Antibacterial activities of new (E) 2-cyano-3-(3′,4′- dimethoxyphenyl)-2-propenoylamide derivatives

Article abstract of DOI:10.1080/00397910701575491

(E) 2-Cyano-3-(3′,4′-dimethoxyphenyl)-2-propenoyl chloride (2) underwent mono- and binucleophilic displacement with hydrazines, amines, ureas, and aromatic bifunction amines to give new 2-propenoyl hydrazines (4 and 5), 2-propenoylamide (6, 7, 12, 13, 15,

Full text of DOI:10.1080/00397910701575491

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Antibacterial Activities of New (E)
2‐Cyano‐3‐(3′,4′‐dimethoxyphenyl)‐2‐propenoyla
Derivatives
a
a
A. K. El‐Ziaty & S. A. Shiba
a
Faculty of Science, Chemistry Department , Ain Shams University , Cairo,
Egypt
Published online: 19 Nov 2007.
To cite this article: A. K. El‐Ziaty & S. A. Shiba (2007) Antibacterial Activities of New (E)
2
‐Cyano‐3‐(3′,4′‐dimethoxyphenyl)‐2‐propenoylamide Derivatives, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 37:22, 4043-4057, DOI:
0.1080/00397910701575491
1
To link to this article: http://dx.doi.org/10.1080/00397910701575491
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Synthetic Communications , 37: 4043–4057, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701575491
Antibacterial Activities of New (E) 2-Cyano-
0 0
3-(3 ,4 -dimethoxyphenyl)-2-
propenoylamide Derivatives
A. K. El-Ziaty and S. A. Shiba
Faculty of Science, Chemistry Department, Ain Shams University, Cairo,
Egypt
0
0
Abstract: (E) 2-Cyano-3-(3 ,4 -dimethoxyphenyl)-2-propenoyl chloride (2) underwent
mono- and binucleophilic displacement with hydrazines, amines, ureas, and aromatic
bifunction amines to give new 2-propenoyl hydrazines (4 and 5), 2-propenoylamide
(6, 7, 12, 13, 15, 17, 19, 21), and 2-thiol propenoate (22–24). Some of these
products were cyclized to give novel heterocyclic derivatives (8, 10, 14, 16, and 20).
Keywords: benzimidazole, benzoxazine, 1,3,5-oxadiazine-2,4-dione
INTRODUCTION
In the present study, we continue our investigation of the 2-propenoyl chloride
1–4]
[
derivative’s chemistry.
0
Synthesis and reactivity of new (E) 2-cyano-3-
3 ,4 -dimethoxyphenyl)-2-propenoyl chloride (2) toward some aliphatic
0
(
and/or aromatic nitrogen, oxygen and sulfur nucleophilic reagents are the
main targets in this report, and we aim to produce some new derivatives
and study their biological activities.
RESULTS AND DISCUSSION
Condensation of acid chloride (2) with hydrazine hydrate afforded a
0
[5]
mixture of the 3,4-dimethoxybenzaldehyde azine (3) and N,N -dipropenoyl
Received in the U.K. October 20, 2006
Address correspondence to S. A. Shiba, Faculty of Science, Chemistry Department,
Ain Shams University, Cairo, Egypt. E-mail: ahm512@yahoo.com
4
043

4
044
A. K. El-Ziaty and S. A. Shiba
hydrazine derivative (4), whereas with benzoylhydrazine, the expected
0
N-benzoyl-N -propenoyl hydrazine derivative (5) was obtained. On the other
hand, reaction of (2) with p-anisidine yielded the corresponding amide (6)
(Scheme 1). Treatment of 2 with ethanol amine gave the unexpected N,N-
dipropenoyl ethanol amine (7) (Scheme 1).
Condensation of 2 with urea produced a mixture of the unexpected 1,3,5-
0
0
0
oxadiazine-2,4-dione (8) and N-carboxy N -[2- cyano -3 (3 ,4 -dimethoxyphenyl)-
-propenoyl]urea (9) (Scheme 1), which might be formed according to the
following mechanism:
2
With methylthiourea and/or phenylthiourea, acid chloride (2) condensed
to give the probable pyrimidine derivative (10) and/or the thiourea derivative
(11) (Scheme 1).
Furthermore, treatment of acid chloride (2) with bifunction
aromatic compounds, such as o-phenylenediamine, o-aminophenol, and/or
o-amino-thiophenol, produced varieties of mono- and bisubstituted deriva-
tives as shown in Scheme 2.
With o-phenylenediamine (1:1 mol), acid chloride (2) gave a mixture of
0
monosubstituted derivative (12) and N,N -disubstituted derivative (13),

