Design, synthesis, and antibacterial activity of novel Schiff base derivatives of quinazolin-4(3H)-one

Article abstract of DOI:10.1016/j.ejmech.2014.02.053

Novel imine derivatives of quinazolin-4(3H)-one were designed and synthesized by using aminoethyl moieties to increase the amine bridge of quinazolin-4(3H)-one amine and then introducing various aromatic aldehydes. The target compounds were characterized

Full text of DOI:10.1016/j.ejmech.2014.02.053

European Journal of Medicinal Chemistry 77 (2014) 65e74
Contents lists available at ScienceDirect
European Journal of Medicinal Chemistry
journal homepage: http://www.elsevier.com/locate/ejmech
Original article
Design, synthesis, and antibacterial activity of novel Schiff base
derivatives of quinazolin-4(3H)-one
,
,
*
Xiang Wang a b, Juan Yin a, Li Shi a, Guoping Zhang a, Baoan Song a
a State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering,
Ministry of Education, Research, and Development Center for Fine Chemicals, Guizhou University, Guiyang 550025, People’s Republic of China
b College of Chemistry and Materials Engineering, Kaili University, Kaili 556011, People’s Republic of China
a b s t r a c t
Keywords:
Schiff base derivative
Quinazolin-4(3H)-one
Synthesis
Ralstonia solanacearum
Antibacterial activity
Novel imine derivatives of quinazolin-4(3H)-one were designed and synthesized by using aminoethyl
moieties to increase the amine bridge of quinazolin-4(3H)-one amine and then introducing various ar-
omatic aldehydes. The target compounds were characterized by proton nuclear magnetic resonance
spectroscopy (1H NMR), carbon nuclear magnetic resonance spectroscopy (13C NMR), mass spectrometry
(MS), infrared spectroscopy (IR), elemental analysis, and X-ray diffraction crystallography. Bioassay re-
sults indicated that some of the compounds showed good to excellent antibacterial activities against
tobacco bacterial wilt and tomato bacterial wilt. The 50% effective concentrations (EC50) of the com-
pounds against tobacco and tomato bacterial wilts ranged from 63.73
38.64 g/mL to 81.39 g/mL, respectively, which are lower than that the positive control thiodiazole
copper (216.70 and 99.80 g/mL). These results indicated that novel Schiff base derivatives containing
the 4(3H)-quinazolinone moiety can effectively control tobacco and tomato bacterial wilts.
Ó 2014 Published by Elsevier Masson SAS.
mg/mL to 201.52 mg/mL and
m
m
m
1. Introduction
search for alternative antibacterial agents remains a daunting task
in pesticide science [6,7].
Ralstonia solanacearum (R. solanacearum), one of the highest
destructive and widespread soil-borne phytopathogenic bacteria.
The hosts of R. solanacearum include economically important
plants, such as tomato, tobacco, potato, banana, pepper, and pea-
nut. R. solanacearum can enter plant roots through wounds and
multiply in the cortical tissue before invading the xylem elements
[1e5]. The high incidence of plant mortality and the lack of effective
control methods make R. solanacearum the world’s most destruc-
tive plant pathogen. Currently available traditional bactericides,
such as inorganic bactericides (e.g., copper formulations), are not
highly effective and can even enhance resistance in host tobacco
and tomato plants. Each year, pathogenic bacteria are responsible
for billions of dollars of economic losses worldwide. Therefore, the
The Schiff base family is composed of natural products with
critical pharmacophores [8]. It can be used as ideal lead structures to
develop agrochemicals and medicines, including fungicide [9,10],
bactericide [11], antiviral agent [12], herbicide [13], insecticide [14],
antioxidant agent [15], antiproliferative [16,17], and antimicrobial
drug [18,19]. Various natural alkaloids with critical pharmacophores
contain quinazolinone groups. For example, febrifugine, iso-
febrifugine, thiabutazide, (ꢀ)-benzomalvin A, 2-(4-hydroxybutyl)
quinazolin-4-one, and luotonin F was found in the plants, animals,
and microorganisms (Fig.1) [20e22], Luotonins A, B, C, D, E, and Fare
novel alkaloids that have been isolated from the aerial parts of
Peganum nigellastrum Bunge, which has a long history in Chinese
medicine for the treatmentof rheumatism, inflammation, abscesses,
and other maladies [23]. Meanwhile, 4(3H)-quinazolinone de-
rivatives have attracted considerable attention in recent years
because of their broad-spectrum biological properties, such as
antiinflammatory [24], antifungal [25], antibacterial [26,27], anti-
coccidial [28], antiviral [29e31], and antimicrobial [32] activities.
The efficient bioactivity of these compounds is mainly attributed to
the alkyl/aryl/heteroaryl group with multi-substituents in the qui-
nazolin-4(3H)-one core or attached to the C]N moiety. The current
researchonthe activityofimine derivatives of quinazolin-4(3H)-one
Abbreviations: TLC, thin layer chromatography; mp, melting point; IR, Infrared;
1H NMR, proton nuclear magnetic resonance; 13C NMR, carbon nuclear magnetic
resonance; MS, mass spectroscopy; EC50, 50% effective concentration; SAR, struc-
tureeactivity relationship; R. solanacearum, Ralstonia solanacearum.
* Corresponding author.
E-mail address: songbaoan22@yahoo.com (B. Song).
http://dx.doi.org/10.1016/j.ejmech.2014.02.053
0223-5234/Ó 2014 Published by Elsevier Masson SAS.

66
X. Wang et al. / European Journal of Medicinal Chemistry 77 (2014) 65e74
Fig. 1. Examples of natural products bearing quinazolin-4-one skeleton.
and their analogues has mainly focused on antimicrobial inhibition
of Escherichia coli, Salmonella typhimurium, Candida albicans and
Aspergillus flavus [33], antibacterial and antifungal activities [34]. In
our previous work, we reported that some quinazolin or C]N con-
taining compounds elicited antiviral activities against tobacco
mosaic virus and cucumber mosaic virus [29,31]. We also found that
a series of arylimine derivatives containing a 3-aminoethyl-2-[(p-
group in position 3 on the quinazolinone core might sufficiently
enhance the flexibility of the molecular backbone.
On the basis of these considerations, a series of new (E)-3-[2-
(substituted-arylideneamino) ethyl]-2-[substituted-anilino]quina-
zolin-4(3H)-one derivatives were designed and synthesized from
4(3H)-quinazolinone derivatives and various aromatic aldehydes
via condensation reaction (Scheme 1), and their antibacterial ac-
tivities against tobacco and tomato bacterial wilts were systemat-
ically evaluated for the first time. Results of bioassays indicate that
most synthesized compounds exhibit strong antibacterial activities
trifluoromethoxy)anilino]-4(3H)-quinazolinone
moiety
could
inhibit the growth of R. solanacearum and Xanthomonas oryzae [35].
We proposed that an N-aryl group in position 2 and an aminoethyl
Scheme 1. Schematic for the synthesis of final compounds 6ae6y.

X. Wang et al. / European Journal of Medicinal Chemistry 77 (2014) 65e74
67
against tobacco and tomato bacterial wilts. In particular, the EC50
values of compound 6x against tobacco and tomato bacterial wilts
with the standard drug thiodiazole copper. The inhibition rates of
compounds 6g, 6l, 6o, 6p, and 6w at 100 g/mL were 67%, 79%, 68%,
66%, and 61%, respectively, which were much higher than those of
thiodiazole copper (50%) at 200 g/mL. In addition, the inhibition
rates of compounds 6q, 6t, 6v, and 6x at 200 g/mL against tomato
m
were 84.72 and 49.26
showed much higher than thiodiazole copper (EC50 216.70 and
99.80 g/mL).
mg/mL, respectively. Notably, compound 6x
m
m
m
bacterial wilt were all 100%, which was equivalent to that of the
2. Results and discussion
standard drug thiodiazole copper. Compounds 6f, 6q, 6v, and 6x at
100
mg/mL showed 81%, 91%, 71%, and 78% inhibition rates,
2.1. Chemistry
respectively, which exceeded that of thiodiazole copper (67%).
Basing on previous in vitro bioassays, we found that some of the
compounds showed excellent activities against plant pathogens,
including tobacco and tomato bacterial wilts. The EC50 values for
some of the synthesized compounds are calculated and summa-
rized in Tables 4 and 5. Most of the evaluated compounds exhibited
A series of new Schiff base derivatives containing the 4(3H)-
quinazolinone moiety were rapidly synthesized with good yields by
condensation reactions. The structures of the compounds were
characterized by 1H NMR, 13C NMR, MS, IR, elemental analysis, and
X-ray diffraction crystallography. Spectral data are provided in
Tables 1 and 2. The compounds were screened for their in vitro
antimicrobial activities against tobacco and tomato bacterial wilts.
The EC50 of some of the synthesized compounds were also
determined.
Table 1
Physical and analytical date of synthesized compounds 6ae6y.a
Compd. Molecular
Time Yield Elemental analysis (%): found/calcd.
