Synthesis and E/Z configuration determination of novel derivatives of 3-Aryl-2-(benzothiazol-2′-ylthio) acrylonitrile, 3-(benzothiazol-2′- ylthio)-4-(furan-2′ ′-yl)-3-buten-2-one and 2-(1-(Furan-2′ ′-yl)-3′-oxobut-1′ ′-en-2-ylthio)-3-phenylquinazolin- 4(3H)-one

Article abstract of DOI:10.3390/molecules16076129

Knoevenagel condensation of 2-(benzothiazol-2-ylthio) acetonitrile (2) with either furan-2-carbaldehyde or thiophene-2-carbaldehydes leads to E-isomers 4a-b exclusively, while the condensation of the compound 2 with benzaldehyde or parasubstituted benzaldehydes with an electron-donating group afforded E/Z mixtures 4c-e with preferentially formation of the E-isomer. Condensation of furan-2-carbaldehyde (3a) with either 1-(benzothiazol-2′-ylthio) propan-2-one (5) or 2-(2′-oxo propylthio)-3-phenylquinazolin- 4(3H)-one (9) leads exclusively to the Z-isomers of 6 and 10, respectively. The structures of the newly synthesized compounds were elucidated by elemental analyses, ¹H-NMR and ¹³C-NMR spectra, COSY, HSQC, HMBC, NOE, MS and X-ray crystallographic investigations.

Full text of DOI:10.3390/molecules16076129

Molecules 2011, 16, 6129-6147; doi:10.3390/molecules16076129
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Synthesis and E/Z Configuration Determination of Novel
Derivatives of 3-Aryl-2-(benzothiazol-2'-ylthio) Acrylonitrile,
3-(Benzothiazol-2'-ylthio)-4-(furan-2''-yl)-3-buten-2-one and
2-(1-(Furan-2''-yl)-3'-oxobut-1''-en-2-ylthio)-3-
phenylquinazolin-4(3H)-one
Fatima Al-Omran 1,*, Rafat M. Mohareb 2,3 and Adel Abou El-Khair 1
1
Department of Chemistry, Faculty of Science, Kuwait University, P.O. box 12613,
safat 13060, Kuwait
2
Department of Chemistry, Faculty of Science, Cairo University, Giza, A.R., Egypt
3
Department of Organic Chemistry, Faculty of Pharmacy, October University for Modern Sciences
and Arts, Elwahaat Road, October City, A.R., Egypt
* Author to whom correspondence should be addressed; E-Mail: fatima.alomran@ ku.edu.kw.
Received: 21 June 2011; in revised form: 11 July 2011 / Accepted: 14 July 2011 /
Published: 20 July 2011
Abstract: Knoevenagel condensation of 2-(benzothiazol-2-ylthio) acetonitrile (2) with
either furan-2-carbaldehyde or thiophene-2-carbaldehydes leads to E-isomers 4a–b
exclusively, while the condensation of the compound 2 with benzaldehyde or para-
substituted benzaldehydes with an electron-donating group afforded E/Z mixtures 4c–e
with preferentially formation of the E-isomer. Condensation of furan-2-carbaldehyde (3a)
with either 1-(benzothiazol-2'-ylthio) propan-2-one (5) or 2-(2'-oxo propylthio)-3-phenyl-
quinazolin-4(3H)-one (9) leads exclusively to the Z-isomers of 6 and 10, respectively. The
structures of the newly synthesized compounds were elucidated by elemental analyses,
1H-NMR and 13C-NMR spectra, COSY, HSQC, HMBC, NOE, MS and X-ray crystallographic
investigations.
Keywords: benzothiazole; 2-mercaptobenazothiazole; 3-phenylquinazolin-4(3H)-one;
methyl vinyl ketone; acrylonitrile

Molecules 2011, 16
6130
1. Introduction
The benzothiazole nucleus is a highly important scaffold for drug development, which has been
reported to show good biological activities ranging from anti-microbial [1], anti-inflammatory [1],
antibacterial [2], antitumor [3] and anticancer [4,5] to antifungal [6]. On other hand, quinazolin-4-
(3H)-ones substituted in the 3-position with a heterocyclic system are attracting the attention of
chemists, because of their biological activities ranging from antibacterial, antimicrobial, antifungal,
anticonvulsive, sedative, anti-inflammatory, to hypnotic and CNS depression [7-12]. Furthermore,
several other publications have pointed out the value of 3-arylacylonitriles with either triazole [13] or
benzimidazole [14] substituents in position 2 of the acrylonitrile also have good cytotoxic activity on
human cancer cells and are antibacterial agents [14]. It was recently reported that 2-acetyl-3-
(6-methoxybenzothiazo)-2-yl-amino-acylonitrile (AMBAN) possesses significant anti-proliferative
activity and is a potent inducer programmed cell death in human leukemia cells [5].
Based on the abovementioned effects of benzothiazoles, 3-arylacrylonitriles and quinazolin-4-(3H)-
ones a series of novel 3-arylacrylonitriles with 2-mercaptobenzothiazoles moiety in the position 2- of
the acrylonitrile were synthesized to obtain new potential biologically active agents. On other hand, a
series of 4-aryl-3-buten-2-ones with either 2-mercaptobenzothiazole or quinazolin-4-(3H)-one rings in
the 3-position of 4-aryl-3-buten-2-one were synthesized. The structures of the newly synthesized
compounds have been established by x-ray diffraction studies and on the basis of their spectral data.
2. Result and Discussion
In continuation to our recent research programme dealing with the synthesis of heterocyclic
systems, particularly those containing the 2-mercaptobenzothiazole moiety [15,16], 1-(benzothiazol-2-
yl-thio)acetonitrile (2) was readily prepared in an excellent yield by treatment of 2-mercapto-
benzothiazole (1) with α-chloroacetonitrile in refluxing acetone containing anhydrous potassium
carbonate (cf. Scheme 1). The structure of 2 was unambiguously confirmed by X-ray crystallography
[17] as well as on the basis of its spectral data (cf. Figure 1 and Tables 1–3).
Scheme 1. Synthesis of 2.
N
S
S
ClCH2CN
SH
S
N
K2CO3/acetone
N
heat
2
1
Figure 1. Perspective view and atom labeling of the X-ray structure of compound 2.

