Control of photophysical properties of 1,8-naphthalimides by electron-withdrawing substituents introduced into N-alkyl side chains

Article abstract of DOI:10.1246/bcsj.20100276

The fluorescence intensity of naphthalimides 1-7 in dichloromethane was found to be remarkably enhanced by the introduction of an electron-withdrawing substituent, such as OCOMe, CO₂Me, Cl, and CN, into the N-alkyl side chain. The rate constants of the fluorescence emission k_f, the intersystem crossing k_isc, and the internal conversion k_ic for 1-7 in dichloromethane and in acetonitrile were determined based on the measurements of the fluorescence lifetimes τ_f, by using picosecond single photon counting, and the quantum yields of the intersystem crossing φ_isc determined by time-resolved thermal lensing. These results indicate that the value of k_isc decreases with an increase in the electron-withdrawing ability of the substituent. Furthermore, an almost linear Hammett relationship (ρ = -1.48 in dichloromethane, ρ = -1.85 in acetonitrile) between the logarithm of kisc and the substituent constant ·I for inductive effect of the substituent through the σ bond was observed. The enhancement of the fluorescence intensity by the introduction of electron-withdrawing substituents was thus explained by a decrease in the efficiency of the intersystem crossing from ¹(ππ*) to ³(nπ*), whose energy was increased by the inductive effect of the substituent through the · bonds.

Full text of DOI:10.1246/bcsj.20100276

5
20
Bull. Chem. Soc. Jpn. Vol. 84, No. 5, 520–525 (2011)
© 2011 The Chemical Society of Japan
Control of Photophysical Properties of 1,8-Naphthalimides
by Electron-Withdrawing Substituents Introduced
into N-Alkyl Side Chains
1
1
1
2
2
Kazuhiko Matsubayashi, Chisato Kajimura, Yasuo Kubo,* Toshitada Yoshihara, and Seiji Tobita
1Department of Materials Science, Faculty of Science and Engineering, Shimane University, Matsue, Shimane 690-8504
2Department of Chemistry, Gunma University, Kiryu, Gunma 376-8515
Received September 27, 2010; E-mail: kubo@riko.shimane-u.ac.jp
The fluorescence intensity of naphthalimides 1­7 in dichloromethane was found to be remarkably enhanced by the
introduction of an electron-withdrawing substituent, such as OCOMe, CO2Me, Cl, and CN, into the N-alkyl side chain.
The rate constants of the fluorescence emission kf, the intersystem crossing kisc, and the internal conversion kic for 1­7 in
dichloromethane and in acetonitrile were determined based on the measurements of the fluorescence lifetimes ¸f, by using
picosecond single photon counting, and the quantum yields of the intersystem crossing Φisc determined by time-resolved
thermal lensing. These results indicate that the value of kisc decreases with an increase in the electron-withdrawing ability
of the substituent. Furthermore, an almost linear Hammett relationship (μ = ¹1.48 in dichloromethane, μ = ¹1.85 in
acetonitrile) between the logarithm of kisc and the substituent constant ·I for inductive effect of the substituent through the
·
bond was observed. The enhancement of the fluorescence intensity by the introduction of electron-withdrawing
1
3
substituents was thus explained by a decrease in the efficiency of the intersystem crossing from (³³*) to (n³*), whose
energy was increased by the inductive effect of the substituent through the · bonds.
Naphthalimides are known to be promising anticancer
The photoreactions of naphthalimides have been inves-
tigated over the past decade by Kubo and co-workers.
1
5
agents, showing broad-spectrum activity against a variety of
1
human solid tumor cells. Some naphthalimides have reached
Matsubayashi and Kubo have recently shown that the fluores-
cence intensity and photoreactivity of N-methyl-1,8-naphthal-
imide (1) are remarkably increased by intermolecular hydrogen
2
the phase of clinical trials. Their DNA binding or enzyme
inhibitory activity is believed to be pivotal in exerting
antitumor effects. The dicationic compounds have proven to
1
6
bonding with alcohols. Furthermore, Kubo and co-workers
have reported that intramolecular hydrogen bond formation in
1,8-naphthalimide derivatives decreases the rate of intersystem
3
be more potent than the monocationic analogs. 1,8-Naphthal-
imide derivatives with intramolecular dialkylammonium moie-
ties exhibit much stronger association to oligodeoxynucleotides
than the corresponding neutral molecules due to electrostatic
interactions with the phosphate groups.4
1
3
crossing from (³³*) to (n³*), that results from an increase
3
in the energy of the (n³*) level due to the presence of the
hydrogen bonding, while the rates of fluorescence emission and
1
7
Photoinduced processes of naphthalimides are also of
particular interest because of their broad-ranging applications
in fundamental studies and advanced technology as well as
in biological and medical areas. Naphthalimides are capable
internal conversion were minimally affected. In the course
of our investigations, we have found that the introduction of
electron-withdrawing substituents into the N-methyl group of
1 gave rise to a surprising enhancement in the fluorescence
intensities. In this paper, we present our systematic investiga-
tion on the effect of the introduction of electron-withdrawing
substituents, such as OCOMe, CO2Me, Cl, and CN, into the
N-alkyl side chains on the photophysical properties of 1,8-
naphthalimides 1­7 (Chart 1).
