Synthesis and antimicrobial evaluation of novel pyrazolo[1,5-a]pyrimidine, pyrimido[1,2-a]benzimidazole, triazolo[4,3-a]pyrimidine and pyrido[1,2-a]benzimidazole derivatives incorporated phenylsulfonyl moiety

Article abstract of DOI:10.3987/COM-08-11471

Phenylsulfonylacetonitrile (1) reacts with dimethylformamide dimethyl acetal (DMF-DMA) to afford 3-(dimethylamino)-2-(phenylsulfonyl)acrylonitrile (2). Enaminonitrile 2 reacts with 5-aminopyrazole derivatives 3a-e, 5-amino-1,2,4-triazole (7) and 2-aminobenzimidazole (11) to afford new pyrazolo[1,5-a]pyrimidine, triazolo[4,3-a]pyrimidine and pyrimido[1,2-a]benzimidazole derivatives 4a-e, 9 and 12, respectively. Also, 3-(dimethylamino)-2-(phenylsulfonyl)acrylonitrile (2) reacts with 2-(1H-benzimidazol-2-yl)acetonitrile (13) to give the corresponding pyrido[l,2-a]benzimidazole derivative 15. Some of the newly synthesized compounds were tested in vitro for their antibacterial and antifungal activities, and showed promising results.

Full text of DOI:10.3987/COM-08-11471

HETEROCYCLES, Vol. 75, No. 12, 2008
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HETEROCYCLES, Vol. 75, No. 12, 2008, pp. 3005 - 3014. © The Japan Institute of Heterocyclic Chemistry
Received, 24th June, 2008, Accepted, 1st August, 2008, Published online, 4th August, 2008. COM-08-11471
SYNTHESIS AND ANTIMICROBIAL EVALUATION OF NOVEL
PYRAZOLO[1,5-a]PYRIMIDINE, PYRIMIDO[1,2-a]BENZIMIDAZOLE,
TRIAZOLO[4,3-a]PYRIMIDINE AND PYRIDO[1,2-a]BENZIMIDAZOLE
DERIVATIVES INCORPORATED PHENYLSULFONYL MOIETY
Mohamed R. Shaaban
Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt
E-mail: rabiemohamed@hotmail.com
Abstract – Phenylsulfonylacetonitrile (1) reacts with dimethylformamide
dimethyl
acetal
(DMF-DMA)
to
afford
3-(dimethylamino)-2-
(phenylsulfonyl)acrylonitrile (2). Enaminonitrile 2 reacts with 5-aminopyrazole
derivatives 3a-e, 5-amino-1,2,4-triazole (7) and 2-aminobenzimidazole (11) to
afford
new
pyrazolo[1,5-a]pyrimidine,
triazolo[4,3-a]pyrimidine
and
pyrimido[1,2-a]benzimidazole derivatives 4a-e, 9 and 12, respectively. Also, 3-
(dimethylamino)-2-(phenylsulfonyl)acrylonitrile (2) reacts with 2-(1H-
benzimidazol-2-yl)acetonitrile (13) to give the corresponding pyrido[1,2-
a]benzimidazole derivative 15. Some of the newly synthesized compounds were
tested in vitro for their antibacterial and antifungal activities, and showed
promising results.
INTRODUCTION
Sulfones1-2 are versatile class of compounds due to their applications in many pharmaceutical fields.3-9
Thus, sulfones have attracted many authors and great efforts have been done to develop new approaches
to a variety of heterocycles incorporating phenylsulfonyl moiety for biological screening. On the other
hand, enamines10 are important building blocks for the synthesis of many heterocyclic systems of great
value from biological point of view. In continuation to our interest in the synthesis of new fused
heterocycles with expected biological activity,11-13 this work deals with the synthesis of the
multifunctional, 3-(dimethylamino)-2-(phenylsulfonyl)acrylonitrile (2), its utility as a reactive
intermediate for the synthesis of the title compounds and to evaluate their biological activity.

