Reaction of (E)-3-(Benzo[d][1,3]dioxol-5-yl)-2- cyanoacryloyl chloride with nucleophilic reagents containing nitrogen and sulfur

Article abstract of DOI:10.1080/10426500903176547

(E)-3-(Benzo[d][1,3]dioxol-5-yl)-2-cyanoacryloyl chloride was reacted with nucleophilic reagents containing nitrogen and sulfur to give new acryloyl amides, imides, thioesters, and heterocyclic systems. Some of these products showed moderate activities ag

Full text of DOI:10.1080/10426500903176547

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Phosphorus, Sulfur, and Silicon and the
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Reaction of (E)-3-(Benzo[d][1,3]dioxol-5-
yl)-2- Cyanoacryloyl Chloride with
Nucleophilic Reagents Containing
Nitrogen and Sulfur
S. A. Shiba a , A. K. El-Ziaty a , N. K. El-Aasar a & H. A. Al-Saman a
a Chemistry Department, Faculty of Science , Ain Shams University ,
Cairo, Egypt
Published online: 02 Aug 2010.
To cite this article: S. A. Shiba , A. K. El-Ziaty , N. K. El-Aasar & H. A. Al-Saman (2010) Reaction of
(E)-3-(Benzo[d][1,3]dioxol-5-yl)-2- Cyanoacryloyl Chloride with Nucleophilic Reagents Containing
Nitrogen and Sulfur, Phosphorus, Sulfur, and Silicon and the Related Elements, 185:8, 1645-1657, DOI:
10.1080/10426500903176547
To link to this article: http://dx.doi.org/10.1080/10426500903176547
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Phosphorus, Sulfur, and Silicon, 185:1645–1657, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903176547
REACTION OF (E)-3-(BENZO[d][1,3]DIOXOL-5-YL)-2-
CYANOACRYLOYL CHLORIDE WITH NUCLEOPHILIC
REAGENTS CONTAINING NITROGEN AND SULFUR
S. A. Shiba, A. K. El-Ziaty, N. K. El-Aasar, and H. A. Al-Saman
Chemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
(E)-3-(Benzo[d][1,3]dioxol-5-yl)-2-cyanoacryloyl chloride was reacted with nucleophilic
reagents containing nitrogen and sulfur to give new acryloyl amides, imides, thioesters,
and heterocyclic systems. Some of these products showed moderate activities against an-
tibacterial and antifungal agents.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental
file.
Keywords Benzimidazoles; benzothiazipines; 2-cyanoacryloyl chloride; pyrimidinethiones
INTRODUCTION
The recent widespread uses of 2-acryloyl chloride derivatives in the synthesis of
highly important products, such as precursors of herbicides,1,2 antifungal,3 and pharma-
ceutical intermediates4 make them worthy to be studied and encouraged us to use new
derivatives of these categories in the synthesis of new analogous of 2-acryloyl amides5
and esters,6–9 besides many interesting biologically and pharmacologically active hete-
rocyclic systems, such as benzimidazoles,10,11 benzthiazoles,12 benzothiazepines,13,14 and
pyrimidinethiones.15
RESULTS AND DISCUSSION
In continuation of our previous studies,16–20 we report in this article the reactions of
(E)-3-(benzo[d][1,3]dioxol-5-yl)-2-cyanoacryloyl chloride16 (3; prepared as mentioned in
Scheme 1) with some nucleophilic reagents containing sulfur and nitrogen. The present
investigation was planned to study the effect of the 2-cyano group on the reactivity and
stability of C2 C3 double bond towards different strong to weak nucleophiles, besides
Received 10 May 2009; accepted 10 July 2009.
Address correspondence to S. A. Shiba, Chemistry Department, Faculty of Science, Ain Shams University,
Cairo, Egypt. E-mail: sayedahmedshiba@yahoo.com
1645

