Arylhydrazonals as the aldehyde component in Baylis-Hillman reactions

Article abstract of DOI:10.1016/j.tet.2008.06.026

Arylhydrazonals were added to acrylonitrile or methyl vinyl ketone in the presence of DABCO or benzotriazole to yield the intermediate Baylis-Hillman adduct that cyclized under the reaction conditions with water elimination to yield dihydropyridazines. A pyridazine reacted with DMAD to yield a pyridine via a [4+2] Diels-Alder addition followed by retro Diels-Alder elimination of methylene aniline. Two pyridazines were condensed with DMFDMA to yield the corresponding enaminones that reacted with NH₂NH₂ to afford the pyrazolylpyridazines.

Full text of DOI:10.1016/j.tet.2008.06.026

Tetrahedron 64 (2008) 8202–8205
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Arylhydrazonals as the aldehyde component in Baylis–Hillman reactions
*
Nouria A. Al-Awadi , Maher R. Ibrahim, Ismail A. Abdelhamid, Mohamed H. Elnagdi
Chemistry Department, Faculty of science, Kuwait University, PO Box 5969, Safat 13060, Kuwait
a r t i c l e i n f o
a b s t r a c t
Article history:
Arylhydrazonals were added to acrylonitrile or methyl vinyl ketone in the presence of DABCO or ben-
zotriazole to yield the intermediate Baylis–Hillman adduct that cyclized under the reaction conditions
with water elimination to yield dihydropyridazines. A pyridazine reacted with DMAD to yield a pyridine
via a [4þ2] Diels–Alder addition followed by retro Diels–Alder elimination of methylene aniline. Two
pyridazines were condensed with DMFDMA to yield the corresponding enaminones that reacted with
NH2NH2 to afford the pyrazolylpyridazines.
Received 29 March 2008
Received in revised form 19 May 2008
Accepted 5 June 2008
Available online 10 June 2008
Keywords:
Ó 2008 Published by Elsevier Ltd.
Baylis–Hillman reaction
Dihydropyridazine
Furopyridine
Pyrazolylpyridazine
O
1. Introduction
OH
OH
X
X
Y
Y
H
X
Y
DABCO
Arylhydrazonals 1 are readily obtained versatile reagents1–8
with an electrophilic carbonyl carbon and a nucleophilic hydrazone
nitrogen suitably located to enable their utility as a four-atom
component for the synthesis of five- and six-membered ring
systems. We have already shown that they are valuable precursors
to pyrazoles, pyridazines, and cinolines.4–8 We now report on the
reactivity of 1 as aldehyde components in Baylis–Hillman re-
actions9–11 that lead to the synthesis of 1,6-dihydropyridazines,
new azadienes with a unique substitution pattern.
pathway A
+
N
N
mw, 160 °C
5 min
NH
Ar
1a-g
N
NH
Ar
3
N
Ar
4
2
-H2O
pathway B -H2O
X
Y
X
Y
N
N
N
N
Ar
Ar
6a-i
2. Results and discussion
5
(79-95%)
Heating the arylhydrazonals 1a–g with acrylonitrile or methyl
vinyl ketone in the presence of 1,4-diazabicyclo[2.2.2]octane
(DABCO) utilizing microwaves as the energy source for 5 min in the
absence of solvent resulted in the formation of condensation
products via water elimination (Scheme 1). 13C NMR spectroscopy
Compd.
X
Ar
Y
6 (%yield)
COC6H5
COC6H4Cl(p)
CO2Et
thiophene-2-yl-methanone C6H5
furane-2-yl-methanone
COC6H5
COC6H5
COC6H5
furane-2-yl-methanone
C6H5
C6H5
C6H4Cl(p)
CN
CN
CN
CN
CN
85
90
79
88
86
83
88
92
95
1,6
a
b
c
d
e
f
indicated the presence, in each case, of a sp3 carbon at
d 44 ppm in
C6H5
C6H4CH3(p) CN
C6H4Cl(p)
C6H5
C6H5
addition to a cyano or carbonyl carbon as expected for structure 6.
Compounds 6a–i were assumed to result from cyclization and
dehydration of the initially formed Baylis–Hillman adduct 3. One
would assume ready conversion of 3 to 4, which then undergo
either E1 or E2 water elimination to yield the final isolable pyr-
idazines (pathway A). Alternatively, dehydration of the adduct via
a six-membered transition state, similar to those commonly
COCH3
COCH3
COCH3
g
h
i
Scheme 1.
encountered in our pyrolytic reactions,12,13 to yield the azadiene 5
that then would undergo 6 electrocyclization to yield the pyr-
idazine 6 (pathway B) cannot, however, be overlooked. A third
p
* Corresponding author. Tel.: þ965 4985537; fax: þ965 4816482.
