Heteroaromatization with sulfonamido phenyl ethanone, part II: Synthesis of novel thiazolyl acetonitriles and thiazolyl acrylonitriles and their derivatives containing dimethylsulfonamide moiety

Article abstract of DOI:10.1080/10426500802176523

Thiazolyl acetonitrile (2) was prepared and converted to pyrazolo[5,1-c][1,2,4]triazine (5), thiazoline-4-one derivatives (10,12), thiazolo[3,2-a]pyridine (13), coumarin (14), and benzo[f]coumarin (16) derivatives through reactions with a variety of organ

Full text of DOI:10.1080/10426500802176523

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Heteroaromatization with
Sulfonamido Phenyl Ethanone,
Part II: Synthesis of Novel
Thiazolyl Acetonitriles and
Thiazolyl Acrylonitriles and
Their Derivatives Containing
Dimethylsulfonamide Moiety
Saber M. Hassan a , Mahmoud M. Abdel Aal a , Ahmed
A. El-Maghraby a & Mahmoud S. Bashandy a
a Chemistry Department, Faculty of Science, Al-
Azhar University, Nasr City, Cairo, Egypt
Version of record first published: 04 Feb 2009
To cite this article: Saber M. Hassan, Mahmoud M. Abdel Aal, Ahmed A. El-
Maghraby & Mahmoud S. Bashandy (2009): Heteroaromatization with Sulfonamido
Phenyl Ethanone, Part II: Synthesis of Novel Thiazolyl Acetonitriles and Thiazolyl
Acrylonitriles and Their Derivatives Containing Dimethylsulfonamide Moiety,
Phosphorus, Sulfur, and Silicon and the Related Elements, 184:2, 427-452
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Phosphorus, Sulfur, and Silicon, 184:427–452, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802176523
Heteroaromatization with Sulfonamido Phenyl Ethanone,
Part II: Synthesis of Novel Thiazolyl Acetonitriles and
Thiazolyl Acrylonitriles and Their Derivatives Containing
Dimethylsulfonamide Moiety
Saber M. Hassan, Mahmoud M. Abdel Aal, Ahmed A.
El-Maghraby, and Mahmoud S. Bashandy
Chemistry Department, Faculty of Science, Al-Azhar University, Nasr
City, Cairo, Egypt
Thiazolyl acetonitrile (2) was prepared and converted to pyrazolo[5,1-
c][1,2,4]triazine (5), thiazoline-4-one derivatives (10,12), thiazolo[3,2-a]pyridine
(13), coumarin (14), and benzo[f]coumarin (16) derivatives through reactions
with a variety of organic electrophiles and nucleophiles. Thiazolyl acrylonitrile
derivatives (17, 18, 21, 26–28, 31–33) were also prepared, and their activity with
a variety of reagents was investigated. The structure of these compounds was
elucidated on the basis of elemental analysis, IR, 1 H-NMR, and mass spectra.
The antimicrobial and antifungal activities of the prepared compounds are also
reported.
Keywords N,N-Dimethylbenzenesulfonamide; pyrazolo-[5,1-c][1,2,4]triazine; thiazo
line-4-one; thiazolo[3,2-a]pyridine; thiazolyl acetonitrile; thiazolyl acrylonitrile
INTRODUCTION
Thiazole derivatives have attracted a great deal of interest owing to
their antibacterial,1 antifungal,2 antiinflammatory,3 and antiviral4–6
activities. They are also useful as antiallergic,7 anthelmintic8 agents
and as sedative hypnotics.9 In addition to being used in the pharmaceu-
tical industry, thiazoles also find a wide application in the dye10 and
photographic industry.10 Sulfonamides also have a variety of biologi-
cal activities such as antibacterial,11 insulin releasing,12 carbonic an-
hydrase inhibitory,13,14 anti-flammatory,15 and antitumor activities.16
Thus, the present investigation deals with the synthesis of some new
Received 19 February 2008; accepted 2 May 2008.
Address correspondence to Mahmoud M. Abdel Aal, Chemistry Department, Faculty
of Science, Al-Azhar University, Nasr City, Cairo, Egypt. E-mail: abdelall sci@yahoo.com
427

428
S. M. Hassan et al.
thiazoles containing a sulfonamide moiety using 4-(2-bromo acetyl)-
N,N-dimethylbenzenesulfonamide (1)17 as starting material (Table I).
RESULTS AND DISCUSSION
When 4-(2-bromoacetyl)-N,N-dimethylbenzenesulfonamide (1) was
treated with 2-cyanothioacetamide in refluxing ethanol, the reaction
afforded a single product identified as 4-(2-cyanomethylthiazol-4-yl)-
N,N-dimethylbenzenesulfonamide (2) on the basis of its spectral data.
The methylene group in thiazolyl acetonitrile derivative (2) proved
to be highly reactive. Thus, compound (2) underwent coupling with
an equimolar amount of p-tolyl diazonium chloride in ethanol solution
containing sodium acetate, at 0∼5◦C, to afford a colored product for
which two isomeric structures (3) or (4) seemed possible. However the
appearance of (CN and NH) absorption bands at 2216 and 3190 cm−1
,
respectively in the IR spectrum of the isolated product, the lack of
the signal due to methylene protons, and the appearance of the signal
due to the H-thiazole at 7.7 ppm. in the 1H-NMR spectrum provided a
firm support for structure (3) and ruled out the other possible isomer
(4). The structure (3) was also obtained via direct reaction of (1) with
2-cyano-2-p-tolylazo thioacetamide.
In the same manner, thiazolyl acetonitrile (2) couples with 4-
cyano-3-methylthio-1H-pyrazole-5-diazonium chloride to afford the
pyrazolo[5,1-c][1,2,4]triazine derivative (5) in moderate yields. The lat-
ter structure was established on the basis of its elemental analysis and
spectral data (Scheme 1).
In contrast to their behavior, it has been found that a buffered solu-
tion of 1H-[1,2,4]-triazol-3-yl diazonium chloride couples smoothly, and
in high yield, with compound (2) to afford a product for which two iso-
meric structures (6) or (7) seemed possible. However, the appearance of
(CN and NH) absorption bands at 2220 and 3418 cm−1, respectively, in
the IR spectrum of the isolated product and the absence of any signals
corresponding to (NH2) group provided a firm support for structure (6)
and ruled out the other possible isomer (7) (Scheme 1).
Formation of compounds (8a–c) is assumed to take place via the
condensation of the active methylene group in (2) with aromatic alde-
hydes, namely benzaldehyde, p-chloro, and p-methoxy benzaldehyde,
respectively. The structure of compounds (8a–c) was established on the
basis of their elemental analysis and spectral data. A final evidence for
the proposed structures comes from synthesizing compounds (8a–c)
via reaction of phenacyl bromide derivative (1) with 2-cyano-3-aryl
thioacrylamide (a–c) to afford products identical in all aspects (m.p.,

