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

Article abstract of DOI:10.14233/ajchem.2014.17429

2-(2-Butylamine)-6-[(2-butylamine)amino]-5-nitro-1H-benzo[de]-isoquinoline-1,3(2H)-dione (2) was synthesized and then characterized by FT-IR, NMR and elemental analysis. The crystal structure of compound 2 was investigated using X-ray diffraction and SHELXTL97 software and the result indicated that compound 2 crystallized in the monoclinic system, space group C2/c with a = 32.1094 (19), b = 7.1888 (4), c = 16.7750 (9) ?, V = 3827.2 (4) ?³; Z = 8. The free radical scavenging activity screening results showed that compound 2 exhibited good scavenging activity against 2,2-diphenyl-1-picrylhydrazyl radical (DPPH^?), with IC₅₀ of 214.7 μM.

Full text of DOI:10.14233/ajchem.2014.17429

Asian Journal of Chemistry; Vol. 26, No. 21 (2014), 7457-7459
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2014.17429
Synthesis, Characterization, Crystal Structure and Free Radical Scavenging Activities of
-(2-Butylamine)-6-[(2-butylamine)amino]- 5-nitro-1H-benzo[de]-isoquinoline-1,3(2H)-dione
2
1
2
2,*
3,*
XIAOLIN TANG , YE ZHANG , WEN QIN and YONGZHI LIAO
1
2
3
School of Chemistry & Pharmaceutical Science, Guangxi Normal University, Guilin 541004, Guangxi, P.R. China
Department of Chemistry & Pharmaceutical Science, Guilin Normal College, Guilin 541001, Guangxi Province, P.R. China
Guangxi Academy of Fishery Sciences, Nanning 530021, P.R. China
*
Corresponding authors: Fax: +86 77 32806321; Tel: +86 77 32823285; E-mail: glqinwen@163.com; liao0777@163.com
Received: 20 February 2014; Accepted: 5 May 2014; Published online: 30 September 2014;
AJC-16161
2-(2-Butylamine)-6-[(2-butylamine)amino]-5-nitro-1H-benzo[de]-isoquinoline-1,3(2H)-dione (2) was synthesized and then characterized
by FT-IR, NMR and elemental analysis. The crystal structure of compound 2 was investigated using X-ray diffraction and SHELXTL97
software and the result indicated that compound 2 crystallized in the monoclinic system, space group C2/c with a = 32.1094 (19), b =
3
7
.1888 (4), c = 16.7750 (9) Å, V = 3827.2 (4) Å ; Z = 8. The free radical scavenging activity screening results showed that compound 2
•
exhibited good scavenging activity against 2,2-diphenyl-1-picrylhydrazyl radical (DPPH ), with IC50 of 214.7 µM.
Keywords: Naphthalimides, Synthesis, Crystal, Free radical scavenging activity.
on a PE Spectrum One FI-IR spectrometer as KBr pellets.
INTRODUCTION
1
13
H NMR and C NMR spectra were recorded on a BRUKER
AVANCE 500 spectrometer in CDCl . Mass spectra were
Previous work showed that naphthalimides exhibited good
3
inhibition activity toward multifarious murine and human tumor
recorded on BRUKER ESQUIRE HCT or VG ZAB-HS spec-
trometer. All elemental analyse were performed by PE 2400II
analyzer. The data of single crystal were collected in a Rigaku
Mercury CCD Area Detector.
1,2
cells . Two compounds of this kind derivatives, amonifide
and mitonafide, had been even reported as undergoing clinical
2
trials . Therefore, the synthesis of naphthalimides derivatives
has recently been the subject of many chemists.
Synthesis: Compound 2 was synthesized as outlined in
Fig. 1. 4-bromo-1,8-naphthalic anhydride (BNA) was treated
with the mixture of potassium nitrate and sulphuric acid to
offer 3-nitro-4-bromo-1,8-naphthalic anhydride in good yield,
The importance of free radicals and reactive oxygen
3
-5
species in the pathogenesis of multifarious diseases has
prompted chemists to the synthesis for screening for efficient
new free radical scavenging agents. Continuing our research
program on the synthesis of radical scavenger effective ,
naphthalimide skeleton is chosen in the present work as active
structural core and butyl and nitro groups are introduced to
explore its radical scavenging activity. The present study was
to synthesize and characterize a naphthalimide derivative (2)
and to evaluate the free radical activity.
6
according to the literature . The mixture of butylamine (2.1
6
-8
mmol), dimethylfomamide (DMF, 10 mL) and 4-bromo-3-
nitro-1,8-naphthalic anhydride (1 mmol) was refluxed at
100 ºC for 7 h. Once cooled to room temperature, red crystals
of compound 2 were obtained in 82 % yields. Compound 2
was then characterized by FT-IR, NMR and elemental analysis:
-1
m.p. 236.5-236.7 °C (from DMF). IR (KBr, νmax, cm ): 3462,
1
3
060, 2958, 2929, 2873, 1698, 1649, 1606, 1577, 1538; H
NMR (500 MHz, CDCl ) δ 9.92 (s, 1H, NH), 9.32 (s, 1H),
.68 (dd, J = 7.4 and 8.5 Hz, 2H), 7.71 (t, J = 7.8 Hz, 1H),
4.18 (t, J = 7.5 Hz, 2H), 3.99 (t, J = 5.5 Hz, 2H), 1.45-1.88 (m,
EXPERIMENTAL
3
8
2
,6-Diter-butyl-4-toluene (BHT) and 1,1-diphenyl-2-
•
13
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
8H), 1 (s, 6H, CH ); C NMR (125 MHz): 14, 14.2, 19.9,
3
20.2, 30.1, 32.1, 49.2, 110, 122.8, 123.8, 126.7, 129.5, 129.8,
131.4, 133.1, 133.5, 149.4, 162.5, 163.5; MS (ESI) m/z: 368
+
(M -1); Anal. (%) Calcd. for C20
H
23
N
3
O : C, 65.03; H, 6.28;
4
N, 11.37. Found: C, 65.16; H, 6.47; N, 11.24.