5
of initiating the photocleavage of DNA and photochemical
crosslinking of proteins.6 Irradiation of their brominated
derivatives with visible light has been shown to generate
7
photoproducts with strong antiviral activity.
Additionally, investigations of the photophysical behavior of
naphthalimides have contributed to the development of new
8
9
Results and Discussion
fluorescent probes and optical sensors. The marked changes
of the fluorescence intensity and maximum of 6-(N,N-di-
methylamino)-2,3-naphthalimide corresponding to the changes
of the microenvironment can be implemented for monitoring
protein­protein interactions.10 Dual fluorescence has been
UV Spectra. To clarify the effect of the introduction of
electron-withdrawing substituents into the N-alkyl side chain of
1,8-naphthalimides in the ground state, UV spectra of 1­7 were
measured in dichloromethane (Figure 1). Figure 1 shows the
slight red shift of the absorption spectra with an increase of the
electron-withdrawing ability of the substituents.
11
reported for several substituted N-phenylnaphthalimides and
the relative intensity of the two fluorescence bands has been
1
2
shown to be sensitive to solvent polarity, temperature,
viscosity, and pressure.
Fluorescence Spectra.
To clarify the effect of the
1
3
14
introduction of electron-withdrawing substituents into the N-
Published on the web April 30, 2011; doi:10.1246/bcsj.20100276

K. Matsubayashi et al.
Bull. Chem. Soc. Jpn. Vol. 84, No. 5 (2011)
521
R
7
O
N
O
5
4
, 6
1
2
3
4
5
6
7
; R = H
; R = (CH ) OCOMe
2
2
1
; R = CH OCOMe
2
; R = OCOMe
400
500
; R = CO Me
wavelength / nm
2
; R = Cl
; R = CN
Figure 2. Fluorescence spectra of naphthalimides 1 and 4­7
0.060 mM) in dichloromethane with an excitation wave-
length of 333 nm.
(
Chart 1.
1
4
Abs
7
1
-6
3
0
3
00
wavelength / nm
380
2
1
Figure 1. Absorption spectra of naphthalimides 1­7 (0.060
mM) in dichloromethane.
4
00
500
alkyl side chain of 1,8-naphthalimides in the singlet excited
state, fluorescence spectra of 1­7 were measured in dichloro-
methane. The spectra of 1 and 4­7, and 1­4 are shown in
Figures 2 and 3, respectively. Figure 2 shows that the fluores-
cence intensity of 1 (R = H, Chart 1), 4 (R = OCOMe), 5
wavelength / nm
Figure 3. Fluorescence spectra of naphthalimides 1­4
0.060 mM) in dichloromethane with an excitation wave-
length of 333 nm.
(
(
R = CO Me), 6 (R = Cl), and 7 (R = CN) increases with an
2
increase in the electron-withdrawing ability of the substituent
introduced into the N-methyl group of 1. Figure 3 shows that
the fluorescence intensity of 1 (R = H, Chart 1), 2 [R =
the enhancement of the fluorescence intensity by hydrogen
bond formation was observed only in nonpolar and less polar
solvents.
1
6
(
CH ) OCOMe], 3 (R = CH OCOMe), and 4 (R = OCOMe)
The quantum yields of the intersystem crossing Φisc of 1­7
in aerated dichloromethane and acetonitrile at 293 K were
determined by using time-resolved thermal lensing (TRTL).
The quantum yields of the internal conversion Φic were derived
using the following equation:
2
2
2
decreases as the number of methylene groups between the
imide and the electron-withdrawing OCOMe group increases,
indicating that the effect of the electron-withdrawing substitu-
ent introduced into the N-alkyl side chains on the fluorescence
intensity is caused by the inductive effect of the substituent
through · bonds.
