Behavior of 3-benzylamino-5-aryl-2(3H)-furanones towards some nitrogen nucleophiles

Article abstract of DOI:10.1002/jhet.5570430422

Ring closure of 2-N-benzylamino-3-aroylpropionic acids (3) with acetic anhydride afforded 3-N-benzylamino-5-aryl-2(3H)-furanones (4). The reaction of the furanones (4) with benzylamine in benzene was found to be time dependent. Thus refluxing the reaction

Full text of DOI:10.1002/jhet.5570430422

Jul-Aug 2006
957
Behavior of 3-Benzylamino-5-aryl-2(3H)-furanones Towards Some
Nitrogen Nucleophiles
Kamal A. Kandeel, Ahmed S. A. Youssef, Wael S. I. Abou-Elmagd,* and Ahmed I. Hashem
Chemistry Department, Faculty of Science, Ain Shams University, Abbassia, Cairo, Egypt
E-mail: waelmagd97@yahoo.com
Received September 27, 2006
H
N
Ph
O
HN
Ph
Ac2O
OH
Ar
Ar
O
O
O
Ring closure of 2-N-benzylamino-3-aroylpropionic acids (3) with acetic anhydride afforded 3-N-
benzylamino-5-aryl-2(3H)-furanones (4). The reaction of the furanones (4) with benzylamine in benzene
was found to be time dependent. Thus refluxing the reaction mixture for 1 h only afforded the open-chain
amides (5a-c). When the reaction was conducted for 3 h the 2(3H)-pyrrolones (6) were obtained.
Hydrazine hydrate affected ring opening of the furanones to give the hydrazides (5d-f). Also,
semicarbazide converted (4) into the corresponding semicarbazide derivatives (5g-i). The hydrazides (5d-f)
were reacted with benzoyl chloride to give the corresponding diaroylhydrazines (5j-l). The open-chain
derivatives (5) were converted into a variety of heterocycles: isothiazolones (7), dihydropyridazinones (8),
1,3,4-oxadiazoles (9) and 1,2,4-triazole derivatives (10) via cyclization reactions.
J. Heterocyclic Chem., 43, 957 (2006).
benzylamino-3-aroylpropionic acids (3) [12] (obtained
from addition of benzylamine to 3-aroylacrylic acids),
using the method described previously by one of us [13].
Introduction.
The chemistry of 2(3H)-furanones has received great
attention in the last decades [1-5]. The importance of
these compounds is due to facile opening of the lactone
ring to give acyclic products which on recyclization can
afford other heterocyclic systems. The conversion of
2(3H)-furanones into a variety of synthetically and
biologically important heterocycles e.g. pyrrolones,
pyridazinones, triazoles, oxadiazoles and isothiazolones
was reported by a number of investigators [6-10]. It was
reported that when 3-aryl-5-phenyl-2(3H)-furanones (1)
were treated with benzylamine, isomerization occurred to
give the thermodynamically more stable isomers 3-aryl-5-
phenyl-2(5H)-furanones (2) [11].
H
N
Ph
O
HN
Ph
Ac2O
OH
Ar
O
O
Ar
O
4
3
a, Ar = C6H5–; b, Ar = 4-ClC6H4–; c, Ar = 4-CH3OC6H4–
The structure of compounds (4a-c) was elucidated from
analytical and spectral data. Thus, the IR spectra of 4
showed a strong absorption at 1778 cm-1 characteristic of
1
five membered lactone ring (Table 1). The H NMR
Ar
Ar
spectra of compounds (4a-c) showed absorptions
correlated to methine, methylene and olefinic protons in
addition to the NH and aromatic protons.
