Novel synthesis of n-arylpyrrole, pyrrolo[1,2-a]quinazoline, and pyrrolo[3,4-d]pyridazine derivatives

Article abstract of DOI:10.1080/00397910902883710

Phenacyl-malononitrile derivatives 1a,b react with dimethyl formamide dimethyl acetal (DMFDMA) in refluxing toluene to afford the enaminones 2a,b respectively. Compounds 2a and 2b react with the aromatic amines (aniline, p-toluidine, p-anisidine) in reflu

Full text of DOI:10.1080/00397910902883710

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Novel Synthesis of N-
Arylpyrrole, Pyrrolo[1,2-
a]quinazoline, and Pyrrolo[3,4-
d]pyridazine Derivatives
Fathy M. Abdelrazek a & Nadia H. Metwally a
a Chemistry Department, Faculty of Science, Cairo
University, Giza, Egypt
Version of record first published: 16 Oct 2009.
To cite this article: Fathy M. Abdelrazek & Nadia H. Metwally (2009): Novel Synthesis
of N-Arylpyrrole, Pyrrolo[1,2-a]quinazoline, and Pyrrolo[3,4-d]pyridazine Derivatives,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 39:22, 4088-4099
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Synthetic Communications1, 39: 4088–4099, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902883710
Novel Synthesis of N-Arylpyrrole,
Pyrrolo[1,2-a]quinazoline, and
Pyrrolo[3,4-d]pyridazine Derivatives
Fathy M. Abdelrazek and Nadia H. Metwally
Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt
Abstract: Phenacyl-malononitrile derivatives 1a,b react with dimethyl formamide
dimethyl acetal (DMFDMA) in refluxing toluene to afford the enaminones 2a,b
respectively. Compounds 2a and 2b react with the aromatic amines (aniline,
p-toluidine, p-anisidine) in refluxing ethanol to afford the pyrroles 4a–f and with
anthranilonitrile and methyl anthranilate to afford the pyrrolo[1,2-a]quinazolines
5a,b and 6a,b respectively. The pyrrole derivatives 4a–f react with hydrazine
hydrate and phenyl hydrazine in refluxing ethanol to afford the pyrrolo[3,4-d]
pyridazine derivatives 7a–f and 8a–f respectively.
Keywords: Phenacylmalononitriles, pyrroles, pyrrolo[3,4-d]pyridazines, pyrrolo
[1,2-a]quinazolines
INTRODUCTION
The diverse biological activity of pyrroles and their fused derivatives
as well as their importance in pharmaceutical industries have stimu-
lated intensive research in this area, and many articles have been
published.[1–5]
In the past two decades, we have been involved in a program to
develop new simple routes for the synthesis of pyrrole, N-substituted pyr-
role, and fused-pyrrole derivatives of biological interest.[6–11] Recently,
Received December 9, 2008.
Address correspondence to Fathy M. Abdelrazek, Chemistry Department,
Faculty of Science, Cairo University, Giza, Egypt. E-mail: prof_fmrazek@
yahoo.com
4088

N-Arylpyrroles and Derivatives
4089
Scheme 1. Synthesis and reactions of N-aryl pyrroles.
some pyrrolo[2,3-b]pyridine derivatives were shown to be effective as
inhibitors of tumor necrosis factor alpha.[4] In the context of our pro-
gram, some new N-substituted pyrrole and pyrrolopyridazine derivatives
were required for biological evaluation. 2-(2-Oxo-2-phenyl or [2-p-
tolyl]-ethyl)-malononitrile derivatives 1a,b (Scheme 1) seemed suitable
to fulfill our objective via their reaction with dimethyl formamide
dimethyl acetal (DMFDMA) and then reacting the resulting enaminones
with different aromatic amines.
RESULTS AND DISCUSSION
Thus, compounds 1a,b were prepared according to our previously
reported methods.[12,13] Compounds 1a,b were allowed to react with
DMFDMA in refluxing toluene to afford the enamines 2a,b respectively.