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HETEROCYCLES, Vol. 75, No. 12, 2008
RESULTS AND DISCUSSION
Treatment of phenylsulfonylacetonitrile (1) with dimethylformamide dimethyl acetal (DMF-DMA), in
refluxing xylene, afforded the corresponding 3-(dimethylamino)-2-(phenylsulfonyl)acrylonitrile (2) in an
excellent yield (Scheme 1).
O
O
S
CN
1
NH2
O
O
S
Me
Me
MeO
CH-N
N
MeO
R1
N
O
O
NH2
NH
N
5
R1
S
CN
Me
-Me2NH
R2
N
+
N
NH2
N
R2
O O
S
N
Me
3a-e
MeO
2
R2
Me
CH-N
Me
N
R1
MeO
4a-e
4a R1= H, R2 = C6H5
b R1= H, R2 = Me
N
Me
N
R1
c R1= Me, R2 = C6H5
d R1= H, R2 = C6H4-Clp
e R1= H, R2 = C6H4-Brp
1
Me
NH
N
R2
6a-e
Scheme 1
The reactivity of compound 2 towards some heterocyclic amines as potential precursors for fused
heterocyclic systems was also investigated. Thus, when enaminonitrile 2 was treated with 1H-5-
aminopyrazole derivatives 3a-e in refluxing ethanol, in the presence of piperidine, it afforded the
corresponding 7-amino-6-(phenylsulfonyl) pyrazolo[1,5-a]pyrimidine derivatives 4a-e (Scheme 1). The
structures of compounds 4a-e were established on the basis of their elemental analyses and spectral data,
besides their independent synthesis via the reaction of 3-N-(N,N-dimethylaminomethylene)iminopyrazole
derivatives 6a-e with phenylsulfonylacetonitrile (1) which afforded products identical in all respects (mp,
mixed mp, and IR spectra) with those obtained previously from the reaction of enaminonitrile 2 with 5-
amino-1H-pyrazole derivatives 3a-e (Scheme 1).

HETEROCYCLES, Vol. 75, No. 12, 2008
3007
In a similar manner, the reaction of 1H-5-amino-1,2,4-triazole (7) with compound 2 in refluxing pyridine
afforded 5-amino-6-(phenylsulfonyl) [1,2,4]triazolo[1,5-a]pyrimidine (9) (Scheme 2). The structure of
compound 9 was established on the basis of its elemental analysis and spectral data as well as its
independent synthesis of product 9 from the reaction of N,N-dimethyl-N'-(1H-1,2,4-triazol-5-
yl)formimidamide (10) and phenylsulfonylacetonitrile (1) (Scheme 2).
O
O
H
O
O
NH2
NH
S
CN
HN
S
N
N
CN
Me
N
+
N
Me2N
N
N
H
Me
8
7
2
DMF-DMA
NH2
O O
S
1
N
N
N
N
Me
N
N
Me
N
NH
N
9
10
Scheme 2
The formation of compound 9 is therefore assumed to take place via the addition of the exocyclic amino
group in compound 7 to the activated double bond in enaminonitrile 2 to give the acyclic non-isolable
intermediate 8, which undergoes cyclization and aromatization via the loss of dimethylamine molecule
affording the final isolable product 9 as shown in Scheme 2. The presence of amino group in compound 9
was evidenced by the appearance of two absorption bands at 3421 and 3410 cm-1 in its IR spectrum and
as a broad D2O-exchangable signal at δ 8.83 in its 1H NMR spectrum.
Prompted by the aforementioned results, compound 2 was allowed to react with 2-aminobenzimidazole
(11), under the same experimental conditions, which afforded a white crystalline product in good yield.
The structure of the obtained product was assigned as 5-amino-6-(phenylsulfonyl)pyrimido[1,2-
a]benzimidazole (12) (Scheme 3).
The reaction of enaminonitrile 2 with 2-(1H)-benzimidazoleacetonitrile (13) in refluxing ethanol, in the
presence of a catalytic amount of piperidine, afforded the 2-(phenylsulfonyl)-3-(piperdin-1-
yl)acrylonitrile (14). However, when the reaction was carried out in pyridine it afforded 7-amino-6-
(phenylsulfonyl)pyrido[1,2-a]benzimidazole-8-carbonitrile (15) rather than the isomeric structure 16
(Scheme 3). The IR spectrum of the product 15 revealed bands at 3459, 3308 and 2219 cm-1 due to the
1
amino and nitrile functions, respectively. The H NMR spectrum of the latter product revealed a broad

