Microwaves in organic synthesis: Synthesis of pyridazinones, phthalazinones and pyridopyridazinones from 2-oxo-arylhydrazones under microwave irradiation

Article abstract of DOI:10.1002/jhet.5570430622

The phenylhydrazones 1a-d condensed with ethyl cyanoacetate to yield pyridazinones 2a-d that reacted with sulphur in presence of piperidine to yield the aminothienopyridazineones 3a,b that reacted with electron poor olefins and acetylenes to yield phthala

Full text of DOI:10.1002/jhet.5570430622

Nov-Dec 2006
1575
Microwaves in Organic Synthesis: Synthesis of Pyridazinones,
Phthalazinones and Pyridopyridazinones from
2-Oxo-Arylhydrazones Under Microwave Irradiation.
Balkis AL-Saleha*, Noha M. Hilmyb, Morsy Ahmed EL-Apaserya
and Mohamed H. Elnagdib.
aChemistry Department; Faculty of Science; University of Kuwait; P.O. Box 5969; Safat; 13060-Kuwait.
bDepartment of Chemistry; Faculty of Science; Cairo University, Giza; A. R. Egypt
E-mail: shelmy@access.com.eg
Received February 21, 2006
R
R
S
O
NH2
CN
S/ pip
R
N
N
N
O
N
N
O
NHAr
Ar
Ar
Y
X
Y
R
N
X
NH2
N
O
Ar
The phenylhydrazones 1a-d condensed with ethyl cyanoacetate to yield pyridazinones 2a-d that reacted
with sulphur in presence of piperidine to yield the aminothienopyridazineones 3a,b that reacted with
electron poor olefins and acetylenes to yield phthalazines 10-12. The condensed aminothiophenes 3a,b
reacted with dimethylformamide dimethylacetal to yield amidines 13a,b. Compounds 2a,b condensed with
dimethylformamide dimethylacetal to yield the trans enamines 16a,b that cyclized readily into the
pyridopyridazinones 17a,b on treatment with ammonium acetate in presence of acetic acid. Compounds
2a-d reacted also with benzylidenemalononitrile to yield the phthalazinones 21a-d. The reactions were
conducted both by microwave heating and conventional heating. Better yields in much shorter reaction
times were achieved by microwave heating.
J. Heterocyclic Chem., 43, 1575 (2006).
In conjunction to previous recent interest in adopting
yields on refluxing 3a,b with sulphur in DMF solution in
presence of piperidine for 4 hours. The synthesis of 2 and
3 is an extension to our previously well-established
synthesis 3-carboxylic ester derivatives of 2 and 3 [13-
15].
Compound 3b reacted readily with ethyl acrylate 4,
maleimide 5a and N-methylmaleimide 5b in a mixture of
acetic acid and dioxane in focused microwave at 210 ºC
for 15 minutes and compounds 3a,b reacted with
naphthoquinone 6 in ethanol at 100 ºC for 15 minutes in
focused microwave to yield products of addition and
hydrogen sulphide elimination. These products were also
obtained on refluxing 3a,b with 4-6 in the same solvents
for 8 hours.
The condensation products of 3 with 4-6 were assumed
to be formed via intermediary of 4+2 cycloadducts 7-9
which readily loses hydrogen sulphide to yield products
10-12 respectively. In no case C-1 alkylation products of
thiepines similar to those claimed earlier to be formed on
reacting thienocoumarin with dimethyl acetylene-
dicarboxylate and ethyl propiolate were formed [16-20]
(Scheme 1).
microwaves as energy source for synthesis of
polyfunctional heteroaromatics [1-5], we report here
efficient synthesis of title compounds utilizing 1a-d as
starting materials and microwaves as energy source. The
title compounds are biologically interesting molecules and
their chemistry and pharmacology is receiving
considerable recent interest [6-8]. Moreover utilizing
microwaves as environmentally eco-friendly energy
sources is being also now explored [9-12].
The starting 1a-d condensed with ethyl cyanoacetate on
heating in focused microwave at 170 ºC for 4 minutes in
presence of ammonium acetate to yield pyridazinones 2a-
d in 52 to 62% yields. The same compounds could also be
obtained on heating 1a-d with ethyl cyanoacetate in acetic
acid and in presence of ammonium acetate for ten hours,
in 50 to 55% yields.
The pyridazinones 2a-d readily reacted with sulphur in
presence of piperidine on heating in a focused microwave
oven for 5 minutes in dioxane as reaction medium to yield
aminothienopyridazines 3a,b in 74 and 76% yields. Again
thienopyridazines 3a,b were obtained in 69 and 72%

1576
B. AL-Saleh, N. M. Hilmy, M. A. EL-Apasery and M. H. Elnagdi
Vol 43
Scheme 1
with the same reagent and under the same reaction
condition, formed compound 15 (Scheme 2).
O
R
R
CN
O
NC
CO2Et
Compounds 2a,b reacted with dimethylfrormamide
dimethylacetal on heating in focused microwave oven at
180 ºC for 5 minutes or on reflux in DMF for 6 hours. The
condensation products were assigned the trans structure
16a,b based on the 1H NMR which showed olefinic
doublets at ~ ꢀH 5.1 and 8.3 (J = 12.8 Hz). Cis-olefinic
N
N
NH
Ar
N
Ar
1a, R = CH3, Ar = C6H5
2a, R = CH3, Ar = C6H5
b, R = CH3, Ar = 4-CH3C6H4
c, R = C2H5, Ar = C6H5
b, R = CH3, Ar = 4-CH3C6H4
c, R = C2H5, Ar = C6H5
d, R = C2H5, Ar =4-CH3C6H4
d, R = C2H5, Ar =4-CH3C6H4
S
Pip
protons should show lower
J values (8-10 Hz).
O
S
R
Compounds 16a,b were readily converted into the
pyrido[3,4-d]pyridazine-4,5-diones 17a,b on treatment
with ammonium acetate and acetic acid in focused
microwave oven at 150 ºC for 5 minutes or on reflux in
the same mixture for 3 hours. Compounds 2a-d reacted
with benzylidenemalononitrile 18 in pyridine in focused
microwave oven at 175 ºC for 5 minutes to yield 21a-d or
on reflux in pyridine for 5 hours. This is a further
extension to our established phthalazine synthesis [21,22],
which is believed to proceed via intermediary of 19 and
20 (Scheme 3).