O
O
Ph
Ph
O
O
1
2
The furanones (4) reacted with benzylamine in
refluxing benzene to give products depending on the
reaction time. Thus, when the reaction was conducted for
1 h, the open-chain amides (5a-c) were obtained; whereas
refluxing for 3 h, afforded the pyrrolones (6a-c), which
were also obtained via ring closure of (5a-c) by refluxing
in HCl/CH3COOH mixture. It is to be mentioned that the
amides (5a-c) were also obtained when the reaction was
carried out in ethanol at room temperature. Similarly, the
furanones (4) reacted with the hydrazine hydrate and
semicarbazide to give the hydrazide derivatives (5d-f) and
the semicarbazide derivatives (5g-i), respectively. The
latter products were obtained by an unambiguous route
This isomerization was believed to occur via a
carbanion intermediate, created by the effect of the amine,
which is stabilized by the presence of aryl group at
position 3. We wish to report here the behavior of some
2(3H)-furanones bearing
carbanion destabilizing group, towards some nitrogen
nucleophiles.
a
benzylamino group,
a
Results and Discussion.
The starting materials 3-N-benzylamino-5-aryl-2(3H)-
furanones (4) were prepared by ring closure of 2-N-

958
K. A. Kandeel, A. S. A. Youssef, W. S. I. Abou-Elmagd, and A. I. Hashem
Vol 43
Table 1
IR and 1H NMR (300 MHz) spectral data of compounds (4 and 6).
No.
IR (ꢀmax
(KBr) cm-1
ꢀNH ꢀC=O
)
1H-NMR (DMSO–d6)
4a
3400 1778 ꢁ = 3.40 (d, 1, CH, J = 1.4 Hz), 3.68 (d, 2, N-CH2, J = 5.4 Hz), 3.80 (d, 1,
CH, J = 1.5 Hz), 4.08 (d, 2, N-CH2, J = 5.4 Hz), 6.78 (d, 1, =CH, J =1.6
Hz), 6.82 (d, 1, =CH, J = 1.4 Hz), 7.36-7.56 (m, 20, ArH), 8.69 (brs, NH,
exchangeable)
4b
4c
6a
6b
6c
3380 1777 ꢁ = 3.34 (d, 1, CH, J = 1.4 Hz), 3.68 (d, 2, N-CH2, J = 5.4 Hz), 3.81 (d, 1,
CH, J = 1.5 Hz), 3.81 (d, 1, CH, J = 1.5 Hz), 4.08 (d, 2, N-CH2, J = 5.4
Hz), 6.80 (d, 1, =CH, J = 1.4 Hz), 6.83 (d, 1, =CH, J = 1.4 Hz), 7.32-7.61
(m, 18, ArH), 8.69 (brs, NH, exchangeable)
3388 1779 ꢁ = 3.36 (d, 1, CH, J = 1.4 Hz), 3.66 (d, 2, N-CH2, J = 5.4 Hz), 3.76 (s, 3,
OCH3), 3.82 (d, 1, CH, J = 1.5 Hz), 4.08 (d, 2, N-CH2, J = 5.4 Hz), 6.82
(1, =CH, J = 1.4 Hz), 6.85 (d, 1, =CH, J = 1.4 Hz), 7.32-7.61 (m, 18,
ArH), 8.69 (brs, NH, exchangeable)
3250 1651 ꢁ = 3.71 (ABq, 2, N-CH2), 3.92 (ABq, 2, N-CH2), 4.09 (ABq, 2, N-CH2),
4.88 (d, 1, CH, J = 6.0 Hz), 4.90 (d, 1, CH, J = 6.6 Hz), 6.63 (d, 1, =CH, J
= 7.2 Hz), 6.65 (d, =CH, J = 6.9 Hz), 7.55-8.03 (m, 30, ArH), 8.18 (s, NH,
exchangeable), 8.20 (s, NH, exchangeable)
3350 1651 ꢁ = 3.76 (ABq, 2, N-CH2), 3.93 (ABq, 2, N-CH2), 4.06 (ABq, 2, N-CH2),
4.88 (d, 1, CH, J = 6.0 Hz), 4.90 (d, 1, CH, J = 7.2 Hz), 6.64 (d, 1, =CH, J
= 7.2 Hz), 7.61-8.15 (m, 28, ArH), 8.18 (s, NH, exchangeable), 8.20 (s,