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HETEROCYCLES, Vol. 75, No. 12, 2008
D2O-exchangable signal at δ 8.63 and due to NH2 group, a singlet at δ 8.47 due to a pyridine proton and
multiplets signals in the region of 7.33-8.45 due to aromatic rings protons. An evidence for the formation
of the product 15 stems from its conversion into the corresponding 4-amino-12-
(phenylsulfonyl)pyrimido[5',4':3,4]pyrido[1,2-a]benzimidazole (17) upon treatment with formamide. The
structure of the latter product 17 was confirmed on the basis of its elemental analysis and spectral data
(see Experimental Part).
H
N
NH2
O
O
NH2
N
N
11
S
∆ / EtOH
piperidine
N
N
12
O
O
S
CN
O
O
S
NMe2
∆ / EtOH
N
2
H
N
CN
piperidine
-Me2NH
14
N
13
CN
∆
pyridine
NH2
NH2
N
O
O
O
O
CN
S
S
N
N
N
CN
15
16
O
O
O
N
N
N
S
NH2
H
NH2
N
17
Scheme 3
EXPERIMENTAL
Melting points were measured on a Gallenkamp melting point apparatus. The IR spectra were recorded as
KBr pellets on a Pye-Unicam SP 3-3oo spectrophotometer. 1H NMR spectra were recorded in deuterated
chloroform or dimethylsulfoxide at 300 MHz on a Varian Mercury VX NMR spectrometer using

HETEROCYCLES, Vol. 75, No. 12, 2008
3009
tetramethylsilane as an internal reference, and results are expressed as δ values. Mass spectra were
performed on a Shimadzu GCMS-QP 1000 Ex mass spectrometer at 70 e.V. Elemental analyses were
carried out at the Microanalytical Center of Cairo University.
Phenylsulfonylacetonitrile (1)14 and aminopyrazoles 3a-e15-17 and their dimethylaminomethylene
derivatives 6a-e11 were prepared according to procedures reported in the literature.
3-(Dimethylamino)-2-(phenylsulfonyl)acrylonitrile (2) and N,N-dimethyl-N'-(1H-1,2,4-triazol-5-
yl)formimidamide (10) .
A mixture of phenylsulfonylacetonitrile (1) or 1H-5-amino-1,2,4-triazole (7) (20 mmol) and
dimethylformamide dimethyl acetal (DMF-DMA) (0.23 g, 20 mmol) in dry xylene (30 mL) was refluxed
for 1-3 h, then allowed to cool. The colorless precipitated product was filtered off, washed with light
petroleum (bp 40-60 ˚C) and dried. Recrystallization from benzene gave the corresponding 3-
(dimethylamino)-2-(phenylsulfonyl)acrylonitrile
(2)
and
N,N-dimethyl-N'-(1H-1,2,4-triazol-5-
yl)formimidamide (10), respectively.
3-(Dimethylamino)-2-(phenylsulfonyl)acrylonitrile (2)
1
85% yield; mp 110-111 ˚C; IR (KBr)υmax /cm-1: 2183 (C≡N); H NMR (CDCl3) δ 3.24 (6H, s, 2CH3),
13
7.59-7.85 (5H, m, ArH's), 7.66 (1H, s, alkenic-CH); C NMR (CDCl3) δ 38.51, 47.65, 82.35, 115.30,
128.32, 129.00, 132.73, 141.77, 154.21; MS (m/z) 236 (M+, 33.65%). Anal. Calcd for C11H12N2O2S: C,
55.91; H, 5.12; N, 11.86; S, 13.57. Found: C, 55.95; H, 5.10; N, 11.91; S, 13.67.
N,N-Dimethyl-N'-(1H-1,2,4-triazol-5-yl)formimidamide (10)
89% yield; mp 180-181 ˚C; IR (KBr) υmax /cm-1: 3483 (NH), 1610 (C=N); 1H NMR (CDCl3) δ 2.95 (6H,
s, 2CH3), 7.56 (1H, s, alkenic-CH), 8.36 (1H, s, triazole-CH), 12.28 (1H, s, broad NH); 13C NMR
(CDCl3) δ 38.51, 47.65, 82.35, 115.30, 154.21. MS (m/z) 139 (M+, 27.35%) Anal. Calcd for C5H9N5: C,
43.15; H, 6.52; N, 50.33. Found: C, 43.25; H, 6.50; N, 50.33.
Reaction of enaminonitrile 2 with heterocyclic amines
General procedure
A mixture of the enaminonitrile 2 (10 mmol) and the appropriate heterocyclic amine (aminopyrazole
derivatives 3a-e, 1H-5-amino-1,2,4-triazole (7), or 2-aminobenzimidazole (11)) (10 mmol), EtOH (30
mL) and few drops of piperidine was refluxed for 8 h, then left to cool to rt. The precipitated product was
filtered off, washed with EtOH and dried. Recrystallization from DMF-EtOH afforded the corresponding
pyrazolo[1,5-a]pyrimidine, triazolo[1,5-a]pyimidine, and pyrimido[1,2-a]benzimidazole derivatives 4a-e,
9, and 12, respectively.
7-Amino-2-phenyl-6-(phenylsulfonyl)pyrazolo[1,5-a]pyrimidine (4a)
1
(71% yield); mp 242-243 ˚C; IR (KBr) υmax /cm-1: 3402, 3301 (NH2); H NMR (DMSO-d6) δ 7.46-7.69
(10H, m, ArH's), 8.08 (1H, s, pyrazole-CH), 8.11 (1H, s, pyrimidine-CH) 8.54 (2H, br, D2O-