R
O
X
S
O
O
S
X
R
OEt
NH2
NH
2 O
N
5a, X = NH
b, X = NCH3
4
CO2Et
NH2
N
N
O
N
O
N
Ar
Ar
N
O
8
3a, R = H, Ar = 4-CH3C6H4
b, R = CH3, Ar = C6H5
Ar
7
- H2S
O
O
X
- H2S
H3C
O
H
OEt
N
H
H3C
N
O
N
O
H
N
O
Ph
N
O
Scheme 3
NMe2
11a, X = NH
b, X = NCH3
H
O
S
R
N
Ph
H
N
10
NH2
O
N
CN
N
O
DMFDMA
NH4OAc / AcOH
O
H
H
O
2a-d
O
N
R
Ar
9
N
N
Ar
N
O
N
O
- H2S
N
N
Ph
CN
CN
Ar
Ar
16a, Ar=C6H5
b, Ar=4-CH3C6H4
17a, Ar=C6H5
18
O
b, Ar=4-CH3C6H4
12a, R = H, Ar = 4-CH3C6H4
b, R = CH3, Ar = C6H5
Ph
Ph
CN
Ph
R
CN
CN
R
N
R
CN
CN
Reaction of compounds 3a,b with dimethylformamide
CN
NH2
-HCN
dimethylacetal (DMFDMA) in focused microwave at 200
ºC for 15 minutes in the presence of a few drops of
dimethylformamide afforded condensation products
13a,b; no trace of C-1 alkylation products were observed.
Compounds 3a upon reflux in AcOH/c.HC1 mixture (3:1
by volume), afforded derivative 14 whose structure based
NH
N
N
O
N
N
O
N
O
Ar
Ar
Ar
21a, R=H, Ar=C6H5
b, R=H, Ar=4-CH3C6H4
c, R=CH3, Ar=C6H5
19
20
d, R=CH3, Ar=4-CH3C6H4
on the H NMR and 13C NMR spectra, that reveal the
1
presence of methylene proton at ꢀH = ca 4.41 and ꢀC = ca
32.7 ppm respectively, while compound 3b when treated
In conclusion microwaves heating is an efficient
method for obtaining polyfunctionally substituted title
compounds in equal or much higher yields than those
obtained by conventional heating in much shorter time.
Scheme 2
S
O
EXPERIMENTAL
N
R
N
O
S
NMe2
Ar
N
All melting points are uncorrected. IR spectra were recorded
in KBr disks using a Perkin-Elmer System 2000 FT-IR
spectrophotometer. 1H and 13C-NMR spectra were recorded on a
Bruker DPX 400, 400MHz super-conducting NMR spectrometer
in deuteriochloroform or dimethylsulfoxide-d6 as solvent and
TMS as internal standard; chemical shifts are reported in ꢀ
units (ppm). Mass spectra were measured on a VG Autospec-
Q (high resolution, high performance, tri-sector GC/MS/MS).
DMFDMA
14,Ar = 4-CH3C6H4
AcOH / HCl
Reflux
3a,b
N
R
O
N
O
S
Ar
CH3
N
H
13a, R = H, Ar = 4-CH3C6H4
b, R = CH3, Ar = C6H5
N
N
O
Ar
15, R = CH3, Ar = C6H5

Nov-Dec 2006
Microwaves in Organic Synthesis: Synthesis of Pyridazinones, Phthalazinones and
Pyridopyridazinones from 2-Oxo- Arylhydrazones Under Microwave Irradiation
1577
Microanalyses were performed on
a
LECO CHNS-932
D2O exchangeable), 13C nmr (dimethylsulfoxide-d6): ꢁ = 200.0
(CO), 142.0, 134.3, 131.4, 130.4, 114.4, 30.0 (CH2), 21.3 (CH3),
9.5 (CH3).
Elemental Analyzer. Focused microwave experiments were
conducted in a CEM Explorer microwave. Compounds 1a was
prepared following published procedure [23].
Anal. Calcd. For C11H14N2O (190.24): C, 69.45; H,
7.42; N, 14.73. Found C, 69.56; H, 7.34; N, 14.73.
General Procedure for the Preparation of Compounds 1a-d.
General Procedure for the Preparation of Compounds 2a-d.
The mixture of (3.5 g) of potassium hydroxide in (100 ml) of
water, (6.5 g) of ethyl acetoacetate was allowed to stir at room
temperature for 24 hours. The solution of potassium acetate was
cooled to 0 ºC and (4.5 ml) of concentrated hydrochloric acid in
(15 ml) of ice-water was added slowly with stirring, then
gradually treated under stirring with a solution of aryldiazonium
chloride (prepared from the corresponding aromatic amine (0.01
mol) and the appropriate quantities of both hydrochloric acid
and sodium nitrite. The mixture is made basic by addition of (8.2
g) of sodium acetate dissolved in (30 ml) of water. The solid
product, so formed, was collected by filtration and crystallized
from toluene.
A mixture of 1a-d (0.01 mol), ethyl cyanoacetate (1.13 g, 0.01
mol), ammonium acetate (2 g) and acetic acid (0.6 mol) was
irradiated in focused microwave at 150 Watt, 170 ºC for 4 minutes,
then left to cool and triturated with ethanol. The solid product, so
formed, was collected by filtration and crystallized from toluene.
5-Methyl-3-oxo-2-phenyl-2,3-dihydropyridazine-4-carbonitrile (2a).
Compound 2a was obtained as gray crystals (1.21 g, 57%),
mp. 158.160 ºC, ir (KBr) ꢀmax = 2233 (CN), 1659 (CO) cm-1; ms:
m/z = 211 (M+); 1H nmr (dimethylsulfoxide-d6): ꢁ = 2.60 (s, 3H,
CH3), 7.53-7.55 (m, 5H, phenyl-H), 8.24 (s, 1H, pyridazine-H),
13C nmr (dimethylsulfoxide-d6): ꢁ = 157.0 (CO), 152.6, 141.5,
139.9, 129.8, 129.7, 126.8, 114.4, 114.0, 19.1 (CH3).
1-(Phenyl-hydrazono)-propan-2-one (1a).
Compound 1a was obtained as yellowish green crystals (1.44
g, 89%), mp. 152 ºC (Lit.,150 ºC), ir (KBr) ꢀmax = 3249 (NH),
1649 (CO) cm-1; ms: m/z = 162 (M+); 1H nmr (dimethyl-
sulfoxide-d6 ): ꢁ = 2.31 (s, 3H, CH3), 6.93 (t, 1H, J = 7.4 Hz,
phenyl-H), 7.17 (t, 2H, J = 7.7 Hz, phenyl-H), 7.24 (s,1H, imine-
H), 7.29 (d, 2H, J = 8 Hz, phenyl-H), 11.33 (s, 1H, NH, D2O
exchangeable).