Antibacterial Activities
4045
Scheme 1.
whereas at 1:2 mol, only the disubstituted derivative (13) was obtained in
fairly good yield (Scheme 2). Treatment of both 12 and 13 with POCl3
yielded the same benzimidazole derivative (14), via the normal cyclodehydra-
[6]
tion of 12 or dehydration with subsequent hydrolysis of the intermediate [A]
to give the acid (1) as shown in Scheme 2.
Scheme 2.

4
046
A. K. El-Ziaty and S. A. Shiba
Condensation of 2 with anthranilic acid yielded the N-propenoyl anthra-
nilic acid derivative (15), which upon treatment with Ac O cyclized to the
benzoxazinone derivative (16) (Scheme 2).
2
Condensation of 2 with o-aminophenol gave a surprising mixture of
products: N-propenoyl derivative (17), N,N-dipropenoyl derivative (18),
N-propenoyl-O-propenoyl derivative (19), and the benzoxazole derivative
(20) (Scheme 2). Formation of benzoxazole derivative (20) was also
supported by dehydration of 17 with POCl (Scheme 2). On the other hand,
3
(
N) vs (S) substitution was confirmed by condensation of (2) with
o-aminothiophenol to give a mixture of N-propenoyl derivative (21) (minor
yield) and S-propenoyl derivative (22) (Scheme 2).
[
7,8]
In contrast to the results of Britsun,
-imidazolidinethione and/or 2-benzimidazolthiol in different conditions
to give only the S-substituted derivatives (23, 24) rather than the thiazino
acid chloride (2) reacted with
2
[
3,2-a]benzimidazole derivatives (25) (Scheme 2).
The structure of all products (2–24) was confirmed by elemental analysis,
1
Table 1) and IR, HNMR, and MS spectroscopy (Tables 2 and 3).
(
Biological Activity
The recent importance of 2-propenoyl amides, 2-propenoates,
[9]
[10,11]
pyrimi-
[15,17,19]
[
12–14]
[15–17]
[18]
dines,
and oxadiazine
benzimidazoles,
[
benzoxazine,
derivatives as biologically and pharmacologically active
benzoxazoles,
20]
compounds makes them worthy of synthesis to obtain new structures of poten-
tially enhanced potency.
Experimental Determination of Biological Activity
The antibacterial activity of 14 synthesized products were determined using
hole plate and filter-paper disc method.
[21]
The tested compounds (100 mg)
were loaded on Whatman No. 1 filter-paper discs in sterile conditions. The
discs were evaporated to dryness; after that, the discs were placed on the
surface of nutrient agar media inoculated with the tested organisms. The
plates were incubated for 2 h in the refrigerator, then incubated for 24 h at
378C. A variety of species of gram-positive and gram-negative bacteria
such as Bacillus subtilis, Staphylococcus, Escherichia coli, and Pseudomonas
aurignosa were used. The inhibition zones were measured in mm. The results
are summarized in Table 4.
EXPERIMENTAL
Melting points are uncorrected. IR spectra were recorded on a Pye Unicam SP
1
1
200 spectrophotometer using the KBr wafer technique. H NMR spectra were