(%)b
92
95
90
92
88
95
90
88
89
93
84
94
94
92
84
87
88
58
89
88
84
93
99
87
99
2.2. Analytical spectral data of compounds 6ae6y
formular (M.W) (h)
C
H
N
6a
6b
6c
6d
6e
6f
C23H18Cl2N4O
(436.1)
C23H19FN4O
(386.2)
C27H22N4O
(418.2)
C23H18Cl2N4O
(436.1)
C23H19ClN4O
(402.1)
C24H22N4O2
(398.2)
1
63.30/63.17 4.37/4.15 12.47/12.81
71.62/71.49 5.04/4.96 14.64/14.50
77.19/77.49 5.53/5.30 13.53/13.39
63.16/63.17 3.99/4.15 12.73/12.81
68.53/68.57 4.50/4.75 13.84/13.91
71.99/72.34 5.54/5.57 14.22/14.06
69.53/69.55 4.96/5.35 13.45/13.52
72.84/72.97 5.91/6.12 17.14/17.02
72.00/71.98 5.58/5.29 13.93/13.99
70.34/70.08 5.77/5.65 13.05/13.08
77.83/77.75 5.67/5.59 12.96/12.95
62.30/62.48 4.86/4.59 12.09/12.14
67.13/67.44 5.05/4.95 16.19/16.38
67.06/67.44 4.97/4.95 16.78/16.38
69.47/69.14 5.14/5.08 13.64/13.44
73.79/73.39 6.53/6.40 16.09/16.46
63.98/63.87 4.19/4.47 12.45/12.41
72.02/71.98 4.99/5.29 14.12/13.99
72.08/72.34 5.19/5.57 14.37/14.06
57.35/57.27 3.58/3.55 14.25/14.52
68.54/68.57 4.58/4.75 13.58/13.91
61.29/61.68 4.23/4.05 15.39/15.64
66.24/66.59 4.78/4.89 13.01/12.94
64.57/64.21 4.82/4.72 12.88/12.48
67.43/67.33 5.04/5.42 15.77/15.70
The IR spectral data of compounds 6ae6y showed characteristic
absorption bands at 3531 cmꢀ1e3184 cmꢀ1, which were assigned to
the NeH of QueNHeAr. The absorption bands of the C]O and C]N
groups of the skeletal stretching frequency appeared at
1678 cmꢀ1e1654 cmꢀ1 and 1631 cmꢀ1e1604 cmꢀ1, respectively.
The absorption bands at 1598 cmꢀ1e1471 cmꢀ1 belonged to the
stretching frequency of C]C on benzene and to the bending of NeH
on QueNHeAr. A singlet varying from 9.45 ppme8.16 ppm in the
1H NMR spectra belonged to QueNHeAr and eN]CHe, and the
singlet or triplet that appeared at dH 4.68 ppme4.01 ppm revealed
the presence of ]NeCH2e and QueCH2e. The chemical shifts from
169.91 ppme158.21 ppm and at nearly 45.00 ppm and 59.00 ppm
in the 13C NMR spectra confirmed the existence of C]O or C]N
and ¼ NeCH2e and QueCH2e, respectively. All the final products
were confirmed by MS according to their molecular formulae. All
the spectra exhibited parent peaks because of molecular ions
(Mþ1), and the halogen-substituted compounds produced the
1.5
0.5
1
0.3
0.5
0.5
0.5
0.2
1
6g
6h
6i
C24H22N4O3
(414.2)
C25H25N5O
(411.2)
C24H21FN4O
(400.2)
6j
C25H24N4O3
(428.2)
6k
6l
C28H24N4O
(432.2)
C24H21BrN4O
(460.1)
0.5
1
(Mþ2)
peak.
The
structure
of
(E)-3-[2-((4-chloro-3-
nitrobenzylidene)amino)ethyl]-2-[(4-chlorophenyl)-amino]quina-
zolin-4(3H)-one 6t was also confirmed by X-ray diffraction (Fig. 2).
Crystallographic data (excluding structure factors) for the structure
had been deposited with the Cambridge Crystallographic Data
Center as supplementary publication No. CCDC-971755 [38].
6m
6n
6o
6p
6q
6r
C24H21N5O3
(427.2)
C24H21N5O3
(427.2)
C24H21ClN4O
(416.2)
C26H27N5O
(425.2)
C24H20Cl2N4O
(450.1)
C24H21FN4O
(400.2)
4
4
8
2.3. In vitro antibacterial bioassay
1
The antibacterial activity of all the test compounds were
determined by performing a turbidimeter test as previously
described [35,36]. The commercial plant bactericide thiodiazole
copper was used to compare the antibacterial activities of the
compounds (Table 3). The title compounds with excellent anti-
bacterial activities were tested against tobacco and tomato bacterial
wilts at five double-declining concentrations (e.g., 200, 100, 50, 25,
8
3
6s
C24H22N4O2
(398.2)
3
6t
C23H17Cl2N5O3 1.5
(481.1)
6u
6v
6w
6x
6y
C23H19ClN4O
(402.1)
C23H18ClN5O3
(447.1)
C24H21ClN4O2
(432.1)
C24H21ClN4O3
(448.1)
1.5
1.5
2
and 12.5
mg/mL), and their corresponding EC50 values were ob-
tained. The average EC50 was computed from at least three separate
analyses of growth inhibition using the software package SPSS 17.0.
Screening results are summarized in Tables 4 and 5.
As shown in Table 3, the primary in vitro bioassay results
2
revealed that all test compounds at 100
mg/mL or 200 mg/mL
exhibited moderate to excellent antibacterial activities against to-
bacco and tomato bacterial wilts. In particular, compounds 6g, 6h,
C25H24ClN5O
(445.2)
0.7
a
6k, 6l, 6n, 6o, 6p, 6t, and 6x at 200
mg/mL showed comparable
The reaction was performed according to general experimental program.
Isolated yields based on Intermediate 4ae4d.
b
antibacterial activities against tobacco bacterial wilt compared

68
X. Wang et al. / European Journal of Medicinal Chemistry 77 (2014) 65e74
CH3 and the corresponding R2 substituted with the 2-F-Ph, 3-OH-
4-OCH3-Ph, 1-naphthyl, 4-Br-Ph, 3-NO2-Ph, or 4-Cl-Ph group; R1
substituted with 3-CH3 and the corresponding R2 substituted with
the 4-F-Ph, 4-OH-Ph, or 4-N,N-di-CH3-Ph group; R1 substituted
with 4-Cl and the corresponding R2 substituted with the 3-NO2-Ph,
4-Cl-3-NO2-Ph, 3-OH-4-OCH3-Ph, or 4-N,N-di-CH3-Ph group. The
strongest activity against tomato bacterial wilt was observed when
R1 was adjusted to 3-CH3, 4-Cl was substituted with an anilino
group, and R2 was substituted with the 2,6-di-Cl-Ph, 4-Cl-3-NO2-
Ph, 3-OH-4-OCH3-Ph, or 3-NO2-Ph group. These compounds were
found to be as potent as thiodiazole copper. The resulting com-
pounds revealed efficient broad-spectrum activities against the two
plant bacteria when R1 was 4-Cl and R2 was changed to the 4-Cl-3-
NO2-Ph, 3-OH-4-OCH3-Ph, or 3-NO2-Ph group.
Table 2
Crystal structure data collection and handling of synthesized compound 6t.
Entry
Items
Data collection and handling
1
2
3
4
5
6
7
8
Crystal system
Crystal Size
Wavelength
m
Monoclinic, yellow crystal
0.23 ꢁ 0.20 ꢁ 0.20 mm3
ꢀ
Mo Ka radiation (0.71073 A)
2.11 cmꢀ1
Diffractometer, scan mode
Bruker APEX-II CCD, 4 and u
52ꢂ
16092, 4231
Iobs > 2 s(Iobs), 3581
291
SHELX-97
E
2
qmax
N(hkl)measured, N(hkl)unique
Criterion for Iobs, N(hkl)gt
N(param)refined
Programs
Spatial configuration
9
10
11
The data in Tables 3e5 show the relationships between anti-
bacterial activities against tobacco and tomato bacterial wilts and
different aryl groups (style and position) of aromatic aldehydes. A
close analysis of the screening results and structures of the active
compounds revealed that the electron-donating substituents of the
phenyl ring (6f, 6g, 6h, 6j, 6k, 6p, 6s, 6x, and 6y) can increase
antimicrobial activity. Compared with the compounds bearing
electron-withdrawing groups, compounds 6q, 6t, 6v, and 6x with
chlorine-substituted ring exhibited more potent antibacterial ac-
tivities against tomato bacterial wilt. The presence of the eNO2, e
CH3, eCl, eBr, or eOH group in a compound was more effective in
improving antibacterial activity than that of other groups. For
instance, compounds 6g (R1 ¼ H, R2 ¼ 2-OH-5-OCH3-Ph), 6h
(R1 ¼ H, R2 ¼ 4-N,N-di-CH3-Ph), 6k (R1 ¼ 4-CH3, R2 ¼ 1-naphthyl),
6l (R1 ¼ 4-CH3, R2 ¼ 4-Br-Ph), 6n (R1 ¼ 4-CH3, R2 ¼ 3-NO2-Ph), 6o
(R1 ¼ 4-CH3, R2 ¼ 4-Cl-Ph), 6p (R1 ¼ 3-CH3, R2 ¼ 4-N,N-di-CH3-Ph),
6t (R1 ¼ 4-Cl, R2 ¼ 4-Cl-3-NO2-Ph), and 6x (R1 ¼ 4-Cl, R2 ¼ 3-OH-4-
favourable inhibitory activities against tobacco and tomato bacte-
rial wilts. Notably, compounds 6g, 6h, 6l, 6n, 6p, and 6x exhibited
excellent activities against tobacco bacterial wilt, with EC50 values
of 63.73, 76.46, 89.43, 99.37, 87.04, and 84.72 mg/mL, respectively.
