Unusual large Stokes shift and solvatochromic fluorophore: Synthesis, spectra, and solvent effect of 6-substituted 2,3-naphthalimide

Article abstract of DOI:10.1016/j.jphotochem.2010.09.002

In this article, four new series of 6-substituted 2,3-naphthalimides (1a-d, 2a-d, 3a-d, 4a-d and 4 e-h) have been designed and synthesized through the formation of key cyclic anhydride intermediate, which was the precursor of the well known environment-sensitive fluorophore [6-N,N-dimethylaminonaphthalimides (6-DMN)] and other 6-substituted 2,3-naphthalimide series (2, 3, 4). Based on 6-amino-2,3-naphthalimide (6-ANP) compound, a new type of fluorophore was found to exhibit moderate to unusual large Stokes shift (297-303 nm). 6-ANP derivatives display relatively low fluorescence quantum yields in high polar protic solvents such as water (Φ_F ～ 0.004, 571-576 nm) and a significant unusual red shift due to (1) hydrogen bonding interaction of the excited state of the molecule with the solvents, which presumably enhance the intersystem crossing process in the system to quench fluorescence, (2) this large Stokes shift was assumed to be the consequence of a substantial change of the geometric structure from the ground state (S₀) to the first excited state (S₁). Compared with the other compounds studied, the fluorescence of the nitro- and halo-derivatives was rather weak, probably due to the efficient intersystem crossing leading to a non-reactive triplet state.

Full text of DOI:10.1016/j.jphotochem.2010.09.002

Journal of Photochemistry and Photobiology A: Chemistry 216 (2010) 24–34
Contents lists available at ScienceDirect
Journal of Photochemistry and Photobiology A:
Chemistry
journal homepage: www.elsevier.com/locate/jphotochem
Unusual large Stokes shift and solvatochromic fluorophore: Synthesis, spectra,
and solvent effect of 6-substituted 2,3-naphthalimide
Kishore Baathulaa, Yufang Xu, Xuhong Qian∗
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 June 2010
Received in revised form 29 August 2010
Accepted 3 September 2010
Available online 25 September 2010
In this article, four new series of 6-substituted 2,3-naphthalimides (1a–d, 2a–d, 3a–d, 4a–d
and 4 e–h) have been designed and synthesized through the formation of key cyclic anhydride
intermediate, which was the precursor of the well known environment-sensitive fluorophore [6-N,N-
dimethylaminonaphthalimides (6-DMN)] and other 6-substituted 2,3-naphthalimide series (2, 3, 4).
Based on 6-amino-2,3-naphthalimide (6-ANP) compound, a new type of fluorophore was found to exhibit
moderate to unusual large Stokes shift (297–303 nm). 6-ANP derivatives display relatively low fluo-
rescence quantum yields in high polar protic solvents such as water (˚F ∼ 0.004, 571–576 nm) and a
significant unusual red shift due to (1) hydrogen bonding interaction of the excited state of the molecule
with the solvents, which presumably enhance the intersystem crossing process in the system to quench
fluorescence, (2) this large Stokes shift was assumed to be the consequence of a substantial change of the
geometric structure from the ground state (S0) to the first excited state (S1). Compared with the other
compounds studied, the fluorescence of the nitro- and halo-derivatives was rather weak, probably due
to the efficient intersystem crossing leading to a non-reactive triplet state.
Keywords:
6-Substituted 2,3-naphthalimide
Large Stokes shift
Photophysics
Solvent effect
Environment-sensitive fluorophore
© 2010 Elsevier B.V. All rights reserved.
1. Introduction
contributed to the development of new fluorescent probes [15]
and optical sensors [16], and the dual fluorescence was observed
Environment-sensitive fluorophores are
a
special class of
for several substituted phenyl naphthalimides [17–20]. From pre-
vious reports the fluorescence of 4-aminonaphthalimide and its
derivatives were characterized by the high quantum yield in all
the examined solvents, but, their Stokes shifts were not very large,
which would hinder their applications in solar fluorescence mate-
rial and sensor as the presence of intersecting self-absorption
between their emissions and excitations. Ones hope has fluores-
cent sensor with large Stokes shift in aqueous solution or water,
as most of sensors will get application in environmental or bio-
logical condition. Additionally fluorescent materials with large
Stokes shifts have advantages that they could be more easily
detected in the presence of other fluorescent materials, for exam-
ple, immunoassays are typically carried out in body, which contain
many endogenous fluorescent molecules, such as bilins, flavins
and drugs. Since the vast majority of interfering fluorescent mate-
rials have relatively short Stokes shifts, the use of a fluorescent
label that emits at a wavelength far greater than its excitation
wavelength makes the label easier to distinguish from background
fluorescence. Fluorescent materials with a large Stokes shift can be
used in combination with those with a smaller Stokes shift where
both materials excite at the same wavelength, but emit at differ-
ent wavelengths, giving multiple signals that can be resolved using
optical filters or monochromators. Recently, Imperiali et al. have
synthesized and studied the fluorescence properties of the new
environmentally sensitive fluorophore, 6-N,N-dimethylamino-2,3-
molecules that have spectroscopic properties depending on the
physicochemical properties of their immediate surroundings. Typ-
ical examples of these fluorophores include donor–acceptor
systems like 4-dimethylamino phthalimide (4-DMAP) [1],
2-propionyl-6-dimethylaminonaphthalene
(PRODAN)
[2],
4-amino-1,8-naphthalimide (4-DMN) [3] 6-N,N-dimethylamino-
2,3-naphthalimide (6-DMN) [4] and 6-chloro-2,3-naphthalimide
derivative (6-ClNP) [5] (Fig. 1). The applications of these new
solvatochromic fluorophores have greatly expanded the scope of
potential as unique chemical tools [6–8]. On one hand, peptides
containing the 4-DMAP and 6-DMN residues have been developed
recently as probes for the phosphotyrosine binding SH2 and
for the phosphoserine and phospothreonine binding [14-3-3]
domains [9], and on the other hand, PRODAN has been used to
measure RNase assembly [10], ␦-opioid antagonist binding, and
electrostatics within protein G [11].
Naphthalimide (NP) belongs to a class of chromophores for
which the excited-state properties can be drastically changed by
the nature of a substituent presented on the aromatic ring [12–14].
The studies of the photophysical behavior of naphthalimides have
∗
Corresponding author.
E-mail address: xhqian@ecust.edu.cn (X. Qian).
1010-6030/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jphotochem.2010.09.002

K. Baathulaa et al. / Journal of Photochemistry and Photobiology A: Chemistry 216 (2010) 24–34
25
(400 MHz). Absorption measurements were performed with a Var-
ian Cary 500 spectrophotometer (1 cm quartz cell) and fluorescence
spectra were recorded on a Varian Cary Eclipse fluorescence spec-
trophotometer (1 cm quartz cell). The experimental solutions were
prepared just before taking measurements. Mass spectra (MS) were
recorded on an MA1212 instrument using standard conditions
(ESI, 70 eV). All the experiments were performed at 25.0 0.1 ◦C.
Melting points were determined by an X-6 micro-melting point
apparatus and uncorrected.
O
N
O
O
NMe2
Me2N
NMe2
SO2Cl
DANSYL-Cl
4DMN
PRODAN
O
O
N
O
O
N
N
2.2. Synthesis
Me2N
Me2N
Cl
O
O
The designed target compounds of 6-sub-2,3-naphthalimides
(1a–d, 2a–d, 3a–d, 4a–d and 4e–4h) were synthesized from com-
mercially available starting materials which are illustrated in
Schemes 1 and 2.
