Chemoselectivity of 2-arylmethyleneaminoisoindolin-1,3-diones toward arenes under friedel-crafts conditions: An efficient synthesis of benzophenones integrated with 2-substituted hydrazone moieties

Article abstract of DOI:10.1002/jhet.854

Treatment 2-arylmethyleneaminoisoindole-1,3-diones 1a-c with arenes in the presence of AlCl₃-DMF complex as a catalyst afforded the novel compounds, 2-((arylidenehydrazono)(aryl)-methyl)benzophenones 3a-n in satisfactory yields. The structure of the obtained products 3a-n was confirmed by the use of IR, ¹H-NMR, ¹³C-NMR, mass spectra, and elemental analyses.

Full text of DOI:10.1002/jhet.854

700
Chemoselectivity of 2-Arylmethyleneaminoisoindolin-1,3-diones
toward Arenes under Friedel–Crafts Conditions: An Efficient
Synthesis of Benzophenones Integrated with 2-Substituted
Hydrazone Moieties
Vol 49
*
Hamed A. Derbala
Department of Chemistry, Faculty of Science, Ain Shams University, Abbassia 11566, Cairo, Egypt
*
E-mail: h_derbala@hotmail.com
Received December 10, 2010
DOI 10.1002/jhet.854
View this article online at wileyonlinelibrary.com.
Treatment 2-arylmethyleneaminoisoindole-1,3-diones 1a–c with arenes in the presence of AlCl3-DMF
complex as a catalyst afforded the novel compounds, 2-((arylidenehydrazono)(aryl)-methyl)benzophenones
3a–n in satisfactory yields. The structure of the obtained products 3a–n was confirmed by the use of IR,
1H-NMR, 13C-NMR, mass spectra, and elemental analyses.
J. Heterocyclic Chem., 49, 700 (2012).
INTRODUCTION
of unsymmetrical benzophenones [23–28]. Earlier work
adopting Lewis acid-catalyzed reaction of 2-arylmethyle-
neaminoisoindol-1,3-diones 1 with arenes, revealed that
no benzophenones were produced; however, ready trans-
formation into 4-arylphthalazinones has occurred via a
pathway that was believed to involve the formation of
transient benzophenone structure intermediates followed
by subsequent cyclization with elimination of the aldehyde
moiety [29,30]. Herein, this work presents an efficient
methodology for the synthesis of the novel anticipated
biologically active benzophenones 3a–n, integrated with
2-substituted hydrazone segment possessing an azomethine
—N¼CH proton, recently used for the development of
new drugs [31], via the aforementioned reaction type on
the heterocyclic substrates 1a–c.
Benzophenones, in particular, nitrogen-containing
analogs constitute the core structure of many relevant bio-
logically active compounds because of their diverse pharma-
ceutical activities, namely, antioxidant, cytotoxic, analgesic,
and anti-inflammatory activities. For examples, N-ethyl-
piperidine and -morpholine moieties integrated with ben-
zophenone framework verified their anti-inflammatory
activities, while the benzophenone analog, 6-benzoyl-
benzothiazolone, proved its potent analgesic properties
[1–3]. Further, a series of nitrogen-containing benzophe-
none analogs showed inhibition of TNF-alpha and IL-6
with significant antioxidant activities [4]. Recently, it
has been revealed that introduction of amino groups at
the C-2 or C-3 of 4-methoxybenzophenones plays an
integral role for increased growth inhibition of tubulin
polymerization and for maximal cytotoxicity. Morever,
similar benzophenone structures with an amino group
positioned at C-2 have shown antivascular effects, as well
as 4-aminobenzophenones were found to be potent and
selective p38 MAP kinase inhibitors [5–9]. Azines have
achieved a great significance in organic synthesis, syn-
thetic transformation, and they constitute an important
class of compounds with unexpected biological activity
[10–15]. Conventionally, Friedel–Crafts acylation of aro-
matics for the preparation of benzophenone have received
more attention [16–22]. Application of this protocol on
activated nitrogen heterocycles involving 2-indolinone,
benzoxazolones, and benzothiazolones provided a library
RESULTS AND DISCUSSION
The substrates, 2-arylmethyleneaminoisoindolin-1,3-
diones 1a–c, were quantitatively prepared following the
reported methodologies involving that reported earlier by
the author. The structure of 1 was confirmed by analogy
with literature mp measurements and spectral data [29,32].
