2-Arylhydrazono-3-oxopropanals in heterocyclic synthesis: Synthesis of arylazopyrazole, arylazoisoxazole and dialkylpyridazine-5,6-dicarboxylate derivatives. New one-step synthesis of arylazopyrimidines

Article abstract of DOI:10.1002/jhet.5570410501

A novel synthesis of arylpyrazole, isoxazole, dialkyl 1,6-dihydropyridazine 5,6-dicarboxylate derivatives and a new one-step synthesis of azolopyrimidines under microwave-assisted conditions are reported.

Full text of DOI:10.1002/jhet.5570410501

Sep-Oct 2004
647
2-Arylhydrazono-3-oxopropanals in Heterocyclic Synthesis:
Synthesis of Arylazopyrazole, Arylazoisoxazole and
Dialkylpyridazine-5,6-dicarboxylate Derivatives.
New One-step Synthesis of Arylazopyrimidines.
Mariam A. Al-Shiekh1, Abdellatif M. Salah El-Din2, Ebtisam A. Hafez2*, and
Mohamed H. Elnagdi2*
1
Department of Chemistry, Girls College of Education, Jeddah, P.O. 334
Jeddah 21341, Kingdom of Saudi Arabia
Department of Chemistry, Faculty of Science, Cairo University, Giza-Egypt
2
Received November 4, 2003
A novel synthesis of arylpyrazole, isoxazole, dialkyl 1,6-dihydropyridazine 5,6-dicarboxylate derivatives
and a new one-step synthesis of azolopyrimidines under microwave-assisted conditions are reported.
J. Heterocyclic Chem., 41, 647 (2004).
Some time ago an easy synthesis of 2-arylhydrazono-
of2b,d,f and phenylhydrazine in a microwave oven for 5-10
minutes at full power. Products of microwave reaction were
found to be more pure in crude form and to be formed in bet-
ter yields. Reacting 2a, c with hydrazine hydrate also
afforded the hydrazones 4i, j. While hydrazones of structure
similar to 4 were reported earlier to cyclize readily into pyra-
zoles [2], cyclization of 4a-d proceeded with difficulty. Only
after long reflux in pyridine 4-8 hours, could 4c,g be cyclized
into 5a,b. However, the hydrazones 4i,j, on the other hand,
cyclized into 5c,d on reflux in pyridine for 4 hours.
The reaction of 2a-d with hydroxylamine hydrochloride
in ethanolic sodium acetate has afforded, similar to earlier
reports on arylhydrazones [2,5], oximes 6a-d. Compounds
6a,b were also obtained on treatment of 2a,b with hydrox-
ylamine hydrochloride and sodium carbonate in a
microwave oven at full power (cf. Table 1). Compounds
6a-d cyclized into isoxazoles 7a-d on reflux in acetic
anhydride. In contrast to this 2c afforded the nitrile 8 on
treatment with hydroxylamine in acetic acid and in the
presence of ammonium acetate in a microwave oven. It is
believed that the initially formed oxime is acylated to yield
9 under these conditions and readily then underwent a
thermal pericyclic elimination of acetic acid via a six
membered transition state (Figure 2).
propanals has been reported from our laboratories [1-3].
Since that time we have been involved in investigations
aimed at exploring synthetic potentialities of this class of
compounds [1-5]. In a continuation to this work we report
the synthesis of 2-arylhydrazonals 2a-h via coupling 1a,b
with aromatic diazonium salts. The reactivity of 2a-h
toward nitrogen nucleophiles by microwave heating
"green technology" [6,7] in the absence of solvent is
reported. Results are compared with those obtained from
conventional heating utilizing procedures similar to those
reported earlier [1-5,8-11]. Moreover further examples of
the novel 1,6-dihydropyridazine-5,6-dicarboxylate via
reacting 2-arylhydrazonals with dimethyl acetylenedicar-
boxylate and triphenylphosphine [4] is reported. Thus, 2a-
h were obtained in 50-80% yields via coupling 1a,b with
1
aromatic diazonium salts. H-NMR of the products indi-
cated that they exist at least in DMSO solution as mixtures
of the anti form 2 and syn form 3. The anti form generally
predominated (Figure 1).
Compound 2a condensed with 5-amino-1H- 1 , 2 , 4 - t r i a-
zole 10a to yield 11a whose structure was established by
single crystal X-ray diffraction (Figure 3). Similarly, con-
densation of aminopyrazoles 10b-d with 2b,c afforded the
pyrazolo[1,5-a]pyrimidines 11b-d. It is believed that 10a-
d initially condense with 2 to yield 12 which then cyclises
into 11 (Figure 4).
The reaction of 2a,c with 2-aminobenzimidazole (1 3)
afforded a product that was assigned to structure 14 rather
than 15 based on NOE difference that revealed that the
ethyl function and benzimidazole H are spatially proximal.
The ethylpyridazine carboxylate 16 could be readily
obtained via condensing 2c with diethylmalonate in
ethanolic piperidine (Figure 5).
Figure 1
Compounds 2a-h reacted with phenylhydrazine in reflux-
ing ethanol for one hour to yield the phenylhydrazones 4a-h.
Phenylhydrazones 4b,d,f could be also obtained on heating
In a previous work [4] it has been reported that the reaction
of 2-arylhydrazonals with dimethylacetylene dicarboxylate

648
M. A. Al-Shiekh, A. M. Salah El-Din, E. A. Hafez, and M. H. Elnagdi
Vol. 41
Figure 2
Figure 3. Molecular structure of 11a with atoms labeling scheme.
(DMAD) and triphenylphosphine affords dihydropyri-
dazines. Although alternative structures were also possible
no conclusive evidence for the proposed structure was
offered. Also no mechanism to account for formation of the
reaction product has been presented. In the present study, a
facile one-pot synthesis of dimethyl 1,6-dihydropyridazine-
5,6-dicarboxylates 18 in high yield utilizing the 3-oxo-2-
(arylhydrazono)pentanal 2a-d or 3-(4-acetylphenyl)-3-oxo-
2-(arylhydrazono)-propionaldehyde 2e-g as precursors for
this ring system is reported. Thus, compounds 2a-d reacted
with DMAD in the presence of tripheylphosphine at room
temperature in dichloromethane solution to yield a product
Figure 4
for which structures 18-20 seemed possible. Structures 19,20
could be readily ruled out based on H NMR that revealed
1
the absence of signals either for NH or ring CH2 (Figure 6).
Thus, the structure 18 was established as the reaction
product. Compound 18 is assumed to be formed via initial
addition of the ylide "formed by adding triphenyl phos-
phine to the acetylenedicarboxylate" to hydrazone 2 yield-
ing 17 and then elimination of triphenylphosphine oxide to

Sep-Oct 2004
2-Arylhydrazono-3-oxopropanals in Heterocyclic Synthesis
649
Table 1
Comparison Between Reaction Times and Yields Obtained from
Conventional and Microwave Heating
Conventional Δ
Microwave Δ
Compd Yield (%) Time (min.) Yield (%) Time (min.)