Anal. Calcd. For C12H9N3O (211.22): C, 68.24; H, 4.29; N,
19.89. Found C, 68.37; H, 4.38; N, 19.42.
5-Methyl-3-oxo-2-p-tolyl-2,3-dihydropyridazine-4-carbonitrile
(2b).
Compound 2b was obtained as gray crystals (1.18 g, 52%),
mp. 209 ºC, ir (KBr) ꢀmax = 2229 (CN), 1658 (CO) cm-1; ms: m/z
1
= 225 (M+); H nmr (dimethylsulfoxide-d6): ꢁ = 2.37 (s, 3H,
Anal. Calcd. For C9H10N2O (162.19): C, 66.65; H, 6.21; N,
17.27. Found C, 66.63; H, 6.07; N, 17.27.
CH3), 2.50 (s, 3H, CH3), 7.31 (d, 2H, J = 8.3 Hz, p-tolyl-H), 7.41
(d, 2H, J = 8.3 Hz, p-tolyl-H), 8.22 (s, 1H, pyridazine-H), 13C
nmr (dimethylsulfoxide-d6): ꢁ = 157.0 (CO), 152.4, 139.7,
139.3, 139.1, 130.2, 126.3, 114.5, 113.9, 21.7 (CH3), 19.0 (CH3).
Anal. Calcd. For C13H11N3O (225.25): C, 69.32; H, 4.92; N,
18.66. Found C, 69.18; H, 4.90; N, 18.34.
1-(p-Tolyl-hydrazono)-propan-2-one (1b).
Compound 1b was obtained as light green crystals (1.06 g,
60%), mp. 128-130 ºC, ir (KBr) ꢀmax = 3246 (NH), 1652 (CO)
1
cm-1; ms: m/z = 176 (M+); H nmr (dimethylsulfoxide-d6): ꢁ =
2.24 (s, 3H, CH3), 2.30 (s, 3H, CH3), 7.07 (d, 2H, J = 8.6 Hz, p-
tolyl-H), 7.11 (d, 2H, J = 8.6 Hz, p-tolyl-H), 7.21 (s, 1H, imine-
H), 11.25 (s, 1H, NH, D2O exchangeable), 13C nmr
(dimethylsulfoxide-d6): ꢁ = 197.0 (CO), 141.9, 135.0, 131.5,
130.8, 114.4, 25.1 (CH3), 21.3 (CH3).
5-Ethyl-3-oxo-2-phenyl-2,3-dihydropyridazine-4-carbonitrile (2c).
Compound 2c was obtained as light green crystals (1.26 g,
56%), mp. 100 ºC, ir (KBr) ꢀmax = 2234 (CN), 1657 (CO) cm-1;
ms: m/z = 225 (M+); 1H nmr (dimethylsulfoxide-d6): ꢁ = 1.26 (t,
3H, J = 7.6 Hz, CH3), 2.74 (q, 2H, J = 7.6 Hz, CH2), 7.47-7.57
(m, 5H, phenyl-H), 8.32 (s, 1H, pyridazine-H), 13C nmr
(dimethylsulfoxide-d6): ꢁ = 157.2 (CO), 157.0, 141.6, 138.9,
129.8, 129.7, 126.6, 114.2, 113.2, 26.4 (CH2), 13.8 (CH3).
Anal. Calcd. For C13H11N3O (225.25): C, 69.32; H, 4.92; N,
18.66. Found C, 69.56; H, 5.05; N, 18.77.
Anal. Calcd. For C10H12N2O (176.22): C, 68.16; H, 6.86; N,
15.90. Found C, 68.26; H, 6.81; N, 15.91.
1-(Phenyl-hydrazono)-butan-2-one (1c).
Compound 1c was obtained as red crystals (1.08 g, 61%), mp.
150-152 ºC, ir (KBr) ꢀmax = 3251 (NH), 1656 (CO) cm-1; ms: m/z
= 176 (M+); 1H nmr (dimethylsulfoxide-d6 ): ꢁ = 1.01 (s, 3H, J =
7.6 Hz, CH3), 2.77 (q, 2H, J = 7.2 Hz, CH2), 6.92 (t, 1H, J = 7.4
Hz, phenyl-H), 7.17 (t, 2H, J = 7.7 Hz, phenyl-H), 7.24 (s,1H,
imine-H), 7.29 (d, 2H, J = 8 Hz, phenyl-H), 11.27 (s, 1H, NH,
D2O exchangeable), 13C nmr (dimethylsulfoxide-d6): ꢁ = 200.2
(CO), 144.3, 134.9, 130.4, 122.5, 114.4, 30.1 (CH2), 9.5 (CH3).
Anal. Calcd. For C10H12N2O (176.22): C, 68.16; H, 6.86; N,
15.90. Found C, 68.50; H, 6.89; N, 15.92.
5-Ethyl-3-oxo-2-p-tolyl-2,3-dihydropyridazine-4-carbonitrile (2d).
Compound 2d was obtained as light green crystals (1.49 g,
62%), mp. 91 ºC, ir (KBr) ꢀmax = 2231 (CN), 1659 (CO) cm-1;
ms: m/z = 239 (M+); 1H nmr (dimethylsulfoxide-d6): ꢁ = 1.26 (t,
3H, J = 7.6 Hz, CH3), 2.37 (s, 3H, CH3), 2.73 (q, 2H, J = 7.6 Hz,
CH2), 7.31 (d, 2H, J = 8.2 Hz, p-tolyl-H), 7.42 (d, 2H, J = 8.2
Hz, p-tolyl-H), 8.30 (s, 1H, pyridazine-H), 13C nmr (dimethyl-
sulfoxide-d6): ꢁ = 157.2 (CO), 156.8, 139.3, 139.2, 138.8, 130.2,
126.3, 114.2, 113.1, 26.3 (CH2), 21.7 (CH3), 13.7 (CH3).
Anal. Calcd. For C14H13N3O (239.27): C, 70.28; H, 5.48; N,
17.56. Found C, 70.21; H, 5.52; N, 17.51.
1-(p-Tolyl-hydrazono)-butan-2-one (1d).