1
9
ꢀ
ic ¼ 1 ꢀ ꢀf ꢀ ꢀisc
ð1Þ
Photophysical Properties. The fluorescence lifetimes ¸ of
The rate constants of the fluorescence emission k , the
f
f
1
­7 in aerated dichloromethane and acetonitrile at 293 K were
intersystem crossing k , and the internal conversion k were
isc
ic
measured by picosecond single photon counting. The fluores-
calculated from the equations given below:
ꢀ
1
cence quantum yields Φ of 1­7 in aerated dichloromethane and
f
k ¼ ꢀ ¸
kisc ¼ ꢀisc¸f
kic ¼ ꢀic¸f
ð2Þ
ð3Þ
ð4Þ
f
f f
acetonitrile were determined as relative values to that of 1 in
ꢀ
1
18
acetonitrile (Φ = 0.027). It should be emphasized here that
f
ꢀ1
the enhancement of the fluorescence intensity by the introduc-
tion of the electron-withdrawing substituent occurred even in
polar acetonitrile as well in less polar dichloromethane, while
The photophysical parameters of 1­7 in dichloromethane
and acetonitrile are summarized in Table 1. The data show that

5
22
Bull. Chem. Soc. Jpn. Vol. 84, No. 5 (2011)
Photophysical Properties of 1,8-Naphthalimide
Table 1. Photophysical Parameters for Naphthalimides 1­7
Solvent
CH2Cl2
Imide
¸f/ps
Φf
Φisca)
Φic
kf/108 s¹1
kisc/109 s¹1
kic/108 s¹1
·Ib)
1
2
3
4
5
6
7
1
2
3
4
5
6
7
180
218
292
620
688
716
1010
177
205
303
797
863
952
1450
0.030
0.033
0.046
0.104
0.110
0.111
0.180
0.027
0.033
0.047
0.110
0.140
0.145
0.230
0.92
0.91
0.89
0.84
0.85
0.83
0.77
0.92
0.91
0.89
0.83
0.79
0.80
0.70
0.05
0.06
0.06
0.06
0.04
0.06
0.05
0.05
0.06
0.06
0.06
0.07
0.06
0.07
1.7
1.5
1.6
1.6
1.6
1.6
1.8
1.5
1.6
1.6
1.4
1.6
1.5
1.6
5.1
4.2
3.0
1.4
1.2
1.2
0.78
5.2
4.4
2.9
1.0
0.92
0.84
0.48
2.8
2.8
2.1
0.97
0.58
0.84
0.50
2.8
2.9
2.0
0.75
0.81
0.63
0.48
0
0.05
0.14
0.39
0.30
0.47
0.58
0
c)
MeCN
0.05
0.14
0.39
0.30
0.47
0.58
c)
a) The Φisc values were determined using TRTL. b) The substituent constants ·I for the inductive effect through · bonds for the
substituents R shown in Chart 1. c) The ·I values for CO2R.
9
¹1
the values of k (µ10 s ) are significantly larger than those
isc
¹1
8
8
¹1
0
0.2
0.4
0.6
0.8
2
of k (µ10 s ) and k (µ10 s ) for 1­7 in both dichloro-
f
ic
1
ρ
= -1.48 in CH Cl
2
2
methane and acetonitrile, indicating that the intersystem cross-
-
-
-
-
ing is the most dominant relaxation process (Φ > 0.70) from
isc
1
the lowest singlet excited state (³³*) of 1­7. Furthermore,
3
these results indicate that the introduction of electron-with-
drawing substituents into the N-alkyl side chains mainly affects
4
6
the rate constant of the intersystem crossing k , and the values
5
7
isc
of kisc remarkably decrease with an increase of the electron-
withdrawing ability of the substituent.
Hammett Relationship. To evaluate the inductive effect
of the substituents introduced into the N-methyl group of N-
methyl-1,8-naphthalimide (1), the Hammett relationship was
applied:
ρ
= -1.85 in MeCN
-1
-1.2
-
0.1
0.1
0.3
0.5
logðkisc=kiscHÞ ¼ μ·I
ð5Þ
σ
I
An almost linear Hammett relationship (μ = ¹1.48 in
dichloromethane, μ = ¹1.85 in acetonitrile) between the
Figure 4. Hammett plot for the rate constants of the
intersystem crossing kisc in dichloromethane ( ) and
acetonitrile ( ) versus substitution constant ·I for
naphthalimides 1­7.