1646
S. A. SHIBA ET AL.
O
O
CHO
O
O
pip.
COOC2H5 EtOH
CN
+
CN
H
OC2H5
O
(1)
1) NaOH / EtOH
2)HCl
O
O
O
O
SOCl2
CN
CN
H
OH
H
Cl
O
(2)
O
(3)
Scheme 1
its enhancement of nucleophilic addition at C2 C3 double bond to give new heterocyclic
derivatives.
Treatment of 3 with hydrazine hydrate16 and/or hydrazinecarbodithioc acid yielded
the aldazine21 (4) as sole product, while with thiosemicarbazide (3) gave a mixture of
2-propenoyl hydrazide derivative (5) and piperonal thiosemicarbazone22,23 (6) (Scheme 2).
O
O
S
O
O
CN
H
O
O
N2H4
H2N
N
C
SH
Cl
CHO
or
H2N NH2
N
H
O
(3)
H
2
S
(4)
H
H2N
N
C
NH2
S
H
O
O
H2N
N
C
NH2
CN
O
O
O
+
S
H
NHNH2
H
N
N
C
NH2
H
(5)
(6)
Scheme 2
Formation of these products can be explained according to the following pathway:

NUCLEOPHILIC REAGENTS CONTAINING NITROGEN AND SULFUR
1647
(b)
N
Ar
C
C
(a)
S
H
Cl
SH
H2N
C
S
O
NH
HN
C
(3)
r
H2N
)
o
u
b
(
NH2
t
e
&
)
a
(
a
(
)
S
NHNHC SH
CN
Ar
CN
S
NH2
Ar
H
C
NHNH
C
NH2
S
NHNHC SH
NH
C
O
(b)
(a)&
H
C
O
S
NH2
-HNCS
CN
Ar
S
S
Ar
H
NHNHC NH2
CN
CN
H
N
S
N
C
SH
H
NHNH2
+
Ar
C
O
NHNHC SH
O
(5)
S
H
C
O
NHNHC NH2
-CS2
Ar-CH
(3)
N
N
NH2
CN
S
S
Ar
H
N
N
C
NH2
C
O
NHNH
C
NH2
+
H
Ar-CH
(6)
2
-HNCS
NHNH2
(4)
NC
O
O
O
Ar =
The structures of aldazine21 (4) and carbazone22,23 (6) were established by comparison
with authentic samples prepared by condensation of piperonal with hydrazine hydrate and/or
thiosemicarbazide, in addition to spectral data.
Li et al.24,25 condensed the ester16 (1) with thiourea in the presence of sodium methox-
ide or K2CO3 to give 4-oxo-2-thioxohexahydropyrimidine derivative (7) (in cis/trans forms)
in excellent yield (Scheme 3). In condensation of the acid chloride (3) with thiourea in the
presence of Et3N as a base, only the imide (8) was isolated in pure form (Scheme 3).
O
O
O
O
O
O
CN
CN
CN
S
(3)
(1)
X
O
C
+
H2N
NH2
NH
Et3N
Dioxane
CH3ONa
CH3OH
H
O
HN
NH
H
O
1) X = OC2H5
3) = Cl
2
S
(8)
(7)
Scheme 3
Condensation of ester (1) with N-methyl thiourea in sodium methoxide afforded
a mixture of 4-oxo-2-thioxopyrimidine derivative25 (9) (cis/trans form 50:50) and the
transesterification26 product (E)-methyl 3-(benzo[d][1,3]dioxol-5-yl)-2-cyanoacrylate (10)

