Synthesis, analgesic and anti-inflammatory activity of 4-(2-phenoxyphenyl) semicarbazones

Article abstract of DOI:10.1002/ardp.200700045

A series of 4-(2-phenoxyphenyl)semicarbazones was synthesized and evaluated for their analgesic and anti-inflammatory activities. Several compounds (e.g. 10h, 10i, and 11i) were found to be more potent than the reference drug mefenamic acid in the formalin test. Based on the results of an anti-inflammatory study, 1-(1-(2,5-dimethoxyphenyl)ethylidene)-4-(2- phenoxyphenyl)semicarbazide 11i was the most active compound.

Full text of DOI:10.1002/ardp.200700045

Arch. Pharm. Chem. Life Sci. 2007, 340, 409–415
A. Rineh et al.
409
Full Paper
Synthesis, Analgesic and Anti-Inflammatory Activity of
4-(2-Phenoxyphenyl)semicarbazones
Ardeshir Rineh1, Nosratollah Mahmoodi1, Mohammad Abdollahi2, Alireza Foroumadi3,
Maedeh Sorkhi3, and Abbas Shafiee3
1 Department of Chemistry, University of Guilan, Rasht, Iran
2 Department of Pharmacology and Toxicology, Faculty of Pharmacy and Pharmaceutical Sciences Research
Center, Tehran University of Medical Sciences, Tehran, Iran
3 Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center,
Tehran University of Medical Sciences, Tehran, Iran
A series of 4-(2-phenoxyphenyl)semicarbazones was synthesized and evaluated for their analgesic
and anti-inflammatory activities. Several compounds (e.g. 10h, 10i, and 11i) were found to be
more potent than the reference drug mefenamic acid in the formalin test. Based on the results
of an anti-inflammatory study, 1-(1-(2,5-dimethoxyphenyl)ethylidene)-4-(2-phenoxyphenyl)semi-
carbazide 11i was the most active compound.
Keywords: Analgesic activity / Anti-inflammatory activity / Semicarbazones /
Received: March 6, 2007; accepted: June 12, 2007
DOI 10.1002/ardp.200700045
Introduction
Non steroidal anti-inflammatory drugs (NSAID's) are
widely used in the treatment of pain and inflammation.
NSAID's reduce the pain and swelling associated with
arthritis by blocking the metabolism of arachidonic acid
(AA) through the enzyme cyclooxygenase (COX) and
thereby the production of prostaglandins, e.g. PGE2,
which sensitizes nociceptors at nerve fiber terminals
[1, 2].
Additionally, the 5-lipoxygenase (5-LO) products such
as leukotriene B4 (LTB4) also contributes to the hyperalge-
sia seen during inflammation by decreasing the mechan-
ical and thermal thresholds of C fibers [3]. Leukotrienes,
especially LTB4 together with prostaglandins are impli-
cated in the acute ulceration induced by NSAID's [4]. For
these reasons, compounds that achieve dual inhibition
Figure 1. Structures of hydrazones 1–4.
of the enzymes COX and 5-LO reduce side effects and
improved the efficacy in the combat of pain in inflamma-
tory diseases [5]. Compound 1 (Fig. 1) was described as a
dual COX/5-LO inhibitor [6, 7]. Furthermore, there are sev-
eral reports about the synthesis and pharmacological
evaluation of new bioactive N-aroylarylhydrazones act-
ing at the AA cascade enzyme level (Fig. 1, compounds 2–
4) [8–10]. As a part of our ongoing research program [11–
13] to find novel anti-inflammatory and analgesic com-
pounds, herein, we describe the synthesis, analgesic and
anti-inflammatory activity of 4-(2-phenoxyphenyl)semi-
carbazones.
Correspondence: Abbas Shafiee, Department of Medicinal Chemistry,
Faculty of Pharmacy and Pharmaceutical Sciences Research Center,
Tehran University of Medical Sciences, Tehran, 14174 Iran.
E-mail: ashafiee@ams.ac.ir
Fax: +98 21 664-61178
Abbreviations: arachidonic acid (AA), cyclooxygenase (COX); leuko-
triene B4, (LTB4); 5-lipoxygenase (5-LO); non steroidal anti-inflammatory
drugs (NSAID's)
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410
A. Rineh et al.
Arch. Pharm. Chem. Life Sci. 2007, 340, 409–415
Table 1. Physical properties of compounds 10a–j and 11a–j.
Compound R
No.
X
Mp.
(8C)
Yield
(%)
Formulaa)
10a
10b
10c
10d
10e
10f
10g
10h
10i
H
H
H
H
H
H
H
H
H
H
2-Cl
3-Cl
4-Cl
2-OH
3-OH
4-OH
2-NO2
3-NO2
4-NO2
4-Me
150–152 85
160–162 75
189–190 80
202–204 60
197–200 55
194–196 55
160–162 85
175–177 80
235–236 80
187–189 90
214–216 75
240–243 70
236–238 70
166–168 70
210–212 65
214–216 65
198–200 60
215–217 60
C20H16ClN3O2
C20H16ClN3O2
C20H16ClN3O2
C20H17N3O3
C20H17N3O3
C20H17N3O3
C20H16N4O4
C20H16N4O4
C20H16N4O4
C21H19N3O2
C21H18N4O4
C21H18N4O4
C21H18N4O4
C21H18ClN3O2
C21H18ClN3O2
C21H18ClN3O2
C21H18BrN3O2
C21H18BrN3O2
C23H23N3O4
C22H21N3O3
Reagents and conditions: (i) SOCl2, C6H6/reflux, 3 h; (ii) NaN3 /PhN(Et)2, C6H6; (iii)
C6H6D/; (iv) NH2NH26H2O, diethyl ether/r.t.; (v) substituted benzaldehyde, EtOH; (vi)
substituted acetophenone, EtOH.
Scheme 1 Synthesis route of compounds 5–11.
10j
11a
11b
11c
11d
11e
11f
11g
11h
11i
CH3 2-NO2
CH3 3-NO2
CH3 4-NO2
CH3 2-Cl
CH3 3-Cl
CH3 4-Cl
CH3 3-Br
CH3 4-Br
Chemistry
The designed compounds were synthesized according to
Scheme 1. Reaction of 2-phenoxybenzoic acid 5 with thi-
onyl chloride followed by sodium azide afforded azido(2-
phenoxyphenyl)methanone 7. Heating of compound 7 in
dry benzene gave 2-phenoxybenzeneisocyanate 8 as an
intermediate. Reaction of hydrazine hydrate with com-
pound 8 afforded 4-(2-phenoxyphenyl)semicarbazide 9 in
high yield. Reaction of compound 9 with various benzal-
dehydes and acetophenones in ethanol yielded the corre-
sponding semicarbazones 10 and 11, respectively
(Table 1).