2
0
logarithm of kisc for 1­7 and the substituent constant ·I for
the inductive effect through · bonds for the substituents R
shown in Chart 1 was observed. Some deviations were
observed for 5, possibly due to the uncertainty of the
substituent constant · for CO Me (Figure 4). These results
1
*
3
*
R
R
I
2
suggest that a considerable positive charge is developed on the
nitrogen atom of naphthalimides 1­7 in the course of the
intersystem crossing from the lowest singlet excited state
δ+
O
N
O
O
N
O
kisc
1
3
δ-
(
³³*) to the upper triplet excited state (n³*), whose n and
³
* orbital localize mainly in the imide moiety and in the
naphthalene ring, respectively (Scheme 1).
Mechanism. Wintgens et al. have reported that the (³³*)
S1 (ππ*)
Tn (nπ*)
1
log (kisc/kiscH) = ρσΙ
3
18
and (n³*) levels of 1 are close together in energy. The
present investigation reveals that the intersystem crossing from
Scheme 1.
1
3
(
³³*) to (n³*) is the most important deactivation process of
the singlet excited state of 1­7 and the value of kisc remarkably
decreases with an increase of the electron-withdrawing ability
of the substituent introduced into the N-alkyl side chains. The
introduction of the electron-withdrawing substituent may
by the inductive effect of the substituents through · bonds
since a considerable positive charge is developed on the
3
nitrogen atom in the triplet excited state (n³*). The value of
1
3
kisc from the (³³*) to the (n³*) state was thus decreased
3
1
increase the energy of the upper triplet excited state (n³*)
because of an increasing energy gap between the (³³*) and
the (n³*) (Scheme 2).
1
3
state relative to that of the lowest singlet excited state (³³*)

K. Matsubayashi et al.
Bull. Chem. Soc. Jpn. Vol. 84, No. 5 (2011)
523
nπ*
S2
nπ*
nπ*
ΔE
Tn
S2
kisc = 5.1
kisc = 0.78
9
-1
nπ*
ππ*
9
-1
τf = 180 ps
× 10 s
τ = 1010 ps
f
1
× 10 s
Tn
T1
ΔE
S1
S
ππ*
ππ*
T1
ππ*
h
ν
hν
Φf = 0.030
Φf = 0.180
S0
S0
CN
Me
O
N
O
O
N
7
O
1
σI = 0
σI = 0.58
Scheme 2.
The picosecond lifetime measurements were carried out by
Conclusion
using a self-mode-locked Ti:sapphire laser (center wavelength:
800 nm, pulse width: ca. 70 fs, repetition rate: 82 MHz) pumped
The photophysical properties and the excited-state reac-
tivity of 1,8-naphthalimide derivatives have been widely
3
+
by a Nd :YAG laser (532 nm, 4.5 W). The generation of
the second harmonic (400 nm, pulse width: ca. 200 fs) was
performed in a lithium triborate (LBO) crystal. The third
harmonic (266 nm, pulse width: ca. 250 fs) was generated by a
sum frequency mixing of the fundamental and the second
harmonic. The repetition frequency of the excitation pulse was
reduced to 4 MHz by using a pulse picker. The second
harmonic (400 nm) in the output beam was used as trigger
pulse. The fluorescence from the sample solution was observed
through a polarizer at the magic angle (54.7°) with respect to
the polarization direction of the excitation laser pulse. The
emission light was detected by a microchannel plate after
passing through a monochromator. The instrument response
function had a half-width of 20­25 ps. Analysis of the
fluorescence decay curves was carried out using deconvolution.
The picosecond lifetime measurements were carried out at
293 K under aerated conditions.
13
21
studied by Kossanyi and co-workers, Pardo et al., Brown
2
2
23
5c,11d,24
and co-workers, Samanta et al., and others.
How-
ever, to our knowledge there has been little systematic
information on the inductive (nonresonance) effect of the
substituents through · bonds. It is interesting that the simple
introduction of an electron-withdrawing group into the N-alkyl
side chain can markedly control the photophysical properties
of 1,8-naphthalimide derivatives used in numerous applica-
tions.
We have found that the fluorescence intensity of 1 is
remarkably increased by hydrogen bond formation with
1
6,17
alcohols.
While the effect of the hydrogen bond formation
with alcohols has some resemblance to the effect of the
introduction of the electron-withdrawing substituent into the N-
alkyl side chain, the effect of the introduction of the substituent
has advantages in that additives such as alcohols are not
required, and that these derivatives will work even in polar
solvents, such as acetonitrile.