4b
4d
4f
6a
6b
11a
11b
14a
71
70
71
70
60
65
79
60
60
60
60
240
240
360
360
360
89
90
82
86
85
97
99
95
10
5
10
10
5
2
2
2
Figure 5
1
pellets on a Pye Unicam SP 3-300 Spectrophotometer. H NMR
spectra were recorded in hexadeuterated dimethylsulfoxide
(DMSO-d ) or deuteriochloroform (CDCl ) at 200 or 300 MHz
6
3
on a Varian Gemini NMR spectrometer using tetramethylsilane
(TMS) as an internal reference and results are expressed as δ val-
ues. Mass spectra were performed on a Shimadzu GCMS-QP
1000 Ex mass spectrometer at 70 eV. Elemental analyses were
carried out at the Microanalytical center of Cairo University.
Preparation of Compounds 2a-h.
General Procedure.
A cold solution of aryldiazonium salt (10 mmol) was prepared
by adding a solution of sodium nitrite (10 mmol into H O) to a
2
cold solution of the aromatic amine hydrochloride or heterocyclic
amine derivatives with stirring. The resulting solution of the aryl-
diazonium salt was added to a cold solution of 1-dimethyl-
aminopent-1-en-3-one (1 a ) (1.27 g, 10 mmol) or 1-(4-
acetylphenyl)-3-dimethylaminopropenone (1b) in ethanol (50
ml) containing sodium acetate (5 g). The reaction mixture was
stirred at room temperature for 30 min. The solid product, so
formed, was collected by filtration, washed with water and crys-
tallized from the proper solvent.
3-Oxo-2-(phenylhydrazono)pentanal (2a).
This compound was obtained in 70 % yield; mp 93 ºC; red
crystals from dilute ethanol, IR (KBr): ν 3500(br NH), 1680(CO
-1
1
aldehyde), 1648 cm (CO ketone); H NMR (d -DMSO): δ = 1.1
6
(t, 3H, CH ), 2.9(q, 2H, CH ), 7.3-7.4(m, 3H, Ar-H) 7.6(d, 2H,
3
Ar-H), 9.9, 9.5(s, 1H, CHO), 14.1, 14.5(s, 1H, NH); MS (EI, 70
2
+
EV): m/z 203(32.6%) [M-1] .
Anal. Calcd. for C H N O (204.23): C, 64.69; H, 5.92; N,
Figure 6
11 12
13.72 %. Found: C, 64.80; H, 5.89; N, 13.60.
2 2
3-Oxo-2-(p-tolylhydrazono)pentanal (2b).
yield 18. Similarly the arylhydrazones 2e-g reacted with
DMAD in the presence of triphenylphosphine to yield the
pyridazine dicarboxylate derivatives 18e-g. Compound
18a reacted with hydrazine hydrate to afford 22 most
likely via intermediacy of 21 (Figure 6).
This compound was obtained in 72 % yield, mp 133 ºC; orange
1
crystals from ethanol, H NMR (d -DMSO): δ = 1.1 (t, 3H,
6
CH ), 2.3 (s, 3H, CH ), 3.0 (q, 2H, CH ), 7.3-8.6 (m, 4H, Ar-H),
3
9.6, 9.9 (s, 1H, CHO), 14.5, 15.0(s, 1H, NH); MS (EI, 70 EV):
3
2
+
m/z 218 (87.2%) (M ).
Anal. Calcd. for C H N O (218.25): C, 66.04; H, 6.47; N,
12 14
2 2
12.84 %. Found: C, 66.00; H, 6.49; N, 13.00.
EXPERIMENTAL
3-Oxo-2-(4-Nitrophenylhydrazono)pentanal (2c).
All melting points were measured on a Gallenkamp elec-
trothermal melting point apparatus and are uncorrected.
Microwave oven SJO 390W. IR spectra were recorded as KBr
This compound was obtained in 72 % yield, mp 125 ºC; red
1
crystals from ethanol, H NMR (d -DMSO): δ = 1.1 (t, 3H, CH ),
6
3

650
M. A. Al-Shiekh, A. M. Salah El-Din, E. A. Hafez, and M. H. Elnagdi
Vol. 41
2.9 (q, 2H, CH ), 6.7-7.9 (m, 4H, Ar-H), 9.2, 9.8 (s, 1H, CHO),
+
refluxed in ethanol for 1 h. The solid product obtained was col-
lected by filtration and crystallized from the proper solvent.
2
13.9, 14.5 (s, 1H, NH); MS (EI, 70 EV): m/z 249 (34.1%) (M ).
Anal. Calcd. for C H N O (249.22): C, 53.01; H, 4.45; N,
11 11
3 4
16.86 %. Found: C, 53.20; H, 4.50; N, 16.75.
Method B, Microwave Heating.
A mixture of 2-arylhydrazonopentanals (2b,d) or arylhydra-
zonopropanal (2f) (10 mmol) with phenylhydrazine (1.08 g, 10
mmol) was heated in a domestic microwave oven at full power
for 10 minutes. The resulting product was collected by filtration,
washed with ethanol and crystallized from the proper solvent (mp
mixed mp and TLC).
3-Oxo-2-(4-Methoxyphenylhydrazono)pentanal (2d).
This compound was obtained in 72 % yield, mp 120 ºC; red
1
crystals from ethanol, H NMR (d -DMSO): δ = 1.09 (t, 3H,
6
CH ), 2.8 (q, 2H, CH ), 3.7 (s, 3H, OCH ), 7.06 (d, 2H, Ar-H),
3
2
7.6(d, 2H, Ar-H), 9.4, 9.9(s, 1H, CHO), 14.3, 14.7 (s, 1H, NH);
3
+
MS (EI, 70 EV): m/z 234 (15.2%) (M ).
Anal. Calcd. for C H N O (234.25): C, 61.53; H, 6.02; N,
1, 2-Bis-(phenylhydrazono)pentan-3-one (4a).
12 14
11.96 %. Found: C, 61.35; H, 6.09; N, 11.77.
2 3
This compound was obtained in 70 % yield, mp 236 ºC; red
-1
crystals from ethanol, IR (KBr): ν 3255(NH), 1620 cm (CO);
3-(4-Acetylphenyl)-3-oxo-2-(Phenylhydrazono)propionaldehyde
(2e).
1
H NMR (d -DMSO): δ = 1.08 (t, 3H, CH ), 3.1 (q, 2H, CH ),
6
7.1-7.4 (m, 10H, Ar-H), 8.2 (s, 1H, H-1), 10.8 (s, 1H, NH), 13.1
3
2
+
(s, 1H, NH); MS (EI, 70 EV): m/z 294(62.9%) (M ).
