Heteroaromatization with sulfonamido phenyl ethanone, part I: Synthesis of novel pyrrolo[2,3-D]pyrimidine and pyrrolo[3,2-E][1,2,4]triazolo[1,5-C] pyrimidine derivatives containing dimethylsulfonamide moiety

Article abstract of DOI:10.1080/10426500802111207

4-(5-Amino-4-cyano-1-p-tolyl-1H-pyrrol-3-yl)-N,N-dimethyl- benzenesulfonamide (4) was prepared and converted to several pyrrolo[2,3-d]pyrimidin-5-yl)-N,N-dimethyl-benzenesulfonamide derivatives (5,7,9, and 13). Cyclocondensation of 13 with different elect

Full text of DOI:10.1080/10426500802111207

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Phosphorus, Sulfur, and Silicon
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Heteroaromatization
with Sulfonamido Phenyl
Ethanone, Part I: Synthesis
of Novel Pyrrolo[2,3-
D]Pyrimidine and Pyrrolo[3,2-
E][1,2,4]Triazolo[1,5-
C]Pyrimidine
Derivatives Containing
Dimethylsulfonamide Moiety
Saber M. Hassan a , Ahmed A. El-Maghraby a ,
Mahmoud M. Abdel Aal a & Mahmoud S. Bashandy a
a Chemistry Department, Faculty of Science, Al-
Azhar University, Nasr City, Cairo, Egypt
Version of record first published: 03 Feb 2009.
To cite this article: Saber M. Hassan , Ahmed A. El-Maghraby , Mahmoud M. Abdel
Aal & Mahmoud S. Bashandy (2009): Heteroaromatization with Sulfonamido Phenyl
Ethanone, Part I: Synthesis of Novel Pyrrolo[2,3-D]Pyrimidine and Pyrrolo[3,2-E]
[1,2,4]Triazolo[1,5-C]Pyrimidine Derivatives Containing Dimethylsulfonamide Moiety,
Phosphorus, Sulfur, and Silicon and the Related Elements, 184:2, 291-308
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Phosphorus, Sulfur, and Silicon, 184:291–308, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802111207
Heteroaromatization with Sulfonamido Phenyl
Ethanone, Part I: Synthesis of Novel
Pyrrolo[2,3-D]Pyrimidine and
Pyrrolo[3,2-E][1,2,4]Triazolo[1,5-C]Pyrimidine Derivatives
Containing Dimethylsulfonamide Moiety
Saber M. Hassan, Ahmed A. El-Maghraby, Mahmoud M.
Abdel Aal, and Mahmoud S. Bashandy
Chemistry Department, Faculty of Science, Al-Azhar University, Nasr
City, Cairo, Egypt
4-(5-Amino-4-cyano-1-p-tolyl-1H-pyrrol-3-yl)-N,N-dimethyl-benzenesulfonamide
(4) was prepared and converted to several pyrrolo[2,3-d]pyrimidin-5-yl)-N,N-
dimethyl-benzenesulfonamide derivatives (5,7,9, and 13). Cyclocondensation
of 13 with different electrophilic carbon reagents afforded several 4-(N,N-
dimethylaminosulfonylphenyl)]pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]-pyrimidine
derivatives (14–17,19, and 20); IR, 1HNMR, and mass spectra of the newly
synthesized compounds were recorded. Most of the obtained compounds were
screened against Gram-positive and Gram-negative bacteria and fungi, for which
some of these derivatives gave promising results.
Keywords
Antimicrobial and antifungal activities; 4-(2-bromoacetyl)-N,N-
dimethyl-benzenesulfonamide;
e][1,2,4]triazolo-[1,5-c]pyrimidines;
benzenesulfonamide
4-(N,N-dimethylaminosulfonylphenyl)]pyrrolo[3,2-
pyrrolo[2,3-d] pyrimidin-5-yl)-N,N-dimethyl-
INTRODUCTION
The pyrrolo[2,3-d]pyrimidine ring system has aroused considerable in-
terest due to its presence in several natural products. It is contained in
the nucleoside antibiotics tubercidin, toyocamyin, and sangivamycin.1
Also, sulfonamides are drugs of therapeutic importance, and they have
a wide spectrum of antibacterial activities.2−6 In continuation of our
research program concerning the synthesis of fused pyrimidines7−12
from enaminonitriles, we report here the synthesis of a variety
Received 19 February 2008; accepted 8 April 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
291

292
S. M. Hassan et al.
of new pyrrolo[3,2-d]pyrimidine and pyrrolo[3,2-e][1,2,4]triazolo[1,5-
c]pyrimidine derivatives containing sulfonamide moiety, utilizing the
novel starting material 4-(5-Amino-4-cyano-1-p-tolyl-1H-pyrrol-3-yl)-
N,N-dimethyl-benzenesulfonamide (4) (Table I).
RESULTS AND DISCUSSION
Bromination of 4-acetyl-N,N-dimethylbenzenesulfonamide (1)13 in
dioxane/ether mixture afforded 4-(2-bromoacetyl)-N,N-dimethy- lben-
zenesulfonamide(2), which reacts with p-toludine in boiling ethanol to
give N,N-dimethyl-4-(2-p-tolylaminoacetyl-benzenesulfonamide (3).
Compound (3) reacts with malononitrile in ethanolic sodium
ethoxide solution to give the starting material 4-(5-amino-4-
cyano-1-p-tolyl-1H-pyrrol-3-yl)-N,N-dimethylbenzenesulfonamide (4),
which upon treatment with boiling formic acid to obtain N,N-
dimethyl-4-(4-oxo-7-p-tolyl-4,7-dihydro-3H-pyrrolo[2,3-d] pyrimidin-5-
yl)benzenesulfonamide (5), the reaction is believed to proceed
through the cyclization of aminopyrrolecarboxamide intermediate [A]
(Scheme 1).
SCHEME 1
Acetylation and benzoylation of 4 afforded the corresponding acety-
lamino and benzoylamino pyrrolo derivatives (6a,b) respectively.

