Microwaves in organic synthesis: Facile synthesis of biologically active pyridazinone and iminopyridazine derivatives

Article abstract of DOI:10.1002/jhet.5570440615

(Chemical Equation Presented) Condensation of Wittig reagents 1a,b with arylhydrazones 2a,b by conventional and by microwave heating techniques furnished the corresponding pyridazines 3a-e. The arylhydrazones 7a,b were allowed to react with 1a,b under the same conditions to produce the pyridazinones 10a,b and iminopyridazines 11a,b respectively. On the other hand, the arylhydrazones 12a-c reacted with 1a to afford the pyridazinones 13a-c. Treatment of 3b with dimethylformamide dimethyl acetal (DMFDMA) produced the adduct 15. The utility of microwave heating technique led to the reduction of the reaction times to few minutes and to the improvement of the yields of the products. The in vitro biological activity of some newly prepared compounds against four types of fungi was studied.

Full text of DOI:10.1002/jhet.5570440615

Nov-Dec 2007
1333
Microwaves in Organic Synthesis: Facile Synthesis of Biologically
Active Pyridazinone and Iminopyridazine Derivatives.
Nadia Ragab Mohamed,*a Manal Mohamed Talaat El-Saidi,a Yasser Mahmoud Ali,a
Mohamed Hilmy Elnagdi.b
a: Department of Photochemistry, National Research Centre, Dokki, Giza, Egypt.
b: Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt.
Corresponding author: E-mail: nadia_ragab_m@hotmail.com
Received November 27, 2006
2
O
R
O
O
1
R
1
2
R
R
MW, 3-6 min
N
Ph P CHR
1a, R= COOEt
b, R= CN
+
N
3
N
X
NH
Ar
Ar
X= O, NH
O
CH
3
O
CH
3
H C
3
DMFDMA
Me N
2
N
N
N
O
N
O
Ar
Ar
Condensation of Wittig reagents 1a,b with arylhydrazones 2a,b by conventional and by microwave
heating techniques furnished the corresponding pyridazines 3a-e. The arylhydrazones 7a,b were allowed to
react with 1a,b under the same conditions to produce the pyridazinones 10a,b and iminopyridazines 11a,b
respectively. On the other hand, the arylhydrazones 12a-c reacted with 1a to afford the pyridazinones
13a-c. Treatment of 3b with dimethylformamide dimethyl acetal (DMFDMA) produced the adduct 15. The
utility of microwave heating technique led to the reduction of the reaction times to few minutes and to the
improvement of the yields of the products. The in vitro biological activity of some newly prepared
compounds against four types of fungi was studied.
J. Heterocyclic Chem., 44, 1333 (2007).
RESULTS AND DISCUSSION
INTRODUCTION
We reported earlier on the synthesis of polyfunctional
bioactive azines using microwave heating as an efficient
heating method [12,13]. In conjunction to this previous
interest in developing polyfunctionally substituted hetero-
aromatics utilizing readily obtainable building blocks, we
report here on the utility of arylhydrazones as precursors
to substituted pyridazines (Scheme I).
The biological activities of poly-functionally
substituted azines and condensed azines have recently
stimulated considerable interest in the chemistry of
these compounds [1-3]. The pharmaceutical uses of
azines are shown by the large number of publications
filed in this area, for example condensed azines act as
anti-bacterials [4], and antihypertensive agents [5].
Recent studies in this field have also revealed their
activities as antiplatelet agents [6], and inhibitors for
platelet aggregation [7].
Since the first report by Gedye et al. [8] on the utility of
microwaves as energy source in organic synthesis,
the adoption of this technique as an environmentally
friendly synthetic approach has been of considerable
interest [9-11].