In connection to the aforementioned Lewis acid-
catalyzed reactions of 2-indolinone with benzoyl chloride
or its isomeric derivative, 2-arylideneaminoisoindolinones
with arenes that afforded various products involving
alternative utilities of both heterocycles, this work aims at
reinvestigating chemoselectivity of the heterocyclic substrate 1
© 2012 HeteroCorporation

May 2012 Chemoselectivity of 2-Arylmethyleneaminoisoindolin-1,3-diones toward Arenes under Friedel–Crafts 701
Conditions: An Efficient Synthesis of Benzophenones Integrated with 2-Substituted Hydrazone Moieties
toward arenes under Friedel–Crafts conditions in the hope
to synthesize benzophenones 3. Herein, compound 1
suspended in CH2Cl2 was treated with 7 equiv of benzene,
toluene, and m-xylene in the presence of catalytic amounts
of anhydrous AlCl3, and the reaction was refluxed from
4–6 h (monitored by TLC). Examination of the yielded
products by the aid of TLC, melting points, and mixed
melting points revealed that no benzophenones were pro-
vided; however, 4-arylphthalazinones 2 were produced
whose structure was compatible with the literature com-
pounds formed by the use of excess arenes (coreactant
and cosolvent) [29,33]. Accordingly, the reaction was
repeated by performing under alternative conditions.
Herein, 7 equiv of the coreactant arene–namely, benzene,
toluene, m-xylene, anisole, and bromobenzene–were sub-
mitted to react at room temperature with a stirred solution
mixture of the substrate 1 (10 mmol) dissolved in DMF
(5.2 mL, 70 mmol) in the presence of anhydrous AlCl3
(300–500 mmol). Whenever a reddish brown paste was
formed, the reaction mixture was heated under reflux on
an oil-bath over time, 2–6 h. (The reaction was monitored
by TLC). After the reaction was completed, the obtained
products have been carefully investigated by the aid of
TLC, mp, mmp, and spectral data. Interestingly, it was
found that a smooth reaction proceeded via two Friedel-
Crafts C—C bond formations in situ to provide sufficient
yields of the novel products which were identified as
2-((arylidenehydrazono)(aryl)methyl)benzophenones 3a–n
(Scheme 1). It was evident that under the reaction condi-
tions the heterocycle 1 behaved efficiently as a bidentate
substrate that reacted with two molecules of arenes to
incorporate two aryl moieties. The reaction route was be-
lieved to involve initial acylation type, followed by a sub-
sequent arylation type in situ of the electrophile,
azomethine C¼N group formed with progress of the
reaction under the effect of the employed catalyst which
finally led to the formation of the desired benzophenone
derivatives 3a–n. Obviously, this reaction route was alter-
native to the aforementioned reaction pathway which has
been described to involve acylation of one molecule of
arene followed by cyclization to give the phthalazinones
2 [29,33].
To accomplish the reaction in sufficient yields and
to achieve the optimal catalytic efficiency, it was necessary
to modify the molar ratio of the catalyst AlCl3-DMF
(Table 1). Thus, the formation of 3b, 3c, 3g, and 3m
required the use of a 4:1 molar ratio that was increased up
to 7:1 to yield 3e, 3j, and 3n. The structure of the obtained
products was inferred from a study of their spectroscopic
data. Herein, the IR spectra showed the carbonyl absorption
frequency of aromatic ketones at 1684–1672 cmꢀ1, in addi-
tion to the absorption bands exhibited at 1657–1621 cmꢀ1
due to the azomethine C¼N functionalities. Further compel-
ling evidences for establishment of the assigned structure
were received from the 1H-NMR spectra. Accordingly, they
revealed a singlet peak in the more downfield region at
d 10.08–8.36 ppm due to azomethine proton HC¼N, as well
as the signals appeared at the upfield region attributable to
absorptions of aromatic CH3 and —OCH3 group protons.
For example, the structure of 3c was based on the three sin-
glets revealed at d 2.39 (6H, 2CH3), 2.31 (3H, CH3), and
2.17 (3H, CH3) ppm stand to the four aromatic CH3 protons
centered at 2- and 4-positions of the incorporated aromatic
rings. However, the structure of 3i was inferred from the
two singlets displayed at d 3.78 and 3.69 ppm due to the
4-substituted —OCH3 protons. In addition, the EI-MS
showed m/z (%) 408 (12.46) and 303 (100) stand to
(M+-CH2O) and the base peak (M+-C6H5CO+,-CH2O),
respectively. In turn, the EI-MS of 3k showed the base
peak at m/z (%) 285 (100) due to (M+-C4H3CNS).
It was believed that the incorporation of the two aryl
moieties has occurred via ring cleavage of N-acylhy-
drazonium ion 4 generated under the effect of Lewis acid
catalyst, followed by the subsequent intermolecular
Friedel–Crafts acyalkylation reaction types in situ
(Scheme 2).