1648
S. A. SHIBA ET AL.
(Scheme 4). On the other hand, treatment of acid chloride (3) with N-methyl thiourea gave
only the pyrimidinthione (9) (Scheme 4).
Condensation of (3) with phenyl thiourea in the presence of Et3N yielded a mixture
of amide (11) and imide (12) (Scheme 5).
The structure of amide (11) was established chemically by condensation of (3)
with aniline under the same condition (Scheme 5). Also, this compound was prepared
by condensation of piperonal with N-phenyl cyanoacetamide in the presence of a base27
(Scheme 5).
Formation of 11 and 12 can be explained according to the following pathway:
(b)
(a)
CN
S
Ar
NH
CN
H
S
C
Ar
N
NH2
Ar
CN
O
S
C6H5
NH-C6H5
H2N
N
H
N
Cl
route (a)
S
NH
O
H
HN
O
C
+
C6H5
S
HN
C6H5
(3)
CN
route (b)
CN
Ar
NH-C6H5
Ar
S
H
O
NH
NH2
O
+
(11)
C6H5-N=C=S
HN
C6H5
(3)
CN
O
Ar
CN
Ar
NH
H
O
S
NH
O
Ar =
HN
O
(12)
C6H5
Condensation of 3 with benzimidazolethione in boiling dioxane and/or heating with-
out solvent at 140◦C afforded the thioester (13) (Scheme 6). Formation of S-acyl (13) rather
than N-acyl derivative (I) was established chemically by heating of 13 with POCl3 to give
O
O
O
O
CN
CN
S
(1)
X
O
C
CH3
+
H2N
N
CH3ONa
CH3OH
H
H
O
HN
N
CH3
1) X = OC2H5
3) = Cl
S
(9)
+
O
(3)
Et3N/Bz
O
CN
OCH3
(9)
H
O
(10)
Scheme 4

NUCLEOPHILIC REAGENTS CONTAINING NITROGEN AND SULFUR
1649
O
O
O
O
CN
O
S
O
O
CN
Et3N
CN
C
C6H5
Cl
H2N
N
+
NH
H
H
H
O
S
NH
O
(3)
NH-C6H5
(12)
+
CHO
NH2
O
O
O
O
C6H5HN
NC
O
CN
Et3N
C
(3)
+
NH-C6H5
py./pip. 600
C
H
O
(11)
Scheme 5
H
H
N
Ar
CN
N
Cl
S
+
S
H
H
N
H
N
O
O
Ar
(3)
CN
(I)
N
S
O
POCl3
N
b
CN
u
t
a
n
o
H
N
l
p
Ar
(III)
i
H
p
.
/
N
S
Ar
Cl
POCl3
N
N
H
O
CN
(13)
O
Ar
CN
(II)
O
O
Ar =
Scheme 6
unchanged product instead of the expected 2-chloro-benzimidazole derivative (II) (Scheme
6). Also, in contrast to Britsun et al.,28–30 this reaction gave only the open product 13 rather
than the cyclic product (III). Refluxing of 13 in butanol in the presence of piperidine and/or
pyridine failed to give the cyclic system (III) (Scheme 6).
This supports our previous studies17 about the highest reactivity of S versus N.
Reaction of cinnamic acid derivatives (14) with 2-amino thiophenol in the presence
of a base31–37 afforded the 1,5-benzothiazepine-4-ones (15) (Scheme 7).
NH2
Ar
S
Ar
H
HS
+
H
OH
N
H
O
O
(14)
(15)
Scheme 7

1650
S. A. SHIBA ET AL.
When we repeat this reaction with our starting material 2-cyanopropenoic acid deriva-
tive (2) in different conditions, we get 2-(benzo[d][1,3]dioxol-5-yl)benzo[d]thiazole12 (16)
as the sole product (Scheme 8).
O
O
NH2
O
CN
HS
S
O
+
H
OH
N
O
(16)
(2)
Scheme 8
Formation of (16) established the idea about the effect of a cyano group on the
reactivity of α,β-unsaturated double bond towards nucleophilic reagents, which facilitates
the C C bond cleavage with formation of the imine (17), which then undergoes ring closure
with subsequent oxidation under reaction conditions to give 16 as shown on the following
pathway:
SH
NH2
N
SH
N
COOH
CN
HS
C
Ar
C
+
HN
Ar
N=CH-Ar
COOH
H
OH
H
(17)
O
~H+
S
O
S
-H2
Ar
Ar =
Ar
O
N
N
H
(16)
When we carried the condensation reaction of 2-propenoyl chloride (3) with 2-
amino thiophenol in the presence of Et3N at room temperature, a mixture of thiopropenoate
derivative (18) and 1,5-benzothiazepin derivative (19) was obtained (Scheme 9). Compound
19 was identified in a mixture of 18 and 19 by 1H NMR. Treatment of both pure 18 and 18
+ 19 mixture with POCl3 afforded the same benzothiazole derivative (20) as a sole product
(Scheme 9).
The structure of benzothiazole (20) was established chemically by condensa-
tion of 2-cyanomethylbenzthiazole (21) with piperonal in the presence of NaOH as a
base.38
Formation of benzthiazole (20) can be achieved according to the following pathway:

NUCLEOPHILIC REAGENTS CONTAINING NITROGEN AND SULFUR
1651
O
NH2
S
CN
CN
S
Ar
+
N
H
(19)
O
H
Ar
(18)
POCl3
Cl
NH2
S
OPOCl2
CN
CN
Ar
S
+
N
H
Cl
OPOCl2
H
Ar
[A]
OPOCl
-
2
Cl
CN
Cl
S
H
Ar
S
+
CN
Ar
H2N
N
H
H
[B]
-H+
CN
Ar
H
Cl
CN
S
S
+
N
H
Ar
Cl
N
H
H
[C]
-HCl
H
Ar
S
N
CN
(20)
The POCl3 attacks the carbonyl carbon atom to give the intermediate39 [A], which
lost OPOCl2 to give the carbocation [B]. [Conformational analysis40 for the most stable
conformer [B], (Figure S1, Supplemental Materials, available online) shows that the nitro-
gen atom at position 5- is very near to the carbon 2- (3.22 A◦)]. Nucleophilic attack of the
N atom into the carbocation with ring contraction gave the intermediate [C], which lost
HCl to give benzthiazole (20).

1652
S. A. SHIBA ET AL.
O
H
SH
O
O
CN
H
S
H2N
O
O
NH2
CN
CN
Cl
S
N
+
H
O
O
O
H
H
(19)
POCl3
(3)
(18)
O
POCl3
O
H
S
O
S
Ar-CHO
NaOH
N
CN
N
CN
(21)
(20)
Scheme 9
Measurement of Antimicrobial and Antifungal Activities Using
Diffusion Disc Method
Antimicrobial activity was measured in the Microanalytical Center, Cairo University,
Giza, Egypt.
Method
A filter paper sterilized disc saturated with measured quantity of the sample with
concentration of 20 mg/mL was placed on a plate containing solid bacterial medium
(nutrient agar broth) or fungal medium (Dox’s medium), which was heavily seeded with
the spore suspension of the tested organism. After inoculation, the diameter of the clear
zone of inhibition surrounding the sample was taken as a measure of the inhibitory power
of the sample against the particular test organism.41–44 The experimental details and results
are summarized in the Supplemental Materials (Table S1).
EXPERIMENTAL
Melting points reported are uncorrected. IR spectra were recorded on Pye Unicam SP
1200 spectrophotometer using the KBr wafer technique. 1H NMR spectra were determined
on a Varian FT-200 and a Bruker AC-300 MHz using TMS as internal standard. All chemical
shifts (δ) are expressed in ppm. All the NH or OH protons disappeared upon addition of
D2O. The mass spectra were determined using an MP model MS-5988 and a Shimadzu
single focusing mass spectrophotometer (70 eV). Elemental analyses were investigated by
an Elementar analyzer Vario EL III.
(E)-3-(Benzo[d][1,3]dioxol-5-yl)-2-cyanoacryloyl chloride (3)
A mixture of (E)-3-(benzo[d][1,3]dioxol-5-yl)-2-cyanoacrylic acid (10 g) and thionyl
chloride (15 mL) was heated on a water bath for 3 h. The excess SOCl2 was distilled under
reduced pressure, and the solid separated was collected, triturated with petroleum ether
40–60◦C, dried, and crystallized to give 3.

