A new approach for the synthesis of some fused pyrazolo-, triazolo-, tetrazolo-, diazepino-, oxazepino-, and thiazepinopyridazine derivatives

Article abstract of DOI:10.1080/10426500307951

Hydrazinolysis of 4-benzoyl-5,6-diphenyl-pyridazin-3(2H)-one 1a in acetic acid or 3-chloropyridazine derivative 2 in ethanol afforded the pyrazolo[3,4-c]pyridazine derivative 3. While boiling 1a with hydrazine hydrate in ethanol gave the corresponding hydrazono derivative 4. Reaction of compound 2 with benzhydrazide in refluxing 1-butanol yielded triazolo[4,3-b]pyridazine 5. On treatment of 2 with sodium azide tetrazolopyridazine 6 resulted. The reaction of 1a (in acetic acid) or 2 (in ethanol) with o-phenylenediamine and o-aminophenol yielded diazepino- and oxazepinopyridazine derivatives 7a and 7b, respectively, while 2 with o-aminothiophenol in ethanol gave thiazepinopyridazine derivative 7c. Moreover, treatment of 1a (in acetic acid) or 2 (in ethanol) with ethylenediamine and 2-aminoethanol produced 8a, 8b and 9a, 9b respectively. Chlorination of the carbinol derivatives 11a and 11b with phosphorus oxychloride gave the dichloro derivatives 12a and 12b, which reacted with hydrazine to form pyrazolopyridazines 13a and 13b respectively. However, thionation of 11b gave the thionated product 14. Compound 14 was confirmed by methylation and hydrazinolysis forming 15 and 16 respectively.

Full text of DOI:10.1080/10426500307951

Phosphorus, Sulfur and Silicon, 2003, Vol. 178:199–210
C
Copyright 2003 Taylor & Francis
1042-6507/03 $12.00 + .00
DOI: 10.1080/10426500390170336
A NEW APPROACH FOR THE SYNTHESIS OF SOME
FUSED PYRAZOLO-, TRIAZOLO-, TETRAZOLO-,
DIAZEPINO-, OXAZEPINO-, AND
THIAZEPINOPYRIDAZINE DERIVATIVES
Alyaa A. Shalaby
Ain Shams University, Abbassia, Cairo, Egypt
(Received October 30, 2001; accepted April 2, 2002)
Hydrazinolysis of 4-benzoyl-5,6-diphenyl-pyridazin-3(2H)-one 1a in
acetic acid or 3-chloropyridazine derivative 2 in ethanol afforded the
pyrazolo[3,4-c]pyridazine derivative 3. While boiling 1a with hydrazine
hydrate in ethanol gave the corresponding hydrazono derivative 4.
Reaction of compound 2 with benzhydrazide in refluxing 1-butanol
yielded triazolo[4,3-b]pyridazine 5. On treatment of 2 with sodium
azide tetrazolopyridazine 6 resulted. The reaction of 1a (in acetic acid)
or 2 (in ethanol) with o-phenylenediamine and o-aminophenol yielded
diazepino- and oxazepinopyridazine derivatives 7a and 7b, respec-
tively, while 2 with o-aminothiophenol in ethanol gave thiazepinopy-
ridazine derivative 7c. Moreover, treatment of 1a (in acetic acid) or 2
(in ethanol) with ethylenediamine and 2-aminoethanol produced 8a,
8b and 9a, 9b respectively. Chlorination of the carbinol derivatives
11a and 11b with phosphorus oxychloride gave the dichloro deriva-
tives 12a and 12b, which reacted with hydrazine to form pyrazolopy-
ridazines 13a and 13b respectively. However, thionation of 11b gave
the thionated product 14. Compound 14 was confirmed by methylation
and hydrazinolysis forming 15 and 16 respectively.
Keywords: Chlorination; fused pyridazines; methylation of pyridazi-
none derivatives; N-nucleophiles; thionation
In an effort to synthesize new fused pyridazines, I selected 4-benzoyl-
5,6-diphenylpyridazin-3(2H)-one1 1a and its chlorinated product
4-benzoyl-3-chloro-5,6-diphenylpyridazine2 2, 5,6-diphenyl-4-(1,1-
diphenyl-l-hydroxymethyl)-2,3-dihydropyridazin-3-one1 11a and 5,6-
diphenyl-4-(1,1-dibenzyl-l-hydroxymethyl)-2,3-dihydropyridazin-3-one1
11b as the starting materials. Thus, refluxing 1a in glacial acetic acid
Address correspondence to Alyaa A. Shalaby, Chemistry Department, Faculty of
Science, Ain Shams University, Abbassia, Cairo, Egypt. E-mail: dr.alyaa@msn.com
199