Compound 1d was obtained as wine red crystals (1.26 g,
66%), mp. 134-136 ºC, ir (KBr) ꢀmax = 3236 (NH), 1651 (CO)
1
cm-1; ms: m/z = 190 (M+); H nmr (dimethylsulfoxide-d6): ꢁ =
General Procedure for the Preparation of Compounds 3a,b.
1.01 (t, 3H, J = 7.4 Hz, CH3), 2.24 (s, 3H, CH3), 2.75 (q, 2H, J =
7.4 Hz, CH2), 7.05 (d, 2H, J = 8.4 Hz, p-tolyl-H), 7.10 (d, 2H, J
= 8.4 Hz, p-tolyl-H), 7.21 (s, 1H, imine-H), 11.21 (s, 1H, NH,
To a suspension of compounds 2a or 2c (0.01 mol) in
dioxane (2 ml), elemental sulphur (0.32 g, 0.01 mol) and few

1578
B. AL-Saleh, N. M. Hilmy, M. A. EL-Apasery and M. H. Elnagdi
Vol 43
drops of piperidine were added. The reaction mixture was
irradiated in focused microwave at 150 Watt, 200 ºC for 5
minutes and then poured onto water. The solid product, so
formed, was collected by filtration and crystallized from ethanol.
NH, D2O exchangeable). 7.43 (t, 1H, J = 7.0 Hz, phenyl-H), 7.51
(t, 2H, J = 7.4 Hz, phenyl-H), 7.58 (d, 2H, J = 7.8 Hz, phenyl-
H), 8.56 (br s, 1H, NH, D2O exchangeable). 8.67 (s, 1H,
pyridazine-H), 11.38 (br s, 1H, NH, D2O exchangeable). 13C
nmr (dimethylsulfoxide-d6): ꢁ = 170.8, 170.0, 161.3 (CO),
146.6, 142.1, 137.3, 136.3, 134.6, 129.7, 129.1, 127.1, 120.6,
117.1, 111.3, 12.1 (CH3).
7-Amino-2-p-tolyl-2H-thieno[3,4-d]pyridazin-1-one (3a).
Compound 3a was obtained as green crystals (1.91 g, 74%),
mp. 135 ºC, ir (KBr) ꢀmax = 3410 and 3299 (NH2), 1648 (CO)
Anal. Calcd. For C17H12N4O3 (320.30): C, 63.75; H, 3.78; N,
17.49. Found C, 63.77; H, 3.92; N, 17.69.
1
cm-1; ms: m/z = 257 (M+); H nmr (dimethylsulfoxide-d6): ꢁ =
2.33 (s, 3H, CH3), 6.76 (s, 1H, H-5), 7.21 (d, 2H, J = 7.7 Hz, p-
tolyl-H), 7.36 (d, 2H, J = 8.0 Hz, p-tolyl-H), 7.48 (s, 2H, NH2,
D2O exchangeable). 7.93 (s, 1H, pyridazine-H), 13C nmr
(deuteriochloroform): ꢁ = 168.1 (CO), 164.2, 144.5, 141.7,
135.5, 134.9, 134.4, 131.0, 109.8, 107.8, 26.4 (CH3).
9-Amino-5,7-dimethyl-2-phenyl-2H-pyrrolo[3,4-g]phthalazine-
1,6,8-trione (11b).
Compound 11b was obtained as yellow crystals (1.98 g,
59%), mp. 273 ºC, ir (KBr) ꢀmax = 3444 and 3307 (NH2), 1747,
1696, 1650 (CO) cm-1; ms: m/z = 334 (M+); 1H nmr
(deuteriochloroform): ꢁ = 2.82 (s, 3H, CH3), 3.14 (s, 3H, CH3),
6.99 (br s, 1H, NH, D2O exchangeable). 7.44 (t, 1H, J = 7.0 Hz,
phenyl-H), 7.52 (t, 2H, J = 7.4 Hz, phenyl-H), 7.61 (d, 2H, J =
8.0 Hz, phenyl-H), 8.48 (s, 1H, pyridazine-H), 8.77 (br s, 1H,
NH, D2O exchangeable). 13C nmr (deuteriochloroform): ꢁ =
169.6, 169.0, 161.5 (CO), 146.9, 141.5, 136.3, 136.1, 133.7,
129.5, 129.0, 126.3, 120.8, 117.6, 110.5, 24.3 (CH3), 12.2 (CH3).
Anal. Calcd. For C18H14N4O3 (334.33): C, 64.66; H, 4.22; N,
16.76. Found C, 64.23; H, 4.33; N, 16.77.
Anal. Calcd. For C13H11N3OS (257.31): C, 60.68; H, 4.31; N,
16.33; S, 12.46. Found C, 60.79; H, 4.30; N, 16.30; S, 11.87.
7-Amino-5-methyl-2-phenyl-2H-thieno[3,4-d]pyridazin-1-one
(3b).
Compound 3b was obtained as brown crystals (1.96 g, 76%),
mp. 209 ºC, ir (KBr) ꢀmax = 3422 and 3285 (NH2), 1627 (CO)
1
cm-1; ms: m/z = 257 (M+); H nmr (dimethylsulfoxide-d6): ꢁ =
2.44 (s, 3H, CH3), 7.27 (t, 1H, J = 7.6 Hz, phenyl-H), 7.33 (s,
2H, NH2, D2O exchangeable). 7.40 (t, 2H, J = 8.3 Hz, phenyl-H),
7.48 (d, 2H, J = 8.6 Hz, phenyl-H), 8.01 (s, 1H, pyridazine-H),
13C nmr (dimethylsulfoxide-d6): ꢁ = 160.8 (CO), 159.4, 142.3,
135.4, 129.8, 128.9, 127.3, 126.6, 116.7, 104.2, 12.4 (CH3).
Anal. Calcd. For C13H11N3OS (257.31): C, 60.68; H, 4.31; N,
16.33; S, 12.46. Found C, 60.73; H, 4.34; N, 16.33; S, 12.57.
Reaction of Compounds 3a,b with 1,4-Naphthoquinone.
A mixture of each of 3a,b (10 mmol) with 1,4-naphtho-
quinone (1.58 g, 0.01 mol) in ethanol (4 ml) was irradiated in
focused microwave at 125 Watt, 100 ºC for 15 minutes. The
solvent was removed and the residue cooled to deposit a solid,
which was crystallized from dimethylformamide.
General Procedure for the Preparation of Compounds 10 and
11a,b.