NUCLEOPHILIC REAGENTS CONTAINING NITROGEN AND SULFUR
1653
(2E,N’E)-3-(Benzo[d][1,3]dioxol-5-yl)-N’-(benzo[d][1,3]dioxol-5-
ylmethylene)-2-cyanoacrylohydrazide (4)
To a solution of 3 (1.18 g, 0.005 mol) in dioxane (20 mL) in the presence of triethy-
lamine (0.505 g, 0.005 mol), hydrazinecarbodithioc acid (0.45 g, 0.005 mol) was added.
The reaction mixture was refluxed for 1 h. The solid formed (Et3NHCl) was filtered, and the
filtrate was concentrated. The remaining semisolid was crystallized from petroleum-ether
(80–100◦C) to give 4 as yellow crystals; mp: 179–180◦C, yield 79%. IR (ν): absence of
NH, CN, CO. 1H NMR(DMSO-d6) δ 6.09 (s, 4H, 2 × O CH2 O), 7.38 (s, 2H), 7.00 (d, J
= 7.8, 2H), 7.33 (d, J = 8.1, 2H), 8.56 (s, 2H, 2 × = CH). MS: 296 ([M]+., 100), 269 (78),
175 (53), 174 (10), 152 (25), 148 (33). Anal. Calcd. for C16H12N2O4 (296.28): C, 64.86;
H, 4.08; N, 9.45. Found: C, 65.01; H, 4.23; N, 9.67.
(E)-3-(Benzo[d][1,3]dioxol-5-yl)-2-cyanoacrylohydrazide (5)
and 1-(Benzo[d][1,3] dioxol-5-ylmethylene)thiosemicarbazide (6)
To a solution of 3 (1.18 g, 0.005 mol) in dioxane (20 mL) in the presence of triethy-
lamine (0.505 g, 0.005 mol), thiosemicarbazide (0.45 g, 0.005 mol) was added. The reaction
mixture was refluxed for 1 h. The solid formed was filtered, and the filtrate was concen-
trated. The remaining semisolid was triturated with boiling petroleum-ether (60–80◦C) to
give 6 as yellow crystals, and the insoluble solid was crystallized from toluene to give 5 as
yellow crystals.
5: Mp: 181–182◦C, yield 56%. IR (ν): 3420 (NH, NH2), 2212 (CN), 1623 (C O)
cm−1. 1H NMR(DMSO-d6) δ 6.05 (s, 2H, O CH2 O), 6.89 (d, CH J = 6.9, 1H), 6.92 (d,
CH J = 8.9, 1H), 7.62 (s, 1H, CH), 7.95 (s, 1H, CH), 7.99 (s, 1H, NH), 8.07 (s, 1H, NH),
11.28 (s, 1H, NH). MS: 231 ([M]+., 72), 230 (34), 219 (14), 190 (19), 175 (21), 174 (49),
165 (20), 164 (17), 147 (30), 86 (100). Anal. Calcd. for C11H9N3O3 (231.202): C, 57.14;
H, 3.92; N, 18.17. Found: C, 57.34; H, 3.72; N, 18.26.
Compound 6 was established by authentic sample22,23 prepared by condensation of
piperonal with thiosemicarbazide.
(2E)-3-(1,3-Benzodioxol-5-yl)-N-[(2E)-3-(1,3-benzodioxol-5-yl)-2-
cyanoprop-2-eno-yl]-2-cyanoacrylamide (8)
To a solution of 3 (1.18 g, 0.005 mol) in dioxane (20 mL) in the presence of triethy-
lamine (0.505 g, 0.005 mol), thiourea (0.38 g, 0.005 mol) was added. The reaction mixture
was refluxed for 3 h. The solid formed was filtered, and the filtrate was concentrated. The
remaining semisolid was crystallized from petroleum-ether (80–100◦C) to give 8 as yellow
crystals; mp: 159–160◦C, yield 45%. IR (ν): br. 3425 (NH), 2213 (CN), 1736 (C O) cm−1
.
1H NMR(DMSO-d6) δ 6.13 (s, 4H, 2 × O CH2 O), 7.08 (d, J = 7.8, 2H), 7.53 (d, J =
6.9, 2H), 7.62 (s, 2H), 8.14 (s, 2H, = CH), 8.53 (br.s, 1H, NH). MS: 415 [M+.], 217 (100),
172 (32), 142 (10), 114 (27). Anal. Calcd. for C22H13N3O6 (415.34): C, 63.62; H, 3.15; N,
10.12. Found: C, 63.42; H, 3.24; N, 10.03.
6-(Benzo[d][1,3]dioxol-5-yl)-1-methyl-4-oxo-2-thioxo-
hexahydropyrimidine-5-carbonitrile (9)
To a solution of 3 (1.18 g, 0.005 mol) in dry benzene (50 mL) in the presence of tri-
ethylamine (0.505 g, 0.005 mol), N-methyl thiourea (0.45 g, 0.005 mol) was added, and the
reactionmixturewas refluxed for 40 min. The solidformedwas collected, washedwithwater