Heteroaromatization with Sulfonamido Phenyl Ethanone, Part II
429
TABLE I Physical and Analytical Data for the Newly Prepared
Compounds
M.p.◦C
Calculated/Found (%)
(Solvent of
Comp. recrystallization) (Yield%)
Color
M. formula
(M. Wt.)
C
H
N
O
S
2
120
(Et.)
150
(Et./B.)
235
(Et./B.)
233
(Et./B.)
227
(Et.)
192
(Et.)
160
(Et.)
210
(Et./B.)
217
(Et./B.)
230
(Et./B.)
240
(Et./B.)
270
(Et./B.)
260
(Et./B.)
300
(DMF)
190
(B.)
250
Yellow
(60)
Yellow
(78)
Brown
(79)
White
(80)
White
(70)
Brown
(72)
Brown
(80)
Black
(70)
Black
(82)
Yellow
(80)
White
(89)
White
(92)
Orange
(80)
White
(79)
White
(70)
White
(75)
C13H13N3O2S2
(307)
50.79 4.26 13.67 10.41 20.86
50.77 4.25 13.64 10.38 20.82
56.45 4.50 16.46 7.52 15.07
56.42 4.47 16.44 7.50 14.97
45.75 3.41 23.71 6.77 20.36
45.73 3.38 23.68 6.74 20.33
44.77 3.51 27.84 7.95 15.93
44.74 3.48 27.82 7.92 15.90
60.74 4.33 10.62 8.09 16.22
60.71 4.30 10.60 7.99 16.20
3
C
C
C
C
20H19N5O2S2
(425)
18H16N8O2S3
(472)
15H14N8O2S2
(402)
20H17N3O2S2
(395)
5
6
8a
8b
8c
9
C
20H16ClN3O2S2 55.87 3.75 9.77
7.44 14.92
7.42 14.90
(429)
21H19N3O3S2
(425)
55.85 3.72 9.74
C
59.27 4.50 9.87 11.28 15.07
59.24 4.49 9.85 11.25 14.99
45.73 4.43 12.31 9.37 28.17
45.70 4.40 12.29 9.35 28.15
48.34 4.82 10.57 12.07 24.20
48.32 4.80 10.55 11.97 24.18
55.90 4.89 8.15 12.41 18.65
55.88 4.87 8.13 12.40 18.63
50.33 3.52 16.30 7.45 22.39
50.31 3.50 16.27 7.43 22.37
58.24 3.91 6.79 15.52 15.55
58.22 3.88 6.77 15.50 15.53
62.45 4.15 9.10 10.40 13.89
62.43 4.13 9.08 10.35 13.87
62.32 3.92 6.06 13.84 13.86
62.30 3.90 6.04 13.82 13.84
52.87 4.71 11.56 13.21 17.64
52.85 4.70 11.54 13.20 17.62
53.02 5.01 15.46 8.83 17.69
52.99 4.98 15.44 8.81 17.67
47.87 3.77 24.42 7.97 15.97
47.85 3.74 24.40 7.95 15.94
48.39 3.63 20.79 6.79 20.40
48.35 3.60 20.77 6.77 20.38
48.12 4.33 20.04 9.16 18.35
48.10 4.30 20.00 9.13 18.31
47.99 4.03 15.99 13.70 18.30
47.97 4.00 15.97 13.67 18.28
47.86 4.28 22.32 8.50 17.04
47.85 4.24 22.30 8.48 17.00
58.21 3.82 17.71 6.74 13.51
58.20 3.80 17.70 6.72 13.50
C
C
C
C
C
C
C
C
C
C
C
C
C
C
C
13H15N3O2S3
(341)
16H19N3O3S3
(397)
24H25N3O4S3
(515)
18H15N5O2S3
(429)
20H16N2O4S2
(412)
24H19N3O3S2
(461)
24H18N2O4S2
(462)
16H17N3O3S2
(363)
16H18N4O2S2
(362)
16H15N7O2S2
(401)
19H17N7O2S3
(471)
14H15N5O2S2
(349)
14H14N4O3S2
(350)
15H16N6O2S2
(376)
23H18N6O2S2
(474)
10
12
13
14
15
16
17
18
19
20
21
23
24
25
(Et./B.)
298
(D.)
300
(D.)
220
(Et.)
315
(Et./B.)
215
(Et./B.)
320
White
(82)
Brown
(72)
Brown
(69)
Yellow
(80)
White
(78)
White
(89)
(DMF)
(Continued on next page)

430
S. M. Hassan et al.
TABLE I Physical and Analytical Data for the Newly Prepared
Compounds (Continued)
M.p.◦C
Calculated/Found (%)
(Solvent of
Comp. recrystallization) (Yield%)
Color
M. formula
(M. Wt.)
C
H
N
O
S
26
275
(Et./B.)
210
(Et.)
330
(Et./B.)
350
(DMF)
160
(Et.)
130
(Et.)
140
(Et.)
170
(Et./B.)
310
(Et./B.)
320
(Et./B.)
265
(Et./B.)
250
Yellow
(80)
Orange
(75)
White
(70)
Yellow
(75)
Yellow
(85)
White
(80)
White
(85)
Brown
(80)
White
(89)
Yellow
(79)
Orange
(70)
Yellow
(89)
C21H20N4O2S3 55.24 4.41 12.27 7.01 21.07
(456) 55.21 4.40 12.25 7.00 21.02
24H24N4O4S3 54.53 4.58 10.60 12.11 18.20
(528) 54.51 4.55 10.57 12.09 18.18
26H23N5O2S2 62.25 4.62 13.96 6.38 12.78
(501) 62.22 4.60 13.93 6.34 12.74
22H18N4O3S3 54.75 3.76 11.61 9.95 19.93
(482) 54.73 3.73 11.60 9.91 19.90
20H18N4O2S3 54.28 4.10 12.66 7.23 21.74
(442) 54.25 4.08 12.64 7.20 21.71
14H13N3O2S4 43.84 3.42 10.96 8.34 33.44
(383) 43.81 3.40 10.94 8.32 33.42
16H17N3O2S4 46.69 4.16 10.21 7.77 31.16
(411) 46.67 4.14 10.20 7.75 31.14
20H16N4O2S3 54.52 3.66 12.72 7.26 21.83
(440) 54.50 4.73 12.70 7.24 21.80
20H16N4O3S2 56.59 3.80 13.20 11.31 15.11
(424) 56.57 3.78 13.18 11.30 15.10
20H17N5O2S2 56.72 4.05 16.54 7.56 15.14
(423) 56.70 4.02 16.52 7.54 15.11
17H19N5O2S2 52.42 4.92 17.98 8.22 16.46
(389) 52.40 4.90 17.95 8.20 16.43
17H19N5O2S2 52.42 4.92 17.98 8.22 16.46
(389) 52.39 4.91 17.97 8.19 16.45
27
C
C
C
C
C
C
C
C
C
C
C
28
29
31
32
33
34a
34b
34c
35a
35b
(Et./B.)
B., benzene; D., dioxane; DMF, dimethylformamide; Et., ethanol.
TLC, IR, and mass spectra) with those obtained previously from the
reaction of compound (2) with aromatic aldehydes as described before
(Scheme 1).
Compound (2) was treated with H2S gas in ethanol containing
triethylamine as a catalyst at room temperature to afford 2-[4-(4-
dimethylsulfamoylphenyl)thiazol-2-yl]thioacetamide (9), which upon
treatment with ethyl chloroacetate in refluxing ethanol contains fused
sodium acetate afforded thiazolinone derivative (10). The latter com-
pound was also obtained via direct reaction of thiazolyl acetonitrile (2)
with mercapto acetic acid in pyridine.
Efforts to cyclize (10) with p-methoxybenzylidine malononitrile to af-
ford enaminonitriles (11) were not successful; instead the product was
identified as 4-2-[5-(4-methoxy benzylidene)-4-oxo-4,5-dihydro thiazol-