Molecules 2011, 16
6131
Table 1. Bond lengths (Å) for compound 2.
atom distance atom atom distance
atom
S1
S2
S3
S4
S5
S6
N1
N2
N3
N5
N6
C1
C3
C5
C10
C11
C13
C17
C19
C21
C23
C1
C7
1.730(3)
1.747(3)
1.732(3)
1.745(3)
1.731(3)
1.747(3)
1.400(4)
1.136(5)
1.292(3)
1.402(3)
1.136(6)
1.404(4)
1.388(5)
1.384(4)
1.392(4)
1.366(4)
1.373(5)
1.447(5)
1.400(4)
1.391(4)
1.386(4)
S1
S2
C7
C8
1.741(3)
1.802(3)
1.750(3)
1.806(3)
1.748(3)
1.807(3)
1.293(3)
1.396(4)
1.131(6)
1.296(4)
1.391(5)
1.375(5)
1.370(5)
1.460(5)
1.403(3)
1.389(4)
1.386(4)
1.394(4)
1.373(5)
1.383(4)
1.446(5)
C10
C16
C19
C25
C6
S3
S4
S5
S6
N1
N3
N4
N5
C1
C16
C17
C25
C26
C7
C15
C18
C25
C2
C9
C16
C24
C27
C6
C2
C3
C4
C4
C5
C6
C8
C9
C11
C12
C14
C18
C24
C22
C24
C10
C12
C14
C19
C20
C22
C26
C15
C13
C15
C20
C21
C23
C27
o
Table 2. Bond angles ( ) for compound 2.
atom
C1
C10
C19
C6
C24
S1
C1
C3
N1
C1
S1
S2
S3
C11
C11
C13
N3
atom
S1
S3
atom
C7
C16
C25
C7
C25
C6
C3
C5
C1
C5
N1
angle
88.34(12)
88.53(12)
88.36(12)
109.3(2)
109.60(18)
109.9(2)
117.7(3)
120.9(3)
114.9(2)
120.0(3)
117.6(2)
112.7(3)
129.56(18)
120.7(3)
121.1(3)
119.0(3)
125.2(2)
118.30(13)
atom
C7
C16
C25
C15
S1
C2
C2
C4
N1
S1
S2
N2
S3
C10
C12
N3
C10
S3
atom
S2
S4
S6
N3
C1
C1
C3
C5
C6
C7
C7
C9
C10
C11
C13
C15
C15
C16
atom
C8
C17
C26
C16
C2
C6
C4
C6
C5
S2
N1
C8
C15
C12
C14
C10
C14
N3
angle
98.36(13)
98.83(13)
99.08(12)
109.99(19)
129.17(19)
121.0(3)
121.5(4)
118.9(3)
125.1(3)
117.68(14)
124.7(2)
179.6(3)
109.71(19)
118.5(3)
121.0(3)
115.0(3)
119.8(3)
116.8(2)
S5
N1
N5
C1
C2
C4
C6
C6
C7
C8
C10
C10
C12
C14
C15
C16
C9
C11
C15
C13
C15
C14
S4
S3

Molecules 2011, 16
6132
Table 2. Cont.
atom
S4
N4
atom
C16
C18
C19
C20
C22
C24
C24
C25
C26
atom
N3
angle
124.92(18)
178.8(4)
110.11(16)
117.9(3)
120.9(3)
114.8(2)
120.3(2)
117.12(16)
112.65(17)
atom
S4
S5
C20
C20
C22
N5
S5
S6
N6
atom
C17
C19
C19
C21
C23
C24
C25
C25
C27
atom
C18
C20
C24
C22
C24
C23
S6
angle
112.2(3)
128.9(2)
121.0(3)
121.5(3)
118.4(3)
124.9(2)
117.87(15)
125.00(16)
178.8(3)
C17
C24
C21
C23
C19
C23
N5
S5
C19
C21
N5
C19
S5
N5
C26
S6
C27
Table 3. Bond lengths involving hydrogen’s (Å) for compound 2.
atom
C2
C4
atom distance atom
atom
H3
H5
H8B
H12
H14
H17B
H21
H23
H26B
distance
0.930
0.930
0.970
0.930
0.930
0.970
0.930
0.930
0.970
H2
H4
0.930
0.930
0.970
0.930
0.930
0.970
0.930
0.930
0.970
C3
C5
C8
H8A
H11
H13
H17A
H20
H22
H26A
C8
C11
C13
C17
C20
C22
C26
C12
C14
C17
C21
C23
C26
Knoevenagel condensation of the ethanolic solution of 1-(benzothiazol-2-yl-thio) acetonitrile (2)
with either hetero-2-carbaldehydes 3a–b or benzaldehyde or para-substituted benzaldehydes 3c–e with
an electron-donating group at the para-position, as depicted in Scheme 2. The reactions were carried
out in the presence of a catalytic amount of piperidine at the reflux temperature leading to novel 3-aryl-
2-(benzothiazol-2'-ylthio)acrylonitriles 4a–e (cf. Scheme 2).
Scheme 2. Syntheses of 4.
N
C
S
EtOH/pip
S
S
ArCH2O
+
S
reflux
N
CN
N
3a-e
2
Ar
4a-e
3-4 a : Ar =2-furyl
b: Ar= 2-thienyl
c: Ar = phenyl
d: Ar = p-methoxyphenyl
e: Ar = p-hydroxyphenyl

Molecules 2011, 16
6133
The new 3-aryl-2-(benzothiazol-2'-ylthio)acrylonitrile derivatives 4a–e which were formed are
highly conjugated systems containing heteroaromatic or phenyl rings, or para-substituted phenyl rings
with an electron-donating group in the para- position such as –OCH3 or –OH. One the other hand, all
systems are linked to the benzothiazole nuclei through an S linkage at the α-vinylic carbon. The
formation of a carbon-carbon double bond usually lead to the creation of acrylonitriles with either E or
Z configuration or a mixture of E and Z isomers (cf. Scheme 2). The yields are based on isolated
products and the E/Z ratio was affected by the kind of substitution of the aryl aldehydes 3a–e. The E/Z
1
ratio was determined on the basis of the H-NMR spectra of the products. The structures of isolated
S-alkylated acrylonitrile products 4a–e were confirmed on the basis of elemental analysis and spectral
data. The mass spectrum of 4a revealed a molecular ion peak (M+) with m/z 284. The chemical shifts
of protons for 4a were assigned using the COSY (correlation spectroscopy) measurement which
1
provided the proton-proton couplings. The H-NMR revealed in addition to an aromatic multiplet, a
singlet signal for a vinylic proton (H-3), that appears at δH 8.06 ppm. Moreover, the chemical shifts of
carbons for compound 4a were assigned using HSQC (Heteronuclear Single Quantum Coherence) and
HMBC (Heteronuclear Multiple Bond Coherence) measurements. The 13C-NMR spectrum for 4a is
characterized by two signals at δC 142.2 and δC 91.9 ppm for the carbon-carbon double bond group.
13
13
The C signal of the β carbon at the higher frequency coupled with a proton, while the C signal of
the α-carbon appears at lower frequency (cf. Figure 2).
Figure 2. The complete assignment of H1 and 13C chemical shift for 4a based on the
COSY, HSQC and HMBC experiments.
H
8.0
(
121
.6)
6
7.3
0
(14
8.2
)
(14
2.2
)
3''
(113
.8)
C
4'
'
6.8
4
2''
3
2
S
C
5''
(1
(9
O
1.9
)
(
1
6
4
.6
48.8
)
15
)
8.
N
C
2
'
(1
16.
9)
(
1
5
3
.1
)
S
N
8.0
9
4
'
(
1
3
5
.3
)
(1
22.
1)
7
'
5
'
(
1
2
9
1
4
.9
)
7.4
3
6
'
7
.
(12
5.2
)
(
1
2
6
.
.
8
)
7
5
1
Nuclear Overhauser Effect (NOE) experiments were run to establish the stereo-orientation for
acrylonitrile derivatives 4 as either E or Z isomers. NOE experiments for 4a showed an enhanced
triplet signal (H-4'') at δH 6.84 ppm upon irradiating the doublet signal (H-5'') at δH 8.15 ppm. On
irradiating the doublet signal (H-3”) at δH 7.30 ppm both the triplet signal (H-4”) and the singlet signal
(H-3) at δH 6.84 and 8.06 ppm, respectively, were enhanced, while the benzothiazole protons showed
no effect, confirming that the benzothiazol-2-ylthio moiety and 2'-furyl groups are on opposite sides of
the double bond as required by the E-form. The structure of 4a was unambiguously confirmed by X-ray
crystallography [18] (cf. Figure 3 and Tables 4–6).

