)); 11.28 (s, 1 Н,
NН). 13C NMR (CDCl3), δ: 116.0, 118.5, 120.5 (2 С), 124.1,
124.4, 126.2, 126.5, 129.0 (2 С), 134.8, 138.0, 156.2, 160.7, 162.8,
177.4. Found (%): C, 72.57; H, 4.22; N, 5.18. C16H11NO3.
Calculated (%): C, 72.45; H, 4.18; N, 5.28.
6-Methyl-4-oxo-N-phenyl-4H-chromen-3-carboxamide (2b).
White crystals, yield 0.3 g (54%), m.p. 187—189 C (see Ref. 17).
1Н NMR (CDCl3), δ: 2.53 (s, 3 H, CH3); 7.16 (t, 1 H, HAr´
,
J = 7.3 Hz); 7.39 (t, 2 H, HAr´, J = 7.7 Hz); 7.49 (d, 1 H, HAr
,
J = 8.5 Hz); 7.60 (d, 1 H, HAr, J = 8.5 Hz); 7.75 (d, 2 H, HAr´
,
J = 8.0 Hz); 8.12 (s, 1 H, H(5)); 9.06 (s, 1 H, H(2)); 11.46 (s, 1 H,
NН). 13C NMR (CDCl3), δ: 21.0, 115.8, 118.2, 120.5 (2 C), 123.7,
124.4, 125.5, 129.0 (2 C), 136.1, 136.7, 138.0, 154.5, 160.8, 162.6,
177.4. Found (%): C, 73.18; H, 4.73; N, 5.10. C17H13NO3.
Calculated (%): C, 73.11; H, 4.69; N, 5.02.
N-(4-Methoxyphenyl)-4-oxo-4H-chromen-3-carboxamide
(2c). White crystals, yield 0.15 g (50%), m.p. 168—170 C (see
Ref. 18). 1Н NMR (CDCl3), δ: 3.81 (s, 3 H, CH3); 6.92 (d, 2 H,
R = Ph (a), 2-MeC6H4 (b), 4-MeC6H4 (c),
furan-2-yl (d), thiophen-2-yl (e)
The reaction of enaminones 5 with isocyanates led
to the formation of carbamoylchromones 6a—f with
substituents in position 2 (Scheme 6).
H
Ar´, J = 8.9 Hz); 7.51—7.71 (m, 4 H, HAr, HAr´); 7.80 (t, 1 H,
Scheme 6
HAr, J = 7.2 Hz); 8.34 (d, 1 H, H(5), J = 8.1 Hz); 9.08 (s, 1 H,
H(2)); 11.28 (s, 1 H, NH). Found (%): C, 69.18; H, 4.23; N, 4.60.
C17H13NO4. Calculated (%): C, 69.15; H, 4.44; N, 4.74.
N-(3-Methoxyphenyl)-4-oxo-4H-chromen-3-carboxamide
(2d). White crystals, yield 0.16 g (71%), m.p. 160—161 C (see
Ref. 18). 1H NMR (DMSO-d6), δ: 3.77 (s, 3 H, CH3); 7.26
(m, 2 Н, H(5´), H(6´)); 6.72 (d, 1 Н, H(4´), J = 8.6 Hz); 7.64
(t, 1 Н, H(6), J = 7.7 Hz); 7.42 (s, 1 H, H(2´)); 7.81 (d, 1 Н,
H(8), J = 8.1 Hz); 7.94 (t, 1 Н, H(7), J = 7.6 Hz); 8.24 (d, 1 Н,
H(5), J = 8.2 Hz); 9.17 (s, 1 Н, H(2)); 11.28 (s, 1 H, NH).
Found (%): C, 69.05; H, 4.52; N, 4.64. C17H13NO4. Calculat-
ed (%): C, 69.15; H, 4.44; N, 4.74.