E-mail address: nouria@kuc01.kuniv.edu.kw (N.A. Al-Awadi).
0040-4020/$ – see front matter Ó 2008 Published by Elsevier Ltd.
doi:10.1016/j.tet.2008.06.026

N.A. Al-Awadi et al. / Tetrahedron 64 (2008) 8202–8205
8203
possibility is initial cyanoethylation of the arylhydrazone nitrogen
and subsequent cyclization. To decide upon the most feasible
mechanism, the arylhydrazonal 1a was reacted with acrylonitrile in
THF, NaHCO3, and benzotriazole at room temperature. After two
days, a 1:1 adduct was isolated, although contaminated with some
condensation product. 1H NMR spectroscopy as well as 13C NMR
spectroscopy of this adduct indicated that it is 4a formed via
addition of the arylhydrazone NH to the methylene moiety in 3.
Attempts to isolate 4 in pure form failed, which suggests that the
conversion of 3 into 4 proceeds either by pathway A or by cyano-
ethylation. Moreover, the cyanoethylation possibility was excluded
as arylhydrazones did not undergo cyanoethylation under the
reaction condition. We thus believe that the reaction proceeds via
pathway A. In a similar way arylhydrazonals 1a,e,g reacted with
methyl vinyl ketone to yield the corresponding dihydropyridazine
derivatives 6h,i,g.
an eluent. The starting arylhydrazonals 1a–g were prepared and
characterized by mp and 1H NMR spectroscopy as reported.4
4.2. Preparation of starting compounds 1a–g
General procedure. A cooled solution (0–5 ꢀC) of the diazonium
salt (10 mmol) [prepared by adding a cooled solution of sodium
nitrite (0.7 g) in water (5 mL) to a solution of the appropriate
arylamine (10 mmol) in concd HCl (5 mL)] was added to a cooled
solution (0–5 ꢀC) of the appropriate enaminones in ethanol (50 mL)
containing NaOH (1.6 g). The mixture was then stirred at room
temperature for 1 h, and the solid precipitated was collected and
crystallized from ethanol to give 1a–g.
4.2.1. 3-Oxo-3-phenyl-2-phenylhydrazonopropanal 1a
Red crystals from ethanol, mp 82–83 ꢀC (lit.4 mp 82–84 ꢀC).
Compound 6a reacted with dimethyl acetylenedicarboxylate
(DMAD) under microwave conditions at 180 ꢀC for 5 min to yield
the pyridine 9 formed most likely via intermediate cycloadduct 7.
This then undergoes retroaddition via loss of methylene aniline to
yield 8 that is converted under the reaction conditions to 9. Also,
compounds 6g,h reacted with dimethylformamide dimethylacetal
(DMFDMA) in the microwave at 160 ꢀC for 5 min to yield the
enaminones 10a,b that can be readily used for the synthesis of
azoles and azines.14,15 For example, reacting pyridazine derivatives
10a,b with hydrazine hydrate afforded the corresponding pyr-
azolopyridazines 11a,b (Scheme 2).
4.2.2. 3-Oxo-3-(p-chlorophenyl)-2-phenylhydrazonopropanal 1b
Red crystals from ethanol, mp 135–36 ꢀC (lit.4 mp 135–37 ꢀC).
4.2.3. 3-Ethoxy-3-oxo-2-p-chlorophenylhydrazonopropanal 1c
Red crystals from ethanol, mp 82–83 ꢀC (lit.16 mp 86–88 ꢀC).
4.2.4. 3-Oxo-2-phenylhydrazono-3-(2-thienyl)propanal 1d
Yellow crystals from ethanol, mp 113–114 ꢀC (lit.4 mp 114–
115 ꢀC).
4.2.5. 3-(2-Furyl)-3-oxo-2-phenylhydrazonopropanal 1e
Red crystals from ethanol, mp 114–15 ꢀC (lit.4 mp 114–16 ꢀC).
CN
MeO2C
MeO2C
Y
O
Y
CO2Me
CO2Me
DMAD
6a
4.2.6. 3-Oxo-3-phenyl-2-p-tolylhydrazonopropanal 1f
O
N
-
NPh
mw, 180 °C
5 min.
Red crystals from ethanol, mp 116–118 ꢀC (lit.17 mp 115–17 ꢀC).