200
A. A. Shalaby
SCHEME 1
or 2 in ethanol with hydrazine hydrate afforded the pyrazolo[3,4-c]
pyridazine derivative 3 (Scheme 1). The structure of the product 3
was deduced from its spectral data. While boiling 1a with hydrazine
hydrate in ethanol for 3 h gave the corresponding hydrazono derivative
4 (Scheme 1). The structure of compound 4 was verified from its
spectral data.
The action of benzhydrazide on compound 2 in 1-butanol3 produced
triazolo[4,3-b]pyridazine 5 (Scheme 1). The structure of the product 5
was deduced from its analytical and spectral data. The IR spectrum
revealed a carbonyl group of an unsaturated ketone at 1669 cm 1. The
mass spectrum showed the molecular ion peak [M+. = 452, 3%] and the
base peak at [m/e = 103], corresponding to the benzonitrile molecule.
Reaction of compound 2 with sodium azide in dimethylformamide4
afforded tetrazolo[4,5-b]pyridazine 6 (Scheme 1). This structure was
confirmed by its IR spectrum, which showed carbonyl absorption of a
1
conjugated ketone at 1677 cm 1. The H-NMR spectrum showed only
a multiplet for 15 protons of the three phenyl groups. The mass spec-
trum revealed the molecular ion with low intensity [M+. = 377, 1%], and
the base peak at [m/e = 321], corresponding to [M+.-2N2], which was
indicative for the excepted structure.

Pyrazolo-, Triazolo-, Tetrazolo-, Diazepino-, Oxazepino-, and Thiazepinopyridazine 201
Refluxing compound 2 in ethanol with o-phenylenediamine, o-amino-
phenol, and o-aminothiophenol gave diazepino-, oxazepino-, and thi-
azepinopyridazine derivatives 7a–c, respectively. However, compounds
7a and 7b also were obtained by treatment of 1a in acetic acid with
o-phenylenediamine and o-aminophenol respectively. The structure of
the products 7a–c were verified by their analytical and spectral data
(cf. Experimental and Scheme 1).
The reaction of compound 1a with ethylenediamine and 2-amino-
ethanol in acetic acid yielded pyridazino-diazepine 8a and pyridazino-
oxazepine 8b, respectively (Scheme 1). The structures of the prod-
ucts 8a and 8b were established by their IR, 1H-NMR, and mass
spectra.
However, the reaction of 2 with ethylenediamine and 2-amino-
ethanol either in ethanol or 1-butanol for a long time afforded the un-
expected pyridazine derivatives 9a and 9b, respectively (Scheme 1).
The structures of these products were verified by their spectral data.
Their IR spectra showed carbonyl absorptions of conjugated ketones at
1
1
1667 cm and two bands at 3428, 3378 cm for symmetric and un-
symmetric stretching vibration of a NH2 group. The structure of com-
pound 9b also was confirmed by condensing it with benzaldehyde in the
presence of piperidine forming the Schiff’s base 10 (Scheme 1). The IR
spectrum of 10 lacked the bands characteristic for NH2 group, which
means that compound 9b is an ether derivative. The mass spectrum of
9b confirmed the proposed structure.
Moreover, chlorination of the carbinol derivatives1 11a and 11b, with
phosphorus oxychloride yielded the dichloropyridazine derivatives 12a
and 12b respectively (Scheme 2). The structures for compounds 12a
and 12b were established from their IR spectra, which lacked the bands
characteristic for OH groups. Their 1H-NMR showed the aromatic pro-
tons, besides the methylene protons in case of 12b and lacked any pro-
tons characteristic for OH groups. The mass spectrum for compound
12b showed a complicated structure due to the presence of the two
chlorine atoms and their isotopes.
The dichloro derivatives 12a and 12b reacted with hydrazine
in ethanol to give pyrazolopyridazines 13a and 13b, respectively
(Scheme 2). The structures of 13a and 13b were verified by their spec-
tral data. Their IR spectra showed bands characteristic for NH groups
at (3214, 3176) and (3271, 3176) cm 1, respectively, their 1H-NMR spec-
tra revealed two protons for two NH groups at 9.15 and 8.35 be-
sides the aromatic and the methylene protons for compound 13b. The
mass spectrum for compound 13a showed the molecular ion peak with
low intensity, but its base peak appeared at m/e 412 corresponding to
[M+. N], while the mass spectrum for compound 13b lacked the