4090
F. M. Abdelrazek and N. H. Metwally
Structures 2a,b were assigned on the basis of the correct elemental
analyses as well as spectral data. The 13C NMR spectrum of 2a showed
a pattern that is completely applicable to the depicted structure (see
Experimental).
Compounds 2a and 2b react with the aromatic amines (aniline,
p-toluidine, p-anisidine, anthranilonitrile, and methyl anthranilate) in
refluxing ethanol to afford yellow- to brown-colored products. Elemental
analyses of these products showed that the NMe2 moiety in 2 was substi-
tuted by the aromatic amine residue; however, the appearance of a signal
in the 1H NMR spectra of all the products at d ꢀ 6.9 ppm and integrated
for (1 H) points to a pyrrole 5-H proton. Thus, the pyrrole structures 4a–f
were assigned to the products of the reaction of 2a,b with aniline, p-tolui-
dine, or p-anisidine derivatives respectively based on the correct elemen-
tal analyses and the spectral data. The 13C NMR spectrum of 4a also is in
agreement with the assigned structure. The formation of 4a–f from the
reaction of 2a,b with the aromatic amines is assumed to take place via
the attack of the aromatic amine on the enaminone carbon with elimina-
tion of dimethyl amine to afford the intermediate 3, which undergoes
cyclization to afford 4a–f.
The reaction of 2a,b with anthranilonitrile apparently follows the
same pathway, however, the resulting pyrrole in this case undergoes a
further cyclization via addition of the formed pyrrole NH2 to the cyano
group on the phenyl ring to afford the imino-pyrrolo[1,2-a]quinazolines
5a,b respectively. Methyl anthranilate reacts with both 2a and 2b,
seemingly following the same route; however, the second cyclization
takes place in this case via elimination of methanol to afford 6a and 6b
respectively. Structures 5a,b and 6a,b were confirmed by the analytical
and spectral data. Furthermore compounds 5a,b could be quantitatively
transformed into 6a,b upon reflux in ethanolic HCl. The resulting
products are completely identical with those obtained from the reaction
of 2a,b with methyl anthranilate.
On the other hand, c-ketonitriles are known versatile reagents in
heterocyclic synthesis. We now explore the c-ketonitrile moiety in the
pyrrole derivatives 4a–f to synthesize some novel pyrrolo[3,4-d]pyridazine
derivatives. Thus, compounds 4a–f were allowed to react with hydrazine
hydrate and phenyl hydrazine in refluxing ethanol to afford yellow- to
brown-colored products. Elemental analyses of these products showed
that they are 1:1 adducts after elimination of water. The infrared (IR)
spectra of these new compounds do not show any absorption bands at
the range of tmax ꢀ 1990–2230 cmꢁ1 due to cyano groups or at
tmax ꢀ 1650–1690 cmꢁ1 due to carbonyl groups. Based on these data,
the pyrrolo[3,4-d] pyridazine derivatives 7a–f and 8a–f were assigned to

N-Arylpyrroles and Derivatives
4091
these products respectively. Analytical and spectral data are in complete
agreement with these structures.
EXPERIMENTAL
Melting points were measured on an Electrothermal 9100 apparatus
and are uncorrected. IR spectra were recorded as KBr pellets on a
Perkin-Elmer 1430 spectrophotometer. The 1H NMR and 13C NMR
spectra were taken on a Varian Gemini 300-MHz spectrometer in
dimethyl sulfoxide (DMSO-d6) using tetramethylsilane (TMS) as inter-
nal standard, and chemical shifts are expressed in d ppm values. Mass
spectra were taken on a Shimadzu GCMS-GB 1000 PX (70 ev).
Elemental analyses were carried out at the Micro-analytical Center
at Cairo University.
Preparation of the Enaminone Derivatives 2a,b
A mixture of each of compounds 1a,b (10 mmol) and DMFDMA
(1.19 g, 10 mmol) in dry toluene (10 ml) was refluxed for 4 h. The reac-
tion mixture was evaporated under reduced pressure until it was one
third its original volume, and then it was left to cool overnight to yield
crude products, which were recrystallized from toluene to give
compounds 2a,b.
2-(1-Benzoyl-2-dimethylamino-vinyl)-malononitrile 2a
Pale yellow crystalline product; yield 1.8 g (75%); mp 128–130ꢂC. tmax
¼
2210 (CN), 1653 (CO); MS: m=z ¼ 239 (Mþ). dH ¼ 3.08 (s, 6 H, 2 CH3),
7.08 (s, 1 H, CH), 7.35–7.75 (m, 5 H, Ar-H), 8.44 (s, 1 H, CH);
dC ¼ 18.09 (d), 37.44 (q), 38.31 (q), 78.17 (s), 106.93 (s), 129.04 (d),
129.43 (d), 134.33 (d), 134.89 (s), 155.33 (d), 194.47 (s). Anal. calcd. for
C14H13N3O (239.27): C, 70.28; H, 5.48; N, 17.56. Found: C, 70.40; H,
5.55; N, 17.40.
2-[2-Dimethylamino-1-(4-methylbenzoyl)-vinyl]-malononitrile 2b
Yellow crystals; yield 1.8 g (73%); mp 123–125ꢂC. tmax ¼ 2208 (CN), 1655
(CO); MS: m=z ¼ 253 (Mþ). dH ¼ 2.32 (s, 3 H, CH3), 2.95 (s, 6 H, 2CH3),
7.12 (s, 1 H, CH), 7.23–7.28 & 7.60–7.66 (2d, 4 H, Ar-H), 8.42 (s, 1 H,