N
N
PhCO
X
N
Ph
X
O
7
8
9 (57%)
4.2.7. 2-p-Chlorophenylhydrazono-3-oxo-3-phenylpropin-
aldehyde 1g
O
O
Red crystals from ethanol, mp 143–145 ꢀC. MS: m/z¼286 (Mþ,
35%), 250 (15%), 132 (75%), 105 (100%). IR: 3166, 3084, 1653, 1643,
1489, 1312, 1293, 1267, 1091, 957, 890, 822, 712. 1H NMR (CDCl3)
O
N
Ph
NH
DMFDMA
NH NH .H O
N
Ph
6g,h
N
Me
2
2
2
N
N
mw, 160 °C
5 min
EtOH
N
Ar
Me
d
14.85 (s, 1H, NH), 10.25 (s, 1H), 7.97 (d, 2H, J¼7.8 Hz), 7.58 (t, 1H,
Ar
J¼7.6 Hz), 7.54 (t, 2H, J¼7.6 Hz), 7.38–7.26 (m, 4H). 13C NMR (CDCl3):
Ar
10a (76%)
10b (80%)
11a (77%)
11b (79%)
10,11a C6H4Cl(p)
10,11b C6H5
d
191.2 (CO), 189.8 (CO), 139.8 (C), 136.9 (C), 132.5 (C), 132.4 (CH),
131.7 (C), 130.4 (2CH), 129.9 (2CH), 128.0 (2CH), 117.7 (2CH). Anal.
Calcd for C15H11ClN2O2 (286.7): C, 62.84; H, 3.87; N, 9.77. Found: C,
62.79; H, 3.69; N, 9.75.
Scheme 2.
4.3. Preparation of 6-aroylpyridazine 6a–i
3. Conclusion
Method A. A mixture of the corresponding arylhydrazonal de-
rivatives 1a–g (1 mmol), acrylonitrile or methyl vinyl ketone
(2 mmol) and DABCO (0.112 g, 1 mmol) was mixed and placed in
a single mode cavity Explorer Microwave Synthesizer (CEM Cor-
poration, NC, USA) and irradiated at temperature 160 ꢀC for 5 min.
The reaction product was extracted with ethyl acetate (50 mL), the
solvent was removed in vacuo, and purified with silica gel flash
column chromatography using ethyl acetate/pet. ether (60–80) as
an eluent to give 6a-i, which was recrystallized from ethanol.
Method B. To a stirred mixture of arylhydrazonal 1a (0.5 mmol)
and benzotriazole (0.5 mmol) in 1 M NaHCO3 (2 mL) and THF
(0.5 mL) was added acrylonitrile (0.75 mmol). The mixture was
stirred at ambient temperature and monitored by TLC. Upon
completion or after the indicated reaction time, the mixture was
quenched with 1 N HCl (3 mL) and extracted with ethyl acetate
(50 mL). The organic layer was dried over anhydrous Na2SO4 and
the solvent was removed in vacuo. The residue was purified with
column chromatography using EtOAc/ pet. ether as an eluent.
The present study offers an interesting new simple and efficient
route to dihydropyridazines via the first reported Baylis–Hillman
reaction of arylhydrazonals with electron-poor olefins. Moreover,
the formed pyridazines proved active azadienes.
4. Experimental
4.1. General
IR spectra were recorded in KBr disks on a Perkin–Elmer System
2000 FT-IR spectrophotometer. 1H and 13C NMR spectra were
recorded on a Bruker DPX 400, 400 MHz super-conducting NMR
spectrometer. Mass spectra were measured on VG Autospec-Q
(high resolution, high performance, tri-sector GC/MS/MS). Micro-
analyses were performed on LECO CH NS-932 Elemental Analyzer.
Separation of reaction products was performed using silica gel
column chromatography using ethyl acetate/pet. ether (60–80) as

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N.A. Al-Awadi et al. / Tetrahedron 64 (2008) 8202–8205
4.3.1. 6-Benzoyl-2-phenyl-2,3-dihydropyridazin-4-carbonitrile 6a
Yellow crystals from ethanol, yield (0.25 g) 85%, mp 142–43 ꢀC.
MS: m/z¼287 (Mþ, 80%), 149 (70%), 105 (100%). IR: 3433, 3081,
2221, 1619, 1595, 1514, 1498, 1380, 1319, 1219, 1178, 921, 723. 1H
722. 1H NMR (CDCl3):
7.52 (s, 1H), 7.48 (t, 2H, J¼7.8 Hz), 7.28–7.18 (m, 4H), 4.69 (s, 2H),
2.38 (s, 3H). 13C NMR (CDCl3):
187.9 (CO), 141.8 (C), 136.7 (C), 136.5
(C), 135.5 (C), 132.2 (CH), 130.4 (2CH), 130.1 (2CH), 128.4 (CH), 127.9
(2CH),116.5 (C),116.4 (2CH),100.3 (CN), 44.5 (CH2), 21.0 (CH3). Anal.