R = R´ = Ph (6a); R = 4-MeC6H4, R´ = Ph (6b);
R = furan-2-yl, R´ = Ph (6c);
R = furan-2-yl, R´ = 2,4-Cl2C6H3 (6d);
R = furan-2-yl, R´ = 4-CF3C6H4 (6e);
R = thiophen-2-yl, R´ = 2,4-Cl2C6H3 (6f)
6,7-Dichloro-4-oxo-N-phenyl-4H-chromen-3-carboxamide
(2e). White crystals, yield 0.16 g (71%), m.p. 250—252 C.

Synthesis of 3-(N-arylcarbamoyl)chromones
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 1, January, 2019
107
1H NMR (DMSO-d6), δ: 7.14 (d, 1 H, HAr, J = 6.7 Hz);
7.33—7.42 (m, 2 H, HAr); 7.66 (d, 2 H, HAr, J = 7.4 Hz); 8.19
(s, 1 H, H(8)); 8.31 (s, 1 H, H(5)); 9.08 (s, 1 H, H(2)); 10.90
(s, 1 H, NH). Found (%): C, 57.45; H, 2.65; N, 4.12. C16H9Cl2NO3.
Calculated (%): C, 57.51; H, 2.71; N, 4.19.
11.62 (s, 1 H, NН). 13C NMR (CDCl3), δ: 115.2, 120.5, 120.7,
121.9 (2 C), 125.0, 126.2, 128.9, 129.3 (2 C), 136.3, 138.5, 155.0,
162.2, 163.9, 176.4. Found (%): C, 55.80; H, 2.90; Br, 23.31.
C16H10BrNO3. Calculated (%): C, 55.84; H, 2.93; Br, 23.22.
6-Bromo-N-(3-chlorophenyl)-4-oxo-4H-chromen-3-carbox-
amide (2m). White crystals, yield 0.34 g (61%), m.p. 274—275 C.
1Н NMR (CDCl3), δ: 7.26 (t, 1 Н, J = 7.9 Hz); 7.36 (t, 1 Н,
J = 7.9 Hz); 7.50 (d, 1 Н, J = 7.9 Hz); 7.58 (d, 1 Н, J = 8.9 Hz);
7.70 (s, 1 Н); 7.96 (d, 1 Н, J = 8.9 Hz); 8.46 (s, 1 Н, H(5)); 9.21
(s, 1 Н, H(2)); 11.69 (s, 1 Н, NН). 13C NMR (CDCl3), δ: 120.1,
120.5, 120.9, 121.4, 122.2, 124.8, 126.4, 128.8, 130.2, 134.9, 137.0,
138.8, 155.0, 160.2, 164.3, 176.6. Found (%): C, 50.78; H, 2.44;
N, 3.78. C16H9BrClNO3. Calculated (%): C, 50.76; H, 2.40;
N, 3.70.
6-Bromo-N-(1-naphthyl)-4-oxo-4H-chromen-3-carboxamide
(2n). White crystals, yield 0.21 g (52%), m.p. 228—229 C.
1Н NMR (CDCl3), δ: 7.28—7.55 (m, 3 H); 7.65 (t, 1 H,
J = 7.6 Hz); 7.72 (d, 1 H, J = 8.1 Hz); 7.89 (d, 2 H, J = 8.5 Hz);
8.24 (d, 1 H, J = 8.3 Hz); 8.34 (d, 1 H, J = 7.3 Hz); 8.54 (s, 1 H,
H(5)); 9.16 (s, 1 H, H(2)); 11.97 (s, 1 H, NН). 13C NMR (CDCl3),
δ: 116.4, 119.1, 120.3, 120.4, 120.9, 125.3, 125.9, 126.1 (2 C),
126.7, 128.7, 129.0, 131.3, 132.8, 134.1, 138.0, 155.0, 160.9, 163.3,
176.6. Found (%): C, 60.88; H, 3.06; N, 3.58. C20H12BrNO3.
Calculated (%): C, 60.94; H, 3.07; N, 3.55.
N-(3-Chlorophenyl)-6-methyl-4-oxo-4H-chromen-3-carbox-
amide (2o). White crystals, yield 0.29 g (92%), m.p. 222—223 C.