Molecules 2011, 16
Figure 3. Perspective view and atom labeling of the X-ray structure of 4a.
6134
Table 4. Bond lengths (Å) for compound 4a.
atom
S1
S2
O1
N1
N2
C1
C3
C5
C8
C10
C12
atom
C1
C7
C10
C6
C14
C6
C4
C6
C14
C11
C13
distance
1.727(3)
1.762(3)
1.381(3)
1.391(4)
1.136(4)
1.403(4)
1.382(6)
1.387(5)
1.438(4)
1.356(4)
1.322(4)
atom
S1
S2
O1
N1
C1
C2
C4
C8
C9
atom distance
C7
C8
1.747(3)
1.770(3)
1.352(4)
1.298(4)
1.406(5)
1.363(5)
1.355(7)
1.349(4)
1.401(4)
1.403(4)
C13
C7
C2
C3
C5
C9
C10
C12
C11
Table 5. Bond lengths involving hydrogen's (Å) for compound 4a.
atom
C2
C4
C9
C12
atom distance atom
atom distance
H2
H4
0.93
0.93
0.93
0.93
C3
C5
H3
H5
0.93
0.93
0.93
0.93
H9
H12
C11
C13
H11
H13
The condensation of 2 with thiophene-2-carbaldehyde (3b) afforded a mixture of (E)- and (Z)-2-
(benzothiazol-2'-ylthio)-3-(2''-thienyl) acrylonitriles in a ratio of 6:0.5 based on the 1H-NMR spectrum,
which revealed, in addition to the expected aromatic signals, two downfield signals at δH 8.52 and
8.70 ppm assignable to the E and Z-vinylic protons. Upon recrystallization of the crude product from a
1
mixture of ethanol and diethyl ether in a ratio of 3:2 one isomer 4b was obtained. The H-NMR
spectrum of the crystallized product showed the vinylic proton resonance at δH 8.52 ppm. In order to
determine the configuration of the obtained isomer, different NMR experiments have been carried out
such as COSY, HSQC and NOE experiments. The NOE experiments showed a strong NOE coupling
between H-3 and (vinylic-H) and the thiophene protons H-3'' and H-4'' and no coupling between the
benzothiazole and the thienyl ring protons, indicating that the benzothiazole and the thienyl rings are
on opposite sides of the double bond, confirming that compound 4b exists in the E-configuration.

Molecules 2011, 16
6135
o
Table 6. Bond angles ( ) for compound 4a.
atom
C1
C10
S1
C2
C2
C4
N1
S1
S2
S2
C8
O1
C10
O1
atom
atom
C7
C13
C2
C6
C4
C6
C5
S2
N1
C14
C10
C11
C12
C12
angle
88.04(14)
106.66(19)
128.6(3)
121.3(3)
119.6(4)
119.9(4)
126.9(3)
121.46(15)
121.0(3)
114.9(2)
129.9(3)
107.9(2)
107.7(3)
111.2(3)
atom
C7
C6
S1
C1
C3
N1
C1
S1
atom
S2
N1
C1
C2
C4
C6
C6
C7
C8
C8
C10
C10
C12
C14
atom
C8
C7
C6
C3
C5
C1
C5
N1
C9
C14
C9
C11
C13
C8
angle
101.83(13)
109.2(3)
110.1(3)
118.6(4)
122.5(4)
115.2(3)
118.0(3)
117.5(3)
120.82(19)
123.9(3)
119.7(3)
132.4(3)
106.6(3)
174.9(3)F
S1
O1
C1
C1
C3
C5
C6
C7
C7
C8
C9
C10
C11
C13
S2
C9
O1
C9
C11
N2
On the other hand, condensation of 2 with either benzaldehyde or para-substituted benzaldehydes
3c–e in refluxing ethanol containing a catalytic amount of piperidine, afforded a mixture of E and Z
1
isomers of 3-aryl-2-(benzothiazol-2'-ylthio) acrylonitriles 3c–e in a ratio of 7:2 based on the H-NMR
1
13
spectra of the crude products. The chemical shifts of the H- and C- spectra were assigned on the
basis of the proton-proton and the carbon-proton coupling patterns observed in the COSY and HSQC
1
spectra. The H-NMR spectra display vinylic proton singlets in the δH 8.12–8.29 ppm region. The
chemical shifts for the carbon-carbon double bond are observed at δC 91–97 and at δC 157–158 ppm
for the α- and β carbon, respectively. Moreover, Nuclear Overhauser Effect (NOE) experiments were
run to establish the stereo-orientation for either the E or Z isomers of 2-(benzothiazol-2'-ylthio)-3-(4''-
methoxyphenyl)acylonitrile 4d. On irradiating the singlet of the vinylic proton at δH 8.17 ppm the
doublet of H-2'' of phenyl ring at δH 8.00 ppm was enhanced. On irradiating the doublet signal of the
phenyl ring H-3'' at δH 7.15 ppm both the doublet of the phenyl ring H-2'' and the para-methoxy group
protons at δH 8.00 and 3.87 ppm, respectively, were enhanced, while the benzothiazole protons showed
no effect, indicating that the benzothiazole and the 4-methoxyphenyl rings are on opposite sides of the
double bond, as required by an E-form.
In a similar manner, the 1-(benzothiazol-2'-ylthio)propan-2-one (5) used in our experiments has
been recently prepared in an excellent yield by treatment of 2-mercaptobenzothiazole (1) with
α-chloroacetone in refluxing acetone containing anhydrous potassium carbonate [15]. The structure of 5
was unambiguously confirmed by X-ray crystallography [19] (cf. Scheme 3, Figure 4 and Tables 7–9).
Condensation of 5 with the furan-2-carbaldehyde in refluxing ethanol containing a catalytic amount
of piperidine afforded 3-(benzothiazol-2'-ylthio)-4-(furan-2''yl)-3-buten-2-one in excellent yield
(cf. Scheme 3). The structure of the isolated product was confirmed on the basis of its elemental
analysis and spectral data (see Experimental section).