Heteroaromatization with Sulfonamido Phenyl Ethanone, Part I
293
TABLE I Physical and Analytical Data for the Newly Prepared
Compounds
Calculated / Found (%)
m.p.◦C (Solvent of
Comp. recrystallization) (Yield%)
Colour
M.formula
(M.Wt.)
C
H
N
O
S
2
80
(B.)
White (95) C10H12BrNO3S (205) 39.23 3.95 4.57 15.68 10.47
39.21 3.94 4.55 15.67 10.45
3
150
(Et.)
230
(Et./B.)
270
(Et./B.)
150
(Et./B.)
243
(Et./B.)
<360
(DMF)
190
(Benzene)
240
(Et./B.)
157
(Et./B.)
220
(Et./B.)
165
(Et.)
263
(Et./B.)
225
(Et./B.)
240
(Et./B.)
250
(Et./B.)
253
(Et./B.)
197
(Et./B.)
300
(D.)
265
(Et./B.)
192
(Et.)
237
Yellow (60)
Yellow (78)
Brown (79)
C
C
C
17H20N2O3S (332) 61.42 6.06 8.43 14.44 9.65
61.40 6.10 8.41 14.39 9.64
20H20N4O2S (380) 63.14 5.30 14.73 8.41 8.43
63.12 5.28 14.71 8.40 8.42
21H20N4O3S (408) 61.75 4.94 13.72 11.75 7.85
61.72 4.92 13.70 11.73 7.84
4
5
6a
6b
7
White (80) C22H22N4O3S (422) 62.54 5.25 13.26 11.36 7.59
62.53 5.23 13.24 11.34 7.56
White (70)
Brown (70)
Brown (80)
Black (70)
Black (82)
Yellow (80)
White (89)
White (92)
White (80)
White (79)
Yellow (66)
Brown (70)
White (82)
Brown (72)
Yellow (80)
Brown (69)
C
C
C
C
C
C
C
C
27H24N4O3S (484) 66.92 4.99 11.56 9.91 6.62
66.90 4.88 11.53 9.90 6.63
21H21N5O3S (423) 59.56 5.00 16.54 11.33 7.57
59.54 4.97 16.52 11.29 7.55
23H24N4O3S (436) 63.28 5.54 12.83 11.00 7.35
63.26 5.52 12.81 10.89 7.34
21H21N5O2S (407) 61.90 5.19 17.19 7.85 7.87
61.89 5.17 17.09 7.79 7.86
23H25N5O2S (435) 63.43 5.79 16.08 7.35 7.36
63.41 5.77 16.10 7.35 7.36
22H23N5O2S (421) 62.69 5.50 16.61 7.59 7.61
62.67 5.48 16.59 7.56 7.59
21H22N6O2S (422) 59.70 5.25 19.89 7.57 7.59
59.68 5.23 19.87 7.54 7.57
22H20N6O2S (432) 61.10 4.66 19.43 7.40 7.41
61.08 4.64 19.42 7.38 7.40
8
9
10
12
13
14
15a
15b
15c
15d
15e
16
17a
17b
19
20
C23H21ClN6O2S (480) 57.44 4.40 17.47 6.65 6.67
57.39 4.39 17.45 6.62 6.65
24H21N7O2S (471) 61.13 4.49 20.79 6.79 6.80
61.09 4.46 20.75 6.76 6.78
24H22N6O3S (474) 60.75 4.67 17.71 10.11 6.76
60.73 4.59 17.69 10.10 6.75
23H22N6O2S (446) 61.87 4.97 18.82 7.17 7.18
61.85 4.85 18.81 7.16 7.09
26H26N6O4S (518) 60.22 5.05 16.21 12.34 6.18
60.19 5.04 16.20 12.32 6.08
C
C
C
C
C
22H20N6O2S2 (464) 56.88 4.34 18.09 6.89 13.80
56.79 4.33 18.10 6.87 13.77
C
23H23N7O2S (461) 59.85 5.02 21.24 6.93 6.95
59.82 5.01 21.23 6.91 6.93
28H25N7O2S (523) 64.23 4.81 18.73 6.11 6.12
64.22 4.78 18.71 6.09 6.10
C
White (78) C23H22N6O3S (462) 59.73 4.79 18.17 10.38 6.93
59.71 4.78 18.09 10.35 6.91
White (89)
(Et./B.)
327
(DMF)
C
28H24N6O2S (508) 66.12 4.76 16.52 6.29 6.30
66.10 4.75 16.51 6.27 6.29
B., benzene; D., dioxane; DMF, dimethylformamide; Et., ethanol.