Heteroaromatization with Sulfonamido Phenyl Ethanone, Part II
431
CN
O
C
CN
N
N
X
CH
CSNH2
Ar
CH2Br
CSNH2
(1)
Ar
N
CH2CSNH2
CN
S
N
H
N
Ar
Ar
C
X
CHO
N
N
Cl
NC
X
N
S
N
S
(3)
CH2CN
a; X=H
b; X=Cl
c; X=OCH3
CN
Ar
N
N
(2)
(8 a,b,c)
N
S
CN
CH2CN
(4)
HN
N
Ar
N=N
HN
N
N
N
CN
N=N Cl
H3CS
(6)
NH2
N
NH2
N
N
N=N Cl
Ar
N
SCH3
Ar
N
H
N
N
N
N
N
N
CN
(5)
(7)
Ar
O
Ar
Ar =
N
S
O
=
N
S
SCHEME 1
2-ylmethyl]thiazol-4-yl-N,N-dimethylbenzenesulfonamide (12) on the
basis of elemental analysis and spectral data.
The structure of (12) was further confirmed by an independent syn-
thesis of 4-thiazolinone derivative (10) with p-anisaldehyde in ethano-
lic piperidine solution.
The formation of (12) from 4-thiazolinone (10) and p-methoxy ben-
zylidene malononitrile can be explained by the addition of an active
methylene group of 4-thiazolinone (10) at the olefinic bond of ben-
zylidene malononitrile forming the intermediate [A], which undergoes
spontaneous elimination of malononitrile to give the final product (12)
(Scheme 2).
Reaction of (2) with 2-cyano-3,3-dimethyl thio acrylonitrile18,19
in DMF in the presence of anhydrous potassium carbonate led
to 4-(6,8-Dicyano-5-imino-7-methylsulfanyl-5H-thiazolo[3,2-a]pyridin-
3-yl)-N,N-dimethylbenzenesulfonamide (13) (Scheme 3). The elemen-
tal analysis and spectral data of the latter structure were in agreement
with its assigned structure.

432
S. M. Hassan et al.
OCH3
Ar
Ar
N
S
N
S
CN
S
CH2CN
O
OCH3
Ar
N
O
NH2
(12)
(2)
(11)
CHO
OCH3
OCH3
CN
CN
Ar
H3CO
CH
Ar
S
N
ClCH2COOEt
C2H5OH / AcONa
N
S
H
H
CN
S
CH2C(S)NH2
O
S
CN
N
Ar
(10)
(9)
O
[A]
Ar
O
S
Ar
=
N
Ar =
N
O
SCHEME 2
Our investigation was also extended to study the reaction of (2)
with o-phenolic aldehydes,20 namely salicyaldehyde, and 2-hydroxy-
1-naphthaldehyde. Thus, cyclocondensation of (2) with an equimo-
lar amount of salicyaldehyde in boiling ethanol solution containing
piperidine as a catalyst gave the corresponding N,N-di-methyl-4-[2-
(2-oxo-2H-chromen-3-yl)thiazol-4-yl]benzenesulfonamide (14). The for-
mation of (14) was assumed to occur via the intermediacy of the
Knovenagel condensed intermediate [B], intramolecular cyclization
via an anticipated Michael-type addition21 of the acidic (OH) group
to the (CN) function, and spontaneous hydrolysis of the imino func-
tion into a carbonyl function under the experimental reaction condi-
tions employed. Similar hydrolysis phenomena have been previously
reported22,23 (Scheme 3).
The latter structure was established on the basis of its elemental
analysis and spectral data. A final evidence for the proposed structure
comes by boiling coumarin-3-carbothioc acid amide with phenacyl bro-
mide derivative (1) in ethanol. But, when compound (2) was treated
with 2-hydroxy-1-naphthaldehyde at the same reaction condition, the
reaction afforded the isolable iminobenzocoumarin derivative (15),

Heteroaromatization with Sulfonamido Phenyl Ethanone, Part II
433
Ar
Ar
HN
CN
N
CN
methanol
H
H
OEt
(17)
(18)
S
CN
Ar
Ar
N
)
3
t
E
O
(
HN
SCH3
O
C
H
C 2
HN
O
A
CN
(15)
(13)
CHO
H3CS
H3CS
CN
CN
OH
Ar
N
S
ethanol / piperidine
DMF / K2CO3
CH2CN
O
C
Ar
O
(2)
Ar
CH2Br
CHO
OH
(1)
O
(16)
NH2
S
Ar
Ar
O
O
CN
HO
O
O
[B]
(14)
Ar
O
Ar
Ar = N S
O
=
N
S
SCHEME 3
which when heated with glacial acetic acid in the presence of few drops
of HCl afforded benzocoumarin derivative (16) (Scheme 3).
On the other hand, when compound (2) was allowed to react
with triethyl orthoformate at reflux temperature, afforded 4-[2-(1-
cyano-2-ethoxyvinyl)thiazol-4-yl]-N,N-dimethylbenzenesulfonamide
(17), which on treatment with dimethylamine in refluxing methanol
afforded 1-cyano-2-dimethylaminovinylthiazolyl-N,N-dimethyl ben-
zenesulfonamide (18). The latter compound was also obtained via
direct reaction of thiazolyl acetonitrile (2) with dimethylformamide-
dimethylacetal in xylene (Scheme 3).
The behavior of 3-ethoxyacrylonitrile derivative (17) towards some
heterocyclic amines are investigated, thus compound (17) reacted with

434
S. M. Hassan et al.
3-amino-1,2,4-triazole in DMF24 under reflux to afford triazolo[4,3-
a]pyrimidine derivative (19). The formation of (19) is assumed to pro-
ceed through the addition of exocyclic amino group of aminotriazole to
α ,β -unsaturated moiety of (17) to yield acyclic intermediate [C], which
undergoes intramolecular cyclization with elimination of ethanol to af-
ford the final product triazolo[4,3-a]pyrimidine (19) (Scheme 4).
NH2
NH2
Ar
C
N
Ar
Ar
H N
N
N
N
N
N
N
N
SCH3
N
EtO
N
N
H
CN
(20)
(19)
[C]
N
N
H2N
N
H
H3CS
CN
N
N
Ar
CN
Ar
N
H
CH2CN
N
NH2
N
H
H2N
N
H
OEt
CN
(17)
(25)
NH2
Ar
CN
Ar
Ar
NH2
NH
Ar
NH2
N
O
H
NHNH2
N
N
NH2
Ar
N
(21)
(24)
(23)
(22)
O
N S
O
=
N
S
SCHEME 4
In the same manner, compound (17) reacted with 5-amino-3-
methylthio-1(H)-pyrazole-4-carbonitrile25 in refluxing DMF to give
pyrazolo[1,5-a]pyrimidine derivative (20).
The reactivity of compound (17) towards some nitrogen nucleophiles
was also investigated. Thus, when (17) was treated with hydrazine
hydrate in refluxing ethanol, the reaction afforded acyclic product 3-
hydrazinoacrylonitrile derivative (21) and ruled out the amino pyra-