The condensation of Wittig reagent 1a with arylhydra-
zones 2a,b in refluxing toluene has been shown earlier by
us to produce pyridazinone 3a,b [14]. Likewise reacting
2c with 1a afforded a product that could be formulated as
either 3c or isomeric 6. Structure 6 was ruled out based on
1H-NMR that revealed the presence of two methyl groups
at ꢀ= 2.41 and 2.54 ppm respectively. Similarly the
reaction of 1b with 2b,c afforded 3d,e while 3e was
converted into 3c on reflux in AcOH-HCl (Scheme II).
Furthermore, we have investigated the previously
reported reactions by microwave heating technique.
Reactions of 2a-c with 1a,b could be carried out in
Two environmentally friendly simple methods that
either do not utilize organic solvents or utilize a
small quantity of high boiling solvents have been
adopted [9].

1334
N. R. Mohamed, M. M. T. El-Saidi, Y. M. Ali, M. H. Elnagdi
Vol 44
aniline in DMF under reflux at 150 °C. Similarly reacting
7a,b with 1b under the same conditions, afforded 11a,b in
good yields. The latter was converted to 10a,b on reflux
in AcOH-HCl (Scheme III).
Scheme I
O
O
R1
R2
Ph3P CHR
N
1a, R= COOEt
b, R= CN
NH
Ar
Scheme III
O
CH
2a, R1= OEt, R2= CH3, Ar= Ph
b, R1= R2= CH3, Ar= Ph
3
O
O
c, R1= R2= CH3, Ar= 4-CH3C6H4
PhHN
PhHN
CH
3
O
R2
1a
N
COOEt
N
MW, 6 min
R1
NH
Ar
NH
Ar
N
N
X
8
7a, Ar= Ph
b, Ar= 4-CH C H
6 4
Ar
3
-EtOH
3a, R1= OEt, R2= CH3, Ar= Ph, X= O
b, R1= R2= CH3, Ar= Ph, X= O
MW
4-5 min
X
1b
c, R1= R2= CH3, Ar= 4-CH3C6H4, X= O
d, R1= R2= CH3, Ar= Ph, X= NH
e, R1= R2= CH3, Ar= 4-CH3C6H4, X= NH
O
O
CH
3
O
CH
3
Ph
O
N
PhHN
PhHN
AcOH/HCl
reflux, 1h
microwave oven using a small amount of dimethylform-
amide adopting MORE (Microwave-induced Organic
Reactions Enahancement) technology invented by Bose
[15,16]. The reactions discussed above were completed
within 3-6 min. The yields were also improved (cf.
Table 1).
N
N
CH
3
N
NH
N
O
N
9
NHAr
Ar
Ar
10a, Ar= Ph
b, Ar= 4-CH C H
6 4
11a, Ar= Ph
b, Ar= 4-CH C H
6 4
3
3
PhNH
2
3a
o
DMF, reflux 8 h, 150
C
Scheme II
The reactivity of the arylhydrazones 12a-c [19] with 1a
was also investigated. Refluxing 1a with 12a-c in toluene
for 8 hours afforded the pyridazinones 13a-c. In contrast,
the same reaction was completed within a range of 3-5
minutes using microwave heating technique. Trials to
condense 12a-c with 1b failed under a variety of
conditions (Scheme IV).
H COC
3
O
CH
3
CH
3
H C
3
N
O
-Ph PO
3
1a
2c
N
COOEt
NH
Ar
PPh
3
NH
Ar
MW, 6 min
COOEt
5
4
-EtOH
X
Scheme IV
X
X
CHO
O
CH
N
OH
3
O
CH
N
1a
3
N
N
MW, 3-5 min
N
O
NH
Ar
H C
3
AcOH/HCl
reflux, 1 h
H C
3
Ar
N
N
NH
HO
CH
3
13a-c
12a-c
O
Ar
3e
N
6
N Ar
Ar
3c
12,13a, X= PhCO
b, X= CN
Ar= 4-CH3C6H4
Ar= Ph
2
O
R
CO
c, X=
Ar= Ph
1
R
1b
MW, 3-4 min
2b,c
N
N
NH
The reactivity of methyl functions in 3b and 10a toward
dimethyformamide dimethyl acetal (DMFDMA) was also
investigated. Although methyl group in 3,5-difunctionally
substituted pyridazinone has been reported to react readily
with DMFDMA [20], the methyl group in 10a failed to
condense with DMFDMA under variety of conditions.