In can be concluded that the synthesis of benzophenones
2 with hydrazone moiety contained at 2-position has been
efficiently achieved by the treatment of 2-arylmethylenea-
minoisoindolin-1,3-diones 1 with arenes in the presence
of AlCl3-DMF complex as a catalyst. Interestingly, this
reaction reports the first utility of the heterocycle 1 as
acylating agent to produce the novel benzophenones
3a–n.
Scheme 1
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

702
H. A. Derbala
Vol 49
Table 1
Synthesis of 2-((arylidenehydrazono)(aryl)methyl)benzophenones 3a–n.
Entry
Product
Yield
Time
AlCl3 (g,mmol)
Ar
Ar0
1
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
71
83
64
61
47
68
53
59
62
41
74
66
58
46
3.5
3.5
3
6
4.5
5
3.5
6
4
5
5
50g, 370
40g, 300
40g, 300
36g, 474
67g, 504
45g, 338
42g, 316
49g, 370
56g, 420
70g, 526
53g, 400
56g, 420
42g, 316
66g, 500
C6H5
C6H5
C6H5
C6H5
C6H5
Furan-2-yl
Furan-2-yl
Furan-2-yl
Furan-2-yl
C6H5
2
3
4
5
6
7
8
9
10
11
12
13
14
C6H4CH3 p-
C6H3(CH3)2 2,4
C6H4OCH3 p-
C6H4 Br p-
C6H5
C6H4 CH3 p-
C6H3 (CH3)2 2,4-
C6H4OCH3p-
C6H4 Br p-
Furan-2-yl
Thiophen-2-yl
Thiophen-2-yl
Thiophen-2-yl
Thiophen-2-yl
C6H5
3.5
3.5
4
C6H4 CH3 p-
C6H3 (CH3)2 2,4-
C6H4 OCH3p-
1
Scheme 2
1627 (C¼N). H-NMR (CDCl3, d ppm) 9.50 (s,1H, HC¼N), 7.89
(dd, J = 3.8, 4.9 Hz, 2Hthio), 7.76 (m, 2H, ArH) 7.51( dd, J = 8.2
Hz, 2H, ArH), 7.11 (dd, J = 4.6, 3.4 Hz, 1H, H-4thio). EI-Ms: m/z
(%); 258 (1.11, M+2), 256(23.1, M+), 147 (9.4), 105(100), 104
(56.3). Anal. Calcd. C13H8N2O2S (256.28): C,60.92; H,3.14; N,
10.93; S,12.51. Found: C, 60.61; H, 3.45; N, 10.61; S, 12.23.
Reaction of 2-(arylmethyleneamino)isoindole-1,3-diones
(1a–c) with arenes in CH2Cl2 in presence of anhydrous
AlCl3: Synthesis of 4-arylphthalazinones 2a–c.
EXPERIMENTAL
General procedure. Anhydrous aluminium chloride (3.33 g,
25 mmol) was added portionwise at room temperature to
a stirred solution of arene (70 mmol) and CH2Cl2 (20 mL).
2-Arylmethylene amino-isoindole-1,3-diones (10 mmol) were
added to the solution mixture with continuous stirring and
heated on water bath at the refluxing temperature for 4 h. After
completion of the reaction (monitored by TLC), it was cooled
and then hydrolyzed by the addition of ice-concentrated HCl
(30 mL). The resulting mixture was distilled, and the excess
solvent was removed under reduced pressure. The solid
product obtained was fitered off and crystsllized from benzene
to afford the corresponding 4-arylphthalazin-1-ones 2a–c whose
structure was in accordance with the literature [29,33].
All melting points were taken on a Gallen Kamp electric
melting point apparatus. IR spectra were recorded in KBr and
were determined on a Perkin Elmer 2000 FTIR system. NMR
spectra were determined on a Varian Gemini 300 MHz for
1H-NMR and 50 MHz for 13C-NMR, in CDCl3 or DMSO-d6 as
a solvent and TMS as internal standard; chemical shifts are
reported in d (ppm). Mass spectra were measured on VG Autospec
QMS 30 and MS 9 (AEI) spectrometers with EI 70 eV. TLC was
performed using TLC aluminium sheets silica gel F254 (Merck).
Elemental analyses were performed using a Perkin Elmer 2400
CHN Elemental Analyzer. Compounds 1a–c were prepared
following the reported methodologies [29,32].
Reaction of 2-arylmethyleneaminoisoindole-1,3-diones
(1a–c) with arenes in the presence of AlCl3-DMF complex:
Synthesis of 2-(((arylidene)hydrazono)(aryl)-methyl) benzo-
phenones 3a–n.
2-Benzylideneaminoisoindole-1,3-dione (1a). Pale yellow
crystals (EtOH), m.p. 161–163ꢁC (lit.32 163–165ꢁC). IR (KBr,
n cmꢀ1): 1783 (CO5-memb.), 1716 (CO5-memb.), 1623 (C¼N).