1Н NMR (CDCl3), δ: 2.53 (s, 3 H, CH3); 7.19 (d, 1 H, J = 7.9 Hz);
7.31 (t, 1 H, J = 8.0 Hz); 7.52 (t, 2 H, J = 8.6 Hz); 7.64 (d, 1 H,
J = 8.4 Hz); 7.73 (s, 1 H, H(2´)); 8.08 (s, 1 H, H(5)); 9.15 (s, 1 H,
H(2)); 11.81 (s, 1 H, NН). 13C NMR (CDCl3), δ: 21.0, 114.7,
118.4, 119.5, 121.6, 123.2, 125.4, 125.6, 130.1, 134.8, 136.8, 137.5,
137.9, 154.6, 162.4, 163.7, 177.7. Found (%): C, 65.10; H, 3.79;
N, 4.49. C17H12ClNO3. Calculated (%): C, 65.08; H, 3.86;
N, 4.46.
N-(2,4-Dichlorophenyl)-4-oxo-4H-chromen-3-carboxamide
(2f). White crystals, yield 0.16 g (58%), m.p. 208—209 C.
1Н NMR (CDCl3), δ: 7.26 (d, 1 Н, HAr´, J = 9.7 Hz); 7.42
(s, 1 Н, HAr´); 7.51—7.61 (m, 2 Н, HAr); 7.79 (t, 1 Н, HAr
,
J = 7.8 Hz); 8.37 (d, 1 Н, J = 7.9 Hz); 8.53 (d, 1 Н, H(5),
J = 8.9 Hz); 9.05 (s, 1 Н, H(2)); 11.84 (s, 1 Н, NН). Found (%):
C, 57.60; H, 2.68; N, 4.25. C16H9Сl2NO3. Calculated (%):
C, 57.51; H, 2.71; N, 4.19.
4-Oxo-N-(4-trifluoromethylphenyl)-4H-chromen-3-carb-
oxamide (2g). White crystals, yield 0.16 g (71%), m.p. 252 C (see
Ref. 3: m.p. 251—254 C). 1H NMR (DMSO-d6), δ: 7.66 (d, 1 H,
HAr, J = 7.6 Hz); 7.73 (d, 2 H, HAr´, J = 8.7 Hz); 7.81 (d, 1 H,
HAr, J = 8.1 Hz); 7.93 (m, 3 H, HAr´, HAr); 8.25 (d, 1 H, H(5),
J = 8.1 Hz); 9.17 (s, 1 H, H(2)); 11.50 (s, 1 H, NH). Found (%):
C, 61.15; H, 3.08; N, 4.14. C17H10F3NO3. Calculated (%):
C, 61.27; H, 3.02; N, 4.20.
7-Methoxy-4-oxo-N-phenyl-4H-chromen-3-carboxamide (2h).
1
White crystals, yield 0.16 g (71%), m.p. 167—169 C. Н NMR
(CDCl3), δ: 3.96 (s, 3 H, СН3); 6.97 (s, 1 H, HAr); 7.05—7.21
(m, 2 H, HAr, HAr´); 7.38 (t, 2 H, HAr´, J = 7.7 Hz); 7.75 (d, 2 H,
HAr´, J = 7.7 Hz); 8.24 (d, 1 H, H(5), J = 9.0 Hz); 9.01 (s, 1 H,
H(2)); 11.53 (s, 1 H, NH). Found (%): C, 69.22; H, 4.35; N, 4.62.
C17H13NO4. Calculated (%): C, 69.15; H, 4.44; N, 4.74.
N-(3-Chlorophenyl)-4-oxo-4H-chromen-3-carboxamide (2i).
White crystals, yield 0.34 g (69%), m.p. 220—221 C. 1Н NMR
(CDCl3), δ: 7.19 (d, 1 H, J = 7.9 Hz); 7.33 (t, 1 H, J = 8.0 Hz);
7.52 (d, 1 H, J = 8.0 Hz); 7.59—7.68 (m, 2 H); 7.74 (s, 1 H,
H(2´)); 7.88 (t, 1 H, J = 8.3 Hz); 8.33 (d, 1 H, H(5), J = 8.0 Hz);
9.20 (s, 1 H, H(2)); 11.77 (s, 1 H, NН). 13C NMR (CDCl3), δ:
114.6, 118.5, 119.5, 121.6, 123.2, 125.7, 126.0, 127.0, 130.0, 134.5,
135.5, 137.4, 156.0, 162.3, 163.9, 177.6. Found (%): C, 64.13;
H, 3.38; N, 4.74. C16H10СlNO3. Calculated (%): C, 64.12;
H, 3.36; N, 4.67.