Calcd for C19H15N3O (301.3): C, 75.73; H, 5.02; N, 13.94. Found: C,
75.66; H, 5.06; N, 14.00.
d
7.98 (d, 2H, J¼7.6 Hz), 7.58 (t, 1H, J¼7.6 Hz),
d
NMR (CDCl3):
2H, J¼7.8 Hz), 7.44 (t, 2H, J¼7.8 Hz), 7.32 (s,1H), 7.28 (m, 3H), 4.71 (s,
2H). 13C NMR (CDCl3):
188.0 (CO), 144.0 (C), 136.8 (C), 136.5 (C),
d
7.98 (d, 2H, J¼7.6 Hz), 7.59 (t, 1H, J¼7.2 Hz), 7.51 (t,
d
132.3 (CH), 130.4 (2CH), 129.5 (2CH), 128.4 (CH), 128.0 (2CH), 125.4
(CH), 116.4 (2CH), 116.3 (C), 101.2 (CN), 44.3 (CH2). Anal. Calcd for
4.3.7. 1-[6-Benzoyl-2-p-chlorophenyl-2,3-dihydropyridazin-4-
yl]ethanone 6g
C
18H13N3O (287.3): C, 75.25; H, 4.56; N, 14.62. Found: C, 75.15; H,
4.67; N, 14.70.
Orange crystals from ethanol, yield (0.3 g) 88%, mp 185–87 ꢀC.
MS: m/z¼338 (Mþ, 75%), 296 (25%), 105 (100%). IR: 3435, 3068,
2919, 1657, 1626, 1490, 1337, 1253, 1211, 1095, 919, 823, 721. 1H NMR
4.3.2. 6-p-Chlorobenzoyl-2-phenyl-2,3-dihydropyridazine-4-
carbonitrile 6b
Yellow crystals from ethanol, yield (0.29 g) 90%, mp 214–216 ꢀC.
MS: m/z¼321 (Mþ, 90%),139 (100%),111 (50%). IR: 3432, 3084, 2215,
1642, 1630, 1589, 1518, 1379, 1262, 959, 922, 828, 748, 683. 1H NMR
(CDCl3):
d
7.98 (dd, 2H, J¼8.0, 1.4 Hz), 7.68 (s, 1H), 7.60 (dt, 1H, J¼8.0,
1.2 Hz), 7.50 (t, 2H, J¼7.8 Hz), 7.37 (dd, 2H, J¼7.8, 1.2 Hz), 7.30 (dd,
2H, J¼8.0, 1.2 Hz), 4.68 (s, 2H), 2.54 (s, 3H). 13C NMR (CDCl3):
d 196.7
(CO), 189.1 (CO), 143.2 (C), 137.1 (C), 136.8 (C), 132.2 (CH), 130.3
(2CH), 130.2 (C), 129.4 (2CH), 128.0 (2CH), 123.1 (CH), 117.4 (2CH),
117.3 (C), 43.6 (CH2), 25.1 (CH3). Anal. Calcd for C19H15ClN2O2
(338.8): C, 67.36; H, 4.46; N, 8.27. Found: C, 67.32; H, 4.39; N, 8.25.
(DMSO-d6):
d
7.91 (d, 2H, J¼8.4 Hz), 7.60 (d, 2H, J¼8.4 Hz), 7.44 (t,
2H, J¼7.8 Hz), 7.42 (s, 1H), 7.39 (d, 2H, J¼7.8 Hz), 7.28 (t, 1H,
J¼7.6 Hz), 4.84 (s, 2H). 13C NMR (DMSO-d6):
d 191.7 (CO), 149.0 (C),
142.2 (C), 141.4 (C), 140.6 (C), 137.0 (2CH), 134.6 (2CH), 133.4 (2CH),
132.6 (CH), 130.3 (CH), 122.0 (2CH), 121.9 (C), 107.5 (CN), 49.1 (CH2).
Anal. Calcd for C18H12ClN3O (321.8): C, 67.19; H, 3.72; N, 13.06.
Found: C, 67.10; H, 3.55; N, 13.10.
4.3.8. 1-[6-Benzoyl-2-phenyl-2,3-dihydropyridazine-4-yl]-
ethanone 6h
Orange crystals from ethanol, yield (0.28 g) 92%, mp 160–62 ꢀC.