294
S. M. Hassan et al.
Reaction of aminopyrrole carbonitrile (4) with urea afforded
4-(4-amino-2-oxo-7-p-tolyl-2,7-dihydro-1H-pyrrolo[2,3-d] pyrimidin-5-
yl)-N,N-dimethylbenzenesulfonamide (7) (Scheme 2).
SCHEME 2
Enaminonitrile(4) was reacted with triethyl orthoformate in boiling
acetic anhydride to give N-[3-cyano-4-(4-dimethylsulfamoylphenyl)-
1-p-tolyl-1H-pyrrol-2-yl]formimidic acid ethyl ester (8), which on am-
monolysis in ethanol at room temperature gave 4-(4-amino-7-p-tolyl-
7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N,N-dimethylbenzenesulfonamide
(9). The structure of 9 is supported by spectral data and by an
independent synthesis of the same product from the reaction of 4 with
formamide (m.p., mixed m.p., and identical IR spectrum) (Scheme 3).
Interaction of
8 with dimethylamine in refluxing ethanol
afforded 4-[4-cyano-5-(dimethylaminomethyleneamino)-1-p-tolyl-1H-
pyrrol-3-yl]-N,N-dimethylbenzenesulfonamide (10). The latter struc-
ture is supported by spectral data and by an independent synthesis of
the same product from reaction of 4 with dimethylformamide dimethy-
lacetal in refluxing xylene (m.p., mixed m.p., and identical IR spectrum)
(Scheme 3).
Interaction of (8) with methylamine in ethanol afforded the open
chain product (12), instead of the expected cyclic pyrrolo pyrimidine
derivative (11); the appearance of (CN and NH) absorption bands at

Heteroaromatization with Sulfonamido Phenyl Ethanone, Part I
295
SCHEME 3
2199 and 3410 cm−1, respectively, in IR spectrum of this product sup-
ported the open chain product.
Treatment of 8 with hydrazine hydrate afforded 4-(3-amino-4-
imino-7-p-tolyl-4,7-dihydro-3H-pyrrolo[2,3-d]-pyrimidin-5-yl)-N,N-
dimethylbenzenesulfonamide (13).
The bifunctional derivative 13 was used as starting material
through cyclocondensation with electrophilic carbon reagents to give
pyrrolotriazolopyrimidine derivatives. Thus, treatment of amino-
imino derivative (13) with oxalic acid in refluxing xylene provided
carboxylic acid derivative intermediate [B]. This compound could
not be isolated, and it was decarboxylated to produce7-p-tolyl-9-[4-
(N,N-dimethylaminosulfonylphenyl)] pyrrole[3,2-e][1,2,4]triazolo[1,5-
c]pyrimidine (14) (Scheme 4).
The structure of 14 was confirmed on the basis of elemental and spec-
tral data. When 13 was treated with formic acid, triethyl orthoformate
or DMF–DMA afforded a product, which was found to be identical in

296
S. M. Hassan et al.
SCHEME 4
all respects (m.p., mixed m.p., and spectral data) with compound (14)
previously obtained from 13 and oxalic acid. The formation of the latter
compound from reaction of 13 with DMF-DMA could be explained via
formation of intermediate [C], intramolecular cyclization to intermedi-
ate [D], followed by elimination of dimethylamine (Scheme 4).
Reaction of 13 with chloroacetyl chloride and ethyl cyanoacetate
yielded the corresponding 2-chloromethyl and 2-cyanomethyl deriva-
tives(15a,b) respectively, while when reacted with pyruvic acid in re-
fluxing butanol, 2-acetyl derivative (15c) was obtained (Scheme 5).
Refluxing of a mixture of 13 and acetic anhydride produced 2-methyl
derivative (15d). The structure of the latter product was supported
by spectral data and independent synthesis of the same product from
reaction of 13 with triethyl orthoacetate or acetic acid (Scheme 5).
In addition, cyclocondensation of 13 with diethylmalonate yielded
2-ethoxycarbonylmethyl derivative (15e).

Heteroaromatization with Sulfonamido Phenyl Ethanone, Part I
297
SCHEME 5
Interaction of 13 with CS2 in the presence of KOH afforded the 2-
thione derivative (16), while when reacted with methyl isothiocyanate
and phenyl isothiocyanate afforded 2-methylamino and 2-phenylamino
derivatives (17a,b) respectively (Scheme 5).
When aminoimino (13) reacted with equimolar ratio of methylchloro
formate in refluxing dry benzene, the 2-methoxytriazolopyrimidine
derivative (19) was obtained in excellent yield rather than the expected
2-oxotriazolopyrimidine derivative (18). The formation of (19) could be
explained by the formation of methylester intermediate [E], which un-
dergoes spontaneous intramolecular cyclization to give intermediate
[F] followed by elimination of water rather than ethanol molecule un-
der the reaction conditions (Scheme 6).
Aminoimino (13) reacted with benzaldehyde in refluxing dioxane
to give 2-phenyltriazolopyrimidine derivative (20). The formation of
the latter structure could be explained by the formation of ben-
zylidineamino intermediate [G], which undergoes spontaneous in-
tramolecular cyclization to non-isolable intermediate [H], followed by
aromatization. The structure of 20 was confirmed on the basis of ele-
mental analysis and spectral data; further confirmation was obtained
by the synthesis of the same product through reaction of 13 with ben-
zoyl chloride.

