Synthesis, characterization, crystal structure and free radical scavenging activities of 2-(2-benzylamine)-6-[(2-benzylamine)amino]-5-nitro-1H-benzo[de]-isoquinoline-1,3(2H)-dione

Article abstract of DOI:10.14233/ajchem.2014.17444

2-(2-Benzylamine)-6-[(2-benzylamine)amino]-5-nitro-1H-benzo[de]-isoquinoline-1,3(2H)-dione (BBNID, 3) was synthesized and then characterized by FT-IR, NMR and elemental analysis. The crystal structure of BBNID was investigated using X-ray diffraction and

Full text of DOI:10.14233/ajchem.2014.17444

Asian Journal of Chemistry; Vol. 26, No. 21 (2014), 7460-7462
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2014.17444
Synthesis, Characterization, Crystal Structure and Free Radical Scavenging Activities of
2-(2-Benzylamine)-6-[(2-benzylamine)amino]-5-nitro-1H-benzo[de]-isoquinoline-1,3(2H)-dione
1
1
1,*
YE ZHANG , WEN QIN , YONGZHI LIAO2,* and XIANGHUI YI
1Department of Chemistry & Pharmaceutical Science, Guilin Normal College, Guilin 541001, Guangxi Province, P.R. China
2Guangxi Academy of Fishery Sciences, Nanning 530021, P.R. China
*Corresponding authors: Fax: +86 77 32806321; Tel: +86 77 32823285; E-mail: liao0777@163.com, yixianghui2008@163.com
Received: 22 February 2014;
Accepted: 5 May 2014;
Published online: 30 September 2014;
AJC-16162
2-(2-Benzylamine)-6-[(2-benzylamine)amino]-5-nitro-1H-benzo[de]-isoquinoline-1,3(2H)-dione (BBNID, 3) was synthesized and then
characterized by FT-IR, NMR and elemental analysis. The crystal structure of BBNID was investigated using X-ray diffraction and
SHELXTL97 software and the result indicated that BBNID crystallized in the monoclinic system, space group C2/c with a = 8.8032 (14),
b = 8.822 (2), c = 13.994 (4) Å, V = 1005.9 (4) Å3; Z = 2. The free radical scavenging activity screening results showed that BBNID
exhibited better scavenging activity than the commercial antioxidant BHT against 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•), with
IC50 of 43.10 µM.
Keywords: Naphthalimides, Synthesis, Crystal, Free radical scavenging activity.
INTRODUCTION
EXPERIMENTAL
The significance of free radicals and reactive oxygen species
in the pathogenesis of multifarious diseases has attracted a
great deal chemist's interest1-3. Free radical scavenger are now
fabricated as the drug candidates to counter many diseases,
including carcinogenesis, inflammation, atherogenesis and
aging in aerobic organisms4,5. So recently, there has been
considerable investment in efforts to develop efficient new free
radical scavenging agents.
Naphthalimides, which are characterized by the presence
of a coplanar chromophore and, usually, a π-deficient aromatic
system, as well as one or two basic side chains, constitute an
important class of prodrugs in anticancer therapy6,7. They
display high levels of antitumor activity toward multifarious
murine and human tumor cells8,9. Two members of this class
of compounds, amonifide and mitonafide, are undergoing
clinical trials9. Previous work demonstrated that good anti-
tumor activity may lead to good free radical activity or anti-
oxidant activity. It is thus to expect that naphthalimides may
possess potential free radical activity. So the present study was
to synthesize and characterize a naphthalimide derivative 2-(2-
benzylamine)-6-[(2-benzylamine)amino]-5-nitro-1H-benzo-
[de]-isoquinoline-1,3(2H)-dione (BBNID) and to evaluate the
free radical activity.
2,6-Diter-butyl-4-toluene (BHT) and 1,1-diphenyl-2-
picrylhydrazyl radical (DPPH•) were purchased from Sigma
Chemicals Co. (St. Louis, MO, USA). Other chemicals were
purchased from China National Medicine Group Shanghai
Corporation (Shanghai, China). All chemicals and solvents
used were of analytical grade. Infrared spectra were recorded
on a PE Spectrum One FI-IR spectrometer as KBr pellets. 1H
NMR and 13C NMR spectra were recorded on a BRUKER
AVANCE 500 spectrometer in CDCl3. Mass spectra were
recorded on BRUKER ESQUIRE HCT orVG ZAB-HS spectro-
meter. All elemental analyse were performed by PE 2400II
analyzer. The data of single crystal were collected in a Rigaku
Mercury CCD Area Detector.
Synthesis: 2-(2-Benzylamine)-6-[(2-benzylamine)amino]-
5-nitro-1H-benzo[de]-isoquinoline-1,3(2H)-dione was
synthesized as outlined in Fig. 1. 4-Bromo-1,8-naphthalic
anhydride was treated with the mixture of potassium nitrate
and sulphuric acid to offer 3-nitro-4-bromo-1,8-naphthalic
anhydride in good yield10. The mixture of benzylamine (2.2
mmol), dimethylfomamide (DMF, 10 mL) and 4-bromo-3-
nitro-1,8-naphthalic anhydride (1 mmol) was refluxed at
100 ºC for 6 h. Once cooled to room temperature, red crystals
of BBNID were obtained in 88 % yields. BBNID was then