4092
F. M. Abdelrazek and N. H. Metwally
CH). Anal. calcd. for C15H15N3O (253.30): C, 71.13; H, 5.97; N, 16.59.
Found: C, 71.40; H, 5.85; N, 16.55.
Preparation of the Pyrrole Derivatives 4a–f and the Pyrrolo[1,2-a]quiazo-
line Derivatives 5a,b and 6a,b (General Procedure)
A mixture of each of compounds 2a or 2b (10 mmol) and the respective
aromatic amine (aniline, p-toluidine, p-anisidine, anthranilonitrile, or
methyl anthranilate) (10 mmol) in ethanol (15 ml) was refluxed for 3 h
(with monitoring by thin-layer chromatography, TLC). The reaction
mixture was left to cool and then was poured onto ice water. The solid
precipitates thus formed were collected by filtration and recrystallized
from ethanol=DMF (4:1).
2-Amino-4-benzoyl-1-phenyl-1H-pyrrole-3-carbonitrile 4a
Pale yellow crystals; yield 1.7 g (60%); mp 187–188ꢂC. tmax ¼ 3350, 3230
(NH2), 2220 (CN), 1660 (CO); dH ¼ 5.6 (s, 2 H D2O exch., NH2), 6.95
(s, 1 H, CH), 7.33–7.80 (m, 10 H, Ar-H). dC ¼ 99.13 (s), 112.14 (s),
120.28 (d), 124.15 (d), 125.34 (d), 128.76 (d), 129.13 (d), 129.23 (d),
140.38 (s), 150.03 (s), 154.01 (s), 158.65 (d), 166.25 (s), 189.57 (s). MS:
m=z ¼ 287 (Mþ). Anal. calcd. for C18H13N3O (287.32): C, 75.25; H,
4.56; N, 14.63. Found: C, 75.35; H, 4.60; N, 14.75.
2-Amino-4-(4-methylbenzoyl)-1-phenyl-1H-pyrrole-3-carbonitrile 4b
Brownish yellow crystals; yield 1.8 g (60%); mp 207–208ꢂC.
tmax ¼ 3350, 3230 (NH2), 2218 (CN), 1663 (CO); dH ¼ 2.42 (s, 3 H,
CH3), 5.58 (s, 2 H D2O exch., NH2), 6.94 (s, 1 H, CH), 7.30–7.78
(m, 9 H, Ar-H). MS: m=z ¼ 301 (Mþ). Anal. calcd. for C19H15N3O
(301.34): C, 75.73; H, 5.02; N, 13.94. Found: C, 75.80; H, 5.15;
N, 14.05.
2-Amino-4-benzoyl-1-(4-methylphenyl)-1H-pyrrole-3-carbonitrile 4c
Brownish yellow crystals; yield 1.8 g (60%); mp 203–204ꢂC.
tmax ¼ 3350, 3230 (NH2), 2217 (CN), 1661 (CO); dH ¼ 2.41 (s, 3 H,
CH3), 5.59 (s, 2 H D2O exch., NH2), 6.94 (s, 1 H, CH), 7.28–7.80 (m,
9 H, Ar-H). MS: m=z ¼ 301 (Mþ). Anal. calcd. for C19H15N3O (301.34):
C, 75.73; H, 5.02; N, 13.94. Found: C, 75.85; H, 5.10; N, 14.15.