Table 1. Physical data of the synthesized compounds
Analysis calc. (found)
H
Comp. no.
Mp (8C)
Yield (%)
Molecular formula
C H ClNO3
Molecular weight
C
N
2
4
5
6
7
8
9
138–140
250–252
182–184
180–182
220–222
200–202
200–202
188–190
142–144
150–152
218–220
224–226
256
95
40
50
70
30
65
12
50
50
35
60
92
70
88
44
15
16
10
15
75
50
60
251.66
462.44
351.34
338.34
491.25
301.13
319.14
305.20
367.41
323.33
538.53
305.32
352.33
334.32
324.32
539.52
539.52
306.33
340.38
340.38
317.35
365.40
57.27 (57.07)
62.28 (62.25)
64.95 (64.92)
67.45 (67.08)
63.52 (63.29)
55.79 (55.60)
52.65 (52.60)
55.10 (55.07)
62.11 (62.07)
66.87 (66.72)
66.91 (66.72)
70.81 (70.72)
64.75 (64.71)
68.26 (68.23)
66.66 (66.59)
66.79 (66.77)
66.79 (66.69)
70.52 (70.32)
63.52 (63.51)
63.52 (63.49)
76.77 (76.75)
62.45 (62.39)
4.01 (3.98)
4.79 (4.77)
4.87 (4.83)
5.36 (5.32)
5.13 (5.10)
3.68 (3.62)
4.11 (4.02)
4.95 (4.89)
4.66 (4.56)
5.30 (5.27)
4.86 (4.81)
4.95 (4.90)
4.57 (4.52)
4.22 (4.15)
4.97 (4.91)
4.67 (4.62)
4.67 (4.60)
4.61 (4.57)
4.73 (4.69)
4.73 (4.70)
4.76 (4.74)
4.13 (4.10)
5.57 (5.54)
12.11 (12.09)
11.96 (11.94)
8.28 (8.19)
1
2
10
22
17
C
C
24
19
H
H
N
N
4
O
O
6
4
4
7
5
6
3
3
3
6
2
5
4
4
7
7
3
3
3
C H N O
1
9
18
25
11
2
3
3
C
C
26
14
H
H
N
N
O
O
8.56 (8.52)
13.96 (13.89)
13.17 (12.95)
13.77 (13.70)
11.44 (11.42)
13.00 (12.89)
10.40 (10.33)
13.76 (13.72)
7.95 (7.92)
C H N O
1
4
13
15
17
3
3
3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
C
C
14
19
H
H
N
N
O
O
S
S
C H N O
8 17 3
1
C H N O
3
0
26
15
16
4
3
2
C
C
18
H
H
N
N
O
O
19
226–228
190–192
180–182
190–192
186–188
208–210
220–222
156–158
160–162
C H N O
8.38 (8.35)
8.64 (8.61)
1
9
14
16
25
2
2
3
C
C
18
30
H
H
N
N
O
O
7.79 (7.78)
7.79 (7.69)
C H N O
3
0
25
14
16
3
2
2
C
C
18
18
H
H
N
N
O
O
9.15 (9.09)
8.23 (8.19)
S
C H N O S
8.23 (8.16)
13.24 (13.20)
11.50 (11.46)
1
8
16
15
15
2
3
3
3
3
3
C
C
15
19
H
H
N
N
O
O
S
S

Table 2. IR and mass spectral data of compounds prepared
2
1
)
IR (cm
Comp.
OH, NH
C 55 O
C ;; N
MS, m/z (abundance, %)
233[M] , (100), 216 (22.5), 188 (9.3), 189 (28), 162 (12.7), 128 (10.3), 145 (11), 119
þ
1
3000–3550 br
1685
2210
(
8.5), 103 (15.4)
2
3
4
5
6
7
8
9
—
—
1734
—
2219
—
—
—
þ.
3383
1631
2210
2213
2204
2215
2210
2212
2262
2215
2204
2202
2227
2203
2220
2205
2217
2212
2220
2201
2201
2222
2219
462 [M] (7.5), 231 (40.2), 216 (100), 162 (11.28), 119 (7.5)
3265
1692, 1660
1676
—
—
3358
þ.
3420
1794, 1722
1753, 1709
1660, 1690
1731
[M] not detected, 446 (33), 233 (27), 216 (100), 188 (17.7)
þ.
3424
301 [M] (8.7), 285 (20), 259 (100), 232 (31.7), 217 (28), 189 (20)
þ.
3100–3600 br
3195
318 [M –1] (22.6), 301 (10), 259 (80), 216 (100), 188 (26.2)
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
—
þ.
3319
1681
367 [M] (5.9), 308 (42.5), 231 (22.2), 151 (20.3), 135 (15)
3359–3315
3405
1681
—
—
1690
þ.
3290
—
305 [M] (50), 304 (100), 188 (20), 116 (32), 216 (14), 91 (12)
3400–2638 br
—
1683
—
þ.
þ.
þ.
þ.
1767
334 [M] (100), 291 (26.9), 265 (27.1), 260 (9.5), 216 (8.9), 188 (6.3)
3379–3284
3350
1665
324 [M] (27.3), 216 (100), 188 (13)
1793, 1725
1710, 1695
—
539 [M] (17.41), 306 (32.9), 216 (100), 188 (11.6)
þ.
3240
539 [M] (10.2), 538 [M 2 1] (100), 307 (23.4), 231 (25.4), 188 (13.2)
306 [M ] (15.2), 290 (10.8), 214 (82.0), 74 (52), 188 (100)
þ.
þ.
þ.
þ.
—
3324
1682
340 [M ] (100), 188 (64.9), 152 (33), 216 (16.5), 109 (30.9)
3378, 3298
3246
1687
340 [M ] (10.9), 322 (29.8), 296 (10.1), 216 (100), 188 (18.3)
1681
317 [M ] (40.27), 232 (10.9), 216 (100), 188 (6.2)
þ.
3154
1689
365 [M ] (30.8), 339 (28.5), 216 (27.7), 149 (26.2)