6DMN
4DMAP
6ClNP
Fig. 1. Structures of some common environment-sensitive fluorophores.
naphthalimide (6-DMN) [4] and Katritzky et al. synthesized a novel
environmentally sensitive chlorine substituted naphthalimide-
based fluorophore (6-ClNP) which can be utilized for the labelling of
amino acids [5]. The fluorescence quantum yield of 6-DMN chro-
mophore changes from ˚F = 0.225 in chloroform to ˚F = 0.002 in
water and the fluorescence quantum yield of 6-ClN chromophore
changes from ˚F = 0.53 in chloroform to ˚F = 0.15 in water. The
Stokes shift of 6-DMN was reported around 204 nm and that of 6-
ClN was around 141 nm in aqueous solutions. Therefore, we here
concentrated to design and synthesize some naphthalimides with
unusual large Stokes shift, especially in aqueous or water solution.
In addition, it was observed from the literature [4,5,21] that
the synthesis of 6-substituted naphthalimides required multiple
synthetic steps and special purification methods. Synthesis of the 6-
N,N-dimethylamino-2,3-naphthalene anhydride required 6 steps
and resulted the mixture of isomers at positions 2 and 4 in a 1:1
ratio in the second step, the yield of the desired product 2-(2-
phenylsufonylmethyl-5-nitrophenyl)-1,3-dioxolane is only 35%,
which reflects the overall yield of the synthesis. On the other hand,
chlorine substituted 2,3-naphthalimide required 5 steps.
Thus in this work we also reported the short and efficient
synthesis of three new groups of 6-nitro, 6-amino and 6-iodo-
substituted derivatives 2, 3, 4 and their spectral characterization.
Finally, we also reported the detailed investigation of the photo-
physical behavior in solvents of diverse polarity including polar to
non-polar and protic to aprotic solvents. We examined the effects
of substituents on 2nd position of 2,3-naphthalimide ring substi-
tuted by phenyl, alkyl and on 6th position of naphthalene ring
substituted from electron donating (6-NH2-NP and 6-Me2N-NP)
to electron-withdrawing (6-nitro-1H-benzo[f]isoindole-1,3(2H)-
dione, O2N–NP), and halogenated groups (6-Cl-NP, 6-I-NP).
Then greater attention was paid to 6-amino-2,3-naphthalimide
(6-ANP) and the unusual large Stokes shift of 6-ANP (highest value
297–303 nm) was systemically studied in aqueous solution. The
results showed that: (1) amino group acts as electron donor in all
the solvents except water. In water it behaves as a proton accep-
tor since proton-donating capability of water was reported to be
more (hence a blue shift relatively ꢀabs = 274 nm), respectively; (2)
water can interact at two sites with the two lone pairs of amino and
imino groups. So, the delocalization of two lone pairs is restricted.
Hence, these interactions cause a significant blue shift in absorption
spectra.
Preparation of 1, 2-bis (dibromomethyl)-4-nitrobenzene (5): 4-
Nitro-o-xylene (15.1 g, 100 mmol) in 100 mL of chlorobenzene was
placed in two-necked flask equipped with dropping funnel, and a
reflux condenser attached to a sodium hydroxide trap for evolved
hydrogen bromide (HBr) gas. Liquid bromide (67.2 g, 420 mmol) in
50 mL chlorobenzene was added drop wise while the solution was
irradiated with 250 W tungsten lamp. When the addition was com-
pleted, the reaction mixture was then cooled, washed successively
with aqueous NaHSO3 and distilled water, dried over magnesium
sulfate, filtered, and concentrated with a rotary evaporator. The
resulting yellowish precipitate which was recrystallized from CCl4
and dried 100 ◦C to afford the desired compound as a pale yel-
low powder (82%). m.p. 125–127 ◦C; 1H NMR (400 MHz, CDCl3, ı):
8.57 (s, 1H), 8.29 (dd, J1 = 8.4 Hz, J2 = 8.8 Hz, 1H), 7.96 (d, J = 7.2 Hz,
1H), 7.15 (s, 1H), 7.10 (s, 1H). HRMS-EI (m/z): [M−Br] calcd for
C8H5NO2Br3: 385.7850. Found: 385.7847.
6-Nitro-2,3-naphthalenedicarboxylic acid (6): The procedure of
Carlson [28] was employed with minor modifications. A mix-
ture of tetrabromide 5 (20.0 g, 42.82 mmol), maleic anhydride
(12.59 g, 128.46 mmol), potassium iodide (46.2 g, 0.278 mol), and
dry dimethylformamide (150 mL) was stirred at 65 ◦C for 16 h
under N2. The cooled reaction mixture was poured into ice water
(1000 mL), and the brown color due to iodine was discharged by the
gradual addition of aqueous sodium hydrogen sulfite. The yellow
precipitate was dissolved in dilute sodium hydroxide, the solution
decolorized by charcoal, filtered and the filtrate acidified with conc.
sulfuric acid under cool condition. The yellow precipitate of diacid
was washed with cold water and dried, which was recrystallized
from dichloromethane to give compound 6 as light yellow crystals
(9.72 g, 87.0%). m.p. 179–181 ◦C; 1H NMR (400 MHz, DMSO-d6, ı):
13.9 (br, 2H, –COOH), 9.16 (s, 1H), 8.72 (s, 1H), 8.51 (s, 1H), 8.37
(dd, J = 2.2 Hz, 1H), 8.34 (s, 1H). 13C NMR (DMSO-d6): 168.6, 168.3,
147.0, 135.9, 134.0, 132.2, 132.1, 132.0, 131.0, 129.67, 125.5, 121.8.
HRMS-ESI (m/z): [M−H+] calcd for C12H6NO6: 260.0195. Found:
260.0208.
6-(Dimethylamino)-2,3-naphthalenedicarboxylic anhydride (1) 6-
DMN precursor: Compound 6 (4 g) was dissolved in MeOH (400 mL).
Formalin (40 mL) and Pd/C 10% (1 g) were added to the solution.
The resulting mixture was stirred under hydrogen for 2.5–3 h until
TLC showed that the starting material has been consumed. The
reaction mixture was then filtered through celite and concen-
trated under reduced pressure to get the crude precipitate which
was washed thoroughly with water to eliminate formalin frac-
tion to give the desired pure diacid product (3.40 g, 85%, Rf = 0.5
20% CH3OH/DCM). m.p. 248–250 ◦C; 1H NMR (400 MHz, DMSO-
d6, ı): 8.15 (s, 1H), 7.87 (s, 2H), 7.32 (dd, J1 = 9.2 Hz, J2 = 2.6 Hz,
1H), 7.05 (s, 1H), 3.05 (s, 6H); 13C NMR (400 MHz, DMSO-d6, ı):
169.6, 168.2, 150.0, 135.1, 131.3, 129.7, 129.5, 126.1, 124.7, 123.6,
117.6, 105.3, 48.8(2). For diacid intermediate: HRMS-ESI (m/z):
[M−H+] Calcd for C14H12NO4: 258.0766. Found: 258.0764. 3 g of
2. Experimental
2.1. General
All reagents and solvents were obtained from commercial
suppliers and used without further purification. 1H NMR spec-
tra were collected in CDCl3/DMSO at 25 ◦C in NMR spectrometer

26
K. Baathulaa et al. / Journal of Photochemistry and Photobiology A: Chemistry 216 (2010) 24–34
O
O
O2N
O2N
Amine
O
N
R
Toluene
7
reflux, 2 h
O
O
2 a-d
Maleic anhydrie
KI, DMF, 65 0C,16 h
Br
Maleic anhydrie
O2N
O2N
COOH
COOH
O2N
Br2, C6H5Cl
KI, DMF,65 0C,16 h
NaOH,H3O+
Br
Br
250W tangstan lamp
reflux,2 h
6
5
Br
O
A.10%Pd/C,H2 (1 atm)
37% Formalin rt, 4 h
B. Ac2O reflux, 1h
O
Amine
N
N
N
R1
O
O
toluene
reflux
O
1a-d
1
6-DMN precursor
O
N
O
O
O
N
N
N
N
N
NH
N
O
O
1c
1b
2a
1a
1d
O
N
O
O
O2N
O2N
N
N
NH
O
O
O
O
O
2b
N
O2N
O2N
N
N
N
O
O
2d
2c
Scheme 1. Preparation of 1a–d and 2a–d.
the diacid was placed in a 250 mL flask containing 15 mL acetic
anhydride and reflux for 1 h, remove the solvent on a rotary evapo-
rator at 25 ◦C. Dissolve the solid residue in a 100 mL of toluene and
remove the solvent on a rotary evaporator two times. The crude
product was purified by column chromatography (EtOAc/hexanes:
30/70) to furnish 2.7 g (90%) of desired anhydride 1 (Rf = 0.64, 30%
EtOAc/hexanes). m.p. 245–247 ◦C; 1H NMR (400 MHz, CDCl3, ı):
8.34 (s, 1H), 8.26 (s, 1H), 7.98 (d, J = 9.2 Hz, 1H), 7.44 (dd, J1 = 9.2 Hz,
J2 = 2.6 Hz, 1H), 7.21 (d, J = 2.4 Hz, 1H), 3.22 (s, 6H); HRMS-EI (m/z):
calcd for C14H11NO3: 241.0739. Found: 241.0738.