202
A. A. Shalaby
SCHEME 2
molecular ion peak, but exhibited a peak at m/e 436 (19%), correspond-
ing to [M+. (NH3, .H)] and the base peak at m/e 356.
Thionation of compound 11b with phosphorus pentasulfide in dry
xylene afforded compound 14 (Scheme 2) through elimination of H2S
gas; its structure was deduced from its analytical and spectral data
together with its chemical reactions.
Methylation of 14 with methyl iodide afforded a quantitative yield
of thiomethyl derivative 15 (Scheme 2). Hydrazinolysis of 14 with hy-
drazine in ethanol gave 16 (Scheme 2). The structures of compounds 15
and 16 were established from their analytical and spectral data.
EXPERIMENTAL
All melting points were taken on Giffin and George melting point ap-
paratus and are uncorrected. IR absorption spectra were determined
1
with a Moltson-1000 series FTIR spectrometer. H-NMR spectra were

Pyrazolo-, Triazolo-, Tetrazolo-, Diazepino-, Oxazepino-, and Thiazepinopyridazine 203
determined on Bruker DRX500 or Bruker AC-200. The mass spectra
were determined using AMD 604 spectrometer; SHIMADZU single fo-
cusing mass spectrometer at a beam energy 70 eV or Finnigan SSQ
7000. Elemental analysis were carried out at the Microanalytical Unit,
Faculty of Science, Ain Shams University by using Perkin-Elmer 2400
CHN Elemental Analyzer.
Reaction of 4-Benzoyl-3-chloro-5,6-diphenylpyridazine2
2 or 4-Benzoyl-5,6-diphenylpyridazin-3(2H)-one1
1a with Hydrazine Hydrate. Synthesis of 7H-3,4,5-
Triphenylpyrazolo[3,4-c]pyridazine 3
A solution of 2 (0.371 g, 0.001 mmol) in ethanol (15 mL) or 1a (0.352 g,
0.001 mmol) in acetic acid (15 mL) was treated with hydrazine hydrate
(0.002 mmol), and the reaction mixture was heated under reflux for
3 h, cooled, and poured on crushed ice. The solid products obtained
were filtered off, washed with water, and dried. Recrystallization from
benzene yielded identical products 3 as orange crystals. Compound 3
1
had m.p. 270–271 C (89% yield); IR: cm 3146 (NH), 3061 (C Har),
1653 (C N), 1572, 1510, 1445 (pyridazine ring stretching vibrations);
1H-NMR (CDCl3): 8.9 (s, 1H, NH), 7.45–6.95 (m, 15H, 3 C6H5); MS:
m/e [%] 348 [M+., 46], 347 [(M+. 1), 73], 332 [2], 319 [6], 291 [3], 271
[9], 256 [3], 216 [4], 189 [16], 163 [2], 155 [12], 128 [9], 115 [3], 79 [9],
78 [100%], 51 [6].
Reaction of 4-Benzoyl-5,6-diphenylpyridazin-3(2H)-one
1a with Hydrazine Hydrate. Synthesis of 5,6-
Diphenyl-4-hydrazonobenzylpyridazin-3(2H)-one 4
Compound 1a (0.352 g, 0.001 mmol) and excess hydrazine hydrate
(0.003 mmol) were refluxed in ethanol (20 mL) for 3 h. The reaction
mixture was poured into ice cold water. The solid obtained was filtered
off, washed with water, and recrystallized from ethanol to give 4 as yel-
1
low crystals. Compound 4 had m.p. 250–252 C (90% yield); IR: cm
3358, 3219 (symmetric and unsymmetric stretching for NH2 group),
3061 (C Har), 1680 (CO), 1638 (C N); 1H-NMR (CDCl3): 12.4 (broad,
1H, NH for pyridazine moiety), 7.5–6.8 (m, 15H, 3 C6H5), 3.6 (broad
N NH2 group).
Reaction of 4-Benzoyl-3-chloro-5,6-diphenylpyridazine
2 with Benzhydrazide. Synthesis of 8-Benzoyl-3,6,7-
triphenyl-1,2,4-triazolo[4,3-b]pyridazine 5
A solution of 2 (0.371 g, 0.001 mmol) and benzhydrazide (0.136 g,
0.001 mmol) in l-butanol3 (15 mL) was refluxed for 48 h. On cooling,