Treatment of 3b with DMFDMA in toluene afforded a
condensation product that may be formulated as 14 or
isomeric 15. Structure 14 was excluded because all
spectroscopic data were in accordance with structure 15.
Ar
3d,e
The arylhydrazones 7a,b, which were prepared
according to the classical method [17,18], were allowed to
react with 1a under reflux and by microwave heating. The
products may be formulated as pyridine 9 or pyridazinone
10. The pyridazinone structure 10 was established for the
reaction product based on the identity of the product
obtained from reaction of 3a prepared earlier [14] with

Nov-Dec 2007
Microwaves in Organic Synthesis
1335
tested compounds were capable of inhibiting the growth
of Candida Albicans and Saccharomyces Cerviseae. They
were inactive towards Asperigllus Flavus and Aspragillus
Niger. The examined compounds 3b,c, 10b, 11b, 15
exhibited significant antifungal activity, while the
compounds 10a, 11a showed moderate activity.
Furthermore, structure 15 seemed more likely as the
methyl group in 10a has failed to condense with
DMFDMA. (Scheme V).
Scheme V
NMe
2
Conclusion. Microwave heating is considered to be a
green method for the synthesis of bioactive pyridazines
via the utility of simply prepared arylhydrazones and
Wittig reagents. The newly prepared pyridazinones and
iminopyridazines have shown antifungal activity. In this
technique: 1) A small amount of solvent like dimethyl-
formamide was used (MORE technology). 2) The reaction
times of were reduced to a few minutes. 3) The yields of
the products were improved.
O
H C
3
X
N
O
N
O
Ph
14
DMFDMA
3b
Toluene, reflux 8 h
CH
3
Me N
2
N
EXPERIMENTAL
N
O
Ph
All melting points were determined on gallenkamp
electrothermal melting point and were uncorrected. The IR
spectra were expressed in cm-1 and recorded in KBr pellets on a
FT IR-8201 PC spectrophotometer. 1H-NMR spectra were
obtained on a Varian Gemini NMR spectrometer, 300 MHz
spectrometer in CDCl3 as solvent and using tetramethylsilane
(TMS) as internal reference. Chemical shifts (ꢁ) were expressed
in ppm. Mass spectra were performed on MS-50 Kratos (A.E.I)
spectrometer. Elemental analyses were performed with all final
compounds on Elmentro, Vario EL. Microbiological analyses
were carried out by the Micro-analytical Centre Cairo
University, Egypt. Microwave experiments were conducted in a
domestic microwave oven SHARP model 340D, 1000 W at
medium power. The reactions were monitored by thin layer
chromatography (TLC) using aluminum sheets with silica gel 60
F254 (Merck).
15
The mass spectrum of 15 revealed a base peak at m/z=
98 characteristic to the fragment [Me2N-CH=CHCO]+.
The IR spectrum showed two bands at ꢀ= 1647, 1681
cm-1 for the carbonyl group and the pyridazine carbonyl
group respectively. In addition, the 1H-NMR spectrum
revealed two doublet signals at ꢁ= 5.71 ppm, (J= 12 Hz)
and 7.42 ppm, (J= 12 Hz) for the two olefinic protons of
compound 15. If the produced product was 14, the
chemical shifts for the two olefinic protons in this case
expected to appear at ꢁ= 5.25, 6.05 ppm [21].
The comparison between the conventional and
microwave heating techniques in terms of the reaction
times and the yields of the produced products is
summarized in Table 1.
General procedure for the Reaction of Wittig reagents 1a,b
with 2a-c, 7a,b and 12a-c.