NH, exchangeable)
3250 1652 ꢁ = 3.59 (s, 3, OCH3), 3.71 (ABq, 2, N-CH2), 3.92 (ABq, 2, N-CH2), 4.12
(ABq, 2, N-CH2), 4.88 (d, 1, CH, J = 6.0 Hz), 4.90 (d, 1, CH, J = 6.6 Hz),
6.62 (d, 1, =CH, J = 7.2 Hz), 6.64 (d, 1, =CH, J = 6.9 Hz), 7.61-8.15 (m,
28, ArH), 8.18 (s, NH, exchangeable), 8.20 (s, NH, exchangeable)
(Tables 1 & 2). Moreover, the 1H NMR spectra of
compounds (5a,d and g) are in a good agreement with the
proposed structure (Table 2). Evidently, the formation of
compounds (5 and 6) indicates that existence of a
benzylamino group at position 3 of the furanone nucleus
rendered isomerization [11] less favorable and ring opening
was the preferred pathway. It was of interest to the authors
to convert the amides (5a-c) into the corresponding
from the hydrazides (5d-f) by the action of potassium
cyanate. Also, the hydrazides (5d-f) were converted into
the corresponding diaroylhydrazines (5j-l) by treatment
with benzoyl chloride.
The structures of compounds (5 and 6) were
substantiated from analytical and spectral data. Thus, the IR
spectra of compounds (5a,d,g and 6a-c) showed the
functional groups correlated with the assigned structures
4a-c
+
R-NH2
a, R = C6H5CH2-
b, R = H2N-
c, R = H2NNHCO-
H
H
N
N
Ph
Ph
Ar
O
Ar
N
O
HN
O
-
CH2Ph
R
6
5
-
a, Ar = C6H5 , R = C6H5CH2
b, Ar = 4-ClC6H4 , R = C6H5CH2
c, Ar = 4-CH3OC6H4 , R = C6H5CH2
a, Ar = C6H5-
b, Ar = 4-ClC6H4-
c, Ar = 4-CH3OC6H4-
-
-
-
-
-
d, Ar = C6H5 , R = H2N
e, Ar = 4-ClC6H4 , R = H2N-
-
f, Ar = 4-CH3OC6H4 , R = H2N-
-
g, Ar = C6H5 , R = H2NCONH-
-
-
h, Ar = 4-ClC6H4 , R = H2NCONH-
i, Ar = 4-CH3OC6H4 , R = H2NCONH-
-
j, Ar = C6H5 , R = PhCONH-
-
k, Ar = 4-ClC6H4 , R = PhCONH-
-
-
l, Ar = 4-CH3OC6H4 , R = PhCONH

Jul-Aug 2006 Behavior of 3-Benzylamino-5-aryl-2(3H)-furanones Towards Some Nitrogen Nucleophiles
959
isothiazolone derivatives (7a-c) by treatment with thionyl
chloride at room temperature. Debenzoylation of (7a-c)
was affected by heating with solid NaOH to give (7d).
analgesic and anti-inflammatory [16]. Also, 1,3,4-
oxadiazoles were reported to have carcinostatic activity
against several types of tumors [17], antiarrhythmic [18]
and anticholesterolsmic [19] activities. These reported
activities prompted us to use compounds (5) as precursors
for these biologically active compounds. Thus, the
hydrazides (5d-f) were cyclized into the corresponding
dihydropyridazinones (8a-c) and the diaroylhydrazines
(5j-l) were converted into (8d-f) by refluxing with
HCl/AcOH mixture. Also, treatment of (5j-l) with
phosphorus oxychloride afforded the corresponding 1,3,4-
oxadiazoles (9a-i). The triazolone derivatives (10a-c)
were obtained from (5g-i) by the action of aqueous
sodium hydroxide.