MS: m/z¼304 (Mþ 50%), 262 (15%),105 (100%). IR: 3435, 3059,1654,
1627, 1503, 1487, 1373, 1243, 1213, 1031, 921, 715. 1H NMR (CDCl3):
4.3.3. 1-p-Chlorophenyl-5-cyano-1,6-dihydropyridazin-3-
carboxylic acid ethyl ester 6c
d
8.01 (d, 2H, J¼8.0 Hz), 7.70 (s,1H), 7.59 (t,1H, J¼7.8 Hz), 7.50 (t, 2H,
Orange crystals from ethanol, yield (0.23 g) 79%, mp 155–56 ꢀC.
MS: m/z¼289 (Mþ, 90%), 260 (20%), 111 (100%). IR: 3428, 3080,
2981, 2215, 1701, 1516, 1493, 1416, 1325, 1210, 1176, 1092, 921, 820.
J¼7.6 Hz), 7.42 (m, 4H), 7.22 (m, 1H), 4.73 (s, 2H), 2.54 (s, 3H). 13
C
NMR (CDCl3): d 196.7 (CO), 189.1 (CO), 144.6 (C), 137.2 (C), 136.6 (C),
132.0 (CH), 130.4 (2CH), 129.4 (2CH), 127.8 (2CH), 127.5 (C), 124.9
(CH), 123.3 (CH), 116.4 (2CH), 43.6 (CH2), 25.2 (CH3). Anal. Calcd for
1H NMR (DMSO-d6):
d
7.52 (d, 2H, J¼8.8 Hz), 7.45 (d, 2H, J¼8.8 Hz),
7.25 (s, 1H), 4.72 (s, 2H), 4.25 (q, 2H, J¼7.2 Hz), 1.28 (t, 3H, J¼7.2 Hz).
13C NMR (DMSO-d6):
161.9 (CO), 142.7 (C), 130.5 (C), 129.1 (2CH),
C19H16N2O2 (304.3): C, 74.98; H, 5.30; N, 9.20. Found: C, 74.97; H,
d
5.29; N, 9.33.
128.8 (C), 128.0 (CH), 118.2 (2CH), 116.6 (C), 101.3 (CN), 60.8 (CH2),
43.3 (CH2), 14.1 (CH3). Anal. Calcd for C14H12ClN3O2 (289.7): C,
58.04; H, 4.17; N, 14.50. Found: C, 57.90; H, 4.20; N, 14.30.
4.3.9. 1-[6-(Furan-2-carbonyl)-2-phenyl-2,3-dihydropyridazin-4-
yl]ethanone 6i
Orange crystals from ethanol, yield (0.28 g) 95%, mp 190–92 ꢀC.
MS: m/z¼294 (Mþ, 70%), 252 (15%), 95 (100%). IR: 3433, 2918, 1653,
1627, 1503, 1488, 1373, 1243, 1213, 1031, 921, 715. 1H NMR (CDCl3):
4.3.4. 2-Phenyl-6-(thiophene-2-carbonyl)-2,3-dihydropyridazine-
4-carbonitrile 6d
Yellow crystals from ethanol, yield (0.26 g) 88%, mp 156–58 ꢀC.
MS: m/z¼293 (Mþ, 80%), 174 (10%), 111 (100%). IR: 3421, 3079, 2217,
1614, 1512, 1499, 1413, 1387, 1345, 1262, 1160, 1045, 921, 744. 1H
d
7.74 (d, 1H, J¼8.0 Hz), 7.66 (s, 1H), 7.60 (dd, 1H, J¼7.6, 1.2 Hz), 7.50
(m, 4H), 7.27 (t, 1H, J¼7.8 Hz), 6.60 (dd, 1H, J¼3.2, 1.2 Hz), 4.73 (s,
2H), 2.52 (s, 3H). 13C NMR (CDCl3):
196.6 (CO), 175.0 (CO), 150.5
d
NMR (DMSO-d6):
d
8.08 (m, 2H), 7.57–7.52 (m, 4H), 7.43 (s, 1H), 7.27
178.0 (CO), 144.3 (C),
(C), 146.9 (CH), 144.8 (C), 137.3 (C), 129.5 (2CH), 126.8 (C), 125.2
(CH), 122.6 (CH), 121.4 (CH), 117.0 (2CH), 112.2 (CH), 43.6 (CH2), 25.2
(CH3). Anal. Calcd for C17H14N2O3 (294.3): C, 69.38; H, 4.79; N, 9.52.
Found: C, 69.32; H, 4.79; N, 9.55.
(m, 2H), 4.86 (s, 2H). 13C NMR (DMSO-d6):
d
138.7 (C), 137.2 (C), 136.5 (CH), 135.3 (CH), 129.9 (2CH), 128.3 (CH),
127.5 (CH), 125.7 (CH), 117.9 (2CH), 117.2 (C), 102.6 (CN), 44.6 (CH2).