CH3 2,5-OMe 166–168 55
CH3 4-OMe 176–178 70
11j
a)
All compounds were analyzed for C, H, N. Analytical results
obtained for these elements were within l 0.4% of the calcu-
lated value for the formula shown.
(5% w/v) 30 min before formalin injection. Mefenamic
acid (Hakim Pharmaceutical Co., Tehran, Iran) (30 mg/kg,
ip.) was used as standard drug under the same condi-
tions. The control group received vehicle (0.2 mL/20g, ip.)
alone.
Pharmacology
All the tested compounds were initially dissolved in
DMSO and diluted with H2O. The final concentration of
DMSO was 5%. Male NMRI mice weighing 20–25 g and
male Wistar rats weighing 200–250 g (from the animal
house of the Faculty of Pharmacy, TUMS) were used for
the formalin test and the carrageenan-induced paw
edema, respectively. The animals were housed in colony
cages, conditions of constant temperature (22 l 28C), a
12 h light/dark schedule, and allowed free access to
standard diet and tap water except during the experi-
ment. The animals were allowed to habituate to the labo-
ratory environment for 2 h before the experiments were
initiated. All ethical manners for use of laboratory ani-
mals were considered carefully and the protocol of study
was approved by TUMS ethical committee. The com-
pounds were administered intraperitoneally (ip.) (30 mg/
kg; 0.2 mL/20g) as a suspension in saline and tween 80
Formalin-induced test
All final compounds (10 and 11) were tested in the for-
malin-induced pain test. Twenty-five microliters of for-
malin (0.5%) was injected subcutaneously into the dorsal
surface of the right hind paw of the mouse using a micro
syringe with a 26-gauge needle. Immediately after the for-
malin injection, animals were placed individually in
glass cylinder (20 cm wide, 25 cm long) and a glass door
and a mirror were arranged at a 458 angle under the cyl-
inder to allow clear observation of the paws of the ani-
mals. The total time in seconds that the animal spent
licking or biting the injected paw during the period of
0–10 min was considered as indicator of neurogenic
pain (early phase) and during the 10–30 min (late phase)
represented the inflammatory pain [14].
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Arch. Pharm. Chem. Life Sci. 2007, 340, 409–415
4-(2-Phenoxyphenyl)semicarbazones
411
Table 2. Analgesic activity of 4-(2-phenoxyphenyl)semicarba-
zones.
Anti-inflammatory activity
The anti-inflammatory activity was determined in vivo
using the carrageenan-induced rat paw edema test
[10, 15]. A solution of 0.1 mL of 1% carrageenan (Sigma-
Aldrich, Dorset, UK) in saline was injected subplantarly
in the right hind paw of the rats 1 h after ip. administra-
tion of the compounds. The paw thickness was measured
from the ventral to the dorsal surfaces using a dial cali-
per immediately prior to carrageenan injection and then
at each hour, up to 4 h after the subplantar injection. The
edema was calculated as the thickness variation between
the carrageenan- and saline-treated paw. Anti-inflamma-
tory activity was expressed as percent of inhibition of the
edema when compared with the control group.
Compound Dose
(mg/kg)a)
Nociception Inhibition Relative
(mean l SEM) (%)b)
Activityc)
Control
–
83 l 6.72
–
–
Mefenamic 30
acid
34.75 l 2.66 58.13
1**
10a
10b
10c
10d
10e
10f
10g
10h
10i
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
32.5 l 5.12 60.84
32 l 4.41 61.44
35 l 5.58 57.83
40 l 4.46 51.80
38 l 5.21 54.21
1.04**
1.05**
0.99**
0.89**
0.93**
0.05
80.5 l 7.59
3.01
25 l 7.26 69.88
12.5 l 4.48 84.93
14 l 3.10 83.13
1.20**
1.46**
1.43**
0.93**
1.10*
1.26**
1.25**
0.97*
0.83**
1.06*
1.29**
1.01*
1.37**
0.68*
10j
38 l 3.24 54.21
11a
11b
11c
11d
11e
11f
11g
11h
11i
29.75 l 5.80 64.15
22.25 l 7.05 73.19
22.50 l 4.53 72.89
36 l 10.52 56.62
42.75 l 3.81 48.49
31.75 l 6.30 61.75
Statistics
The results are expressed as the mean l SEM of four ani-
mals per group. The data were statistically analyzed by
one-way analysis of Variance (ANOVA) followed by Tukey
multi-comparison test. Differences with P a 0.05 between
experimental groups were considered statistically signifi-
cant.
20.5 l 3.2
75.30
34.25 l 11.27 58.73
16.5 l 2.33 80.12
50.0 l 13.52 39.75
11j
a)
Number of animals in each group n = 4.
Percentage if inhibition obtained by comparison with vehicle
control group.
Analgesic activity relative to mefenamic acid. * and ** differed
from control group P a 0.05 and P a 0.01, respectively.
b)
c)
Results and discussion
The analgesic effects of aldehyde and acetophenone semi-
carbazones 10a–10j and 11a–11j are shown in Table 2.
As it could be seen from Table 2, all compounds except
10f showed significant reduction of formalin-induced
nociception. This effect was comparable or better than
the reference drug mefenamic acid. In aldehyde series,
compounds 10g, 10h, and 10i were more potent that
mefenamic acid. In this series, all isomeric nitrophenyl
analogues were active and the order of analgesic activity
was 3-NO2 F 4-NO2 A 2-NO2. The same order of analgesic
activity was observed in the nitro-analogues of acetophe-
none series, compounds 11b, 11c, and 11a. In addition, it
seems that OH substituent caused the decrease or elimi-
nation of activity, compounds 10d, 10e and 10f. All halo-
genated derivatives, 11d–11h also showed moderate
analgesic activity. In the acetophenone series, com-
pounds 11a, 11b, 11c, 11g, and 11i were more active than
mefenamic acid and the order of activity was 11i A 11g A
11b A 11c A 11a. In general, aldehydes were more active
than ketones. The anti-inflammatory activity of the syn-
thesized compounds is summarized in Table 3. Compari-
son of the anti-inflammatory activity of all tested com-
pounds revealed that compound 11i was the most active
compound in both aldehyde and acetophenone semicar-
bazone series. As can be seen from Table 3, both, 3-nitro
phenyl analogues of aldehyde or acetophenone, 10h and
11b, were also potent anti-inflammatory agents in com-
parison to indomethacin as the reference drug. Among
aldehydes, the tested compounds 10g, 10h, and 10i
showed significant anti-inflammatory activity. The most
active compound was 10h which was comparable to indo-
methacin as the reference drug. Among acetophenones,
compounds 11b, 11g, and 11i showed a significant anti-
inflammatory effect. Compound 11i was the most potent
in this series. In contrast to the good analgesic activity of
halogenated derivatives, all halogenated analogues,
except 11g, showed no anti-inflammatory activity. In
summary, the analgesic activity of the synthesized com-
pounds was better than anti-inflammatory activity.