298
S. M. Hassan et al.
SCHEME 6
Finally, treatment of 13 with ethyl acetoacetate in refluxing ethanol
afforded a single product, which analyzed correctly for [C23H22N6O2S],
which was identified as previously prepared compound (15d). This re-
action may proceed through the formation of diazepine intermediate
[I], which rearranged to the more stable triazolopyrimidine derivative
(15d) through elimination of ketene (Scheme 7).
Antimicrobial and Antifungal Activities
The results of antimicrobial screening (Table II) show that compounds
(2, 7, 13, 15c, 16, 17a,b, 19, 20) are highly active compounds against
Gram-positive (B. subtilis, S. aureus, S. maxima), Gram-negative (K.
pneumonia, Salmonella, P. aeruginosa), and antifungal activity [uni-
cellular fungi (C. abicans) and filamentous fungi (Rhizopus, A. fumi-
gatus)]. While the compounds (3, 4, 10, 14, 15a,b,e) showed moderate
activity, and the remaining compounds (5, 6a,b, 8, 9, 12, 15d) showed

Heteroaromatization with Sulfonamido Phenyl Ethanone, Part I
299
SCHEME 7
weak activity. It seems that most activity was exhibited with pyrrolo-
triazolopyrimidine derivatives.
EXPERIMENTAL
Melting points are uncorrected. IR spectra (KBr) were recorded on FT-
IR 5300 spectrometer and Perkin Elmer spectrum RXIFT-IR system
1
(ν, cm−1). The HNMR spectra were recorded at 300 MHz on a Varian
Gemini NMR spectrometer (δ, ppm) using TMS as an internal standard.
Mass spectra were obtained on GC Ms-QP 1000 EX mass spectrometer
at 70 ev. Elemental analyses were carried out by the Microanalytical
Research Center, Faculty of Science, Cairo University and Al-Azhar
University.
4-(2-Bromoacetyl)-N,N-dimethylbenzenesulfonamide (2)
To a stirring solution of 4-acetyl-N,N-dimethylbenzenesulfon-amide (1;
0.01 mol) in dioxane/ether mixture (30 mL), the bromine (0.01 mol)
was added dropwise with constant stirring after complete addition the

300

Heteroaromatization with Sulfonamido Phenyl Ethanone, Part I
301
reaction was left for 1h, then the reaction was poured in cold water
(100 mL). The separated solid was filtered off and recrystallized to give
(2) (Table I). IR (film) v = 3062 (CH-arom.), 2922 (CH-aliph.), 1658
(C O), 1334, 1158 cm−1(SO2).
N,N-Dimethyl-4-(2-p-tolylaminoacetyl)benzenesulfonamide (3)
A mixture of phenacyl bromide derivative (2; 0.01 mol) and p-toludine
(0.01 mol) in ethanol (50 mL) was refluxed for 1. The obtained prod-
uct was collected and recrystallized to give (3) (Table I). IR (film)
v = 3410 (NH), 3061 (CH-arom.), 2917 (CH-aliph.) 1690 (CO), 1342,
1
1160 cm−1(SO2). H-NMR (CDCl3): δ = 2.47 (s, 3H, CH3), 2.79 (s, 6H,
N(CH3)2), 4.30 (s, 2H, CH2), 7.37 and 7.56 (dd, 4H, AB-ArH), 7.91 and
8.49 (dd, 4H, AB-ArH), 9.05 ppm (s, 1H, NH).
4-(5-Amino-4-cyano-1-p-tolyl-1H-pyrrol-3-yl)-N,N-dimethyl-
benzenesulfonamide (4)
To a solution of phenacyl bromide derivative (2; 0.01 mol) in absolute
ethanol (30 mL) malonitrile (0.01 mol) was added. The mixture was
then heated under reflux while stirring, and sodium ethoxide (0.9 g
in 20 mL ethanol) was added dropwise. Heating was continued for 3
h. The solid product that separated out after cooling was filtered off,
washed with cold ethanol, dried, and recrystallized to give (4) (Table
I). IR (film) v = 3418, 3310 (NH2), 3130 (CH-arom.), 2917 (CH-aliph.),
2204 (CN), 1338, 1164 cm−1(SO2). MS: m/z (%) =380 (100; M+), 272
(59.3; M+-SO2N(CH3)2), 155 (11.2), 91 (11.2).
N,N-Dimethyl-4-(4-oxo-7-p-tolyl-4,7-dihydro-3H-pyrrolo[2,3-d]
pyrimidin-5-yl)benzenesulfonamide (5)
A mixture of (4; 0.01 mol) and formic acid (30 mL) was refluxed for 5 h.
The solvent was concentrated until dry. After cooling, the solid product
that formed was collected and recrystallized to give (5) (Table I). IR
(film) v = 3400 (NH), 3142 (CH-arom.), 2848 (CH-aliph.), 1658 (CO),
1334, 1166 cm−1(SO2). MS: m/z (%) = 408 (70.5; M+), 316 (15.9), 301
(100; M+-SO2N(CH3)2), 272 (4.9), 172 (13.8), 91 (15.5).
N-[3-Cyano-4-(4-dimethylsulfamoylphenyl)-1-p-tolyl-1H-pyrrol-
2-yl]acetamide (6a)
A mixture of (4; 0.01 mol) and acetyl chloride (30 mL) was refluxed for
3 h. The solvent was removed under reduced pressure, and the residue
was collected by filtration and recrystallized to give (6a) (Table I). IR