N-Arylpyrroles and Derivatives
4093
2-Amino-4-(4-methylbenzoyl)-1-(4-methylphenyl)-1H-pyrrole-3-
carbonitrile 4d
Brown crystals; yield 1.95 g (62%); mp 195–197ꢂC. tmax ¼ 3347, 3235
(NH2), 2210 (CN), 1655 (CO); dH ¼ 2.39 (s, 3 H, CH3), 2.40 (s, 3 H,
CH3), 5.55 (s, 2 H D2O exch., NH2), 6.93 (s, 1 H, CH), 7.33–7.80 (m,
8 H, Ar-H). MS: m=z ¼ 315 (Mþ). Anal. calcd. for C20H17N3O (315.37):
C, 76.17; H, 5.43; N, 13.32. Found: C, 76.25; H, 5.55; N, 13.40.
2-Amino-4-benzoyl-1-(4-methoxyphenyl)-1H-pyrrole-3-carbonitrile 4e
Yellow crystals; yield 2.0 g (65%); mp 210–212ꢂC. tmax ¼ 3350, 3230
(NH2), 2218 (CN), 1662 (CO); dH ¼ 3.84 (s, 3 H, CH3), 5.59 (s, 2 H
D2O exch., NH2), 6.77–7.78 (m, 10 H, Ar-H). MS: m=z ¼ 317 (Mþ). Anal.
calcd. for C19H15N3O (317.34): C, 71.91; H, 4.76; N, 13.24. Found: C,
71.85; H, 4.70; N, 13.35.
2-Amino-4-(4-methylbenzoyl)-1-(4-methoxyphenyl)-
1H-pyrrole-3-carbonitrile 4f
Dark yellow crystals; yield 2.1 g (63%); mp 218–220ꢂC. tmax ¼ 3345, 3228
(NH2), 2207 (CN), 1659 (CO); dH ¼ 2.38 (s, 3 H, CH3), 3.80 (s, 3 H, CH3),
5.58 (s, 2 H D2O exch., NH2), 6.78–7.70 (m, 9 H, Ar-H). MS: m=z ¼ 331
(Mþ). Anal. calcd. for C20H17N3O2 (331.37): C, 72.49; H, 5.17; N, 12.68.
Found: C, 72.55; H, 5.20; N, 12.85.
2-Benzoyl-5-imino-4,5-dihydropyrrolo[1,2-a]quinazoline-
3-carbonitrile 5a
Yellow crystalline solid; yield 2.28 g (73%); mp 215–216ꢂC. tmax ¼ 3330,
3325 (NH), 2215 (CN), 1664 (CO); dH ¼ 6.93 (s, 1 H, CH), 7.23 (s, 1 H
D2O exch., NH), 7.25–7.85 (m, 9 H, Ar-H), 10.20 (s, 1 H D2O exch.,
NH). MS: m=z ¼ 312 (Mþ). Anal. calcd. for C19H12N4O (312.32): C,
73.07; H, 3.87; N, 17.94. Found: C, 73.17; H, 3.80; N, 17.85.
5-Imino-2-(4-methylbenzoyl)-4,5-dihydropyrrolo[1,2-a]quinazoline-3-
carbonitrile 5b
Dark yellow crystalline solid; yield 2.28 g (70%); mp 225–227ꢂC. tmax
3332, 3327 (NH), 2218 (CN), 1665 (CO); dH ¼ 2.36 (s, 3 H, CH3), 6.95
¼