This compound was obtained in 70 % yield; mp 153 ºC; yellow
crystals from dilute ethanol, IR (KBr): ν 3118 (NH), 1660, 1641
Anal. Calcd. for C
19.03%. (Found: C, 69.41; H, 6.20; N, 19.01.
H N O (294.36): C, 69.37; H, 6.16; N,
17 18 4
-1
cm (CO); H NMR (CDCl ): δ = 2.6 (s, 3H, CH ), 6.4-7.9 (m,
1
3
9H, Ar-H), 9.5, 10.0 (s, 1H, CHO), 13.2, 14.2 (s, 1H, NH); MS
3
1-(Phenylhydrazono)-2-(p-tolylhydrazono)pentan-3-one (4b).
+
(EI, 70 EV): m/z 293 (32.9%.) [M-1] .
Anal. Calcd. for C H N O (294.31): C, 69.38; H, 4.79; N,
This compound was obtained in 71 % yield by Method A after
60 min. reflux while Method B yielded 89% after heating for 10
min in a domestic microwave oven at full power. Mp 244 ºC;
17 14
9.52 %. Found: C, 69.19; H, 4.69; N, 9.42.
2 3
1
3-(4-Acetylphenyl)-3-oxo-2-(4-nitrophenylhydrazono)propi-
onaldehyde (2f).
dark orange crystals from ethanol/dioxan (1:1), H NMR (d -
6
DMSO): δ = 1.1 (t, 3H, CH ), 2.3 (s, 3H, CH ), 2.9 (q, 2H, CH ),
3
6.8-7.3 (m, 9H, Ar-H), 8.2 (s, 1H, H-1), 10.7 (s, 1H, NH), 13.1 (s,
3
2
This compound was obtained in 72 % yield, mp 149 ºC; red
1
crystals from ethanol/dioxan (1:1), H NMR (d -DMSO): δ = 2.6
+
1H, NH). MS (EI, 70 EV): m/z 308(38.2%) (M ).
6
(s, 3H, CH ), 6.7-7.9 (m, 8H, Ar-H), 9.6, 10.1 (s, 1H, CHO),
Anal. Calcd. for C
H N O (308.38): C, 70.11; H, 6.54; N,
18 20 4
18.17%. Found: C, 70.00; H, 6.49; N, 17.98.
3
12.9, 14.0 (s, 1H, NH); MS (EI, 70 EV): m/z 339 (16.5%) (M ).
Anal. Calcd. for C H N O (339.30): C, 60.18; H, 3.86; N,
+
17 13
12.38 %. Found: C, 60.21; H, 3.78; N, 12.39.
3 5
1-(Phenylhydrazono)-2-(4-nitrophenylhydrazono)pentan-3-one
(4c).
3-(4-Acetylphenyl)-2-(4-methoxyphenylhydrazono)-3-oxopropi-
onaldehyde (2g).
This compound was obtained in 65 % yield, mp 131 ºC; orange
1
crystals from ethanol, H NMR (d -DMSO): δ = 1.2 (t, 3H,
6
CH ), 2.9 (q, 2H, CH ), 6.8-7.3 (m, 9H, Ar-H), 8.2 (s, 1H, H-1),
This compound was obtained in 70 % yield, mp 136 ºC; red
-1
3
10.7 (s, 1H, NH), 13.2 (s, 1H, NH); MS (EI, 70 EV): m/z 339
2
crystals from methanol, IR (KBr): ν 3424(NH), 1714, 1676 cm
1
(CO); H NMR (d -DMSO): δ = 2.6 (s, 3H, CH ), 3.8 (s, 3H,
+
(M ).
6
OCH ), 7.0 (d, 2H, Ar-H), 7.4 (d, 2H, Ar-H), 7.9 (d, 2H, Ar-H),
3
Anal. Calcd. for C H N O (339.35): C, 60.17; H, 5.05; N,
17 17 5 3
20.64%. Found: C, 60.25; H, 5.00; N, 20.79.
3
8.1 (d, 2H, Ar-H), 9.6, 10.0 (s, 1H, CHO), 13.2, 14.4 (s, 1H, NH);
+
MS (EI, 70 EV): m/z 324(17.1%) (M ).
Anal. Calcd. for C H N O (324.33): C, 66.66; H, 4.97; N,
1-(Phenylhydrazono)-2-(4-methoxyphenylhydrazono)pentan-3-
one (4d).
18 16
8.64 %. Found: C, 66.56; H, 4.91; N, 8.68.
2 4
This compound was obtained in 70 % yield by Method A, after
60 min. reflux while Method B yielded 90% after heating for 5
min in a domestic microwave oven at full power. Mp 230 ºC; red
3-(4-Acetylphenyl)-2-(2-methoxyphenylhydrazono)-3-oxo-pro-
pionadehyde (2h).
1
crystals from ethanol/dioxan (1:1), H NMR (d -DMSO): δ = 1.1
6
(t, 3H, CH ), 2.9 (q, 2H, CH ), 3.7 (s, 3H, OCH ), 6.8-7.3 (m,
This compound was obtained in 85 % yield, mp 139 ºC; orange
1
crystals from ethanol/dioxan (1:1), H NMR (d -DMSO): δ = 2.6
3
9H, Ar-H), 8.2 (s, 1H, H-1), 10.7 (s, 1H, NH), 13.2 (s, 1H, NH);
2
3
6
(s, 3H, CH ), 3.7 (s, 3H, OCH ), 6.3-8.1 (m, 8H, Ar-H), 9.6, 10.0
3
(s, 1H, CHO), 13.2, 14.3 (s, 1H, NH); MS (EI, 70 EV): m/z 324
3
13
C NMR: δ 9.4 (CH3), 29.4 (CH ), 56.1 (OCH ), 112.7, 115.8,
2
116.5, 120.6, 130.1, 132.0, 132.3, 156.4 (phenyl carbon), 136.9
3
+
(47%) (M ).
+
(C-1), 144.5 (C-2); MS (EI, 70 EV): m/z 325 (34.2%) [M+1] .
Anal. Calcd. for C H N O (324.38): C, 66.65; H, 6.21; N,
Anal. Calcd. for C H N O (324.33): C, 66.66; H, 4.97; N,
18 16
2 4
8.64 %. (Found: C, 66.65; H, 4.92; N, 8.55.
Preparation of Compounds 4a-j.
General Procedures.
18 20
17.27%. Found: C, 66.58; H, 6.30; N, 17.32.
4 2
1-(4-Acetylphenyl)-2,3-bis-(phenylhydrazono)propan-l-one (4e).
This compound was obtained in 69 % yield, mp 239 ºC; orange
crystals from ethanol/dioxan (1:1), IR (KBr): ν 3263 (NH), 1620
Method A, Thermal Reaction.