1
Table 3. H NMR of prepared compounds
Comp. no.
C
1
-H or C
2
H(s)
C
3
-H(s)
C
4
-H(s)
C
5
-H(d)
C
6
-H(d)
NH(s)
Others
2
4
6
3.97, 3.99
3.88, 3.81
3.88, 3.85
8.24
8.17
8.16
7.88
7.70
7.71
7.60 (J ¼ 28)
7.62 (J ¼ 28)
7.60 (J ¼ 28)
7.01 (J ¼ 28)
7.1 (J ¼ 28)
7.17 (J ¼ 28)
—
10.56
10.17
—
—
3.81 (s, OCH
3
), 6.92 (d, J ¼ 21,
2
syl protons)
H), 7.55 (d, J ¼ 20, 2H (ani-
1
1
0
2
3.79, 3.77
3.98, 3.97
—
7.72
7.74
7.72 (J ¼ 28)
7.53 (J ¼ 28)
7.31 (J ¼ 28)
6.95 (J ¼ 28)
—
3
5.17 (dd, 2H), 3.74 (s, 3H, CH ),
1
0.4 (s, 1H, NH)
7.37 (d, 1H, J ¼ 28), 7.12 (t, 1H),
.87 (tt, 2H)
8.33
8.04
6
(
continued)

Table 3. Continued
Comp. no. -H or C
C
1
2
H(s)
C
3
-H(s)
C
4
-H(s)
C
5
-H(d)
C
6
-H(d)
NH(s)
8.67
Others
13
14
15
3.97, 3.95
3.89
8.4
7.73
7.75
7.76
7.64 (J ¼ 28)
7.61 (J ¼ 28)
7.71 (J ¼ 28)
6.9 (J ¼ 28)
6.92 (J ¼ 28)
7.21 (J ¼ 28)
7.33 (dd, 2H, J ¼ 28), 7.52 (dd,
2
H, J ¼ 28)
8.28
8.36
—
7.18–7.28 (m,5H), 4H Ar H &
NH
3.87, 3.83
10.17
7.18 (t, 2H), 8.04 (d, 1H, J ¼ 25),
8
.64 (d, 1H, J ¼ 38, 12.19
(
s, 1H, COOH)
6.85–7.38 (m, 4H, Ar-H), 9.17
s, 1H, OH)
7.28–7.53 (m, 4H, Ar), 6.7
s, 1H, SH)
7.28–7.54 (m, 4H, Ar-H), 10.11
br, 2H, NH
3.5–3.65 (m, 4H, 2CH
sbr, 1H, NH)
17
21
22
23
3.89, 3.83
3.88, 3.82
3.87, 3.81
3.81, 3.82
8.18
8.22
8.22
8.25
7.72
7.69
7.70
7.76
7.67 (J ¼ 28)
7.65 (J ¼ 28)
7.65 (J ¼ 28)
7.70 (J ¼ 28)
7.17 (J ¼ 28)
7.16 (J ¼ 28)
7.18 (J ¼ 28)
7.20 (J ¼ 28)
10.18
10.11
—
(
(
(
s
2
)
—
2
), 7.98
(