Experimental
Chemicals were purchased from Merck Chemical Company
(Darmstadt, Germany). Melting points were taken on a Kofler
hot stage apparatus (Reichert, Vienna, Austria) and are uncor-
rected. 1H-NMR spectra were obtained using a Brucker FT-80 and
a Brucker FT-500 spectrometer (Brucker, Rheinstetten, Ger-
many). Tetramethylsilane was used as an internal standard.
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412
A. Rineh et al.
Arch. Pharm. Chem. Life Sci. 2007, 340, 409–415
Table 3. Anti-inflammatory activity of 4-(2-phenoxyphenyl)semi-
Table 3. Continued
carbazones.
Compound
Time
(h)
Dose
Thickness var- Inhibition
Compound
Time
(h)
Dose
Thickness var- Inhibition
(mg/kg)a) iation (mm)b) (%)c)
(mg/kg)a) iation (mm)b) (%)c)
11e
1
2
3
4
30
30
30
30
0.90 l 0.09
1.38 l 0.10
1.66 l 0.10
1.67 l 0.06
–12.5
14.81
–6.74
–9.86
Control
1
2
3
4
–
–
–
–
0.8 l 0.24
1.62 l 0.09
1.78 l 0.15
1.52 l 0.27
–
–
–
–
11f
11g
11h
11i
1
2
3
4
30
30
30
30
0.77 l 0.12
1.19 l 0.15
1.34 l 0.1
3.75
26.54
24.72
23.68
Indomethacin
1
2
3
4
30
30
30
30
0.58 l 0.45
0.94 l 0.43
0.81 l 0.33
0.36 l 0.25
7.5*
41.98**
54.49**
76.32**
1.16 l 0.04
1
2
3
4
30
30
30
30
0.64 l 0.10
0.82 l 0.05
0.78 l 0.08
0.71 l 0.05
20.0*
10b
10c
10g
10h
10i
1
2
3
4
30
30
30
30
1.12 l 0.49
1.48 l 0.44
2.1 l 0.26
–40.0
8.65
–17.97
–28.29
49.38**
56.18**
53.29**
1.95 l 0.34
1
2
3
4
30
30
30
30
0.96 l 0.10
1.57 l 0.14
1.90 l 0.09
1.93 l 0.13
–20
3.08
–6.74
–26.97
1
2
3
4
30
30
30
30
0.87 l 0.37
1.59 l 0.51
2.23 l 0. 66
2.27 l 0. 59
–8.75
1.85
–25.28
–49.34
1
2
3
4
30
30
30
30
0.46 l 0.04
0.65 l 0.04
0.63 l 0.04
0.55 l 0.03
42.5**
1
2
3
4
30
30
30
30
0.68 l 0.17
0.93 l 0.17
0.88 l 0.23
0.93 l 0.45
15.0*
59.88**
64.61**
63.82**
42.60**
50.56**
38.82**
11j
1
2
3
4
30
30
30
30
1.13 l 0.48
1.51 l 0.43
2.18 l 0.34
1.96 l 0.33
–41.25
6.79
–22.47
–28.94
1
2
3
4
30
30
30
30
0.52 l 0.07
0.68 l 0.05
0.67 l 0.16
0.58 l 0.2
35.0*
58.02**
62.36**
61.84**
a)
Number of animals in each group n = 4.
b)
1
2
3
4
30
30
30
30
0.66 l 0.26
0.96 l 0.40
0.91 l 0.29
0. 88 l 0.19
17.5*
Thickness variation is the difference between the thickness
of the carrageenan-treated paw and the saline-treated paw.
Percentage of inhibition obtained by comparison with the
vehicle. * and ** differed from control group P a 0.05 and P a
0.01, respectively.
40.74**
48.88**
42.11**
c)
10j
1
2
3
4
30
30
30
30
1.02 l 0.13
1.55 l 0.24
1.74 l 0.22
1.67 l 0.32
–27.5
4.32
2.24
Mass spectra were obtained using a Finnigan Mat TSQ-70 spec-
trometer at 70 eV (Finnigan Mat, Bremen, Germany). The IR spec-
tra were obtained using Nicolet FT-IR Magna 550 spectrographs
(KBr disks) (Nicolet, Madison, WI, USA). The purity of compounds
was confirmed by TLC using different mobile phases. The results
of the elemental analyses (C, H, N) were within l 0.4% of theoret-
ical values for C, H and N.
–9.87
11a
11b
11c
11d
1
2
3
4
30
30
30
30
0.75 l 0.11
1.16 l 0.13
1.24 l 0.09
1.14 l 0.03
6.25
28.39
30.34
25.00
1
2
3
4
30
30
30
30
0.53 l 0.11
0.83 l 0.10
0.82 l 0.15
0.67 l 0.11
33.75*
48.77**
53.93**
55.92**
2-Phenoxybenzoyl chloride 6
To a stirring solution of 2-phenoxybenzoic acid 5 (1 mmol) in
benzene (50 mL), thionyl chloride (2 mmol) was added. The reac-
tion contents were heated under reflux for 3 h and the solvent
was removed under reduced pressure. The residue was crystal-
lized from n-heptane to give compound 6. Yield 85%; mp. 35–
88C. IR (KBr): m cm– 1 1774 (C=O). 1H-NMR (CDCl3): d = 7.85 (dd, J =
7.8, 1.7 Hz, 1H, H6), 7.59 (dt, J = 7.8, 1.7 Hz, 1H, H4), 7.34 (t, J =
7.8 Hz, 2H, H39, H59), 7.29 (t, J = 7.8 Hz, 1H, H49), 7.07 (t, J = 7.8 Hz,
1H, H5), 7.06 (d, J = 7.8 Hz, 1H, H3), 6.89 (d, J = 7.8 Hz, 2H, H29, H69).
MS: m/z (%) 234 [M++2] (5), 232 [M+] (15), 196 (100), 192 (20), 167
(10), 114 (25), 76 (85), 49 (60). Anal. Calcd. for C13H9ClO2: C, 67.11;
H, 3.90. Found: C, 66.93; H, 3.98.