6-Amino-2,3-naphthalenedicarboxylic anhydride (9): A solution
of diacid 8 (12 g, 0.05 mol) in acetic anhydride (50 mL) was refluxed
for 15 min. The solvent was removed under reduced pressure.
Benzene (150 mL) was added to it, and the solvent was again evapo-
rated to remove traces of acetic anhydride, affording (93%) of cyclic
anhydride as yellow solid. m.p. 212–214 ◦C; 1H NMR (400 MHz,
CDCl3, ı): 8.44 (s, 1H), 8.29 (s, 1H), 7.98 (d, J = 2.4 Hz, 1H), 7.24
(dd, J1 = 8.8 Hz, J2 = 9.2 Hz, 1H), 7.04 (s, 1H), 2.83 (s, 2H); 13C NMR
(DMSO-d6): 168.6, 168.5, 134.1, 133.2, 133.1, 132.5, 131.7, 131.6,
131.1, 130.7, 130.6, 129.0, 127.5; EIMS m/z 213.0.
6-Amino-2,3-naphthalenedicarboxylic acid (8): Compound
6
6-Chloro-2,3-naphthalenedicarboxylic anhydride (10): A hetero-
geneous mixture of 6-amino-2,3-naphthalenedicarboxylic acid
(4.20 g, 20 mmol) in 10 mL of concentrated HCl was stirred at
0 ◦C as a solution of NaNO2 (1.66 g, 24 mmol) in 10 mL of ice
water was added. The resultant homogeneous orange solution
was stirred at 0 ◦C for 1 h, and then added slowly with stirring
to a solution of CuCl2 (6.8 g, 50 mmol) in 30 mL of water at 0 ◦C.
The reaction mixture was slowly warmed to room temperature
over 2 h. The aqueous solution was extracted with EtOAc, and the
organic layer was washed with water, and brine, dried, and con-
centrated to give 4.39 g (89%) of the diacid. m.p. 245–247 ◦C; 1H
NMR (400 MHz, DMSO-d6, ı): 15.5 (b, 2H), 8.56 (s, 1H), 8.50 (s, 1H),
8.23 (s, 1H), 8.14 (d, J = 8.8 Hz, 1H), 7.66 (d, J = 8.4 Hz, 1H); 13C NMR
(15 g) was dissolved in MeOH (1500 mL) and Pd/C 10% (1.5 g) was
added to the solution. The resulting mixture was stirred under
hydrogen for 3–6 h until TLC showed that the starting material has
been consumed. The reaction mixture was then filtered through
celite and concentrated under reduced pressure to get the crude
precipitate diacid product (12.50 g, 85%, Rf = 0.3, 20% CH3OH/DCM).
m.p. 127–129 ◦C; 1H NMR (400 MHz, DMSO-d6, ı): 14.0 (b, 2H),
8.20 (s, 1H), 7.85 (s, 1H), 7.74 (d, J = 8.8 Hz, 1H), 7.04 (dd, J1 = 1.2 Hz,
J2 = 1.6 Hz, 1H), 6.88 (s, 1H), 6.02 (Br, 2 NH,); 13C NMR (DMSO-d6):
170.0, 168.8, 149.6, 135.9, 132.1, 131.3, 130.1, 126.9, 125.7, 124.2,
120.5, 106.0; HRMS-ESI (M−H+): Calcd for C12H8NO4: 230.0532.
Found: 230.0475.

K. Baathulaa et al. / Journal of Photochemistry and Photobiology A: Chemistry 216 (2010) 24–34
27
O
HCl / NaNO2
CuCl / KI
10% Pd/C,
H2 (1 atm)
rt,4 h
H2N
COOH
COOH
X
O2N
COOH
COOH
10 ( X = Cl )
11 ( X = I )
O
Ac2O
reflux
O
8
6
Amine
Aceticacid
Ac2O
reflux
reflux, 2 h
O
O
O
H2N
X
H2N
Amine
N R
O
N R
O
O
Aceticacid
reflux, 2 h
O
9
3a-d
X= Cl 4a-d
X= I 4f-h
N
O
N
O
O
H2N
H2N
H2N
NH
N
O
O
O
O
O
3c
X
3b
3a
3d
N
X = Cl and I
O
H2N
X
N
N
NH
O
O
O
N
O
O
4a,4e
4d,4h
4b,4f
N
X
N
X
N
O
O
4c,4g
Scheme 2. Preparation of 3a–d and 4a–d and 4e–h.
(DMSO-d6): 168.6, 168.5, 134.1, 133.2, 132.5, 131.7, 131.6, 131.1,
130.7, 130.6, 129.0, 127.5; HRMS-EI (m/z): Calcd for C12H7ClO4:
250.0033. Found: 250.0040. Follow the same procedure mentioned
for 6-amino-2,3-naphthalenedicarboxylic anhydride except start-
ing material afford anhydride of chloro compound (10) as colorless
solid. m.p. 218–220 ◦C; 1H NMR (400 MHz, CDCl3, ı): 8.56 (s, 1H),
8.48(s, 1H), 8.15 (d, J = 2 Hz, 1H), 8.12(d, J = 9.6 Hz, 1H), 7.78(dd, J = 2,
2 Hz, 1H); 13C NMR (CDCl3, ı): 162.5(2), 136.9, 136.7, 134.3, 131.8,
131.5, 129.1, 127.7, 127.1, 126.7, 126.2; HRMS-EI (m/z): Calcd for
162.6, 162.5, 139.2, 139.1, 137.1, 134.8, 131.4, 127.8, 126.8, 126.4,
126.3, 97.58; HRMS-EI (m/z) calcd for C12H5IO3: 323.9283. Found:
323.9279.
2.2.1. General procedure for the synthesis of
N-phenyl-naphthalimides (1a–4a and 4e) [22]
Compounds 1a–4a and 4e have been synthesized by mixing
equimolar quantities of anhydride (1 mmol) and aniline (1 mmol)
in glacial acetic acid were stirred under reflux for 1 h and the solvent
was evaporated under reduced pressure to yield the crude product,
which was recrystallized from acetone or acetic acid.
C12H5ClO3: 231.9927. Found: 231.9928.
6-Iodo-2,3-naphthalenedicarboxylic anhydride (11): A hetero-
geneous mixture of 6-amino-2,3-naphthalenedicarboxylic acid
(4.20 g, 20 mmol) in 10 mL of concentrated HCl was stirred at 0 ◦C
as a solution of NaNO2 (1.66 g, 24 mmol) in 10 mL of ice water was
added. The resultant homogeneous orange solution was stirred at
0 ◦C for 1 h, and then added slowly with stirring to a solution of KI
(8.3 g, 50 mmol) in 30 mL of water at 0 ◦C. The reaction mixture was
slowly warmed to room temperature over 2 h. The aqueous solution
was extracted with EtOAc, and the organic layer was washed with
water, aqueous saturated sodium metabisulfite, and brine, dried,
and concentrated to give 5.7 g (85%) of diacid as a brown solid. m.p.