302
S. M. Hassan et al.
(film) v = 3426 (NH), 3093 (CH-arom.), 2928 (CH-aliph.), 2226 (CN)
1728 (CO), 1336, 1162 cm−1(SO2). MS: m/z (%) =422 (76.5; M+), 380
(100; M+-CH2 =C O), 272 (26.4), 91 (20.1), 44 (29.4).
N-[3-Cyano-4-(4-dimethylsulfamoyl-phenyl)-1-p-tolyl-1H-
pyrrol-2-yl]benzamide (6b)
A mixture of (4; 0.01 mol) and benzoylchloride (10 mL) was refluxed
for 2 h. Then it was allowed to cool and was treated with petroleum
ether (60–80 ◦C) (50 mL), whereby petroleum ether was decanted, and
the solid product was separated, collected by filtration, washed with
petroleum ether (60–80◦C) several times, dried, and recrystallized to
give (6b) (Table I). IR (film) v = 3282 (NH), 3118 (CH-arom.), 2922
(CH-aliph.), 2228 (CN) 1664 (CO) , 1336, 1158 cm−1(SO2). MS: m/z (%)
=484 (9.9; M+), 407 (16.2), 299 (7.9), 271 (2.6), 105 (100; C6H5CO), 77
(23.8), 44 (5.4).
4-(4-Amino-2-oxo-7-p-tolyl-2,7-dihydro-1H-pyrrolo[2,3-d]
pyrimidin-5-yl)-N,N-dimethylbenzenesulfonamide (7)
A mixture of (4; 0.01 mol) and urea (0.02 mol) was heated at 160 ◦C for
20 min, and the heating was continued for another 1 h at 200 ◦C until
the mixture became solid. The resulting solid was dissolved in a hot
dilute sodium hydroxide solution, and the boiling basic was allowed to
stand approximately 10 min and then filtered off. Further purification
was accomplished by the reprecipitation froma hot solution with acetic
acid. The separated solid was filtered off and recrystallized to give (7)
(Table I). IR (film) v = 3466, 3340 (NH2), 3410 (NH), 3054 (CH-arom.),
2782 (CH-aliph.), 1726 (CO), 1335, 1155 cm−1(SO2). MS: m/z (%) = 423
(0.24; M+), 408 (0.77), 354 (0.58), 301 (0.75), 129 (100), 70 (9.4), 44
(52.8).
N-[3-Cyano-4-(4-dimethylsulfamoyl-phenyl)-1-p-tolyl-1H-
pyrrol-2-yl]formimidic Acid Ethyl Ester (8)
A mixture of (4; 0.01 mol) and triethylorthoformate (0.01 mol) in acetic
anhydride (25 mL) was heated under reflux for 6 h. The reaction mix-
ture was concentrated until dry. The solid that was obtained was col-
lected by filtration and recrystallized to give (8) (Table I). IR (film) v =
3092 (CH-arom.), 2932 (CH-aliph.), 2208 (CN), 1336, 1166 cm−1(SO2).
1H-NMR (CDCl3): δ =1.29 (t, 3H, OCH2CH3), 2.40 (s, 3H, CH3), 2.72
(s, 6H, N(CH3)2), 4.24 (q, 2H, OCH2CH3), 6.98 (s, 1H, CH-pyrrole) 7.28

Heteroaromatization with Sulfonamido Phenyl Ethanone, Part I
303
and 7.0 (dd, 4H, AB-ArH), 7.79 and 7.80 (dd, 4H, AB-ArH), 8.37 ppm
(s, 1H, CHOC2H5).
4-(4-Amino-7-p-tolyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N,N-
dimethylbenzenesulfonamide (9)
Procedure A
A mixture of (4; 0.01 mol) and formamide (10 mL) was heated under
reflux for 8 h. The solvent was removed under vacuum, and the solid
obtained was recrystallized to give (9) (Table I).
Procedure B
Compound (8; 0.01 mol) was treated with methanolic ammonia (100
mlL) at room temperature for 3 h. The separated solid was collected and
recrystallized. M.p. and mixed m.p determined with authentic sample
gave no depression. IR (film) v = 3484, 3306 (NH2), 3116 (CH-arom.),
2917 (CH-aliph.), 1340, 1162 cm−1(SO2). MS: m/z (%) =407 (100; M+),
299 (66.1), 172 (10.6), 105 (13.8) 91 (12.1), 44 (63.9).
4-[4-Cyano-5-(dimethylaminomethyleneamino)-1-p-tolyl-1H-
pyrrol-3-yl]-N,N-dimethylbenzenesulfonamide (10)
Procedure A
A mixture of (4; 0.01 mol) and N,N-dimethylformamide dimethylac-
etal (0.01 mol) in xylene (20 mL) was refluxed for 2 h. The solvent was
removed under reduced pressure, and the residue was collected and
recrystallized to give (10) (Table I).
Procedure B
A solution of (8; 0.01 mol) and dimethylamine (0.01 mol) in ethanol
(50 mL) was stirred for 45 min. The solid that was obtained was filtered
off and recrystallized. M.p. and mixed m.p determined with authentic
sample gave no depression. IR (film) v = 3135 (CH-arom.), 2876 (CH-
aliph.) 2207 (CN), 1335, 1163 cm−1(SO2). 1H-NMR (CDCl3): δ = 2.40 (s,
3H, CH3), 2.73 (s, 6H, SO2N(CH3)2), 2.95 and 3.09 (2s, 6H, N(CH3)2),
6.86 (s, 1H, CH-pyrrole), 7.25 and 7.38 (dd, 4H, AB-ArH), 7.78 and 7.80
(dd, 4H, AB-ArH), 8.20 ppm (s, 1H, N=CH).
4-4-Cyano-5-[(N-methylformimidoyl)amino]-1-p-tolyl-1H-
pyrrol-3-yl-N,N-dimethylbenzenesulfonamide (12)
To a solution of (8; 0.01 mol) in absolute ethanol (50 mL), methyl amine
(0.01 mol) was added. The reaction mixture was stirred for 1 h. the
solid that was obtained was filtered off and recrystallized to give (12)