A mixture each of maleimide, N-methylmaleimide and ethyl
acrylate (0.01 mol) and 3b (2.57 g, 0.01 mol) in a mixture of
acetic acid (2 ml) and dioxane (2 ml) was irradiated in focused
microwave at 250 Watt, 210 ºC for 15 minutes. The reaction
mixture was evaporated then washed with ethanol. The solid
products, so formed, were collected by filtration and crystallized
from dioxane.
12-Amino-2-p-tolyl-2H-2,3-diazanaphthacene-1,6,11-trione
(12a).
Compound 12a was obtained as red crystals (2.13 g, 82%),
mp. 264 ºC, ir (KBr) ꢀmax = 3349 and 3235 (NH2), 1658 (br)
1
(CO), 1573 (CO) cm-1; ms: m/z = 381 (M+); H nmr (deuterio-
chloroform): ꢁ = 2.45 (s, 3H, CH3), 7.34 (d, 2H, J = 8.0 Hz, p-
tolyl-H), 7.49 (d, 2H, J = 8.2 Hz, p-tolyl-H), 7.73-7.81 (m, 2H,
arom-H), 7.84 (t, 1H, J = 7.4 Hz, arom-H), 8.28(s, 1H,
pyridazine-H), 8.30 (d, 1H, J = 7.6 Hz, arom-H), 8.38 (d, 1H, J
= 7.6 Hz, arom-H), 9.98 (br s, 1H, NH, D2O exchangeable),
10.21 (br s, 1H, NH, D2O exchangeable). 13C nmr (dimethylsul-
foxide-d6): ꢁ = 184.6, 183.3, 161.5 (CO), 154.9, 139.4, 139.1,
139.0, 138.8, 137.0, 135.8, 135.4, 135.2, 134.0, 133.1, 130.1,
127.7, 127.6, 126.1, 116.6, 111.5, 21.8 (CH3).
Ethyl 5-Amino-8-methyl-4-oxo-3-phenyl-3,4-dihydrophthalaz-
ine-6-carboxylate (10).
Compound 10 was obtained as wine red crystals (2.23 g,
69%), mp. 185 ºC, ir (KBr) ꢀmax = 3419 and 3288 (NH2), 1687,
1
1638 (CO) cm-1; ms: m/z = 323 (M+); H nmr (dimethylsul-
foxide-d6): ꢁ = 1.32 (t, 3H, J = 7.0 Hz, CH3), 2.57 (s, 3H, CH3),
4.27 (q, 2H, J = 7.0 Hz, CH2), 7.41-7.57 (m, 5H, phenyl-H), 8.01
(s, 1H, H-7), 8.14 (br s, 1H, NH, D2O exchangeable), 8.46 (s,
1H, pyridazine-H), 9.17 (br s, 1H, NH, D2O exchangeable). 13C
nmr (dimethylsulfoxide-d6): ꢁ = 167.5, 161.7 (CO), 152.1,
142.5, 138.4, 137.3, 133.7, 129.8, 128.8, 127.3, 119.1, 113.0,
110.3, 67.3 (CH2), 18.0 (CH3), 15.1 (CH3).
Anal. Calcd. For C23H15N3O3 (381.38): C, 72.43; H, 3.96; N,
11.02. Found C, 71.97; H, 4.07; N, 11.27.
12-Amino-5-methyl-2-phenyl-2H-2,3-diazanaphthacene-1,6,11-
trione (12b).
Compound 12b was obtained as wine red crystals (3.24 g,
85%), mp. > 300 ºC, ir (KBr) ꢀmax = 3351 and 3240 (NH2), 1650
(br) (CO), 1593 (CO) cm-1; ms: m/z = 381 (M+); 1H nmr
(deuteriochloroform): ꢁ = 2.66 (s, 3H, CH3), 7.45 (t, 1H, J = 7.2
Hz, arom-H), 7.54 (t, 2H, J = 7.6 Hz, arom-H), 7.63 (d, 2H, J =
7.9 Hz, arom-H), 7.74 –7.82 (m,2H, arom-H), 8.17 (d, 1H, J =
7.4 Hz, arom-H), 8.27 (d, 1H, J = 7.4 Hz, arom-H), 8.64 (s,1H,
pyridazine-H), 10.10 (s, 1H, NH, D2O exchangeable), 10.42 (s,
1H, NH, D2O exchangeable).
Anal. Calcd. For C18H17N3O3 (323.35): C, 66.86; H, 5.30; N,
13.00. Found C, 66.48; H, 5.29; N, 13.01.
9-Amino-5-methyl-2-phenyl-2H-pyrrolo[3,4-g]phthalazine-1,6,8-
trione (11a).
Compound 11a was obtained as yellow crystals (2.02 g,
63%), mp. > 300 ºC, ir (KBr) ꢀmax = 3426 and 3289 (NH2), 3180
(NH), 1751, 1708, 1651 (CO) cm-1; ms: m/z = 320 (M+); 1H nmr
(dimethylsulfoxide-d6): ꢁ = 2.72 (s, 3H, CH3), 7.11 (br s, 1H,

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Pyridopyridazinones from 2-Oxo- Arylhydrazones Under Microwave Irradiation
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Anal. Calcd. For C23H15N3O3 (381.38): C, 72.43; H, 3.96; N,
11.02. Found C, 72.15; H, 4.08; N, 11.31
= 2.29 (s, 3H, CH3), 2.69 (s, 3H, CH3), 7.28-7.59 (m, 5H,
phenyl-H), 8.07 (s,1H, pyridazine-H), 10.97 (s, 1H, NH, D2O
exchangeable). 13C nmr (deuteriochloroform): ꢁ = 167.6, 159.7
(CO), 142.9, 141.2, 134.7, 129.4, 128.2, 127.8, 126.4, 124.9,
112.1, 23.7 (CH3), 12.4 (CH3)
General Procedure for the Preparation of Compounds 13a,b.
A solution of each of 3a,b (10 mmol) and DMFDMA (1.19 g,
10 mmol) in the presence of a few drops of dimethylformamide
was irradiated in focused microwave at 250 Watt, 200 ºC for 15
minutes. The solid products obtained were crystallized from
ethanol.
Anal. Calcd. For C15H13N3O2S (299.35): C, 60.18; H, 4.38; N,
14.04; S, 10.71. Found C, 60.19; H, 4.44; N, 14.18; S, 10.77.
General Procedure for the Preparation of Compounds 16a,b.
A solution of each of 2a,b (10 mmol) and DMFDMA (1.19 g,
10 mmol) was irradiated in a focused microwave at 150 Watt,
180 ºC for 5 minutes. The solid product obtained was
crystallized from dioxane.