1
2
3
4
30
30
30
30
0.86 l 0.05
1.21 l 0.06
1.48 l 0.04
1.47 l 0.11
–7.5
25.30
16.85
3.28
1
2
3
4
30
30
30
30
1.10 l 0.23
1.50 l 0.10
1.72 l 0.11
1.53 l 0.35
–37.5
7.40
3.37
–0.65
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Arch. Pharm. Chem. Life Sci. 2007, 340, 409–415
4-(2-Phenoxyphenyl)semicarbazones
413
7.6 Hz, 1H, H699), 7.61 (d, J = 7.6 Hz, H499), 7.56 (t, J = 7.6 Hz, 1H, H599),
7.44 (t, J = 7.5 Hz, 2H, H39, H59), 7.39 (t, J = 8.1 Hz, 1H, H4), 7.22 (t, J =
8.1 Hz, 1H, H5), 7.11 (t, J = 7.5 Hz, 1H, H49), 7.09 (d, J = 7.5 Hz, 2H,
H29, H69), 7.04 (d, J = 8.1 Hz, 1H, H3). MS: m/z (%) 367 [M++2] (32), 365
[M+] (100), 308 (10), 255 (15), 211 (55), 185 (75), 136 (55), 93 (20),
83 (15). Anal. Calcd. for C20H16ClN3O2: C, 65.67; H, 4.41; N, 11.49.
Found: C, 65.59; H, 4.30; N, 11.61.
Azido(2-phenoxyphenyl)methanone 7
To a stirring solution of 2-phenoxybenzoyl chloride (2.32 g,
0.01 mol) in benzene (30 mL) at –58C was added a solution of
sodium azide (0.65 g, 0.01 mol) in water (24 mL) and N,N-diethy-
lanilline (1.49 g, 0.01 mol). After the addition was completed,
the mixture was stirred at room temperature overnight. The
organic layer was washed with 10% aqueous hydrochloric acid,
10% sodium carbonate solution and water. The organic layer
was dried (Na2SO4) and filtered. The solvent was evaporated and
the residue was crystallized from absolute ethanol to give 1.91 g
of 7 (80%); mp. 53–558C. IR (KBr): m max cm– 1 2136 (N3), 1716
(C=O).1H-NMR (CDCl3): d = 7.85 (d, J = 7.7 Hz, 1H, H6), 7.41-6.68 (m,
8H, aromatic). MS: m/z (%) 239 [M+] (25), 211 (10), 183 (100), 76
(85). Anal. Calcd. for C13H9N3O2: C, 65.27; H, 3.79; N, 17.56. Found:
C, 65.18; H, 3.99; N, 17.72.
1-(4-Chlorobenzylidene)-4-(2-
phenoxyphenyl)semicarbazide 10c
Mp. 189–1908C. IR (KBr) m: max cm– 1 3354 (NH), 1690 (C=O). 1H-
NMR (DMSO-d6): d = 11.04 (s, 1H, NH), 8.66 (bs, 1H, NH), 8.28 (d, J =
7.8 Hz, 1H, H6), 7.93 (s, 1H, HC=N), 7.91 (d, J = 8.5 Hz, 2H, H299, H699),
7.59 (d, J = 8.5 Hz, 2H, H399, H599), 7.43 (t, J = 7.6 Hz, 2H, H39, H59), 7.24
(t, J = 7.8 Hz, 1H, H4), 7.13 (t, J = 7.6 Hz, 1H, H49), 7.11 (t, J = 7.8 Hz,
1H, H5), 7.10 (d, J = 7.8 Hz, 1H, H3), 7.02 (d, J = 7.6 Hz, 2H, H29, H69).
MS: m/z (%) 367 [M++2] (21), 365 [M+] (65), 272 (30), 210 (25), 185
(45), 176 (90), 153 (60), 119 (100), 109 (55), 93 (40), 82 (10). Anal.
Calcd. for C20H16ClN3O2: C, 65.67; H, 4.41; N, 11.49. Found: C,
65.35; H, 4.56; N, 11.71.
4-(2-Phenoxyphenyl)semicarbazide 9
A solution of compound 7 (2.39 g, 0.01 mol) in benzene (10 mL)
was refluxed and the progress of the reaction was followed by
TLC. After the rearrangement was complete (about 2 h) the sol-
vent was evaporated. The residue was dissolved in diethyl ether
(20 mL) and hydrazine hydrate (500 mg, 0.01 mol) was added to
it. The mixture was stirred for 4 h at room temperature. The
white solid was filtered and crystallized from ethanol to give
2.31 g of 9 (95%); mp. 124–1258C. IR (KBr): m max cm– 1 3243,
3350 (NH2), 1678 (C=O). 1H-NMR (CDCl3): d = 8.95 (bs, 1H, NH), 8.31
(d, J = 7.8 Hz, 1H, H6), 7.69 (s, 1H, NH), 7.39 (dt, J = 7.6, 0.8 Hz, 2H,
H39, H59), 7.14 (t, J = 7.6 Hz, 1H, H49), 7.10 (t, J = 7.8 Hz, 1H, H4), 7.00
(dd, J = 7.6, 0.8 Hz, 2H, H29, H69), 6.93 (t, J = 7.8 Hz, 1H, H5), 6.88 (d, J
= 7.8 Hz, 1H, H3), 4.48 (bs, 2H, NH2). MS: m/z (%) 243 [M+] (95), 211
(100), 168 (30), 154 (55), 128 (32), 77 (85). Anal. Calcd. for
C13H13N3O2: C, 64.19; H, 5.39; N, 17.27. Found: C, 64.28; H, 5.25;
N, 17.09.
1-(2-Hydroxybenzylidene)-4-(2-
phenoxyphenyl)semicarbazide 10d
Mp. 202–2048C. IR (KBr): m max cm– 1 3416 (OH), 3331 (NH), 1685
(C=O). 1H-NMR (DMSO-d6): d = 10.88 (s, 1H, NH), 10.05 (bs, 1H, OH),
8.71 (bs, 1H, NH), 8.31 (d, J = 8.4 Hz, 1H, H6), 8.20 (s, 1H, HC=N),
7.41 (t, J = 7.7 Hz, 2H, H39, H59), 7.30 (d, J = 7.7 Hz, 1H, H699), 7.22 (t, J
= 8.4 Hz, 1H, H4), 7.19 (dd, J = 8.2, 7.7 Hz, 1H, H499), 7.13 (t, J =
7.7 Hz, 1H, H49), 7.08 (t, J = 8.4 Hz, 1H, H5), 7.07 (t, J = 8.4 Hz, 1H,
H3), 7.02 (d, J = 7.7 Hz, 2H, H29, H69), 6.86 (d, J = 8.2 Hz, 1H, H399), 6.77
(t, J = 7.7 Hz, 1H, H599). MS: m/z (%) 347 [M+] (30), 272 (25), 295 (27),
239 (40), 212 (12), 185 (60), 135 (100), 106 (35), 77 (30). Anal.