As indicated in Table 4, these compounds had stronger antibacterial
activities than the commercial bactericide thiodiazole copper
(216.70
tivities against tomato bacterial wilt in vitro, with EC50 values of
38.64, 81.39, 50.18, and 49.26 g/mL, respectively. As shown in
mg/mL). Compounds 6q, 6t, 6v, and 6x showed strong ac-
m
Table 5, these compounds had stronger antibacterial activities
against tomato bacterial wilt than the commercial bactericide thi-
odiazole copper (99.80 mg/mL). Particularly, compound 6x showed
a comparable or stronger antibacterial activity against tobacco and
tomato bacterial wilts compared with thiodiazole copper. Thus,
compound 6x was regarded as the most promising antibacterial
agent and chosen for further evaluation.
OCH3-Ph) at 200
bacco bacterial wilt. These compounds had EC50 values ranging
from 63.73 g/mL to 201.52 g/mL, which were superior to that of
mg/mL showed 100% inhibition rate against to-
2.4. SAR of the Schiff base derivatives of quinazolinones
m
m
the commercial plant antibacterial agent thiodiazole copper
A SAR for test compounds 6ae6y can be drawn from the above
antibacterial bioassay evaluation as follows. Most of the final
compounds at 200 mg/mL showed moderate to good antibacterial
activities against tobacco and tomato bacterial wilts. Stronger ac-
tivities against tobacco bacterial wilt compared with thiodiazole
copper were demonstrated by the compounds having R1
substituted with H and R2 substituted with the 2-OH-5-CH3-Ph, 2-
OH-5-OCH3-Ph, or 4-N,N-di-CH3-Ph group; R1 substituted with 4-
(216.70
m
g/mL). Moreover, compounds 6q (R1 ¼ 4-CH3, R2 ¼ 2,6-di-
Cl-Ph), 6t (R1 ¼ 4-Cl, R2 ¼ 4-Cl-3-NO2-Ph), 6v (R1 ¼ 4-Cl, R2 ¼ 3-
NO2-Ph), and 6x (R1 ¼ 4-Cl, R2 ¼ 4-N,N-di-CH3-Ph) at 200
mg/mL
consistently showed 100% inhibition rate against tomato bacterial
wilt. These compounds had EC50 values of 38.64, 81.39, 50.18, and
45.96
mg/mL, which were superior to that of the commercial plant
antibacterial agent thiodiazole copper (99.80
mg/mL). Notably,
Fig. 2. Crystal structure of 6t.

X. Wang et al. / European Journal of Medicinal Chemistry 77 (2014) 65e74
69
Table 3
Table 4
Antibacterial activity of compounds 6ae6y against tobacco and tomato bacterial
wilts.
Inhibitory effect of compounds 6g, 6h, 6k, 6l, 6n, 6o, 6p, 6t and 6x against tobacco
bacterial wilt.a
Compd. R1
R2
Inhibition rate (%)a
Compd.
EC50
(m
g/mL)
pEC50
(
mM)
Y ¼ Bx þ A
R
Tobacco bacterial
wilt
Tomato bacterial
wilt
6g
6h
6k
6l
6n
6o
6p
6t
63.73
76.46
179.93
89.43
99.37
110.03
87.04
201.52
84.72
216.70
3.8129
3.7250
3.3806
3.7114
3.6334
3.5778
3.6889
3.3779
3.7234
/
y ¼ 2.3409x þ 0.7616
y ¼ 1.6289x þ 1.9321
y ¼ 1.3939x þ 1.8566
y ¼ 2.2979x þ 0.5157
y ¼ 1.7781x þ 1.4487
y ¼ 2.0650x þ 0.7843
y ¼ 1.5888x þ 1.9182
y ¼ 1.1613x þ 2.3240
y ¼ 2.0091x þ 0.9530
y ¼ 1.0312x þ 2.9418
0.9849
0.9950
0.9911
0.9838
0.9829
0.9784
0.9945
0.9710
0.9753
0.9903
200
g/mL)
100
g/mL)
200
g/mL)
100
(mg/mL)
(
m
(
m
(
m
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
6p
6q
6r
H
H
H
H
H
H
H
H
2,6-di-Cl-Ph
2-F-Ph
1-naphthyl
3,4-di-Cl-Ph
2-Cl-Ph
89
40
34
58
52
26
59
67
56
39
42
51
79
31
44
68
66
21
14
32
46
50
41
61
52
47
30
0
60
40
37
33
55
41
81
58
26
48
19
25
28
27
52
51
15
91
29
32
61
62
71
54
78
21
67
0
73
66
93
66
98
70
61
63
81
85
67
48
60
53
45
54
74
55
78
46
100
58
48
100
74
100
65
6x
Thiodiazole
b
copper
2-OH-5-CH3-Ph
2-OH-5-OCH3-Ph 100
4-N,N-di-CH3-Ph 100
a
Average of three replicates.
The commercial agricultural antibacterial thiodiazole copper was used for the
b
4-CH3 2-F-Ph
93
93
100
100
86
comparison of activity.
4-CH3 3-OH-4-OCH3-Ph
4-CH3 1-naphthyl
4-CH3 4-Br-Ph
4-CH3 2-NO2-Ph
4-CH3 3-NO2-Ph
4-CH3 4-Cl-Ph
particularly the mechanisms underlying their enhanced antibac-
terial activity, should be performed in future investigations.
100
100
3-CH3 4-N,N-di-CH3-Ph 100
4. Experimental
3-CH3 2,6-di-Cl-Ph
3-CH3 4-F-Ph
3-CH3 4-OH-Ph
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
44
90
97
100
85
93
6s
6t
4.1. General methods
4-Cl-3-NO2-Ph
Ph
3-NO2-Ph
4-OCH3-Ph
6u
6v
6w
6x
6y
Unless noted, all solvents and reagents were freshly distilled or
purified according to standard procedures. The IR spectra were
recorded on a Bruker VECTOR 22 spectrometer in KBr disk. 1H NMR
and 13C NMR were performed using deuterated chloroform (CDCl3)
or dimethyl sulfoxide (DMSO)-d6 as a solvent on a JEOL-ECX 500
NMR spectrometer at room temperature operating at 500 and
125 MHz, respectively, with trimethylsilyl (TMS) as an internal
standard. X-ray data for 6t were collected using a Bruker Smart
Apex CCD area detector diffractometer with Mo-Ka radiation.
Elemental analysis was performed on an Elementar Vario-III CHN
analyzer. Mass spectral studies were conducted on an Agilent 5973
organic mass spectrometer. Melting points were uncorrected and
determined with an XT-4 binocular microscope (Beijing Tech In-
strument Co., China). The following abbreviations were used to
designate chemical shift multiplicities: s ¼ singlet, d ¼ doublet,
t ¼ triplet, m ¼ multiplet, and bs ¼ broad singlet. All first-order
splitting patterns were assigned based on the appearance of the
multiplet. Splitting patterns that could not be easily interpreted
were designated as m or br. Analytical thin layer chromatography
(TLC) was performed on silica gel GF254. Flash column chromatog-
raphy was carried out on a 200e300 mesh silica gel.
81
3-OH-4-OCH3-Ph 100
100
50
100
0
4-N,N-di-CH3-Ph
96
50
0
thiodiazole copperb
CK
a
Average of three replicates.
b
The commercial agricultural antibacterial thiodiazole copper was used for the
comparison of activity.
compound 6x at 200 and 100
(78%) inhibition rates against tobacco and tomato bacterial wilts,
with EC50 values 84.72 and 45.96 g/mL, respectively.
mg/mL exhibited 100% (52%) and 100%
m
The results of primary in vitro antibacterial bioactivity assay and
preliminary SAR analysis revealed that the Schiff base derivatives
containing 4(3H)-quinazolinone cores had good antibacterial ac-
tivity. We can infer that these compounds were introduced with an
N-aryl group in position 2 of the quinazolinone fragment of the
target compounds, resulting in the retainment of the hydrogen-
bonding donor group. An aminoethyl group was then inserted on
the quinazolinone fragment in position 3, which might enhance the
flexibility of the molecular backbone, allowing it to combine with
the lowest energy and receptor protein molecular pathogenic
bacteria. The nitrogen atom in the C]N bond having a lone pair of
electrons caused by SP2 hybridization can be regarded as a
hydrogen-bond acceptor, which was perhaps the key to improve
the antibacterial activity of the target compounds.
4.2. General procedure for the preparation of intermediates 4ae4d
According to the reported procedures [23,37], the key in-
termediates 4ae4d were synthesized by a two-step process, as
3. Conclusion
Table 5
Inhibition effect of the compounds 6q, 6t, 6v and 6x against tomato bacterial wilt.a
In the present study, twenty-five novel Schiff base ramifications
containing quinazolinone nucleus were synthesized and their
biological activities were preliminary evaluated in vitro. Compound
6x exhibited stronger antibacterial activities against tobacco and
tomato bacterial wilts compared with the commercial plant
bactericide thiodiazole copper. Preliminary SAR analysis indicated
that the eCH3, eNO2, eOH, eCl, or N, N-di-methyl group on the
benzene ring (substituted for R2) enhanced the antibacterial ac-
tivity of the synthesized compounds. Further evaluation of the
in vivo antibacterial activity properties of the compounds,
Compd.