Ph
R
N
O
H
S
N
CH2Ph
7
a, R = C6H5CO
b, R = 4-ClC6H4CO-
c, R = 4-CH3OC6H4CO-
d, R = H
The structure of (7) was confirmed from analytical
and spectral data. The IR spectra of compounds (7a
and 7d) showed absorption correlated to NH, C=O and
The structures of the above compounds were
substantiated from analytical and spectral data. Thus, the
IR spectra of (8a,d, 9a and 10) showed absorption bands
Scheme 1
O
H
N
O
HN
Cl
Ph
O
Cl
Ph
O
HN
Ph
H
SOCl2
Ar
- HCl
N
Ph
Ar
S
Ar
N
O
:
S
NH
Ph
O
Cl
Ph
5a-c
O
H
N
Ph
Ar
- HCl
S
N
O
Ph
7a-c
C=C. Moreover, the 1H NMR spectra showed
absorptions corresponding to methylene, aromatic and
NH protons for compounds (7a and 7d) in addition to
absorption for olefinic proton in case of compound
(7d). Based on similar reports [11,14], the formation
of isothiazolones (7a-c) can be represented as outlined
in Scheme 1.
characteristic of NH and carbonyl groups either for ketone
or amide (Table 2).
Moreover, the 1H NMR spectra of compounds (8a,d, 9a
and 10) were in a good agreement with the assigned
1
structure (Table 2). It is worth mentioning that the H
NMR spectrum of (8a) did not show any absorption
corresponding to an olefinic proton but did show a
splitting pattern for the CH2–CH group. This inferred the
existence of (8a) mainly in the tautomeric form B.
Dihydropyridazinones are known to have diverse
pharmacological activities, e.g. antihypertensive [15],
H
Ph
N
N
NH
O
N
N
H
N
Ph
O
N
O
Ar
O
NH
H
Ar
N
R
Ar
Ph
NH
Ph
O
8
9
10
-
-
-
a, Ar = C6H5
a, Ar = C6H5 , R = H
a, Ar = C6H5
-
-
-
b, Ar = 4-ClC6H4
c, Ar = 4-CH3OC6H4
b, Ar = 4-ClC6H4 , R = H
b, Ar = 4-ClC6H4
c, Ar = 4-CH3OC6H4
-
-
-
c, Ar = 4-CH3OC6H4 , R = H
-
d, Ar = C6H5 , R = PhCO-
e, Ar = 4-ClC6H4 , R = PhCO-
-
f, Ar = 4-CH3OC6H4 , R = PhCO-
-

960
K. A. Kandeel, A. S. A. Youssef, W. S. I. Abou-Elmagd, and A. I. Hashem
Vol 43
Table 2
IR and 1H NMR (300 MHz) spectral data of compounds (5 and 7 – 10).
IR (ꢀmax
)
(KBr) cm-1
No.
1H NMR (DMSO–d6)
ꢀNH
ꢀC=O
ꢁ = 3.16 (d, 2, CH2CO, J = 7.2 Hz), 3.80 (brs, 2, N-CH2), 4.16 (brs, 2, N-CH2),
4.78 (t, 1, CH, J = 7.2 Hz), 5.89 (brs, NH, exchangeable), 7.24-7.48 (m, 15,
ArH), 8.51 (br s, NH, exchangeable).