1H-NMR (CDCl3, d ppm): d 9.38 (s, 1 H, N¼CH), 7.90
(m, 4H, ArH), 7.76 (m, 2 H, ArH), 7.45 (m, 3 H, ArH). Anal.
Calcd. C15 H10 N2 O2 (250.26): C, 71.99, H 4.03, N 11.19.
Found: C, 72.13, H, 3.86, N, 11.45.
General Procedure. Anhydrous AlCl3 (40–66.6 g; 300–500
mmol) was added portionwise to the substrate 1a–c (10 mmol;
1a, 2.5 g; 1b, 2.4 g; 1c, 2.6 g) in DMF (5.2 mL, 70 mmol) with
stirring at room temperature, and arene (70 mmol) was added in
one portion to the solution mixture with continuous stirring and
during the addition a reddish brown paste was formed. Then, the
reaction mixture was heated on an oil-bath at 60ꢁC for 2–6 h (the
reaction was monitored by TLC). The reaction mixture was
hydrolyzed by the addition of ice-concentrated HCl (30 mL). The
organic layer was separated and neutralized with 10% aqueous
NaHCO3 solution and then washed with water (3 × 30 mL). The
organic product was extracted with ethyl acetate, dried over
Na2SO4, and concentrated. The crude product was purified by
column chromatography using ethyl acetate and hexane (1:10) as
an eluent to yield the products 3a–n in 57–73% yields. The
volumes of the used arenes (50 mmol) were as follows: benzene
2-(Furan-2-yl)methyleneamino-isoindole-1,3-dione (1b).
Yellow crystals (EtOH), m.p. 160–1ꢁC (lit.29 164–5ꢁC), Yield
(57%). IR (KBr, n cmꢀ1): 1785(CO5-memb.), 1720 (CO5-memb.),
1612 (C¼N). 1H-NMR (CDCl3, d ppm) 9.44 (s, 1H, HC¼N),
7.81 (d, J = 1.8 Hz, 1H, H-5fur.), 7.53 (m, 2H, ArH), 7.42 (d, J =
3.6 Hz, 1H, H-3fur.), 7.38 (m, 2H, ArH), 6.84 (dd, J = 2.3, 1.2
Hz, 1H, H-4fur.). EI-MS: m/z (%); 240 (19.7), 147 (35.6), 105
(100). Anal. Calcd. C13H8N2O3 (240.21): C,64.99; H,3.53;
N,11.66. Found: C, 64.73; H, 3.40; N, 11.70.
2-(Thiophen-2-yl)methyleneamino-isoindole-1,3-dione (1c).
Yellow crystals (EtOH), mp.156–70ꢁC (lit.32 159–161ꢁC), Yield
(63%). IR (KBr, n cmꢀ1): 1782(CO5-memb.), 1723 (CO5-memb.),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2012 Chemoselectivity of 2-Arylmethyleneaminoisoindolin-1,3-diones toward Arenes under Friedel–Crafts 703
Conditions: An Efficient Synthesis of Benzophenones Integrated with 2-Substituted Hydrazone Moieties
(4.4 mL), toluene (5.3 mL), m-xylene (5.9 mL), anisole (5.4 mL),
and bromobenzene (5.3 mL).
(C¼O), 165.2 (C¼N), 164.7 (C¼N), 150.6, 142.2, 131.3,
129.1, 114.3, 22.1, 20.7. EI-Ms: m/z (%): 406 (17.43), 315
(29.61), 313 (100, M-C4H3CNO), 295 (17.04), 105(6.08).
Anal. Calcd. C27H22N2O2 (406.44): C, 79.79; H, 5.45; N,
6.89. Found: C, 79.66; H, 5.18; N, 7.13.
2-((Benzylidenehydrazono)(phenyl)methyl)benzophenone
(3a).
Bright yellow crystals, mp 194–6ꢁC. IR (KBr, υ cmꢀ1):
1
1681 (C¼O); 1632 (C¼N), 1624 (C¼N). H-NMR (DMSO-d6,
d ppm) 8.72(s,1H, HC¼N), 7.83–7.41(m, 8H, ArHs), 7.37–6.84
(m, 9H, ArHs), 6.68 (m, 2H, ArHs). 13C-NMR (DMSO-d6,
d ppm): 195.3 (C¼O); 166.1 (C¼N); 153.4 (C¼N); 133.6; 132.2;
130.5; 129.2; 128.4. Anal. Calcd. C27H20N2O (388.44): C, 83.49;
H, 5.18; N, 7.21. Found: C, 83.73; H, 4.96; N, 7.43.
2-(((2-Furfurylidenehydrazono)(2,4-dimethyphenyl)methyl)-
2,4-dimthyl)benzophenone (3h).