4094
F. M. Abdelrazek and N. H. Metwally
(s, 1 H, CH), 7.22 (s, 1 H D2O exch., NH), 7.28–7.72 (m, 8 H, Ar-H),
10.25 (s, 1 H D2O exch., NH). MS: m=z ¼ 326 (Mþ). Anal. calcd. for
C20H14N4O (326.35): C, 73.61; H, 4.32; N, 17.17. Found: C, 73.65; H,
4.40; N, 17.27.
2-Benzoyl-5-oxo-4,5-dihydropyrrolo[1,2-a]quinazoline-3-carbonitrile 6a
Pale yellow crystalline solid; yield 2.35 g (75%); mp 235–236ꢂC.
tmax ¼ 3333, 3327 (NH), 2217 (CN), 1665 & 1678 (2CO); dH ¼ 6.91
(s, 1 H, CH), 7.38–7.85 (m, 9 H, Ar-H), 8.21 (s, 1 H D2O exch., NH).
MS: m=z ¼ 313 (Mþ). Anal. calcd. for C19H11N3O2 (313.31): C, 72.84;
H, 3.54; N, 13.41. Found: C, 72.95; H, 3.60; N, 13.50.
2-(4-Methylbenzoyl)-5-oxo-4,5-dihydropyrrolo[1,2-a]quinazoline-3-
carbonitrile 6b
Yellow crystalline solid; yield 2.40 g (74%); mp 239–241ꢂC. tmax ¼ 3328,
3325 (NH), 2223 (CN), 1663 & 1675 (2CO); dH ¼ 2.35 (s, 3 H, CH3),
6.92 (s, 1 H, CH), 7.28–8.05 (m, 8 H, Ar-H), 8.24 (s, 1 H D2O exch.,
NH). MS: m=z ¼ 327 (Mþ). Anal. calcd. for C20H13N3O2 (327.34): C,
73.38; H, 4.00; N, 12.84. Found: C, 73.40; H, 4.05; N, 12.94.
Transformation of Compounds 5a,b into 6a,b
To a solution of 5a or 5b (10 mmol) in 25 ml of ethanol 5 ml of conc. HCl
were added. The reaction mixture was refluxed for 1 h in each case. After
cooling to room temperature, the reaction mixture was diluted with cold
water and cautiously neutralized with ammonia. The precipitated solids
were collected by filtration and recrystallized from ethanol to afford com-
pounds 6a and 6b respectively. The identity of these products was
deduced from matching melting points and spectral data.
Preparation of the Pyrrolo[3,4-d]pyridazine Derivatives 7a–f and 8a–f
To a solution of each of 4a–f (10 mmol) in ethanol (20 mL), 10 mmol of
either hydrazine hydrate or phenyl hydrazine were added. The reaction
mixture was refluxed for 2 h in each case and then left to cool overnight.
The reaction mixture was poured on ice-cold water and acidified with dil.
HCl until it was just neutral. The precipitated solid in each case was
filtered off and recrystallized from the ethanol=DMF mixture (4:1) to

N-Arylpyrroles and Derivatives
4095
afford compounds 7a–f in the case of hydrazine hydrate and 8a–f in the
case of phenyl hydrazine.
4,6-Diphenyl-6H-pyrrolo[3,4-d]pyridazine-1,7-diamine 7a
Yellow crystals; yield 2.0 g (68%); mp 225–227ꢂC. tmax ¼ 3350, 3230
(NH2); dH ¼ 4.59 (s, 2 H D2O exch., NH2), 6.95 (s, 1 H, CH),
7.12–7.75 (m, 10 H, Ar-H), 8.10 (s, 2 H D2O exch., NH2). dC ¼ 98.15
(s), 120.24 (d), 125.35 (d), 127.3 (d), 128.76 (d), 129.13 (d), 129.23
(d), 136.72 (s), 140.48 (s), 150.10 (s), 154.01 (s), 156.65 (d), 166.25
(s), 163.67 (s). MS: m=z ¼ 301 (Mþ). Anal. calcd. for C18H15N5
(301.35): C, 71.74; H, 5.02; N, 23.24. Found: C, 71.70; H, 5.05; N,
23.30.
6-Phenyl-4-(4-methylphenyl)-6H-pyrrolo[3,4-d]
pyridazine-1,7-diamine 7b
Dark yellow powder; yield 2.0 g (68%); mp 230–232ꢂC. tmax ¼ 3348, 3232
(NH2); dH ¼ 2.33 (s, 3 H, CH3), 4.60 (s, 2 H D2O exch., NH2), 6.94 (s, 1 H,
CH), 7.20–7.74 (m, 9 H, Ar-H), 8.09 (s, 2 H D2O exch., NH2). MS:
m=z ¼ 315 (Mþ). Anal. calcd. for C19H17N5 (315.37): C, 72.36; H, 5.43;
N, 22.21. Found: C, 72.40; H, 5.55; N, 22.30.
4-Phenyl-6-(4-methylphenyl)-6H-pyrrolo[3,4-d]
pyridazine-1,7-diamine 7c
Yellow crystals; yield 2.0 g (68%); mp 225–227ꢂC. tmax ¼ 3350, 3234
(NH2); dH ¼ 2.31 (s, 3 H, CH3), 4.59 (s, 2 H D2O exch., NH2), 6.95
(s, 1 H, CH), 7.12–7.52 (m, 9 H, Ar-H), 8.10 (s, 2 H D2O exch., NH2).
MS: m=z ¼ 315 (Mþ). Anal. calcd. for C19H17N5 (315.37): C, 72.36; H,
5.43; N, 22.21. Found: C, 72.42; H, 5.56; N, 22.35.
4,6-Di-(4-methylphenyl)-6H-pyrrolo[3,4-d]
pyridazine-1,7-diamine 7d
Brown powder; yield 2.2 g (67%); mp 219–220ꢂC. tmax ¼ 3350, 3230
(NH2); dH ¼ 2.37 (s, 3 H, CH3), 2.39 (s, 3 H, CH3), 4.58 (s, 2 H D2O
exch., NH2), 6.93 (s, 1 H, CH), 7.27–7.71 (m, 8 H, Ar-H), 8.10
(s, 2 H D2O exch., NH2). MS: m=z ¼ 329 (Mþ). Anal. calcd. for