Heteroaromatization with Sulfonamido Phenyl Ethanone, Part II
435
zole derivative (22), due to the fact that the IR spectrum showed an
absorption band for (CN) at 2196 cm−1
.
Similarly, compound (17) reacts with NH2OH.HCl and
guanidine.HCl in refluxing ethanol containing sodium acetate to
afford aminoisoxazole derivative (23) and 2,4-diaminopyrimidine
derivative (24) respectively (Scheme 4).
Moreover (17) reacts smoothly with 2-(1H)-benzimidazole acetoni-
trile in refluxing dioxane to afford only one isolable product, identified
as benzo[4,5]imidazo[1,2-a]pyridine derivative (25).
The IR spectrum of the latter product revealed absorption bands at
3460, 3374, 2200 cm−1 due to the NH2 and CN.
The base-promoted nucleophilic addition of the thiazolyl acetonitrile
(2) to an equimolar amount of phenyl isothiocyanate in dry DMF in the
presence of KOH at room temperature afforded the non-isolable potas-
sium salt [D], which reacted with halogenated compounds (methyl io-
dide and ethyl bromoacetate) to give acyclic compound (26,27) deriva-
tives, respectively (Scheme 5).
3-Methylsulfanyl-3-phenylaminoacrylonitrile derivative (26) re-
acted with aniline in refluxing ethanol afforded 3,3-bis phenyl amino
acrylonitrile derivative (28), which was established on the basis of ele-
mental analysis and spectral data.
Compound (27), when heated in ethanol in the presence of piperi-
dine as a catalyst, afforded only one isolable product from two proposed
structures 4-thiazolidinone (29) and thiophene (30). IR spectrum indi-
cated the disappearance of (NH2) bands and showed absorption band
for (CN) group at 2263 cm−1, and 1H-NMR spectrum showed the lack of
the signal due to protons of ester group and the appearance of a signal
due to the methylene group at 3.94 ppm. These spectral data provided
a firm support for structure (29) and ruled out the other possible struc-
ture (30) (Scheme 5).
Acidified of intermediate [D] with 1N HCl yielded the N-phenyl
cyanothioacetamide derivative (31).
Additionally, when thiazolyl acetonitrile (2) was reacted with CS2 (in
the presence of potassium hydroxide) in DMF, the non-isolated potas-
sium dithiolate [E] was obtained, and converted into cyano dithioacetic
acid derivative (32) by treatment with 1N HCl. But when compound
(32) was treated with 2 mol of methyl iodide afforded 3,3ꢀ-bis methyl-
sulfanylacrylonitrile derivative (33) (Scheme 5).
Cyclization of ketendithioacetal (33) with o-substituted aniline (o-
amino thiophenol, o-amino phenol, and o-phenylene diamine) afforded
benzothiazole, benzoxazole, and benzoimidazole derivatives (34 a–c),
respectively.

436
S. M. Hassan et al.
NH2
R
Ar
CN
NH
R
Ar
Ar
H2N
CN
S
CN
n
HN
H
S
H3CS
SCH3
n
NH2
XH
(33)
(32)
(35 a,b)
1N
HCl
Ar
CN
Ar
CN
SK
X
HN
/
CS2
KOH
Ar
CH2CN
(2)
PhN
KS
C
S
K
OH
(34 a,b,c)
[E]
1 mol
Ar
Ar
CN
S
CN
Ar
CN
BrCH2COOEt
O
CH3I
PhHN
PhHN
SCH3
NH2
PhHN
SK
OEt
(26)
(27)
[D]
1N
HCl
Ar
Ph
CN
Ar
CN
Ar
Ar
CN
NH2
COOEt
S
N
PhHN
O
S
PhHN
PhHN
NHPh
S
O
(31)
(28)
(30)
(29)
a; X=S
b; X=O
c; X=NH
N S
a; n=1; R=CH3
b; n=2; R=H
Ar
=
O
N
S
SCHEME 5
Finally, the reaction of ketene (33) with 1,2-propane diamine and 1,3-
propane diamine afforded 4-methylimidazolidine and tetrahydropyrim-
idine derivatives (35 a,b) respectively (Scheme 5).
From most the important routes, fragmentation patterns of the
compounds are as follows. Loss of N(CH3)2 and SO2 moieties from
compounds (2, 8b, 18, 19, 34c, 35b);26–28 loss of (H2S, thiiran-2-one,

Heteroaromatization with Sulfonamido Phenyl Ethanone, Part II
437
3-(4-methoxybenzylidene)thiiran-2-one, CH2 =CH2 =CO, NH2CN,
PhNCNPh, PhNCS, CS2) from compounds (9, 10, 12, 17, 21, 28, 31,
32) respectively to form thiazolyl acetonitrile derivative at m/e = 307;
and loss of R(CN)2 R= (p−ClPhCH C, N(CH3)2CH C, CH2) from
2-substituted thiazole to form phenyl thiairidine ion at m/e = 133 for
most prepared thiazole derivatives. The mass fragmentation pattern
is depicted in Chart 1.29−33
Antimicrobial and Antifungal Activities
The results of antimicrobial screening (Table II) show that compounds
(2, 3, 5, 6, 8b, 13, 20, 21, 25, 34a,c) are highly active compounds against
antimicrobial activity, gram-positive (B. subtilis, S. aureus, S. maxima),
gram-negative (K. pneumonia, Salmonella, P. aeruginosa), antifungal
activity, unicellular fungi (C. abicans), and filamentous fungi (Rhizopus,
A. fumigatus), while the compounds (8a,c, 15, 17, 18, 23, 24, 28, 29,
34b) showed moderately active, and the remaining compounds (9, 10,
12, 14, 16, 19, 26, 27, 31–33, 35a,b) showed weakly active. It seems
that most activity was exhibited by derivatives with thiazole containing
a sulfonamide moiety (Table II).
CONCLUSION
For synthesis of heterocyclic compounds containing sulfonamide moi-
ety, which cannot be prepared by direct chlorosulfonation, the reac-
tion of thiazolyl acetonitrile containg N,N-dimethylsulfonamide moiety
with different electrophilic reagents afforded heterocyclic compounds
with N,N-dimethyl-sulfonamide moiety, which cannot prepared by di-
rect chlorosulfonation.
EXPERIMENTAL
Melting points are uncorrected. IR spectra (KBr) were recorded on FT-
IR 5300 spectrometer and Perkin Elmer spectrum RXIFT-IR system
(ν, cm−1). The 1H-NMR spectra were recorded at 300 MHz on a Varian
Gemini NMR spectrometer (δ , ppm) using TMS as an internal stan-
dard. Mass spectra were obtained on GC Ms-QP 1000 EX mass spec-
trometer at 70 eV. Elemental analyses were carried out by the Micro-
analytical Research Center, Faculty of Science, Cairo University and
Al-Azhar University.