ꢁ = 3.20 (d, 2, CH2CO, J = 6.0 Hz), 3.92 (ABq, 2, N-CH2, J = 6.0 Hz), 4.21 (br s,
NH, exchangeable), 4.88 (t, 1, CH, J = 6.3 Hz), 6.02 (brs, 2, NH2, exchangeable),
7.60-8.14 (m, 10, ArH), 8.50 (br s, 1, NHCO, exchangeable)
ꢁ = 3.41 (d, 2, CH2CO, J = 6.3 Hz), 4.33 (s, 2, CH2-N), 4.78 (s, 1, NH-CH2,
exchangeable), 4.89 (t, 2, CH2-CH, J = 6.3 Hz), 7.50-7.60 (m, 10, ArH), 8.64 (s,
2, H2N–CO, exchangeable), 10.49 (s, 2, CO–NH–NHCO, exchangeable)
ꢁ = 3.38 (d, 2, CH2CO, J = 6.3 Hz), 4.29 (s, 2, CH2-N), 4.89 (t, 2, CH2-CH, J =
6.3 Hz), 6.64 (br s, 1, NH-CH2, exchangeable), 7.50-7.95 (m, 15, ArH), 10.49 (s,
2, CO-NH-NH-CO, exchangeable)
1700(sh.)
1685
5a
5d
5g
5j
3330
3201
3170
1695 (sh)
1668
1702 (sh)
1675
3390
3400
3325
1705 (sh)
1662
ꢁ = 3.91 (s, 2, N-CH2), 3.99 (s, 2, N-CH2), 7.34-7.54 (m, 15, ArH), 8.64 (br s,
NH, exchangeable)
ꢁ = 3.99 (s, 4, 2N-CH2), 6.64 (s, 1, =CH), 7.24-7.53 (m, 10, ArH), 8.58 (br s, NH,
exchangeable)
7a
7d
3380
3293
1687
1638
ꢁ = 2.97 (d, 2, CH-CH2, J = 6.3 Hz), 3.76 (ABq, 2, N-CH2), 4.89 (t, 1, CH-CH2, J
= 6.3 Hz), 7.50-7.95 (m, 10, ArH), 8.64 (br s, NH, exchangeable), 10.49 (s,
NHCO, exchangeable)
8a
3294
1639
ꢁ = 3.92 (s, 2, N-CH2), 4.78 (s, 1, -CH-), 6.64 (s, 1, =CH), 7.36 (s, 1, NH-CH2,
exchangeable), 7.50-7.95 (m, 15, ArH), 10.49 (s, 1, NHCO, exchangeable)
ꢁ = 3.06 (d, 2, CH2-CH, J = 4.8 Hz), 3.98 (s, 2, NCH2), 4.21 (br s, NH,
exchangeable), 4.89 (t, CH2CH, J = 4.8 Hz), 7.60-8.14 (m, 15, ArH)
ꢁ = 3.19 (d, 2, CH2–CH, J = 6.3 Hz), 3.85 (ABq, 2, N-CH2), 4.15 (s, NH,
8d
9a
3294
3150
1630
1679
10a 3324 1718, 1679 exchangeable), 4.88 (t, 1, CH2CH, J = 6.3 Hz), 7.26-7.45 (m, 10, ArH), 13.04 (br
s, 2, NHCONH, exchangeable)
Table 3 (continued)
Yield %
H
H
N
Ph
Ph
Ph
Ph
N
No.
mp°C
(Calcd./Found)
H
O
O
C
N
NH
NH
N
H
N
160-162
(ethanol)
259-260
(ethanol)
190-192
(benzene)
270-271
(benzene)
161-162
(benzene)
260-261
(ethanol)
254-25
66.05
66.12
69.60
69.58
81.35
81.36
74.10
74.14
78.13
78.15
72.00
72.10
66.28
66.21
69.77
70.01
68.91
68.90
6.40
6.40
5.80
5.80
6.20
6.21
5.40
5.40
6.25
6.29
5.00
5.02
4.37
4.35
5.12
5.13
5.41
5.46
12.84
12.85
9.74
9.65
7.90
7.79
7.20
7.35
7.29
7.30
7.00
6.94
6.44
6.45
6.51
6.55
9.45
9.35
5f
5l
80
55
80
73
65
45
57
60
75
A
B
6a
6b
6c
7a
7b
7c
7d
Table 3
Physical and analytical data of compounds (4-7).
mp°C
(Solvent)
(Calcd./Found)
H
No.