EC50
(m
g/mL) pEC50
(
mM) Toxic regression equation
R
6q
6t
6v
6x
38.64
81.39
50.18
49.26
4.0665
3.7721
3.9508
3.9586
/
y ¼ 2.2748x þ 1.3896
y ¼ 1.9813x þ 2.2146
y ¼ 2.3448x þ 1.0125
y ¼ 2.5260x þ 0.7247
y ¼ 1.0301x þ 2.9414
0.9859
0.9690
0.9497
0.9322
0.9913
Thiodiazole 99.80
b
copper
a
Average of three replicates.
b
The commercial agricultural antibacterial thiodiazole copper was used for the
comparison of activity.

70
X. Wang et al. / European Journal of Medicinal Chemistry 77 (2014) 65e74
shown in Scheme 1. Different aromatic isocyanates 2ae2d
(3 mmol) were added to a solution of iminophosphorane 1 (1.28 g,
3.0 mmol) in anhydrous tetrahydrofuran (THF, 10 mL) at room
temperature. The resulting mixture was stirred at 0 ꢂCe5 ꢂC for
10 he12 h to generate carbodiimides 3ae3d, which were used
directly without further purification. Subsequently, 3ae3d were
added dropwise into a solution of ethanediamine (3.0 mmol) in THF
(10 mL), and the reaction mixture was stirred for 6 he10 h at room
temperature. The solvent was removed under reduced pressure,
and the residue was recrystallized from CH2Cl2/CH3OH (1:1, v:v) to
yield 63%e80% of intermediates 4ae4d. The data for 4ae4d are
shown below.
product was filtered, washed, and then dried to produce title
compounds 6ae6y.
4.3.1. (E)-3-[2-((2,6-dichlorobenzylidene)amino)ethyl]-2-
anilinoquinazolin-4(3H)-one (6a)
White solid; IR (KBr, cmꢀ1
) n: 3246 (NeH, Qu-ringeNHeAr),
3034 (AreCeH), 1666 (C]O), 1608 (C]N), 1473e1581 (C]C and
NeH, benzene and Qu-ring and bending of NeH), 1444 (CeH), 1350
(CeN), 727e779 (CeCl); 1H NMR (500 MHz, CDCl3)
d in ppm: 9.02
(s, 1H, Qu-ringeNHeAr), 8.54 (s, 1H, eN]CHeAr), 8.18 (d, 1H,
J ¼ 8.00 Hz, QueH), 7.60 (t,1H, J ¼ 7.72 Hz, QueH), 7.14e7.44 (m, 9H,
AreH and QueH), 6.97 (t, 1H, J ¼ 6.87 Hz, AreH), 4.64 (s, 2H, C]Ne
CH2e), 4.21 (s, 2H, Qu-ringeCH2e); 13C NMR (125 MHz, CDCl3)
d in
4.2.1. 3-Aminoethyl-2-anilinoquinazolin-4(3H)-one (4a)
White solid; m.p. 159 ꢂCe160 ꢂC (literature [1], 160 ꢂCe161 ꢂC);
ppm: 163.70, 160.53, 148.86, 148.65, 139.48, 134.60, 134.37, 132.41,
131.13, 128.77, 128.63, 126.78, 125.81, 123.59, 122.83, 120.54, 118.22,
59.90, and 44.90; MS (ESI) m/z: 437.2 ([MþH]þ), 459.2 ([MþNa]þ).
yield, 80%; 1H NMR (500 MHz, CDCl3)
d in ppm: 11.14 (s, 1H, Qu-
ringeNHeAr), 8.12 (d, J ¼ 8.0 Hz,1H, QueH), 7.02e7.58 (m, 3H, Que
H and 5H, AreH), 4.20 (t, J ¼ 4.6 Hz 2H, QueCH2), 3.18 (t, J ¼ 4.6 Hz
2H, CH2NH2), 1.82 (s, 2H, CH2NH2); 13C NMR (125 MHz, CDCl3)
d in
4.3.2. (E)-3-(2-((2-fluorobenzylidene)amino)ethyl)-2-
anilinoquinazolin-4(3H)-one (6b)
ppm: 163.56, 149.20, 148.73, 139.99, 134.32, 128.92, 126.83, 125.54,
123.37, 122.71, 120.11, 118.17, 47.36, and 41.44. MS (ESI) m/z: 281.1
([MþH]þ), 303 ([MþNa]þ).
White solid; IR (KBr, cmꢀ1
) n: 3460 (NeH, Qu-ringeNHeAr),
3059 (AreCeH), 1674 (C]O), 1610 (C]N), 1473e1585 (C]C and
NeH, benzene and Qu-ring and bending of NeH), 1444 (CeH), 1278
4.2.2. 3-Aminoethyl-2-[4-methylanilino]quinazolin-4(3H)-one (4b)
White solid; m.p. 179 ꢂCe180 ꢂC; yield, 71%; 1H NMR (500 MHz,
(CeN), 1172e1253 (CeF); 1H NMR (500 MHz, CDCl3)
d in ppm: 8.83
(s, 1H, Qu-ringeNHeAr), 8.68 (s, 1H, eN]CHeAr), 8.19 (d, 1H,
J ¼ 8.05 Hz, AreH), 7.90 (t, 1H, J ¼ 6.87 Hz, AreH), 7.43e7.62 (m, 5H,
AreH), 7.03e7.30 (m, 6H, AreH and QueH), 4.63 (s, 2H, ]NeCH2e
CDCl3)
d
in ppm: 10.92 (s, 1H, Qu-ringeNHeAr), 8.13 (d, J ¼ 8.0 Hz,
1H, QueH), 7.55e7.59 (m, 1H, QueH), 7.12e7.45 (m, 3H, QueH and
4H, AreH), 4.26 (t, J ¼ 4.6 Hz 2H, QueCH2), 3.25 (t, J ¼ 4.6 Hz 2H,
CH2NH2), 2.30 (s, 3H, AreCH3), 1.78 (bs, 2H, eCH2NH2); 13C NMR
Ar), 4.12 (s, 2H, Qu-ring eCH2e); 13C NMR (125 MHz, CDCl3)
d in
ppm: 163.58, 158.56, 148.75, 148.48, 139.33, 134.36, 133.56, 133.49,
128.89,128.03,126.82,125.76,124.49,123.76,123.05,120.50,118.33,
116.38, 116.22, 60.17, and 45.21; MS (ESI) m/z: 387.3 ([MþH]þ),
409.3 ([MþNa]þ).
(125 MHz, CDCl3)
d in ppm: 163.64, 149.42, 148.90, 137.30, 134.26,
132.33, 129.42, 126.82, 125.57, 123.18, 120.35, 118.05, 47.33, 41.49,
and 20.97. MS (ESI) m/z: 295.1 ([MþH]þ), 317.1 ([MþNa]þ).
4.2.3. 3-Aminoethyl-2-[3-methylanilino]quinazolin-4(3H)-one (4c)
White solid; m.p. 177 ꢂCe178 ꢂC; yield, 68%; 1H NMR (500 MHz,
4.3.3. (E)-3-(2-((naphthalen-1-ylmethylene)amino)ethyl)-2-
CDCl3)
d
in ppm: 10.94 (s, 1H, Qu-ringeNHeAr), 8.14 (d, J ¼ 8.0 Hz,
anilinoquinazolin-4(3H)-one (6c)
White solid; IR (KBr, cmꢀ1
) n: 3278 (NeH, Qu-ringeNHeAr),
1H, QueH), 7.59 (t, J ¼ 7.2 Hz, 1H, QueH), 7.35e7.45 (m, 2H, QueH),
7.20e7.24 (m, 3H, AreH), 6.88 (d, J ¼ 7.5 Hz, 1H, AreH), 4.29 (t,
J ¼ 4.6 Hz 2H, QueCH2), 3.29 (t, J ¼ 4.6 Hz, 2H, eCH2NH2), 2.36 (s,
3059 (AreCeH), 1666 (C]O), 1614 (C]N), 1473e1587 (C]C and
NeH, benzene and Qu-ring and bending of NeH), 1444 (CeH), 1307
3H, AreCH3), 1.81 (bs, 2H, CH2NH2); 13C NMR (125 MHz, CDCl3)
d in
(CeN); 1H NMR (500 MHz, CDCl3)
d in ppm: 9.11 (s, 1H, Qu-ringe
ppm: 163.61, 149.25, 148.78, 139.85, 138.70, 134.28, 128.79, 126.83,
125.60, 123.64, 123.30, 120.77, 118.12, 117.41, 47.38, 41.48, and 21.73.
MS (ESI) m/z: 295.1 ([MþH]þ), 317.1 ([MþNa]þ).
NHeAr), 9.01 (s, 1H, eN]CHeAr), 8.56 (d, 1H, J ¼ 8.60 Hz, AreH),
8.20 (d, 1H, J ¼ 7.70 Hz, AreH), 7.91e7.98 (m, 3H, AreH), 7.40e7.59
(m, 5H, AreH), 7.08e7.25 (m, 5H, AreH and QueH), 7.90 (t, 1H,
J ¼ 7.45 Hz, AreH), 4.68 (s, 2H, ]NeCH2eAr), 4.23 (s, 2H, Qu-ring e
CH2e); 13C NMR (125 MHz, CDCl3)
d in ppm: 163.71, 148.93, 148.58,
4.2.4. 3-Aminoethyl-2-[4-chlorineanilino]quinazolin-4(3H)-one
(4d)
139.11, 134.39, 133.86, 132.18, 131.30, 130.79, 128.98, 128.67, 128.31,
127.64,126.81,126.45, 125.78,125.25,123.67,123.45,122.88,120.65,
118.32, 60.70, and 45.45; MS (ESI) m/z: 419.3 ([MþH]þ), 441.3
([MþNa]þ).