Method A: Conventional heating. A mixture of arylhydra-
zone 2a-c or 7a,b and or 12a-c (0.01 mol) and the ylides 1a,b
(0.01 mol) in 30 ml toluene was heated under reflux with stirring
until the starting materials could no longer be detected by TLC.
The solvent was evaporated under reduced pressure and the
residue was treated with petroleum ether 60-80 °C. The solid
product was collected by filtration and either crystallized
from benzene or purified with column chromatography.
Triphenylphoshine oxide (TPPO) was separated from the
reaction medium as white crystals mp 157 °C (by mixed mp)
[22].
Method B: Using microwave heating technique. A mixture
of arylhydrazones 2a-c or 7a,b and or 12a-c (0.01 mol) and the
ylides 1a,b (0.01 mol) in 2 ml DMF were placed in domestic
microwave oven and irradiated for 3-6 min. The reaction
mixture was left to cool at room temperature. The resulting
products were triturated with petroleum ether 60-80 °C. The
formed precipitates were collected by filtration and crystallized
from benzene.
Table 1
Comparison between the conventional and microwave heating
techniques.
Compound
Conventional heating
Microwave heating
Reaction
Yield %
Reaction
time
Yield %
time
(hours)
10
10
10
10
10
30
30
30
30
8
8
8
(minutes)
3a[14]
3b[14]
3c
3d
3e
10a
10b
11a
11b
13a
13b
13c
82
80
70
60
73
65
70
60
65
60
65
62
5
6
6
4
3
6
6
4
5
5
6
4
89
90
87
85
87
85
87
80
82
80
85
87
Ethyl 4-methyl-6-oxo-1-phenyl-1,6-dihydro-pyridazin-3-
carboxylate, 3a. Conventional heating afforded yield 2.11 g
(82%) after 10 h (Lit.[14]); microwave heating afforded 2.29 g
(89%) after 5 min; mp 103 °C; yellow crystals; ms: (m/z) 258
Bioactivity. The in vitro antifungal activity of some
newly prepared compounds 3b,c, 10a,b, 11a,b and 15
against four types of fungi was investigated. The seven

1336
N. R. Mohamed, M. M. T. El-Saidi, Y. M. Ali, M. H. Elnagdi
Vol 44
(M+, 32%); Anal. Calcd. for C14H14N2O3: C 65.11%, H 5.46%, N
10.85%. Found: C 64.89%, H 5.32%, N 10.78%.
(60%) after 30 h; microwave heating afforded 2.43 g (80%) after
4 min; the product were isolated by silica gel (60 mesh) column
chromatography using eluent (ethyl acetate: petroleum ether 40-
60 °C, 2:8); mp 222 °C; yellow crystals; ir (KBr): ꢀ 3421 (NH),
6-Acetyl-5-methyl-2-phenylpyridazin-3(2H)-one, 3b. Con-
ventional heating afforded yield 1.82 g (80%) after 10 h
(Lit.[14]); microwave heating afforded 2.05 g (90%) after 6 min;
mp 132 °C; yellow crystals; ms: (m/z)= 228 (M+, 47%); Anal.
Calcd. for C13H12N2O2: C 68.41%, H 5.30%, N 12.27%. Found:
C 68.38%, H 5.21%, N 12.20%.
1
2923 (CH3), 1678 (CO) cm-1; H nmr (CDCl3): ꢁ= 2.41 (s, 3H,
CH3), 6.31 (s, 1H, CH), 7.22-7.42 (m, 5H, aromatic protons),
7.49-7.58 (m, 5H, aromatic protons), 13.16 (s, 1H, NH), 14.40
(s, 1H, NH); ms: (m/z) 304 (M+, 25%); Anal. Calcd. for
C18H16N4O: C 71.04%, H 5.30%, N 18.41%. Found: C 70.93%,
H 5.22%, N 18.35%.