Molecules 2011, 16
6136
Synthesis of compound .
Scheme 3.
6
S
SH
N
1
ClCH2OCCH3
K2CO3/acetone ,heat
CH3
3a
O
S
C
N
EtOH/pip
reflux
S
S
S
N
COCH3
O
5
6
Figure 4. Perspective view and atom labeling of the X-ray structure of 5.
Table 7. Bond lengths (Å) for compound 5.
atom
S1
S2
O1
N1
C2
C4
C6
C9
atom
C1
C1
C9
C7
C7
C5
C7
C10
distance
1.758(3)
1.738(3)
1.206(4)
1.392(4)
1.410(4)
1.393(7)
1.389(5)
1.494(5)
atom
S1
S2
N1
C2
C3
C5
C8
atom distance
C2
C8
C1
C3
C4
C6
C9
1.730(4)
1.785(3)
1.289(4)
1.387(5)
1.369(6)
1.371(5)
1.501(4)

Molecules 2011, 16
Table 8. Bond lengths involving hydrogen's (Å) for compound 5.
6137
atom
C3
C5
C8
C10
C10
atom distance
atom
C4
C6
C8
C10
atom distance
H3
H5
0.930
0.930
0.970
0.960
0.960
H4
H6
0.930
0.930
0.970
0.960
H8A
H10A
H10C
H8B
H10B
Table 9. Bond angles (o) for compound 5.
atom
C1
C1
S1
atom
S1
atom
C2
C7
N1
C3
C7
C5
C7
C6
C9
angle
atom atom atom angle
88.71(14)
110.6(3)
116.3(3)
129.9(3)
120.5(3)
120.8(4)
118.8(4)
125.4(3)
116.2(3)
122.3(3)
C1
S1
S2
S1
C2
C4
N1
C2
O1
C8
S2
C1
C1
C2
C3
C5
C7
C7
C9
C9
C8
S2
101.10(14)
116.94(16)
126.8(2)
109.6(3)
118.8(4)
121.3(4)
114.8(3)
119.8(3)
122.8(3)
114.9(3)
N1
C1
C2
C2
C4
C6
C7
C8
C9
N1
C7
C4
C6
C2
C6
C8
C10
S1
C3
C3
C5
N1
S2
O1
C10
The mass spectrum of 6 revealed a molecular ion peak [M+]. with m/z 301 The effect of the
conjugatation of the carbonyl group with the carbon-carbon double bond reduces the frequency of the
absorption at υmax 1662cm−1. It is considered lower than the isolated carbonyl group in compound 5,
which revealed a carbonyl stretching band at υmax 1720 cm−1 [15]. The chemical shift of protons for 6
were assigned using COSY (correlation spectroscopy) measurements which provided the proton-
proton coupling. The 1H-NMR spectrum showed a resonance at δH 8.25 ppm corresponding to H-4 of
the vinylic proton. Moreover, the 13C-NMR chemical shift assignments were straightforward using
13
HSQC (Heteronuclear Quantum Coherence) measurements (cf. Figure 5). The C-NMR spectrum of
the reaction product revealed a low field signal at δC 194.8 that corresponds to the carbonyl carbon.
Also were revealed two low field signals at ca. δC 148 and 136 ppm corresponding to a carbon coupled
with a proton. As in the furan ring system, the carbon resonating at ca. δC 148 ppm corresponds to C-
5'', while the carbon resonating at ca. δC 136 ppm corresponds to the vinylic carbon C-4. The complete
assignment of H1 and 13C chemical shifts for 6 are presented in Figure 6.
Moreover, the configuration of the product 6 was assigned as the Z-isomer based on Nuclear
Overhauser Effect (NOE) experiments; on irradiating the methyl proton at δH 2.54 ppm only the signal
at δH 8.25 ppm for the vinylic proton was enhanced and there is no effect on the benzothiazole protons
or furyl protons, which indicate that acetyl group and the vinylic proton are on the same side of the
carbon 3,4 double bond as numbered, therefore it has the Z configuration. On irradiating the vinylic
H-4 at δH 8.25 ppm both the singlet and doublet signals at δH 2.54 and 7.47 ppm, respectively, were
enhanced. The signal at δH 2.54 ppm corresponds to the acetyl group, while the doublet signal at
δH 7.47 ppm corresponds to the furyl system H-3". On other hand, on irradiating the doublet signal of
the H-4' proton at δH 7.92 ppm only the triplet signal at δH 7.32 ppm was enhanced. These two signals

Molecules 2011, 16
6138
correspond to the benzothiazole H-4' and H-5' protons. On irradiating the triplet signal H-4'' at
δH 6.74 ppm both the H-5'' and H-3'' signals at δH 8.05 and 7.47 ppm, respectively, were enhanced. The
NOE experiments show that the Z-isomer of compound 6 was preferred over the E-isomer indicating
that the furyl and 2-benzothiazol-2-thio nuclei are on the same sides of the double bond, but away from
each other in space.
13C-HSQC spectra for the compound in DMSO-d .
Figure 5.
6
6
Figure 6. The complete assignment of H1 and 13C chemical shifts for 6 based on the COSY
and HSQC experiments.
2.54
(121.3)
7.82
CH3
(194.8)
2
(26.6)
O
(126.4
7.43
7'
(135.8)
8.25
6'
5'
S
H
(123.9)
3
7.32
(124.5)
C
4
(166.3)
(136.0)
C
2'
4'
(Z)
S
7.92
(121.7)
(153.2)
(149.2)
N
7.47
(121.4)
2''
3''
O
4''
5''
8.05
6.74
(113.7)
(148.4)
Thus it can be concluded that Knoevenagel condensation of 2-(benzothiazol-2-ylthio) acetonitrile
with furan-2-carbaldehyde leads preferentially to (E)-2-(benzothiazol-2'-ylthio)-3-(furan-2''-yl)
acrylonitrile (4a). In this conformation the lone pair electrons of the sulfur atom can conjugated with
the π orbital of the double bond, and thereby stabilize the molecule. That is why this conformation is
the most stable conformer. On the other hand, the Knoevenagel condensation of 3-(benzothiazl-2'-
ylthio) propan-2-one with furan-2-carbaldehyde lead preferentially to (Z)-3-(benzothiazol-2'-ylthio)-4-
(furan-2''-yl)-3-buten-2-one. By changing the size and the geometry of the group attached to the
α-carbon from a cyano group to an acetyl group, the conformation changes from E to Z. One may