Bright yellow needles, mp
206–7ꢁC. IR (KBr, υ cmꢀ1): 1682 (C¼O); 1641 (br, 2 C¼N).
1H-NMR (CDCl3, d ppm): 9.05 (s, 1H, HC¼N), 7.88 (s, 2H),
7.64 (d, J = 3.4 Hz, 2Hfur, H-3, H-5), 7.52 (m, 6H, ArH), 7.34-
7.16 (m, 2H, ArH), 6.80 (dd, J = 2.1, 0.8 Hz, 1Hfur, H-4) 2.42
(s, 6H, 2CH3), 2.31(s, 3H, CH3), 2.24 (s, 3H, CH3). EI-Ms: m/z
(%): 434 (6.26), 404 (45.76), 328 (100, M-C7H+7,—CH3), 105
(31.48), 91(73.29). Anal.Cacld. C29H26N2O2 (434.49): C, 80.17;
H, 6.02; N, 6.45. Found: C, 80.35; H, 5.87; N, 6.26.
2-(((Benzylidenehydrazono)(p-tolyl)methyl)-4-methyl)benzo-
phenone (3b). Bright yellow crystals, mp 212–3ꢁC. IR (KBr,
υ cmꢀ1): 1679 (C¼O); 1638 (C¼N), 1628 (C¼N). 1H-NMR
(DMSO-d6, d ppm): 9.14 (s,1H, HC¼N), 8.07–7.64 (m, 5H,
ArHs), 7.31 (dd, J = 8.6, 2.1 Hz, 2H, ArH), 7.14–6.82 (m, 8 H,
ArHs), 6.88 (m, 2H, ArHs), 2.41 (s,3H, CH3), 2.27(s,3H,
CH3). Anal. Calcd. C29H24N2O (416.49): C, 83.63; H, 5.80; N,
6.72. Found: C, 83.47; H, 5.91; N, 6.43.
2-(((2-Furfurylidenehydrazono)(4-methoxyphenyl)methyl)-4-
methoxy)benzophenone (3i). Yellow powder, mp 238–9ꢁC. IR
(KBr, υ cmꢀ1): 1676 (C¼O); 1637 (C¼N), 1626 (C¼N).
1H-NMR (CDCl3, d ppm): 9.26 (s, 1H, HC¼N), 7.94 (s, 4H),
7.82 (m, 6H), 7.69 (d, J = 8.2 Hz, 2H, ArH), 7.53 (d, J = 3.1 Hz,
2Hfur), 7.36 (t, J = 7.6 Hz, 1H, ArH), 3.78 (s, 3H, OCH3), 3.69
(s, 3H, OCH3). EI-MS: m/z (%): 408 (12.46, M-CH2O), 407
(27.09, M-CH3O), 303 (100, M-C6H5CO+, —CH2O), 239
(60.21), 105(27.04). Anal. Cacld. C27H22N2-O4 (438.42): C,
73.97; H, 5.05; N, 6.39. Found: C, 74.35; H, 4.87; N, 6.56.
2-(((2-Furfurylienehydrazono)(4-bromophenyl)methyl)-4-
bromo)benzophenone (3j). Bright yellow crystals, mp 153–5ꢁC.
IR (KBr, υ cmꢀ1): 1683 (C¼O); 1634 (br, 2C¼N). 1H-NMR
(CDCl3, d ppm): 8.66 (s, 1H, HC¼N), 8.24 (d, J = 8.6 Hz, 1H,
ArH), 7.92 (s, 3H), 7.79-7.53 (m, 6H, ArH), 7.41 (d, J = 2.9 Hz,
2Hfur), 7.32 (s, 3H). EI-MS: m/z (%): 534 (14.66), 536 (29.30),
538 (14.64), 184(100), 105(37.52). Anal.Cacld.C25H16N2O2Br2
(536.18): C, 56.0; H, 3.0; N, 5.22; Br, 29.80. Found: C, 55.76; H,
3.18.; N, 4.93; Br, 30.05
2-(((Benzylidenehydrazono)(2,4-dimethylphenyl)methyl)-4,
6-dimethyl)benzophenone (3c).
Bright yellow crystals, mp
177–8ꢁC. IR (KBr, υ cmꢀ1): 1676 (C¼O); 1637 (C¼N), 1621
1
(C¼N). H-NMR (CDCl3, d ppm): 8.36 (s,1H, HC¼N), 7.85–
7.44 (m, 7H, ArHs), 7.73 (s,1H, ArHs), 7.54–7.03 (m, 6H,
ArHs), 6.88 (m,1H, ArHs), 2.39 2.39 (s, 6H, 2CH3), 2.31
(s,3H, CH3), 2.17 (s,3H, CH3). Anal. Calcd. C31H28N2O
(444.54): C, 83.76; H, 6.34; N, 6.30. Found: C, 83.55; H,
6.47; N, 6.51.