6-Methyl-N-(1-naphthyl)-4-oxo-4H-chromen-3-carboxamide
(2p). White crystals, yield 0.17 g (51%), m.p. 243—244 C.
1Н NMR (CDCl3), δ: 2.53 (s, 3 H, CH3); 7.49—7.62 (m, 5 H);
7.68 (t, 1 H, J = 8.5 Hz); 7.89 (d, 1 H, J = 8.1 Hz); 8.20 (s, 1 H,
H(5)); 8.33 (d, 1 H, J = 8.5 Hz); 8.47 (d, 1 H, J = 7.6 Hz); 9.13
(s, 1 H, H(2)); 12.09 (s, 1 H, NН). 13C NMR (CDCl3), δ: 21.0,
116.1, 118.2, 118.7, 120.9, 123.7, 124.9, 125.6, 125.8, 125.9, 126.1,
126.5, 128.6, 133.1, 134.0, 136.1, 136.8, 154.5, 161.9, 162.8, 177.8.
Found (%): C, 76.59; H, 4.63; N, 4.33. C21H15NO3. Calculat-
ed (%): C, 76.58; H, 4.59; N, 4.25.
N-(4-Chlorophenyl)-4-oxo-4H-chromen-3-carboxamide (2j).
White crystals, yield 0.36 g (63%), m.p. 254—256 C (see Ref. 2:
m.p. 255—259 C). 1Н NMR (CDCl3), δ: 7.32 (d, 2 Н, J = 8.6 Hz);
7.38—7.67 (m, 4 Н); 7.86 (t, 1 Н, J = 7.6 Hz); 8.34 (d, 1 Н,
J = 7.9 Hz); 9.18 (s, 1 Н, H(2)); 11.75 (s, 1 Н, NН). 13C NMR
(CDCl3), δ: 114.7, 118.7, 122.7 (2 C), 123.4, 126.3, 127.1, 129.2
(2 C), 129.9, 130.8, 135.6, 156.9, 162.9, 163.8, 178.1. Found (%):
C, 64.16; H, 3.34; N, 4.72. C16H10СlNO3. Calculated (%):
C, 64.12; H, 3.36; N, 4.67.
4-Oxo-N-phenyl-4H-benzo[h]chromen-3-carboxamide (2q).
1
White crystals, yield 0.22 g (71%), m.p. 241—242 C. Н NMR
(CDCl3), δ: 7.25—7.27 (m, 1 H); 7.43 (t, 2 H, J = 7.7 Hz); 7.67
(d, 2 H, J = 7.8 Hz); 7.75—7.84 (m, 2 H); 7.93 (d, 1 H, J = 8.7 Hz);
8.00 (d, 1 H, J = 7.8 Hz); 8.17 (d, 1 H, J = 8.8 Hz); 8.58 (d, 1 H,
H(5), J = 7.9 Hz); 9.35 (s, 1 H, H(2)); 11.15 (s, 1 H, NН).
13C NMR (CDCl3), δ: 116.2, 119.9, 120.1, 121.9 (2 C), 122.5,
123.4, 126.2, 127.5, 128.3, 128.3, 129.3 (2 C), 130.8, 136.3, 136.5,
154.4, 162.4, 162.8, 177.6. Found (%): C, 76.24; H, 4.20; N, 4.38.
C20H13NO3. Calculated (%): C, 76.18; H, 4.16; N, 4.44.
N-(1-Naphthyl)-4-oxo-4H-chromen-3-carboxamide (2k).