CN
- H ,
- Ph
NCS
- CH2(CN)2
- C=S
- N(CH3
)
2
- SO2
-P
438

439

440

Heteroaromatization with Sulfonamido Phenyl Ethanone, Part II
441
4-(2-Cyanomethylthiazol-4-yl)-N,N-dimethylbenzenesulfon-
amide (2)
A mixture of phenacyl bromide derivative (1; 0.01 mol) and 2-
cyanothioacetamide (0.01 mol) in ethanol (50 mL) was heated under
reflux for 1 h. The solvent was concentrated, after cooling the solid prod-
uct that formed was collected and recrystallized to give (2) (Table I).
IR (film) v = 3130 (CH-arom.), 2964 (CH-aliph.), 2220 (CN), 1330, 1160
cm−1 (SO2). MS: m/z (%) = 307 (45.8; M+), 263 (19.4), 199 (100), 133
(12.2), 89(10.3).
4-[2-(Cyano(p-tolylhydrazono)methyl]thiazol-4-yl]-N,N-
dimeth-ylbenzenesulfonamide (3)
Procedure (A)
p-Tolyl diazonium chloride (prepared by adding sodium nitrite (0.01
mol) to p-toluidine (0.01 mol) in conc. HCl (6 mL) at 0∼ 5◦C under
stirring) was added dropwise to a cold solution of thiazolyl acetonitrile
derivative (2; 0.01 mol). In ethanol (20 mL) containing sodium acetate
(0.08 mol), the obtained product was collected and recrystallized to give
(3) (Table I).
Procedure (B)
A mixture of phenacyl bromide derivative (1; 0.01 mol) and 2-cyano-
2-p-tolylazo thioacetamide (0.01 mol) in ethanol (50 mL) was heated
under reflux for 1 h. The resulting solid was collected to give the com-
pound (3), m.p. and mixed m.p. determined with authentic sample,
which was obtained in procedure (A) gave no depression. IR (film)
v = 3190 (NH), 3096 (CH-arom.), 2917 (CH-aliph.), 2216 (CN), 1340,
1
1162 cm−1 (SO2). H-NMR (CDCl3): δ = 2.40 (s, 3H, CH3), 2.78 (s, 6H,
N(CH3)2), 7.20 and 7.35 (dd, 4H, AB-ArH), 7.73 (s, 1H, CH-thiazole),
7.91 and 8.04 (dd, 4H, AB-ArH; J=8.1 Hz), 13.98 ppm (s, 1H, NH).
General Procedure for Preparation of (5,6)
To a stirred solution of (2; 0.01 mol) in ethanol (50 mL) containing
sodium acetate (3 g) pyrazole diazonium salt, or triazole diazonium salt
(prepared by adding sodium nitrite (0.01 mol) to heterocyclic amines
(0.01 mol) in conc. HCl (6 mL) at 0∼ 5◦C under stirring) was added
dropwise while cooling to 0∼ 5◦C and stirring. The reaction mixture was
then left at room temperature for 2 h, and the solid product formed was

442
S. M. Hassan et al.
collected by filtration and recrystallized from the appropriate solvent
to give (5,6), respectively (Table I).
4-[2-(4-Amino-8-cyano-7-methylsulfanylpyrazolo[5,1-c][1,2,4]-
triazin-3-yl)thiazol-4-yl]-N,N-dimethylbenzenesulfonamide (5)
IR (film) v = 3483, 3305 (NH2), 3198 (CH-arom.), 2916 (CH-aliph.),
2224 (CN), 1340, 1160 cm−1 (SO2). MS: m/z (%) = 472 (100; M+), 409
(33.1), 374 (21.4), 308 (28.9), 240 (28.2), 185 (58.3).
{
}
4- 2-[Cyano(2H-[1,2,4]triazol-3-ylazo)methyl]thiazol-4-yl -N,N-
dimethylbenzenesulfonamide (6)
IR (film) v = 3418 (NH), 3106 (CH-arom.), 2922 (CH-aliph.), 2220
(CN), 1332, 1156 cm−1 (SO2). MS: m/z (%) = 403 (100; M++1), 402
(91.7; M+), 294 (60.3), 197 (26.0), 134 (19.1).
General Procedure for Preparation of (8a–c)
Procedure (A)
A mixture of (2; 0.01 mol) and the appropriate aromatic aldehyde
(0.01 mol) in ethanol (40 mL) containing few drops of piperidine was
refluxed for 2 h The obtained product that formed was collected by
filtration and recrystallized from the appropriate solvent to give (8a–c)
(Table I).
Procedure (B)
A mixture of phenacyl bromide derivative (1; 0.01 mol) and the ap-
propriate arylidine (0.01 mol) in ethanol (40 mL) was refluxed for 2 h.
The product obtained was collected and recrystallized. M.p. and mixed
m.p. determined with authentic sample gave no depression.
4-[2-(1-Cyano-2-phenylvinyl)thiazol-4-yl]-N,N-
dimethylbenz-enesulfonamide (8a)
IR (film) v = 3100 (CH-arom.), 2920 (CH-aliph.), 2222 (CN), 1334,
1158 cm−1 (SO2). 1H-NMR (CDCl3): δ =2.74 (s, 6H, N(CH3)2), 7.51 and
8.02 (m, 5H, ArH), 7.73 (s, 1H, CH-thiazole), 7.84 and 8.16 (dd, 4H,
AB-ArH; J=8.2 Hz), 8.27 ppm (s, 1H, C CH).
4-{2-[2-(4-Chlorophenyl)-1-cyanovinyl]thiazol-4-yl}-N,N-
dimethylbenzenesulfonamide (8b)
IR (film) v = 3100 (CH-arom.), 2930 (CH-aliph.), 2216 (CN), 1326,
1154 cm−1 (SO2). MS: m/z (%) = 429 (66.0; M+), 385 (5.3), 321 (88.9),
133 (12.9) 89(12.3).

Heteroaromatization with Sulfonamido Phenyl Ethanone, Part II
443
4-{2-[1-Cyano-2-(4-methoxyphenyl)vinyl]thiazol-4-yl}-N,N-
dimethylbenzenesulfonamide (8c)
IR (film) v = 3104 (CH-arom.), 2926 (CH-aliph.), 2214 (CN), 1334,
1164 cm−1 (SO2).
1H-NMR (CDCl3): δ = 2.75 (s, 6H, N(CH3)2), 3.91 (s, 3H, OCH3), 7.02
and 7.86 (dd, 4H, AB-ArH; J=8.4 Hz), 7.69 (s, 1H, CH-thiazole), 8.03
and 8.15 (dd, 4H, AB-ArH; J=8.1 Hz), 8.20 ppm (s, 1H, C CH).
2-[4-(4-Dimethylsulfamoylphenyl)thiazol-2-yl]
thioacetamide (9)
To a solution of (2; 0.01 mol) in ethanol (30 mL) triethyl amine (0.1
mol) was added, and the mixture was saturated with H2S for 3 h and
then left overnight. The precipitated solid was separated by filtration
and purified by recrystallization to give (9) (Table I). IR (film) v = 3402,
3307 (NH2), 3117 (CH-arom.), 2917 (CH-aliph.), 1576 (CS), 1340, 1160
cm−1 (SO2). MS: m/z (%) = 341 (1.6; M+), 307 (24.1), 263 (26.3), 199
(33.8), 133 (6.3), 89 (21.1).
N,N-Dimethyl-4-[2-(4-oxo-4,5-dihydrothiazol-2-ylmethyl)-
thiazol-4-yl]benzenesulfonamide (10)
Procedure (A)
A mixture of (9; 0.01 mol) and ethyl chloroacetate (0.01 mol) in
ethanol (20 mL) containing (1 g) of sodium acetate was refluxed for
2 h. The obtained product that formed was collected and recrystallized
to give (10).
Procedure (B)
A mixture of (2; 0.01 mol) and thioglycolic acid (0.01 mol) in pyridine
(10 mL) was refluxed for 45 min. The solid obtained was filtered off and
recrystallized, m.p. and mixed m.p. determined with authentic sample
gave no depression (Table I). IR (film) v = 3108 (CH-arom.), 2872 (CH-
aliph.), 1708 (CO), 1336, 1158 cm−1 (SO2). MS: m/z (%) =381 (100; M+),
307 (28.5), 199 (52.8), 133 (29.1), 89 (5.8).