4096
F. M. Abdelrazek and N. H. Metwally
C20H19N5 (329.40): C, 72.93; H, 5.81; N, 21.26. Found: C, 73.05;
H, 5.90; N, 21.35.
4-Phenyl-6-(4-methoxyphenyl)-6H-pyrrolo[3,4-d]pyridazine-
1,7-diamine 7e
Dark yellow powder; yield 2.2 g (66%); mp 224–225ꢂC. tmax ¼ 3359, 3236
(NH2); dH ¼ 3.81 (s, 3 H, CH3), 4.58 (s, 2 H D2O exch., NH2), 6.68–7.55
(m, 10 H, Ar-H), 8.07 (s, 2 H D2O exch., NH2). MS: m=z ¼ 331 (Mþ).
Anal. calcd. for C19H17N5O (331.37): C, 68.87; H, 5.17; N, 21.13. Found:
C, 68.95; H, 5.10; N, 21.00.
4-(4-Methylphenyl)-6-(4-methoxyphenyl)-6H-pyrrolo[3,4-
d]pyridazine-1,7-diamine 7f
Brown powder; yield 2.17 g (63%); mp 221–222ꢂC. tmax ¼ 3356, 3235
(NH2); dH ¼ 2.38 (s, 3 H, CH3), 3.82 (s, 3 H, CH3), 4.57 (s, 2 H D2O exch.,
NH2), 6.75–7.42 (m, 9 H, Ar-H), 8.05 (s, 2 H D2O exch., NH2). MS:
m=z ¼ 345 (Mþ). Anal. calcd. for C20H19N5O (345.40): C, 69.55; H,
5.54; N, 20.28. Found: C, 69.60; H, 5.59; N, 20.35.
4-Imino-1,3,6-triphenyl-4,6-dihydro-3H-pyrrolo[3,4-d]
pyridazin-5-ylamine 8a
Brown crystals; yield 2.6 g (69%); mp 235–237ꢂC. tmax ¼ 3350, 3230, 3182
(NH2, NH); dH ¼ 4.61 (s, 2 H D2O exch., NH2), 6.55–7.62 (m, 16 H,
Ar-H), 11.46 (s, 1 H D2O exch., NH). MS: m=z ¼ 377 (Mþ). Anal. calcd.
for C24H19N5 (377.44): C, 76.37; H, 5.07; N, 18.55. Found: C, 76.50; H,
5.17; N, 18.63.
4-Imino-3,6-diphenyl-1-(4-methylphenyl)-4,6-dihydro-
3H-pyrrolo[3,4-d]pyridazin-5-ylamine 8b
Brown crystals; yield 2.66 g (68%); mp 229–231ꢂC. tmax ¼ 3352, 3230,
3184 (NH2, NH); dH ¼ 2.37 (s, 3 H, CH3), 4.60 (s, 2 H D2O exch.,
NH2), 6.53–7.65 (m, 15 H, Ar-H), 11.45 (s, 1 H D2O exch., NH). MS:
m=z ¼ 391 (Mþ). Anal. calcd. for C25H21N5 (391.47): C, 76.70; H, 5.41;
N, 17.89. Found: C, 76.75; H, 5.50; N, 17.95.