2-(((Benzylidenehydrazono)(p-methoxyphenyl)methyl)-4-
methoxy)benzophenone (3d). Orange crystals, mp 224–6ꢁC. IR
(KBr, υ cmꢀ1): 1681 (C¼O); 1633 (C¼N), 1625 (C¼N).1H-NMR
(DMSO-d6, d ppm): 8.64 (s,1H, HC¼N), 7.87–7.65 (m, 8H,
ArHs), 7.42–6.82 (m, 4H, ArHs), 7.31 (dd, J = 7.8, 2.3 Hz, 1H,
ArH), 6.68–6.51 (m, 4H, ArHs), 3.78 (s,3H, OCH3), 3.70 (s,3H,
OCH3). Anal. Calcd. C29H24N2O3 (448.54): C, 77.65; H, 5.39;
N, 6.24. Found: C, 77.81; H, 5.53; N, 6.07.
2-(((Benzylidenehydrazono)(p-bromophenyl)methyl)-4-bromo)
benzophenone (3e). Pale yellow crystals, mp 189–191ꢁC. IR
(KBr, υ cmꢀ1): 1684 (C¼O); 1657 (C¼N), 1629 (C¼N).
1H-NMR (DMSO-d6, d ppm): 8.41 (s,1H, HC¼N), 8.18–7.66
(m, 5H, ArHs), 7.43 (m, 2H,ArH), 7.32–7.06 (m, 8H, ArHs),
6.72–6.64 (m, 2H, ArHs). Anal. Calcd. C27H18N2OBr2 (546.23):
C, 59.37; H, 3.32; N, 5.13; Br, 29.25. Found: C, 59.53; H, 3.42;
N, 5.12; Br, 29.58.
2-(((2-Thienylidene)hydrazono)(phenyl)methyl)benzophenone
(3k). Bright yellow crystals, mp 227–9ꢁC. IR (KBr, υ cmꢀ1):
1
1678 (C¼O); 1638 (C¼N), 1622 (sh, C¼N). H-NMR (CDCl3
d ppm): 10.08 (s, 1H, HC¼N), 7.90 (d, J = 7.8 Hz, 1H, ArH),
7.56 (d, J = 3.4 Hz,1Hfur, H-5), 7.54-7.49 (m, 3H), 7.46 (d, J =
7.5 Hz,1H, ArH), 7.37 (d, J = 2.9 Hz,1Hfur, H-3), 7.26 (m, 8H,
ArH), 7.05 (d, J = 1.4 Hz,1Hfur, H-4), 6.99 (s,1H). EI-MS: m/z
(%): 396 (4.06), 394 (67.63), 285 (100, M+-C4H3CNS), 286
(24.84), 208 (60.07), 165 (26.46), 77 (19.83). Anal. Calcd.
C25H18N2OS (394. 47): C, 76.12; H, 4.59; N, 7.10, S, 8.13.
Found: C, 76.24; H, 4.37; N, 7.26, S, 8.27.
2-((2-Furfurylidenehydrazono)(phenyl)methyl)benzophenone
(3f). Bright yellow crystals, mp 194–6ꢁC. IR (KBr, υ cmꢀ1):
1
1674 (C¼O); 1639(C¼N), 1628 (C¼N). H-NMR (DMSO-d6,
2-(((2-Thienylidenehydrazono)(p-tolyl)methyl)-4-methyl)
benzophenone (3l). Brownish yellow crystals, mp 209–10ꢁC.
IR (KBr, υ cmꢀ1): 1679 (C¼O); 1655 (br, 2C¼N). 1H-NMR
(CDCl3, d ppm): 9.27 (s, 1H, HC¼N), 7.83 (d, J = 5.3 Hz,
1Hthio), 7.54 (m, 5H, ArH), 7.38 (d, J = 7.8 Hz, 2H, ArH), 7.30
(m, 4H, ArH), 6.93 (d, J = 4.4 Hz, 2Hthio), 6.57 (t, J = 7.8 Hz,
1H, ArH), 2.39(s, 3H, CH3), 2.32(s, 3H, CH3). 13C-NMR
(CDCl3, d ppm): 197.6 (C¼O), 163.8 (C¼N), 137.9 (C¼N,
131.4, 128.7, 22.4 (CH3), 21.8 (CH3). EI-MS: m/z (%): 331(100,
M-C7H+7), 313 (13.65, M-C4H3CNS), 297 (44.71), 119 (32.09),
91(74.31). Anal. Cacld. C27H22N2OS (422.52): C, 76.75; H, 5.24;
N, 6.63; S, 7.59. Found: C, 77.03; H, 4.87; N, 6.74; S, 7.38.