Calcd. for C20H17N3O3: C, 69.15; H, 4.93; N, 12.10. Found: C, 69.32;
H, 4.87; N, 12.04.
General procedure for the preparation of compounds
10a–j and 11a–j
1-(3-Hydroxybenzylidene)-4-(2-
phenoxyphenyl)semicarbazide 10e
To a stirring solution of aldehyde or ketone (0.01 mol) in abso-
lute ethanol (25 mL) compound 9 (2.43 g, 0.01 mol) was added.
The progress of the reaction was followed by TLC. After the com-
pletion of the reaction, the precipitate was filtered and the resi-
due was crystallized from a suitable solvent.
Mp. 197–2008C. IR (KBr): m max cm– 1 3397 (OH), 3336 (NH), 1678
(C=O). 1H-NMR (DMSO-d6): d = 10.91 (s, 1H, NH), 9.58 (bs, 1H, OH),
8.68 (s, 1H, NH), 8.30 (d, J = 8.2 Hz, 1H, H6), 7.80 (s, 1H, HC=N),
7.46 (d, J = 7.8 Hz, 1H, H699), 7.41 (t, J = 7.6 Hz, 2H, H39, H59), 7.22 (t, J
= 8.2 Hz, 1H, H4), 7.16 (t, J = 7.8 Hz, 1H, H599), 7.11 (t, J = 7.6 Hz, 1H,
H49), 7.09 (t, J = 8.2 Hz, 1H, H5), 7.07 (d, J = 8.2 Hz, 1H, H3), 7.04 (d, J
= 7.6 Hz, 2H, H29, H69), 6.94 (s, 1H, H299), 6.88 (d, J = 7.8 Hz, 1H, H499).
MS: m/z (%) 347 [M+] (30), 272 (20), 239 (100), 211 (40), 185 (50),
136 (85), 134 (40), 120 (20), 77 (98). Anal. Calcd. for C20H17N3O3: C,
69.15; H, 4.93; N, 12.10. Found: C, 69.02; H, 4.96; N, 11.89.
1-(2-Chlorobenzylidene)-4-(2-
phenoxylphenyl)semicarbazide 10a
Mp. 150–1528C. IR (KBr): m max cm– 1 3365 (NH), 1695 (C=O). 1H-
NMR (DMSO-d6): d = 11.19 (bs, 1H, NH), 8.70 (bs, 1H, NH), 8.28 (d, J
= 7.6 Hz, 1H, H6), 8.27 (s, 1H, HC=N), 7.53 (d, J = 7.6 Hz, 1H, H699),
7.49 (d, J = 7.6 Hz, 1H, H399), 7.41 (t, J = 7.6 Hz, 3H, H39, H59, H599), 7.32
(t, J = 7.6 Hz, 1H, H499), 7.23 (t, J = 7.6 Hz, 1H, H4), 7.12 (t, J = 7.6 Hz,
1H, H49), 7.11 (t, J = 7.6 Hz, 1H, H5), 7.09 (d, J = 7.6 Hz, 1H, H3), 7.02
(d, 2H, J = 7.6 Hz, H29, H69). MS: m/z (%) 367 [M++2] (35), 365 [M+]
(100), 330 (45), 275 (20), 216 (60), 211 (28), 184 (98), 152 (75), 135
(50), 119 (95), 109 (80), 93 (65). Anal. Calcd. for C20H16ClN3O2: C,
65.67; H, 4.41; N, 11.49. Found: C, 65.82; H, 4.36; N, 11.78.
1-(4-Hydroxybenzylidene)-4-(2-
phenoxyphenyl)semicarbazide 10f
Mp. 194–1968C. IR (KBr): m max cm– 1 3457 (OH), 3344 (NH), 1670
(C=O). 1H-NMR (DMSO-d6): d = 10.76 (s, 1H, NH), 9.85 (s, 1H, OH),
8.69 (s, 1H, NH), 8.32 (d, J = 8.2 Hz, 1H, H6), 7.78 (s, 1H, HC=N),
7.41 (t, J = 7.6 Hz, 2H, H39, H59), 7.24 (d, J = 8.6 Hz, 2H, H299, H699), 7.25
(t, J = 7.7 Hz, 1H, H4), 7.13 (dd, J = 8.2, 7.7 Hz, 1H, H5), 7.10 (d, J =
7.7 Hz, 1H, H3), 7.09 (t, J = 7.6 Hz, 1H, H49), 7.02 (d, J = 7.6 Hz, 2H,
H29, H69), 6.75 (d, J =8.6 Hz, 2H, H399, H599). MS: m/z (%) 347 [M+] (5), 239
(15), 211 (50), 185 (100), 135 (25), 77 (20). Anal. Calcd. for
C20H17N3O3: C, 69.15; H, 4.93; N, 12.10. Found: C, 68.82; H, 5.09;
N, 12.45.
1-(3-Chlorobenzylidene)-4-(2-
phenoxyphenyl)semicarbazide 10b
Mp. 160–1628C. IR (KBr): m max cm– 1 3365 (NH), 1685 (C=O). 1H-
NMR (DMSO-d6): d = 11.10 (s, 1H, NH), 8.72 (bs, 1H, NH), 8.27 (d, J =
8.1 Hz, 1H, H6), 7.94 (s, 1H, HC=N), 7.88 (s, 1H, H299), 7.86 (d, J =
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Arch. Pharm. Chem. Life Sci. 2007, 340, 409–415