The quantum yields for intersystem crossing (Φ ) in
isc
naphthalimides were determined by means of time-resolved
thermal lensing (TRTL). For TRTL measurements, the third
Experimental
3+
harmonic (355 nm) of a nanosecond Nd :YAG laser (pulse
General. UV spectra were measured at ambient temper-
ature under aerated conditions by use of a JASCO UVIDEC-
width: 6 ns) was utilized for the excitation source. A He-Ne
laser beam (633 nm) was used as the monitoring light. The
probe light was introduced into a monochromator after passing
through an optical filter and a small pinhole (300 ¯m diameter).
The intensity change of the probe beam was detected by a
photomultiplier. The TRTL signals were recorded on a digitiz-
ing oscilloscope and were averaged over five hundred laser
shots to improve the signal-to-noise ratio. The absorbance of
the sample solutions for the TRTL measurements was adjusted
to ca. 0.10 at the excitation wavelength. The TRTL experiments
were carried out at 293 K under aerated conditions.
6
50 spectrometer. Fluorescence spectra were obtained at
ambient temperature under aerated conditions on a Hitachi
50 spectrophotometer. Melting points were measured on a
8
Yanagimoto micro melting point apparatus and are uncorrected.
NMR spectra were recorded on a JEOL JNM-AL-400 (400
MHz) instrument. Chemical shifts are reported in ppm (¤)
relative to an internal standard (SiMe4). IR spectra were
obtained using a JASCO FT/IR-350 spectrometer. Mass
spectra (EI, 70 eV) were recorded on a Hitachi M-80B mass
spectrometer. Combustion analyses were performed on a
Yanagimoto CHN corder MT-5.
The quantum yields of the intersystem crossing Φisc of 1­7
are given by:

5
24
Bull. Chem. Soc. Jpn. Vol. 84, No. 5 (2011)
Photophysical Properties of 1,8-Naphthalimide
naphthalimide (8): To a formalin solution (30 mL) of 1,8-
naphthalimide (1.0 g, 5.1 mmol), was added a small amount of
pyridine. The solution was refluxed for 2 h. After cooling, the
solution was poured into 300 mL of water and the precipitate
was filtered. The crude product was purified by chromatog-
raphy and recrystallized from methanol. The yield of 8
Uslow
Utotal
ꢀiscET
¼
ð6Þ
Eex ꢀ ꢀfhEsi
where Uslow/Utotal, E , E , and hEsi are the ratio of the intensity
T
ex
of the slow rise component (U ) and that of the total TRTL
slow
3
signal (Utotal), the 0­0 transition energy of 1­7*, the excitation
photon energy (80.5 kcal mol , 28170 cm ), and the average
energy dissipated by fluorescence from 1­7*, respectively. The
¹
1
¹1
1
was 0.96 g (4.2 mmol, 83%). Mp 252.0­254.0 °C. H NMR
1
(CDCl ): ¤ 3.65 (t, J = 8.7 Hz, 1H), 5.76 (d, J = 8.7 Hz, 2H),
3
E values of 1, 2, 3, 4, 5, 6, and 7 were determined to be 52.9,
7.79 (t, J = 8.5 Hz, 2H), 8.25 (d, J = 8.5 Hz, 2H), 8.64 (d,
T
¹1
13
5
2.9, 52.8, 53.0, 52.9, 53.1, and 53.0 kcal mol from the 0­0
J = 8.5 Hz, 2H). C NMR (DMSO-d ): ¤ 62.6 (CH ), 121.9
6
2
bands of the phosphorescence spectra of 1, 2, 3, 4, 5, 6, and 7 in
EPA at 77 K, and the hEsi values of 1, 2, 3, 4, 5, 6, and 7 were
determined to be 75.64, 75.44, 75.44, 75.44, 75.44, 75.24, and
(C), 127.2 (CH), 127.6 (C), 130.7 (CH), 131.3 (C), 134.5 (CH),
163.2 (C=O). IR (KBr): 3407, 1698, 1661, 1589, 1509, 1459,
¹
1
1340, 1240, 1059, 781 cm . Found: C, 68.49; H, 4.07; N,
¹
1
7
5.04 kcal mol in dichloromethane from the wavelength of
6.01%. Calcd for C H NO : C, 68.72; H, 3.99; N, 6.16%.
1
3
9
3
the maximum intensity of the fluorescence of 1­7 and to be
A mixture of 8 (0.50 g, 2.2 mmol), acetic anhydride
(0.80 mL), and sulfuric acid (5.0 mL) was heated until it
dissolved. After cooling, the solution was poured into 100 mL
of 5% sodium carbonate aqueous solution and the precipitate
was filtered. The crude product was purified by chromatog-
raphy and recrystallized from methanol. The yield of 4 was
¹1
7
6.04, 76.04, 76.04, 75.44, 75.44, 75.24, and 75.24 kcal mol
in acetonitrile, respectively.