2-(((2-Thienylidenehydrazono)(2,4-dimethyphenyl)methyl)-
d ppm): 9.63 (s, 1H, HC¼N), 7.86–7.7 (m, 8H), 7.66 (d, J = 3.2
Hz, 2Hfur, H-3, H-5), 7.31 (s, 2H, ArH), 7.14 (d, J = 1.8 Hz,
1Hfur, H-4) ,7.06 (d, J = 8.6 Hz, 2H, ArH), 6.82 (t, J = 7.4 Hz,
2H, ArH). C-NMR (DMSO-d6, d ppm): 195.7 (C¼O), 164.6
(C¼N), 162.3 (C¼N), 143.4, 142.8, 132.5, 131.1, 129.3, 127.2.
EI-MS: m/z (%): 378 (13.25), 273 (100, M-C6H5CO+), 181
(28.46), 105 (4.62). Anal. Calcd. C25H18 N2 O2 (378.39): C,
79.35; H, 4.79; N, 7.40. Found: C, 79.43; H, 4.86; N, 7.61.
2-(((2-Furfurylidenehydrazono)(p-tolyl)methyl)-4-methyl)
benzophenone (3g).
Bright yellow needles, mp143–4ꢁC. IR
(KBr, υ cmꢀ1): 1677 (C¼O); 1641 (C¼N), 1632 (sh, C¼N).
1H-NMR (DMSO-d6, d ppm): 9.05 (s, 1H, HC¼N), 7.91 (d,
J = 2.9 Hz, 1Hfur, H-5), 7.56 (d, J = 3.8 Hz, 1Hfur, H-3), 7.31
(m, 8H, ArH), 6.98 (m, 4H, ArH), 6.82 (dd, J = 2.3, 1.4 Hz,
1Hfur, H-4), 2.32(s, 3H, CH3), 2.24(s, 3H, CH3). 2.32 (s, 3H,
CH3), 2.24 (s, 3H, CH3). 13C-NMR (CDCl3, d ppm): 198.1
2,4-dimethyl)benzophenone (3m).
Brownish yellow powder,
mp 174–5ꢁC. IR (KBr, υ cmꢀ1): 1682 (C¼O); 1657 (C¼N)
,1633 (sh, C¼N). 1H-NMR (CDCl3, d ppm): 9.40 (s, 1H,
HC¼N), 7.61 (d, J = 5.2 Hz,1Hthio), 7.54 (d, J = 8.2 Hz, 1H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

704
H. A. Derbala
Vol 49
[8] Liou, J. P.; Tseng, H. Y.; Yang, Y. N.; Kuo, F. M.; Tseng, H. Y.;
Lee, S. J.; Chang, Y. L.; Chang, C. N.; Hsieh, H. P.; Wang, C. C. J Med
Chem 2004, 47, 4247.
[9] Ottesen, E. R.; Sorensen, M. D.; Bjorkling, F.; Shak-Nielsen, T.;
Fjording, M. S.; Aaes, H.; Binderup, L. J Med Chem 2003, 46, 5651.
[10] Hai-Zhen, J.; Zhang-Jiao, R.; We, W.; Long-Gang, S. J Shan
Univ 2005, 9, 369.
[11] Khouzani, H. L.; Sadeghi, M. M.; Safari, J.; Fini, O. S. J Sci IR
Iran 2001, 12, 233.
[12] Afeefy, H. A. J Pharm Sci 1995, 4, 67.
[13] Kolb, V. M.; Kuffel, A. C.; Spiwek, H. O. J Org Chem 1989,
54, 2771.
ArH), 7.58 (d, J = 4.8 Hz, 2Hthio), 7.30ꢀ7.06 (m, 8H, ArH),
6.92 (t, J = 7.4 Hz, 1H), 2.41 (s, 3H, CH3), 2.33 (s, 6H,
2CH3), 2.27 (s, 3H, CH3). 13C-NMR (DMSO-d6, d ppm):
196.5 (C¼O), 162.8 (C¼N), 139.1 (C¼N), 131.3, 22.3 (CH3),
21.8 (CH3). EI-MS: m/z (%): 452 (2.82), 450 (56.34), 345
(100, M-C7H+7,—CH3), 341(28.02), 317 (36.70), 91(37.82).
Anal. Cacld. C29H26N2OS (450.57): C, 77.31; H, 5.81; N,
6.22; S, 7.12. Found: C, 77.23.; H, 6.07; N, 6.34; S, 6.89.
2-(((2-Thienylidenehydrazono)(4-methoxyphenyl)methyl)-4-
methoxy)benzophenone (3n). Yellow powder, mp 226–8ꢁC.
IR (KBr, υ cmꢀ1): 1682 (C¼O); 1637 (C¼N), 1631 (C¼N).