180–182 ◦C; 1H NMR (400 MHz, DMSO-d6, ı): 14.3 (b, 2H), 8.59
(s, 1H), 8.31 (s, 1H), 8.24 (s, 1H), 7.94 (dd, J1 = 1.2 Hz, J2 = 1.6 Hz,
1H), 7.90 (s, 1H); 13C NMR (DMSO-d6, ı): 168.9, 168.8, 137.2, 137.0,
134.8, 131.9, 131.2, 130.7, 130.6, 129.6, 128.3, 95.9; HRMS-EI (m/z)
calcd for C12H7IO4: 341.9389. Found: 341.9399. Follow the same
procedure as mentioned for compound 9 except starting material
given Iodo anhydride as light red color solid. m.p. 196–198 ◦C; 1H
NMR (400 MHz, CDCl3, ı): 8.57 (s, 1H), 8.53 (s, 1H), 8.44 (s, 1H),
8.07 (dd, J = 1.6 Hz, 1H), 7.88 (d, J = 8.4 Hz, 1H); 13C NMR (CDCl3, ı):
6-(Dimethylamino)-2-phenyl-1H-benzo[f]isoindole-1,3(2H)-
dione (1a): Green yellow solid. m.p. 248–249 ◦C; 1H NMR (400 MHz,
DMSO-d6, ı): 8.33 (s 1H), 8.22 (s, 1H), 8.04 (d, J = 7.2 Hz, 1H), 7.51 (d,
J = 4.8 Hz, 2H), 7.49 (d, J = 6.0 Hz, 4H), 7.27 (s, 1H), 3.09 (s, 6H); 13
C
NMR (DMSO-d6, ı) 167.4, 167.3, 150.9, 137.9, 132.7, 131.6, 129.2,
128.4, 128.3, 127.7, 127.4, 125.27, 125.23, 124.9, 122.8, 122.4,
118.5, 107.9, 40.2 (2); HRMS-EI calcd for C20H16N2O2: 316.1212.
Found: 316.1208.
6-Nitro-2-phenyl-1H-benzo[f]isoindole-1,3(2H)-dione (2a): Col-
orless solid. m.p. 296–299 ◦C; 1H NMR (400 MHz, DMSO-d6, ı):
9.30 (s, 1H), 8.93 (s, 1H), 8.78 (s, 1H), 8.49 (qt, J = 22.4, 22 Hz,
2H), 7.47–7.58 (m, 5H); 13C NMR (DMSO-d6, ı): 166.6 (2), 147.3,
138.3, 134.8, 132.6, 132.3, 131.2, 129.6, 129.3, 129.0, 128.7, 127.8,
127.0, 126.7, 124.9, 122.7, 119.4; HRMS-EI calcd for C18H10N2O4:
318.0641. Found: 318.0642.
6-Amino-2-phenyl-1H-benzo[f]isoindole-1,3(2H)-dione
(3a):
Green solid. m.p. 278–279 ◦C; 1H NMR (400 MHz, DMSO-d6, ı):
8.27 (s 1H), 8.11 (s, 1H), 7.93 (d, J = 9.2 Hz, 1H), 7.43-7.53 (m, 5H),
7.15 (dd, J = 2.4, 2.4 Hz, 1H), 7.11 (s, 1H), 6.13 (s, 2H-NH2); 13C NMR

28
K. Baathulaa et al. / Journal of Photochemistry and Photobiology A: Chemistry 216 (2010) 24–34
(DMSO-d6, ı) 167.5, 167.4, 150.7, 138.3, 132.8, 131.9, 129.2, 128.3,
128.2, 127.8, 127.7, 125.4, 124.9, 122.1, 121.9, 121.4, 121.0, 108.9;
HRMS-EI calcd for C18H12N2O2: 288.0899. Found: 288.0900.
6-Chloro-2-phenyl-1H-benzo[f]isoindole-1,3(2H)-dione (4a): col-
orless solid. m.p. > 300 ◦C; 1H NMR (400 MHz, DMSO-d6, ı): 8.66
(s, 1H), 8.60 (s, 1H), 8.44 (s, 1H), 8.34 (d, J = 8.4 Hz, 2H), 7.83 (d,
J = 8.0 Hz, 1H), 7.46–7.56 (m, 5H); 13C NMR (DMSO-d6, ı): 166.8,
166.7, 136.4, 136.2, 134.4, 134.2, 134.1, 132.7, 132.4, 130.1, 129.33,
129.30, 129.0, 128.6, 128.3, 127.8, 125.2, 124.4; HRMS-EI calcd for
(2 × 50 mL), and then dried (Na2SO4). Purified by chromatography
and yields of these imides was generally high 75–85%.
6-(Dimethylamino)-2-(2-(dimethylamino)
ethyl)-1H-
benzo[f]isoindole-1,3(2H)-dione (1c): Green yellow solid. m.p.
182–185 ◦C; 1H NMR (400 MHz, CDCl3, ı): 8.11 (s, 1H), 8.05 (s,
1H), 7.83 (d, J = 9.2 Hz, 1H), 7.22 (d, J = 8.8 Hz, 1H), 6.99 (s, 1H), 3.85
(t, J1 = 6.4 Hz, J2 = 6.6 Hz, 2H), 3.28 (s, 6H), 2.65 (t, J = 2H, 6.4 Hz,
2H), 2.33 (s, 6H); 13C NMR (DMSO-d6, ı): 168.65, 168.57, 150.36,
137.55, 131.18, 128.69, 127.30, 124.53, 123.14, 122.49, 117.60,
107.82, 57.11, 45.46, 40.32, 35.84. HRMS-ESI (M+H+): calcd for
C18H21N3O2: 312.1712. Found: 312.1699.
C18H10ClNO2: 307.0400 Found: 307.0398.
6-Iodo-2-phenyl-1H-benzo[f]isoindole-1,3(2H)-dione (4e): Bright
color solid. m.p. 276–278 ◦C; 1H NMR (400 MHz, DMSO-d6, ı): 8.75
(d, J = 1.2 Hz, 1H), 8.58 (s, 1H), 8.52 (d, J = 1.2 Hz, 1H), 8.04 (s, 2H),
7.49–7.58 (m, 5H); 13C NMR (DMSO-d6, ı): 166.9, 166.8, 138.9,
137.9, 137.0, 134.5, 134.4, 132.4, 132.2, 132.1, 129.2, 128.65, 128.63,
128.2, 127.8, 125.3, 124.1, 97.3; HRMS-EI calcd for C18H10INO2:
398.9756. Found: 398.9753.
6-(Dimethylamino)-2-(3-(dimethylamino)propyl)-1H-
benzo[f]isoindole-1,3(2H)-dione (1d): Green yellow solid. m.p.
155–158 ◦C; 1H NMR (400 MHz, CDCl3, ı): 8.12 (s, 1H), 8.06 (s, 1H),
7.85 (d, J = 9.2 Hz, 1H), 7.23 (dd, J = 2.2 Hz, 1H), 7.01 (s, 1H), 3.77 (t,
J1 = 7.2 Hz, J2 = 6.8 Hz, 2H), 3.14 (s, 6H), 2.41 (t, J1 = 7.2 Hz, J2 = 7.6 Hz,
2H), 2.26 (s, 6H), 1.70–1.90 (m, 2H); 13C NMR (DMSO-d6, ı): 168.66,
168.59, 150.39, 137.56, 131.18, 128.68, 127.31, 124.47, 123.14,
122.43, 117.62, 107.83, 57.05, 45.29, 40.31, 36.22, 26.60; HRMS-ESI
(M+H+): calcd for C19H23N3O2: 326.1869. Found: 326.1864.
2.2.2. General procedure for the synthesis of N-(H)imides (1b–4b
and 4f)
A mixture of anhydride (1.1 mmol) and urea (2.2 mmol) was
heated at 170 ◦C for 2 h. The mixture was cooled and triturated
with water (30 mL) and the resulting solid collected by filtration
and dried to give desired imide (95%). The following compounds
were prepared by this general method.