Yield %
C
N
185-187
(benzene/ethanol)
266-268
(benzene/ethanol)
170-173
76.98
77.12
68.11
68.10
73.2
5.66
5.64
4.67
4.59
5.76
5.80
6.40
6.41
5.66
5.71
6.47
6.48
6.39
6.41
5.43
5.51
5.28
5.35
4.67
4.69
4.75
4.76
7.50
7.47
6.89
6.85
6.97
6.94
14.14
14.19
12.67
12.71
4a
4b
4c
5a
5b
5c
5d
80
85
65
60
60
50
80
(ethanol)
276-278
(ethanol)
170-172
(ethanol)
(benzene/ethanol)
200-202
72.9
77.40
77.56
70.80
70.85
74.60
74.90
68.69
68.61
61.54
61.50
(ethanol)
290-292
(ethanol)
193-195
(ethanol)
134-136
(ethanol)
178-180
EXPERIMENTAL
Melting points were measured on an electrothermal
melting point apparatus and are uncorrected. Elemental
analyses were carried out at the Micro-Analytical Unit,
Cairo University, Giza. IR spectra were measured on a
Unicam SP-1200 spectrophotometer using KBr wafer
5e
80
(ethanol)

Jul-Aug 2006 Behavior of 3-Benzylamino-5-aryl-2(3H)-furanones Towards Some Nitrogen Nucleophiles
961
The solid obtained was collected by filtration and recrsytallized
from a suitable solvent (Table 3) to give 2-benzyl-4-N-
benzylamino-5-aroyl-3(2H)-isothiazolones (7a-c).
Table 4
Physical and analytical data of compounds (8-10).
(Calcd./Found)
mp°C
(Solvent)
Yield
%
General Procedure for the Debenzoylation of (7a-c).
No.
C
N
H
A mixture of (7a-c) (0.01 mol) and solid NaOH (0.1 g, 0.0025
mol) in 20 mL of benzene was stirred at rt for 1 h. When a
fading of the initial yellowish colour was observed, the benzene
layer was separated and concentrated under vacuum to give a
solid residue which was recrystallized from ethanol (Table 3), to
give 2-benzyl-4-N-benzylamino-3(2H)-isothiazolone (7d).
160-162
(ethanol)
158-160
(ethanol)
165-166
(ethanol)
182-183
(benzene)
179-180
73.12
73.19
65.18
65.17
69.90
69.92
75.19
75.05
68.98
68.85
72.64
72.55
75.19
75.30
68.98
69.00
72.64
72.57
67.08
67.10
60.59
60.62
64.77
64.75
6.09
6.11
5.11
5.10
6.15
6.11
5.48
5.45
4.79
4.72
5.57
5.51
5.48
5.46
4.79
4.75
5.57
5.55
5.59
5.61
4.77
4.76
5.68
5.67
15.05
15.12
13.42
13.40
13.59
13.52
10.97
10.11
10.06
10.15
10.17
10.01
10.97
11.02
10.06
10.02
10.17
10.21
17.39
17.34
15.71
15.73
15.91
15.88
8a
8b
8c
50
50
50
60
62
60
70
65
75
45
40
40
8d
8e
General Procedure for the Reactions of 3-N-Benzylamino-5-
aryl-2(3H)-furanones (4a-c) with Hydrazine Hydrate.
(benzene/ethanol)
185-187
(benzene/ethanol)
140-142
To a solution of the furanones (4a-c) (1 mol) in ethanol (20 mL),
(100%) hydrazine hydrate (35.5 mL, 1.1 mol) was added at rt for 5
min. The product obtained was collected by filtration, washed with
ethanol and the product was shown to be 2-N-benzylamino-3-
aroylpropionic acid hydrazides (6d-f), (Table 3). When the reaction
mixture was refluxed in ethanol the product was shown to be 6-
aryl-4-N-benzylamino-4,5-dihydropyridazin-3-(2H)-one (8a-c)
which were recrystalized from suitable solvents (Table 4).