N,N-Dimethyl-N'-(4-oxo-3-p-tolyl-3,4-dihydrothieno[3,4-d]pyri-
dazin-5-yl) formamidine (13a).
Compound 13a was obtained as brown crystals (2.00 g, 64%),
mp. 198-200 ºC, ir (KBr) ꢀmax = 1648 (CO) cm-1; ms: m/z = 312
1
(M+); H nmr (dimethylsulfoxide-d6 ): ꢁ = 2.30 (s, 3H, CH3),
5-(2-Dimethylamino-vinyl)-3-oxo-2-phenyl-2,3-dihydropyrida-
zine-4-carbonitrile (16a).
2.98 (s, 3H, N-CH3), 3.06 (s, 3H, N-CH3), 7.12 (s,1H, thiophene-
H), 7.22 (d, 2H, J = 8.2 Hz, p-tolyl-H), 7.32(d, 2H, J = 8.2 Hz,
p-tolyl-H), 7.39 (s,1H, amidine-H), 8.06 (s,1H, pyridazine-H),
13C nmr (dimethylsulfoxide-d6): ꢁ = 167.4 (CO), 158.4, 157.6,
140.5, 136.9, 136.2, 132.6, 130.3, 127.2, 126.5, 112.1, 35.1 (N-
CH3), 21.6 (CH3).
Compound 16a was obtained as yellowish green crystals
(1.92 g, 72%), mp. 225 ºC, ir (KBr) ꢀmax = 2203 (CN), 1616
1
(CO) cm-1; ms: m/z = 266 (M+); H nmr (dimethylsulfoxide-d6):
ꢁ = 2.99 (s, 3H, N-CH3), 3.24 (s, 3H, N-CH3), 5.17 (d, 1H, J =
12.8 Hz, vinylic-H), 7.36-7.52 (m, 5H, phenyl-H), 8.32 (d, 1H, J
= 12.8 Hz, vinylic-H), 8.43 (s, 1H, pyridazine-H), 13C nmr
(dimethylsulfoxide-d6): ꢁ = 158.4 (CO), 154.1, 148.8, 142.0,
134.4, 129.5, 128.5, 126.5, 117.2, 92.0, 90.3, 46.1 (N-CH3), 37.8
(N-CH3).
Anal. Calcd. For C16H16N4OS (312.39): C, 61.52; H, 5.16; N,
17.93; S, 10.26. Found C, 61.47; H, 5.16; N, 17.69; S, 10.01.
N,N-Dimethyl-N'-(7-methyl-4-oxo-3-phenyl-3,4-dihydrothieno-
[3,4-d]pyridazin-5-yl) formamidine (13b).
Anal. Calcd. For C15H14N4O (266.30): C, 67.69; H, 5.30; N,
21.04. Found C, 67.58; H, 5.41; N, 20.96.
Compound 13b was obtained as light green crystals (2.23 g,
71%), mp. 165 ºC, ir (KBr) ꢀmax = 1655 (CO) cm-1; ms: m/z =
312 (M+); 1H nmr (dimethylsulfoxide-d6 ): ꢁ = 2.57 (s, 3H, CH3),
2.96 (s, 3H, N-CH3), 3.04 (s, 3H, N-CH3), 7.29-7.47 (m, 5H,
phenyl-H), 7.99 (s,1H, amidine-H), 8.15 (s,1H, pyridazine-H),
13C nmr (dimethylsulfoxide-d6): ꢁ = 164.0 (CO), 158.1, 157.6,
143.0, 134.9, 129.7, 128.9, 127.5, 127.0, 125.6, 112.4, 35.1 (N-
CH3), 13.0 (CH3).
5-(2-Dimethylamino-vinyl)-3-oxo-2-p-tolyl-2,3-dihydropyridazine-
4-carbonitrile (16b).
Compound 16b was obtained as green crystals (2.10 g, 75%),
mp. 210 ºC, ir (KBr) ꢀmax = 2209 (CN), 1630 (CO) cm-1; ms: m/z
1
= 280 (M+); H nmr (dimethylsulfoxide-d6): ꢁ = 2.34 (s, 3H,
CH3), 2.97 (s, 3H, N-CH3), 3.22 (s, 3H, N-CH3), 5.15 (d, 1H, J =
12.8 Hz, vinylic-H), 7.24 (d, 2H, J = 8.2 Hz, p-tolyl-H), 7.37 (d,
2H, J = 8.2 Hz, p-tolyl-H), 8.18 (d, 1H, J = 12.8 Hz, vinylic-H),
8.39 (s, 1H, pyridazine-H), 13C nmr (dimethylsulfoxide-d6): ꢁ =
158.4 (CO), 154.0, 148.7, 139.6, 137.9, 134.2, 129.9, 126.1,
117.2, 92.1, 90.2, 46.1 (N-CH3), 37.9 (N-CH3), 21.6 (CH3).
Anal. Calcd. For C16H16N4O (280.32): C, 68.55; H, 5.75; N,
19.99. Found C, 68.52; H, 5.87; N, 19.96.
Anal. Calcd. For C16H16N4OS (312.39): C, 61.52; H, 5.16; N,
17.93; S, 10.26. Found C, 61.51; H, 5.25; N, 17.82; S, 10.08.
General Procedure for the Preparation of Compounds 14 and
15.
A solution of each of 13a,b (0.01 mol) in acetic acid /
hydrochloric acid (4 ml, 3:1 by volume) was refluxed for 3 hrs,
and then allowed to cool to room temperature. The solid product
so formed was collected by filtration and crystallized from
ethanol.
General Procedure for the Preparation of Compounds 17a,b.
A solution of each of 16a,b (0.01 mol), acetic acid (2 ml) and
ammonium acetate (1 g) was irradiated in focused microwave at
150 Watt, 150 ºC for 5 minutes, then allowed to cool to room
temperature. The solid product so formed was collected by
filtration and crystallized from acetic acid.
2-p-Tolyl-2H,5H-thieno[3,4-d]pyridazine-1,7-dione (14).
Compound 13a was obtained as green crystals (1.60 g, 62%),
mp. 196 ºC, ir (KBr) ꢀmax = 1794 and 1692 (CO) cm-1; ms: m/z =
1
258 (M+); H nmr (deuteriochloroform): ꢁ = 2.32 (s, 3H, CH3),
4.41 (s, 2H, CH2), 7.28 (d, 2H, J = 7.6 Hz, p-tolyl-H), 7.47 (d,
2H, J = 7.6 Hz, p-tolyl-H), 8.15 (s, 1H, pyridazine-H), 13C nmr
(deuteriochloroform): ꢁ = 192.2, 155.7 (CO), 139.5, 138.6,
134.6, 131.5, 130.0, 126.1, 125.6, 32.7 (CH2), 21.8 (CH3).