6-Acetyl-5-methyl-2-(4-methylphenyl)pyridazin-3-(2H)-one,
3c. Conventional heating afforded yield 1.60 g (70%) after 10 h;
microwave heating afforded 2.10 g (87%) after 6 min; mp 140
°C; yellow crystals; ir (KBr): ꢀ 2923 (CH3), 1689 (CO), 1624
6-Imino-4-methyl-1-(4-methylphenyl)-N-phenyl-1,6-dihydro-
pyridazine-3-carboxamide, 11b. Conventional heating afforded
yield 2.06 g (65%) after 30 h; microwave heating afforded 2.60
g (82%) after 5 min; the product was isolated by silica gel (60
mesh) column chromatograohy using eluent (ethyl acetate:
petroleum ether 40-60 °C, 2:8); mp 228 °C; yellow crystals; ir
(KBr): ꢀ 3445 (NH), 2918 (CH3), 1682 (CO) cm-1; 1H nmr
(CDCl3): ꢁ= 1.61 (s, 3H, CH3), 2.37 (s, 3H, CH3), 6.26 (s, 1H,
H-5 pyridazine), 7.22-7.25 (m, 5H, aromatic protons), 7.26-7.53
(m, 4H, aromatic protons), 13.18 (s, 1H, NH), 14.40 (s, 1H,
NH); ms: (m/z) 318 (M+, 100%); Anal. Calcd. for C19H18N4O: C
71.68%, H 5.70%, N 18.60%. Found: C 71.52%, H 5.64%, N
18.51%.
Conversion of 3e, 11a,b to 3c, 10a,b respectively. A
solution of 3e or 11a,b (0.01 mol) in 10 ml AcOH containing 2
ml of concentrated hydrochloric acid was heated under reflux for
1 h. After cooling the reaction mixture was poured on ice/water
mixture. The solid product formed was collected by filtration
and crystallized from benzene. A comparison with authentic
samples 3c and 10a,b was carried out.
1
(CO) cm-1; H nmr (CD3Cl): ꢁ= 1.65 (s, 3H, CH3), 2.41 (s, 3H,
CH3), 2.54 (s, 3H, CH3), 6.81 (s, 1H, H-5 pyridazine), 7.41-7.66
(m, 4H, aromatic protons); ms: (m/z) 242 (M+, 33%); Anal.
Calcd. for C14H14N2O2: C 69.41%, H 5.82%, N 11.56%. Found:
C 69.38%, H 5.74%, N 11.45%.
1-(6-Imino-4-methyl-1-phenyl-1,6-dihydropyridazin-3-yl)-
ethanone, 3d. Conventional heating afforded yield 1.36 g (60%)
after 10 h; microwave heating afforded 1.93 g (85%) after 4
min; mp 126 °C; yellow crystals; ir (KBr): ꢀ 3436 (NH), 2927
1
(CH3), 1693 (CO) cm-1; H nmr (CDCl3): ꢁ= 2.50 (s, 3H, CH3),
2.61 (s, 3H, CH3), 6.30 (s, 1H, H-5, pyridazine), 7.34-7.67 (m,
5H, aromatic protons), 14.75 (s, 1H, NH); ms: (m/z) 227 (M+,
29%); Anal. Calcd. for C13H13N3O: 68.71%, H 5.77%, N
18.49%. Found: C 68.62%, H 5.63%, N 18.35%.
1-(6-Imino-4-methyl-1-(4-methylphenyl)-1,6-dihydropyri-
dazin-3-yl)-ethanone, 3e. Conventional heating afforded yield
1.76 g (73%) after 10 h; microwave heating afforded 2.10 g
(87%) after 3 min; mp 128 °C; yellow crystals; ir (KBr): ꢀ 3421
(NH), 2993 (CH3), 1678 (CO) cm-1; 1H nmr (CD3Cl): ꢁ= 1.58 (s,
3H, CH3), 2.38 (s, 3H, CH3), 2.67 (s, 3H, CH3), 6.29 (s, 1H, H-5
pyridazine), 7.42-7.68 (m, 4H, aromatic protons), 14.38 (s, 1H,
NH); ms: (m/z) 241 (M+, 42%); Anal. Calcd. for C14H15N3O: C
69.69%, H 6.27%, N 17.41%. Found: C 69.64%, H 6.19%, N
17.37%.