204
A. A. Shalaby
a yellow solid was precipitated and filtered. The solid obtained was re-
crystallized from CHCl3 to give 5 as yellow crystals (78% yield) m.p.
290–292 C; IR: cm 1 3059 (C Har), 1669 (CO), 1598 (C N), 1463, 1400
(pyridazine ring stretching vibrations); 1H-NMR (CDCl3): 7.4–6.8 (m,
20H, 4 C6H5); MS: m/e [%] 452 [M+., 4], 451 [15], 450 [41], 436 [13],
348 [12], 347 [(M+.-PhCO), 27], 332 [12], 305 [8], 229 [5], 217 [7], 214
[7], 203 [7], 190 [9], 189 [18], 180 [16], 179 [15], 178 [11], 165 [9], 153
[7], 128 [7], 115 [10], 105 [20], 104 [76], 103 [100], 91 [24], 78 [12], 77
[16], 76 [28], 67 [12], 66 [7], 65 [8], 50 [17].
Reaction of 4-Benzoyl-3-chloro-5,6-diphenylpyridazine
2 with Sodium Azide. Synthesis of 8-Benzoyl-6,7-
diphenyltetrazolo[4,5-b]pyridazine 6
A solution of compound 2 (0.25 g) in dimethylformamide (10 mL) and
sodium azide4 (0.5 g, in few drops of H2O) was refluxed for 2 h. The
reaction mixture was poured into ice cold water. The solid obtained was
filtered off, washed with water, and recrystallized from benzene to give
1
6 (82% yield) as pale yellow crystals, had m.p. 227 C decomp.; IR: cm
3059 (C Har.), 1677 (CO), 1596 (C N), 1453, 1345 (pyridazine ring),
1229 (C O); 1H-NMR (CDCl3): 7.4–6.9 (m, 15H, 3 C6H5); MS: m/e
[%] 377 [M+., 1], 353 [2], 337 [13], 322 [25], 321 [(M+.-2N2), 100], 320
[45], 306 [25], 292 [13], 265 [10], 217 [11], 216 [53], 189 [9], 163 [4], 105
[43], 77 [34], 51 [24].
Reaction of 4-Benzoyl-3-chloro-5,6-diphenylpyridazine
2 or 4-benzoyl-5,6-diphenylpyridazin-3(2H)-one 1a
with o-Phenylenediamine. Formation of 11H-3,4,5-
Triphenylbenzo[b]pyridazino[4,3-f][1,4]diazepine 7a
A solution of compound 2 (0.371 g, 0.001 mmol) in ethanol (20 mL)
or 1a (0.352 g, 0.001 mmol) in acetic acid (15 mL) was treated with
o-phenylenediamine (0.108 g, 0.001 mmol). The reaction mixture was
refluxed for 3 h, filtered while hot, and left to cool. The solid product
formed was filtered off and recrystallized from ethanol to give 7a as
pale yellow crystals. Compound 7a had m.p. 230–232 C (ethanol) (82%
1
yield); IR: cm 3270, 3180 (NH), 3054 (C Har.), 1639 (C N); 1H-NMR
(CDCl3): 8.25 (s, 1H, NH for pyridazine moiety), 7.4–6.9 (m, 15H, 3
C6H5); MS: m/e [%] 424 [M+., 3], 352 [17], 323 [35], 275 [12], 247 [6],
218 [5], 189 [10], 165 [7], 129 [5], 105 [50], 89 [19], 78 [15], 77 [100], 63
[12], 51 [30].
Analysis Calcd. for C29H20N4: C, 82.05; H, 4.75; N, 13.20. Found: C,
81.76; H, 4.66;N, 13.04.