444
S. M. Hassan et al.
4-{2-[5-(4-Methoxybenzylidene)-4-oxo-4,5-dihydrothiazol-2-
ylmethyl]thiazol-4-yl}-N,N-dimethylbenzenesulfonamide (12)
Procedure (A)
A mixture of (10; 0.01 mol) and 2-(4-methoxy benzylidene) malonon-
itrile (0.01 mol) in ethanol (50 mL) was refluxed for 2 h. The solid
obtained was filtered off and recrystallized to give (12).
Procedure (B)
A mixture of (10; 0.01 mol) and p-anisaldehyde (0.01 mol) in ethanol
(20 ml) and few drops of piperidine was refluxed for 3 h. The mixture
was cooled, and the separated solid was filtered off and recrystallized,
m.p. and mixed m.p. determined with authentic sample gave no de-
pression (Table I). IR (film) v = 3110 (CH-arom.), 2870 (CH-aliph.),
1658 (CO), 1336, 1168 cm−1 (SO2). MS: m/z (%) = 499 (23.3; M+), 307
(8.6), 199 (28.7), 133 (21.5), 89 (74.2).
4-(6,8-Dicyano-5-imino-7-methylsulfanyl-5H-thiazolo[3,2-a]-
pyridin-3-yl)-N,N-dimethylbenzenesulfonamide (13)
A mixture of (2; 0.01 mol), anhydrous potassium carbonate (0.012 mol),
and 2-cyano-3,3-dimethyl thio acrylonitrile (0.01 mol) in DMF (30 mL)
was heated at 50∼ 60◦C with stirring until odor of the methane thiol
is ceased. After cooling, the reaction mixture poured into crushed ice
(100 g) then acidified with 1N HCl. The solid product that formed was
collected and recrystallized to give (13) (Table I). IR (film) v = 3282
(NH), 3046 (CH-arom.), 2916 (CH-aliph.), 2202, 2197 (2CN), 1334, 1162
cm−1 (SO2). MS: m/z (%) =429 (28.0; M+), 428 (73.2; M+ -1), 367 (21.8),
333 (35.0), 261 (11.4), 212 (17.2), 170 (100).
N,N-Dimethyl-4-[2-(2-oxo-2H-chromen-3-yl)thiazol-4-
yl]benzenesulfonamide (14)
Procedure (A)
To a mixture of (2; 0.01 mol) and salicyldehyde (0.01 mol) in ethanol
(50 mL), a few drops of piperidine was added as a catalyst. The reaction
mixture was refluxed for 3 h, and the solid product was collected by
filtration and recrystallized to give (14).
Procedure (B)
A mixture of (1; 0.01 mol) and coumarin-3-carbothioic acid amide
(0.01 mol) in ethanol (50 mL) was refluxed for 2 h. The solid obtained
was filtered off and recrystallized, m.p. and mixed m.p. determined

Heteroaromatization with Sulfonamido Phenyl Ethanone, Part II
445
with authentic sample gave no depression (Table I). IR (film) v = 3047
(CH-arom.), 2900 (CH-aliph.), 1720 (CO), 1340, 1162 cm−1 (SO2). MS:
m/z (%) =412 (100; M+), 378 (68.3), 304 (93.4), 241 (32.4), 134 (21.1).
4-[2-(3-Imino-3H-benzo[f]chromen-2-yl)thiazol-4-yl]-N,N-di-
methylbenzenesulfonamide (15)
To a mixture of (2; 0.01 mol) and 2-hydroxy-1-naphthaldehyde (0.01
mol) in ethanol (50 mL), a few drops of piperidine was added as catalyst.
The reaction mixture was refluxed for 5h. The isolated product was
collected and recrystallized to give (15) (Table I). IR (film) v =3308
(NH), 3050 (CH-arom.), 2910 (CH-aliph.), 1340, 1158 cm−1 (SO2). MS:
m/z (%) =461 (67.2; M+), 444 (100), 336 (17.1), 193 (15.3), 133 (3.6).
N,N-Dimethyl-4-[2-(3-oxo-3H-benzo[f]chromen-2-yl)thiazol-4-
yl]benzenesulfonamide (16)
To a mixture of 30 mL acetic acid and 3 mL of HCl, 0.01 mol of compound
(15) was added and refluxed for 2 h. The precipitate obtained after
cooling was filtered off and recrystallized to give (16) (Table I). IR
(film) v = 3108 (CH-arom.), 2872 (CH-aliph.), 1708 (CO), 1336, 1158
cm−1 (SO2).
4-[2-(1-Cyano-2-ethoxyvinyl)thiazol-4-yl]-N,N-
dimethylbenzenesulfonamide (17)
A mixture of (2; 0.01 mol) and triethyl orthoformate (0.01 mol) in acetic
anhydride (0.01 mol) was refluxed for 3 h. The reaction mixture was
concentrated to 10 mL. After cooling, the solid product was collected
by filtration and washed with ethanol then recrystallized to give (17)
(Table I). IR (film) v = 3100 (CH-arom.), 2950 (CH-aliph.), 2218 (CN),
1
1342, 1162 cm−1 (SO2). H-NMR (CDCl3): δ = 1.52 (t, 3H, CH3), 2.72
(s, 6H, N(CH3)2), 4.42 (q, 2H, CH2), 7.43 (s, 1H, C CH), 7.65 (s, 1H,
CH-thiazole), 7.81 and 8.12 ppm (dd, 4H, AB-ArH; J = 8.1 Hz). MS: m/z
(%) = 363 (100; M+), 335 (78.6), 307 (15.1), 263 (1.0), 199 (29.3), 133
(9.6).