-1
cm (CO); H NMR (d -DMSO): δ = 2.6 (s,3H,CH ), 7-7.4 (m,
1
A mixture of 2-arylhydrazonopentanals (2a-d) or arylhydra-
zonopropanal (2e-h) (10 mmol) with phenylhydrazine (1.08 g, 10
mmol) or hydrazine hydrochloride (1.04 g, 10 mmol) was
6 3
14H, Ar-H), 8.4 (s, 1H, H-3), 9.5 (s, 1H, NH), 11.0 (s, 1H, NH);
+
MS (EI, 70 EV): m/z 384 (14.2%) (M ).

Sep-Oct 2004
2-Arylhydrazono-3-oxopropanals in Heterocyclic Synthesis
651
Anal. Calcd. for C H N O (384.44): C, 71.86; H, 5.24; N,
23 20 4 2
14.57%. Found C, 71.80; H, 5.32; N, 14.60.
Ar-H), 8.09 (s, 1H, H-3), 8.3 (d, 2H, Ar-H); MS (EI, 70 EV): m/z
+
321 (M ).
Anal. Calcd. for C H N O (321.34): C, 63.54; H, 4.70; N,
17 15 5 2
21.79%. Found: C, 63.47; H, 4.77; N, 21.88.
1-(4-Acetylphenyl)-2-(4-nitrophenylhydrazono)-3-(phenylhy -
drazono)propan-1-one (4f).
5-(4-Acetylphenyl)-4-(4-methoxyphenylazo)-1-phenylpyrazole
(5b).
This compound was obtained in 71 % yield by Method A, after
60 min. reflux while Method B yielded 82% after heating for 10
min in a domestic microwave oven at full power. Mp 210 ºC;
This compound was obtained in 60 % yield, mp 206 ºC; pale
-1
1
1
dark red crystals ethanol, H NMR (d -DMSO): δ = 2.6 (s, 3H,
6
CH ), 7.1-8.3 (m, 13H, Ar-H), 8.3 (s, 1H, H-3), 11.2 (s, 1H, NH),
brown crystals from ethanol, IR (KBr):ν 1681 cm (CO); H NMR
(d -DMSO): δ = 2.6 (s, 3H, CH ), 3.7(s, 3H, OCH ), 6.8-7.9 (m,
3
13.4 (s, 1H, NH); MS (EI, 70 EV): m/z 429 (M ).
Anal. Calcd. for C H N O (429.43): C, 64.33; H, 4.46; N,
6
3
3
+
+
13H, Ar-H), 7.5 (s, 1H, H-3); MS (EI, 70 EV): m/z 397 [M+1] .
Anal. Calcd. for C H N O (396.45): C, 72.71; H, 5.08; N,
14.13%. Found: C, 72.66; H, 5.14; N, 14.24.
23 19
16.31%. Found: C, 64.24; H, 4.42; N, 16.23.
5 4
24 20
4 2
1-(4-Acetylphenyl)-2-(4-methoxyphenylhydrazono)-3-(phenyl -
hydrazono)propan-l-one (4g).
3-Ethyl-4-(phenylazo)pyrazole (5c).
This compound was obtained in 70 % yield, mp 90 ºC; brown
-1
crystals from ethanol, IR (KBr): ν 3398 cm (NH); H NMR (d -
1
This compound was obtained in 70 % yield, mp 175 ºC; red
1
crystals from ethanol/dioxan (1:1), H NMR (d -DMSO): δ = 2.6
6
DMSO): δ = 1.3 (t, 3H, CH ), 2.99 (q, 2H, CH ), 7.4-7.7 (m, 5H,
6
(s, 3H, CH ), 3.7 (s, 3H, OCH3), 7.01-8.0 (m, 13H, Ar-H), 8.5 (s,
3
Ar-H), 7.75 (s, 1H, H-5), 13.19 (br s, 1H, NH); MS (EI, 70 EV):
2
3
1H, H-3), 9.5 (s, 1H, NH), 11.0 (s, 1H, NH). MS (EI, 70 EV): m/z
+
m/z 200 (M ).
+
414 (M ).
Anal. Calcd. for C H N (200.24): C, 65.98; H, 6.04; N,
11 12 4
27.98%. Found: C, 66.01; H, 6.09; N, 27.85.
Anal. Calcd. for C H N O (414.46): C, 69.55; H, 5.35; N,
24 22
13.52 %. Found: C, 69.72; H, 5.29; N, 13.50.
4
3
3-Ethyl-4-(4-nitrophenylazo)pyrazole (5d).
1-(4-Acetylphenyl)-2-(2-methoxyphenylhydrazono)-3-(phenyl -
hydrazono)propan-l-one (4h).
This compound was obtained in 75 % yield, mp 115 ºC; dark
1
brown crystals from ethanol, H NMR (d -DMSO): δ = 1.4 (t,
6
3H, CH ), 3.1 (q, 2H, CH ), 7.4-7.7 (m, 5H, Ar-H), 7.9 (s, 1H, H-
This compound was obtained in 70 % yield, mp 188 ºC; dark
1
orange crystals from ethanol, H NMR (d -DMSO): δ = 2.6 (s,
3
2
+
6
3H, CH ), 4.0 (s, 3H, OCH3), 6.9-8.4 (m, 13H, Ar-H), 8.3(s, 1H,
5),13.3 (br s,1H, NH); MS (EI, 70 EV): m/z 245 (M ).
Anal. Calcd. for C H N O (245.24): C, 53.87; H, 4.52; N,
3
H-3), 10.9 (s, 1H, NH), 13.3 (s, 1H, NH); MS (EI, 70 EV): m/z
11 11
5 2
28.56%. Found: C, 54.00; H, 4.41; N, 28.44.
Preparation of Compounds 6a-d.
General Procedures.
+
415 (M+1) .
Anal. Calcd. for C H N O (414.46): C, 69.55; H, 5.35; N,
24 22
13.52 %. Found: C, 69.49; H, 5.25; N, 13.49.
4 3
1-Hydrazono-2-(phenylhydrazono)pentan-3-one (4i).
This compound was obtained in 77 % yield, mp 101 ºC; orange
Method A, Thermal Reaction.
A warm solution of hydroxylamine hydrochloride (0.69 g, 10
mmol) and sodium carbonate (1.26 g, 12 mmol) in (10 ml) water
were added to a stirred solution of the arylhydrazonopentanals
(2 a - d) (10 mmol) in ethanol (4 ml) The reaction mixture was
stirred at room temperature for 4 h. The oximes soon separated as
semisolid crystals that were solidified by cooling in crushed ice.
The solid product, so formed, was collected by filtration and
crystallized from the proper solvent.
1
crystals from ethanol, H NMR (d -DMSO): δ = 1.07 (t, 3H,
6
CH ), 2.44 (q, 2H, CH ), 6.4-7.1 (m, 7H, Ar-H, NH ), 8.3 (s, 1H,
3
2
2
+
H-1), 12.6 (br s, 1H, NH); MS (EI, 70 EV): m/z 218 (M ).