The values of Φisc were reproducible to about «1­2% on
repeated measurements.
Materials. N-Methyl-1,8-naphthalimide (1) was prepared
according to a published procedure.25
1
0.21 g (0.78 mmol, 35%). Mp 183.0­184.5 °C. H NMR
N-(3-Acetyloxypropyl)-1,8-naphthalimide (2): A mixture
of N-(3-hydroxypropyl)-1,8-naphthalimide (1.0 g, 3.9 mmol),
acetic anhydride (0.80 mL), and sulfuric acid (5.0 mL) was
heated until it dissolved. After cooling, the solution was poured
into 100 mL of 5% sodium carbonate aqueous solution and the
precipitate was filtered. The crude product was purified by
(CDCl ): ¤ 2.10 (s, 3H), 6.25 (s, 2H), 7.79 (dd, J = 7.3,
3
1
7
8.3 Hz, 2H), 8.26 (d, J = 8.3 Hz, 2H), 8.66 (d, J = 7.3 Hz, 2H).
1
3
C NMR (CDCl ): ¤ 20.8 (CH ), 63.6 (CH ), 122.0 (C), 127.0
3 3 2
(CH), 128.6 (C), 131.7 (C), 131.8 (CH), 134.6 (CH), 163.5
(C=O), 169.9 (C=O). IR (KBr): 1734, 1712, 1670, 1443,
¹
1
1394, 1353, 1215, 1027, 970, 780 cm . MS (70 eV): m/z 269
+
chromatography and recrystallized from methanol. The yield of
(M , 9), 210 (34), 199 (31), 198 (100), 180 (60), 152 (35),
1
2
(
was 0.23 g (0.77 mmol, 21%). Mp 95.8­96.5 °C. H NMR
126 (25). Found: C, 66.54; H, 3.95; N, 5.00%. Calcd for
C H NO : C, 66.91; H, 4.12; N, 5.20%.
CDCl ): ¤ 2.02 (s, 3H), 2.10 (m, 2H), 4.19 (t, J = 6.7 Hz, 2H),
3
15 11
4
4
.31 (t, J = 6.7 Hz, 2H), 7.76 (dd, J = 7.3, 8.1 Hz, 2H), 8.22 (d,
N-(Methoxycarbonylmethyl)-1,8-naphthalimide
(5):
13
J = 8.1 Hz, 2H), 8.61 (d, J = 7.3 Hz, 2H). C NMR (CDCl ): ¤
Naphthalimide 5 was prepared by esterification of N-(carboxy-
methyl)-1,8-naphthalimide (9): A dimethylformamide (DMF)
solution (250 mL) of 1,8-naphthalic anhydride (10.0 g, 51
mmol) and glycine (7.5 g) was refluxed for 6 h. After cooling,
the solution was poured into 300 mL of water and the
precipitate was filtered. The crude product was purified by
chromatography and crystallized from acetone­ether. The yield
3
2
1
1
1
2
0.9 (CH ), 27.3 (CH ), 37.5 (CH ), 62.4 (CH ), 112.6 (C),
26.9 (CH), 128.2 (C), 131.2 (CH), 131.6 (C), 133.9 (CH),
64.1 (C=O). IR (KBr): 1730, 1693, 1663, 1589, 1447, 1389,
347, 1241, 1057, 783 cm . MS (70 eV): m/z 297 (M , 16),
3 2 2 2
¹1
+
22 (100), 210 (28), 198 (67), 180 (56), 153 (28), 152 (46).
Found: C, 68.59; H, 5.02; N, 4.59%. Calcd for C H NO : C,
17
15
4
1
6
8.68; H, 5.09; N, 4.71%.