Molecules 2011, 16
6139
therefore conclude that under these circumstances the most E-isomer is unlikely to be the most stable
conformer, because of the steric strain between the acetyl group and furan ring. The steric strain makes
this conformation energetically highly unfavorable in the E-isomer so the conformer changes from E to Z.
On the other hand, 2-(2'-oxopropylthio)-3-phenylquinazolin-4(3H)-one (9) was readily prepared in
good yield by the treatment of 2-mercapto-3-phenylquinazolin-4(3H)-one (8) [20] with
α-chloroacetone in refluxing acetone containing potassium carbonate. The structure was established on
the basis of its spectral data. The mass spectrum of the reaction product showed a molecular ion peak
1
at m/z 310. The H-NMR spectrum revealed, in addition to aromatic signals, two upfield singlets at
δH 2.33 and 4.06 ppm, assignable to methyl and methylene protons, respectively. Moreover, the
13C-NMR spectrum showed two downfield signals at δC 202.5 and 161.1 ppm. The signal at δC 202.5
ppm corresponds to the ketone carbonyl carbon, while that at δC 161.1 ppm corresponds to the cyclic
amide carbon .The data are therefore consistent with structure 9 (cf. Scheme 4).
Synthesis of and .
10
Scheme 4.
9
O
C
COOH
N
PhNCS
NH2
EtOH/Et3N
reflux
N
SH
7
8
K2CO3,
acetone/reflux
ClCH2COCH3
O
C
O
N
C
N
3a
N
S
N
S
EtOH, pip.
reflux
COCH3
9
COCH3
O
10
Condensation of 2-(2'-oxopropylthio)-3-phenylquinazolin-4(3H)-one (9) with furan-2-carbaldehyde
(3a) afforded a product which could have been either E or Z-isomer of α,β-unsaturated ketone 10
(cf. Scheme 4). The structure of α,β-unsaturated ketone 10 was deduced from its elementanal anaylsis
and spectra data. The mass spectrum revealed a molecular ion peak (M+) with m/z 388. The chemical
shifts of the protons for 10 were assigned using COSY (correlation spectroscopy) measurements which
1
provided the proton-proton coupling. The H-NMR revealed in addition to an aromatic multiplet, a
singlet for a vinylic proton (H-1') which appears at low field at ca. δH 7.88 ppm. Moreover, the
13C-NMR chemical shift assignments were straightforward using HSQC (Heteronuclear Single
13
Quantum Coherence) measurements (cf. Figure 7). The C-NMR spectrum for 10 is characterized by
two signals at δC 132.0 and δC 119.7 ppm for the α,β-unsaturated ketone group. The vinylic carbons at

Molecules 2011, 16
6140
the higher frequency is the one coupled with a proton, while the other one is a disubstituted sp2 carbon.
The complete assignment of H1 and 13C chemical shift for 10 are presented in Figure 8.
13C-HSQC spectra for the compound
in DMSO-d .
10
Figure 7.
6
Figure 8. The complete assignment of H1 and 13C chemical shifts for 10 based on the
COSY and HSQC experiments.
7.46
(126.2)
7.77
(134.6)
7
8.08
(126.6)
6
8
7.42
(126.0)
5
4'
(149.2)
O
(195.5)
2.48
(26.7)
CH3
(125.1)
C
N
3'
(160.7)
4
(119.7)
(155.9)
2
C
(Z)
O
7.88
H
2'
N
S
C
(132.0)
1'
(136.2)
1'''
7.18
2''
6'''
5'''
(118.2)
2'''
3''
4''
7.59-7.67
(129.2,129.7,130.1)
O
5''
6.68
(113.2)
3'''
4'''
7.92
(147.0)
Moreover, the configuration of the product 10 was assigned as the Z-isomer based on Nuclear
Overhauser Effect (NOE) experiments; on irradiating the methyl proton at δH 2.48 ppm the vinylic
proton signal at δH 7.88 ppm was enhanced. There is no effect on the 3-phenylquinazolin-4(3H)-one or
furan protons, which indicates that the acetyl group and the vinylic proton are on the same side of the
C1',2' double bond as numbered, which therefore has Z configuration. On irradiating the vinylic H'-1 at
δH 7.88 ppm the methyl signal at δH 2.48 ppm was enhanced.
On the other hand irradiation of the H-8 proton at δH 8.08 ppm has no effect, confirming that
the 3-phenylquinazolin-4(3H)-one moiety and 2'-furyl groups are on same sides of the double bondas
required by a Z-form. The structure of 10 was also confirmed by X-ray crystallography [21] (cf. Figure 9
and Tables 10–12).

Molecules 2011, 16
Figure 9.
6141
Perspective view and atom labeling of the X-ray structure of
.
10
Table 10. Bond lengths (Å) for compound 10.
atom
S1
O1
O2
N1
N1
N2
C1
C3
atom
C8
C7
C20
C7
C9
C8
C6
C4
C6
C10
C11
C13
C16
C17
C19
C22
distance
1.7609(19)
1.219(3)
1.398(4)
1.402(3)
1.440(3)
1.285(3)
1.397(3)
1.388(4)
1.399(4)
1.378(4)
1.393(5)
1.354(6)
1.354(3)
1.424(3)
1.385(4)
1.499(4)
atom
S1
O2
O3
N1
N2
C1
C2
C4
atom
C15
C17
C21
C8
C1
C2
C3
C5
distance
1.7687(19)
1.350(3)
1.216(3)
1.400(3)
1.389(3)
1.404(3)
1.382(4)
1.365(4)
1.456(3)
1.382(4)
1.374(6)
1.384(5)
1.483(3)
1.345(4)
1.324(5)
C5
C9
C6
C9
C7
C14
C12
C14
C21
C18
C20
C10
C12
C15
C16
C18
C21
C11
C13
C15
C17
C19
Table 11. Bond lengths involving hydrogen's (Å) for compound 10.
atom
C2
C4
C10
C12
C14
C18
C20
C22
atom
H2
H4
H10
H12
H14
H18
H20
H22B
distance atom atom distance
0.930
0.930
0.930
0.930
0.930
0.930
0.930
0.960
C3
C5
H3
H5
0.930
0.930
0.930
0.930
0.930
0.930
0.960
0.960
C11
C13
C16
C19
C22
C22
H11
H13
H16
H19
H22A
H22C