N-Arylpyrroles and Derivatives
4097
4-Imino-1,3-diphenyl-6-(4-methylphenyl)-4,6-dihydro-3H-pyrrolo
[3,4-d]pyridazin-5-ylamine 8c
Brown crystals; yield 2.58 g (66%); mp 232–233ꢂC. tmax ¼ 3352, 3225,
3176 (NH2, NH); dH ¼ 2.36 (s, 3 H, CH3), 4.62 (s, 2 H D2O exch.,
NH2), 6.55–7.65 (m, 15 H, Ar-H), 11.44 (s, 1 H D2O exch., NH). MS:
m=z ¼ 391 (Mþ). Anal. calcd. for C25H21N5 (391.47): C, 76.70; H, 5.41;
N, 17.89. Found: C, 76.80; H, 5.52; N, 18.00.
4-Imino-3-phenyl-1,6-di-(4-methylphenyl)-4,6-dihydro-3H-pyrrolo
[3,4-d]pyridazin-5-ylamine 8d
Brown crystals; yield 2.58 g (66%); mp 237–239ꢂC. tmax ¼ 3350, 3228,
3180 (NH2, NH); dH ¼ 2.36 (s, 3 H, CH3), 2.37 (s, 3 H, CH3), 4.59 (s,
2 H D2O exch., NH2), 6.50–7.55 (m, 14 H, Ar-H), 11.45 (s, 1 H D2O
exch., NH). MS: m=z ¼ 405 (Mþ). Anal. calcd. for C26H23N5 (405.49):
C, 77.01; H, 5.72; N, 17.27. Found: C, C, 77.05; H, 5.85; N, 17.37.
4-Imino-1,3-diphenyl-6-(4-methoxyphenyl)-4,6-dihydro-3H-pyrrolo
[3,4-d]pyridazin-5-ylamine 8e
Coffee brown crystals; yield 2.65 g (65%); mp 240–241ꢂC. tmax ¼ 3355,
3232, 3184 (NH2, NH); dH ¼ 3.81 (s, 3 H, CH3), 4.58 (s, 2 H D2O exch.,
NH2), 6.50–7.63 (m, 15 H, Ar-H), 11.47 (s, 1 H D2O exch., NH). MS:
m=z ¼ 407 (Mþ). Anal. calcd. for C25H21N5O (407.47): C, 73.69; H,
5.19; N, 17.19. Found: C, 73.70; H, 5.25; N, 17.30.
4-Imino-6-(4-methoxyphenyl)-3-phenyl-1-(4-methylphenyl)-
4,6-dihydro-3H-pyrrolo[3,4-d]-pyridazin-5-ylamine 8f
Dark brown crystals; yield 2.74 g (65%); mp 245–247ꢂC. tmax ¼ 3356,
3225, 3179 (NH2, NH); dH ¼ 2.37 (s, 3 H, CH3), 3.78 (s, 3 H, CH3),
4.63 (s, 2 H D2O exch., NH2), 6.48–7.56 (m, 14 H, Ar-H), 11.46 (s, 1 H
D2O exch., NH). MS: m=z ¼ 421 (Mþ). Anal. calcd. for C26H23N5O
(421.49): C, 74.09; H, 5.50; N, 16.62. Found: C, 74.15; H, 5.55; N, 16.83.
CONCLUSION
We could prepare series of N-substituted pyrrole, pyrrolo[1,2-a]quinazo-
line, and pyrrolo[3,4-d]pyridazine derivatives of anticipated diverse

4098
F. M. Abdelrazek and N. H. Metwally
biological activities from laboratory-available starting materials. The
synthetic methods used throughout are rather simple and ecofriendly
because no heavy metals or hazardous solvents were involved.
ACKNOWLEDGMENTS
F. M. Abdelrazek thanks the Alexander von Humboldt Foundation
(Germany) for granting short research fellowships, continuous help,
and support and Professor Peter Metz, Institut fur Organische Chemie,
¨
TU Dresden, for his kind hospitality.
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