Anal. Calcd for C16H11N3OS (293.4): C, 65.51; H, 3.78; N, 14.32; S,
10.95. Found: C, 65.40; H, 3.89; N, 14.25; S, 10.79.
4.4. Reaction of compound 6a with dimethyl
acetylenedicarboxylate (DMAD)
4.3.5. 6-(Furan-2-carbonyl)-2-phenyl-2,3-dihydropyridazine-4-
carbonitrile 6e
A mixture of compounds 6a (1 mmol) and DMAD (2 mmol) was
mixed and placed in a microwave oven and irradiated at temper-
ature 180 ꢀC for 5 min. The reaction product were extracted with
ethyl acetate and purified with column chromatography using ethyl
acetate/pet. ether as an eluent to give 9.
Orange crystals from ethanol, yield (0.24 g) 86%, mp 145–46 ꢀC.
MS: m/z¼277 (Mþ, 90%), 158 (10%), 95 (100%). IR: 3430, 3130, 3110,
2213, 1626, 1498, 1459, 1394, 1279, 1196, 1112, 1015, 925, 820, 750.
1H NMR (CDCl3):
d
7.74 (d, 1H, J¼3.8 Hz), 7.56 (d, 1H, J¼3.6 Hz), 7.52
(m, 3H), 7.40 (d, 2H, J¼7.8 Hz), 7.32 (t, 1H, J¼7.4 Hz), 6.59 (dd, 1H,
J¼3.2, 1.6 Hz), 4.70 (s, 2H). 13C NMR (CDCl3):
d
174.0 (CO), 150.1 (C),
4.4.1. 2-Benzoyl-4-cyano-furo[3,4-b]pyridine-5,7-dione 9
147.2 (CH), 144.1 (C), 137.4 (C), 129.7 (2CH), 127.7 (CH), 125.7 (CH),
121.6 (CH), 117.0 (2CH), 116.3 (C), 112.3 (CH), 100.3 (CN), 44.5 (CH2).
Anal. Calcd for C16H11N3O2 (277.3): C, 69.31; H, 4.00; N, 15.15.
Found: C, 69.19; H, 3.99; N, 15.11.
Yellow crystals from ethanol, yield (0.16 g) 57%, mp 188–90 ꢀC.
MS: m/z¼278 (Mþ, 100%), 167 (60%), 149 (100%). IR: 3423, 3111,
2959, 2213, 1728, 1626, 1499, 1459, 1394, 1279, 1197, 1114, 1015, 925,
821, 749. 1H NMR (CDCl3):
d
8.92 (s, 1H), 7.72 (d, 2H, J¼7.8 Hz), 7.66
(t, 1H, J¼7.6 Hz), 7.52 (t, 2H, J¼7.6 Hz). 13C NMR (CDCl3):
d 189.7
4.3.6. 6-Benzoyl-2-p-tolyl-2,3-dihydropyridazine-4-carbonitrile 6f
Yellow crystals from ethanol, yield (0.25 g) 83%, mp 173–75 ꢀC.
MS: m/z¼301 (Mþ, 40%), 215 (30%), 185 (35%), 85 (100%). IR: 3426,
3090, 2217, 1620, 1505, 1378, 1352, 1263, 1220, 1177, 1040, 922, 810,
(CO), 165.5 (CO), 164.4 (CO), 153.7 (C), 145.9 (C), 137.7 (C), 137.5 (C),
131.6 (CH), 130.4 (CH), 129.2 (2CH), 127.8 (2CH), 124.1 (C), 116.2
(CN). Anal. Calcd for C15H6N2O4 (278.2): C, 64.76; H, 2.17; N, 10.07.
Found: C, 64.65; H, 2.09; N, 10.05.

N.A. Al-Awadi et al. / Tetrahedron 64 (2008) 8202–8205
8205
4.5. Reaction of compounds 6g,h with N,N-
dimethylformamide dimethylacetal (DMFDMA)
6H), 6.82 (dd, 1H, J¼7.4, 1.2 Hz), 4.94 (s, 2H). 13C NMR (CDCl3):
d 190.0 (CO), 156.9 (C), 149.6 (C), 144.3 (C), 137.9 (C), 137.6 (C), 131.5
(CH), 130.5 (2CH), 129.2 (2CH), 128.6 (CH), 127.8 (2CH), 125.9 (C),
116.6 (2CH), 110.3 (CH), 103.1 (CH), 45.1 (CH2). Anal. Calcd for
A mixture of each of compounds 6g,h (1 mmol) and DMFDMA
(2 mmol) was mixed and placed in a microwave oven and irradi-
ated at temperature 160 ꢀC for 5 min. The reaction product were
extracted with ethyl acetate and purified with column chroma-
tography using ethyl acetate/pet. ether as an eluent to give 10a,b.