Anal. Calcd. For C13H10N2O2S (258.30): C, 60.45; H, 3.90; N,
10.85; S, 12.41. Found C, 60.37; H, 4.08; N, 11.52; S, 12.38.
3-Phenyl-3H,6H-pyrido[3,4-d]pyridazine-4,5-dione (17a).
Compound 17a was obtained as light green crystals (1.87 g,
89%), mp. 298 ºC, ir (KBr) ꢀmax = 3300 (NH), 1691 (CO) cm-1;
ms: m/z = 239 (M+); 1H nmr (dimethylsulfoxide-d6): ꢁ = 6.49 (d,
1H, J = 6.4 Hz H-8), 7.39-7.52 (m, 5H, phenyl-H), 7.80 (d, 1H,
J = 6.4 Hz H-7), 8.28 (s, 1H, pyridazine-H), 12.10 (s, 1H, NH,
D2O exchangeable). 13C nmr (dimethylsulfoxide-d6): ꢁ = 159.7,
157.2 (CO), 154.7, 142.8, 142.3, 139.0, 137.1, 129.6, 127.2,
107.7, 101.7.
N-(7-Methyl-4-oxo-3-phenyl-3,4-dihydrothieno[3,4-d]pyridazin-
5-yl)acetamide (15).
Compound 13b was obtained as light green crystals (2.10 g,
70%), mp. 235 ºC, ir (KBr) ꢀmax = 3306 (NH), 1684 and 1637
(CO) cm-1; ms: m/z = 299 (M+); 1H nmr (deuteriochloroform): ꢁ
Anal. Calcd. For C13H9N3O2 (239.23): C, 65.27; H, 3.79; N,
17.56. Found C, 65.09; H, 3.98; N, 17.64.

1580
B. AL-Saleh, N. M. Hilmy, M. A. EL-Apasery and M. H. Elnagdi
Vol 43
3-p-Tolyl-3H,6H-pyrido[3,4-d]pyridazine-4,5-dione (17b).
Anal. Calcd. For C22H16N4O (352.39): C, 74.98; H, 4.58; N,
15.90. Found C, 75.36; H, 4.62; N, 15.92.
Compound 17b was obtained as light green crystals (1.62 g,
64%), mp. 295 ºC, ir (KBr) ꢀmax = 3290 (NH), 1689 (CO) cm-1;
ms: m/z = 253 (M+); 1H nmr (dimethylsulfoxide-d6): ꢁ = 2.36 (s,
3H, CH3), 6.48 (d, 1H, J = 6.4 Hz H-8), 7.27 (d, 2H, J = 8.0 Hz,
p-tolyl-H), 7.29 (d, 2H, J = 8.0 Hz, p-tolyl-H), 7.79 (d, 1H, J =
6.4 Hz H-7), 8.25 (s, 1H, pyridazine-H), 12.00 (s, 1H, NH, D2O
exchangeable). 13C nmr (dimethylsulfoxide-d6): ꢁ = 159.7, 157.2
(CO), 154.8, 142.7, 140.0, 138.2, 136.9, 130.0, 126.8, 107.7,
101.7, 21.7 (CH3).
5-Amino-8-methyl-4-oxo-7-phenyl-3-p-tolyl-3,4-dihydrophthal-
azine-6-carbonitrile (21d).
Compound 21d was obtained as yellowish green crystals
(2.50 g, 68%), mp. 238 ºC, ir (KBr) ꢀmax = 3454 and 3310 (NH2),
2207 (CN), 1651 (CO) cm-1; ms: m/z = 366 (M+); 1H nmr
(dimethylsulfoxide-d6): ꢁ = 2.15 (s, 3H, CH3), 2.39 (s, 3H, CH3),
7.28 (br s, 2H, NH2, D2O exchangeable), 7.32-7.35 (m, 4H,
arom-H), 7.42-7.47 (m, 2H, arom-H), 7.50-7.58 (m, 3H, arom-
H), 8.59 (s, 1H, pyridazine-H), 13C nmr (dimethylsulfoxide-d6):
ꢁ = 161.0 (CO), 152.1, 151.0, 139.8, 138.8, 138.4, 137.5, 133.2,
130.2, 130.1, 129.6, 126.9, 126.3, 119.3, 117.2, 111.8, 97.8,
21.7 (CH3), 15.6 (CH3).
Anal. Calcd. For C14H11N3O2 (253.26): C, 66.40; H, 4.38; N,
16.59. Found C, 66.30; H, 4.45; N, 16.60.
General Procedure for the Preparation of Compounds 21a-d.
A solution of each of 2a-d (10 mmol) in pyridine (3 ml) was
treated with benzylidenemalononitrile (1.54 g, 0.01 mol). The
reaction mixture was irradiated in a focused microwave at 150
Watt, 175 ºC for 5 minutes, then poured onto water and acidified
with dilute hydrochloric acid. The solid product obtained was
crystallized from dioxane
Anal. Calcd. For C23H18N4O (366.42): C, 75.39; H, 4.95; N,
15.29. Found C, 74.88; H, 5.09; N, 15.40.
Acknowledgement.
The authors are grateful to University of Kuwait, Research
Administration for financial support through project SC 02/02.
Analytical facilities provided by SAF are greatly appreciated.
5-Amino-4-oxo-3,7-diphenyl-3,4-dihydrophthalazine-6-carbo-
nitrile (21a).
Compound 21a was obtained as gray crystals (2.21 g, 65%),
mp. 259-261 ºC, ir (KBr) ꢀmax = 3455 and 3301 (NH2), 2208
REFERENCES AND NOTES
1
(CN), 1658 (CO) cm-1; ms: m/z = 338 (M+); H nmr (deuterio-
[1] M. A. Al-Shiekh, A. M. S. El-Din, E. A. Hafez and M. H.
Elnagdi, J. Chem. Res., 174 (2004).
[2] M. A. Al-Shiekh, A. M. S. El-Din, E. A. Hafez and M. H.
Elnagdi, J. Heterocyclic Chem., 41, 647 (2004).
[3] B. Al-Saleh, H. Bahbehani, M. A. El-Apasery and M. H.