2-(2-(Dimethylamino)
ethyl)-6-nitro-1H-benzo[f]isoindole-
1,3(2H)-dione hydrochloride (2c): Colorless solid. m.p. > 300 ◦C; 1H
NMR (400 MHz, DMSO-d6, ı): 9.32 (d, J = 1.6 Hz, 1H), 8.90 (s, 1H),
8.72 (s, 1H), 8.51 (dd, J1 = 9.2 Hz, J2 = 2.0 Hz, 1H), 8.49 (d, J = 2 Hz,
1H), 3.79 (t, J = 6.4 Hz, 2H), 2.85 (s„ 6H), 2.3 (t, J = 8.4 Hz, 1H); 13C
NMR (DMSO-d6, ı): 167.67, 167.59, 147.37, 138.26, 134.69, 132.58,
131.44, 129.83, 126.74, 126.59, 124.55, 122.68, 54.63, 54.511,
42.48, 35.61, 23.61; HRMS-ESI (M+H+): calcd for C16H15N3O4:
314.1141. Found: 314.1135.
6-(Dimethylamino)-1H-benzo[f]isoindole-1,3(2H)-dione
(1b):
Dark yellow solid. m.p. 290–292 ◦C; 1H NMR (400 MHz, DMSO-d6,
ı): 11.19 (s, 1H NH), 8.15 (s, 1H), 8.04 (s, 1H), 7.97 (d 1H, J = 8.4 Hz),
7.74 (d 1H, J = 7.6 Hz), 7.19 (s, 1H), 3.07 (s, 6H); 13C NMR (DMSO-d6,
ı): 169.68, 169.58, 150.68, 137.69, 131.4, 129.7, 127.31, 124.48,
123.97, 122.17, 118.31, 107.92, 40.2 (2); EIMS m/z 240.1.
2-(3-(Dimethylamino)
propyl)-6-nitro-1H-benzo[f]isoindole-
1,3(2H)-dione hydrochloride (2d): Light solid. m.p. > 300 ◦C; 1H
NMR (400 MHz, DMSO-d6, ı): 9.31 (d„ J = 1.6 Hz, 1H), 8.88 (s,
1H), 8.72 (s, 1H), 8.50 (dd, J1 = 9.2 Hz, J2 = 2.0 Hz, 1H), 8.47 (d,
J = 2.0 Hz, 1H), 3.73 (t, J = 6.4 Hz, 2H), 3.14 (qt, J1 = 5.2 Hz, J2 = 4.4 Hz,
2H), 2.72 (s, 6H), 2.30 (t, J = 8.4 Hz, 1H); 13C NMR (DMSO-d6, ı):
167.67, 167.59, 147.37, 138.26, 134.69, 132.58, 131.44, 129.83,
126.74, 126.59, 124.55, 122.68, 54.63, 54.511, 42.48, 35.61, 23.61;
HRMS-ESI (M+H+): calcd for C17H17N3O4: 328.1297. Found:
328.1292.
6-Nitro-1H-benzo[f]isoindole-1,3(2H)-dione (2b): Colorless solid.
m.p. > 300 ◦C; 1H NMR (400 MHz, DMSO-d6, ı): 11.8 (br 1-NH),
9.21 (s, 1H), 8.72 (s, 1H), 8.56 (s, 1H), 8.41 (dd, 2H, J1 = 18.8 Hz,
J2 = 18.4 Hz); 13C NMR (DMSO-d6, ı): 168.67 (2C), 150.37, 147.18,
138.19, 134.68, 132.47, 130.77, 126.65, 126.50, 124.37, 122.31;
EIMS m/z 242.1.
6-Amino-1H-benzo[f]isoindole-1,3(2H)-dione (3b): Dark green
solid. m.p. > 300 ◦C; 1H NMR (400 MHz, DMSO-d6, ı): 11.12 (s, 1H,
NH), 8.12 (s, 1H), 7.9 (s, 1H), 7.89 (d 1H, J = 8.8 Hz), 7.11 (dd, 1H,
J1 = 1.6 Hz, J2 = 1.6 Hz), 7.06 (s, 1H), 6.06 (s, 2H); 13C NMR (DMSO-d6,
ı): 169.77, 169.69, 151.70, 150.68, 150.46, 138.14, 131.83, 129.71,
127.65, 123.46, 121.43, 120.87, 108.38; EIMS m/z 212.0.
6-Chloro-1H-benzo[f]isoindole-1,3(2H)-dione (4b): Dark color
solid. m.p. 280–284 ◦C; 1H NMR (400 MHz, DMSO-d6, ı): 11.57 (s,
1H, –NH), 8.49 (s, 1H), 8.43 (s, 1H), 8.38 (d, 1H, J = 2.0 Hz), 8.28 (d
1H, J = 8.8 Hz), 7.78 (dd, 1H, J1 = 2.0 Hz, J2 = 2.0 Hz); 13C NMR (DMSO-
d6, ı): 169.05 (2C), 136.36, 134.17, 133.97, 132.61, 130.28, 129.88,
129.57, 129.26, 124.61, 123.83; EIMS m/z 231.0. DMSO-d6.
6-Iodo-1H-benzo[f]isoindole-1,3(2H)-dione (4f): Dark red solid.
m.p. 215–218 ◦C; 1H NMR (400 MHz, DMSO-d6, ı): 11.58 (s, 1H, NH),
8.73 (s, 1H), 8.42 (d, 2H, J = 21.2 Hz), 8.02 (s, 2H); 13C NMR (DMSO-
d6, ı): 169.11, 169.04, 138.90, 137.67, 136.95, 134.31, 132.14,
129.93, 129.52, 124.72, 123.56, 96.91; EIMS m/z 323.0.
6-Amino-2-(2-(dimethylamino)
ethyl)-1H-benzo[f]isoindole-
1,3(2H)-dione (3c): Green solid. m.p. 198–201 ◦C; 1H NMR
(400 MHz, DMSO-d6, ı): 8.16 (s, 1H), 8.00 (s, 1H), 7.89 (d, J = 8.8 Hz,
1H), 7.11 (dd, J = 2.0 Hz, 1H), 7.07 (s, 1H), 6.10 (s, 2H), 3.70 (t,
J = 6.4 Hz, 2H), 2.57 (t, J = 5.6 Hz, 2H), 2.23 (s, 6H); 13C NMR
(DMSO-d6, ı): 168.36, 168.27, 150.65, 138.08, 131.93, 128.48,
127.47, 124.89, 122.12, 121.71, 120.88, 108.54, 56.80, 45.30,
35.70; HRMS-ESI (M+H+): calcd for C16H17N3O2: 284.1399. Found:
284.1394.
6-Amino-2-(3-(dimethylamino)propyl)-1H-benzo[f]isoindole-
1,3(2H)-dione (3d): Green solid. m.p. 130–133 ◦C; 1H NMR
(400 MHz, DMSO-d6, ı): 8.15 (s, 1H), 7.99 (s, 1H), 7.88 (d, J = 8.4 Hz,
1H), 7.10 (dd, J = 2.0 Hz, 1H), 7.06 (s, 1H), 6.08 (s, 2H), 3.60 (t,
J = 7.2 Hz, 2H), 2.24 (t, J1 = 7.2 Hz, J2 = 6.8 Hz, 2H), 2.18 (s, 6H),
1.67-1.74 (m, 2H); 13C NMR (DMSO-d6, ı): 168.43, 168.36, 150.59,
138.07, 131.89, 128.54, 127.46, 124.80, 122.20, 121.63, 120.82,
108.53, 56.93, 45.47, 36.20, 26.45; HRMS-ESI (M+H+): calcd for
C17H19N3O2: 298.1556. Found: 298.1541.