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HETEROCYCLES, Vol. 75, No. 12, 2008
13
exchangeable, NH2); C NMR (DMSO-d6) δ 94.48, 100.64, 126.52, 128.75, 128.89, 129.45, 130.55,
132.65, 134.12, 142.07, 145.84, 148.82, 149.63, 156.14; MS (m/z) 350 (M+, 31.96%). Anal. Calcd for
C18H14N4O2S: C, 61.70; H, 4.03; N, 15.99; S, 9.15. Found: C, 61.73; H, 4.00; N, 15.79; S, 9.12.
7-Amino-2-methyl-6-(phenylsulfonyl)pyrazolo[1,5-a]pyrimidine (4b)
(76% yield); mp 215-216 ˚C; IR (KBr) υmax /cm-1: 3404, 3302 (NH2); 1H NMR (DMSO-d6) δ 2.39 (3H, s,
CH3), 7.52-7.67 (5H, m, ArH's), 8.00 (1H, s, pyrazole-CH), 8.11 (1H, s, pyrimidine-CH) 8.48 (2H, br,
13
D2O-exchangeable, NH2); C NMR (DMSO-d6) δ 14.48, 97.48, 99.64, 126.52, 129.75, 133.69, 142.27,
145.74, 148.52, 149.43, 156.34; MS (m/z) 288 (M+, 22.99%). Anal. Calcd for C13H12N4O2S: C, 54.15; H,
4.20; N, 19.43; S, 11.12. Found: C, 54.21; H, 4.16; N, 19.44; S, 11.23.
7-Amino-3-methyl-2-phenyl-6-(phenylsulfonyl)pyrazolo[1,5-a]pyrimidine (4c)
(66% yield); mp 268-270 ˚C; IR (KBr) υmax /cm-1: 3382, 3306 (NH2); 1H NMR (DMSO-d6) δ 2.39 (3H, s,
CH3), 7.46-7.67 (10H, m, ArH's), 8.11 (1H, s, pyrimidine-CH) 8.48 (2H, br, D2O-exchangeable, NH2);
13C NMR (DMSO-d6) δ 14.49, 96.48, 100.68, 126.56, 128.55, 128.99, 129.85, 130.95, 132.85, 134.52
142.17, 145.64, 148.72, 149.53, 156.44; MS (m/z) 364 (M+, 31.21%). Anal. Calcd for C19H16N4O2S: C,
62.62; H, 4.43; N, 15.37; S, 8.80. Found: C, 62.42; H, 4.40; N, 15.57; S, 8.760.
7-Amino-2-(4-chlorophenyl)-6-(phenylsulfonyl)pyrazolo[1,5-a]pyrimidine (4d)
1
(66% yield); mp 240-241 ˚C; IR (KBr) υmax /cm-1: 3417, 3318 (NH2); H NMR (DMSO-d6) δ 7.46-7.69
(10H, m, ArH's), 8.18 (1H, s, pyrazole-CH), 8.11 (1H, s, pyrimidine-CH) 8.54 (2H, br, D2O-
13
exchangeable, NH2); C NMR (DMSO-d6) δ 94.66, 100.66, 126.42, 128.07, 128.78, 129.55, 130.68,
133.55, 134.09, 142.03, 145.83, 148.81, 149.91, 155.12; MS (m/z) 384 (M+, 37.45%). Anal. Calcd for
C18H13ClN4O2S: C, 56.18; H, 3.40; Cl, 9.21; N, 14.56; S, 8.33. Found: C, 56.20; H, 3.43; Cl, 9.31; N,
14.36; S, 8.23.
7-Amino-2-(4-bromophenyl)-6-(phenylsulfonyl)pyrazolo[1,5-a]pyrimidine (4e)
1
(71% yield); mp 269-270 ˚C; IR (KBr) υmax /cm-1: 3456, 3344 (NH2); H NMR (DMSO-d6) δ 7.46-7.69
(10H, m, ArH's), 8.18 (1H, s, pyrazole-CH), 8.11 (1H, s, pyrimidine-CH) 8.54 (2H, br, D2O-
13
exchangeable, NH2); C NMR (DMSO-d6) δ 94.28, 100.34, 126.24, 128.35, 128.59, 129.05, 130.35,
132.45, 134.10, 141.58, 145.74, 148.72, 149.43, 155.74; MS (m/z) 427 (M+, 41.75%). Anal. Calcd for
C18H13BrN4O2S: C, 50.36; H, 3.05; Br, 18.61; N, 13.05; S, 7.47. Found: C, 50.16; H, 3.15; Br, 18.41; N,
13.25; S, 7.67.
7-Amino-6-(phenylsulfonyl) [1,2,4]triazolo[1,5-a]pyrimidine (9)
(88% yield); mp 297 ˚C; IR (KBr) υmax /cm-1: 3421, 3410 (NH2); 1H NMR (DMSO-d6) δ 7.59-8.15 (5H,
m, ArH's), 7.61 (1H, s, pyrimidine-CH), 8.58 (1H, s, triazole-CH), 8.83 (2H, br, D2O-exchangeable,
NH2); 13C NMR (DMSO-d6) δ 103.27, 126.77, 129.54, 133.78, 141.35, 146.90, 154.11, 155.83, 156.04;