Elnagdi, J. Chem. Res., 575 (2004).
[4] B. Al-Saleh, M. A. El-Apasery and M. H. Elnagdi, J. Chem.
Res., 578 (2004)..
[5] K. M. Al-Zaydi, R. M. Borik and M. H. Elnagdi, Molecules,
8, 910 (2003).
chloroform): ꢁ = 6.92 (s, 1H, H-8), 7.28 (br s, 2H, NH2, D2O
exchangeable), 7.43-7.47 (m, 1H, arom-H), 7.53-7.57 (m, 5H,
arom-H), 7.61-7.64 (m, 4H, arom-H), 8.17 (s, 1H, pyridazine-
H), 13C nmr (deuteriochloroform): ꢁ = 161.0 (CO), 154.2, 151.5,
141.6, 139.2, 138.1, 134.2, 130.2, 129.6, 129.3, 129.0, 128.9,
126.4, 117.0, 113.8, 110.8, 96.4.
Anal. Calcd. For C21H14N4O (338.36): C, 74.54; H, 4.17; N,
16.56. Found C, 74.66; H, 4.17; N, 16.59.
[6] A. Bhandari, B. Li, M. A. Gallop, J. Synthetic Organic
Chemistry, 11, 1951 (1999).
5-Amino-4-oxo-7-phenyl-3-p-tolyl-3,4-dihydrophthalazine-6-
carbonitrile (21b).
[7] G. P. Miller, E. T. Kool, J.Organic Chemistry, 69,
2404 (2004).
Compound 21b was obtained as light green crystals (2.36 g,
67%), mp. 283 ºC, ir (KBr) ꢀmax = 3454 and 3302 (NH2), 2207
(CN), 1656 (CO) cm-1; ms: m/z = 352 (M+); 1H nmr
(dimethylsulfoxide-d6): ꢁ = 2.38 (s, 3H, CH3), 7.11 (s, 1H, H-8),
7.31 (d, 2H, J = 8.0 Hz, p-tolyl-H), 7.44 (d, 2H, J = 8.0 Hz, p-
tolyl-H), 7.56-7.64 (m, 7H, arom-H and NH2), 8.43 (s, 1H,
pyridazine-H), 13C nmr (dimethylsulfoxide-d6): ꢁ = 161.0 (CO),
154.6, 151.2, 139.8, 138.6, 138.4, 134.8, 130.4, 130.2, 130.1,
129.8, 129.5, 127.0, 126.3, 117.5, 114.2, 110.7, 21.7 (CH3).
Anal. Calcd. For C22H16N4O (352.39): C, 74.98; H, 4.58; N,
15.90. Found C, 74.54; H, 4.72; N, 16.22.
[8] P. Grosche, A. Höltzel, T. B. Walk and A. Trautwein, J.
Synthetic Organic Chemistry, 11, 1971 (1999).
[9] J. Clark, P. Macquarriee, “Hand Book of Green Chemistry &
Technology”, Blackwell Science, page 402 (2002).
[10] K. Tanaka,” Solvent- Free Organic Synthesis”, WILEY-VCH
GmbH & Co. KGaA, (2003).
[11] V. Santagada, E. Perissuti and G. Galiendo, Current
Medicinal Chemistry, 9,1251 (2002).
[12] P. Lidström, J. Tierney, B. Wathey and J. Westman.
Tetradedron, 51, 9225 (2001).
[13] M. H. Elnagdi, N. S. Ibraheim, F. M. Abdelrazek and A. W.
Erian, Liebigs Ann. Chem., 909 (1988).
[14] M. H. Elnagdi, N. S. Ibraheim, Sadek and M. H. Mohamed,
Liebigs Ann. Chem., 1009 (1988).
5Amino-8-methyl-4-oxo-3,7-diphenyl-3,4-dihydrophthalazine-
6-carbonitrile (21c).
[15] H. Al-Awadi, F. Al-Omran, M. H. Elnagdi, L.
Infantes, C. Foces-Foces, N. Iagerovic, J. Elguero, Tetrahedron,
51, 12745 (1995).
[16] F. Al-Omran, M. M. Abdelkhalik, H. Al-Awadi and M.
H. Elnagdi, Tetrahedron, 52, 11915 (1996).
[17] A. Al-Etaibi, N. Al-Awadi, F. Al-Omran, M. M.
Abdelkhalik and M. H. Elnagdi, J. Chem. Res. (S), 4 Ibid. (M).
151 (1999).
Compound 21c was obtained as brown crystals (2.15 g, 61%),
mp. 260 ºC, ir (KBr) ꢀmax = 3464 and 3322 (NH2), 2208 (CN),
1647 (CO) cm-1; ms: m/z = 352 (M+); 1H nmr (deuterio-
chloroform): ꢁ = 2.26 (s, 3H, CH3), 7.28 (br s, 2H, NH2, D2O
exchangeable), 7.30-7.33 (m, 2H, arom-H), 7.45-7.64 (m, 8H,
arom-H), 8.43 (s, 1H, pyridazine-H), 13C nmr (deuteriochloro-
form): ꢁ = 161.1 (CO), 151.6, 151.0, 141.7, 138.1, 136.8, 132.9,
130.7, 129.9, 129.7, 129.2, 128.9, 126.0, 119.4, 118.8, 112.0,
98.8, 15.4 (CH3).
[18] M. M. Abdelkhalik, A. M. Negm, A. I. Elkhouly and M. H.
Elnagdi, Heteroatom Chemistry, 15, 502 (2004).

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Microwaves in Organic Synthesis: Synthesis of Pyridazinones, Phthalazinones and
Pyridopyridazinones from 2-Oxo- Arylhydrazones Under Microwave Irradiation
1581
[19] E. Nyiondi-Bonguen, E. Sopbue Fondjo, T. Fomum
and D. Döpp, J. Chem. Soc. Perkin Trans. 1, 2191 (1994).
[20] F. Al-Omran, N. Al-Awadi, A. Elassar, A. El-Khair, J.
Chem. Res. (S), 20 Ibid. (M). 237 (2000).
Evian, Tetrahedron, 45, 3597 (1989).
[22] M. H. Elnagdi, A. M. Negm and K. U. Sadek, Synlett., 27
(1994).
[23] N. Rabjohn, ”Organic Synthesis, Collective Volume
4”, John Wiley & Sons, Inc., page 633 (1963).
[21] M. H. Elnagdi, F. M. Abdelrazek, H. S. Ibrahim and A. W.