C20H15ClN4O (362.8): C, 66.21; H, 4.17; N, 15.44. Found: C, 66.13; H,
4.08; N, 15.39.
4.6.2. Phenyl-[1-phenyl-5-(1H-pyrazol-3-yl)-1,6-dihydropyridazin-
3-yl]methanone 11b
4.5.1. 1-(6-Benzoyl-2-p-chlorophenyl-2,3-dihydropyridazin-4-yl)-
3-dimethylamino-propenone 10a
Orange crystals from ethanol, yield (0.30 g) 76%, mp 208–210 ꢀC.
MS: m/z¼393 (Mþ, 60%), 254 (20%), 98 (100%). IR: 3432, 3054, 1630,
1526, 1491, 1325, 1266, 1208, 1153, 1094, 915, 725. 1H NMR (CDCl3):
Yellow crystals from ethanol, yield (0.26 g) 79%, mp 216–218 ꢀC.
MS: m/z¼328 (Mþ, 100%), 223 (90%), 105 (100%). IR: 3440, 3294,
3056, 1620, 1596, 1524, 1498, 1329, 1266, 1214, 1175, 1150, 924, 762.
1H NMR (CDCl3):
d
8.05 (dd, 2H, J¼7.8, 1.4 Hz), 7.67 (d, 1H, J¼7.4 Hz),
7.58 (t, 1H, J¼7.6 Hz), 7.47 (t, 2H, J¼7.6 Hz), 7.42–7.38 (m, 5H), 7.30
d
7.98 (d, 2H, J¼8.0 Hz), 7.76 (d, 1H, J¼12.0 Hz), 7.58 (t,1H, J¼7.8 Hz),
7.49 (m, 3H), 7.40 (m, 4H), 5.73 (d, 1H, J¼12.0 Hz), 4.77 (s, 2H), 3.19,
2.98 (2s, 2CH3). 13C NMR (CDCl3):
189.7 (CO), 185.3 (CO), 153.8 (C),
(m, 1H), 7.14 (t, 1H, J¼7.6 Hz), 6.82 (d, 1H, J¼7.6 Hz), 4.99 (s, 2H). 13
C
NMR (CDCl3): d 189.9 (CO), 156.9 (C), 149.4 (C), 145.4 (C), 137.8 (CH),
d
134.4 (C), 131.5 (CH), 130.5 (2CH), 129.2 (2CH), 127.7 (2CH), 125.4
(C), 123.4 (CH), 115.6 (2CH), 110.5 (CH), 103.0 (CH), 45.0 (CH2). Anal.
Calcd for C20H16N4O (328.4): C, 73.15; H, 4.91; N, 17.06. Found: C,
73.05; H, 4.88; N, 17.09.
143.7 (C),137.9 (C), 137.6 (C), 131.8 (CH), 130.4 (C),130.3 (2CH),129.4
(CH), 129.2 (2CH), 127.8 (2CH), 117.2 (2CH), 117.1 (CH), 90.6 (CH),
44.5 (CH2), 37.3 (2CH3). Anal. Calcd for C22H20ClN3O2 (393.8): C,
67.09; H, 5.12; N, 10.67. Found: C, 67.00; H, 5.08; N, 10.69.
Acknowledgements
4.5.2. 1-(6-Benzoyl-2-phenyl-2,3-dihydropyridazin-4-yl)-3-
dimethylamino-propenone 10b
The support of the University of Kuwait received through
research grant no. Sc 08/04 and the facilities of ANALAB and SAF
(grant nos. GS01/01, GS01/03, GS03/01) are gratefully
acknowledged.
Orange crystals from ethanol, yield (0.29 g) 80%, mp 192–94 ꢀC.
MS: m/z¼359 (Mþ, 30%), 254 (20%), 98 (100%). IR: 3431, 3059, 1632,
1554, 1439, 1371, 1320, 1234, 1180, 1115, 925, 754. 1H NMR (CDCl3):
d
8.0 (dd, 2H, J¼8.0, 1.6 Hz), 7.77 (d, 1H, J¼12.0 Hz), 7.57 (t, 1H,
J¼7.8 Hz), 7.49 (m, 3H), 7.40 (m, 4H), 7.18 (m, 1H), 5.73 (d, 1H,
References and notes
J¼12.0 Hz), 4.82 (s, 2H), 3.19, 2.97 (2s, 2CH3). 13C NMR (CDCl3):
d
189.7 (CO), 185.5 (CO), 153.7 (C), 145.0 (C), 137.7 (C), 137.5 (C), 131.6
1. Al-Mater, H. M.; Elnagdi, M. H. J. Heterocycl. Chem. 2003, 44, 603–607.
2. Gozlan, S. A.; Abdelhamed, I. A.; Gaber, H. M.; Elnagdi, M. H. J. Heterocycl. Chem.
2005, 42, 1185–1189.