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S. M. Hassan et al.
(Table I). IR (film) v = 3410 (NH) 3130 (CH-arom.), 2924 (CH-aliph.),
1
2199 (CN), 1335, 1159 cm−1(SO2). H-NMR (DMSO): δ = 2.36 (s, 3H,
CH3), 2.64 (s, 6H, N(CH3)2), 2.75 (d, 3H, NHCH3), 3.50 (d, 1H, NHCH3),
7.28 and 7.46 (dd, 4H, AB-ArH) 7.44 (s, 1H, CH-pyrrole), 7.76 and 7.93
(dd, 4H, AB-ArH), 8.18 ppm (d, 1H, CHNH).
4-(3-Amino-4-imino-7-p-tolyl-4,7-dihydro-3H-pyrrolo[2,3-d]-
pyrimidin-5-yl)-N,N-dimethylbenzenesulfonamide (13)
To a stirred solution of (8; 0.01 mol) in ethanol (50 mL), hydrazine
hydrate (0.02 mol) was added. Stirring was continued for 7 h at room
temperature. The solid product was isolated by filtration and recrystal-
lized to give (13) (Table I). IR (film) v = 3408, 3338 (NH2), 3286 (NH),
3130 (CH-arom.), 2920 (CH-aliph.), 1338, 1162 cm−1(SO2). MS: m/z (%)
= 422 (70.1; M+), 300 (32.3), 229 (11.7), 91 (17.2).
7-p-tolyl-9-[4-(N,N-dimethylaminosulfonylphenyl)]pyrrolo[3,2-
e][1,2,4]triazolo[1,5-c]pyrimidine (14)
Procedure A
A mixture of (13; 0.01 mol) and oxalic acid (0.01 mol) in xylene (20
mL) was refluxed for 8 h. The precipitate product was filtered off and
recrystallized to give (14) (Table I).
Procedure B
A mixture of (13; 0.01 mol) and formic acid (0.01 mol) was refluxed
for 6 h. The obtained solid was filtered off and recrystallized to give
(14).
Procedure C
A mixture of (13; 0.01 mol) and triethylorthoformate (0.01 mol) in
benzene (50 mL) was refluxed for 5 h. The obtained solid was filtered
off and recrystallized to give (14).
Procedure D
Compound (13; 0.01 mol) reacted with N,N-dimethylformamide
dimethylacetal (0.01 mol) according to procedure (C) to give (14). M.p.
and mixed m.p determined with authentic sample gave no depression.
IR (film) v = 3072 (CH-arom.), 2924 (CH-aliph.), 1332, 1156 cm−1(SO2).
MS: m/z (%) = 432 (15.8; M+), 325 (100), 184 (13.3), 118 (15.2), 91 (27.5),
65 (16.3).