446
S. M. Hassan et al.
4-[2-(1-Cyano-2-dimethylaminovinyl)thiazol-4-yl]-N,N-
dimethylbenzenesulfonamide (18)
Procedure (A)
A mixture of (17; 0.01 mol) and dimethyl amine (0.01 mol) in
methanol (40 mL) was refluxed for 3 h. The mixture was then cooled,
and the separated solid was collected by filtration and recrystallized to
give (18).
Procedure (B)
A mixture of (2; 0.01 mol) and DMF-DMA (0.01 mol) in dry xylene
(30 ml) was refluxed for 3 h. Then the cooled precipitated product was
filtered off, washed with light petroleum ether, and recrystallized, m.p.
and mixed m.p. determined with authentic sample gave no depression
(Table I). IR (film) v = 3098 (CH-arom.), 2960 (CH-aliph.), 2200 (CN),
1340, 1162 cm−1 (SO2). MS: m/z (%) = 362 (100; M+), 254 (35.3), 210
(5.0), 133 (12.1).
4-[2-(5-Amino[1,2,4]triazolo[4,3-a]pyrimidin-6-yl)thiazol-4-yl]-
N,N-dimethylbenzenesulfonamide (19)
A mixture of (17; 0.01 mol) and 3-amino-1,2,4-triazole (0.01 mol) in
DMF (30 mL) was refluxed for 3 h. After cooling, the product was
collected by filtration then washed with ethanol and recrystallized to
give (19) (Table I). IR (film) v = 3422, 3306 (NH2), 3190 (CH-arom.),
2917 (CH-aliph.), 1340, 1160 cm−1 (SO2). MS: m/z (%) = 401 (100; M+),
293 (42.4), 237 (4.4), 199 (25.8), 133 (11.1), 89 (4.6).
4-[2-(7-Amino-3-cyano-2-methylsulfanylpyrazolo[1,5-a]pyri-
midin-6-yl)thiazol-4-yl]-N,N-dimethylbenzenesulfonamide
(20)
The same experimental procedure described above for the synthesis
of (19) has been followed except for using 5-amino-3-methylthio-1H-
pyrazole-4-yl carbonitrile instead of 3-amino-1,2,4-triazole (Table I).
IR (film) v = 3382, 3360 (NH2), 3099 (CH-arom.), 2970 (CH-aliph.),
1
2216 (CN), 1338, 1164 cm−1 (SO2). H-NMR (DMSO): δ = 2.67 (s, 6H,
N(CH3)2), 2.80 (s, 3H, SCH3), 7.86 and 8.27 (dd, 4H, AB-ArH; J = 7.8
Hz), 8.41 (s, 1H, CH-thiazole), 8.83 (s, 1H, CH-pyrimidine), 9.31 ppm
(br, 2H, NH2).

Heteroaromatization with Sulfonamido Phenyl Ethanone, Part II
447
4-[2-(1-Cyano-2-hydrazinovinyl)thiazol-4-yl]-N,N-dimethyl-
benzenesulfonamide (21)
To a solution of the (17; 0.01 mol) in ethanol (20 mL) hydrazine hydrate
(99%, 0.01 mol) was added. The reaction mixture was refluxed for 2 h,
then cooled. The solid product formed was filtered off, washed with
ethanol, and dried, then recrystallized to give (21) (Table I). IR (film)
v = 3310, 3238 (NH2), 3182 (NH), 3106 (CH-arom.), 2975 (CH-aliph.),
2196 (CN), 1336, 1152 cm−1 (SO2). MS: m/z (%) = 349 (100; M+), 307
(24.0), 199 (48.5), 133 (18.0), 89 (5.8).
4-[2-(5-Aminoisoxazol-4-yl)thiazol-4-yl]-N,N-dimethylben-
zenesulfonamide (23)
To a mixture of (17; 0.01 mol) and NH2OH.HCl (0.015 mol) in ethanol
(30 mL), sodium acetate (0.025 mol) was added. The resulting mixture
was refluxed for 3 h and then allowed to cool to room temperature and
diluted with water (20 mL). The solid product so formed was collected
by filtration, washed with water, and dried, then recrystallized to give
(23) (Table I). IR (film) v = 3410, 3364 (NH2), 3107 (CH-arom.), 2966
(CH-aliph.), 1338, 1162 cm−1 (SO2). MS: m/z (%) = 350 (13.9; M+), 286
(11.6), 249 (15.1), 237 (18.6), 163 (29.1), 131 (47.7).
4-[2-(2,4-Diaminopyrimidin-5-yl)thiazol-4-yl]-N,N-dimethyl-
benzenesulfonamide (24)
The same experimental procedure described above for the synthesis
of (23) has been followed except for using guanidine HCl (0.01 mol)
instead of NH2OH.HCl (Table I). IR (film) v = 3400, 3350, 3256, 3190
(2NH2), 3100 (CH-arom.), 2955 (CH-aliph.), 1330, 1160 cm−1 (SO2). MS:
m/z (%) =376 (7.7; M+), 349 (84.8), 241 (100), 199 (20.0), 133 (10.1).
4-[2-(3-Amino-4-cyanobenzo[4,5]imidazo[1,2-a]pyridin-2-yl)
thiazol-4-yl]-N,N-dimethylbenzenesulfonamide (25)
A mixture of (17; 0.01 mol) and 2-(1H)-benzoimidazole acetonitrile (0.01
mol) in dioxane (50 mL) was refluxed for 5 h. The solid product that
was obtained after cooling was collected by filtration and recrystallized
to give (25) (Table I). IR (film) v = 3460, 3374 (NH2), 3110 (CH-arom.),
2965 (CH-aliph.), 2200 (CN), 1350, 1161 cm−1 (SO2). MS: m/z (%) =473
(3.5; M+ -1), 430 (3.0), 365 (3.1), 199 (17.2), 160 (15.6).

448
S. M. Hassan et al.
General Procedure for Preparation of (26,27)
To a cooled suspension of finely grounded KOH (0.01 mol) in dry DMF
(40 mL), thiazolyl acetonitrile (2; 0.01 mol) and subsequently phenyl
isothiocyanate (0.01 mol) were added. The reaction mixture was stirred
overnight at room temperature, then treated with the appropriate halo
compound (0.01 mol), and left at room temperature for an additional
24 h. The reaction mixture was then triturated with cold H2O (50 mL)
and neutralized with 1N HCl. The resulting precipitated solid was
collected by filtration, washed with water, dried, and recrystallized from
an appropriate solvent (Table I).
4-[2-(1-Cyano-2-methylsulfanyl-2-phenylaminovinyl)thiazol-4-
yl]-N,N-dimethylbenzenesulfonamide (26)
IR (film) v = 3448 (NH), 3102 (CH-arom.), 2924 (CH-aliph.), 2200
(CN), 1336, 1158 cm−1 (SO2). MS: m/z (%) = 456 (24.9; M+), 409 (100),
301 (40.5), 198 (12.9), 133 (18.7).
{2-Cyano-2-[4-(4-dimethylsulfamoylphenyl)thiazol-2-yl]-1-
phenylaminovinylsulfanyl}Acetic Acid Ethyl Ester (27)
IR (film) v = 3114 (NH), 3130 (CH-arom.), 2917 (CH-aliph.), 2198
(CN), 1736 (CO), 1338, 1162 cm−1 (SO2). 1H-NMR (CDCl3): δ = 1.35 (t,
3H, CH2CH3), 2.76 (s, 6H, N(CH3)2), 4.27 (q, 2H, CH2CH3), 6.15 (s, 2H,
SCH2), 7.18 (m, 5H, ArH), 7.52 (s, 1H, CH-thiazole), 7.84 and 8.02 (dd,
4H, AB-ArH; J=7.9 Hz), 11.48 ppm (s, 1H, NH).
4-[2-(1-Cyano-2,2-bisphenylaminovinyl)thiazol-4-yl]-N,N-
dimethylbenzenesulfonamide (28)
A mixture of 1-cyano-2-methylsulfonyl-2-phenylamino vinyl (26;
0.01 mol) and aniline (0.01 mol) in ethanol (50 mL) was refluxed for
3 h after cooling The solid product which formed was collected by filtra-
tion and recrystallized to give (28) (Table I). IR (film) v = 3428, 3348
(2NH), 3126 (CH-arom.), 2968 (CH-aliph.), 2186 (CN), 1338, 1156 cm−1
(SO2). MS: m/z (%) = 501 (54.1; M+), 307 (60.0), 263 (22.7), 199 (89.9),
133 (72.6), 93 (100).
4-{2-[Cyano-(4-oxo-3-phenylthiazolidin-2-ylidene)methyl]
thiazol-4-yl}-N,N-dimethylbenzenesulfonamide (29)
To a mixture of (30 mL) ethanol and (1 mL) of piperidine, (0.01 mol) of
compound (27) was added and refluxed for 3 h. The precipitate obtained
after cooling was filtered off and recrystallized to give (29) (Table I).