N-(2-Acetyloxyethyl)-1,8-naphthalimide (3): A mixture
of 9 was 5.3 g (21 mmol, 41%). Mp 272.8­273.2 °C. H NMR
(CDCl ): ¤ 5.03 (s, 2H), 7.78 (dd, J = 8.3, 8.5 Hz, 2H), 8.26 (d,
3
1
7
13
of N-(2-hydroxyethyl)-1,8-naphthalimide (1.0 g, 4.1 mmol),
J = 8.3 Hz, 2H), 8.64 (d, J = 8.5 Hz, 2H). C NMR (DMSO-
acetic anhydride (0.80 mL), and sulfuric acid (5.0 mL) was
heated until it dissolved. After cooling, the solution was poured
into 100 mL of 5% sodium carbonate aqueous solution and the
precipitate was filtered. The crude product was purified by
d ): ¤ 41.2 (CH ), 121.5 (C), 127.4 (CH), 127.4 (C), 131.1
(CH), 131.4 (C), 134.9 (CH), 163.1 (C=O), 169.4 (C=O). IR
6
2
(KBr): 1728, 1701, 1660, 1587, 1437, 1387, 1357, 1235, 968,
¹
1
777 cm . Found: C, 65.52; H, 3.80; N, 5.17%. Calcd for
C H NO : C, 65.88; H, 3.55; N, 5.49%.
chromatography and recrystallized from methanol. The yield of
1
4
9
4
1
3
was 0.18 g (0.64 mmol, 15%). Mp 133.5­135.0 °C. H NMR
To a methanol solution (100 mL) of 9 (3.0 g, 12 mmol), was
(
4
2
CDCl ): ¤ 2.02 (s, 3H), 4.43 (t, J = 4.9 Hz, 2H), 4.50 (t, J =
added sulfuric acid (5.0 mL). The solution was refluxed for 1 h
and poured into 300 mL of water and the precipitate was
filtered. The crude product was purified by chromatography and
3
.9 Hz, 2H), 7.77 (dd, J = 7.3, 7.6 Hz, 2H), 8.23 (d, J = 7.6 Hz,
H), 8.61 (d, J = 7.3 Hz, 2H). 13C NMR (CDCl ): ¤ 20.8
3
(
CH ), 39.0 (CH ), 61.9 (CH ), 122.5 (C), 126.9 (CH), 128.2
recrystallized from methanol. The yield of 5 was 1.6 g (5.9
3
2
2
1
(
(
C), 131.3 (CH), 131.6 (C), 134.0 (CH), 164.1 (C=O), 170.8
C=O). IR (KBr): 1745, 1696, 1656, 1589, 1437, 1375, 1232,
mmol, 51%). Mp 174.3­175.8 °C. H NMR (CDCl ): ¤ 3.79
3
(s, 3H), 4.97 (s, 2H), 7.78 (dd, J = 7.3, 8.5 Hz, 2H), 8.22 (d,
¹
1
+
13
1
2
6
4
048, 848, 781 cm . MS (70 eV): m/z 283 (M , 26), 222 (23),
10 (37), 198 (100), 180 (47), 152 (34), 126 (24). Found: C,
7.58; H, 4.45; N, 4.78%. Calcd for C H NO : C, 67.84; H,
J = 7.3 Hz, 2H), 8.62 (d, J = 8.5 Hz, 2H). C NMR (CDCl ): ¤
3
41.2 (CH2), 52.5 (CH3), 122.2 (C), 126.9 (CH), 128.3 (C),
131.6 (C), 131.6 (CH), 134.3 (CH), 163.8 (C=O), 168.5
(C=O). IR (KBr): 1752, 1703, 1670, 1590, 1438, 1379, 1328,
16
13
4
.63; N, 4.94%.
N-(Acetyloxymethyl)-1,8-naphthalimide (4): Naphthal-
imide 4 was prepared by acetylation of N-(hydroxymethyl)-1,8-
¹
1
+
1213, 966, 781 cm . MS (70 eV): m/z 269 (M , 19), 237 (16),
210 (100), 180 (40), 154 (21), 152 (27), 126 (18). Found: C,

K. Matsubayashi et al.
Bull. Chem. Soc. Jpn. Vol. 84, No. 5 (2011)
525
6
6.74; H, 4.13; N, 4.94%. Calcd for C H NO : C, 66.91; H,
6
a) M. F. Braña, J. M. Castellano, M. Morán, M. J.
15
11
4
4
.12; N, 5.20%.
N-(Chloromethyl)-1,8-naphthalimide (6): To a thionyl
Pérez de Vega, X. D. Qian, C. A. Romerdahl, G. Kelhauer, Eur. J.
Med. Chem. 1995, 30, 235. b) B. Abraham, L. A. Kelly, J. Phys.
Chem. B 2003, 107, 12534. c) J. Zhang, R. J. Woods, P. B. Brown,
K. D. Lee, R. R. Kane, Bioorg. Med. Chem. Lett. 2002, 12, 853.
chloride solution (30 mL) of 8 (1.0 g, 4.4 mmol), was added a
small amount of pyridine. The solution was refluxed for 1 h.