Antibacterial Activities
4051
Table 4. Antibacterial activity of the tested compounds
Escheri-
chia coli
Pseudomonas
aurignosa
Bacillus
subtilis
Compound no.
Staphylococcus
1
2
6
7
—
—
—
—
—
—
—
—
4.5
—
6.5
—
—
—
—
—
—
—
4.5
—
—
—
—
—
—
—
—
—
—
—
16
—
—
—
—
—
—
—
—
—
—
—
—
—
—
3.5
—
—
—
—
—
—
—
—
—
—
1
1
1
1
1
1
1
2
2
2
1
2
3
4
5
6
9
1
2
3
Note. Diameter of an inhibition zones is measured in mm.
determined on a Varian FT–200 and Brucker AC-200 MHz using TMS
as internal standard. All chemical shifts (d) are expressed in parts
per million (ppm). All NH or OH protons disappeared by deuterium
exchange (addition of D O). Mass spectra were determined on MP model
2
MS-5988 and Shimadzu single-focusing mass spectrophotometer (70 eV)
(Scheme 3).
Synthesis of the Compounds
0 0
-Cyano-3-(3 ,4 -dimethoxyphenyl)-2-propenoyl chloride (2)
2
[
22]
A mixture of acid
water bath for 6 h. The excess thionyl chloride was distilled, and the
(1) (5 g) and thionyl chloride (20 mL) was heated in a
residue was collected and washed with petroleum ether (40–608C) to give
(2) as yellow crystals.
0
0
0
3,4-Dimethoxybenzaldehydeazine (3) and N,N -Bis[2-cyano-3-(3 ,4 -
dimeth-oxyphenyl)-2-propenoyl]-hydrazine (4)
A mixture of 2 (2.51 g, 0.01 mol), triethylamine (1.01 g, 0.01 mol), and
hydrazine hydrate (0.5 g, 0.01 mol) in dry benzene (50 mL) was stirred at
room temperature for 30 min. The solid formed was filtered, washed with
warm water, dried, and crystallized from ethanol–dioxane mixture to give 4

4
052
A. K. El-Ziaty and S. A. Shiba
Scheme 3. Mass fragmentation of acid 1.
as pale yellow crystals. The benzene layer was concentrated, and the solid
separated was collected and crystallized from petroleum ether (80–1008C)
to give 3 as pale yellow crystals. Compound 3 was compared with an
[
5]
authentic sample, which gave the same melting point, mixed melting
point (mmp), and thin layer chromatography (TLC).

Antibacterial Activities
4053
0
0
0
N-Benzoyl-N -[2-cyano-3-(3 ,4 -dimethoxyphenyl)-2-
propenoylhydrazine (5)
A mixture of 2 (2.51 g, 0.01 mol), triethylamine (1.01 g, 0.01 mol), and
benzoylhydrazine, (1.39 g, 0.01 mol) in dry benzene (50 mL) was stirred at
room temperature for 30 min. The solid formed was filtered, washed with
water, dried, and crystallized from a toluene–ethanol mixture to give 5 as
grey crystals.
0
0
N-(p-Anisyl)2-cyano-3-(3 ,4 -dimethoxyphenyl)-2-propenamide (6)
A mixture of 2 (2.51 g, 0.01 mol), triethylamine (1.01 g, 0.01 mol), and
p-anisidine (1.23 g, 0.01 mol) in dry benzene (50 mL) was stirred at room
temperature for 30 min. The solid formed was filtered, washed with warm
water, dried, and crystallized from a toluene–ethanol mixture to give (6) as
canary yellow crystals.
0
0
N,N-Bis-[2-cyano-3-(3 ,4 -dimethoxyphenyl)-2-prpenoyl]-
ethanolamine (7)
A mixture of 2 (2.51 g, 0.01 mol), triethylamine (1.01 g, 0.01 mol), and
ethanolamine (0.61 g, 0.01 mol) in dry benzene (50 mL) was stirred at room
temperature for 30 min. The solid separated was filtered, washed with warm
water, dried, and crystallized from a toluene–ethanol mixture to give 7 as
pale yellow crystals.
0 0 00 00 0
-[1 -Cyano-2 -(3 ,4 -dimethoxyphenyl)-1 -ethenyl]-(3H)-1,3,5-
6
0
0
0
oxadiazin-2,4-dione (8) and N-Carboxy N -[2-cyano -3(3 ,4 -
dimethoxyphenyl)-2-propenoyl] Urea (9).
A mixture of 2 (2.51 g, 0.01 mol), triethylamine (1.01 g, 0.01 mol), and
urea (0.44 g, 0.01 mol) was refluxed in dioxane (50 mL) for 30 min. The
reaction mixture was concentrated, and the solid formed was collected
and crystallized from toluene to give 8 as yellow crystals. The mother
liquor was poured on ice-cold water, and the residue was collected,
dried, and crystallized from an ethanol–dioxane mixture to give (9) as
colorless crystals.
0
0
5
4
-Cyano-6-(3 ,4 -dimethoxyphenyl)-1-methyl-5,6-dihydropyrimidine-
-one-2-thione (10)
A mixture of 2 (2.51 g, 0.01 mol), triethylamine (1.01 g, 0.01 mol), and
methylthiourea (0.76 g, 0.01 mol) was refluxed in dioxane (40 mL) for 4 h.
The reaction mixture was concentrated, and the solid formed was collected
and crystallized from an ethanol–dioxane mixture to give 10 as yellow crystals.