HETEROCYCLES, Vol. 75, No. 12, 2008
3011
MS (m/z) 275 (M+, 26.55%). Anal. Calcd for C11H9N5O2S: C, 47.99; H, 3.30; N, 25.44; S, 11.65. Found:
C, 47.79; H, 3.40; N, 25.24; S, 11.35.
5-Amino-6-(phenylsulfonyl]pyrimido[1,2-a]benzimidazole (12)
1
(58% yield); mp > 300 ˚C; IR (KBr) υmax /cm-1: 3421, 3212 (NH2); H NMR (DMSO-d6) δ 7.35-8.45 (9
H, m, ArH's), 8.51 (1H, s, pyrimidine-CH), 8.64 (2H, br, D2O-exchangeable, NH2); MS (m/z) 324 (M+,
23.87%). Anal. Calcd for C16H12N4O2S: C, 59.25; H, 3.73; N, 17.27; S, 9.89. Found: C, 59.37; H, 3.62; N,
17.20; S, 9.74.
2-(Phenylsulfonyl)-3-(piperidin-1-yl)acrylonitrile(14)
(58% yield); mp > 300 ˚C; IR (KBr) υmax /cm-1: 2212 (C≡N); 1H NMR (DMSO-d6) δ 1.60-1.62 (6H, m),
3.56-3.72 (4H, m), 7.66 (1H, s, alkenic-CH), 7.59-7.85 (5H, m, ArH's); MS (m/z) 276 (M+, 19.54%). Anal.
Calcd for C14H16N2O2S: C, 60.85; H, 5.84; N, 10.14; S, 11.60 . Found: C, 60.95; H, 5.74; N, 10.12; S,
11.80 .
Reaction of phenylsulfonylacetonitrile (1) with dimethylaminomethylene derivatives of heterocyclic
amines and enaminonitrile 2 with (1H)-2-benzimidazol-2-ylacetonitrile 13
A
mixture of phenylsulfonylacetonitrile (1) or the enaminonitrile
2
(2 mmol) and
dimethylaminomethylene derivatives of heterocyclic amines 6a-e, 10, or (1H)-2-benzimidazol-2-
ylacetonitrile 13 (2 mmol) in pyridine (30 mL) was heated under reflux for 4-8h, and then allowed to cool
to rt. The pyridine is evaporated and the precipitated products were filtered off, washed with water, dried
and finally recrystallized from DMF to give the corresponding pyrazolo[1,5-a]pyrimidine, triazolo[4,3-
a]pyrimidine, and pyrido[1,2-a]benzimidazole derivatives 4a-e, 9, and 15, respectively.
7-Amino-6-(phenylsulfonyl)pyrido[1,2-a]benzimidazole-8-carbonitrile (15)
(68% yield); mp > 300 ˚C; IR (KBr) υmax /cm-1: 3459, 3308 (NH2), 2219 (C≡N); 1H NMR (DMSO-d6) δ
7.35-8.45 (9H, m, ArH's), 8.47 (1H, s, pyridine-CH), 8.638 (2H, br, D2O-exchangeable, NH2); 13C NMR
(DMSO-d6) δ 101.41, 115.08, 115.84, 119.12, 120.67, 121.97, 128.05, 128.89, 129.58, 133.71, 138.72,
141.48, 150.74, 154.61, 155.43, 156.94; MS (m/z) 348 (M+, 46.24%). Anal. Calcd for C18H12N4O2S: C,
62.06; H, 3.47; N, 16.08; S, 9.20. Found: C, 62.19; H, 3.36; N, 16.17; S, 9.33.
Reaction of 7-amino-6-(phenylsulfonyl)pyrido[1,2-a]benzimidazole-8-carbonitrile (15) with
formamide.
A mixture of 7-amino-6-(phenylsulfonyl)pyrido[1,2-a]benzimidazole-8-carbonitrile (15) and excess
formaide was heated under reflux for 6h, and then allowed to cool. The excess formamide is was distilled
off under reduced pressure and the precipitated products were filtered off, washed with EtOH, dried and
finally
(phenylsulfonyl)pyrimido[5',4':3,4]pyrido[1,2-a]benzimidazole (17).
4-Amino-12-(phenylsulfonyl)pyrimido[5',4':3,4]pyrido[1,2-a]benzimidazole (17)
recrystallized
from
EtOH/DMF
to
give
the
corresponding
4-amino-12-