Anal. Calcd. for C H N O(218.26): C, 60.53; H, 6.47; N,
25.67 %. Found: C, 60.60; H, 6.52; N, 25.58.
11 14
4
1-Hydrazono-2-(4-nitro-phenylhydrazono)pentan-3-one (4j).
This compound was obtained in 65 % yield, mp 150 ºC; red
1
crystals from ethanol, H NMR (d -DMSO): δ = 1.2 (t, 3H,
Method B, Microwave Heating.
6
CH ), 2.42 (q, 2H, CH ), 6.7-7.9 (m, 7H,Ar-H, NH ), 8.1 (s, 1H,
3
2
2
A mixture of hydroxylamine hydrochloride (0.69 g, 10 mmol),
sodium carbonate (1.26 g, 12 mmol) and arylhydrazonopentanals
(2a,b) (10 mmol) was placed in the microwave oven and heated
for 5 to 10 min at full power. The resulting product was washed
with ethanol and crystallized from the proper solvent.
+
H-1), 13.6 (br s,1H, NH); MS (EI, 70 EV): m/z 263 (M ).
Anal. Calcd. for C H N O (263.25): C, 50.19; H, 4.98; N,
11 13
5 3
26.60 %. Found: C, 50.22; H, 5.05; N, 26.65.
Preparation of Pyrazole Derivatives 5a-d.
General Procedure.
3-Oxo-2-phenylhydrazonopentanal-l-oxime (6a).
This compound was obtained in 70 % yield by Method A, after
240 min. reflux while Method B yielded 86% after heating for 10
min in a domestic microwave oven at full power; mp 180 ºC; red
A solution of compounds 4c,g,i,j (10 mmol) in pyridine (10
ml) were refluxed for 4-8 hours. The solid products obtained
were collected by filtration and crystallized from ethanol to
afford 5a-d respectively.
-1
crystals from dilute ethanol; IR (KBr): ν 3240 (OH), 3210 cm
1
(NH); H NMR (d -DMSO): δ = 1.06 (t, 3H, CH ), 2.9 (q, 2H,
6
CH ), 7.3-7.4 (m, 5H, Ar-H), 8.3 (s, 1H, H-1), 9.92 (s, 1H, NH),
3
5-Ethyl-4-(4-nitrophenylazo)-1-phenylpyrazole (5a).
2
9.99 (s, 1H, oxime-H); MS (EI, 70 EV): m/z 219(M ).
Anal. Calcd. for C H N O (219.24): C, 60.26; H, 5.98; N,
+
This compound was obtained in 70 % yield, mp 153-157 ºC;
1
dark red crystals from ethanol, H NMR (d -DMSO): δ = 1.3 (t,
11 13
19.17%. Found: C, 60.09; H, 5.99; N, 19.30.
3 2
6
3H, CH ), 3.1 (q, 2H, CH ), 7.4-7.5 (m, 5H, Ar-H), 7.9 (d, 2H,
3
2

652
M. A. Al-Shiekh, A. M. Salah El-Din, E. A. Hafez, and M. H. Elnagdi
Vol. 41
3-Oxo -2-(p-tolylhydrazono)pentanal-l-oxime (6b).
Anal. Calcd. for C H N O (246.22): C, 53.66; H, 4.09; N,
11 10 4 3
22.75%. Found: C, 53.72; H, 3.99; N, 22.90.
This compound was obtained in 60 % yield by Method A, after
240 min. reflux while Method B yielded 85% after heating for 5
min in a domestic microwave oven at full power; mp 199 ºC;
orange crystals from ethanol; IR (KBr): ν 3385 (OH), 3145 (NH),
5-Ethyl-4-(4-methoxyphenylazo)isoxazole (7d).
This compound was obtained in 72 % yield, mp 95 ºC; pale brown
1
crystals from AcOH, H NMR (d -DMSO): δ = 1.2 (t, 3H, CH ), 2.6
-1
1
6
(q, 2H, CH ), 3.7 (S, 3H, OCH ), 7.2 (d, 2H, Ar-H), 7.5 (d, 2H, Ar-
3
1650 cm (CO); H NMR (d -DMSO): δ = 1.06 (t, 3H, CH ), 2.3
6
(s, 3H, CH ), 2.9 (q, 2H, CH ), 7.22 (s, 4H, Ar-H), 8.3 (s, 1H,
3
2
3
3
H-1), 11.8 (s, 1H, NH), 12.5 (s, 1H, oxime-H); MS (EI, 70 EV):
2
+
H), 8.1 (s, 1H,isoxazolyl-H); MS (EI, 70 EV): m/z 231 (M ).
Anal. Calcd. for C H N O (231.25): C, 62.33; H, 5.67; N,
18.17%. Found: C, 62.13; H, 5.76; N, 18.20.
+
m/z 233(M ).
Anal. Calcd. for C H N O (233.27): C, 61.79; H, 6.48; N,
12 13
3 2
12 15
18.01%. Found: C, 61.80; H, 6.38; N, 17.89.
3 2
2-[(4-Nitrophenyl)hydrazono]-3-oxo-pentanenitrile (8).
2-(4-Nitrophenylhydrazono)-3-oxopentanal-l-oxime (6c).
This compound was obtained in 60 % yield, mp 163 ºC; red
Mixture of hydroxylamine hydrochloride (0.69 g, 10 mmol),
ammonium acetate (0.77 g, 10 mmol) and arylhydrazonopentanal
2c (10 mmol) was placed in the microwave oven and heated for
10 min at full power. The resulting product was washed with
ethanol and crystallized from ethanol. This compound was
obtained in 95 % yield, mp 212 ºC; dark brown crystals from
1
crystals dilute AcOH, H NMR (d -DMSO): δ = 1.07 (t, 3H,
6
CH ), 2.9 (q, 2H, CH ), 6.7-7.9 (m, 4H, Ar-H), 8.1 (s, 1H, H-
3
1),10.9 (s, 1H, NH), 11.6 (s, 1H, oxime-H); MS (EI, 70 EV): m/z
2
+
264(M ).
1
ethanol, H NMR (d -DMSO): δ = 1.3 (t, 3H, CH ), 2.4 (q, 2H,
13
Anal. Calcd. for C H N O (264.24): C, 50.00; H, 4.58; N,
11 12 4 4
21.20%. Found: C, 49.81; H, 4.49; N, 21.00.
6
CH ), 7.5 (d, 2H, Ar-H),7.6 (d, 2H, Ar-H), 11.2 (s,1H,NH);
3
C
NMR: δ = 8.9 (CH ), 29.8 (CH ), 116.9 (CN), 115.4, 126.5,
2
3
133.7, 143.2 (phenyl carbon), 148.6 (C-2), 198.9 (CO); MS (EI,
2
2-(4-Methoxyphenylhydrazono)-3-oxopentanal-l-oxime (6d).