2.2.3. General procedure for the synthesis of N-(aminoalky1)
imides (1c,d–4c,d and 4g,h)
Unless otherwise stated, all imides reported were prepared by
the following general procedure. To a stirred solution of 0.01 mol
of the proper anhydride in 100 mL of toluene was added drop
wise 0.015 mol of the appropriate N,N-dialky1amino alkylamine
in 10 mL of toluene within 5 min. The mixture was stirred at room
temperature for 60 min and then heated under reflux while con-
nected to a Dean-Stark trap for 2 h. After the theoretical amount of
water was removed, the reaction mixture was cooled, washed suc-
cessively with H2O (2 × 50 mL), 5% NaHCO3 (2 × 50 mL), and H2O
6-Chloro-2-(2-(dimethylamino)ethyl)-1H-benzo[f]isoindole-
1,3(2H)-dione (4c): Colorless solid. m.p. 280–283 ◦C; 1H NMR
(400 MHz, DMSO-d6, ı): 8.57 (s, 1H), 8.51 (s, 1H), 8.43 (s, 2H),
8.32 (d, J = 8.8 Hz, 2H), 7.82 (d, J = 8.8 Hz, 2H), 4.02 (t, J1 = 6.4 Hz,
J2 = 6.0 Hz, 2H), 3.41 (t, J = 5.2 Hz, 2H), 2.83 (s, 6H); 13C NMR
(DMSO-d6, ı): 167.84, 167.79, 136.30, 134.43, 133.90, 132.71,
130.15, 129.40, 129.37, 128.68, 124.82, 124.03, 54.59, 54.53, 42.65,
33.64; HRMS-ESI (M+H+): calcd for C16H15N3O4: 303.0900. Found:
303.0889.

K. Baathulaa et al. / Journal of Photochemistry and Photobiology A: Chemistry 216 (2010) 24–34
29
Table 1
6-Chloro-2-(3-(dimethylamino)propyl)-1H-benzo[f]isoindole-
Photophysical properties of 1a–4a and 4e in DMSO.
1,3(2H)-dione (4d): Colorless solid. m.p. 290–292 ◦C; 1H NMR
(400 MHz, DMSO-d6, ı): 8.55 (s, 1H), 8.50 (s, 1H), 8.41 (s, 2H),
8.31 (d, J = 8.8 Hz, 2H), 7.81 (d, J = 8.8 Hz, 2H), 3.78 (t, J1 = 6.4 Hz,
J2 = 6.0 Hz, 2H), 3.13-3.21 (m, 2H), 2.75 (s, 6H), 2.03 (t, J1 = 7.2 Hz,
J2 = 8.0 Hz, 2H); 13C NMR (DMSO-d6, ı): 168.52, 168.35, 136.34,
134.43, 133.36, 132.01, 130.69, 129.48, 129.29, 127.71, 124.85,
120.33, 54.59, 54.55, 42.69, 33.66, 23.62; HRMS-ESI (M+H+): calcd
for C17H18ClN2O2: 317.1057 Found: 317.1049.
Compound
Absorption
maximum and
excitation (nm)
Emission
maximum (nm)
Quantum yield
(˚)
1a
2a
3a
385 (390)
364 (375)
372 (375)
289 (300)
271 (300)
566
465
537
386
403
0.18
0.13
0.21
0.16
0.09
4a (chloro)
4e (iodo)
2-(2-(Dimethylamino)ethyl)-6-iodo-1H-benzo[f]isoindole-
1,3(2H)-dione hydrochloride (4g): Brown solid. m.p. 285–288 ◦C; 1
H
NMR (400 MHz, DMSO-d6, ı): 8.76 (s, 1H), 8.49 (d, J = 22.4 Hz, 2H),
8.05 (s, 2H), 4.01 (t, J1 = 5.6 Hz, J2 = 6.0 Hz, 2H), 3.41 (t, J = 5.2 Hz, 2H),
2.82 (s, 6H); 13C NMR (DMSO-d6, ı): 167.89, 167.81, 138.95, 137.91,
136.85, 134.23, 132.21, 129.06, 124.90, 123.72, 97.26, 54.48, 54.44,
42.55, 33.61; HRMS-ESI (M+H+): calcd for C16H15IN2O2: 3950256.
Found: 395.0243.
3.2. Absorption and emission spectra
The absorption maximum for unsubstituted 2,3-NP appears at
340–350 nm, while its fluorescence emerges at 380–400 nm. All the
UV spectra of the studied compounds (6-sub 2,3-NP) were ranged in
the 280–390 nm and some of them are shown in Fig. 2. The maxima
of the absorption, excitation and emission wavelength were given
in Table 1. As is typical of a charge-transfer transition, an increase in
the polarity of the medium leads to a Stokes shift of the absorption
maximum. A change of the solvent from toluene to ethanol typically
results in 10–20 nm bathochromic shift of the absorption maximum
of the systems. On one hand, substitution of the hydrogen in N–H
by a alkyl amine group, or by a phenyl group, leads to a slight red
shift of the absorption maximum: 363 nm for N–H compared with
369 nm for N-(CH2)2N(Me)2 and 372 nm for N–Ph (average). On the
other hand, a minor bathochromic shift was observed if the 2,3-
naphthaline ring was substituted with an electron-donating group,
such as dimethyl-amino [6-DMN, 1a–d] (average of 380 nm).
The absorption spectra of 3a in different solvents are shown in
Fig. 3, respectively. Surprisingly, in aqueous medium, it showed sig-
nificant difference in the spectral behavior, the absorption around
the 360 nm became negligible. In polar solvents the large Stokes
shift was due to major stabilization of S1 state with contribution of
an ICT effect and also it was well known that compounds contain-
ing lone pair of electrons undergo a blue shift (to higher energy)
in their n–␲* electronic transition when solvation occurs. The rea-
son for this blue shift was a lowering of the energy of the lone-pair
orbital caused by the molecule’s strong interaction with protic sol-
vents, such as amino group with water through hydrogen-bond
formation.
In the case of 3a, we studied the effect of polarity and hydrogen
bonding interaction of the solvents on the spectroscopic properties,
and the results were reported in Table 2. Increase of the polarity of
aprotic solvents leads to a red shift of the emission wavelength,
from 496 nm in toluene to 515 nm in acetonitrile. The effect was
less important on the absorption maximum than on the emission
maximum, which suggests an excited state more polar than the
ground state. The change in charge distribution following the exci-
tation may be quantified by determination of the dipole moment
variation between the ground state and the excited state using the
Lippert–Mataga equation [23]. The charge transfer occurs from the
amino group to the carbonyl and the phenyl group was more elec-
tronic donating than the hydrogen atom; therefore a lower value of
the dipole moment of 3a was expected. Almost no change of the flu-
orescence quantum yield with the polarity was observed in aprotic
solvents (average of ˚F = 0.20) as in the case of 3a. In protic solvents
such as ethanol and water, an important red shift (Table 2) of the
emission wavelength was noticed compared to polar aprotic sol-
vents (ACN, DMSO). For instance, ꢀfluo max = 559 nm in ethanol and
ꢀfluo max = 515 nm in acetonitrile, although acetonitrile and ethanol
have almost the same polarity, but hydrogen-bonding capacity of
the ethanol leads to n–␲ transition. On the other hand, the unex-
pected large Stokes shift observed in water (nearly 297 nm) was
not attributed to the increase of the solvent polarity, but to the
hydrogen bonding interaction between the carbonyl groups of the
2-(3-(Dimethylamino)propyl)-6-iodo-1H-benzo[f]isoindole-
1,3(2H)-dione hydrochloride (4h): Brown solid. m.p. 292–295 ◦C; 1
H
NMR (400 MHz, DMSO-d6): 8.75 (s, 1H), 8.51 (s, 1H), 8.48 (s, 1H),
8.04 (s, 2H), 3.70 (t, J1 = 6.4 Hz, J2 = 6.0 Hz, 2H), 3.09–3.15 (m, 2H),
2.71 (s, 6H), 2.03 (t, J1 = 7.2 Hz, J2 = 8.0 Hz, 2H); 13C NMR (DMSO-d6,
ı): 167.89, 167.81, 138.93, 136.86, 134.25, 132.19, 128.86, 128.44,
124.86, 123.69, 97.24, 54.60, 54.55, 42.41, 35.47, 23.65; HRMS-ESI
(M+H+): calcd for C17H17IN2O2: 409.0413. Found: 409.0435.