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HETEROCYCLES, Vol. 75, No. 12, 2008
75% yield; mp 210-211 ˚C; IR (KBr)υmax /cm-1: 3460, 3312 (NH2); 1H NMR (DMSO-d6) δ 7.24-8.18 (9H,
m, ArH's), 8.51 (1H, s, pyridine-CH), 8.61 (2H, br, D2O-exchangeable, NH2), 8.95 (1H, s, pyrimidine-
13
CH); C NMR (DMSO-d6) δ 97.85, 104.17, 118.72, 118.72, 125.93, 121.97, 126.66, 129.31, 129.33,
129.72, 132.53, 138.10, 142.75, 153.11, 155.15, 158.10, 168.98; MS (m/z) 375 (M+, 36.24%). Anal.
Calcd for C19H13N5O2S: C, 60.79; H, 3.49; N, 18.66; S, 8.54. Found: C, 60.75; H, 3.46; N, 18.69; S, 8.51.
BIOLOGICAL ACTIVITY
The antibacterial and antifungal activity were carried out in the Microbiology Division of
Microanalytical Center of Cairo university, using the diffusion plate method18-20 a bottomless cylinder
containing a measured quantity (1ml, mg/mL) of the sample is placed on a plate (9 cm diameter)
containing a solid bacterial medium (nutrient agar broth) or fungal medium (Dox's medium) which has
been heavily seeded with the spore suspention of the test organism.
Table 1. Antibacterial and Antifungal Activities of the Synthesized Compounds
Inhibition Zone Diameter (IZD)
(mm/mg Compound Tested)
Gram (-)
Gram (+)
Fungus
(CA)
COMPOUNDS
NO.
(EC)
(PA)
(SA)
(SF)
anaerobic
CONTROL
2
0.0
0.0
0.0
0.0
0.0
14
++
15
++
16
++
16
++
14
++
15
++
18
++
16
++
15
++
--
13
++
15
++
18
++
16
++
14
++
14
++
14
++
15
++
15
++
--
14
++
14
++
15
++
18
++
15
++
14
++
14
++
16
++
14
+
14
++
15
++
15
++
17
++
14
++
14
++
15
++
18
++
15
++
--
15
++
13
++
14
++
12
++
13
++
15
++
13
++
12
++
12
++
18
++
--
4a
4b
4c
4d
4e
9
12
15
Amphotericin B
Tetracycline
--
26
30
22
26
+++
+++
++
+++