White crystals, yield 0.24 g (76%), m.p. 219—220 C. 1Н NMR
(CDCl3), δ: 7.51—7.67 (m, 5 H); 7.77 (d, 1 H, J = 8.1 Hz);
7.83—7.93 (m, 2 H); 8.22 (t, 2 H, J = 8.0 Hz); 8.43 (d, 1 H, H(5),
J = 8.0 Hz); 9.22 (s, 1 H, H(2)); 12.22 (s, 1 H, NН). 13C NMR
(CDCl3), δ: 115.3, 118.5, 120.3, 120.9, 123.7, 125.5, 126.1 (2 C),
126.2 (2 C), 126.7 (2 C), 128.59, 131.0, 134.0, 135.1, 156.1, 162.5,
163.5, 177.7. Found (%): C, 76.23; H, 4.24. C20H13NO3. Calcul-
ated (%): C, 76.18; H, 4.16.
N-(3-Chlorophenyl)-4-oxo-4H-benzo[h]chromen-3-carbox-
amide (2r). White crystals, yield 0.26 g (75%), m.p. 267—269 C.
1Н NMR (CDCl3), δ: 7.24—7.27 (m, 1 H); 7.37 (t, 1 H, J = 7.7 Hz);
7.50 (d, 1 H, J = 7.7 Hz); 7.73 (s, 1 H, H(2´)); 7.80—7.92 (m, 2 H);
7.98—8.07 (m, 2 H); 8.24 (d, 1 H, J = 8.8 Hz); 8.65 (d, 1 H,
H(5), J = 7.9 Hz); 9.46 (s, 1 H, H(2)); 11.82 (s, 1 H, NН).
13C NMR (CDCl3), δ: 105.9, 116.0, 119.4, 119.8, 120.6, 122.7,
6-Bromo-4-oxo-N-phenyl-4H-chromen-3-carboxamide (2l).
1
White crystals, yield 0.34 g (76%), m.p. 211—213 C. Н NMR
(CDCl3), δ: 7.23 (t, 1 H, J = 7.7 Hz); 7.41 (t, 2 H, J = 7.8 Hz);
7.55 (d, 1 H, J = 8.9 Hz); 7.62 (d, 2 H, J = 7.9 Hz); 7.92 (dd, 1 H,
J = 8.9 Hz, J = 2.1 Hz); 8.46 (s, 1 H, H(5)); 9.18 (s, 1 H, H(2));

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Myannik et al.
122.7, 123.4, 126.9, 128.4, 128.5, 128.8, 130.5, 131.5, 135.2, 137.0,
155.2, 163.4, 163.8, 178.5. Found (%): C, 68.74; H, 3.43; N, 4.07.
C20H12ClNO3. Calculated (%): C, 68.68; H, 3.46; N, 4.00.
N-(1-Naphthyl)-4-oxo-4H-benzo[h]chromen-3-carboxamide
(2s). White crystals, yield 0.27 g (75%), m.p. 269—271 C. 1Н
NMR (CDCl3), δ: 7.44—7.83 (m, 3 Н); 7.50—7.58 (m, 2 Н);
7.66 (t, 1 Н, J = 8.0 Hz); 7.88—7.94 (m, 2 Н); 8.00 (d, 1 Н,
J = 8.0 Hz); 8.23—8.30 (m, 3 Н); 8.58 (d, 1 Н, J = 7.3 Hz); 9.34
(s, 1 Н, H(2)); 12.34 (s, 1 Н, NН). 13C NMR (CDCl3), δ: 116.7,
120.2, 120.3, 120.5, 121.0, 122.4, 123.5, 125.3, 126.2 (2 C), 126.8
(2 C), 127.0, 128.0, 128.2, 128.6, 130.4, 132.0, 134.1, 136.4, 154.1,
162.3, 162.5, 177.4. Found (%): C, 78.95; H, 4.17; N, 3.90.
C24H15NO3. Calculated (%): C, 78.89; H, 4.14; N, 3.83.
8-Oxo-N-phenyl-8H-[1,3]dioxolo[4,5-g]chromen-7-carbox-
amide (2t). White crystals, yield 0.16 g (71%), m.p. 270–272 C.