1H-NMR (DMSO-d6, d ppm): 9.08 (s, 1H, HC¼N), 8.24 (d,
J = 8.2 Hz, 1H), 7.63 (m, 3H), 7.53 (m, 6H), 7.41 (d, J = 4.8 Hz,
2Hthio), 7.32 (t, 2H), 6.85 (d, J = 5.5 Hz, 1Hthio), 3.78
(s, 3H, OCH3), 3.69 (s, 3H, OCH3). EI-MS: m/z (%): 424
(24.83, M-CH2O), 423 (54.16, M-OCH3), 345 (100, M-C4H3CNS),
319(12.70), 299(22.69), 105(35.68). Anal.Cacld. C27H22N2O3S
(454.50): C, 71.35; H, 4.87; N, 6.16; S, 7.05. Found: C, 71.18; H,
4.94; N, 6.33; S, 7.28.
[14] Christopher, J. A.; Jennifer, M. P. J Am Chem Soc 1989, 111,
1775.
[15] Kolb, V. M.; Hua, D. H. J Org Chem 1984, 49, 3824.
[16] Zhang, L.; Zhang, J. Y. J Comb Chem 2006, 8, 361.
[17] Khadikar, B. M.; Borkar, S. D. Tetrahedron Lett 1997, 38, 1641.
[18] Peng, X.; Wang, J.; Cui, J.; Zhang, R.; Yan, Y. Synth
Commun 2002, 32, 2361.
[19] Kangani, C. O.; Day, B. W. Org Lett 2008, 10, 2645.
[20] Hwang, J. P.; Parakash, G. K. S.; Olah, G. A. Tetrahedron
2000, 56, 7199.
[21] Xiao, J.; Ross, J. Green Chem 2002, 4, 129.
[22] Gmouh, S.; Yang, H. Y.; Vaultier, M. Org Lett 2003, 5, 2219.
[23] Poupaert, J. H.; Depreux, P.; McCrudy, C. R. Monatsh 2003,
134, 823.
REFERENCES AND NOTES
[24] Aichaoui, H.; Poupaert, J. H.; Lesieur, D.; Henichart, J.-P.
Tetrahedron 1991, 47, 6649.
[1] Khanum, S. A.; Girish, V.; Suparshwa, S. S.; Khanum, N. F.
Bioorg Med Chem Lett 2009, 19, 1887.
[25] Aichaoui, H.; Poupaert, J. H.; Lesieur, D.; HCnichart. J.-P.
Bull Sot Chim Belg 1992, 101, 1053.
[2] Khhanum, S. A.; Girish, V.; Khanum, N. F.; Begum, B. A. Int
J Biomed Sci 2010, 6, 60.
[26] Yous, S.; Poupaert, J. H.; Lesieur. I.; Depreux, P.; Lesieur, D.
J Org Chem 1994, 59, 1574.
[3] Ferreira, S.; Lorenzotti, B.; Devissaguet, M.; Lesieur, D.;
Tsouderos, Y. Br J Pharm 1995, 114, 303.
[27] Pal, S.; Khan, A.; Bindu, P.; Dubey, P. K. Beil J Org Chem
2007, 3, 25.
[4] Bandgar, B. P.; Patil, S. A.; Totre, J. V.; Korbad, B. L.;
Gacche, R. N.; Hote, B. S.; Jalde, S. S.; Chaven, H. V. Bioorg Med Chem
Lett 2010, 20, 2292.
[5] Liou, J. P.; Chang, C. W.; Song, J. S.; Yang, Y. N.; Yeh, C. F.;
Tseng, H. Y.; Lo, Y. K.; Chang, Y. L.; Chang, C. M.; Hsieh, H. P. J Med
Chem 2002, 45, 2556.
[6] Liou, J. P.; Chang, C. W.; Chang, C. Y.; Chang, J. Y.; Kuo, F. M.;
Hsieh, H. P.; Mahindroo, N. J Med Chem 2004, 47, 2897.
[7] Safaei-Ghomi, J.; Fadaeian, M.; Hatami, A. Turk J Chem
2007, 31, 89.
[28] Doepp; Hassan, A. A.; Henkel, G. Lieb Ann 1996, 697.
[29] Derbala, H. A. Afinidad 1994, 51, 383.
[30] Ismail MF; Kandil NG. Acta Chimica Hung 1991, 128(2), 251.
[31] Rollas, S.; Kucakguzel, S. G. Molecules 2007, 12, 1910.
[32] Netchitailo, P.; Ninkam, A. F.; Daich, A.; Decroix, B. Eur J
Org Chem 2003, 4273.
[33] Ismail, M. F; El-Bassiouny, F. A; Younes, H. A. Tetrahedron
1984, 40, 2983.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet