Aqueous-Phase Synthesis and Solid-Phase Fluorescence of 3-(Methoxyphenyl)-2-cyanoacrylamides

Article abstract of DOI:10.1134/S1070428018070217

Reactions of methoxybenzaldehydes with cyanoacetamide in water in the presence of cocamidopropylamine oxide afforded 84–94% of 3-(methoxyphenyl)-2-cyanoacrylamide which showed solid-phase fluorescence with the emission maxima located at λ 421–469 nm.

Full text of DOI:10.1134/S1070428018070217

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2018, Vol. 54, No. 7, pp. 1100–1102. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © D.A. Bezgin, O.V. Ershov, M.Yu. Ievlev, M.Yu. Belikov, I.N. Bardasov, 2018, published in Zhurnal Organicheskoi Khimii, 2018,
Vol. 54, No. 7, pp. 1092–1094.
SHORT
COMMUNICATIONS
Aqueous-Phase Synthesis and Solid-Phase Fluorescence
of 3-(Methoxyphenyl)-2-cyanoacrylamides
a
a
a
a
a
D. A. Bezgin , O. V. Ershov ,* M. Yu. Ievlev , M. Yu. Belikov , and I. N. Bardasov
a
I.N. Ul’yanov Chuvash State University, Moskovskii pr. 15, Cheboksary, 428015 Russia
*
e-mail: oleg.ershov@mail.ru
Received February 14, 2018
Abstract—Reactions of methoxybenzaldehydes with cyanoacetamide in water in the presence of cocamido-
propylamine oxide afforded 84–94% of 3-(methoxyphenyl)-2-cyanoacrylamide which showed solid-phase
fluorescence with the emission maxima located at λ 421–469 nm.
DOI: 10.1134/S1070428018070217
The use of aqueous medium in organic synthesis is
related to obvious advantages of water compared to
organic solvents, in particular to its accessibility,
cheapness, safety, and the lack of toxicity. In some
cases, the use of water as solvent increases the reaction
rate and affects the selectivity of a wide series of
organic reactions [1–3]. Therefore, water plays an im-
portant role as an alternative solvent which can replace
hazardous organic solvents in the synthesis of various
compounds [1–5]. However, the application of water
as reaction medium is limited since most reagents are
poorly soluble therein. This drawback can be over-
come by adding surfactants capable of aggregating
reacting species in micelles [5–7].
search for new simple, environmentally benign, and
efficient methods of their preparation is an important
problem.
(
E)-3-Aryl-2-cyanoacrylamides 1a–1e can be syn-
thesized by mixing the corresponding substituted benz-
aldehyde with cyanoacetamide in water in the presence
of a surfactant at room temperature. Depending on the
surfactant used, the yields attained 94%. Furthermore,
the reaction was stereoselective, and only one of the
possible isomers was formed.
Various surfactants were tried in order to find
optimal conditions for the condensation of cyanoacet-
amide with aromatic aldehydes, namely sodium lauryl
sulfate (SLS, a traditional anionic surfactant), Triton
X-100 (nonionic surfactant), and cocamidopropyl-
amine oxide (CAPO, Oksipav AP, nonionic surfactant
with weak cationic properties). The model reaction
was the condensation of cyanoacetamide with 4-me-
thoxybenzaldehyde. The yields of 1a in the presence of
SLS, Triton X-100, and CAPO were 23, 86%, and
Alkoxybenzylidene derivatives of malononitrile
dimer can be obtained in water in the presence of
a nonionic surfactant, Triton X-100 [5]. Depending on
the number and position of alkoxy groups in the aro-
matic ring, the synthesized compounds showed solid-
phase fluorescence at λ
491–560 nm [5]. In con-
max
tinuation of our works on the development of environ-
mentally safe methods of synthesis of organic com-
pounds with potentially practically important prop-
erties, herein we describe the Knoevenagel condensa-
tion of methoxy-substituted benzaldehydes with
cyanoacetamide in water in the presence of surfactants.
Ar
O
NH2
+
Surfactant
–H
O
NC
Ar
O
O
2
NH2
CN
Methoxybenzylidene derivatives of cyanoacetamide
are precursors to various heterocyclic structures and
inhibitors of thyrosinase [8] and serine proteases
1
a–1e
(
NS2B-NS3) [9]; they exhibit fluorescence [10] and
Ar = 4-MeOC
6
H
4
(a), 3-MeOC H
6 4
(b), 2-MeOC
6
H (c),
4
reversible mechanochromism [11, 12]. Therefore,
3,4-(MeO)
2
C
6
H
3
(d), 3,4,5-(MeO)
3
C
6
H
2
(e).
1
100