Pyrazolo-, Triazolo-, Tetrazolo-, Diazepino-, Oxazepino-, and Thiazepinopyridazine 205
Reaction of 4-Benzoyl-5,6-diphenylpyridazin-3(2H)-one
1a with o-Aminophenol. Synthesis of 3,4,5-
Triphenylbenzo[b]pyridazino[4,3-f][1,4]oxazepine 7b
Compound 1a (0.352 g, 0.001 mmol) was heated with o-aminophenol
(0.109 g, 0.001 mmol) in glacial acetic acid (15 mL) for 4 h. The reac-
tion mixture was poured into ice cold water. The residue was filtered
off, dried, and recrystallized from benzene to give 7b as pink crystals.
Compound 7b had m.p. 271–273 C (63% yield); IR: cm 1 3060 (C Har.),
1638 (C N), 1576, 1464 (pyridazine ring stretching vibrations); 1H-
NMR (CDCl3): 7.5–6.8 (m, 19H, aromatic); MS: m/e [%] 427 [(M+.
+
2), 1], 415 [31], 414 [97], 413 [57], 337 [28], 336 [25], 335 [56], 323 [7],
307 [12], 287 [22], 286 [100], 279 [12], 278 [14], 277 [14], 276 [12], 265
[12], 259 [18], 257 [14], 232 [13], 231 [11], 230 [9], 229 [20], 202 [10],
189 [10], 165 [19], 152 [10], 85 [24], 83 [35], 77 [2], 51 [50].
Reaction of 4-Benzoyl-3-chloro-5,6-diphenylpyridazine
2 with o-Aminothiophenol. Formation of 3,4,5-
Triphenylbenzo[b]pyridazino[4,3-f][1,4]thiazepine 7c
Compound 2 (0.371 g, 0.001 mmol) was heated with o-aminothiophenol
(0.015 mmol) in presence of ethanol (20 mL) for 3 h. The reaction so-
lution was concentrated to give 7c as yellow needles. Compound 7c
had m.p. 193–195 C (ethanol) (85% yield); IR: cm 1 3060 (C Har), 1623
(C N); 1H-NMR (DMSO-d6): 7.7–7.1 (m, 19H, aromatic); MS: m/e [%]
443 [(M+. + 2), 79], 442 [6], 441 [M+., 1], 386 [7], 367 [26], 366 [100],
341 [11], 340 [37], 339 [39], 307 [12], 263 [24], 236 [30], 231 [16], 222
[8], 206 [13], 204 [18], 178 [10], 106 [10], 104 [11], 91 [7], 69 [13], 57
[15], 55 [10], 51 [17].
Analysis Calcd. for C29H19N3S: C, 78.89; H, 4.34; N, 9.52, S, 7.26.
Found: C.79.01; H, 4.22; N, 9.60; S, 7.30.
Reaction of 4-Benzoyl-5,6-diphenylpyridazin-3(2H)-one
1a with Ethylenediamine. Synthesis of 7,8-Trihydro-
3,4,5-triphenylpyridazino[4,3-f][1,4]diazepine 8a
A solution of compound 1a (0.352 g, 0.001 mmol) in acetic acid (20 mL)
was treated with ethylenediamine (0.015 mmol). The reaction mixture
was refluxed for 3 h, filtered while hot, and left to cool. The solid product
formed was filtered off and recrystallized from ethanol to give 8a as
1
white crystals. Compound 8a had m.p. 270–272 C (78% yield); IR: cm
3378 (NH). 3065 (C Har.), 2985, 2872 (C Hal), 1625 (C N), 1515, 1490,
1446 (pyridazine ring stretching vibrations); 1H-NMR (CDCl3): 12.05
(s, 1H, NH of diazepine ring), 7.30–6.47 (m, 15H, 3 C6H5), 2.10–2.05
(t, 2H, N CH2); 1.7–1.6 (t, 2H, HN CH2); MS: m/e [%] 376 [(M+., 0],