White solid; m.p. 152 ꢂCe153 ꢂC (literature [1], 151 ꢂCe153 ꢂC);
yield, 63%; 1H NMR (500 MHz, CDCl3)
d in ppm: 11.21 (s, 1H, Qu-
ringeNHeAr), 8.10 (t, J ¼ 8.0 Hz, 1H, QueH), 7.40e7.58 (m, 3H, Que
H, 1H, AreH), 7.19e7.28 (m, 3H, AreH), 4.23 (s, 2H, QueCH2), 3.23
(s, 2H, CH2NH2), 1.86 (bs, 2H, CH2NH2); 13C NMR (125 MHz, CDCl3)
d
in ppm: 163.47, 148.96, 148.48, 138.59, 134.42, 128.83, 127.43,
4.3.4. (E)-3-(2-((3,4-dichlorobenzylidene)amino)ethyl)-2-
126.85, 125.54, 123.61, 121.35, 118.16, 47.26, and 41.46. MS (ESI) m/z:
anilinoquinazolin-4(3H)-one (6d)
313 ([MꢀH]þ).
White solid; IR (KBr, cmꢀ1
) n: 3321 (NeH, Qu-ringeNHeAr),
3136 (AreCeH), 1668 (C]O), 1610 (C]N), 1475e1591 (C]C and
NeH, benzene and Qu-ring and bending of NeH), 1446 (CeH), 1348
4.3. General procedure for the preparation of title compounds 6ae6y
(CeN), 692e761 (CeCl); 1H NMR (500 MHz, CDCl3)
d in ppm: 8.54
Target Compounds 6ae6y were synthesized as shown in
Scheme 1. Aromatic aldehyde (1.2 mmol) was added to a solution of
intermediates 4ae4d (1 mmol) in anhydrous CH3CH2OH (15 mL) at
(s, 1H, Qu-ringeNHeAr), 8.29 (s, 1H, eN]CHeAr), 8.18 (d, 1H,
J ¼ 6.85 Hz, AreH), 7.91 (d,1H, J ¼ 5.75 Hz, AreH), 7.23e7.61 (m, 9H,
AreH and QueH), 7.09 (t, 1H, J ¼ 6.85 Hz, AreH), 4.63 (s, 2H, ]Ne
CH2eAr), 4.12 (s, 2H, Qu-ring eCH2e); 13C NMR (125 MHz, CDCl3)
0
ꢂCe50 ꢂC. The resulting mixture was heated up to 75 ꢂC with
stirring and refluxing for a specific reaction time (ranging from
12 mine8 h). Upon completion of the reaction indicated by TLC, the
solvent was removed under depressurization, and the residue was
recrystallized from CH2Cl2/CH3CH2OH (1:15, v:v). The obtained
d in ppm: 163.53, 162.44, 148.58, 148.44, 139.07, 136.04, 136.04,
134.70, 134.48, 133.65, 131.01, 129.55, 129.10, 127.88, 126.78, 125.78,
123.81, 123.36, 120.61, 118.24, 59.93, and 45.00; MS (ESI) m/z: 437.2
([MþH]þ), 459.2 ([MþNa]þ).

X. Wang et al. / European Journal of Medicinal Chemistry 77 (2014) 65e74
71
4.3.5. (E)-3-(2-((2-chlorobenzylidene)amino)ethyl)-2-
NeH, benzene and Qu-ring and bending of NeH), 1456 (CeH), 1309
(CeN), 1024e1384 (CeF); 1H NMR (500 MHz, CDCl3)
in ppm: 8.70
(s, 1H, Qu-ringeNHeAr), 8.66 (s, 1H, eN]CHeAr), 8.17 (d, 1H,
J ¼ 6.90 Hz, AreH), 7.89 (d, 1H, J ¼ 5.70 Hz, AreH), 7.07e7.58 (m,
10H, AreH and QueH), 4.61 (s, 2H, ]NeCH2eAr), 4.11 (s, 2H, Qu-
ring eCH2e), 2.31 (s, 3H, AreCH3); 13C NMR (125 MHz, CDCl3)
anilinoquinazolin-4(3H)-one (6e)
d
White solid; IR (KBr, cmꢀ1
)
n
: 3263 (NeH, Qu-ringeNHeAr),
3062 (AreCeH), 1674 (C]O), 1610 (C]N), 1473e1587 (C]C and
NeH, benzene and Qu-ring and bending of NeH), 1444 (CeH), 1303
(CeN), 551e754 (CeCl); 1H NMR (500 MHz, CDCl3)
d in ppm: 8.90
(s, 1H, Qu-ringeNHeAr), 8.82 (s, 1H, eN]CHeAr), 8.19 (d, 1H,
J ¼ 8.05 Hz, AreH), 7.97 (d, 1H, J ¼ 7.40 Hz, AreH), 7.23e7.62 (m,
10H, AreH and QueH), 7.03 (t, 1H, J ¼ 7.15 Hz, AreH), 4.63 (s, 2H, ]
NeCH2eAr), 4.15 (s, 2H, Qu-ring eCH2e); 13C NMR (125 MHz,
d in ppm: 163.61, 161.37, 158.42, 149.05, 148.64, 136.65, 134.35,
133.45, 132.72, 129.41, 128.03, 126.81, 125.71, 124.48, 123.54, 122.85,
120.87, 118.20, 116.20, 60.23, 45.16, and 20.94; MS (ESI) m/z: 401.3
([MþH]þ), 423.3 ([MþNa]þ).
CDCl3)
d in ppm: 163.59, 161.85, 148.74, 148.49, 139.29, 135.71,
134.42, 132.69, 132.25, 130.28, 128.88, 128.54, 127.12,126.83, 125.76,
123.76, 123.04, 120.50, 118.32, 59.87, and 45.21; MS (ESI) m/z: 403.2
([MþH]þ), 425.2 ([MþNa]þ).
4.3.10. (E)-3-[2-((3-hydroxy-4-methoxybenzylidene)amino)ethyl]-
2-(4-methylanilino)quinazolin-4(3H)-one (6j)
White solid; IR (KBr, cmꢀ1
) n: 3365 (NeH and OeH, Qu-ringe
NHeAr and AreOH), 2845 (AreCeH), 1664 (C]O), 1614 (C]N),
1475e1583 (C]C and NeH, benzene and Qu-ring and bending of
NeH), 1438 (CeH), 1273 (CeN), 1020e1242 (CeO); 1H NMR
4.3.6. (E)-3-(2-((2-hydroxy-5-methylbenzylidene)amino)ethyl)-2-
anilinoquinazolin-4(3H)-one (6f)
Yellow solid; IR (KBr, cmꢀ1
)
n: 3417 (NeH and OeH, Qu-ringe
(500 MHz, CDCl3) d in ppm: 8.77 (s, 1H, eOH), 8.21 (s, 1H, eN]CHe
NHeAr and AreOH), 3053 (AreCeH), 2916 (¼CH), 1668 (C]O),
1606 (C]N), 1473e1562 (C]C and NeH, benzene and Qu-ring and
bending of NeH), 1442 (CeH), 1282 (CeN), 1024e1282 (CeO); 1H
Ar), 8.16 (d,1H, J ¼ 7.45 Hz, AreH), 7.10e7.56 (m, 9H, AreH and Que
H), 6.83 (d, 1H, J ¼ 8.00 Hz, AreH), 5.75 (s, 1H, Qu-ringeNHeAr),
4.59 (s, 2H, ]NeCH2eAr), 4.04 (s, 2H, Qu-ring eCH2e), 3.91 (s, 3H,
NMR (500 MHz, CDCl3)
d
in ppm: 12.24 (s, 1H, AreOH), 8.31 (s, 1H,
AreOCH3), 2.31 (s, 3H, AreCH3); 13C NMR (125 MHz, CDCl3)
d in
Qu-ringeNHeAr), 8.18 (d, 1H, J ¼ 7.75 Hz, eN]CHeAr), 7.60 (t, 1H,
J ¼ 7.40 Hz, AreH), 7.390 (t, 4H, J ¼ 6.85 Hz, AreH), 6.86e7.15 (m,
6H, AreH and QueH), 6.72 (s, 1H, AreH), 4.56 (s, 2H, ]NeCH2eAr),
4.14 (s, 2H, Qu-ring eCH2e), 2.23 (s, 3H, AreCH3); 13C NMR
ppm: 164.07, 163.69, 149.63, 149.30, 148.71, 146.12, 136.67, 134.29,
132.65, 129.43, 128.70, 126.77, 125.70, 123.44, 122.20, 121.12, 118.17,
111.53, 110.36, 59.91, 56.14, 45.38, and 20.95; MS (ESI) m/z: 429.3
([MþH]þ), 451.3 ([MþNa]þ).
(125 MHz, CDCl3)
d in ppm: 169.19, 158.21, 148.20, 138.41, 134.78,
134.61, 1334.46, 132.27, 130.24, 128.89, 128.76, 128.66, 126.81,
125.86, 124.00, 123.75, 122.41, 121.22, 118.18, 117.92, 116.91, 59.63,
44.68, and 20.35; MS (ESI) m/z: 399.3 ([MþH]þ), 421.3 ([MþNa]þ).