This compound was obtained in 60 % yield, mp 120 ºC; yellow
+
70 EV): m/z 247[M+1)] .
Anal. Calcd. for C H N O (246.22): C, 53.66; H, 4.10; N,
1
green crystals from ethanol, H NMR (d -DMSO): δ = 1.06 (t,
6
3H, CH ),2.9 (q, 2H, CH ), 3.7 (s, 3H, OCH ), 6.99 (d, 2H, Ar-
11 10
22.75%. Found: C, 53.61; H, 4.00; N, 22.69.
4 3
3
H), 7.3 (d, 2H, Ar-H), 8.3 (s, 1H, H-1), 11.8 (s, 1H, NH), 12.5 (s,
2
3
Preparation of Pyrimidine Derivatives 11a-d, and Pyrimido[1,2-a]-
benzimidazole Derivatives 14a, b.
+
1H, oxime-H); MS (EI, 70 EV): m/z 249(M ).
Anal. Calcd. for C H N O (249.27): C, 57.82; H, 6.07; N,
12 15
3 3
16.86%. Found: C, 57.90; H, 5.97; N, 16.76.
Preparation of Isoxazole Derivatives 7a-d.
General Procedure.
General Procedures.
Method A, Thermal Reaction.
One of the 2-arylhydrazonopentanals 2a,c (10 mmol) in ethanol
(30 ml) was treated with one of the heterocyclic amines 10a-d, 13
(10 mmol). The mixture was heated under reflux for 4-6 h and
allowed to cool at room temperature. The solid product was
collected by filtration and crystallized from the proper solvent.
Each of oximes 6a-d (10 mmol) was refluxed in acetic anhy-
dride (10 ml) for 4 h, and then left to cool at room temperature.
The solid product separated as pale yellow crystals that were col-
lected by filtration and recrystallized from the proper solvent.
Method B, Microwave Heating.
5-Ethyl-4-(phenylazo)isoxazole (7a).
A mixture of arylhydrazonopentanal 2a (10 mmol) with one of
the heterocyclic amines 10a, 13 (10 mmol) was placed in the
microwave oven and heated for 2 min at full power. The resulting
product was washed with ethanol and crystallized from the
proper solvent.
This compound was obtained in 69 % yield, mp 73 ºC; pale red
1
crystals from AcOH, H NMR (d -DMSO): δ = 1.2 (t, 3H, CH ),
6
2.4 (q, 2H, CH ), 7.1-8.3 (m, 5H, Ar-H), 8.12 (s, 1H,isoxazolyl-
3
2
H); MS (EI, 70 EV): m/z 201 (M ).
Anal. Calcd. for C H N O (201.23): C, 65.66; H, 5.51; N,
+
11 11
20.88%. Found: C, 65.46; H, 5.53; N, 21.00.
3
7-Ethyl-6-phenylazo-1,2,4-triazolo[1,5-a]pyrimidine (11a).
5-Ethyl-4-(4-methylphenylazo)isoxazole (7b).
From a mixture of 2a and 10a after 360 min by Method A,
reflux yielded 65% while Method B yielded 97% after heating
for 2 min in a domestic microwave oven; mp 149 ºC; orange
This compound was obtained in 67 % yield, mp 81 ºC; yellow
1
crystals from dilute AcOH, H NMR (d -DMSO): δ = 1.13 (t,
6
3H, CH ), 2.4 (s,3H,CH ), 3.1 (q, 2H, CH ), 7.4 (d, 2H, Ar-H),
1
crystals from ethanol, H NMR (d -DMSO): δ = 1.4 (t, 3H,
6
CH ), 3.7 (q, 2H, CH ), 7.6-7.9 (m, 5H, Ar-H), 8.8 (s, 1H, H-2),
3
3
7.9 (d, 2H, Ar-H), 8.55 (s, 1H,isoxazolyl H); MS (EI, 70 EV): m/z
2
3
2
+
+
215 (M ).
9.2 (s, 1H, H-5); MS (EI, 70 EV): m/z 252 (M ).
Anal. Calcd. for C (252.28): C, 61.89; H, 4.79; N,
33.31%. Found: C, 61.79; H, 4.81; N, 33.41.
H
N
6
Anal. Calcd. for C H N O (215.25): C, 66.96; H, 6.09; N,
12 13 3
19.52%. Found: C, 66.76; H, 6.10; N, 19.70.
13 12
2-Phenyl-6-phenylazo-7-ethylpyrazolol[1,5-a]pyrimidine (11b).
5-Ethyl-4-(4-nitrophenylazo)isoxazole (7c).
From a mixture of 2a and 10b after 360 min. reflux by Method
A yielded 79% while Method B yielded 99% after heating for 2
min in domestic microwave oven. Mp 182 ºC; orange crystals
This compound was obtained in 75 % yield, mp 131 ºC; dark
1
brown crystals from AcOH, H NMR (d -DMSO): δ = 1.15 (t,
6
3H, CH ), 3.13 (q, 2H, CH ), 8.3 (d, 2H, Ar-H), 8.7 (d, 2H, Ar-
13
3
H), 8.73 (s, 1H, isoxazolyl-H); C NMR: δ =8.1 (CH ), 33.5
2
1
from ethanol, H NMR (d -DMSO): δ = 1.4 (t, 3H, CH ), 3.8 (q,
6
2H, CH ), 7.3 (s, 1H, H-3), 7.3-7.4 (m, 10H, Ar-H), 8.9 (s, 1H,
3
3
(CH ), 119.6 (C-4), 120.6, 126.3, 138.4, 143.3 (phenyl carbon),
2
H-5); MS (EI, 70 EV): m/z 327 (M ).
2
147.5 (C-3), 148.9 (C-5); MS (EI, 70 EV): m/z 246 (M ).
+
+

Sep-Oct 2004
2-Arylhydrazono-3-oxopropanals in Heterocyclic Synthesis
653
Anal. Calcd. for C
H
N
(327.39): C, 73.37; H, 5.23; N,
zonopropanals (2e-g) (10 mmol) in (CH Cl ) (10 ml) was added
2 2
20 17
21.39%. Found: C, 73.19; H, 5.31; N, 21.20.
5
drop wise a solution of dimethyl acetylenedicarboxylate (1.4 g,
10 mmol). The mixture was left at room temperature overnight,
and then treated with ethanol and the solid product was collected
by filtration and crystallized from the proper solvent.
2-(4-Chlorophenyl)-6-(4-nitrophenylazo)-7-ethylpyrazolol[1,5-
a]pyrimidine (11c).
This compound was obtained in 80 % yield, from a mixture of
2c and 10c, after 4-6 h reflux; mp >300 ºC; dark red crystals from
Dimethyl-2-phenyl-6-propionyl-2, 3-dihydropyridazine-3,4-
dicarboxylate (18a).