206
A. A. Shalaby
371 [3], 337 [6], 281 [16], 280 [63], 265 [14], 251 [10], 175 [10], 161 [51],
160 [47], 159 [100], 158 [13], 146 [18], 145 [47], 144 [42], 132 [20], 130
[11], 117 [23], 91 [17], 77 [15], 52 [11].
Reaction of 4-Benzoyl-5,6-diphenylpyridazin-3(2H)-one
1a with 2-Aminoethanol. Synthesis of 7,8-Dihydro-3,4,5-
triphenylpyridazino[4,3-f][1,4]oxazepine 8b
Compound 1a (0.352 g, 0.001 mmol) in acetic acid (15 mL) was treated
with 2-aminoethanol (0.015 mmol). The reaction mixture was refluxed
for 3 h, filtered while hot, concentrated, and left to cool to give 8b as
white crystals. Compound 8b had m.p. 262–264 C (acetic acid, 73%
1
yield); IR: cm 3064 (C Har), 2986, 2873 (C Hal), 1625 (C N), 1516,
1490, 1446 (pyridazine ring stretching vibrations) 1265 (C O); 1H-NMR
(DMSO-d6): 7.5–6.8 (m, 15H, 3 C6H5), 4.45 (t, 2H, OCH2 ), 3.62
(t, 2H, CH2N ); MS: m/e [%] 377 [M+., less than 1], 353 [15], 336 [22],
338 [25], 337 [(M+. N, C2H2), 100], 336 [22], 275 [11], 259 [8], 247 [13],
219 [4], 204 [3], 189 [6], 165 [4], 105 [5], 77 [8], 51 [3].
Reaction of 4-Benzoyl-3-chloro-5,6-diphenylpyridazine
2 with Ethylenediamine. Synthesis of 4-Benzoyl-5,6-
diphenyl-3-(2-aminoethylamino)pyridazine 9a
Compound 2 (0.371 g, 0.001 mmol) was treated with ethylene diamine
(0.015 mmol) in ethanol (20 mL). The reaction mixture was refluxed for
3 h, filtered while hot, and left to cool. The solid product formed was
filtered off and recrystallized from benzene to give 9a as yellow crystals.
Compound 9a had m.p. 169–171 C (benzene) (76% yield); IR: cm 1 3428,
3378 (NH, NH2), 3060 (C Har), 2930, 2870 (C Hal.), 1667 (CO), 1600
1
(C N), 1561, 1500, 1472 (pyridazine ring stretching vibrations); H-
NMR (DMSO-d6): 7.5–6.8 (m, 15H, 3 C6H5), 6.2 (broad, 1H, NH-Ar),
3.5 (broad, 2H, NH2), 3.2 (t, 2H, NH CH2 ), 2.8 (t, 2H, CH2NH2);
MS: m/e [%] 394 [M+., 11], 365 [8], 364 [9], 353 [18], 352 [71], 336 [34],
322 [26], 260 [11], 259 [13], 246 [22], 232 [11], 231 [15], 230 [9], 217
[12], 216 [16], 204 [14], 203 [14], 202 [23], 191 [12], 190 [14], 189 [27],
178 [21], 176 [14], 165 [13], 152 [12], 129 [11], 128 [17], 127 [20], 125
[43], 105 [44], 91 [48], 85 [26], 78 [24], 77 [35], 51 [100].
Reaction of 4-Benzoyl-3-chloro-5,6-diphenylpyridazine
2 with 2-Aminoethanol. Synthesis of 4-Benzoyl-5,6-
diphenyl-3-(2-aminoethyloxy)pyridazine 9b
Compound 2 (0.371 g, 0.001 mmol) was refluxed with 2-aminoethanol
(0.015 mmol) in ethanol (20 mL) for 3 h. The reaction solution was then
concentrated to give 9b. Compound 9b had m.p. 183–185 C (benzene,

Pyrazolo-, Triazolo-, Tetrazolo-, Diazepino-, Oxazepino-, and Thiazepinopyridazine 207
1
yellow needles) (72% yield); IR: cm 3432, 3372 (NH2), 3061 (C Har.),
2930, 2840 (C Hal), 1667 (CO), 1584, 1490 (pyridazine ring stretching
vibrations); 1H-NMR (DMSO-d6): 7.45–6.75 (m, 15H, 3 C6H5), 6.05
(t, 2H, NH2), 4.57 (t, 2H, OCH2), 3.50 (t, 2H, CH2NH2); MS: m/e [%]
395 [M+., 3], 377 [(M+ H2O), 3], 352 [6], 351 [13], 323 [9], 322 [35],
246 [11], 214 [4], 202 [8], 189 [17], 165 [4], 152 [5], 128 [4], 105 [69], 91
[16], 78 [25], 77 [100], 51 [20].
Condensation of Compound 9b with Benzaldehyde.
Formation of 4-Benzoyl-5,6-diphenyl-3-
(2-benzalaminoethyloxy)pyridazine 10
Compound 9b (0.2 g) in ethanol 15 mL was refluxed with benzaldehyde
(0.06 mL) in the presence of piperidine for 3 h. The reaction mixture was
1
concentrated to give 10. Compound 10 had m.p. 146–148 C; IR: cm
1
3060 (C Har), 2930, 2840 (C Hal.), 1629 (C N); H-NMR (DMSO-d6):
7.6–6.8 (m, 20H, 4 C6H5), 6.3 (s, 1H, N CH), 4.52 (t, 2H, OCH2 ),
3.53 (t, 2H, CH2 N ).
Chlorination of 5,6-Diphenyl-4-(1,1-diphenyl-
1-hydroxymethyl)-2,3-dihydropyridazin-3-one1 11a.
Synthesis of 3-Chloro-5,6-diphenyl-4-(1,1-diphenyl-
1-chloromethyl)pyridazine 12a
Compound 11a (4.30 g, 0.01 mmol) and phosphorus oxychloride (10 mL)
were heated on an oil-bath at 100 C for 1 h. After cooling, the reaction
mixture was poured into crushed ice and made alkaline with aque-
ous sodium hydroxide solution. The solid product obtained was filtered
off, washed with water, dried, and recrystallized from petroleum ether
80–100 C to give 12a as colorless crystals. Compound 12a had m.p.
1
120–122 C (59% yield); IR: cm 3060 (C Har.), 1653 (C N); 1H-NMR
(DMSO-d6): 7.7–6.9 (m, 20H, 4 C6H5).
Analysis Calcd: for C29H20Cl2N2: Cl, 15.70. Found: 15.32.
Chlorination of 5,6-Diphenyl-4-(1,1-dibenzyl-
1-hydroxymethyl-2,3-dihydropyridazin-3-one1 11b.
Synthesis of 3-Chloro-5,6-diphenyl-4-(1,1-dibenzyl-
1-chloromethyl)pyridazine 12b
A solution of 11b (4.59 g, 0.01 mmol) in phosphorus oxychloride (10 mL)
was heated on an oil-bath at 100 C for 1 h. After cooling, the reaction
mixture was poured on crushed ice and made alkaline with aqueous
sodium hydroxide solution. The solid product was filtered off, washed
with water, dried, and recrystallized from n-hexane to give 12b as