Heteroaromatization with Sulfonamido Phenyl Ethanone, Part II
449
IR (film) v = 2952 (CH-arom.), 2858 (CH-aliph.), 2263 (CN), 1701 (CO),
1
1332, 1172 cm−1 (SO2). H-NMR (CDCl3): δ = 2.69 (s, 6H, N(CH3)2),
3.94 (s, 2H, CH2), 6.30 (s, 1H, CH-thiazole), 7.61 (m, 5H, ArH), 7.79
and 7.86 ppm (dd, 4H, AB-ArH; J = 6.6 Hz).
2-Cyano-2-[4-(4-dimethylsulfamoylphenyl)thiazol-2-yl]-N-
phenyl Thioacetamide (31)
The same experimental procedure described above for the synthesis of
(26,27) has been followed, except the halo compounds were not used
(Table I). IR (film) v = 3348 (NH), 3135 (CH-arom.), 3064 (CH-aliph.),
2188 (CN), 1344, 1162 cm−1 (SO2). MS: m/z (%) =442 (17.9; M+), 307
(36.4), 263 (11.3), 199 (39.0), 133 (39.5).
Cyano[4-(4-dimethylsulfamoylphenyl)thiazol-2-yl]dithio Acetic
Acid (32)
Carbon disulphide (0.01 mol) was added gradually to a cold solution of
thiazolyl acetonitrile (2; 0.01 mol) in DMF (20 mL) containing finely
ground KOH (0.02 mol). The reaction mixture left at room temperature
for an additional 24 h. The reaction mixture was then triturated with
cold H2O (50 mL) and neutralized with 1N HCl. The resulting precip-
itated solid was collected by filtration, washed with water, dried, and
recrystallized to give (32) (Table I). IR (film) v = 2941 (CH-arom.), 2854
(CH-aliph.), 2220 (CN), 1334, 1167 cm−1 (SO2). MS: m/z (%) = 383 (1.9;
M+), 307 (3.0), 263 (2.3), 199 (4.1), 133 (4.4), 76 (100).
4-[2-(1-Cyano-2,2-bismethylsulfanylvinyl)thiazol-4-yl]-N,N-
dimethylbenzenesulfonamide (33)
The same experimental procedure described above for the synthesis
of (32) has been followed except methyl iodide was added (0.02 mol)
before the reaction mixture was left at room temperature (Table I). IR
(film) v = 3116 (CH-arom.), 2920 (CH-aliph.), 2214 (CN), 1340, 1158
cm−1 (SO2). MS: m/z (%) = 411 (50.8; M+), 378 (100), 288 (36.7), 212
(44.0), 134 (21.4).
General Procedure for Preparation of (34a–c)
A mixture of ketene dithio acetal (33; 0.01 mol) and the appropriate
o-substituted aniline (0.01 mol) in ethanol (50 mL) was refluxed for
3 h. The obtained product was collected by filtration and recrystallized
from an appropriate solvent (Table I).

450
S. M. Hassan et al.
4-{2-[(3H-Benzothiazol-2-ylidene)cyanomethyl]thiazol-4-yl}-
N,N-dimethylbenzenesulfonamide (34a)
IR (film) v = 3370 (NH), 3064 (CH-arom.), 2922 (CH-aliph.), 2200
(CN), 1335, 1150 cm−1 (SO2). MS : m/z (%) = 440 (56.9; M+), 378 (100),
288 (25.1), 242 (21.8), 134 (14.0).
4-{2-[(3H-Benzooxazol-2-ylidene)cyanomethyl]thiazol-4-yl}-
N,N-dimethylbenzenesulfonamide (34b)
IR (film) v = 3394 (NH), 2924 (CH-arom.), 2851 (CH-aliph.), 2215
(CN), 1338, 1162 cm−1 (SO2). MS: m/z (%) = 424 (17.2; M+), 392 (22.4),
355 (36.2), 327 (25.8), 281 (24.1), 194 (29.3), 152 (25.8), 69 (100).
4-{2-[Cyano-(1,3-dihydrobenzoimidazol-2-ylidene)methyl]
thiazol-4-yl}-N,N-dimethylbenzenesulfonamide (34c)
IR (film) v = 3214, 3200 (2NH), 2964 (CH-arom.), 2850 (CH-aliph.),
2172 (CN), 1334, 1156 cm−1 (SO2). MS: m/z (%) = 423 (76.5; M+), 315
(100), 199 (27.9), 133 (34.8), 89 (25.7).
General Procedure for Preparation of (35a,b)
A mixture of (33; 0.01 mol) and the appropriate diamine (0.01 mol)
in ethanol (50 mL) was refluxed for 5 h. The obtained product was
collected by filtration and recrystallized from an appropriate solvent
(Table I).
4-{2-[Cyano-(4-methyl imidazolidin-2-ylidene)methyl]
thiazol-4-yl}-N,N-dimethylbenzenesulfonamide (35a)
IR (film) v = 3326, 3300 (2NH), 3130 (CH-arom.), 2917 (CH-aliph.),
1
2178 (CN), 1338, 1164 cm−1 (SO2). H-NMR (DMSO): δ = 1.30 (s, 3H,
CH3), 2.68 (s, 6H, N(CH3)2), 3.15 (br, 2H, CH2), 3.86, 4.11 (2br, 2H,
2NH), 7.77 (s, 1H, CH-imidazolidine), 7.79 (s, 1H, CH-thiazole), 7.75
and 8.21 ppm (dd, 4H, AB-ArH; J = 7.5 Hz).
4-{2-[Cyano(tetrahydropyrimidin-2-ylidene)methyl]thiazol-4-
yl}-N,N-dimethylbenzenesulfonamide (35b)
IR (film) v = 3354, 3118 (2NH), 2930 (CH-arom.), 2874 (CH-aliph.),
2168 (CN), 1334, 1156 cm−1 (SO2). MS: m/z (%) = 389 (100; M+), 281
(32.9), 199 (7.3), 133 (4.0).
Antimicrobial and Antifungal Screening
The prepared compounds were evaluated for their antimicrobial activ-
ity using the agar diffusion technique.34,35 A mg/mL solution in DMF

Heteroaromatization with Sulfonamido Phenyl Ethanone, Part II
451
was used. The test organisms were Gram-positive Bacillus subtilis
(NCTC-1040), Staphylococcus aureus (NCTC-7447), Sarcina maxima
(ATCC-33910); Gram-negative Klebsiella pneumonia (NCIMB-9111),
Salmonella, Pseudomonas aeruginosa (ATCC-10145); and antifungal
activity unicellular fungi Candida abicans (IMRU-3669), filamentous
fungi Rhizopus, and Asperigillus fumigatus. DMF showed no inhibition
zones. The reference antibiotics were Ampicillin (AMD) and Calforan.
The inhibition zones (IZ) of these compounds are listed in (Table II).
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