Molecules 2011, 16
6142
o
Table 12. Bond angles ( ) for compound 10.
atom
C8
C7
C8
N2
atom
S1
N1
N1
C1
atom
C15
C8
C9
C2
angle
atom
C17
C7
C1
N2
C1
atom
O2
N1
N2
C1
atom
C20
C9
C8
C6
angle
106.1(2)
118.33(15)
117.26(15)
122.50(16)
119.7(2)
100.89(9)
121.46(16)
120.21(15)
118.64(16)
118.86(17)
120.9(3)
C2
C2
C1
C3
C6
C4
C2
C4
C3
C5
C3
119.9(3)
C4
C1
O1
N1
S1
N1
C10
C10
C12
S1
C16
O2
C16
C18
O3
C5
C6
C7
C7
C8
C9
C9
C11
C13
C15
C15
C17
C17
C19
C21
C21
C6
C7
N1
C6
120.3(3)
119.83(17)
120.0(2)
114.04(16)
122.04(14)
119.6(2)
121.5(3)
119.7(3)
120.5(3)
121.83(16)
122.06(18)
125.4(2)
125.1(2)
107.6(3)
C1
C5
C6
C6
C7
C8
C8
C9
C10
C12
C14
C15
C16
C17
C18
C20
C21
C5
C7
C6
N1
120.22(19)
119.91(18)
125.9(2)
113.15(13)
124.81(17)
118.9(2)
118.6(3)
121.2(4)
118.6(3)
116.04(14)
131.01(19)
109.4(2)
107.8(3)
109.1(3)
O1
S1
N1
N1
C9
C11
C9
S1
C15
O2
C17
O2
O3
N2
N2
C10
C14
C12
C14
C16
C21
C16
C18
C20
C15
C22
C14
C11
C13
C13
C21
C17
C18
C19
C19
C22
120.5(2)
119.8(2)
119.7(3)
C15
In particular, we were interested in the reasons for the predominance of the s-cis conformation of
the Z configuration and the E/Z determination of the prepared novel derivatives of 2-(benzothiazol-2'-
ylthio)-3-arylacrylonitrile, 3-(benzothiazol-2'-ylthio)-4-(furan-2''-yl)-3-buten-2-one and 2-(1-(furan-2''-yl)-
3-oxobut-1-en-2-ylthio)3-phenylquinazolin-4(3H)-one in accordance with expectations, it was
ascertained that s-trans conformations were more stable than s-cis conformations for both the E and Z
molecular configurations. Thus the disparity displayed here where s-cis conformations in case of
compound 6 dominated over the s-trans conformation was of interest and one supposition was that
electronic interactions could be responsible, e.g., by delocalization of a sulfur lone electron pair with
the unsaturated segments residing in the newly formed heterocyclic ring and attendant side-chains or
through hyperconjugation. The s-cis conformational preference over s-trans in a structurally similar
system has been reported previously [22] and an electronic cause was also postulated, though that
system differed significantly in the distribution of unsaturation. It is obvious to note that compounds
4c–e are predominantly in the E/Z form and this is due to the large range of mesomeric effects due to
large conjugations in the phenyl group present in such compounds. However, the existence of
compounds 4a and 4b in the E form is due to the existence of the heterocyclic, furan and thiophene
rings, respectively, where less conjugation occurs in such compounds.

Molecules 2011, 16
6143
3. Experimental
General
Melting points are reported uncorrected and were determined on a Gallenkamp apparatus. The
1
Infrared spectra were recorded on a Jasco FT/IR-6300 FT-IR using KBr disks. H-NMR and
13C-NMR spectra were measured on a Bruker DPX 400 MHz and Bruker AVANCE ΙΙ 600 MHz
spectrometers, with DMSO-d6 or CDCl3 as solvent using TMS as an internal standard. The methods
used for the purpose of NMR assignment were COSY, HSQC and HMBC. The chemical shifts are
expressed as δ unit in parts per million (ppm) and TMS = 0.00 ppm. The following abbreviation are
used: s = singlet, d = doublet, t = triplet; q = quartet; m = multiple; br. = broad. Mass spectra were
measured on GC/MS DFS, THERMO instrument. Microanalyses were performed on a CHNS-Vario
Micro Cube analyzer, Single crystal X-ray crystallography was perfomed using a Rigaku Rapid ΙΙ
located at the Chemistry Department of Kuwait University. Compound 5 was prepared according to
our recent reference [15] and its X-ray data was reported in reference [19].
2-(Benzothiazol-2-ylthio) acetonitrile (2): A mixture of 1 (1.67 g, 10.0 mmol), chloroacetonitrile (0.63 g,
10.0 mmol), and anhydrous potassium carbonate (1.38 g, 10.0 mmol) in acetone (100 mL), were
heated in water bath for 2 h. The solvent was then evaporated under reduced pressure. The solid
product, so formed, was collected by filtration and crystallized from ethanol as brown crystals. Yield:
1.85 g (90%), mp. 70–72 °C; FT-IR: νmax/cm−1: 2243 (CN); 1H-NMR (DMSO-d6): δH 4.58 (s, 2H, CH2),
7.43 (t, 1H, J = 8.0 Hz, H-5'), 7.52 (t, 1H, J = 8.0 Hz , H-6'), 7.95 (d, 1H, J = 8.0 Hz, H-7'), 8.08 (d,
1H, J = 8.0 Hz, H-4'); 13C-NMR (DMSO-d6): δC 163.8 (C-2'), 152.7 (C-3a'), 135.6 (C-7a'), 127.1 (C-6'),
125.5 (C-5'), 122.6 (C-4'), 122.0 (C-7'), 117.9 (CN), 18.6 (CH2) ppm; MS m/z (%) 206 [M+, 100%].
Anal. Calcd. for C9H6N2S2 (206.28): C, 52.40; H, 2.93; N, 13.57%. Found: C, 52.29; H, 3.19; N,
13.45%.
General Procedure for Synthesis of 3-Aryl-2-(benzothiazol-2'-ylthio) acrylonitriles 4a–e. A mixture of
2 (2.06 g, 10.0 mmol) and aromatic aldehydes 3a–e (10.0 mmol) in ethanol (20 mL) containing a few
drops of piperidine was refluxed for 4 h. The reaction was allowed to cool to room temperature for 24 h.
The solid product so formed was collected by filtration and crystallized from the appropriate solvent.
(E)-2-(Benzothiazol-2'-ylthio)-3-(furan-2''-yl) acrylonitrile (4a): This compound was crystallized from
ethanol as brown crystals. Yield: 2.24g (79%) yield, mp. 134–136 °C; FT-IR: νmax/cm−1: 2209 (CN);
1H-NMR (DMSO-d6): 6.84 (dd, 1H, J = 3.6 & 1.2 Hz, H-4''), 7.30 (d, 1H, J = 3.6 Hz, H-3''), 7.43 (t,
J = 8.2 Hz, H-5'), 7.51 (t, 1H, J = 8.0 Hz, H-6'), 7.94 (d, 1H, J = 8.2 Hz, H-7'), 8.06 (s, 1H, H-3), 8.07 (d,
13
1H, J = 8.0 Hz, H-4'), 8.15 (d, 1H, J = 1.2 Hz, H-5''); C-NMR (DMSO-d6): δC 164.6 (C-2'), 153.1
(3a'), 148.8 (C-5"), 148.2 (C-2''), 142.2 (C-3), 135.3 (C-7a'), 126.8 (C-6'), 125.2 (C-5'), 122.1 (C-4'),
121.9 (C-7'), 121.6 (C-3''), 116.9 (CN), 113.8 (C-4''), 91.9 (C-2) ppm. MS m/z (%) 284 [M+, 18%].
Anal. Calcd. for C14H8N2OS2 (284.36): C, 59.13; H, 2.84; N, 9.85; S, 22.55%. Found: C, 58.95; H,
2.81; N, 10.07; S, 22.56%.