Vol. 26, No. 21 (2014)
Studies of 2-(2-Benzylamine)-6-[(2-benzylamine)amino]-5-nitro-1H-benzo[de]-isoquinoline-1,3(2H)-dione 7461
O
O
O
O
O
O
O
N
O
KNO3/H2SO4
0oC, stir
Benzylamine
Reflux, 4h
NO2
NO2
Br
Br
HN
1
3
2
Fig. 1. Synthetic route of naphthalimides BBNID
characterized by FT-IR, NMR and elemental analysis: m.p.
233.5.4-234.7 °C (from DMF). IR (KBr, νmax, cm-1): 3441,
1
3060, 2923, 2851, 1699, 1655, 1601, 1537; H NMR (500
MHz, CDCl3) δ 10.02 (s, 1H, NH), 9.36 (s, 1H, H-Ar), 8.70
(d, J = 7.4 Hz, 1H, H-Ar), 8.63 (d, J = 8.5 Hz, 1H, H-Ar), 7.67
(d, J = 8.3 Hz, 1H, H-Ar), 7.26-7.65 (m, 10H, H-Ar), 5.38 (s,
2H, CH2), 5.10 (s, 2H, CH2); MS (ESI) m/z: 436 (M+-1);Anal.
Calcd. for C26H19N3O4: C, 71.39; H, 4.38; N, 9.61. Found: C,
71.25; H, 4.51; N, 9.72.
Fig. 2. General appearance of compound BBNID with the atoms
represented by thermal vibration ellipsoids of 50 % probability
X-ray crystallography:An orange bar crystal of BBNID
grown in DMF with dimensions of 0.25 mm × 0.20 mm ×
0.04 mm was used for structural determination. Diffraction
data were collected on a Rigaku Mercury CCDArea diffracto-
meter by using graphite monochromated MoKα radiation (λ =
0.71073 Å). The structure was solved by direct methods with
SHELXS-97 and refined on the F2 by full-matrix least-squares
method with SHELXL-97. All non-hydrogen atoms were
refined anisotropically.
Scavenging activity: To evaluate the free radical scaven-
ging activity, BBNID was allowed to react with a stable free
radical, 1,1-diphenyl-2-picrylhydrazyl radical (DPPH•) accor-
ding to the literature11 with a little modification. Briefly, each
scavenger solution (0.1 mL) in DMF at different concentrations
was added to solution [3.9 mL, 0.004 % (w/v)] of DPPH• in
ethanol. The reaction mixture was incubated at 37 ºC. The
scavenging activity on DPPH• radical was determined by
measuring the absorbance at 517 nm after 30 min. The
scavenging activity was expressed as a percentage of
scavenging activity on DPPH• radical: SC % = [(Acontrol -Atest)/
Acontrol)] × 100 %, whereAcontrol is the absorbance of the control
(DPPH• solution without test sample) andAtest is the absorbance
of the test sample (DPPH• solution plus scavenger). The control
contains all reagents except the scavenger.
Fig. 3. Packing diagram for compound BBNID
TABLE-1
CRYSTALLOGRAPHIC DATA FOR COMPOUND BBNID
m.f.
C26H19N3O4
437.44
Formula weight
Crystal system, space group Monoclinic, C2/c
Unit cell dimensions
a = 8.8032 (14) Å, α = 86.928 (19)°
RESULTS AND DISCUSSION
b = 8.822 (2) Å, β = 76.376 (17)°
c= 13.994 (4) Å, γ = 72.284 (16)°
The crystal configuration of BBNID was confirmed by
X-ray structural analysis. Experimental details for X-ray data
collection were presented in Table-1 and the geometric para-
meters for BBNID were selected and listed in Table-2. The
molecular structure of BBNID (3) is shown in Fig. 2. The mole-
cular geometry is well comparable with that of 2-benzyl-6-
(benzylamino)-1H-benzo-[de]isoquinoline-1,3(2H)-dione12,
apart from the nitro group being substituented in the C-7
position. It features a six-membered imide ring in which two
acyls are coordinated by N atom [C-N-C= 124.2 (5) Å]. All
the atoms of 1,8-naphthalimide unit are almost coplanar. In
the crystal packing of the compound 3 (Fig. 3), there are weak
intermolecular C-H···O and N-H···O hydrogen bonds (Table-3),
which makes the stabilization of the crystal structure.
Volume (Å3)
1005.9 (4)
0.25 × 0.20 × 0.04
153 (2)
Crystal size (mm3)
Temp. (K)
Z
2
DCalc. (g cm–3)
θ range for data collection
µAbsorp. (mm–1)
1.444
3.0 to 25.3°
0.10
Max. and min. transmission 0.996 and 0.756
Limiting indices
F (000)
−10≤h≤10, −10≤k≤10, −16≤ l≤16
456
Reflections collected/unique 9964/3669 [R(int)=0.107]
Data/restraint/parameters
3669/0/299
R1 = 0.112, ωR2 = 0.267
1.10
R [I＞2σ (I)]
Goodness-of-fit on F2
Largest diff. peak/hole
(e/Å3)
0.33 and –0.29