1654
S. A. SHIBA ET AL.
(80 mL), dried, and crystallized from toluene to give 9 as yellow crystals; mp: 239–240◦C,
1
yield 74%. IR (ν): 3384 (NH), 2208 (CN), 1682 (C O) cm−1. H NMR(DMSO-d6) δ
cis/trans 3.47 (s, 3H, N CH3), 3.56 (s, 3H, N CH3), 5.07–5.13 (d,d, 2H), 6.07 & 6.16 (s,
2H), 7.24 & 7.22 (s, 1H), 6.89–7.13 (m, 2H), 10.35 (s, 1H, NH). MS: 289 (M+., 67), 288
([M-1]+., 100), 287 ([M-2]+., 5), 260 (10), 232 (4), 215 (12), 200 (47), 174 (4), 145 (5).
Anal. Calcd. for C13H11N3O3S (289.306): C, 53.47; H, 3.83; N, 14.52. Found: C, 53.57;
H, 3.73; N, 14.61.
13C NMR (DMSO-d6):
101.62
142.9
O
120.46
61.05
113.7
CN
O
147.81
108.35
O
159.14
HN
N
CH3
120.60
S
178.18
in solvent
(E)-Methyl 3-(benzo[d][1,3]dioxol-5-yl)-2-cyanoacrylate (10)
To a solution of (E)-3-(benzo[d][1,3]dioxol-5-yl)-2-cyanoacrylate (1) (1.22 g, 0.005
mol) in methanol (20 mL) and sodium methoxide in methanol (0.54 mL, 0.01 mol), N-
methyl thiourea (0.45 g, 0.005 mol) was added. The mixture was stirred at room temperature
for 1 h. The solid formed was filtered, and the filtrate was acidified by 5% acetic acid. Then
the solid formed was collected, washed with water (50 mL), dried, and crystallized from
toluene to give 9 as yellow crystals, and then from ethanol to give 10 as yellow crystals;
1
mp: 119–120◦C. IR (ν): 2218 (CN), 1726 (C O) cm−1. H NMR(DMSO-d6) δ 3.84 (s,
3H, OCH3), 6.18 (s, 2H, O CH2 O), 7.68 (s, 1H, Ar-H), 7.15 (d, 1H, J = 6.3, Ar-H), 7.64
(d, 1H, J = 4.8, Ar-H), 8.28 (s, 1H, CH). MS: 232 ([M+2]+., 14), 231 ([M]+., 100), 230
(([M-1]+., 42), 200 (27), 199 (12), 171 (247), 170 (62), 142 (27), 114 (60).
(E)-3-(Benzo[d][1,3]dioxol-5-yl)-2-cyano-N-phenylacrylamide (11)
and (E)-1-(1-(Benzo[d][1,3]dioxol-5-yl)-3-(3-(benzo[d][1,3]dioxol-5-yl)-2-
cyanoacrylamido)-2-cyano-3-oxopropyl)-3-phenylthiourea (12)
To a solution of 3 (1.18 g, 0.005 mol) in dioxane (30 mL) in the presence of triethyl
amine (0.505 g, 0.005 mol), phenyl thiourea (0.76 g, 0.005 mol) was added, and the reaction
mixture was refluxed for 1h. The solid formed was filtered, and the filtrate was concentrated.
The remaining semisolid was crystallized from petroleum-ether 80–100◦C to give 11 as
yellow crystals and then from toluene to give 12 as yellow crystals.
11: Mp: 88–90◦C, yield 70%. IR (ν): 3341 (NH), 2212 (CN), 1678 (C O) cm−1
.
MS: 292 (M+., 13), 291 ([M-1]+., 33), 290 (M-2]+., 8), 215 (1), 200 (100), 170 (95), 142
(42). Anal. Calcd. for C17H12N2O3 (292.29): C, 69.85; H, 4.14; N, 9.59. Found: C, 69.87;
H, 4.24; N, 9.49.