Molecules 2011, 16
6144
(E)-2-(Benzothiazol-2'-ylthio)-3-(thiophen-2''-yl) acrylonitrile (4b). This compound was crystallized
from a 3:2 mixture of ethanol/diethyl ether as yellow crystals. Yield: 2.4 g (88%), mp. 98–100 °C;
FT-IR: νmax/cm−1: 2210 (CN); H-NMR (DMSO-d6): δH 7.35 (dd, 1H, J = 4.8 & 3.5 Hz, H-4''),
1
7.43 (t, 1H, J = 7.6 Hz, H-5'), 7.52 (t, 1H, J = 7.6 Hz, H-6'), 7.89 (d, 1H, J = 3.5 Hz, H-3''), 7.95 (d,
1H, J = 8.0 Hz, H-7'), 8.09 (d, 1H, J = 8.0 Hz, H-4'), 8.14 (d, 1H, J = 4.8 Hz, H-5''), 8.52 ppm (s, 1H,
13
H-3); C-NMR (DMSO-d6): δC 164.8 (C-2'), 153.2 (C-3a'), 150.4 (C-3), 137.5 (C-3''), 135.9 (C-2''),
135.3 (C-7a'), 135.1 (C-5''), 128.6 (C-4''), 126.8 (C-6'), 125.2 (C-5'), 122.1 (C-4'), 121.9 (C-7'), 117.1
(CN), 92.3 (C-3) ppm; MS m/z (%) 300 [M+, 14%]. Anal. Calcd. for C14H8N2S3 (300.42): C, 55.97; H,
2.68; N, 9.32; S, 32.01%. Found: C, 56.04; H, 2.52; N, 9.54; S, 32.08%.
(E)-2-(Benzothiazol-2'-ylthio)-3-phenyl acrylonitrile (4c). This compound was crystallized from a 2:1
mixture of ethanol/diethyl ether as yellow crystals. Yield: 2.08 g (71%) , mp. 103–105 °C;
FT-IR: νmax/cm−1: 2206 (CN); H-NMR (DMSO-d6): δH 7.38 (t, 1H, J = 7.8 Hz, H-5'), 7.49 (t, 1H,
1
J = 8.4 Hz, H-6' ), 7.58–7.63 (m, 3H, H-3'', H-4'' & H-5''), 7.96 (d, 1H, J = 8.4 Hz, H-7), 7.97 (d, 2H,
J = 8.4 Hz, H-2''& H-6''), 8.10 (d, 1H, J = 8.0 Hz, H-4'), 8.29 ppm (s, 1H vinylic-H); 13C-NMR
(DMSO-d6): δC 163.7 (C-2'), 157.0 (C-3), 153.1 (C-3a'),135.4 (C-7a'), 132.6 (C-4''), 130.8 (C-1''),
129.5 (C-2'' & C-6''), 128.9 (C-3'' & C-5''),126.8 (C-6'),125.5 (C-5'), 122.2 (C-4'), 122.0 (C-7'), 116.8
(CN), 97.5 (C-2) ppm. MS m/z (%) 294 [M+, 83%]. Anal. Calcd. for C16H10N2S2, (294.39) requires: C,
65.28 ; H, 3.42; N, 9.52; S, 21.78%. Found: C, 64.98; H, 3.25; N, 9.73; S, 22.03%.
(E)-2-(Benzothiazol-2'-ylthio)-3-(4''-methoxyphenyl) acrylonitrile (4d). This compound was
crystallized from ethanol as brown crystals. Yield: 2.62 g (81%), mp. 95–97 °C. FT-IR: νmax/cm−1: 2202
(CN); 1H-NMR (DMSO-d6): δH 3.87 (s, 3H, OCH3), 7.15 (d, 2H, J = 9.0 Hz, H-3'' & H-5''), 7.42 (t,1H,
J = 7.8 Hz, H-5'), 7.51 (t, 1H, J = 7.8 Hz, H-6'), 7.94 (d, 1H, J = 7.8 Hz, H-7'), 8.00 (d, 2H, J = 8.4 Hz,
H-2’’ & H-6’’), 8.06 (d, 1H, J = 7.8 Hz, H-4'), 8.17 ppm (s, 1H, H-3); 13C-NMR (DMSO-d6): δC 165.0
(C-2'), 162.9 (C-4''), 157.3 (C-3), 153.3 (C-3a'), 135.3 (C-7a'), 132.1 (C-2'', C-6"), 126.7 (C-6'), 125.1
(C-5'), 124.9 (C-1''), 122.1 (C-4'), 121.9 (C-7'), 117.5 (CN), 114.8 (C-3'' & C-5"), 92.8 (C-2), 55.7
(OCH3) ppm; MS m/z (%) 324 [M+, 20% ]. Anal. Calcd. for C17H12N2OS2 (324.42): C, 62.94; H, 3.73;
N, 8.63; S, 19.76%. Found: C, 63.06; H, 3.63; N, 8.87; S, 20.06%.
(E)-2-(Benzothiazol-2'-ylthio)-3-(4''-hydroxyphenyl) acrylonitrile (4e). This compound was
crystallized from a 2:1 mixture of ethanol/diethyl ether as yellow crystals. Yield: 2.32 (75%), mp.
1
113–114 °C ; FT-IR: νmax/cm−1: 3417 (OH), 2200 (CN); H-NMR (DMSO-d6): δH 6.97 (d, 2H,
J = 8.4 Hz, H-3'' & H-5''), 7.39 (t, 1H, J = 8.4 Hz, H-5'), 7.50 (t, 1H, J = 8.4 Hz, H-6'), 7.91 (d, 2H,
J = 8.4 Hz, H-2’’ & H-6’’), 7.93 (d, 1H, J = 8.4, Hz, H-7'), 8.06 (d, 1H, J = 8.4 Hz, H-4'), 8.12 (s,1H, H-
3), 9.05 (bs., 1H ,OH, D2O exchangeable); 13C-NMR (DMSO-d6): δC 165.6 (C-2'), 162.2 (C-4''), 158.0 (C-
3), 153.3 (C-3a'), 135.2 (C-7a'), 132.5 (C-2'' & C-6''), 126.7 (C-6'), 125.0 (C-5'), 123.0 (C-1''), 122.1
(C-4'), 121.8 (C-7'), 117.8 (CN), 116.3 (C-3'' & C-5''), 91.2 (C-2) ppm; MS m/z (%) 310 [M+, 44%].
Anal. Calcd. for C16H10N2OS2 (310.39): C, 61.91; H, 3.25 ; N, 9.03; S, 20.66%. Found: C, 61.63; H,
3.40; N, 9.27; S, 20.92%.
(Z)-3-(Benzothiazol-2'-ylthio)-4-(furan-2''-yl)-3-buten-2-one (6): A mixture of 5 (2.33 g, 10.0 mmol)
and furan-2-carbaldehyde 3a (10.0 mmol) in ethanol (20 mL) containing a few drops of piperidine was