4
054
A. K. El-Ziaty and S. A. Shiba
0
0
0
N-[2-Cyano-3-(3 ,4 -dimethoxyphenyl)-2-propenoyl]-N -
phenylthiourea (11)
A mixture of 2 (2.51 g, 0.01 mol), triethylamine (1.01 g, 0.01 mol), and
phenylthiourea (1.38 g, 0.01 mol) was refluxed in dioxane (40 mL) for 4 h.
The reaction mixture was concentrated, and the solid formed was collected
and crystallized from an ethanol–dioxane mixture to give 11 as yellow
crystals.
0
0
N-[2-Cyano-3-(3 ,4 -dimethoxyphenyl)-2-propenoyl]-1,2-
00 00
0
0
0
diaminobenzene (12) and N,N -Bis-[2 -cyano-3 -(3 ,4 -
0
dimethoxyphenyl)-2 -propenoyl]-1,2-diaminobenzene (13)
Procedure 1
A mixture of 2 (2.51 g, 0.01 mol), triethylamine (1.01 g, 0.01 mol), and
p-phenylenediamine (1.08 g, 0.01 mol) in dry benzene (50 mL) was stirred
at room temperature for 45 min. The precipitate formed was filtered,
washed with water, dried, and crystallized from toluene to give 13 as pale
yellow crystals. The benzene layer was concentrated and the residue was
collected and crystallized from a petroleum ether (80–1008C)–benzene
mixture to give 12 as yellow crystals.
Procedure 2
A mixture of 2 (5.02 g, 0.02 mol), triethylamine (2.02 g, 0.02 mol), and
o-phenylenediamine (1.08 g, 0.01 mol) in dry benzene (100 mL) was stirred
at room temperature for 45 min. The precipitate formed was filtered,
washed with water, dried, and crystallized from toluene to give 13 as pale
yellow crystals.
0 0 00 00 0
-[1 -Cyano-2 -(3 ,4 -dimethoxyphenyl)-1 -ethenyl]-[1H]-
2
0
0
benzimidazole (14) and 2-Cyano-3-(3 ,4 -dimethoxyphenyl)-2-
propenoic Acid (1)
A mixture of 12 and/or 13 (1 g) and phosphoryl chloride (10 mL) was heated
on a water bath for 4 h. After cooling, the reaction mixture was poured onto
crushed ice. The precipitate was filtered, washed with water, dried, and
crystallized from toluene to give 14 as brown crystals. The insoluble
residue from treatment of 13 was crystallized from ethanol to give 1 as
yellow crystals.