208
A. A. Shalaby
1
colorless crystals (66% yield), had m.p. 106–108 C; IR: cm
3050
(C Har.), 2900–2840 (C Hal.), 1600 (C N); 1H-NMR (DMSO-d6): 3.85
(s, 4H, 2
CH2Ph), 7.3–6.8 (m, 20H, 4 C6H5); MS: m/e [%] 495 [M+.,
0], 480 [(M+ NH), 19], 164 [100], the spectrum was very complicated.
Analysis Calcd: for C31H24Cl2N2: C, 75.15; H, 4.88; N, 5.65; Found:
C, 75.10; H, 4.90; N, 5.70.
Hydrazinolysis of 3-Chloro-5,6-diphenyl-4-(1,1-diphenyl-
1-chloromethyl)pyridazine 12a. Synthesis of 6,7-Dihydro-
3,4,5,5-tetraphenylpyrazolo[3,4-c]pyridazine 13a
Compound 12a (0.466 g, 0.001 mmol) was refluxed with excess hy-
drazine hydrate (0.003 mmol) in ethanol (20 mL) for 3 h. The reac-
tion solution was concentrated to give 13a. Compound 13a had m.p.
233–235 C (ethanol, 63% yield) as yellow crystals; IR: cm 1 3214, 3176
(2NH), 3057 (C Har), 1652 (C N), 1599, 1561, 1491, 1446 (pyridazine
1
ring stretching vibrations); H-NMR (CDCl3): 9.20, 8.30 (s, for 2NH
groups), 7.6–7 (m, 20H, 4 C6H5); MS: m/e [%] 428 [(M+. + 2), 5], 426
[M+., less than 1], 414 [6], 413 [31], 412 [(M+. N), 100], 370 [7], 355
[13], 317 [4], 294 [18], 265 [12], 239 [1], 215 [2], 189 [2], 176 [1], 165 [1],
139 [1], 95 [1], 77 [1], 51 [1].
Hydrazinolysis of 3-Chloro-5,6-diphenyl-4-(1,1-dibenzyl-
1-chloromethyl)pyridazine 12b. Synthesis of 6,7-
Dihydro-5,5-dibenzyl-3,4-diphenylpyrazolo-
[3,4-c]pyridazine 13b
Compound 12b (0.496 g, 0.001 mmol) was refluxed with excess hy-
drazine hydrate (0.003 mmol) in ethanol (20 mL) for 3 h. The reac-
tion solution was concentrated to give 13b. Compound 13b had m.p.
205–206 C, pale yellow crystals from petroleum ether 60–80 C (54%
1
yield); IR: cm 3271, 3176 (2NH), 3057 (C Har), 2927, 2843 (C Hal),
1642 (C N), 1529, 1492 (pyridazine ring stretching); 1H-NMR (CDCl3):
9.15, 8.35 (s, for 2NH groups), 7.5–6.9 (m, 20H, 4 C6H5), 2.6 and
2.0 (s, 4H, 2 2.0 (s, 4H, 2 CH2Ph); MS: 436 [(M+ NH3, H), 19], 375
[14], 361 [28], 356 [100], 324 [25], 313 [25], 295 [44], 280 [43], 267 [41],
231 [19], 213 [31], 199 [17], 186 [28], 152 [26], 106 [52], 50 [19].
Thionation of 5,6-Diphenyl-4-(1,1-diphenyl-
1-hydroxymethyl)-2,3-dihydropyridazin-3-one 11b.
Synthesis of 4-(1-Benylidenephenethyl)-5,6-diphenyl-
2,3-dihydropyridazin-3-thione 14
To a solution of 11b (4.59 g, 0.01 mmol) in dry xylene (60 mL), phospho-
rus pentasulfide (4.4 g, 0.02 mmol) was added and the reaction mixture