8f
9a
(ethanol)
152-153
(ethanol)
159-160
(ethanol)
230-231
(ethanol)
242-244
9b
9c
10a
10b
10c
General Procedure for the Reaction of Hydrazides (6d-f) with
Potassium Isocyanate.
(ethanol)
235-236
(ethanol)
A solution of potassium isocyanate (1.78 g, 0.022 mol) in
water (10 mL) was added dropwise with stirring at 0 °C to a
solution of the hydrazide derivatives (5d-f) (0.02 mol) in acetic
acid-water (1:1) mixture. The reaction mixture was stirred at rt
for 3 h, the product obtained was collected by filtration, washed
thoroughly with water, and finally recrystallized from a suitable
solvent (Table 3) to give 2-N-benzylamino-3-aroylpropionoyl
acid semicarbazides (5g-i).
The same semicarbazide derivatives (5g-i) were also obtained
from heating a solution of 2(3H)-furanones (4a-c) (0.01 mol) in
ethanol (30 mL) and a mixture of semicarbazide hydrochloride
(1.12 g, 0.01 mol), sodium acetate anhydrous (0.82 g, 0.01 mol)
under reflux at 70 °C for 1 h. The solid obtained was collected
by filtration and recrystallized from a suitable solvent (Table 3).
The solid obtained was identical in all respects (mp, mixed mp
and TLC) with the product obtained above from the reaction
between hydrazides (5d-f) and potassium isocyanate.
1
technique. H NMR spectra were measured in DMSO-d6 on
a Varian plus instrument (300 MHz).
2-N-Benzylamino-3-aroylpropionic acids (3a-c).
These compounds were prepared according to the procedure
described by previous investigators [12].
3-N-Benzylamino-5-aryl-2(3H)-furanones (4a-c).
A mixture of 2-N-benzylamino-3-aroyl propionic acids (3a-c)
[12] (1 mol) and acetic anhydride (270 mL, 3 mol) was heated
under reflux for 20 min, the reaction was then cooled, poured
onto ice, collected by filtration and the product was
recrystallized from a suitable solvent to give (4a-c) (Table 3).
General Procedure for the Reactions of 3-N-Benzylamino-5-
aryl-2(3H)-furanones (4a-c) with Benzylamine.
General Procedure for the Reaction of Hydrazides (5d-f) with
Benzoyl Chloride.
To a solution of the furanones (4a-c) (0.01 mol) in benzene
or ethanol (20 mL), benzylamine (1.1 mL, 0.01 mol) was
added, the reaction mixture was refluxed in benzene at 60 °C
for 1 h or left at rt for 5 min in ethanol. The product was
shown to be 2-N-benzylamino-3-aroyl-N-benzyl–propion-
amides (5a-c), (Table 3). When the reaction mixture was
heated at 100 °C for 3 h, the product obtained was collected
by filtration, washed with benzene and recrystallized from the
suitable solvent (Table 3) to give 1-benzyl-3-N-benzyl amino-
5-aryl-2(3H)-pyrrolones (6a-c).
To a solution of hydrazides (5d-f) (0.01 mol) in 50 mL of dry
benzene, benzoyl chloride (1.5 mL, 0.01 mol) was added. The
reaction mixture was heated under reflux for 2 h. The solvent was
distilled off under reduced pressure. The yellow solid obtained
was washed thoroughly with water, drained, and recrystallized
from the suitable solvent (Table 3) to give 1-benzoyl-2-[ꢀ-N-
benzylamino-ꢁ-aroyl]propionylhydrazines (5j-l).
General Procedure for the Ring Closure of Compounds (5a-f).