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refluxed to 4 h. The reaction was allowed to cool to room temperature for 24 h. The solid product so
formed was collected by filtration and crystallized from the ethanol as yellow crystals. Yield: 2.16 g
(72%) yield, mp. 85–87 °C ; FT-IR: νmax/cm−1: 1662 (CO); H-NMR (DMSO-d6): 2.54 (s, 3H, CH3),
1
6.74 (dd, 1H, J = 3.6 & 1.2 Hz, H-4''), 7.32 (t, 1H, J = 8.0 Hz, H-5'), 7.43 (t, 1H, J = 8.0 Hz,
H-6'), 7.47 (d, 1H, J = 3.6 Hz, H-3''), 7.82 (d, 1H, J = 8.0 Hz, H-7'), 7.92 (d, 1H, J = 8.0 Hz, H-4'),
8.05 (d, 1H, J = 1.6 Hz, H-5''), 8.25 (s, 1H, H-4); 13C-NMR (DMSO-d6): δC 194.8 (C-2), 166.3
(C-2'), 153.2 (C-3a'), 149.2 (C-2''), 148.4 (C-5''), 136.0 (C-4), 135.8 (C-7a'),126.4 (C-6'), 124.5 (C-5'),
123.9 (C-3), 121.7 (C-4'), 121.4 (C-3''), 121.3 (C-7') ,113.7 (C-4''), 26.6 (CH3) ppm; MS m/z (%) 301
[M+, 30%]. Anal. Calcd. for C15H11NO2S2 (301.38): C, 59.78; H, 3.67; N, 4.64%. Found: C, 59.41; H,
3.68; N, 4.80%.
3-(2'-Oxopropylthio)-3-phenylquinazolin-4(3H)-one (9): A mixture 8 (2.54 g, 10.0 mmol), chloro-
acetone (0.79 g, 10.0 mmol), and anhydrous potassium carbonate (1.38 g, 10.0 mmol) in acetone
(100 mL) were heated in water bath for 2 h. The solvent was then evaporated under reduced pressure.
The solid product, so formed, was collected by filtration and crystallized from ethanol as yellow
crystals. Yield: 2.4 g (79%), mp. 140–142 °C. FT-IR: νmax/cm−1: 1725 (CO ketone), 1683 (CO amide);
1H-NMR (DMSO-d6): δH 2.33 (s, 3H, CH3) ,4.06 (s, 2H, CH2), 7.29 (d, 1Hz, J = 7.6 Hz, H-5), 7.35 (t,
1H, J = 7.6 Hz, H-7), 7.63–7.41 (m, 5H, phenyl–H), 7.81 (t, 1H, J = 8.0 Hz, H-6), 8.08 (d, 1H,
J = 7.6Hz, H-8); 13C-NMR (DMSO-d6): δC 202.5 (C-2'), 161.1 (C-4), 157.3 (C-2), 147.5 (C-8a), 136.4
(C-6), 135.4 (C-1''), 130.4, 129.8, 129.5 (phenyl carbons), 127.1 (C-8), 126.5 (C-7), 126.4 (C-5), 123.9
(C-4a), 42.6 (C-1'), 28.7 (CH3) ppm; MS m/z (%) 310 [M+, 12%]. Anal. Calcd. for C17H14N2O2S
(310.37): C, 65.79, H, 4.55, N, 9.03%. Found: C, 65.65, H, 4.30, N, 9.06%.
(Z)-2-(1'-(Furan-2''-yl)-3'-oxobut-1''-en-2-ylthio)-3-phenylquinazolin-4(3H)-one (10): A mixture of 9
(3.10 g, 10 mmol) and 3a (0.83 g, 10 mmol) in ethanol (20 mL) containing a few drops of piperidine
was refluxed for 4 h. The reaction was allowed to cool to room temperature for 24 h. The solid product
so formed was collected by filtration and crystallized from ethanol as brown crystals. Yield: 2.83 g
(73%) yield, mp. 190–192 °C; FT-IR: νmax/cm−1: 1675 (CO ketone), 1610 (CO amide); H-NMR
1
(DMSO-d6): 2.48 (s, 3H, CH3), 6.68 (dd, 1H, J = 3.6 Hz & 1.8 Hz, H-4''), 7.18 (d, 1H, J = 3.6 Hz, H-3''),
7.42 (d, 1H, J = 8.0 Hz, H-5), 7.46 (t, 1H, J = 8.0 Hz, H-7), 7.67–7.59 (m, 5H, phenyl–H),7.77 (t, 1H,
J = 8.0 Hz, H-6), 7.88 (s, 1H, H-1'), 7.92 (d, 1H, J = 1.8 Hz, H-5''), 8.08 (d, 1H, J = 8.0 Hz, H-8) ppm;
13C-NMR (DMSO-d6): δC 195.5 (C-3'), 160.7 (C-4), 155.9 (C-2), 149.2 (C-8a), 147.0 (C-5''), 146.8 (C-2''),
136.2 (C-1'''), 134.9 (C-6), 132.0 (C-1', vinylic–H), 130.1, 129.7, 129.2 (phenyl carbons), 126.6 (C-8),
126.2 (C-7), 126.0 (C-5), 125.1 (C-4a), 119.7 (C-2'), 118.2 (C-3''), 113.2 (C-4''), 26.7 (CH3) ppm;
MS m/z (%) 388 [M+, 82]. Anal. Calcd. for C22H16N2O3S( 388.44): C, 68.02; H, 4.15; N, 7.21; S,
8.25%. Found: C, 67.78; H, 4.26; N, 7.16, S, 8.32%.
4. Conclusions
Knoevenagel condensation of 2-(benzothiazol-2'-ylthio) acrylonitrile (2) with aromatic
benzaldehydes 3a–e leads preferentially to E-isomers. The 3-aryl-2-(benzothiazol-2'-ylthio)
acrylonitriles 4a–e were characterized by spectroscopic measurements. Condensation of furan-2-
carbaldehyde with either 1-(benzothiazol-2'-ylthio)propan-2-one or with 2-(2'-oxopropylthio)-3-

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phenylquinazolin-4(3H)-one afforded compounds 6 and 10 respectively. The condensation products 6
and 10 were characterized by spectroscopic measurements and were shown to be the Z-isomers.
Acknowledgements
This work was financed by the University of Kuwait research grant SC02/08 .We are grateful to the
Faculty of Science, Chemistry Department, SAF facility for the spectral and analytical data (Project
GS01/01, GS03/08, GS01/03).
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