7
458 Tang et al.
Asian J. Chem.
O
O
O
O
O
O
TABLE-1
CRYSTALLOGRAPHIC DATA FOR COMPOUND 2
KNO /H SO
4
3
2
Chemical formula
Formula weight
Crystal system, space group Monoclinic, C2/c
C H N O
20 23 3 4
369.41
o
0
C, stir
NO2
Br
BNA
Br
Unit Cell Dimensions
a = 32.1094 (19) Å, α = 90°
1
b = 7.1888 (4) Å, β = 98.742 (4)°
c= 16.7750 (9) Å, γ = 90°
3
Volume (Å )
3827.2 (4)
0.56 × 0.19 × 0.12
296 (2)
3
Crystal size (mm )
O
N
O
n-Butylamine
Reflux, 4h
Temp (K)
Z
8
–3
Dcalc (g cm )
1.282
NO2
θ range for data collection
2.5 to 25.6°
0.09
–1
HN
µAbsorp. (mm )
Max. and min. Transmission phi and ω scans
2
Limiting indices
F (000)
Reflections collected/unique 18548/4392 [R(int) = 0.038]
−41 ≤ h ≤ 39, −9 ≤ k ≤ 9, −21 ≤ l ≤ 21
1568
Fig. 1. Synthetic route of naphthalimides (2)
Data/restraint/parameters
4392/0/246
X-ray crystallography: An orange bar crystal of com-
R [I＞2σ (I)]
R = 0.068, ωR = 0.219
1
2
pound 2 grown in DMF with dimensions of 0.56 mm × 0.19
mm × 0.12 mm was used for structural determination. Diffrac-
tion data were collected on a Rigaku Mercury CCDArea diffrac-
2
Goodness-of-fit on F
1.06
3
Largest diff. peak/hole(e/Å ) 0.49 and −0.39
tometer by using graphite monochromated MoK
α
radiation (λ
=
0.71073 Å). The structure was solved by direct methods
TABLE-2
SELECTED GEOMETRIC PARAMETERS FOR COMPOUND 2
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: Compound 2 was reacted with a
stable free radical, 1,1-diphenyl-2-picrylhydrazyl radical
Bond
Dist. (Å)
Angle
Data (º)
N1–C5
N1–C15
N1–C4
N2–C9
N2–C17
N3–O3
N3–O4
N3–C8
O1–C15
O2–C5
C1–C2
C2–C3
C3–C4
C5–C6
C6–C7
1.391 (3)
1.400 (3)
1.465 (4)
1.340 (3)
1.463 (3)
1.227 (3)
1.242 (3)
1.440 (3)
1.219 (3)
1.220 (3)
1.798 (14)
1.103 (14)
1.717 (11)
1.462 (4)
1.357 (3)
C5–N1–C15
C5–N1–C4
C15–N1–C4
C9–N2–C17
O3–N3–O4
O3–N3–C8
O4–N3–C8
C3–C2–C1
C2–C3–C4
N1–C4–C3
O2–C5–N1
O2–C5–C6
N1–C5–C6
C7–C6–C16
C7–C6–C5
123.8 (2)
118.1 (2)
118.1 (2)
130.7 (2)
121.2 (2)
119.0 (2)
119.8 (2)
95.1 (11)
102.5 (12)
105.8 (3)
120.0 (2)
122.7 (2)
117.3 (2)
119.0 (2)
119.7 (2)
•
8
(DPPH ) according to the literature 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 deter-
mined by measuring the absorbance at 517 nm after 0.5 h.
The scavenging activity was expressed as a percentage of
scavenging activity on DPPH radical: SC % = [(Acontrol -Atest)/
•
A
control)] × 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.
structure and the centroid-to-centroid distance within the stacks
being 3.4402 Å.
RESULTS AND DISCUSSION