Heteroaromatization with Sulfonamido Phenyl Ethanone, Part I
305
2-Chloromethyl-7-p-tolyl-9-[4-(N,N-dimethylaminosulfonyl
phenyl)]pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (15a)
A mixture of (13; 0.01 mol) and chloroacetylchloride (0.01 mol) in ben-
zene (50 mL) was refluxed for 6 h. The product obtained was filtered off
and recrystallized to give (15a) (Table I). IR (film) v = 3082 (CH-arom.),
2924 (CH-aliph.), 1338, 1156 cm−1(SO2). 1H-NMR (CDCl3): δ = 2.47 (s,
3H, CH3), 2.78 (s, 6H, N(CH3)2), 4.87 (s, 2H, CH2), 7.38 and 7.56 (dd,
4H, AB-ArH) 7.81 (s, 1H, CH-pyrrole), 7.87 and 8.44 (dd, 4H, AB-ArH),
9.09 ppm (s, 1H, CH-pyrimidine).
2-Cyanomethyl-7-p-tolyl-9-[4-(N,N-dimethylaminosulfonyl
phenyl)]pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (15b)
A mixture of (13; 0.01 mol) and ethylcyanoacetate (0.01 mol) in ethanol
(50 mL) was refluxed for 5 h. The solid obtained was collected by fil-
tration and recrystallized to give (15b) (Table I). IR (film) v = 3134
(CH-arom.), 2966 (CH-aliph.) 2966 (CN), 1336, 1162 cm−1(SO2). MS:
m/z (%) = 471 (10.9; M+), 406 (0.4), 364 (21.9), 299 (0.5), 78 (100).
2-Acetyl-7-p-tolyl-9-[4-(N,N-dimethylaminosulfonylphenyl)]-
pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (15c)
A mixture of (13; 0.01 mol) and pyruvic acid (0.01 mol) in butanol (50
mL) was refluxed for 7 h. The solid obtained after concentration of the
reaction mixture was filtered off and recrystallized to give (15c) (Table
I). IR (film) v = 3135 (CH-arom.), 2928 (CH-aliph.) 1650 (CO), 1338,
1160 cm−1(SO2). MS: m/z (%) = 472 (4.8; M+-2), 408 (100), 367 (32.1),
325 (27.0), 300 (32.8), 299 (54.0), 91 (18.2).
2-Metyl-7-p-tolyl-9-[4-(N,N-dimethylaminosulfonylphenyl)]-
pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (15d)
Procedure A
A mixture of (13; 0.01 mol) and acetic anhydride (20 mL) was refluxed
for 5 h. The solvent was removed under vacuum. The solid obtained was
recrystallized to give (15d) (Table I).
Procedure B
Compound (15d) prepared from (13; 0.01 mol) and triethylorthoac-
etate (15 mL) according to procedure A to give (15d).

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S. M. Hassan et al.
Procedure C
A mixture of (13; 0.01 mol) and acetic acid (20 mL) was refluxed for
6 h. The solid obtained was filtered off and recrystallized to give (15d).
Procedure D
The reaction of (13; 0.01 mol) with ethyl acetoacetate (0.01 mol) was
carried out as in the reaction of (13) with ethyl cyanoacetate to give
(15d). M.p. and mixed m.p determined with authentic sample gave no
depression. IR (film) v = 3070 (CH-arom.), 2924 (CH-aliph.), 1334, 1156
1
cm−1(SO2). H-NMR (CDCl3): δ = 2.47 (s, 3H, CH3), 2.67 (s, 3H, CH3-
triazole), 2.79 (s, 6H, N(CH3)2), 7.37 and 7.56 (dd, 4H, AB-ArH) 7.77
(s, 1H, CH-pyrrole), 7.91 and 8.49 (dd, 4H, AB-ArH), 9.04 ppm (s, 1H,
CH-pyrimidine). MS: m/z (%) = 446(39.1; M+), 339 (100), 297 (14.8).
2-Ethoxy carbonyl methyl-7-p-tolyl-9-[4-(N,N-dimethylamino-
sulfonylphenyl)]pyrrolo[3,2-
e][1,2,4]triazolo[1,5-c]pyrimidine (15e)
A mixture of (13; 0.01 mol) and diethylmalonate (0.01 mol) in ethanol
(50 mL) was refluxed for 5 h. The solid obtained was collected by fil-
teration and recrystallized to give (15e) (Table I). IR (film) v = 3142
(CH-arom.), 2950 (CH-aliph.) 1742 (CO), 1336, 1158 cm−1(SO2). MS:
m/z (%) = 518 (3.6; M+), 505 (40.2), 398 (24.0), 339 (100), 91 (14.8).
2-thioxo-7-p-tolyl-9-[4-(N,N-dimethylaminosulfonylphenyl)]-
2,3-dihydropyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (16)
A mixture of (13; 0.01 mol), 30 mL of ethanol, 0.3 g of KOH, and 3
mL of CS2 were refluxed for 5 h. After removal of ethanol, water was
added, and the alkaline solution was filtered. The clear filtrate was
acidified with acetic acid, and the formed precipitate was collected and
recrystallized to give (16) (Table I). IR (film) v = 3432 (NH), 3060 (CH-
arom.), 2926 (CH-aliph.), 1332, 1156 cm−1(SO2). MS: m/z (%) = 464
(5.7; M+), 408 (48.1), 354 (100), 301 (89.7), 229 (10.1), 199 (28.3), 91
(32.4), 44 (46.5).
2-Methylamino-7-p-tolyl-9-[4-(N,N-dimethylaminosulfonyl-
phenyl)]pyrrolo[3,2-e][1,2,4]triazolo[1,5-c] pyrimidine (17a)
A mixture of (13; 0.01 mol) in ethanol (30 mL) was treated with methyl
isothiocyanate (0.012 mol) and refluxed for 3 h. The obtained product
was filtered off and recrystallized to give (17a) (Table I). IR (film) v =