NUCLEOPHILIC REAGENTS CONTAINING NITROGEN AND SULFUR
1655
12: Mp: 118–120 ◦C, yield 30%. IR (ν): 3328, 3320, 3238 (NH), 2217 (CN), 1709,
1674 (C O) cm−1. MS: 551 ([M-OH]+., 0.2), 550 (4), 521 (1), 491 (0.3), 445 (0.5), 429
(0.3), 328 (0.3), 226 (6), 225 (24), 200 (1), 172 (3), 144 (2), 136 (16), 135 (100), 192 (0.8).
Anal. Calcd. for C29H12N5O6S (567.566): C, 61.36; H, 3.73; N, 12.34. Found: C, 61.46;
H, 3.63; N, 12.44.
Reaction of (3) with Aniline, Formation of 11
To a solution of 3 (1.18 g, 0.005 mol) in dry benzene (50 mL) in the presence of
triethyl amine (0.505 g, 0.005 mol), aniline (0.46 gm, 0.005 mol) was added, and the
reaction mixture was refluxed for 1 h. The solid separated was filtered, washed with water
(80 mL), dried, and crystallized from petroleum-ether 80–100◦C to give 11.
(E)-S-1H-Benzo[d]imidazol-2-yl 3-(Benzo[d][1,3]dioxol-5-yl)-
2-cyanoprop-2-enethi-oate (13)
A mixture of 3 (1.18 g, 0.005 mol) and benzimidazolethione (0.75 g, 0.005 mol) was
heated without solvent at 140–150◦C for 30 min. The solid was triturated with ethanol,
collected, and crystallized from toluene to give 13 as orange crystals; mp: 211–212◦C,
yield 82%. IR (ν): 3155 (NH), 2218 (CN), 1688 (C O) cm−1. 1H NMR(DMSO-d6) δ 6.18
(s, 2H, O CH2 O), 7.12 (m, 4H, Ar-H), 7.48–7.70 (m, 3H, Ar-H), 8.21 (s, 1H, = CH),
9.27 (s, 1H, NH). MS: 348 ([M-1]+., 25), 347 ([M-2]+., 94), 346 (M-3]+., 100), 260 (18),
188 (8), 173 (40), 172 (34). Anal. Calcd. for C18H11N3O3S (349.298): C, 61.89; H, 3.17;
N, 12.03. Found: C, 61.78; H, 3.27; N, 11.93.
2-(Benzo[d][1,3]dioxol-5-yl)benzo[d]thiazole (16)
A mixture of (E)-3-(benzo[d][1,3]dioxol-5-yl)-2-cyanoacrylic acid 2 (1.18 g, 0.005
mol) and 2-amino thiophenol (0.5 mL, 0.001 mol) was heated without solvent at 160–180◦C
for 2 h. The solid was triturated with diethyl ether, collected, and crystallized from petroleum
ether 80–100◦C to give 16 as yellow crystals; mp: 181–182◦C, yield 78%. IR (ν): absence
of NH, CN, CO. 1H NMR(DMSO-d6) δ 6.14 (s, 2H, O CH2 O), 7.07 (d, 1H, J = 2.1),
7.59–8.08 (m, 4H, Ar-H), 7.6 (d, 1H, J = 1.5), 7.59 (d, 1H, J = 1.2). Anal. Calcd. for
C14H9NO2S (255.286): C, 65.86; H, 3.55; N, 5.49. Found: C, 65.66; H, 3.75; N, 5.35.
(E)-S-2-aminophenyl 3-(Benzo[d][1,3]dioxol-5-yl)-2-cyanoprop-2-
enethioate (18) and (3R,4R)-4-(Benzo[d][1,3]dioxol-5-yl)-2-oxo-2,3,4,5-
tetrahydrobenzo[b][1,4]thiazep-ine-3-carbonitrile (19)
To a solution of 3 (2.36 g, 0.01 mol) in dry benzene (50 mL) in the presence of triethy-
lamine (1.39 g, 0.01 mol), 2-amino thiophenol (1 mL, 0.01 mol) was added, and the reaction
mixture was stirred for 1 h. The solid separated was filtered, washed with water (80 mL),
dried, and crystallized from petroleum-ether 60–80◦C to give 18 as yellow crystals, then
the insoluble solid was crystallized from toluene to give 19 as yellow crystals.
18: Mp: 159–160◦C, yield 30%. IR (ν): 3330 (NH), 2200 (CN), 1686 (C O) cm−1
.
1H NMR (DMSO-d6) δ 6.2 (s, 2H, O CH2 O), 7.13 (d, J = 8.1, 1Hpip.), 7.25–7.38 (m,
4H, Ar-H), 7.56 (d, J = 8.4, 1H), 7.63 (s, 1Hpip.), 8.20 (s, 1H), 10.02 (s, 2H, NH2). MS:

1656
S. A. SHIBA ET AL.
323 ([M-1]+., 15), 322 ([M-2]+., 44). Anal. Calcd. for C17H12N2O3S (324.356): C, 62.95;
H, 3.73; N, 8.64. Found: C, 62.85; H, 3.83; N, 8.45.
18 + 19: 1H NMR (DMSO-d6) δ 4.57 (d, CH J = 12.3, 1H), 5.12 (d, CH J = 12.3,
1H), 5.85 (s, 2H, O CH2 O), 6.87 (s, 1H, CHpip.), 7.23 (d, CHpip. J = 8.7, 1H), 7.15–7.65
(m, 4H, Ar-H), 10.49 (s, 1H, NH). MS: 324 ([M]+., 10), 323 ([M—1]+., 7). Anal. Calcd.
for C17H12N2O3S (324.356): C, 62.95; H, 3.73; N, 8.64. Found: C, 63.05; H, 3.64; N, 8.73.
(E)-3-(Benzo[d][1,3]dioxol-5-yl)-2-(benzo[d]thiazol-2-yl) acrylonitrile (20)
A mixture of 18 and/or a mixture of 18 + 19 (2 g) with POCl3 (10 mL) was heated
on a water bath for 6 h. After cooling, the reaction mixture was poured onto crushed ice
(50 g). The solid separated was filtered, washed with water (50 mL), dried, and crystallized
from toluene to give 20 as yellow crystals; mp: 219–220◦C, yield 70–90%. IR (ν): 2211
(CN) cm−1. 1H NMR(DMSO-d6) δ 6.19 (s, 2H, OCH2O), 7.15 (d, 1Hpip., J = 8.4), 7.49 (t,
1Harm., J = 6.6, 7.5), 7.57 (t, 1Harm., J = 6.9, 7.8), 7.66 (d, 1Hpip., J = 8.4), 7.72 (s, 1Hpip.),
8.04 (t, 1Harm., J = 8.1), 8.14 (s, 1Harm., J = 8.1), 8.29 (s, 1H, = CH). Anal. Calcd. for
C17H10N2O2S (306.336): C, 66.56; H, 3.29; N, 8.64. Found: C, 66.74; H, 3.69; N, 8.73.
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