1
ethanol/DMF (2:1), H NMR (d -DMSO): δ = 1.2 (t, 3H, CH ),
6
2.59 (q, 2H, CH ),6.5 (s, 1H, H-3), 7.3-8.5 (m, 8H, Ar-H), 9.3 (s,
3
This compound was obtained in 92 % yield, mp 114 ºC; red
crystals from methanol/ethanol, IR (KBr): ν 1744, 1716 (CO
2
1H, H-5); MS (EI, 70 EV): m/z 406 (M ).
+
-1
ester), 1618 cm (CO); H NMR (d -DMSO): δ = 1.1 (t, 3H,
1
Anal. Calcd. for C
H ClN O (406.83): C, 59.05; H, 3.72;
6
CH ), 2.8 (q, 2H, CH ), 3.6 (s, 3H, OCH ), 3.8 (s, 3H, OCH ),
20 15 6 2
N, 20.66%. Found: C, 59.20; H, 3.69; N, 20.74.
3
6.1 (s, 1H, NCH), 7.4 (s, 1H, H-5), 7.2-7.6 (m, 5H, Ar-H); MS
2
3
3
2-Phenyl-3-bromo-6-(4-nitrophenylazo)-7-ethylpyrazolol[1,5-a]-
pyrimidine (11d).
+
(EI, 70 EV): m/z 271(M -59).
Anal. Calcd. for C H N O (330.34): C, 61.81; H, 5.49; N,
17 18
2 5
8.48%. Found: C, 61.93; H, 5.45; N, 8.35.
This compound was obtained in 85 % yield, from a mixture of
2c and 10d after 4-6 h reflux; mp 194 ºC; dark brown crystals
Dimethyl-2- p-tolyl-6-propionyl-2, 3-dihydropyridazine-3, 4-
dicarboxylate (18b).
1
from ethanol, H NMR (d -DMSO): δ = 1.2 (t, 3H, CH ), 2.5 (q,
6
2H, CH ), 7.3-8.2 (m, 9H, Ar-H), 9.26 (s, 1H, H-5); MS (EI, 70
3
2
EV): m/z 453 [M+2] .
Anal. Calcd. for C
+
This compound was obtained in 81 % yield, mp 258 ºC; red
1
crystals from ethanol, H NMR (d -DMSO): δ = 1.07 (t, 3H,
H BrN O (451.28): C, 53.23; H, 3.35;
20 15 6 2
N, 18.62%. Found: C, 53.16; H, 3.45 N, 18.53.
6
CH ), 2.3 (s, 3H, CH ), 2.4 (q, 2H, CH ), 3.67 (s, 3H, OCH ),
3
3
2
3
3.76 (s, 3H, OCH ), 6.2 (s,1H, NCH), 6.3-6.8 (m, 4H, Ar-H), 7.5
3
(s, 1H, H-5); MS (EI, 70 EV): m/z 344 (M ).
Anal. Calcd. for C H N O (344.36): C, 62.78; H, 5.85; N,
3-Phenylazo-4-ethylpyrimido[1,2-a]benzimidazole (14a).
+
This compound was obtained in 60 % yield by Method A, after
360 min. reflux from a mixture of 2a and 13, while Method B
yielded 95% after heating for 2 min in a domestic microwave
18 20
8.13%. Found: C, 62.59; H, 5.76; N, 8.33.
2 5
Dimethyl-2(4-nitrophenyl)-6-propionyl-2,3-dihydropyridazine-
3,4-dicarboxylate (18c).
1
oven at full power; mp 231 ºC; brown crystals from methanol, H
NMR (d -DMSO): δ = 1.2 (t, 3H, CH ), 2.6 (q, 2H, CH ), 7.2-7.7
6
3
2
+
(m, 9H, Ar-H), 9.2 (s, 1H, H-2); MS (EI, 70 EV): m/z 301 (M ).
Anal. Calcd. for C (301.35): C, 71.74; H, 5.02; N,
23.24%. Found: C, 71.87; H, 4.99; N, 23.05.
This compound was obtained in 95 % yield, mp 211 ºC; red
1
crystals from methanol, H NMR (d -DMSO): δ = 1.07 (t, 3H,
H
N
5
18 15
6
CH ), 2.4 (q, 2H, CH ), 3.6 (s, 3H, OCH ), 3.7 (s, 3H, OCH ),
3
6.2 (s, 1H, NCH), 7.4 (s, 1H, H-5), 6.7-7.9 (m, 4H, Ar-H); MS
2
3
3
3-(4-Nitrophenylazo-4-ethylpyrimido[1,2-a]benzimidazole (14b).
This compound was obtained in 72 % yield, from a mixture of
2c and 13 after reflux for 360 min. mp 185 ºC; brown crystals
+
(EI, 70 EV): m/z 375(M ).
Anal. Calcd. for C H N O (375.33): C, 54.40; H, 4.57; N,
17 17
11.20%. Found: C, 54.21; H, 4.66; N, 11.30.
3 7
1
from ethanol, H NMR (d -DMSO): δ = 1.2 (t, 3H, CH ), 2.6 (q,
6
3
2H, CH ), 7.4 (d, 2H, Ar-H), 7.7 (d, 2H, Ar-H), 8.2-8.3 (m, 4H,
Dimethyl-2-(4-methoxyphenyl)-6-propionyl-2,3-dihydropyri -
dazine-3,4-dicarboxylate (18d).
2
Ar-H), 9.3 (s, 1H, H-2); MS (EI, 70 EV): m/z 346 (M ).
Anal. Calcd. for C H N O (346.35): C, 62.42; H, 4.07; N,
+
18 14
24.26%. Found: C, 62.33; H, 3.99; N, 24.30.
6 2
This compound was obtained in 90 % yield, mp 113 ºC; red
1
crystals from ethanol, H NMR (d -DMSO): δ = 1.18 (t, 3H,
6
CH ), 2.9 (q, 2H, CH ), 3.7 (s, 3H, OCH ), 3.8 (s, 3H, OCH ),
3
6.05 (s, 1H, NCH), 7.6 (s, 1H, H-5), 6.9-7.4 (m, 4H, Ar-H); MS
2
3
3
Ethyl-2-(4-nitrophenyl)-3oxo-6-propionyl-2, 3-dihydropyri -
dazine-4-carboxylate (16).
+
(EI, 70 EV): m/z 361 [M+1] .
Anal. Calcd. for C H N O (360.36): C, 59.99; H, 5.59; N,
To a solution of 3-oxo-2-(4-nitrophenylhydrazono)pentanal
(2c) (10 mmol) in ethanol (30 ml), diethylmalonate (1.6 g, 10
mmol) and piperidine (12 mmol) was added. The mixture was
refluxed for 6 h, then left to cool at room temperature. The solid
product, so formed, was collected by filtration and recrystallized
18 20
7.77%. Found: C, 60.10; H, 5.49; N, 7.95.