3. Results and discussions
3.1. Synthesis
There were few reports available on the synthesis of 6-
substituted 2,3-naphthalimide derivatives [4,5, and 21]. Here we
have attempted to synthesize various 6-substituted naphthalim-
ides as described.
Synthesis of 6-sub-2,3-naphthaleneanhydrides and its imide
analogs were derived successfully from key intermediate (6) in
the above efficient route (Schemes 1 and 2), with different groups
like strong (e.g. NO2) and poor electron-withdrawing groups (e.g.
Cl, I) and strong electron-donating groups (NH2). To synthesize
the intermediate 6, started from 1,2-dimethyl 4-nitrobenzene,
which was subjected to photobromination with bromine in
chlorobenzene to get 1,2-bis(dibromomethyl)-4-nitrobenzene (5).
The resultant tetrabromide (5) was treated with maleic anhydride
and KI followed by base hydrolysis to obtain the Diels–Alder adduct
of nitro diacid 6, we found nitro anhydride (7) instead of compound
6 with good yield and high purity, under similar reaction conditions
except base hydrolysis (Scheme 1). The above Diels–Alder adducts
were recrystallized from dichloromethane. The reductive amina-
tion of intermediate (6) with 37% formalin solution and hydrogen in
the presence of catalytic amount of Pd/C at room temperature and
30 psi pressure afforded the desired 6-N,N-dimenthylamino-2,3-
naphthalene dicarboxylic acid in excellent yield with high purity
after several times washing with water, after dehydration on acetic
anhydride under reflux obtained the desired anhydride 1 (6-DMN
Precursor) (Scheme 1).
For the preparation of derivatives 3a–d and 4a–h, we have tried
direct reductive amination of compound 7, but were unsuccessful
due to the instability of the ring. Then we selected the alternative
route as shown in Scheme 2. Compound 6 was subjected to cat-
alytic hydrogenation to get 6-amino dicarboxylic acid (8), which
was further diazotized, followed by Sand Mayer reaction to afford
6-halo dicarboxylic acid. We are the first one to characterize these
diacids. The crude 6-substituted diacid was directly converted to
anhydrides by treating with acetic anhydride under reflux. Then
condensation with appropriate amine in acetic acid as solvent
affords 6-substitued 2,3-naphthalimides.

30
K. Baathulaa et al. / Journal of Photochemistry and Photobiology A: Chemistry 216 (2010) 24–34
In DMSO
R =
comp 1a (566, 0.18)
comp 2a (465, 0.13)
comp 3a (537, 0.20)
comp 4a (386, 0.16)
comp 4e (403, 0.09)
160
150
140
130
120
110
100
90
0.8
0.5
0.3
0.0
comp 1a (385, N(Me)2)
comp 2 a (364, NO2)
comp 3 a (372, NH2)
comp 4 a (289, Cl)
comp 4 e (273, I)
O
N
O
R
80
70
60
50
40
30
20
10
0
400
450
500
550
600
650
300
400
Wave number (nm)
Wave Length (nm)
Fig. 2. Absorption and fluorescence spectra of 6-sub 2,3-naphthalimides (1a–4a and 4e) in DMSO.
DMSO
(537, 0.20)
Toluene (496, 0.18)
Red shift (non polar to polar solvents)
DCM
MeOH
ACN
(515, 0.202)
(564, 0.025)
(515, 0.167)
(559, 0.044)
(571. 0.004)
DMSO (372 nm)
140
Toluene (355 nm)
0.8
EtOH
DCM
MeOH (365 nm)
ACN (356 nm)
EtOH (368 nm)
(351 nm)
120
100
80
60
40
20
0
H
2O
O
N
O
0.6
0.4
0.2
0.0
H2N
H2O
(274 nm)
O
H2N
N
O
3a
400
450
500
550
600
650
300
400
500
Wavelength (nm)
Wavelength (nm)
Fig. 3. Absorption (A) and fluorescence (F) spectra of 6-amino-2,3-naphthalimide (3a) in water, methanol, ethanol, acetonitrile, DMSO, dichloromethane and toluene.
Excitation wavelength: 375 nm and 300 nm (H2O).
naphthalimide (which acts as hydrogen bonding acceptor) and the
hydroxylated solvents (which acts as hydrogen bond donor). This
interaction was also responsible for the decrease of the fluores-
cence quantum yield. In water, ˚F was almost 50 times weaker
than in the aprotic solvents, almost 10–20 times weaker than in
polar and protic solvents, e.g. methanol, ethanol, which also means
that the hydrogen bonding interaction between 3a and water was
much stronger than those between 3a and methanol or ethanol, as
water has more hydrogen bonding sites than methanol and ethanol.
Non-radiative deactivation of the excited state through hydrogen
bonding [24] has been suggested to explain this specific behavior in
protic solvents. The other three compounds of 6-AMN family (3b,
3c, 3d) exhibit similar behaviors in terms of their absorption and
emission properties compared with 3a. Substitution of the hydro-
gen in N-H (3b) by the alkyl amine groups (3c, 3d), leads to a slight
red shift of the absorption maxima and emission spectra.
The absorption and emission spectra of 3b in different solvents
are shown in Fig. 4, respectively. From Fig. 4 the absorption max-
ima of studied compound 3b in all solvents were at 273–368 nm
and emission maxima were at 478–576 nm. The absorption peak
Table 2
Photophysical properties of 3a in different solvents.a
Solvent
Absorption maximum (nm)
Emission maximum (nm)b
Quantum yield (˚)
Solvent type
Water
Methanol
Ethanol
ACN
DMSO
DCM
274
365
368
356
372
351
355
571
564
559
515
537
515
496
0.0042
0.025
0.044
0.167
0.209
0.202
0.182
Protic
Polar aprotic
Apolar aprotic
Toluene
a
With quinine sulfate in 0.1 mol/L sulfuric acid as quantum yield standard (˚ = 0.58) [27].
Excitation wavelength: 375 nm and 300 nm (H2O).
b

K. Baathulaa et al. / Journal of Photochemistry and Photobiology A: Chemistry 216 (2010) 24–34
31
0.3
0.2
0.1
0.0
DMSO (363 nm)
Toluene (352 nm)
DMSO (518 nm, 0.203)
Toluene (478 nm, 0.195)
DCM (505 nm, 0.209)
MeOH (572 nm, 0.029)
DCM
(344 nm)
500
400
300
200
100
0
MeOH (359 nm)
H2O
(273 nm)
H2O
(576 nm, 0.004)
O
O
H2N
H2N
NH
O
NH
O
3b
3b
300
400
400
450
500
550
600
Wavelength (nm)
Wavelength (nm)
Fig. 4. Absorption (A) and fluorescence (F) spectra of 3b in water, methanol, DMSO, dichloromethane and toluene. Excitation wavelength: 375 nm and 300 nm (H2O).
position for 3b was unusually blue-shifted (273 nm) in aque-
ous media relatively to that of other solvents same as 3a
and a minor short wavelength occurs due to imide hydrogen
(–N–H).
The absorption and emission spectra of 3c in different solvents
are shown in Fig. 5, respectively. From Fig. 5 the absorption max-
ima of studied compound 3c in all solvents were at 276–369 nm
and emission maxima were at 482–576 nm. Substitution of the
hydrogen in N–H by a N,N-dimethylethylenediamine and dimethy-
laminopropylamine, leads to a slight red shift of the absorption and
emission maximum.