Heteroaromatization with Sulfonamido Phenyl Ethanone, Part I
307
3404 (NH), 3060 (CH-arom.), 2916 (CH-aliph.), 1334, 1160 cm−1(SO2).
1H-NMR (CDCl3): δ = 2.45 (s, 3H, CH3), 2.76 (s, 6H, N(CH3)2), 3.07 (d,
3H, NH-CH3), 4.73 (d, 1H, NH-CH3), 7.35 and 7.54 (dd, 4H, AB-ArH),
7.69 (s, 1H, CH-pyrrole), 7.83 and 8.38 (dd, 4H, AB-ArH), 8.87 ppm
(s, 1H, CH-pyrimidine). MS: m/z (%) =461 (86.2; M+), 407 (35.7), 354
(100), 270 (10.6), 229 (2.4), 199 (21.9), 91 (10.9).
2-Phenylamino-7-p-tolyl-9-N,N-[4-(N,N-
dimethylaminosulfonyl- phenyl)]
pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (17b)
Compound (17b) was prepared from (13; 0.01 mol) and phenyl isothio-
cyanate (0.012 mol) according to the preparation of (17a) (Table I). IR
(film) v = 3304 (NH), 3050 (CH-arom.), 2964 (CH-aliph.), 1338, 1158
cm−1(SO2). MS: m/z (%) = 423 (93.3; M+), 417 (75.1), 208 (17.0), 91
(27.2).
2-Methoxy-7-p-tolyl-9-[4-(N,N-dimethylaminosulfonylphenyl)]-
pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (19)
Compound (19) was prepared from the reaction of (13; 0.01 mol) and
methyl chloroformate (0.01 mol) according to the procedure used for
preparing (15a). IR (film) v = 3055 (CH-arom.), 2926 (CH-aliph.), 1332,
1
1162 cm−1(SO2). H-NMR (CDCl3): δ = 2.43 (s, 3H, CH3), 2.67 (s, 6H,
N(CH3)2), 3.98 (s, 3H, O-CH3), 7.37 and 7.83 (dd, 4H, AB-ArH), 7.68
(s, 1H, CH-pyrrole), 8.46 and 9.20 (dd, 4H, AB-ArH), 9.53 ppm (s, 1H,
CH-pyrimidine). MS: m/z (%) = 463 (4.0; M+), 357 (10.5), 341 (100), 298
(11.0).
2-Phenyl-7-p-tolyl-9-[4-(N,N-dimethylaminosulfonylphenyl)]-
pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (20)
Procedure A
A mixture of (13; 0.01 mol) and benzaldehyde (0.012 mol) in dioxane
(20 mL) and few drops of piperidine was refluxed for 5 h. The mixture
was then cooled, and the separated solid was filtered off and recrystal-
lized to give (20) (Table I).
Procedure B
A mixture of (13; 0.01 mol) and benzoylchloride (10 mL) was refluxed
for 3 h. The reaction mixture was then diluted with cold NaOH solution,
and the solid obtained was washed with water and recrystallized to give

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S. M. Hassan et al.
(20) (Table I). M.p. and mixed m.p determined with authentic sample
gave no depression. IR (film) v = 3074 (CH-arom.), 2918 (CH-aliph.),
1338, 1160 cm−1(SO2). MS: m/z (%) = 508 (32.9; M+), 401 (100), 297
(19.8), 118 (41.4), 91 (50.0).
Antimicrobial and Antifungal Screening
The prepared compounds were evaluated for their antimicrobial activ-
ity using the agar diffusion technique.14,15 A mg/mL solution in DMF
was used. The test organisms were Gram-positive Bacillus subtilis
(NCTC-1040), Staphylococcus aureus (NCTC-7447), and Sarcina max-
ima (ATCC-33910); Gram-negative Klebsiella pneumonia (NCIMB-
9111), Salmonella, and Pseudomonas aeruginosa (ATCC-10145); and
for 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).
REFERENCES
[1] R. J. Suhadolnik, Nucleoside Antibiotics, (Wiley Interscience, New York, 1970).
[2] R. Shankar, A. R. Devendra, E. R. Jayasena, V. M. Raddy, V. K. Saxena, and R.
Srivastava, J. Indian Chem. Soc., 60, 61 (1983).
[3] V. S. Misra, V. T. Saxena, and R. Srivastava, J. Indian Chem. Soc., 59, 781 (1982).
[4] M. T. L. Labro, Drugs, 15, 319 (1993).
[5] F. Zani and P. Vicini; Arch. Pharm,331, 219 (1998).
[6] C. T. Supuran, A. Scozzafava, B. C. Jurca, and M. A. Illes, Eur. J. Med. Chem., 33,
83 (1998).
[7] S. M. Hassan, M. M. Khafagy, H. A. Emam, and A. A. El-Maghraby; J. Indian Chem.
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[8] S. M. Hassan, Azhar. J. Pharm. Sci., 13, 84 (1994).
[9] A. M. El-Agrody and S. M. Hassan; J. Chem. Res. (S), 100 (1995).
[10] H. A. Emam, S. M. Hassan, and A. A. Al-Najjar, J. Chem. Res. (S), 474 (1995).
[11] S. M. Hassan, Al-Azhar Bull. Sci., 9(2), 535 (1998).
[12] S. M. Hassan, H. A. Emam, and M. A. Habib, Al-Azhar Bull. Sci., 12(2), 137 (2001).
[13] H. S. El-Kashef, B. E. Bayoumy and T. I. Aly, Egypt. J. Pharm. Sci., 27, 27 (1986).
[14] S. R. Jain and A. Kar, Planta Med., 20, 118 (1971).
[15] W. Hewitt and S. Vincent, Theory and Application of Microbiologically Assay (Aca-
demic Press, New York, 1989).