2 6
Dimethyl-6-(4-acetylbenzoyl)-2-phenyl-2,3-dihydropyridazine-
3,4-dicarboxylate (18e).
from ethanol. This compound was obtained in 85 % yield, mp
1
106 ºC; dark red crystals from dilute ethanol, H NMR (d -
This compound was obtained in 82 % yield, mp 165 ºC; red
crystals from dioxan, IR (KBr): ν 1744, 1715(CO ester), 1615
6
DMSO): δ = 1.07 (t, 3H, CH ), 1.4 (t, 3H, CH ), 2.4 (q, 2H,
-1
cm (CO); H NMR (d -DMSO): δ = 2.6 (s, 3H, CH ), 3.6 (s,
1
3
CH ), 4.2 (q, 2H, CH ), 7.3 (s, 1H, H-5), 7.9-8.1 (m, 4H, Ar-H);
3
6
3H, OCH ), 3.7 (s,3H, OCH ), 6.2 (s, 1H, NCH), 6.4-7.9 (m, 9H,
3
2
2
3
3
+
MS (EI, 70 EV): m/z 346 (M+1) .
Anal. Calcd. for C H N O (345.31): C, 55.65; H, 4.38; N,
+
Ar-H), 8.11 (s, 1H, H-5); MS (EI, 70 EV): m/z 420 (M ).
Anal. Calcd. for C H N O (420.42): C, 65.71; H, 4.79; N,
6.66%. Found: C, 65.70; H, 4.71; N, 6.56.
16 15
3 6
23 20
2 6
12.17%. Found: C, 55.56; H, 4.29; N, 12.21.
Preparation of 2,3-Dihydropyridazines Derivatives 18a-g.
General Procedure.
Dimethyl-6-(4-acetylbenzoyl)-2-(4-nitrophenyl)-2,3-dihydropy-
ridazine-3,4-dicarboxylate (18f).
This compound was obtained in 82 % yield, mp 170 ºC; red
1
crystals from methanol, H NMR (d -DMSO): δ = 2.6 (s, 3H,
To a magnetically stirred solution of Ph P (2.6 g, 10 mmol)
3
and each of 2-arylhydrazonopentanals (2a-d) or 2-arylhydra-
6

654
M. A. Al-Shiekh, A. M. Salah El-Din, E. A. Hafez, and M. H. Elnagdi
Vol. 41
+
CH ), 3.6 (s, 3H, OCH ), 3.7 (s, 3H, OCH ), 6.2 (s, 1H, NCH),
NH), 9.9 (br s, 1H, NH); MS (EI, 70 EV): m/z 312(M ).
Anal. Calcd. for C H N O (312.33): C, 57.68; H, 5.16; N,
26.91%. Found: C, 57.62; H, 5.10; N, 26.85.
3
6.6-8.05 (m, 8H, Ar-H), 8.11 (s, 1H, H-5); MS (EI, 70 EV): m/z
3
3
15 16
6 2
+
466 [M+1] .
Anal. Calcd. for C H N O (465.42): C, 59.36; H, 4.11; N,
23 19 3 8
9.03%. Found: C, 59.54; H, 4.08; N, 8.89.
REFERENCES AND NOTES
Dimethyl-6-(4-acetylbenzoyl)-2-(4-methoxyphenyl)2, 3-dihy-
dropyridazine-3,4-dicarboxylate (18g).
[1] F. Al-Omran, M. M. Abdel-Khalik, A. Abuel-Khair and M.
H. Elnagdi, OPPI, 29(3) 285 (1997).
[2] K. M. Al-Zaydi, E. A. Hafez, and M. H. Elnagdi, J. Chem.
Research (S), 154 (2000); (M) 510 (2000).
[3] H. Bahbehani, M. M. Abdel-Khalik, and M. H. Elnagdi,
OPPI, 31, 551 (1999).
[4] M. M. Abdel-Khalik, S. M. Agamy and M. H. Elnagdi.
Synthesis, 1861 (2001).
This compound was obtained in 79 % yield, mp 147 ºC; dark
1
red crystals from dilute methanol, H NMR (d -DMSO): δ = 2.6
6
(s, 3H, CH ), 3.6 (s, 3H, OCH ), 3.71 (s, 3H, OCH ), 3.78 (s, 3H,
3
3
3
OCH ), 6.2(s, 1H, NCH), 6.9 (d, 2H, Ar-H), 7.5 (d, 2H, Ar-H),
3
7.6 (s, 1H, H-5), 7.9 (d, 2H, Ar-H), 8.1 (d, 2H, Ar-H); MS (EI, 70
+
EV): m/z 450 (M ).
Anal. Calcd. for C H N O (449.44): C, 64.14; H, 4.71; N,
24 21
6.23 %. Found: C, 63.99; H, 4.69; N, 6.31.
2 7
[5] N. A. Al-Awadi, M. H. Elnagdi, Y. A. Ibrahim, K. Kaul and
A. Kumar; Tetrahedron, 57, 1609 (2001).
[6] A. S. Matlack in "Introduction to Green Chemistry" Marcel
Dekker Inc., New York, Basel, (2001).
8 - H y d r a z i n o - 1 - p h e n y l - 3 - p r o p i o n y l - 6 , 8 a - d i h y d r o - 1 H- p y r i-
dazino[4,5-c]pyridazin-5-one (22).
[7] J. Clark and D. MacQuarrie in "Handbook of Green
Chemistry and Technology" Blackwell Science Ltd., Paris, (2002).
[8] M. M. Abdel-Khalik, S. M. Agamy and M. H. Elnagdi. Z.
Naturforsch., 55b, 1211 (2000).
[9] A. A. Elassar and A. A. Elkhair, Tetrahedro n, 5 9, 8463
(2003).
[10] A. Almazroa, M. H. Elnagdi, and A .M. SalahEl-Din J.
Heterocyclic Chem., 41, 267 (2004).
[11] M. A. Al-Shiekh, A. M. Salah El-Din, E. A. Hafez, and M.
H. Elnagdi, J. Chem. Research 3, 174 (2004).
A mixture of compound 18a (10 mmol) in EtOH (30 ml) was
treated with hydrazine hydrate (20 mmol). The mixture was
heated under reflux for 1 h and allowed to cool to r.t. The solid
product was collected by filtration and crystallized from EtOH.
This compound was obtained in 90 % yield, mp 177 ºC; pale yel-
low crystals from ethanol/dioxan (1:1), IR (KBr): ν 3420, 3330,
-1
1
2918 (NH, NH ), 1679 (ring CO), 1614 cm (CO); H NMR (d -
2
DMSO): δ = 1.06 (t, 3H, CH ), 2.4 (q, 2H, CH ), 5.7 (s, 1H,
6
3
NCH), 6.7 (s, 1H, H-4), 7-7.4 (m, 7H, Ar-H, NH ), 9.2 (br s, 1H,
2
2