3. Gozlan, S. A.; Abdelhamed, I. A.; Gaber, H. M.; Elnagdi, M. H. J. Chem. Res. 2004,
12, 789–793.
(CH), 131.1 (CH), 130.4 (2CH), 129.2 (2CH), 127.8 (2CH), 124.1 (CH),
117.4 (CH), 116.2 (2CH), 90.6 (CH), 44.5 (CH2), 37.5 (2CH3). Anal.
Calcd for C22H21N3O2 (359.4): C, 73.52; H, 5.89; N, 11.69. Found: C,
73.49; H, 5.83; N, 11.67.
4. Al-awadi, N. A.; Elnagdi, M. H.; Ibrahim, Y. A.; Kaul, K.; Kumar, A. Tetrahedron
2001, 57, 1609–1614.
5. Abdel-khalk, M. M.; Agamy, S. A.; Elnagdi, M. H. Synthesis 2001, 12, 1861–1865.
6. Al-Omran, F.; Abdel-khalk, M. M.; Abou-Elkhair, A.; Elnagdi, M. H. Synthesis
1997, 1, 91–94.
4.6. Reaction of compounds 10a,b with NH2NH2
7. Al-Zaydi, K. M.; Elnagdi, M. H. Z. Naturforsch., B: Chem. Sci. 2004, 59, 721–725.
8. Al-saleh, B.; Makhsseed, S.; Hassaneen, H. M.; Elnagdi, M. H. Synthesis 2005, 1,
59–62.
9. Luo, S.; Mix, X.; Wang, B. G.; Cheng, J. P. Tetrahedron Lett. 2004, 45, 5171–5174.
10. Basavaiah, D.; Gowriswari, V. V. Tetrahedron Lett. 1986, 27, 2031–2032.
11. Caumul, P.; Hailes, H. C. Tetrahedron Lett. 2005, 46, 8125–8127.
12. Al-awadi, N. A.; Abdelhamed, I. A.; Al-Etabi, A. M.; Elnagdi, M. H. Synlett 2007,
2205–2208.
A mixture of each of compounds 10a,b (1 mmol) and hydrazine
hydrate (2 mmol) in ethanol (50 mL) was refluxed for 4 h. The
solvent was then removed in vacuo, cooled water (10 mL) was
added to the reaction mixture, filtered and crystallized from etha-
nol to give 11a,b.
13. Al-awadi, N. A.; Georg, B. J.; Dib, H. H.; Ibrahim, M. R.; Ibrahim, Y. A.; Al-Du-
souqi, O. M. Tetrahedron 2001, 5, 1609–1614.
14. Al-Omran, F.; Al-awadi, N. A.; Abou-Elkhair, A.; Elnagdi, M. H. Org. Prep. Proced.
Int. 1997, 29, 285–292.
15. El-Taweel, F. N.; Elnagdi, M. H. J. Heterocycl. Chem. 2001, 38, 981–984.
16. Makhseed, S.; Hassaneen, H. M.; Elnagdi, M. H. Z. Naturforsch., B: Chem. Sci.
2007, 62, 529–536.
17. Al-Dusouqui, O. M.; Abdel-Khalk, M. M.; Al-awadi, N. A.; Dib, H. H.; Georg, B.;
Elnagdi, M. H. J. Chem. Res. 2005, 5, 295–302.
4.6.1. 1-[p-Chlorophenyl-5-(1H-pyrazol-3-yl)-1,6-dihydro-
pyridazin-3-yl]phenylmethanone 11a
Yellow crystals from ethanol, yield (0.28 g) 77%, mp 186–188 ꢀC.
MS: m/z¼362 (Mþ, 70%), 257 (40%), 105 (100%). IR: 3434, 3260,
3054, 1630, 1595, 1526, 1491, 1325, 1267, 1208, 1177, 1155, 914, 725.
1H NMR (CDCl3):
d
8.03 (dd, 2H, J¼7.8, 1.4 Hz), 7.67 (dd, 1H, J¼7.4,
1.2 Hz), 7.58 (t, 1H, J¼7.6 Hz), 7.47 (t, 2H, J¼7.6 Hz), 7.42–7.38 (m,