4.3.11. (E)-3-(2-((naphthalen-1-ylmethylene)amino)ethyl)-2-(4-
methylanilino)quinazolin-4(3H)-one (6k)
White solid; IR (KBr, cmꢀ1
) n: 3228 (NeH, Qu-ringeNHeAr),
3030 (AreCeH), 1666 (C]O), 1614 (C]N), 1475e1587 (C]C and
NeH, benzene and Qu-ring and bending of NeH), 1435 (CeH),
4.3.7. (E)-3-(2-((2-hydroxy-5-methoxybenzylidene)amino)ethyl)-
2-anilinoquinazolin-4(3H)-one (6g)
1024e1290 (CeN); 1H NMR (500 MHz, CDCl3)
d in ppm: 9.08 (s, 1H,
Yellow solid; IR (KBr, cmꢀ1
)
n: 3400 (NeH and OeH, Qu-ringe
Qu-ringeNHeAr), 8.86 (s, 1H, eN]CHeAr), 8.55 (d, 1H, J ¼ 6.85 Hz,
NHeAr and AreOH), 3061 (AreCeH), 2961 (¼CH), 1658 (C]O),
1604 (C]N), 1471e1562 (C]C and NeH, benzene and Qu-ring and
bending of NeH), 1444 (CeH), 1273 (CeN), 1031e1228 (CeO); 1H
AreH), 8.19 (d, 1H, J ¼ 8.00 Hz, AreH), 7.90e7.97 (m, 3H, AreH),
4
7.37e7.58 (m, 5H, AreH and QueH), 7.25 (dd, 1H, JHH ¼ 6.85 Hz,
3JHH ¼ 9.20 Hz, AreH), 7.07 (d, 1H, J ¼ 8.05 Hz, AreH), 6.91 (d, 1H,
J ¼ 8.00 Hz, AreH), 4.66 (s, 2H, ]NeCH2eAr), 4.22 (s, 2H, Qu-ring e
NMR (500 MHz, CDCl3)
d in ppm: 12.03 (s, 1H, AreOH), 8.32 (s, 1H,
Qu-ringeNHeAr), 8.18 (d, 1H, J ¼ 8.00 Hz, eN]CHeAr), 6.87e7.62
(m, 11H, AreH and QueH), 6.67 (s, 1H, AreH), 4.56 (t, 2H,
J ¼ 5.00 Hz, ]NeCH2eAr), 4.12 (t, 2H, J ¼ 5.00 Hz, Qu-ring eCH2e),
CH2e), 2.24 (s, 3H, AreCH3); 13C NMR (125 MHz, CDCl3)
d in ppm:
163.76, 163.60, 149.19, 148.74, 136.44, 134.32, 133.85, 132.50, 132.14,
131.30, 130.80, 129.17, 128.97, 128.34, 127.63, 126.78, 126.44, 125.76,
125.25, 123.48, 123.46, 120.95, 118.20, 60.75, 45.39, and 20.87; MS
(ESI) m/z: 433.3 ([MþH]þ), 455.3 ([MþNa]þ).
3.71 (s, 3H, AreOCH3); 13C NMR (125 MHz, CDCl3)
d in ppm: 168.86,
166.09, 163.31, 154.64, 152.53, 148.25, 147.72, 138.37, 134.63, 130.24,
128.90, 126.81, 125.87, 124.01, 123.77, 122.40, 121.22, 121.01, 118.06,
117.85, 115.11, 59.66, 55.94, and 44.60; MS (ESI) m/z: 415.3
([MþH]þ), 437.3 ([MþNa]þ).
4.3.12. (E)-3-(2-((4-bromobenzylidene)amino)ethyl)-2-(4-
methylanilino)quinazolin-4(3H)-one (6l)
White solid; IR (KBr, cmꢀ1
) n: 3265 (NeH, Qu-ringeNHeAr),
4.3.8. (E)-3-(2-((4-(dimethylamino)benzylidene)amino)ethyl)-2-
3053 (AreCeH), 1666 (C]O), 1610 (C]N), 1473e1589 (C]C and
NeH, benzene and Qu-ring and bending of NeH), 1444 (CeH),
anilinoquinazolin-4(3H)-one (6h)
Grey solid; IR (KBr, cmꢀ1
)
n
: 3444 (NeH, Qu-ringeNHeAr),
1008e1311 (CeN); 1H NMR (500 MHz, CDCl3)
d in ppm: 8.60 (d, 1H,
3053 (AreCeH), 1676 (C]O), 1604 (C]N), 1496e1583 (C]C and
NeH, benzene and Qu-ring and bending of NeH), 1444 (CeH),
J ¼ 8.60 Hz, Qu-ringeNHeAr), 8.30 (d, 1H, J ¼ 9.15 Hz, N]CHeAr),
8.16 (t, 1H, J ¼ 8.30 Hz, AreH), 7.09e7.58 (m, 11H, AreH and QueH),
4.60 (s, 2H, ]NeCH2eAr), 4.07 (s, 2H, Qu-ring eCH2e), 2.33 (s, 3H,
1165e1305 (CeN); 1H NMR (500 MHz, CDCl3)
d in ppm: 9.33 (s,
1H, Qu-ringeNHeAr), 6.62e8.19 (m, 14H, eCH2]CH, AreH and
QueH), 4.57 (s, 2H, ]NeCH2eAr), 4.01 (s, 2H, Qu-ring eCH2e),
AreCH3); 13C NMR (125 MHz, CDCl3)
d in ppm: 163.42, 148.79,
148.63,136.56,134.20, 133.79, 132.93, 132.18,132.00,129.92,129.73,
129.50, 129.30, 126.78, 126.19, 125.74, 123.55, 123.35,120.90, 120.71,
118.14, 59.92, 45.06, and 20.59; MS (ESI) m/z: 463.2 ([Mþ2þH]þ),
483.2 ([MþNa]þ).
3.00 (s, 6H, AreN(CH3)2); 13C NMR (125 MHz, CDCl3)
d in ppm:
164.42, 163.66, 152.66, 149.15, 148.62, 139.66, 134.26, 130.22,
128.85, 126.81, 125.72, 123.54, 122.88, 122.78, 120.62, 118.35, 111.51,
59.85, 45.68, and 40.25; MS (ESI) m/z: 412.2 ([MþH]þ), 434.1
([MþNa]þ).
4.3.13. (E)-3-[2-((2-nitrobenzylidene)amino)ethyl]-2-(4-
methylanilino)quinazolin-4(3H)-one (6m)
4.3.9. (E)-3-(2-((2-fluorobenzylidene)amino)ethyl)-2-(4-
methylanilino)quinazolin-4(3H)-one (6i)
Yellow solid; IR (KBr, cmꢀ1
) n: 3246 (NeH, Qu-ringeNHeAr),
3032 (AreCeH), 1674 (C]O), 1610 (C]N), 1473e1587 (C]C, N]O
and NeH, benzene and Qu-ring and bending of NeH and eNO2 of
N]O), 1446 (CeH), 1020e1290 (CeN); 1H NMR (500 MHz, CDCl3)
White solid; IR (KBr, cmꢀ1
)
n
: 3253 (NeH, Qu-ringeNHeAr),
3037 (AreCeH), 1674 (C]O), 1610 (C]N), 1473e1585 (C]C and

72
X. Wang et al. / European Journal of Medicinal Chemistry 77 (2014) 65e74
d
in ppm: 8.84 (s, 2H, Qu-ringeNHeAr and eN]CHeAr), 8.18 (d,
Qu-ringeNHeAr), 8.52 (s, 1H, eN]CHeAr), 8.17 (d, 1H, J ¼ 6.00 Hz,
AreH), 7.60 (t, 1H, J ¼ 7.80 Hz, AreH), 7.06e7.46 (m, 7H, AreH and
QueH), 6.83 (s, 1H, QueH), 6.78 (d, 1H, J ¼ 8.00 Hz, AreH), 4.61 (s,
2H, ]NeCH2eAr), 4.19 (s, 2H, Qu-ring eCH2e), 2.14 (s, 3H, eAre
1H, J ¼ 8.05 Hz, AreH), 8.12 (t, 1H, J ¼ 3.45 Hz, AreH), 7.90 (t, 1H,
J ¼ 5.75 Hz, AreH), 7.58e7.65 (m, 3H, AreH), 7.44 (d, 1H,
J ¼ 8.00 Hz, QueH), 7.20e7.26 (m, 3H, QueH), 7.03 (d, 2H,
J ¼ 8.00 Hz, AreH), 4.63 (s, 2H, ]NeCH2eAr), 4.18 (s, 2H, Qu-ring e
CH3); 13C NMR (125 MHz, CDCl3)
d in ppm: 163.72, 160.43, 148.92,
CH2e), 2.29 (s, 3H, AreCH3); 13C NMR (125 MHz, CDCl3)
d
in ppm:
148.72, 134.65, 134.32, 132.51, 131.10, 128.76, 128.50, 128.30, 126.77,
125.84, 123.87, 123.70, 123.49, 121.08, 118.17, 117.95, 59.95, 44.87,
and 21.50; MS (ESI) m/z: 451.1 ([MþH]þ), 473.1 ([MþNa]þ).
163.59, 161.36, 148.80, 148.58, 136.59, 134.43, 134.00, 132.61, 131.69,
130.67, 130.02, 129.37, 126.86, 125.70, 124.90, 123.63, 120.48, 118.20,
59.56, 44.92, and 20.91; MS (ESI) m/z: 428.3 ([MþH]þ), 450.3
([MþNa]þ).