Pyrazolo-, Triazolo-, Tetrazolo-, Diazepino-, Oxazepino-, and Thiazepinopyridazine 209
was heated under reflux for 3 h. The mixture was filtered while hot.
The solid product obtained was recrystallized from ethanol to give 14
as orange crystals, m.p. 243–245 C (82% yield); IR: cm 1 3050 (C Har),
2940–2900, 2840 (C Hal), 1640 (C N); 1H-NMR (DMSO-d6): 4.13 (s,
2H, CH2Ph), 6.7 (s, 1H, CH Ph), 6.8–7.5 (m, 20H, 4 C6H5), 15 (s,
1H, SH); MS: m/e [%] 456 [M+., 0], 418 [1], 386 [2], 367 [1], 357 [3], 356
[10], 355 [37], 354 [100], 353 [83], 339 [5], 325 [8], 324 [20], 323 [18],
322 [44], 321 [21], 320 [10], 305 [3], 295 [4], 275 [5], 244 [6], 231 [5], 215
[5], 202 [6], 189 [10], 165 [5], 140 [3], 115 [5], 91 [4], 78 [3], 77 [2], 51
[3].
Analysis Calcd. for C31H24N2S: C, 81.55; H, 5.30; N, 6.13; S, 7.02.
Found: C, 81.20; H, 5.50; N, 5.90; S, 7.30.
Methylation of 4-(1-Benzylidenephenethyl)-5,6-
diphenyl-2,3-dihydropyridazin-3-thione 14. Synthesis
of 4-(1-Benzylidenephenethyl)-5,6-diphenyl-
3-methylthiopyridazine 15
Compound 14 (0.457 g, 0.001 mmol) and methyl iodide (0.015 mmol)
were refluxed in 30 mL of sodium hydroxide solution (5%) for 3 h. After
cooling, the solid product obtained was filtered off, washed with water,
and dried. Recrystallization from ethanol gave 15 as yellow crystals.
Compound 15 had m.p. 145–146 C (43% yield); IR: cm 1 3050 (C Har.),
2940, 2840 (C Hal.), 1610 (C N).
Analysis Calcd. for C32H26N2S: C, 81.67; H, 5.57; N, 5.95. Found: C,
81.36; H, 5.80; N, 5.73.
Reaction of 4-(1-Benzylidenephenethyl)-5,6-diphenyl-
2,3-dihydropyridazin-3-thione 14 with Hydrazine
Hydrate. Synthesis of 4-(1-Benzylidenephenethyl)-
5,6-diphenyl-3-hydrazinopyridazine 16
Compound 14 (0.457 g, 0.001 mmol) was treated with excess hydrazine
hydrate (0.002 mmol) in ethanol (20 mL). The reaction mixture was
refluxed for 3 h, then concentrated to give 16 as yellow crystals. Com-
1
pound 16 had m.p. 124–126 C (methanol) (69% yield); IR: cm 3380,
3200 (NH, NH2), 3050 (C Har), 2940–2900, 2840 (C Hal), 1645 (C N);
1H NMR (DMSO-d6): 3.9 (s, 2H, CH2Ph), 4.83 (d, 2H, NH2), 6.7 (s,
1H, CH Ph), 6.9–7.45 (m, 20H, 4 C6H5), 9.65 (broad, 1H, NH );
MS: m/e [%] 454 [M+., less than 1], 391 [3], 356 [19], 355 [78], 354 [100],
325 [12], 324 [32], 323 [39], 264 [15], 263 [66], 245 [8], 233 [4], 218 [5],
209 [7], 195 [18], 178 [7], 165 [5], 140 [5], 130 [14], 115 [12], 104 [6], 103
[9], 91 [36], 77 [6], 65 [7], 51 [4].

210
A. A. Shalaby
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