Reaction of 3a with aniline. A mixture of 3a (0.01 mol, 2.58
g) and aniline (0.01 mol, 0.93 g) in 10 ml DMF was heated for 8
h at 150 °C. The reaction mixture was poured onto ice/water
mixture. The formed product was collected by filtration then
crystallized from ethanol. The product was confirmed by
comparison with an authentic sample 10a (mp 212 °C).
2-(4-Methylphenyl)-6-(phenylcarbonyl)-pyridazin-3(2H)-
one, 13a. Conventional heating afforded yield 1.74 g (60%)
after 8 h; microwave heating afforded 2.32 g (80%) after 5 min;
mp 132 °C; yellow crystals; ir (KBr): ꢀ 1681 (CO), 1647 (CO)
4-Methyl-6-oxo-N,1-diphenyl-1,6-dihydropyridazine-3-
carboxamide, 10a. Conventional heating afforded yield 1.98 g
(65%) after 30 h; microwave heating afforded 2.59 g (85%) after
6 min; the product was isolated by silica gel (60 mesh) column
chromatograohy using eluent (ethyl acetate: petroleum ether 40-
60 °C, 3:7); mp 212 °C; yellow crystals; ir (KBr): ꢀ 3407 (NH),
1
cm-1; H nmr (CD3Cl): ꢁ= 2.38 (s, 3H, CH3), 7.13 (d, 1H, H-5
pyridazine, J= 6 Hz), 7.27 (d, 1H, H-4 pyridazine, J= 6 Hz),
7.44-7.48 (m, 5H, aromatic protons), 7.50 (d, 2H, aromatic
protons, J= 9 Hz), 8.06 (d, 2H, aromatic protons, J= 9 Hz); ms:
(m/z) 290 (M+, 76%); Anal Cacld. for C18H14N2O2: C 74.74%, H
4.86%, N 9.65%. Found: C 74.69%, H 4.77%, N 9.59%.
1
2922 (CH3), 1677 (CO), 1629 (CO) cm-1; H nmr (CD3Cl): ꢁ=
2.40 (s, 3H, CH3), 6.31 (s, 1H, H-5 pyridazine), 7.21-7.36 (m,
5H, aromatic protons), 7.39-7.57 (m, 5H, aromatic protons),
14.40 (s, 1H, NH); ms: (m/z) 305 (M+, 95%); Anal Calcd for
C18H15N3O2: C 70.81%, H 4.95%, N 13.76%. Found: C 70.78%,
H 4.87%, N 13.60%.
6-Oxo-1-phenyl-1,6-dihydropyridazine-3-carbonitrile, 13b.
Conventional heating afforded yield 1.16 g (65%) after 8 h;
microwave heating afforded 1.52 g (85%) after 6 min; mp 125
°C; red crystals; ir (KBr): ꢀ 2241 (CN), 1689 (CO) cm-1; 1H nmr
(CD3Cl): ꢁ= 7.12 (d, 1H, H-5 pyridazine, J= 6 Hz), 7.43 (d, 1H,
H-4 pyridazine, J= 6 Hz), 7.44-7.64 (m, 5H, aromatic protons);
ms: (m/z) 197 (M+, 31%); Anal. Cacld. for C11H7N3O: C 67.0%,
H 3.58%, N 21.31%. Found: C 66.98%, H 3.53%, N 21.24%.