4.3.18. (E)-3-[2-((4-fluorobenzylidene)amino)ethyl]-2-(3-
methylanilino)quinazolin-4(3H)-one (6r)
4.3.14. (E)-3-[2-((3-nitrobenzylidene)amino)ethyl]-2-(4-
White solid; IR (KBr, cmꢀ1
) n: 3363 (NeH, Qu-ringeNHeAr),
methylanilino)quinazolin-4(3H)-one (6n)
3029 (AreCeH), 1664 (C]O), 1610 (C]N), 1471e1560 (C]C and
NeH, benzene and Qu-ring and bending of NeH), 1448 (CeH),
Yellow crystal; IR (KBr, cmꢀ1
) n: 3292 (NeH, Qu-ringeNHeAr),
2914 (AreCeH), 1662 (C]O), 1612 (C]N), 1473e1587 (C]C, N]O
and NeH, benzene and Qu-ring and bending of NeH and eNO2 of
N]O), 1436 (CeH), 1352 (N]O), 1033e1284 (CeN); 1H NMR
1029e1280 (CeN and CeF); 1H NMR (500 MHz, CDCl3)
d in ppm:
8.89 (s, 1H, Qu-ringeNHeAr), 8.33 (s, 1H, eN]CHeAr), 8.17 (d, 1H,
J ¼ 6.30 Hz, AreH), 7.06e7.74 (m, 10H, AreH and QueH), 6.88 (d,
1H, J ¼ 7.45 Hz, AreH), 4.60 (s, 2H, ]NeCH2eAr), 4.09 (t, 2H,
J ¼ 5.15 Hz, Qu-ring eCH2e), 2.28 (s, 3H, eAreCH3); 13C NMR
(500 MHz, CDCl3)
d in ppm: 8.67 (s, 1H, Qu-ringeNHeAr), 8.42 (s,
1H, eN]CHeAr), 8.31 (d, 1H, J ¼ 9.70 Hz, AreH), 8.24 (s, 1H, AreH),
8.16 (d, 1H, J ¼ 6.30 Hz, AreH), 7.96 (d, 1H, J ¼ 7.45 Hz, AreH), 7.59
(t, 2H, J ¼ 7.72 Hz, AreH), 7.40 (d, 3H, J ¼ 8.00 Hz, QueH), 7.24 (t,1H,
J ¼ 8.00 Hz, QueH), 7.12 (d, 2H, J ¼ 8.55 Hz, AreH), 4.66 (s, 2H, ]Ne
CH2eAr), 4.17 (s, 2H, Qu-ring eCH2e), 2.31 (s, 3H, eAreCH3); 13C
(125 MHz, CDCl3)
d in ppm: 163.91, 163.58, 163.38, 148.88, 148.56,
139.10, 138.72, 134.38, 131.35, 130.71, 130.64, 128.81, 126.79, 125.78,
124.07, 123.66, 121.28, 118.24, 118.05, 116.18, 116.01, 59.93, 45.18,
and 21.55; MS (ESI) m/z: 401.2 ([MþH]þ), 423.1 ([MþNa]þ).
NMR (125 MHz, CDCl3)
d in ppm: 163.53, 162.44, 148.67, 148.64,
148.55, 136.44, 136.30, 134.47, 134.45, 133.06, 130.11, 129.59, 126.75,
126.08, 125.74, 123.67, 122.65, 120.72, 118.11, 60.20, 44.81, and
20.92; MS (ESI) m/z: 428.3 ([MþH]þ), 450.3 ([MþNa]þ).
4.3.19. (E)-3-[2-((4-hydroxybenzylidene)amino)ethyl]-2-(3-
methylanilino)quinazolin-4(3H)-one (6s)
White solid; IR (KBr, cmꢀ1
) n: 3363 (NeH and OeH, Qu-ringe
NHeAr and AreOH), 3023 (AreCeH), 1654 (C]O), 1608 (C]N),
1473e1558 (C]C and NeH, benzene and Qu-ring and bending of
NeH), 1442 (CeH), 1039e1280 (CeN and CeO); 1H NMR
4.3.15. (E)-3-[2-((4-chlorobenzylidene)amino)ethyl]-2-(4-
methylanilino)quinazolin-4(3H)-one (6o)
White solid; IR (KBr, cmꢀ1
)
n: 3261 (NeH, Qu-ringeNHeAr),
(500 MHz, DMSO-d6) d in ppm: 10.01 (s, 1H, AreOH), 8.83 (s, 1H,
3030 (AreCeH), 1664 (C]O), 1637 (C]N), 1473e1587 (C]C and
NeH, benzene and Qu-ring and bending of NeH), 1436 (CeH),
Qu-ringeNHeAr), 8.27 (s, 1H, eN]CHeAr), 8.01 (d, 1H,
J ¼ 6.90 Hz, AreH), 7.56e7.64 (m, 3H, AreH), 7.47 (d, 1H,
J ¼ 8.60 Hz, AreH), 7.19e7.28 (m, 4H, QueH), 6.89 (d, 1H,
J ¼ 7.45 Hz, AreH), 6.78 (d, 2H, J ¼ 8.60 Hz, AreH), 4.53 (t, 2H,
J ¼ 5.70 Hz, ]NeCH2eAr), 3.91 (t, 2H, J ¼ 6.30 Hz, Qu-ring eCH2e
1033e1294 (CeN); 1H NMR (500 MHz, CDCl3)
d in ppm: 8.61 (s, 1H,
Qu-ringeNHeAr), 8.33 (s, 1H, eN]CHeAr), 8.16 (d, 1H, J ¼ 8.05 Hz,
AreH), 7.65 (d, 2H, J ¼ 8.60 Hz, AreH), 7.60 (t, 1H, J ¼ 6.85 Hz, Are
H), 7.34e7.41 (m, 5H, AreH and QueH), 7.23 (d,1H, J ¼ 7.40 Hz, Que
H), 7.12 (d,1H, J ¼ 8.00 Hz, AreH), 4.61 (s, 2H, ]NeCH2eAr), 4.09 (s,
2H, Qu-ring eCH2e), 2.33 (s, 3H, eAreCH3); 13C NMR (125 MHz,
), 2.26 (s, 3H, eAreCH3); 13C NMR (125 MHz, DMSO-d6)
d in ppm:
163.80, 162.53, 160.83, 149.10, 148.64, 139.57, 138.13, 134.87, 130.56,
128.81, 127.20, 126.88, 125.52, 124.32, 123.57, 122.76, 119.57, 117.93,
115.93, 59.05, 44.01, and 21.54; MS (ESI) m/z: 399.2 ([MþH]þ),
421.1 ([MþNa]þ).
CDCl3)
d in ppm: 163.60, 163.49, 149.00, 148.63, 137.88, 136.56,
134.39,133.39,132.92,129.75,129.49,129.22,126.77,125.74,123.56,
120.92, 118.14, 59.92, 45.10, and 20.59; MS (ESI) m/z: 417.3
([MþH]þ), 43 9.3 ([MþNa]þ).
4.3.20. (E)-3-[2-((4-chloro-3-nitrobenzylidene)amino)ethyl]-2-[(4-
chlorophenyl)amino]quinazolin-4(3H)-one (6t)
4.3.16. (E)-3-[2-((4-(dimethylamino)benzylidene)amino)ethyl]-2-
Yellow crystal; IR (KBr, cmꢀ1
) n: 3265 (NeH, Qu-ringeNHeAr),
(3-methylanilino)quinazolin-4(3H)-one (6p)
3057 (AreCeH), 1674 (C]O), 1606 (C]N), 1471e1581 (C]C, N]O
and NeH, benzene and Qu-ring and bending of NeH and eNO2 of
N]O), 1442 (CeH), 1357 (N]O), 1024e1284 (CeN); 1H NMR
White solid; IR (KBr, cmꢀ1
) n: 3263 (NeH, Qu-ringeNHeAr),
1668 (C]O), 1610 (C]N), 1473e1587 (C]C and NeH, benzene and
Qu-ring and bending of NeH), 1448 (CeH), 1033e1296 (CeN); 1H
(500 MHz, CDCl3)
d in ppm: 8.36 (s, 1H, Qu-ringeNHeAr), 8.31 (s,
NMR (500 MHz, CDCl3)
d
in ppm: 9.19 (s, 1H, Qu-ringeNHeAr), 8.20
1H, eN]CHeAr), 8.28 (s, 1H, AreH), 8.16 (d, 1H, J ¼ 7.45 Hz, AreH),
(s, 1H, eN]CHeAr), 8.17 (d, 1H, J ¼ 8.00 Hz, AreH), 7.18e7.60 (m,
8H, AreH and QueH), 6.86 (d, 1H, J ¼ 7.45 Hz, QueH), 6.65 (d, 1H,
J ¼ 8.60 Hz, AreH), 4.57 (s, 2H, ]NeCH2eAr), 4.01 (s, 2H, Qu-ring e
CH2e), 3.01 (s, 6H, AreN(CH3)2), 2.31 (s, 3H, AreCH3); 13C NMR
7.24e7.74 (m, 9H, QueH and AreH), 4.64 (s, 2H, ]NeCH2eAr), 4.15
(s, 2H, Qu-ring eCH2e); 13C NMR (125 MHz, CDCl3)
d in ppm:
163.32, 161.61, 148.41, 148.12, 148.07, 137.53, 134.67, 134.58, 132.72,
132.56, 130.23, 129.13, 128.35, 126.82, 125.74, 124.41, 124.14, 121.62,
118.24, 60.03, and 44.72; MS (ESI) m/z: 482.2 ([MþH]þ), 504.2
([MþNa]þ).