196—197 C). 1Н NMR (CDCl3), δ: 7.10 (t, 1 H, HAr, J = 7.4 Hz);
7.21—7.34 (m, 4 H, HAr); 7.48—7.57 (m, 4 H, HAr); 7.64 (d, 2 H,
HAr, J = 7.8 Hz); 7.71—7.77 (m, 2 H, HAr); 8.29 (d, 1 H, H(5),
J = 6.8 Hz); 10.59 (s, 1 H, NH). 13C NMR (CDCl3), δ: 116.5,
120.2, 121.3 (2 С), 123.1, 123.9, 124.2, 125.2, 126.9, 127.9 (2 С),
128.0, 128.3 (2 С), 128.6 (2 С), 131.2, 137.3, 156.2, 161.0, 165.9,
177.5. HRMS (ESI), found: m/z 364.1087. Calculated for
C22H15NO3: M + Na = 364.1085.
4-Oxo-N-phenyl-2-(p-tolyl)-4H-chromen-3-carboxamide
(6b). White crystals, yield 0.11 g (31%), m.p. 197—199 C.
1Н NMR (CDCl3), δ: 2.44 (s, 3 H, CH3); 6.51—6.60 (m, 2 H);
7.22—7.30 (m, 2 H, HAr´); 7.33 (d, 2 H, HAr´, J = 7.9 Hz);
7.37—7.46 (m, 2 H, HAr´); 7.50 (d, 1 H, HAr, J = 8.1 Hz); 7.62
(t, 1 H, HAr, J = 7.9 Hz); 8.21 (d, 2 H, HAr´, J = 8.1 Hz); 8.90
(d, 1 H, H(5), J = 7.8 Hz); 11.1 (s, 1 H, NH). 13C NMR (CDCl3),
δ: 20.02, 114.4, 116.5, 120.2, 121.3 (2 С), 123.9, 124.2, 125.2,
126.6, 127.9 (2 С), 128.0, 128.1 (2 С), 128.6 (2 С), 134.4, 136.7,
155.8, 160.0, 163.9, 177.9. HRMS (ESI), found: m/z 378.1210.
Calculated for C23H17NO3: M + Na = 378.1208.
1H NMR (DMSO-d6), δ: 6.27 (s, 2 H, CH2); 7.14 (t, 1 H, HAr´
,
J = 7.4 Hz); 7.32—7.43 (m, 3 H, HAr, HAr´); 7.51 (s, 1 H, HAr);
7.70 (d, 2 H, HAr, J = 8.0 Hz); 9.04 (s, 1 H, H(2)); 11.38 (s, 1 H,
NH). Found (%): C, 66.22; H, 3.55; N, 4.54. C17H11NO5.
Calculated (%): C, 66.02; H, 3.58; N, 4.53. HRMS (ESI), found:
m/z 310.0718. Calculated for C17H11NO5: M + H = 310.0710.
Synthesis of 3,3-disubstituted prop-2-en-1-ones 5 (general
procedure). Solution of 4Н-chromene-4-one 4 (10 mmol) and
corresponding amine (30 mmol) in toluene (10 mL) was refluxed
for 24 h. Then the reaction mixture was evaporated, the dry
residue was dissolved in methylene chloride with the addition of
petroleum ether (PE) and the products were isolated by column
chromatography with eluent СН2Cl2—PE (9 : 1).
(Z)-3-Benzylamino-1-(2-hydroxyphenyl)-3-(o-tolyl)prop-2-
en-1-one (5b). Yellow oil, yield 3.05 g (89%). 1Н NMR (CDCl3),
δ: 2.36 (s, 3 H, CH3); 4.20—4.35 (m, 2 H, CH2—Ph); 5.75—5.89
(s, 1 H, HC=C); 6.81 (t, 1 H, HAr, J = 7.6 Hz); 7.00 (d, 1 H,
HAr, J = 8.3 Hz); 7.18—7.31 (m, 4 H, HAr); 7.31—7.51 (m, 6 H,
HAr); 7.63 (d, 1 H, HAr, J = 8.0 Hz); 11.40 (s, 1 H, OH); 13.59
(s, 1 H, NH). 13C NMR (CDCl3), δ: 19.3, 48.4, 92.0, 118.2,
120.6, 126.0, 127.6, 127.1 (2 С), 127.7, 127.9, 128.0, 128.3, 128.8
(2 С), 129.4, 130.4, 134.8, 135.1, 137.6, 162.4, 167.0, 191.4.