7462 Zhang et al.
Asian J. Chem.
effective activities in antioxidant properties13. The IC50 of com-
mercial antioxidant BHT was also determined for comparison.
The results showed that IC50 of compound BBNID (which was
equivalent to 0.02 mg/mL) was much lower than the standard
value 10 mg/mL, indicating its good radical scavenging
activity. It was important to note that BBNID displayed better
free radical scavenging activity than the commercial anti-
oxidant BHT (IC50 = 65.85 µM), with IC50 of 43.10 µM.
TABLE-2
SELECTED GEOMETRIC
PARAMETERS FOR COMPOUND BBNID
Bond
Dist. (Å)
Angle
Data (º)
O1–C1
O2–C5
O3–N2
O4–N2
N1–C1
N1–C5
N1–C13
N2–C7
N3–C8
N3–C20
C1–C2
C2–C6
C2–C3
C3–C4
C3–C9
1.223 (7)
1.222 (7)
1.231 (6)
1.239 (6)
1.393 (7)
1.397 (7)
1.483 (7)
1.431 (7)
1.362 (7)
1.463 (7)
1.473 (8)
1.367 (8)
1.411 (8)
1.409 (8)
1.425 (8)
C1–N1–C5
C1–N1–C13
C5–N1–C13
O3–N2–O4
O3–N2–C7
O4–N2–C7
C8–N3–C20
O1–C1–N1
O1–C1–C2
N1–C1–C2
C6–C2–C3
C6–C2–C1
C3–C2–C1
C4–C3–C2
C4–C3–C9
124.2 (5)
116.5 (5)
119.1 (5)
121.0 (5)
118.1 (5)
120.8 (5)
129.0 (5)
119.8 (5)
123.2 (5)
117.0 (5)
119.8 (5)
119.4 (5)
120.7 (5)
120.0 (5)
119.8 (5)
ACKNOWLEDGEMENTS
This study was supported by the Fund of Guangxi Key
Laboratory of Functional Phytochemicals Research and Utili-
zation (No. FPRU2011-6; FPRU2013-6), the Guilin Scientific
Research and Technological Development Project (20120108-
6; 20110106-2), the Guangxi Natural Science Foundation (No.
2014GXNSFBA118050) and Guangxi Department of Edu-
cation Research Project (No. 2013YB283; 2013YB284).
TABLE 3
HYDROGEN-BOND GEOMETRY FOR COMPOUND BBNID
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