6.97 (d, J = 7.6 Hz, 1H, H3), 6.85 (d, J = 7.6 Hz, 2H, H29, H69), 2.18 (s,
3H, CH3). MS: m/z (%) 390 [M+] (65), 297 (7), 212 (97), 188 (100), 168
(11), 157 (18), 149 (61), 132 (98), 105 (45), 91 (44), 76 (75), 65 (25),
51 (39), 43 (39). Anal. Calcd. for C21H18N4O4: C, 64.61; H, 4.65; N,
14.35. Found: C, 64.52; H, 4.49; N, 14.23.
1-(2-Nitrobenzylidene)-4-(2-
phenoxyphenyl)semicarbazide 10g
Mp. 160–1628C. IR (KBr): m max cm– 1 3385 (NH), 1695 (C=O),
1531, 1337 (NO2), 1H-NMR (DMSO-d6): d = 11.29 (s, 1H, NH), 8.67 (s,
1H, NH), 8.31 (s, 1H, HC=N), 8.26 (dd, J = 7.6, 1.4 Hz, 1H, H6), 8.04
(d, J = 8.0 Hz, 1H, H399), 7.70 (t, J = 8.0 Hz, 1H, H599), 7.67 (d, J =
8.0 Hz, 1H, H699), 7.63 (t, J = 8.0 Hz, 1H, H499), 7.39 (t, J = 7.6 Hz, 2H,
H39, H59), 7.23 (dt, J = 7.6, 1.4 Hz, 1H, H4), 7.12 (t, J = 7.6 Hz, 1H, H49),
7.09 (d, J = 7.6 Hz, 1H, H3), 7.08 (t, J = 7.6 Hz, 1H, H5), 7.02 (d, J =
7.6 Hz, 2H, H29, H69). MS: m/z (%) 376 [M+] (15), 298 (70), 251 (25),
211 (85), 185 (100), 108 (18), 77 (20). Anal. Calcd. for C20H16N4O4:
C, 63.82; H, 4.28; N, 14.89. Found: C, 64.12; H, 4.49; N, 14.71.
1-(1-(3-Nitrophenyl)ethylidene)-4-(2-
phenoxyphenyl)semicarbazide 11b
Mp. 240–2438C. IR(KBr): m max cm– 1 3365 (NH), 1695 (C=O),
1536, 1347 (NO2). 1H-NMR (DMSO-d6): d = 10.32 (s, 1H, NH), 8.94 (s,
1H, NH), 8.42 (s, 1H, H299), 8.32 (d, J = 7.8 Hz, 1H, H6), 8.21 (d, J =
7.8 Hz, 1H, H499), 8.00 (d, J = 7.8 Hz, 1H, H699), 7.60 (t, J = 7.8 Hz, 1H,
H599), 7.35 (t, J = 7.7 Hz, 2H, H39, H59), 7.20 (t, J = 8.0 Hz, 1H, H4), 7.10
(t, J = 8.0 1H, H5), 7.09 (d, J = 8.0 Hz, 1H, H3), 7.06 (t, J = 7.7 Hz, 1H,
H49), 7.01 (d, J = 7.7 Hz, 2H, H29, H69), 2.30 (s, 3H, CH3). MS: m/z (%)
390 [M+] (10), 389 (10), 325 (100), 310 (75), 263 (18), 212 (5), 203
(15), 162 (25), 115 (98), 74 (96). Anal. Calcd. for C21H18N4O4: C,
64.61; H, 4.65; N, 14.35. Found: C, 64.82; H, 4.59; N, 14.42.
1-(3-Nitrobenzylidene)-4-(2-
phenoxyphenyl)semicarbazide 10h
Mp. 175–1778C. IR (KBr): m max cm– 1 3283 (NH), 1685 (C=O),
1525, 1355 (NO2). 1H-NMR (DMSO-d6): d = 11.21 (s, 1H, NH), 8.72
(bs, 1H, NH), 8.42 (s, 1H, H299), 8.34 (d, J = 7.7 Hz, 1H, H6), 8.26 (d, J =
8.0 Hz, 1H, H499), 8.03 (s, 1H, HC=N), 7.88 (d, J = 8.0 Hz, 1H, H699),
7.67 (t, J = 8.0 Hz, 1H, H599), 7.37 (t, J = 7.7 Hz, 2H, H39, H59), 7.22 (t, J =
7.7 Hz, 1H, H4), 7.10 (t, J = 7.7 Hz, 1H, H49), 7.07 (d, J = 7.7 Hz, 1H,
H3), 7.05 (t, J = 8.5 Hz, 1H, H5), 7.04 (d, J = 8.5 Hz, 2H, H29, H69). MS:
m/z (%) 376 [M+] (35), 298 (85), 251 (17), 226 (5), 211 (75), 185 (100),
204 (20), 176 (98), 130 (19), 89 (20). Anal. Calcd. for C20H16N4O4: C,
63.82; H, 4.28; N, 14.89. Found: C, 63.55; H, 4.48; N, 14.62.
1-(1-(4-Nitrophenyl)ethylidene)-4-(2-
phenoxyphenyl)semicarbazide 11c
Mp. 236–2388C. IR (KBr): m max cm– 1 3375 (NH), 1695 (C=O),
1536, 1337 (NO2). 1H-NMR (DMSO-d6): d = 10.42 (s, 1H, NH), 8.99 (s,
1H, NH), 8.32 (d, J = 8.4 Hz, 2H, H399, H599), 8.22 (d, J = 7.8 Hz, 1H, H6),
7.82 (d, J = 8.4 Hz, 2H, H299, H699), 7.40 (t, J = 7.5 Hz, 2H, H39, H59), 7.22
(t, J = 7.2 Hz, 1H, H4), 7.14 (t, J = 7.5 Hz, 1H, H49), 7.07 (dd, J = 7.8,
7.2 Hz, 1H, H5), 6.98 (d, J = 7.2 Hz, 1H, H3), 6.93 (d, J = 7.5 Hz, 2H,
H29, H69), 2.33 (s, 3H, CH3). MS: m/z (%) 390 [M+] (65), 212 (100), 177
(40), 132 (30), 104 (35), 75 (98), 55 (38). Anal. Calcd. for
C21H18N4O4: C, 64.61; H, 4.65; N, 14.35. Found: C, 64.62; H, 4.32;
N, 14.08.
1-(4-Nitrobenzylidene)-4-(2-
phenoxyphenyl)semicarbazide 10i
Mp. 235–2368C. IR (KBr): m max cm– 1 3365 (NH), 1690 (C=O),
1527, 1347 (NO2). 1H-NMR (DMSO-d6): d = 11.30 (s, 1H, NH), 8.71 (s,
1H, NH), 8.38 (d, J = 8.7 Hz, 2H, H399, H599), 8.22 (d, J = 7.8 Hz, 1H, H6),
8.17 (d, J = 8.7 Hz, 2H, H299, H699), 7.99 (s, 1H, HC=N), 7.41 (t, J =
7.8 Hz, 2H, H39, H59), 7.25 (t, J = 7.8 Hz, 1H, H4), 7.13 (t, J = 7.8 Hz,
1H, H49), 7.11 (t, J = 7.8 Hz, 1H, H5), 7.09 (d, J = 7.8 Hz, 1H, H3), 7.06
(d, J = 7.8 Hz, 2H, H29, H69). MS: m/z (%) 376 [M+] (10), 298 (65), 251
(18), 211 (8), 176 (100), 130 (20), 103 (15), 58 (8). Anal. Calcd. for
C20H16N4O4: C, 63.82; H, 4.28; N, 14.89. Found: C, 63.72; H, 4.15;
N, 14.78.