Found (%): С, 80.28; H, 6.20; N, 4.05. С23Н21NO2. Calculat-
ed (%): С, 80.44; H, 6.16; N, 4.08.
3-Benzylamino-1-(2-hydroxyphenyl)-3-(thiophen-2-yl)prop-
2-en-1-one (5e). Yellow crystals, yield 2.61 g (78%), m.p. 115—
116 C. 1Н NMR (CDCl3), δ: 3.93 (s, 2 Н, CH2—Ph); 6.35
(s, 1 H, HC=C); 6.96 (d, 1 Н, HAr, J = 7.3); 7.23—7.30 (m, 5 Н,
HAr); 7.47 (d, 1 Н, HAr, J = 8.2 Hz); 7.51 (m, 1 H, HTh); 7.56
(t, 1 Н, HAr, J = 7.3 Hz); 8.05 (d, 1 H, HAr, J = 7.9 Hz); 8.08
(d, 1 H, HTh, J = 3.55 Hz); 8.11 (d, 1 H, HTh, J = 4.47 Hz); 12.19
(s, 1 H, OH); 13.45 (s, 1 Н, NH). 13C NMR (CDCl3), δ: 48.4,
99.2, 118.2, 120.8, 126.1, 126.9 (3 C), 128.1, 128.8 (2 С), 129.0,
133.7, 134.7, 135.9, 136.6, 137.8, 163.1, 163.8, 189.4. Found (%):
С, 71.43; H, 5.70; N, 4.11. С20Н17NO2S. Calculated (%):
С, 71.62; H, 5.11; N, 4.18.
Synthesis of chromone-3-carboxamides 6 (general procedure).
Mixture of β-enaminone 5 (1 mmol) and corresponding phenyl-
isocyanate derivative (2.2 mmol) was heated in a minimal amount
of DMF (1 mL) or toluene (3 mL) at 110 C. After heating for
1—8 h (TLC control) and subsequent cooling, a white precipitate
appeared, which was filtered, washed with ethanol and diethyl
ether, and dried in air. If enaminone remained in the precipitate,
the mixture was recrystallized from ethanol.
2-(Furan-2-yl)-4-oxo-N-phenyl-4H-chromen-3-carboxamide
(6c). White crystals, yield 0.16 g (52%), m.p. 167—169 C.
1H NMR (DMSO-d6), δ: 6.81 (dd, 1 H, HFur, J = 3.5 Hz,
J = 1.7 Hz); 7.12 (t, 1 H, HAr´, J = 7.4 Hz); 7.32—7.44 (m, 3 H,
HAr´ + HFur); 7.56 (t, 1 H, HAr, J = 7.5 Hz); 7.69 (d, 2 H, HAr´
,
J = 7.9 Hz); 7 .77 (d, 1 H, HAr, J = 8.3 Hz); 7.89 (t, 1 H, HAr
,
J = 7.8 Hz); 8.06 (s, 1 H, HFur); 8.11 (d, 1 H, H(5), J = 7.9 Hz);
10.50 (s, 1 H, NH). 13C NMR (DMSO-d6), δ: 113.5, 116.7, 117.9,
118.7, 119.7 (2 С), 123.2, 124.1 (2 С), 125.5, 126.3, 129.3, 135.4,
139.5, 144.9, 148.3, 151.3, 155.3, 161.8, 174.9. Found (%): C, 72.42;
H, 4.30; N, 4.11. C20H13NO4. Calculated (%): C, 72.50; H, 3.95;
N, 4.23. HRMS (ESI), found: m/z 354.0737. Calculated for
C20H13NO4: M + Na = 354.0732.
N-(2,4-Dichlorophenyl)-2-(furan-2-yl)-4-oxo-4H-chromen-
3-carboxamide (6d). White crystals, yield 0.28 g (71%), m.p.