The crystal configuration of compound 2 was confirmed
by X-ray structural analysis. Experimental details for X-ray
data collection were presented in Table-1 and the geometric
parameters for compound 2 were selected and listed in Table-2.
The molecular structure of the title compound 2 is shown in
Fig. 2. The molecular geometry is well comparable with that
of 2-(2-hydroxyethyl)-6-[(2-hydroxyethyl)amino]-5-nitro-1H-
Free radical scavenging activity of compound 2 was deter-
8
mined against DPPH radical, according to the literatures . The
values of IC , the effective concentration at which 50 % of
50
the radicals were scavenged, were calculated to evaluate the
free radical scavenging activity. A lower IC value indicated
50
greater antioxidant activity. IC values of lower than 10 mg/mL
5
0
10
usually implied effective activities in antioxidant properties .
The IC of commercial antioxidant BHT was also determined
9
benzo[de]-isoquinoline-1,3(2H)-dione , apart from the
50
hydroxyethyl substituent replacing with butyl group. It features
a six-membered imide ring in which two acyls are coordinated
by N atom [C-N-C= 123.8 (5) Å]. All the atoms of 1,8-
naphthalimide unit are almost in a coplanar. In the crystal
packing of the title compound 2 (Fig. 3), there are π-π stacking
interactions, which makes the stabilization of the crystal
for comparison. The results showed that IC of compound 2
50
was 214.7 µM, which was equivalent to 0.079 mg/mL and
10
was clearly lower than 10 mg/mL , indicating good radical
scavenging activity of compound 2. It is pity that compound 2
displayed lower radical scavenging activity than BHT (65.8
µM).

Vol. 26, No. 21 (2014)
Studies of 2-(2-Butylamine)-6-[(2-butylamine)amino]- 5-nitro-1H-benzo[de]-isoquinoline-1,3(2H)-dione 7459
ACKNOWLEDGEMENTS
This study was supported by the Fund of Guangxi
Key Laboratory of Functional Phytochemicals Research and
Utilization (No. FPRU2011-6; FPRU2013-6), the Guilin Scientific
Research and Technological Development Project (20120108-6;
2
0110106-2), the Program for Excellent Talents in University
of Guangxi Zhuang Automous Region (No. 2011104), the
Guangxi Natural Science Foundation (No. 2014GXNSFBA-
1
18050) and Guangxi Department of Education Research Project
Fig. 2. General appearance of compound 2 with the atoms represented by
(No. 2013YB283; 2013YB284).
thermal vibration ellipsoids of 50 % probability
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Fig. 3. Packing diagram for compound 2