A solution of (5a-f) (1 g) in a mixture of (HCl-CH3COOH) (1:1)
(30 mL) or ethanol (30 mL), was heated under reflux for 1 h and
then left to cool. The solid obtained was collected by filtration,
washed with water and recrystallized from a suitable solvent (Table
3) to give 1-benzyl-3-N-benzylamino-5-aryl-2(3H)-pyrrolone
(6a-c) in case of (5a-c), 6-aryl-4-N-benzylamino-4,5-dihydropyri-
dazin-3(2H)-ones (8a-c) in case of 5d-f (Table 4).
General Procedure for the Conversion of the Amides (5a-c) into
Isothiazolones (7a-c).
A mixture of N-benzylamide derivatives (5a-c) (0.001 mol)
and thionyl chloride (20 mL, 0.17 mol) was stirred at rt for 24 h.
The excess thionyl chloride was then evaporated under vacuum.

962
K. A. Kandeel, A. S. A. Youssef, W. S. I. Abou-Elmagd, and A. I. Hashem
Vol 43
[4] A. Tsolomitis and C. Sandaris, J. Heterocyclic Chem., 20,
1545(1983).
General Procedure for the Ring Closure of Diaroylhydrazines (5j-l).
Phosphorus oxychloride (10 mL, 0.065 mol) was added
dropwise to 1 g of the diaroylhydrazines (5j-l). The reaction
mixture was refluxed for 20 min, left to cool, and poured onto
crushed ice. The solid obtained was collected by filtration,
washed with water and recrystallized from a suitable solvent
(Table 4) to give 2-aryl-5-[ꢀ-N-benzylamino-ꢁ-benzoyl]ethyl-
1,3,5-oxadiazoles (9a-c).
[5] A. Tsolomitis and C. Sandaris, Heterocycles, 25, 569 (1987).
[6] A. I. Hashem and M. F. Shaban, J. Prakt. Chem., 323, 164 (1981).
[7] G. Kollenz, G. Penn, R. Theuer, W. M. F. Fabian, H. A. Abd
El-Nabi, X. Zhang, K. Peters, E. M. Peters, and H. G. Vonschnering,
Tetrahedron, 52, 5427 (1996).
[8] S. A. El-Assiery and M. A. El-Haiza, Egypt J. Chem.,41,
339(1998).
[9] K. R. Gopidas, B. B. Lokray, S. Rajahurai, R. K. Das, and M.
V. George, J. Org. Chem., 52, 2831 (1987).
Ring Closure of the Semicarbazide Derivatives.
[10] A. Y. Soliman and A. I. Attia, Indian J. Chem., 36B, 75
(1997).
A solution of 2 N NaOH (40 mL, 0.08 mol) was added to the
semicarbazide derivatives (5g-i) (0.01 mol). The reaction mixture
was refluxed for 2 h, filtered while hot and acidified with
hydrochloric acid, diluted with 60 mL of water. The solid formed
was collected by filtration, washed with water and recrystallized
from the suitable solvent (Table 4) to give 3-(ꢀ-N-benzylamino-ꢁ-
aroyl)ethyl-4,5-dihydro-1,2,4-triazol-5-ones (10a-c).
[11] H. A. Derbala, Abdel-Sattar S. Hamad, Waleed A. El-Said,
and A. I. Hashem, Phosphorus, Sulfur and Silicon, 175, 153 (2001).
[12] A. Sammour, M. Selim, A. F. Fahmy, A. A. Nada, and I. A.
Abd-Elmawgond, Egypt J. Chem., 19, 801 (1976).
[13] M. A. Ahmed, A. I. Hashem and N. Iskandar, Rev. Roum.
Chem., 38, 79 (1993).
[14] R. J. S. Beer and D. Wright, Tetrahedron, 37, 3967 (1981).
[15] M. V. Curran, J. Med. Chem., 17, 273 (1974).
[16] G. Nannini, G. Biasoli, E. Perrone, A. Forgione, A.
Buttinoni, and M. Ferrari, Eur. J. Med. Chem. Chim. Ther., 14, 53
(1979).
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