168—171 C. 1H NMR (DMSO-d6), δ: 6.81 (dd, 1 H, HFur
,
J = 3.5 Hz, J = 1.5 Hz); 7.26—7.34 (m, 1 H); 7.41 (d, 1 H, HFur
,
J = 3.6 Hz); 7.44—7.58 (m, 1 H); 7.66 (d, 1 H, J = 2.3 Hz); 7.74
(d, 1 H, J = 8.3 Hz); 7.87 (t, 1 H, J = 7.2 Hz); 8.00—8.11 (m, 1 H,
HFur); 8.17 (m, 1 H, HAr); 8.54 (d, 1 H, H(5), J = 8.9 Hz);
10.17 (s, 1 H, NH). Found (%): C, 60.12; H, 2.83; N, 3.41.
C20H11Cl2NO4. Calculated (%): C, 60.02; H, 2.77; N, 3.50.
HRMS (ESI), found: m/z 421.9957. Calculated for C20H11Cl2NO4:
M + Na = 421.9954.
2-(Furan-2-yl)-4-oxo-N-[4-(trifluoromethyl)phenyl]-4H-
chromen-3-carboxamide (6e). White crystals, yield 0.28 g (71%),
m.p. 192—195 C. 1H NMR (DMSO-d6), δ: 6.76—6.83 (m, 1 H,
H
Fur); 7.40 (d, 1 H, HAr, J = 3.6 Hz); 7.55 (t, 1 H, HAr,
J = 7.6 Hz); 7.69—7.81 (m, 3 H, HAr + HAr´); 7.82—7.94 (m, 3 H,
HAr + HFur); 8.02 (s, 1 H, HFur); 8.09 (d, 1 H, H(4), J = 7.9 Hz);
10.86 (s, 1 H, NH). 13C NMR (DMSO-d6), δ: 113.1, 116.5, 118.3,
119.2 (2 С), 122.7 (2 С), 124.1, 125.0, 126.0, 126.2, 126.3, 126.4,
135.1, 142.4, 144.4, 148.1, 148.1, 150.9, 162.0, 174.5. Found (%):
C, 63.12; H, 3.13; N, 3.22. C21H12F3NO4. Calculated (%):
C, 63.16; H, 3.03; N, 3.51. HRMS (ESI), found: m/z 422.0611.
Calculated for C21H12F3NO4: M + Na = 422.0611.
N-(2,4-Dichlorophenyl)-4-oxo-2-(thiophen-2-yl)-4H-chrom-
en-3-carboxamide (6f). White crystals, yield 0.33 g (80%), m.p.
155—156 C. 1H NMR (DMSO-d6), δ: 7.39 (m, 2 H, HAr);
7.47—7.52 (m, 2 H, HAr + HTh); 7.68 (d, 1 H, HTh, J = 2.2 Hz);
7.74—7.81 (m, 1 H, HAr); 8.03 (d, 1 H, HTh, J = 4.9 Hz); 8.19
(m, 2 H, HAr); 8.23 (s, 1 H, HAr); 10.33 (s, 1 H, NH). 13C NMR
4-Oxo-N,2-diphenyl-4H-chromen-3-carboxamide (6a). White
crystals, yield 0.12 g (35%), m.p. 195—197 C (see Ref. 19: m.p.

Synthesis of 3-(N-arylcarbamoyl)chromones
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 1, January, 2019
109
(DMSO-d6), δ: 118.6, 122.1, 123.8, 125.5, 126.3, 126.6, 127.3,
127.7, 127.9, 128.0, 128.1, 128.8, 129.0, 129.1, 129.5, 131.8,
133.4, 135.3, 155.0, 180.2. Found (%): C, 57.58; H, 2.82; N, 3.20.
C20H11Cl2NO3S. Calculated (%): C, 57.71; H, 2.66; N, 3.36. HRMS
(ESI), found: m/z 437.9729. Calculated for C20H11Cl2NO3S:
M + Na = 437.9729.
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This work was financially supported by the Russian
Foundation for Basic Research (Project No. 16-03-
00761А).
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