1-(1-(2-Chlorophenyl)ethylidene)-4-(2-
phenoxyphenyl)semicarbazide 11d
Mp. 166–1688C. IR (KBr): m max cm– 1 3354 (NH), 1695 (C=O). 1H-
NMR (DMSO-d6): d = 10.19 (s, 1H, NH), 8.83 (bs, 1H, NH), 8.32 (d, J =
8.0 Hz, 1H, H6), 7.48 (d, J = 7.6 Hz, 1H, H699), 7.41 (t, J = 7.6 Hz, 1H,
H599), 7.34 (t, J = 7.6 Hz, 1H, H499), 7.27 (t, J = 7.6 Hz, 2H, H39, H59), 7.26
(d, J = 7.6 Hz, 1H, H399), 7.19 (t, J = 7.7 Hz, 1H, H4), 7.08 (t, J = 7.6 Hz,
1H, H49), 7.04 (dd, J = 8.0, 7.7 Hz, 1H, H5), 7.00 (d, J = 7.7 Hz, 1H,
H3), 6.85 (d, J = 7.7 Hz, 2H, H29, H69), 2.21 (s, 3H, CH3). MS: m/z (%)
381 [M++2] (23), 379 [M+] (70), 377 (60), 287 (10), 209 (18), 188
(100), 165 (98), 131 (96), 101 (55), 75 (98), 50 (98). Anal. Calcd. for
C21H18ClN3O2: C, 66.40; H, 4.78; N, 11.06. Found: C, 66.31; H, 4.92;
N, 11.31.
1-(4-Methylbenzylidene)-4-(2-
phenoxyphenyl)semicarbazide 10j
Mp. 187–1898C. IR (KBr): m max cm– 1 3349 (NH), 1685 (C=O). 1H-
NMR (DMSO-d6): d = 10.91 (s, 1H, NH), 8.70 (bs, 1H, NH), 8.32 (d, J =
8.4 Hz, 1H, H6), 7.85 (s, 1H, HC=N), 7.43 (t, J = 7.4 Hz, 2H, H39, H59),
7.32 (d, J =7.9 Hz, 2H, H299, H699), 7.23 (t, J = 8.4 Hz, 1H, H4), 7.21 (d, J
= 7.9 Hz, 2H, H399, H599), 7.14 (t, J = 7.4 Hz, 1H, H49), 7.09 (t, J = 8.4 Hz,
1H, H5), 7.07 (d, J = 8.4 Hz, 1H, H3), 7.02 (d, J = 7.4 Hz, 2H, H29, H69),
2.33 (s, 3H, CH3). MS: m/z (%) 345 [M+] (15), 344 (18), 212 (25), 185
(15), 132 (100), 109 (15). Anal. Calcd. for C21H19N3O2: C, 73.03; H,
5.54; N, 12.17. Found: C, 72.83; H, 5.69; N, 12.32.
1-(1-(3-Chlorophenyl)ethylidene)-4-(2-
phenoxyphenyl)semicarbazide 11e
Mp. 210–2128C. IR (KBr): m max cm– 1 3375 (NH), 1690 (C=O). 1H-
NMR (DMSO-d6): d = 10.23 (s, 1H, NH), 9.00 (bs, 1H, NH), 8.35(dd, J
= 8.2, 1.3 Hz, 1H, H6), 7.70 (s, 1H, H299), 7.53 (d, J = 7.8 Hz, 1H, H699),
7.40 (d, J = 7.8 Hz, 1H, H499), 7.38 (t, J = 7.4 Hz, 2H, H39, H59), 7.33 (t, J
= 7.8 Hz, 1H, H599), 7.19 (dt, J = 7.4, 1.3 Hz, 1H, H4), 7.12 (t, J =
7.4 Hz, 1H, H49), 7.08 (dd, J = 7.4, 8.2 Hz, 1H, H5), 7.04 (d, J = 7.4 Hz,
2H, H29, H69), 6.99 (d, J = 7.4 Hz, 1H, H3), 2.23 (s, 3H, CH3). MS: m/z
(%) 381 [M++2] (20), 379 [M+] (65), 186 (40), 168 (100), 165 (98), 131
(96), 129 (28), 76 (75), 52 (38). Anal. Calcd. for C21H18ClN3O2: C,
66.40; H, 4.78; N, 11.06. Found: C, 66.58; H, 4.70; N, 10.84.
1-(1-(2-Nitrophenyl)ethylidene)-4-(2-
phenoxyphenyl)semicarbazide 11a
Mp. 214–2168C. IR (KBr): m max cm– 1 3375 (NH), 1690 (C=O),
1
1533, 1345 (NO2). H-NMR (DMSO-d6): d = 10.24 (s, 1H, NH), 8.58
(bs, 1H, NH), 8.31 (d, J = 8.2 Hz, 1H, H6), 7.99 (d, J = 7.6 Hz, 1H, H399),
7.73 (t, J = 7.6 Hz, 1H, H599), 7.65 (t, J = 7.6 Hz, 1H, H499), 7.52 (d, J =
7.6 Hz, 1H, H699), 7.38 (t, J = 7.6 Hz, 2H, H39, H59), 7.12 (t, J = 7.6 Hz,
1H, H49), 7.04 (t, J = 7.6 Hz, 1H, H4), 7.00 (dd, J = 8.2, 7.6 Hz, 1H, H5),
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4-(2-Phenoxyphenyl)semicarbazones
415
1-(1-(4-Chlorophenyl)ethylidene)-4-(2-
phenoxyphenyl)semicarbazide 11f
1-(1-(4-Methoxyphenyl)ethylidene)-4-(2-
phenoxyphenyl)semicarbazide 11j
Mp. 214–2168C. IR (KBr): m max cm– 1 3375 (NH), 3216 (NH), 1700
(CO). 1H-NMR (DMSO-d6): d = 10.19 (s, 1H, NH), 8.98 (bs, 1H, NH),
8.35 (d, J = 8.3 Hz, 1H, H6), 7.58 (d, J = 8.4 Hz, 2H, H299, H699), 7.40 (t, J
= 7.6 Hz, 2H, H39, H59), 7.35 (d, J = 8.4 Hz, 2H, H399, H599), 7.22 (t, J =
7.4 Hz, 1H, H4), 7.13 (t, J = 7.6 Hz, 1H, H49), 7.06 (dd, J = 8.3, 7.4 Hz,
1H, H5), 7.05 (d, J = 7.4 Hz, 1H, H3), 7.03 (d, J = 7.6 Hz, 2H, H29, H69),
2.22 (s, 3H, CH3). MS: m/z (%) 381 [M++2] (19), 379 [M+] (55), 186
(30), 165 (90), 132 (100), 128 (20), 91 (18), 75 (40). Anal. Calcd. for
C21H18ClN3O2: C, 66.40; H, 4.78; N, 11.06. Found: C, 66.46; H, 4.57;
N, 11.16.