AQUEOUS-PHASE SYNTHESIS AND SOLID-PHASE FLUORESCENCE
1101
9
3%, respectively. Presumably, the high yield of 1a
Table 1. Relative intensities and positions of emission
maxima in the solid-phase fluorescence spectra of com-
pounds 1a–1e
with the use of CAPO is determined by the presence in
solution of free (unoxidized) amine molecules contain-
ing a long hydrophobic “tail.” Unoxidized amines act
as a catalyst; they facilitate the reaction via abstraction
of proton from the methylene group of cyanoacet-
amide, and the long alkyl radical solubilizes the reac-
tants in a micelle.
a
Compound no.
λ
fl., nm
Intensity, relative units
1
1
1c
1d
1e
a
b
442
421
451
469
448
1.00
3.61
3.23
7.34
1.70
Compounds 1a–1e were isolated as colorless or
light yellow crystalline solids which showed fluores-
cence in the crystalline state. The emission range
depended on the number and position of methoxy
groups in the benzene ring and was located in the
a
Relative to 1a; fluorescence excitation wavelength λ 365 nm.
2
-Cyano-3-(2-methoxyphenyl)prop-2-enamide
–1
violet to blue region (λ 421–469 nm, Table 1). The
max
(1c). Yield 93%, mp 165–166°C. IR spectrum, ν, cm :
1
highest fluorescence intensity was observed for 3,4-di-
3
398, 3273 (N–H), 2209 (C≡N), 1688 (C=O). H NMR
methoxyphenyl derivative 1d.
spectrum, δ, ppm: 3.90 s (3H, OCH ), 7.11 t (1H,
3
Thus, we have developed a new method of synthe-
sis of 3-aryl-2-cyanoacrylamides in aqueous medium
in the presence of a surfactant. The proposed method is
advantageous due to simple experimental procedure,
high yields, cheap reactants, and no need of using
catalysts and organic solvents. Methoxy-substituted
C H , J = 7.6 Hz), 7.19 d (1H, C H , J = 8.3 Hz), 7.56–
6
4
6
4
7.60 m (1H, C H ), 7.75 br.s and 7.90 br.s (1H each,
6
4
NH ), 7.99 d.d (1H, C H , J = 7.8, 1.6 Hz), 8.40 s (1H,
2
6
4
+
CH). Mass spectrum: m/z 202 (I 100%) [M] . Found,
rel
%
: C 65.28; H 4.96; N 13.91. C H N O . Calculated,
11
10
2
2
%
: C 65.34; H 4.98; N 13.85. M 202.21.
3
-aryl-2-cyanoacrylamides show solid-phase fluores-
2
-Cyano-3-(3,4-dimethoxyphenyl)prop-2-en-
cence with their emission maxima at λ 421–469 nm.
amide (1d). Yield 84%, mp 191–192°C. IR spectrum,
2
-Cyano-3-(4-methoxyphenyl)prop-2-enamide
–1
ν, cm : 3392, 3314 (N–H), 2211 (C≡N), 1692 (C=O).
(
(
(
1a). Cocamidopropylamine oxide, 0.069 g
0.15 mmol), 4-methoxybenzaldehyde, 0.136 g
1 mmol), and cyanoacetamide, 0.084 g (1 mmol),
1
H NMR spectrum, δ, ppm: 3.81 s (3H, OCH ), 3.86 s
3
(
(
(
(
3H, OCH ), 7.16 d (1H, C H , J = 8.5 Hz), 7.57 d.d
3
6
3
1H, C H , J = 8.5, 2.0 Hz), 7.66 br.s (1H, NH ), 7.67 d
6
3
2
were added to 5 mL of water. The mixture was stirred
for 1.5 h at room temperature, and the precipitate was
filtered off, washed with water, and recrystallized from
propan-2-ol. Yield 93%, mp 212–213°C. IR spectrum,
1H, C H , J = 2.0 Hz), 7.79 br.s (1H, NH ), 8.11 s
6
3
2
+
1H, CH). Mass spectrum: m/z 232 (I 100%) [M] .
rel
Found, %: C 61.97; H 5.18; N 12.11. C H N O .
1
2
12
2
3
Calculated, %: C 62.06; H 5.21; N 12.06. M 232.24.
-Cyano-3-(3,4,5-trimethoxyphenyl)prop-2-en-
amide (1e). Yield 90%, mp 197–192°C. IR spectrum,
–
1
ν, cm : 3420, 3304 (N–H), 2204 (C≡N), 1698 (C=O).
1
2
H NMR spectrum, δ, ppm: 3.86 s (3H, OCH ), 7.14 d
3
(
2H, C H , J = 8.9 Hz), 7.67 br.s and 7.80 br.s (1H
6
4
–
1
ν, cm : 3404, 3322 (N–H), 2223 (C≡N), 1693 (C=O).
each, NH ), 7.97 d (2H, C H , J = 8.9 Hz), 8.11 s (1H,
2
6
4
1
+
H NMR spectrum, δ, ppm: 3.77 s (3H, OCH ), 3.83 s
CH). Mass spectrum: m/z 202 (I 100%) [M] . Found,
3
rel
(
(
6H, OCH ), 7.36 s (2H, C H ), 7.73 br.s and 7.84 br.s
%
: C 65.28; H 5.02; N 13.92. C H N O . Calculated,
3
6
2
11
10
2
2
1H each, NH ), 8.13 s (1H, CH). Mass spectrum:
%
: C 65.34; H 4.98; N 13.85. M 202.21.
2
+
m/z 262 (I 100%) [M] . Found, %: C 59.45; H 5.34;
rel
Compounds 1b–1e were synthesized in a similar
N 10.74. C H N O . Calculated, %: C 59.54; H 5.38;
1
3
14
2
4
way.
N 10.68. M 262.26.
2
-Cyano-3-(3-methoxyphenyl)prop-2-enamide
–1
The IR spectra were recorded on an FSM-1202
(
1b). Yield 94%, mp 144–145°C. IR spectrum, ν, cm :
1
spectrometer with Fourier transform from samples
3
391, 3311 (N–H), 2221 (C≡N), 1671 (C=O). H NMR
1
spectrum, δ, ppm: 3.81 s (3H, OCH ), 7.16–7.19 m
dispersed in mineral oil. The H NMR spectra were
3
(
1H, C H ), 7.48 d (1H, C H , J = 7.6 Hz), 7.50–
measured on a Bruker DRX-500 spectrometer at
6
4
6
4
7
.54 m (2H, C H ), 7.78 br.s and 7.92 br.s (1H each,
500.13 MHz using DMSO-d as solvent and tetra-
6
6
4
NH ), 8.16 s (1H, CH). Mass spectrum: m/z 202
methylsilane as internal standard. The mass spectra
(electron impact, 70 eV) were recorded on a Finnigan
MAT INCOS-50 instrument. The solid-phase fluores-
cence spectra were measured with a Flyuorat-02
2
+
(
I 100%) [M] . Found, %: C 65.41; H 4.95; N 13.91.
rel
C H N O . Calculated, %: C 65.34; H 4.98; N 13.85.
11
10
2
2
M 202.21.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 54 No. 7 2018

1
102
BEZGIN et al.
Panorama spectrofluorometer equipped with a “Frog”
accessory for measurements outside the cell compart-
ment. The elemental analyses were obtained on
a Perkin Elmer-2400 CHN analyzer. The melting
points were measured with an OptiMelt MPA100 melt-
ing point apparatus. The progress of reactions and the
purity of products were monitored by TLC on Sorbfil
PTSKh-AF-A-UF plates; spots were visualized under
UV light, by treatment with iodine vapor, or by
thermal decomposition.
This study was performed in the framework of the
base part of state assignment of the Ministry of Educa-
tion and Science of the Russian Federation (project
no. 4.6283.2017/8.9).
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