6-ANP compounds displayed a marked positive solvatochromic
effect in the emission spectra, accompanied by a reduction of the
fluorescence quantum yield (˚F) with increasing solvent’s polar-
ity. The three main reasons given for this effect were namely: (1)
an increase in dipole moment of S1 relative to S0; (2) the formation
of much stronger hydrogen bond in the S1-ICT state than in the
S0 state. Recently Wang et al. reported the results of the theoreti-
cal study on the excited-state hydrogen-bonding dynamics of 4-AP
chromophore (4-aminophthalimide) in hydrogen-donating water
solvent using the TDDFT method [25]. On the other hand, Topp
and co-workers studied the properties of 4-AP and the hydrogen-
bonded 4-AP-(H2O)1,2 complexes under jet-cooled conditions and
showed the results of infrared double-resonance experiments on
these complexes. The structures of the hydrogen-bonded 4AP-
(H2O)1,2 clusters were given [26]. 4-AP and 6-ANP belong to the
same class of family. Then we like to adopt same principle to
our 6-amino 2,3-naphthalimides. The fluorescence maximum was
located at 490 nm for ANP in aprotic solvents, while it was at 570 nm
for hydrogenated solvents. The large red shift was due to the alter-
native formation of intermolecular hydrogen bond C O· · ·H–O and
N–H· · ·O–H (Fig. 6).
Compounds 1a and 1b have similar properties with 6-DMN
described by Loving and Imperiali [3]. The maximum excitation
wavelength of 6-DMN was at 370 nm (water), and contrary to
it, fluorescence of 6-DMN was strongly influenced by polarity of
the medium. The fluorescence in polar methanol or water was
strongly bathochromically shifted from around 482 nm in toluene
up to 585 nm in methanol, and the fluorescence quantum yield
decreased from dichloromethane (˚F = 0.212) to water (˚F = 0.002)
(Fig. 7).
Substitution by –NO2, leads to some changes in the absorp-
tion and emission spectra compared with unsubstituted 2,3-
naphthalimide (free naphthalene ring) (2,3-NP). A red shift about
44 nm was observed relative to the spectra of 2,3-NP (generally
emission maxima ∼ 379 nm) [29], and the absorption and emission
bands become broad and structureless, probably due to an efficient
intersystem crossing (S1–T1) leading to a non-reactive triplet state.
These results were consistent with the presence of the CT excited
states. In the case of O2N–NP, the charge transfer occurs in the
opposite direction: from aromatic ring toward the nitro substituent
(Fig. 8).
O
DMSO (369 nm)
Toluene (352 nm)
H2N
N
DMSO (524 nm, 0.221)
Toluene (482 nm, 0.18)
DCM (503 nm, 0.206)
MeOH (563 nm, 0.027)
N
DCM
MeOH (359 nm)
H2O (276 nm)
(346 nm)
500
400
300
200
100
0
O
H2O
(576 nm, 0.004)
3c
O
H2N
N
N
O
3c
0.0
400
450
500
550
600
300
400
Wavelength (nm)
Wavelength (nm)
Fig. 5. Absorption (A) and fluorescence (F) spectra of 3c in water, methanol, DMSO, dichloromethane and toluene. Excitation wavelength: 375 nm and 300 nm (H2O).

32
K. Baathulaa et al. / Journal of Photochemistry and Photobiology A: Chemistry 216 (2010) 24–34
DMSO (367 nm)
Toluene (353 nm)
700
DMSO (528 nm, 0.225)
Toluene (481 nm, 0.19)
DCM (503 nm, 0.213)
MeOH (577 nm, 0.029)
DCM
(347 nm)
MeOH (362 nm)
600
500
400
300
200
100
0
H O
(276 nm)
2
H2O
(579 nm, 0.004)
O
N
O
N
H2N
O
N
H2N
N
O
3d
3d
0.0
300
400
400
450
500
550
600
Wavelength (nm)
Wavelength (nm)
Fig. 6. Absorption (A) and fluorescence (F) spectra of 3d in water, methanol, DMSO, dichloromethane and toluene. Excitation wavelength: 375 nm and 300 nm (H2O).
800
700
600
500
400
300
200
100
0
DMSO (544, 0.159)
Toluene(482, 0.209)
DCM (507, 0.212)
MeOH (585, 0.013)
DMSO (378 nm)
Toluene (361 nm)
DCM
(368 nm)
MeOH (375 nm)
H2O
(590, 0.002)
H2O
(370 nm)
N
0.5
O
O
N
NH
NH
O
1b
O
1b
0.0
300
400
500
400
450
500
550
600
650
Wavelength (nm)
Wavelength (nm)
Fig. 7. Absorption (A) and fluorescence (F) spectra of 6-dimethyl 2,3-naphthalimide (6-DMN) in DMSO, methanol, dichloromethane, toluene and water. Excitation wavelength:
380 nm.
Substitution by –iodo group leads to minor changes in the
absorption and emission spectra. A small red shift was observed
in the spectra of 6-INP relative to 2,3-NP. The nature of the iodo
substituent was unusual: it was an electron-donating substituent
due to its lone pair of electrons, while it behaves as an electron
withdrawing substituent due to the relative electron negativity of
iodine atom. Thus, the overall effect of iodo substitution was minor,
and the character of the excited state was very similar to the par-
ent 2,3-NP. The absorption maxima (271 nm) and the fluorescence
emission maxima (403 nm) for compound 4e were summarized in
Toluene ( 406, 0.019)
2.5
DCM
( 415, 0.155)
MeOH (406, 0.016)
Toluene ( 376 nm)
H2O
( 423, 0.013)
O
DCM
( 368 nm)
2.0
1.5
1.0
0.5
0.0
MeOH (369 nm)
20
H2O
(379 nm)
O
O2N
NH
O
O2N
NH
O
2b
0
300
400
500
400
450
500
550
600
Wavelength (nm)
Wave Length (nm)
Fig. 8. Absorption (A) and fluorescence (F) spectra of 6-nitro 2,3-naphthalimide (2b) in methanol, dichloromethane, toluene and water. Excitation wavelength: 380 nm.

K. Baathulaa et al. / Journal of Photochemistry and Photobiology A: Chemistry 216 (2010) 24–34
33
70
2.5
2.0
1.5
1.0
0.5
0.0
60
Toluene (408, 0.41)
DCM (413, 0.53)
MeOH (420, 0.113)
Toluene (283 nm)
DCM
(271 nm)
MeOH (266 nm)
50
40
30
20
10
0
H2O
(480, 0.009)
H2O
(273 nm)
O
O
I
I
NH
O
NH
4f
O
300
400
500
400
450
500
550
600
Wave Length (nm)
Wave Length (nm)
Fig. 9. Absorption (A) and fluorescence (F) spectra of 6-iodo 2,3-naphthalimide (4f) in methanol, dichloromethane, toluene and water. Excitation wavelength: 300 nm.
Table 1. From Fig. 9 the absorption maxima of studied compound
4f in all three solvents were at 266–288 nm and emission maxima
were at 400–480 nm.
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4. Conclusion
In this paper we presented the results on the synthesis, spectral
(absorption and emission) and photophysical studies of 6-amino-
2,3-naphthalimides and other 6-sub-2,3-naphthlimides in a range
of solvents. A new environment-sensitive fluorophore, 6-ANP dis-
plays excellent fluorescent properties: long excitation (375 nm)
and emission wavelengths (480–590 nm) and also an acceptable
quantum yield (˚F = 0.2) to (˚F = 0.004), and unusual large Stokes
shift. The unexpected large Stokes shift observed in water (about
300 nm) was not only attributed to the increase of the solvent
polarity, but also to the hydrogen bonding interaction between
the carbonyl groups of the naphthalimide (which act as hydro-
gen bonding acceptor) and the hydroxylated solvents (which act
as hydrogen bond donor). This interaction was also responsible for
the decrease of the fluorescence quantum yield. We also reported
photophysical properties of some other 6-sub-2,3-naphthalimides
(NO2, I).
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Acknowledgements
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This work was financially supported by the Key New Drug
Creation and Manufacturing Program (2009ZX09103-102), the
National High Technology Research and Development Program of
China (863 Program 2006AA10A201), the China 111 Project (Grant
B07023), and the Shanghai Leading Academic Discipline Project
(B507). The author also thanks to Shanghai Municipal Government
for Funding.
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