Mp. 176–1788C. IR (KBr): m max cm– 1 3370 (NH), 1690 (C=O). 1H-
NMR (DMSO-d6): d = 10.02 (s, 1H, NH), 9.05 (bs, 1H, NH), 8.38 (d, J =
8.1 Hz, 1H, H6), 7.51 (d, J = 8.7 Hz, 2H, H299, H699), 7.41 (t, J = 7.6 Hz,
2H, H39, H59), 7.22 (t, J = 7.4 Hz, 1H, H4), 7.14 (t, J = 7.6 Hz, 1H, H49),
7.08 (dd, J = 8.1, 7.4 Hz, 1H, H5), 7.03 (d, J = 7.6 Hz, 2H, H29, H69), 7.0
(d, J = 7.4 Hz, 1H, H3), 6.83 (d, J = 8.7 Hz, 2H, H399, H599), 3.74 (s, 3H,
OMe), 2.19 (s, 3H, CH3). MS: m/z (%) 375 [M+] (40), 211 (11), 184 (45),
163 (100), 92 (12), 75 (25). Anal. Calcd. for C22H21N3O3: C, 70.38; H,
5.64; N, 11.19. Found: C, 70.08; H, 5.84; N, 11.43.
This work was supported by grants from the Research Council
of Tehran University of Medical Sciences and INSF (Iran
National Sciences Foundation).
1-(1-(3-Bromophenyl)ethylidene)-4-(2-
phenoxyphenyl)semicarbazide 11g
Mp. 198–2008C. IR (KBr): m max cm– 1 3359 (NH), 3221 (NH), 1705
(C=O). 1H-NMR (DMSO-d6): d = 10.22 (s, 1H, NH), 8.98 (bs, 1H, NH),
8.34 (d, J = 8.0 Hz, 1H, H6), 7.85 (s, 1H, H299), 7.57 (d, J = 7.7 Hz, 1H,
H699), 7.55 (d, J = 7.7 Hz, 1H, H499), 7.37 (t, J = 7.7 Hz, 2H, H39, H59), 7.27
(t, J = 7.7 Hz, 1H, H599), 7.19 (t, J = 7.7 Hz, 1H, H4), 7.12 (t, J = 7.7 Hz,
1H, H49), 7.05 (dd, J = 8.0, 7.7 Hz, 2H, H29, H69), 7.04 (dd, J = 8.0,
7.7 Hz, 1H, H5), 6.99 (d, J = 7.7 Hz, 1H, H3), 2.23 (s, 3H, CH3). MS: m/
z (%) 425 [M++2] (37), 423 [M+] (38), 211 (100), 184 (30), 132 (25),
126 (18), 75 (60), 50 (27). Anal. Calcd. for C21H18BrN3O2: C, 59.45;
H, 4.28; N, 9.90. Found: C, 59.27; H, 4.41; N, 10.20.
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phenoxyphenyl)semicarbazide 11h
[5] M. D. Mullican, M. W. Wilson, D. T. Connor, C. R. Kostlan,
Mp. 215-2178C. IR (KBr): m max cm– 1 3385 (NH), 1705 (C=O). 1H-
NMR (DMSO-d6): d = 10.19 (s, 1H, NH), 8.98 (bs, 1H, NH), 8.34 (d, J =
7.9 Hz, 1H, H6), 7.51 (d, J = 8.8 Hz, 2H, H299, H699), 7.49 (d, J = 8.8 Hz,
2H, H399, H599), 7.40 (t, J = 7.5 Hz, 2H, H39, H59), 7.22 (t, J = 7.6 Hz, 1H,
H4), 7.13 (t, J = 7.5 Hz, 1H, H49), 7.06 (dd, J = 7.9, 7.4 Hz, 1H, H5),
7.05 (d, J = 7.6 Hz, 1H, H3), 7.03 (d, J = 7.5 Hz, 1H, H29, H69), 2.21 (s,
3H, CH3); MS: m/z (%) 425 [M++2] (52), 423 [M+] (55), 210 (100), 183
(45), 153 (30), 126 (45), 101 (47), 78 (68), 74 (98). Anal. Calcd. for
C21H18BrN3O2: C, 59.45; H, 4.28; N, 9.90. Found: C, 59.67; H, 3.98;
N, 9.78.
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Bonne, Arzneim-Forsch. 1985, 35, 1260–1263.
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1-(1-(2,5-Dimethoxyphenyl)ethylidene)-4-(2-
phenoxyphenyl)semicarbazide 11i
[11] A. Almasirad, M. Sheikhha, R. Hosseini, S. A. Tabatabai,
A. Shafiee, Arch. Pharm. Pharm. Med. Chem. 2004, 337,
193–200.
Mp. 166–1688C. IR (KBr): m max cm– 1 3365 (NH), 1690 (C=O). 1H-
NMR (DMSO-d6): d = 10.02 (s, 1H, NH), 8.90 (s, 1H, NH), 8.33 (d, J =
8.2 Hz, 1H, H6), 7.28 (t, J = 7.8 Hz, 2H, H39, H59), 7.16 (t, J = 7.4 Hz,
1H, H4), 7.09 (t, J = 7.8 Hz, 1H, H49), 7.01 (dd, J = 8.2, 7.4 Hz, 1H, H5),
6.99 (d, J = 8.6 Hz, 1H, H399), 6.94 (d, J = 7.4 Hz, 1H, H3), 6.93 (d, J =
7.8 Hz, 2H, H29, H69), 6.92 (dd, J = 8.6, 3.0 Hz, 1H, H499), 6.79 (d, J =
3.0 Hz, 1H, H699), 3.72 (s, 3H, OMe), 3.61 (s, 3H, OMe), 2.15 (s, 3H,
CH3). MS: m/z (%) 405 [M+] (50), 211 (17), 195 (53), 193 (70), 161
(100), 103 (30), 89 (45), 77 (98). Anal. Calcd. for C23H23N3O4: C,
68.13; H, 5.72; N, 10.36. Found: C, 68.40; H, 5.57; N, 10.61.
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