HETEROCYCLES, Vol. 75, No. 12, 2008
3013
After incubation (24 h for bacteria and 5 days for fungi), the diameter of the clear zone of inhibition
surrounding the sample is taken as measure of the inhibitory power of the sample against the particular
test organism (Table 1).
Most of the compounds were tested in vitro against gram negative bacteria [Escherichia coli anaerobic
(EC) and Pseudomonae aeruginosa (PA)], gram positive bacteria [Staphylococcus aureus (SA), and
Streptococcus faecalis (SF)] and antifungal activity against Candida albicans (CA). The reference
antibiotic Tetracycline and Amphotricine were used as references to evaluate the potency of the tested
compounds under the same condition.
REFERENCES
1. N. S. Simpkin, "Sulfones in Organic Synthesis", Tetrahedron Organic Chemistry Series, ed. by J. E.
Baldwin and P. D. Magnus, vol. 10, Pergamon Press, Oxford (1993).
2. P. D. Magnus, Tetrahedron, 1977, 33, 2013.
3. M. M. F. Helmy, Z. H. Fahmy, and H. Y. Sabry, Experimental Parasitology, 2008, 119, 125.
4. P. Jaishankar, E. Hansell, D. Zhao, P. S. Doyle, J. H. McKerrow, and A. R. Renslo, Bioorg. Med.
Chem. Lett., 2008, 18, 624.
5. U. K. Bandarage, T. Wang, J. H. Come, E. Perola, Y. Wei, and B. G. Rao, Bioorg. Med. Chem. Lett.,
2008, 18, 44.
6. K. Steert, I. El-Sayed, P. V. Veken, A. Krishtal, C. Alsenoy, G. D. Westrop, J. C. Mottram, G. H.
Coombs, K. Augustyns, and A. Haemers, Bioorg. Med. Chem. Lett., 2007, 17, 6563.
7. J. Xiang, M. Ipek, V. Suri, M. Tam, Y. Xing, N. Huang, Y. Zhang, J. Tobin, T. S. Mansour, and J.
McKew, Bioorg. Med. Chem, 2007, 15, 4396.
8. C. Chen, B. Song, S. Yang, G. Xu, P. S. Bhadury, L. Jin, D. Hu, Q. Li, F. Liu, W. Xue, P. Lu, and Z.
Chen, Bioorg. Med. Chem, 2007, 15, 3981.
9. B. Tozkoparan, E. Küpeli, E. Yeşilada, and M. Ertan, Bioorg. Med. Chem., 2007, 15, 1808.
10. ‘Enamines: their Synthesis, Structure and Reactions,’ ed. by A. G. Cook, Marcel Dekker, New York,
1969; H. O. House, ‘Modern Synthetic Reactions,’ 2nd edn, W. A. Benjamin, Inc., Menlo Park, 1972,
p. 570.
11. M. R. Shaaban, T. S. Saleh, A. S. Mayhoub, A. Mansour, and A. M. Farag, Bioorg. Med. Chem., 2008,
16, 6344.
12. M. R. Shaaban, T. S. Saleh, F. H. Osman, and A. M. Farag, J. Heterocycl. Chem., 2007, 44, 177.
13. M. R. Shaaban, T. S. Saleh, and A. M. Farag, Heterocycles, 2007, 71, 1765.
14. J. Troeger and W. Helle, J. Prakt. Chem., 1905, 71, 225.
15. A. Takamizawa and Y. Hamashima, Yakugaku Zasshi, 1964, 84, 1113.

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HETEROCYCLES, Vol. 75, No. 12, 2008
16. M. H. Elnagdi, H. A. Elfahham, S. A. S. Ghozlan, and G. E. Elgemeie, J. Chem. Soc., Perkin Trans.1,
1982, 2663.
17. M. H. Elnagdi, E. M. Kandeel, E. M. Zayed, and Z. E. Kandeel, J. Heterocycl. Chem., 1977, 14, 155.
18. D. N. Muanz, B. W. Kim, K. L. Euler, and L. William, Int. J. Pharmacog., 1994, 32, 337
19. R. J. Grager and J. B. Harbone, Phytochemistry, 1994, 37, 19.
20. O. N. Irab, M. M. Young, and W. A. Anderson, Int. J. Pharmacog., 1996, 34, 87.