(125 MHz, CDCl3)
d in ppm: 164.36, 163.69, 152.66, 149.33, 148.70,
139.42, 138.54, 134.23, 130.27, 128.68, 126.79, 125.74,123.74,123.46,
122.97,121.51,118.25,111.53, 59.97, 45.66, 40.25, and 21.54; MS (ESI)
m/z: 426.4 ([MþH]þ), 448.4 ([MþNa]þ).
4.3.21. (E)-3-[2-(benzylideneamino)ethyl]-2-[(4-chlorophenyl)
amino]quinazolin-4(3H)-one (6u)
4.3.17. (E)-3-[2-((2,6-dichlorobenzylidene)amino)ethyl]-2-(3-
White solid; IR (KBr, cmꢀ1
) n: 3271 (NeH, Qu-ringeNHeAr),
methylanilino)quinazolin-4(3H)-one (6q)
3088 (AreCeH), 1672 (C]O), 1606 (C]N), 1475e1587 (C]C and
NeH, benzene and Qu-ring and bending of NeH), 1435 (CeH),
White solid; IR (KBr, cmꢀ1
) n: 3566 (NeH, Qu-ringeNHeAr),
3039 (AreCeH), 1664 (C]O), 1610 (C]N), 1473e1591 (C]C and
NeH, benzene and Qu-ring and bending of NeH), 1436 (CeH),
1022e1350 (CeN); 1H NMR (500 MHz, CDCl3)
d in ppm: 9.00 (s, 1H,
Qu-ringeNHeAr), 8.38 (s, 1H, eN]CHeAr), 8.18 (d, 1H, J ¼ 6.85 Hz,
1033e1296 (CeN); 1H NMR (500 MHz, CDCl3)
d in ppm: 9.00 (s, 1H,
AreH), 7.39e7.69 (m, 9H, AreH and QueH), 7.22e7.25 (m, 3H, Are

X. Wang et al. / European Journal of Medicinal Chemistry 77 (2014) 65e74
73
H and QueH), 4.60 (s, 2H, ]NeCH2eAr), 4.09 (s, 2H, Qu-ring e
CH2e); 13C NMR (125 MHz, CDCl3)
in ppm: 165.03, 163.49, 148.68,
148.29, 137.98, 134.87, 134.49, 131.96, 128.96, 128.82, 128.54, 127.85,
126.86, 125.71, 123.93, 121.86, 118.35, 59.84, 45.27; MS (ESI) m/z:
403.3 ([MþH]þ), 425.3 ([MþNa]þ).
148.38, 138.31, 134.37, 130.18, 128.77, 127.54, 126.87, 125.66, 123.78,
122.69, 121.88, 118.39, 111.48, 59.79, 45.63, 40.28; MS (ESI) m/z:
446.1 ([MþH]þ), 468.1 ([MþNa]þ).
d
Acknowledgement
4.3.22. (E)-2-[(4-chlorophenyl)amino]-3-[2-((3-nitrobenzylidene)
We gratefully acknowledge assistance from the National Key
Technologies R&D Program (No. 2011BAE06B05-6).
amino)ethyl]quinazolin-4(3H)-one (6v)
White solid; IR (KBr, cmꢀ1
) n: 3271 (NeH, Qu-ringeNHeAr),
2875 (AreCeH), 1672 (C]O), 1606 (C]N), 1475e1587 (C]C, N]O
and NeH, benzene and Qu-ring and bending of NeH and eNO2 of
N]O), 1435 (CeH), 1350 (N]O), 1022e1303 (CeN); 1H NMR
Appendix A. Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.ejmech.2014.02.053.
(500 MHz, CDCl3)
d in ppm: 8.65 (s, 1H, Qu-ringeNHeAr), 8.44 (s,
2H, eN]CHeAr and AreH), 8.32 (d, 1H, J ¼ 8.55 Hz, AreH), 8.17 (d,
1H, J ¼ 6.90 Hz, AreH), 7.94 (d, 1H, J ¼ 8.00 Hz, AreH), 7.62 (dd, 2H,
4JHH ¼ 8.60 Hz, 3JHH ¼ 8.00 Hz, AreH), 7.51 (d, 2H, J ¼ 8.60 Hz, Are
References
4
H), 7.41 (d, 1H, J ¼ 8.00 Hz, QueH), 7.41 (dd, 3H, JHH ¼ 2.30 Hz,
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3034 (AreCeH), 1670 (C]O), 1604 (C]N), 1473e1585 (C]C and
NeH, benzene and Qu-ring and bending of NeH), 1436 (CeH), 1259
(CeN), 1037e1165 (CeO); 1H NMR (500 MHz, CDCl3)
d in ppm: 9.13
(s, 1H, Qu-ringeNHeAr), 8.28 (s, 1H, eN]CHeAr), 8.18 (d, 1H,
J ¼ 8.00 Hz, AreH), 7.23e7.63 (m, 9H, AreH and QueH), 6.90 (d, 2H,
J ¼ 8.55 Hz, AreH and QueH), 4.58 (s, 2H, ]NeCH2eAr), 4.04 (s,
2H, Qu-ring eCH2e), 3.84 (s, 3H, AreOCH3); 13C NMR (125 MHz,
CDCl3)
d in ppm: 164.19, 163.49, 162.58, 148.75, 148.30, 138.10,
134.46, 130.28, 128.83, 127.78, 127.75, 126.85, 125.69, 123.89, 121.83,
118.36, 114.30, 59.77, 55.58, 45.38; MS (ESI) m/z: 433.1 ([MþH]þ),
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4.3.24. (E)-2-[(4-chlorophenyl)amino]-3-[2-((3-hydroxy-4-
methoxybenzylidene)amino)ethyl]quinazolin-4(3H)-one (6x)
Grey solid; IR (KBr, cmꢀ1
) n: 3531 (NeH and OeH, Qu-ringeNHe
Ar and AreOH), 3205 (AreCeH), 2904 (¼CH), 1670 (C]O), 1604
(C]N), 1473e1585 (C]C and NeH, benzene and Qu-ring and
bending of NeH), 1436 (CeH), 1278 (CeN), 1020e1209 (CeO); 1H
NMR (500 MHz, CDCl3)
d in ppm: 9.01 (s, 1H, AreOH), 8.21 (s, 1H,
Qu-ringeNHeAr), 8.16 (s, 1H, eN]CHeAr), 7.11e7.59 (m, 10H, Are
H and QueH), 6.82 (d, 1H, J ¼ 7.45 Hz, AreH), 5.87 (s, 1H, AreH),
4.57 (s, 2H, ]NeCH2eAr), 4.02 (s, 2H, Qu-ring eCH2e), 3.91 (s, 3H,
AreOCH3); 13C NMR (125 MHz, CDCl3)
d in ppm: 164.27, 163.47,
149.75,148.80,148.32, 146.20, 137.99,134.46, 128.84, 128.53, 127.79,
126.84, 125.67, 123.87, 122.20, 122.01, 118.33, 113.38, 110.39, 59.77,
56.16, 45.39; MS (ESI) m/z: 449.1 ([MþH]þ), 471.0 ([MþNa]þ).
4.3.25. (E)-2-[(4-chlorophenyl)amino]-3-[2-((4-(dimethylamino)
benzylidene)amino)ethyl]quinazolin-4(3H)-one (6y)
Grey solid; IR (KBr, cmꢀ1
) n: 3246 (NeH, Qu-ringeNHeAr), 3034
(AreCeH), 1678 (C]O), 1631 (C]N), 1473e1598 (C]C and NeH,
benzene and Qu-ring and bending of NeH), 1438 (CeH), 1031e1365
(CeN); 1H NMR (500 MHz, CDCl3)
d in ppm: 9.45 (s, 1H, Qu-ringe
NHeAr), 8.20 (s, 1H, eN]CHeAr), 8.18 (d, 1H, J ¼ 7.45 Hz, AreH),
7.61 (t,1H, J ¼ 6.85 Hz, AreH), 7.56 (q, 3H, 4JHH ¼ 3JHH ¼ 8.60 Hz, Are
H), 7.43 (d, 1H, J ¼ 8.05 Hz, AreH), 7.23 (t, 4H, J ¼ 7.72 Hz, AreH and
QueH), 6.64 (d, 2H, J ¼ 9.15 Hz, AreH and QueH), 4.57 (s, 2H, ]Ne
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CH2eAr), 4.01 (s, 2H, Qu-ring eCH2e), 3.03 (s, 6H, AreN(CH3)2); 13
C
NMR (125 MHz, CDCl3)
d in ppm: 164.52, 163.55, 152.71, 148.97,

74
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[38] The structure of 6t, which was recrystallized from EtOH, was determined by
single-crystal X-ray diffraction analysis. Data collection: SMART (Bruker,
2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT; pro-
gram(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used
to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON
(Spek, 2003). Crystal data: C24H21ClN4O3, M ¼ 448.90, Monoclinic, P2(1)/c,
¼ 90ꢂ,
b
¼ 93.923(2)ꢂ,
ꢀ
ꢀ
ꢀ
a
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bioactivities of 2-aryl- or 2-methyl-3-(substituted-benzalamino)-4(3H)-qui-
nazolinone derivatives, Molecules 12 (2007) 2621e2642.
a ¼ 8.0890(12) A, b ¼ 12.6753(19) A, c ¼ 21.141(3) A,
3
ꢂ
ꢀ
g
¼ 90 , V ¼ 2162.5(6) A3, Z ¼ 4, Dcalcd ¼ 1.379 g/cm , 16092 collected re-
flections, 4321 independent (Rint ¼ 0.0193), R1 ¼ 0.0370, wR2 ¼ 0.1020.