SYNTHESIS REACTIONS AND SPECTRAL PROPERTIES OF ETHYL ESTERS OF 2-CYANO-3-(5-X-2-FURYL)ACRYLIC ACID

Article abstract of DOI:10.1135/cccc19940444

The reaction of 5-X-2-furaldehydes (X = C6H5, COOCH3, COOC2H5, C6H5O, C6H5S, CH3S, 4-Cl-C6H4S, CH3SO2, C6H5SO2, 4-ClC6H4SO2) with ethyl cyanoacetate in dry ethanol catalyzed by sodium ethoxide yielded the corresponding ethyl 2-cyano-3-(5-X-2-furyl)acrylat

Full text of DOI:10.1135/cccc19940444

444
Kada, Ilavsky, Stetinova, Zalibera, Padour:
SYNTHESIS, REACTIONS AND SPECTRAL PROPERTIES
OF ETHYL ESTERS OF 2-CYANO-3-(5-X-2-FURYL)ACRYLIC ACID
a
a
a
b
Rudolf KADA , Dusan ILAVSKY , Jarmila STETINOVA , Lubomir ZALIBERA
a
and Jiri PADOUR
a Department of Organic Chemistry,
Slovak Technical University, 812 37 Bratislava, The Slovak Republic
b Department of Physical Chemistry,
Slovak Technical University, 812 37 Bratislava, The Slovak Republic
Received February 11, 1993
Accepted May 18, 1993
Dedicated to Professor J. Kuthan on the occasion of his 60th birthday.
The reaction of 5-X-2-furaldehydes (X = C6H5, COOCH3, COOC2H5, C6H5O, C6H5S, CH3S,
4-Cl-C6H4S, CH3SO2, C6H5SO2, 4-Cl-C6H4SO2) with ethyl cyanoacetate in dry ethanol catalyzed by
sodium ethoxide yielded the corresponding ethyl 2-cyano-3-(5-X-2-furyl)acrylates. It was found that
the reactions of these esters with cyanoacetophenone or ethyl acetoacetate do not afford the corre-
sponding 4H-pyran derivatives but that there proceeds the exchange of ethyl acetoacetate or of ethyl
cyanoacetate for the cyanoacetophenone carbanion. The same course has been observed also for the
reactions of these substrates with malononitrile.
Within the framework of the study of furylethylene derivatives, we were interested in
condensation reactions of substituted 2-furaldehydes with malononitrile1,2, methyl
cyanoacetate3, ethyl malonate4, ethyl acetoacetate4, phenylsulfonylacetonitrile and
benzoylacetonitrile5, and furylacetonitrile6. We have found that 2-cyano-3-(5-phenyl-
sulfonyl-2-furyl)acrylate reported in one of our previous works3 undergoes nucleophilic
substitution in position 5 of the furan ring under mild reaction conditions, which leads
to the preparation of some methyl analogues of the derivatives reported in the present
work, e.g. substances Il – In. Kinetic study showed that the reaction rate of the conden-
sation depends on the strength of the C−H acid7.
In the present work we deal with the synthesis of ethyl esters of 2-cyano-3-(5-X-2-
furyl)acrylic acid by reaction of 5-X-2-furaldehydes with ethyl cyanoacetate, using
conditions of the Knoevelage reaction, in dry ethanol with added sodium ethoxide as a
catalyst. These conditions made it possible to obtain the condensation products in about
80% yields, except for sulfones Ih, Ii, and Ij which were obtained in about 50% yields.
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

Ethyl 2-Cyano-3-(5-X-2-furyl)acrylates
445
Therefore, the latter compounds were prepared in high yields by oxidation of sulfides
Ie, If, and Ig by hydrogen peroxide in glacial acetic acid.
Physicochemical constants and elemental analyses of the prepared compounds I are
presented in Table I.
Compounds Il, Im, and In were synthesized by nucleophilic substitution of the read-
ily leaving groups of the derivatives Ie – Ii. The latter substrates reacted with the corre-
sponding secondary heterocyclic amines (pyrrolidine, piperidine, and morpholine) in
several minutes under ambient temperature to give practically quantitative yields of the
mentioned products. Under these conditions, the fastest reaction was observed for pyr-
rolidine, in harmony with the findings reported earlier3.
The reaction of compounds Ie – Ii with ammonium formate in ethanol at a mildly
elevated temperature for 1 h gives ethyl ester of 2-cyano-3-(5-amino-2-furyl)acrylic
acid (Ik) in 48% yield. This reaction is the first example of the direct introduction of the
amino group to furylethylene derivatives under very mild conditions.
The reaction of In with cyanoacetophenone in dry ethanol catalyzed by morpholine
(to exclude the nucleophilic substitution in position 5 of the furan ring) did not yield
the expected 2-amino-3-ethoxycarbonyl-4-(5-morpholino-2-furyl)-5-cyano-6-phenyl-
4H-pyran, but there proceeded the replacement of ethyl cyanoacetate by the carbanion
of cyanoacetophenone, affording the substance II. A similar situation has also been
found for the reactions of the above substrates with ethyl acetoacetate which again did
not give the 4H-pyran derivatives. The reactions of this type which involve nucleo-
philic exchange of the carbanions of C−H acids were studied by several authors8 – 12
.
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

446
Kada, Ilavsky, Stetinova, Zalibera, Padour:
TABLE I
Physicochemical constants of prepared compounds
Calculated/Found
Formula
(M.w.)
M.p.a, °C
Yield, %
Compound
% C
% H
% N
5.24
% S
–
Ia
Ib
Ic
Id
Ie
If
C18H13NO3
(267.3)72
117 – 119
72.24
71.90
4.99
4.90
5.09
C12H11NO5
(249.2)89
125 – 126
57.51
57.83
4.23
4.45
5.48
5.62
5.32
4.94
–
–
C13H13NO5
(263.2)87
95 – 96
59.02
59.31
4.78
4.98
5.01
C18H13NO4
(283.3)70
89 – 90
68.07
67.84
4.74
4.63
4.83
–
C11H11NO3S
(237.3)69
81 – 83
55.44
55.68
4.56
4.67
6.19
5.90
13.5
10.71
14.14
C18H13NO3S
(299.3)73
100 – 102
64.44
64.20
4.48
4.38
4.23
4.68
11.06
Ig
Ih
Ii
C18H12ClNO3S
(333.8)82
81 – 82
58.00
57.57
4.06
3.62
3.88
4.20
9.61
9.31
C11H11NO5S
(269.3)85
133 – 136
49.18
49.06
4.18
4.12
4.99
5.20
11.91
11.97
C18H13NO5S
(331.3)83
139 – 142
57.88
58.00
4.32
3.95
3.76
4.23
3.83
9.68
9.22
Ij
C18H12ClNO5S
(365.8)86
128 – 131
52.01
52.54
3.87
3.31
3.61
8.77
8.85
Ik
Il
C10H10N2O3
(206.2)48
154 – 156
58.14
58.25
4.83
4.89
13.59
10.76
10.21
10.14
15.38
–
–
–
–
–
13.43
C14H18N2O3
(260.3)86
135 – 136
65.44
65.60
6.58
6.20
10.69
Im
In
IIa
C15H18N2O3
(274.3)85
131 – 133
66.12
65.68
7.03
6.61
10.62
C14H18N2O4
(276.3)82
125 – 127
61.25
60.86
6.16
5.84
9.90
C19H18N4O4
(364.3)81
290 – 295
63.06
62.63
4.68
4.43
14.82
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

Ethyl 2-Cyano-3-(5-X-2-furyl)acrylates
447
TABLE I
(Continued)
Calculated/Found
Formula
(M.w.)
M.p.a, °C
Yield, %
Compound
% C
% H
% N
% S
–
IIb
IIc
III
C15H14N4O8
(346.3)
253 – 256
52.02
52.35
4.07
4.20
16.18
15.69
69
–
–
C18H18N4O8
(360.3)
227 – 229
53.33
53.11
4.48
4.23
15.55
15.12
67
C18H16N2O3
(308.3)
178 – 180
70.12
69.82
5.23
4.78
9.09
8.94
37
a Crystallized from ethanol.
These studies have shown that the leaving group is the weaker C−H acid, as the same
effects that increase the acidity of the hydrogens (especially an electron-acceptor effect
of substituents) aid also in the resonance stabilization of the alkene, which shifts the
equilibrium toward formation of the more stable product.
Similar results were obtained by us also in the reactions of substrates I with malono-
nitrile in 5% ethanolic sodium ethoxide solutions. Neither in this case the expected
2-pyridone derivative was formed, the product being that of the nucleophilic replace-
ment of ethyl cyanoacetate by the carbanion of malononitrile.
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

448
Kada, Ilavsky, Stetinova, Zalibera, Padour:
2-Pyridone derivatives IIIa – IIIc were prepared by the reactions of substrates Ia – Ie
(taken to eliminate the SN reaction in position 5 of the furan) with the hydrazide of
cyanoacetic acid in dry ethanol catalyzed by sodium ethoxide. The reactions were car-
ried out at ambient temperature, with intense stirring of the reaction mixture for 2 h.
The IR spectra of compounds Ia – In (Table II) show characteristic bands of the
cyano group in the 2 210 – 2 230 cm−1 region. Also symmetric (1 010 – 1 030 cm−1)
and antisymmetric (1 230 – 1 260 cm−1) ν(C–O–C) bond vibrations are well observ-
able. The stretching ν(C=C) bond vibrations occur in the 1 500 – 1 700 cm−1 region.
The IR spectra of 2-pyridones IIIa – IIIc show in addition to ν(C=O) vibrations of the
ester group at 1 720 cm−1 also absorption maxima at around 1 650 cm−1, which proves
that the studied N-amino-2-pyridones are in the lactame tautomeric form. This is evi-
denced also by the absence of absorption bands belonging to the hydroxyl group. These
conclusions agree well with the results reported by Otta and coworkers13. The spectra
of 1-amino-2-pyridones show also absorption bands corresponding to symmetric (3 310 –
3 220 cm−1) and antisymmetric (3 390 – 3 400 cm−1) NH2 group vibrations.
1
The study of H NMR spectra of compounds Ia – In (Table III) has shown that the
change of the substituent in position 5 of the furan ring affects markedly the chemical
shift of hydrogen in position 4, while that of the hydrogen in position 3 is much less
affected. In the spectra of 1-amino-2-pyridones one observes the distinct singlets of the
amino groups. The amino group attached to the nitrogen shows the singlet in the 5.72
ppm region while that attached to the carbon has the singlet in the 8.53 ppm region.
3
The interaction constants J(C−H) (12 – 13 Hz) obtained by 13C NMR spectroscopy
of substances Ia – Ij demonstrate unambiguously that these compounds are the E
isomers. The chemical shifts of the carbons of 13C derivatives Ia – Ij are presented in
Table IV . The numbering of the carbons is shown in Scheme 1.
SCHEME 1
EXPERIMENTAL
UV absorption spectra were measured on M-40 Zeiss Jena spectrophotometer, using 20 mm cells and
10−4 M solutions of substances in dry ethanol. IR spectra were measured on PU 9800 Phillips instru-
1
ment, using KBr discs. H NMR spectra of compounds Ia – In were measured in CDCl3 and those of
compounds IIa – IIc in (CD3)2SO (BS 487 C Tesla instrument working at 100 MHz), using tetra-
methylsilane as an internal reference. 13C NMR spectra of compounds Ia – Ij were measured in
CDCl3 on Varian XL-300 spectrometer, using tetramethylsilane as an internal reference.
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

Ethyl 2-Cyano-3-(5-X-2-furyl)acrylates
449
TABLE II
IR spectra of ethyl esters of 2-cyano-3-(5-X-2-furyl)acrylic acid (in cm−1)
Compound
ν(CN)
ν(C=O)
ν(C=C)
νs(C–O–C)
νas(C–O–C)
Ia
Ib
Ic
Id
Ie
If
2 218
2 228
2 226
2 218
2 218
2 220
2 220
2 226
2 234
2 230
2 210
2 199
2 197
2 237
1 709
1 714
1 717
1 709
1 711
1 725
1 709
1 715
1 736
1 732
1 668
1 662
1 672
1 718
1 611
1 618
1 617
1 617
1 607
1 605
1 603
1 624
1 615
1 615
1 611
1 584
1 591
1 602
1 032
1 019
1 013
1 022
1 024
1 019
1 020
1 017
1 019
1 013
1 030
1 028
1 022
1 024
1 233
1 250
1 240
1 240
1 242
1 246
1 246
1 258
1 254
1 250
1 250
1 254
1 256
1 249
Ig
Ih
Ii
Ij
Ik
Il
Im
In
TABLE III
1H NMR spectra of ethyl esters of 2-cyano-3-(5-X-2-furyl)acrylic acid
Compound
δHA
δHB
δHC
δHD
δHE
Ia
Ib
Ic
Id
Ie
If
6.91
7.32
7.31
5.62
6.44
6.61
6.66
7.48
aroma
aroma
5.65
5.77
5.76
5.47
aroma
7.60
7.97
8.12
8.13
7.85
7.85
7.93
7.91
8.06
aroma
aroma
7.43
7.41
7.42
7.52
4.37
4.38
4.38
4.34
4.35
4.35
4.35
4.39
4.36
4.37
4.18
4.16
4.16
4.29
1.39
1.39
1.39
1.37
1.37
1.37
1.37
1.40
1.37
1.38
1.26
1.23
1.23
1.35
7.61
aroma
7.27
aroma
aroma
7.30
Ig
Ih
Ii
aroma
aroma
7.58
Ij
Ik
Il
7.56
Im
In
7.56
7.53
a
b
Signal is overlapped with multiplet of hydrogens of the aromatic ring. Signal of NH2 group at
δ = 8.21 ppm.
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

450
Kada, Ilavsky, Stetinova, Zalibera, Padour:
Synthesis of Compounds Ia – Ig
5-X-2-Furaldehyde (0.02 mol) was dissolved in 20 – 50 ml of dry ethanol (the volume depended on
the solubility of a given aldehyde) with mild heating. Then, freshly redistilled ethyl cyanoacetate
(2.2 g; 0.02 mol) and 1 drop of 5% solution of ethanolic sodium ethoxide were added. The reaction
mixture was allowed to stand at −10 °C to 0 °C for 24 h. Then the precipitated condensate was sep-
arated by filtration with suction, followed by recrystallization from ethanol.
Synthesis of Compounds Ih – Ij
Substances Ie – Ig (0.005 mol) were dissolved in 100 ml of glacial acetic acid at mildly elevated
temperature, and then 3 ml of 30% hydrogen peroxide solution were added. The solution was
allowed to stand at ambient temperature for 3 days , then it was condensed to the half volume by
vacuum evaporation and 60 ml of ice water were added. After 2 h, the precipitated sulfone was fil-
tered off with suction and recrystallized from ethanol.
Synthesis of Compound Ik
Ethyl ester of 2-cyano-3-(5-methylthio-2-furyl)acrylic acid (2.37 g; 0.01 mol) was dissolved at 50 °C
in 20 ml of dry ethanol. Then, ammonium formate (0.95 g; 0.015 mol) was added and the reaction
mixture was stirred at 40 – 50 °C for l h. After cooling the reaction mixture to −10 °C, the preci-
pitate so formed was filtered off with suction, washed with distilled water and recrystallized from
ethanol.
TABLE IV
13C NMR spectra of prepared compounds Ia – Ij (in ppm)
Compound
C2
C3
C4
C5
C6
C7
C8
C9
C10
C11
Ia
Ib
Ic
Id
Ie
If
147.69 129.71 108.90 159.80 138.01
96.92 115.75 162.92 62.27
14.11
14.05
14.03
14.10
14.18
14.07
14.05
14.06
13.95
13.96
147.40 120.21 119.70 150.63 139.23 102.96 114.55 161.48 62.92
147.73 120.20 119.47 150.51 139.26 102.79 114.47 161.49 62.86
140.54 126.01
91.09 162.95 138.24
94.23 115.80 162.95 62.10
95.87 115.79 163.05 62.28
97.44 115.16 162.95 62.41
98.62 115.07 162.30 62.49
149.53 124.69 112.09 158.19 137.42
150.50 122.76 117.59 154.48 138.24
150.73 122.67 118.01 152.89 138.09
Ig
Ih
Ii
152.86 119.80 118.26 151.30 138.29 104.41 114.24 161.17 63.20
153.58 120.21 118.25 151.49 134.47 103.76 114.12 161.19 62.98
153.17 120.18 118.35 151.63 137.87 104.03 114.08 161.14 63.05
Ij
a For numbering of carbons see Scheme 1.
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

Ethyl 2-Cyano-3-(5-X-2-furyl)acrylates
451
TABLE V
Spectral characteristics of compounds IIa – IIc
Compound
Type of spectrum
IIa
IIb
IIc
IR spectrum, cm−1
ν(C≡N)
2 209
1 720
1 613
1 654
1 007
3 395
3 311
2 215
1 719
1 601
1 651
1 013
3 393
3 320
2 220
1 719
1 603
1 655
1 013
3 393
3 309
ν(C=O)
ν(C=C)
ν(C=O), lactam.
νs(C−O−C)
νas(NH2)
νs(NH2)
UV spectrum, λmax, nm/log ε
202
203
204
3.34
272
3.40
305
3.08
356
3.20
a
3.32
272
3.38
304
3.05
355
3.18
271
a
300
a
364
a
1H NMR, δ ppm
furan ring
′
H3
6.96
7.46
6.97
7.49
6.99
7.45
′
H4
ester group
−CH2−
4.21
1.22
3.34
0.86
3.89
0.91
−CH3
amino groups
N−NH2
5.73
8.53
5.71
8.53
5.72
8.53
C−NH2
a Saturated solution in methanol.
Collect. Czech. Chem. Commun. (Vol. 59) (1994)

452
Kada, Ilavsky, Stetinova, Zalibera, Padour:
Synthesis of Compounds IIa – IIc
Compounds Ia – Ic were dissolved in 30 ml of dry ethanol, and then hydrazide of cyanoacetic acid
(1 g; 0.01 mol) and sodium ethoxide (1 g) were added. The reaction mixture was stirred at ambient
temperature for 3 h. Then, the precipitate formed was filtered off with suction and recrystallized from
ethanol. Spectral characteristics are given in Table V.
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Collect. Czech. Chem. Commun. (Vol. 59) (1994)