Antibacterial Activities
4055
0
0
2-N-[2-Cyano-3-(3 ,4 -dimethoxyphenyl)-2-propenoyl]aminobenzoic
Acid (15)
To a solution of anthranilic acid (1.37 g, 0.01 mol) in dry pyridine (30 mL), 2
2.51 g, 0.01 mol) was added portionwise with stirring for 30 min. The
(
reaction mixture was stirred for a further 30 min, then poured onto cold
dil. HCL. The precipitate formed was filtered, washed with water, dried,
and crystallized from toluene to give 15 as pale yellow crystals.
0
0
00 00
2
-[1 -Cyano-2 -(3 ,4 -dimethoxyphenyl)-1-ethenyl]-3,1-benzoxazin-
-one (16)
4
A mixture of 15 (3 g) and acetic anhydride (15 mL) was heated on a water bath
for 2 h. After cooling, the precipitated was filtered, washed with dry
petroleum-ether (40–608C), dried, and crystallized from petroleum ether
(80–1008C)–benzene mixture to give 16 as yellow crystals.
0 0 00 00 0
-N-[2 -Cyano-3 -(3 ,4 -dimethoxyphenyl)-2 -propenoyl] aminophenol
2
0 0 00 00 0
(17), 2-N,N-Bis[2 -cyano-3 -(3 ,4 -dimethoxyphenyl)-2 -propenoyl]-
aminophenol (18), 2-N-[2 -Cyano-3 -(-3 ,4 -dimethoxyphenyl)-2 -
0
0
00 00
0
00 00
0
0
propenoyl]-aminophenyl]-2-cyano-3-(3 ,4 -dimethoxyphenyl)-2-
0
0
0
propenoate (19), and 2-[1 -cyano-2 -(3 ,4 -dimethoxyphenyl)-1 -
ethenyl]-benzoxazole (20)
A mixture of 2 (2.51 g, 0.01 mol), triethylamine (1.01 g, 0.01 mol), and
o-aminophenol, (1.09 g, 0.01 mol) in dry benzene (50 mL) was stirred at
room temperature for 30 min. The solid separated was filtered, washed with
water, dried, and crystallized from an ethanol–dioxane mixture to give 17
as yellow crystals. The mother liquor was concentrated to dryness, and the
residue was crystallized from petroleum ether (80–1008C) to give 18 as
yellow crystals. The benzene layer was concentrated, and the residue was
crystallized from petroleum ether (80–1008C)–benzene mixture to give 20
as a pale yellow crystals. The mother liquor was concentrated to give 19 as
yellow crystals.
Conversion of 17 into 20
A mixture of 17 (0.5 g) and phosphoryl chloride (5 mL) was heated on a water
bath for 2 h. After cooling, the crushed ice was added to the mixture and left
overnight. The solid separated was collected, washed with water, dried, and
crystallized from a petroleum ether (80–1008C)–benzene mixture to give
20 as pale yellow crystals, which were identified by mp, mmp, TLC, and
spectral data with that obtained in the previous experiment.

4
056
A. K. El-Ziaty and S. A. Shiba
0
0
00 00
0
2
-N-[2 -Cyano-3 -(3 ,4 -dimethoxyphenyl)-2 propenoyl]-
0
0
0
aminothiophenol (21) and S-(2 -aminophenyl)2-cyano-3-(3 ,4 -
dimethoxyphenyl)-2-thiolpropenoate (22)
A mixture of 2 (2.51 g, 0.01 mol), triethylamine (1.01 g, 0.01 mol), and
o-aminothiophenol (1.25 g, 0.01 mol) in dry benzene (50 mL) was stirred at
room temperature for 30 min. The solid separated was filtered, washed with
water, dried, and crystallized from a toluene–ethanol mixture to give 21 as
yellow crystals. The benzene layer was concentrated and the residue was
collected and crystallized from a petroleum ether (80–1008C)–benzene
mixture to give 22 as pale yellow crystals.
0
0
0
S-[2 -Imidazolidin]2-cyano-3-(3 ,4 -dimethoxyphenyl)-2-thiolpropenoate
23)
(
A mixture of 2 (2.51 g, 0.01 mol), triethylamine (1.01 g, 0.01 mol), and
2
4
-imidazolidinthion, (1.02 g, 0.01 mol) was refluxed in dioxane (50 mL) for
h. The solvent was concentrated, and the solid precipitated was filtered
and crystallized from ethanol to give 23 as brown crystals.
0
0
0
S-[2 -Benzimidazole]2-cyano-3-(3 ,4 -dimethoxyphenyl)-2-
thiolpropenoate (24)
Fusion of 2 (2.51 g, 0.01 mol), 2-benzimidazolethiol (1.5 g, 0.01 mol), and
triethylamine (1.01 g, 0.01 mol) was heated at 1408C without solvent for
15 min. After cooling, the residue was triturated with warm water. The
solid separated was filtered, dried, and crystallized from an ethanol–
dioxane mixture to give 24 as yellow crystals. This reaction at room tempera-
ture and in dioxane at reflux gave no change.
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4057
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