6-(2-Naphthalen-2ylcarbonyl)-2-phenylpyridazin-3(2H)-
one, 13c. Conventional heating afforded yield 2.02 g (62%) after
8 h; microwave heating afforded 2.83 g (87%) after 4 min; mp
122 °C; yellow crystals; ir (KBr): ꢀ 1678 (CO), 1627 (CO) cm-1;
1H nmr (CDCl3): ꢁ (ppm)= 7.13 (d, 1H, H-5 pyridazine, J= 6
Hz), 7.29 (d, 1H, H-4 pyridazine, J= 6 Hz), 7.47-7.67 (m, 5H,
aromatic protons), 7.69-7.94 (m, 6H, naphthyl proton), 8.74 (s,
1H, naphthyl proton); ms: (m/z) 326 (M+, 22%); Anal. Calcd. for
4-Methyl-1-(4-methylphenyl)-6-oxo-N-phenyl-1,6-dihydro-
pyridazine-3-carboxamide, 10b. Conventional heating afforded
yield 2.23 g (70%) after 30 h; microwave heating afforded 2.77
g (87%) after 6 min; the product was isolated by silica gel (60
mesh) column chromatograohy using eluent (ethyl acetate:
petroleum ether 40-60 °C, 3:7); mp 216 °C; yellow crystals; ir
(KBr): ꢀ 3422 (NH), 2925 (CH3), 1668 (CO), 1629 (CO) cm-1;
1H nmr (CD3Cl): ꢁ= 1.58 (s, 3H, CH3), 2.37 (s, 3H, CH3), 6.27
(s, 1H, H-5 pyridazine), 7.22-7.25 (m, 5H, aromatic protons),
7.26-7.53 (m, 4H, aromatic protons), 14.41 (s, 1H, NH); ms:
(m/z) 319 (M+, 100%); Anal. Calcd. for C19H17N3O2: C 71.46%,
H 5.37%, N 13.16%. Found: C 71.34%, H 5.23%, N 13.12%.
6-Imino-4-methyl-N,1-diphenyl-1,6-dihydropyridazine-3-
carboxamide, 11a. Conventional heating afforded yield 1.82 g

Nov-Dec 2007
Microwaves in Organic Synthesis
1337
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C21H14N2O2: C 77.29%, H 4.32%, N 8.58%. Found: C 77.19%,
H 4.23%, N 8.55%.
Reaction of 3b with dimethylformamide dimethyl acetal
(DMFDMA). A mixture of 3b (0.01 mol, 2.28 g) with dimethyl-
formamide dimethyl acetal (DMFDMA) (0.01 mol, 1.19 g) in 30
ml toluene was heated under reflux for 8 h. The solvent was
evaporated under reduced pressure and the residue was treated
with n-hexane. The solid product was collected by filtration and
crystallized from ethanol.
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6-[3-(Dimethylamino)prop-2-enoyl]-5-methyl-2-phenyl-
pyridazin-3(2H)-one, 15. Yield 2.49 g (88 %); mp 142 °C;
yellow crystals; ir (KBr): ꢀ 2920 (CH3), 1681 (CO), 1647 (CO)
1
cm-1; H nmr (CDCl3): ꢁ= 2.48 (s, 3H, CH3), 2.91 (s, 3H, CH3),
3.17 (s, 3H, CH3), 5.71 (d, 1H, CH olefinic, J= 12 Hz), 6.85 (s,
1H, H-5 pyridazine), 7.42 (d, 1H, CH olefenic, J= 12 Hz), 7.44-
7.67 (m, 5H, aromatic protons); ms: (m/z) 283 (M+, 42%); Anal
Cacld for C16H17N3O2: C 67.83%, H 6.05%, N 14.83%. Found:
C 67.76%, H 5.97%, N 14.83%.
Bioassay.
A filter paper sterilized disc saturated with
measured quantity of the sample is placed on plate containing
fungal medium (Dox's medium), which has been heavily seeded
with spore suspension of the tested organism. After inoculation,
the diameter of the clear zone of inhibition surrounding the
sample is taken as a measure of the inhibitory power of the
sample against the particular test organism [23,24].
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18.
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Prep. Proced. Int. 1999, 31, 551.
Acknowledgment. The authors would like to express their great
thanks for Prof. Dr. Ebtisam A. Hafez for her interest and help.
REFERENCES AND NOTES
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