After cooling, the solution was poured into 300 mL of water
and the precipitate was filtered. The crude product was purified
by chromatography and recrystallized from methanol. The
7
T. C. Chanh, D. E. Lewis, M. M. Judy, F. Sogandares-
Bernal, G. R. Michalek, R. E. Utecht, H. Skiles, S.-C. Chang, J. L.
Matthews, Antiviral Res. 1994, 25, 133.
8
9
F. Cosnard, V. Wintgens, Tetrahedron Lett. 1998, 39, 2751.
C.-G. Niu, Z.-Z. Li, X.-B. Zhang, W.-Q. Lin, G.-L. Shen,
yield of 6 was 1.0 g (4.1 mmol, 93%). Mp 213.0­215.5 °C.
1
H NMR (CDCl ): ¤ 6.01 (s, 2H), 7.80 (t, J = 8.3 Hz, 2H), 8.27
3
R.-Q. Yu, Anal. Bioanal. Chem. 2002, 372, 519.
M. E. Vázquez, J. B. Blanco, B. Imperiali, J. Am. Chem.
Soc. 2005, 127, 1300.
a) A. Demeter, T. Bérces, L. Biczók, V. Wintgens, P. Valat,
13
(d, J = 8.3 Hz, 2H), 8.67 (d, J = 8.3 Hz, 2H). C NMR
1
0
(CDCl ): ¤ 47.5 (CH ), 127.0 (C), 127.0 (CH), 131.5 (C),
3
2
1
1
31.7 (C), 131.9 (CH), 134.6 (CH), 162.7 (C=O). IR (KBr)
710, 1679, 1586, 1436, 1308, 1235, 1137, 948, 782, 683
11
J. Kossanyi, J. Chem. Soc., Faraday Trans. 1994, 90, 2635. b) V.
Wintgens, P. Valat, J. Kossanyi, A. Demeter, L. Biczók, T. Bérces,
J. Photochem. Photobiol., A 1996, 93, 109. c) A. Demeter, T.
Bérces, L. Biczók, V. Wintgens, P. Valat, J. Kossanyi, J. Phys.
Chem. 1996, 100, 2001. d) H. Cao, V. Chang, R. Hernandez, M. D.
Heagy, J. Org. Chem. 2005, 70, 4929. e) P. Nandhikonda, M. P.
Begaye, Z. Cao, M. D. Heagy, Chem. Commun. 2009, 4941. f) S.
Paudel, P. Nandhikonda, M. D. Heagy, J. Fluoresc. 2009, 19, 681.
12 P. Valat, V. Wintgens, J. Kossanyi, L. Biczók, A. Demeter,
T. Bérces, Helv. Chim. Acta 2001, 84, 2813.
¹
1
+
cm . MS (70 eV): m/z 245 (M , 24), 211 (26), 210 (100), 180
41), 154 (25), 126 (26), 63 (44). Found: C, 63.70; H, 3.55; N,
.50%. Calcd for C H ClNO : C, 63.56; H, 3.28; N, 5.70%.
(
5
13
8
2
N-(Cyanomethyl)-1,8-naphthalimide (7):
A pyridine
solution (150 mL) of 1,8-naphthalic anhydride (5.0 g, 25 mmol)
and commercially available aminoacetonitrile monosulfate
(5.3 g) was refluxed for 3 h. After cooling, pyridine was
evaporated under reduced pressure. The crude product was
purified by chromatography and crystallized from methanol.
1
3
P. Valat, V. Wintgens, J. Kossanyi, L. Biczók, A. Demeter,
T. Bérces, J. Am. Chem. Soc. 1992, 114, 946.
G. Hui Bon Hoa, J. Kossanyi, A. Demeter, L. Biczók, T.
Bérces, Photochem. Photobiol. Sci. 2004, 3, 473.
Y. Kubo, M. Suto, S. Tojo, T. Araki, J. Chem. Soc., Perkin
Trans. 1 1986, 771.
The yield of 7 was 4.9 g (21 mmol, 82%). Mp 254.0­256.0 °C.
1
H NMR (CDCl ): ¤ 5.09 (s, 2H), 7.82 (dd, J = 8.3, 8.5 Hz,
3
1
4
2
H), 8.29 (d, J = 8.5 Hz, 2H), 8.67 (d, J = 8.3 Hz, 2H).
C NMR (CDCl ): ¤ 27.3 (CH ), 114.6 (CN), 121.6 (C), 127.8
1
3
3
2
1
5
(CH), 128.2 (C), 131.7 (C), 132.1 (CH), 135.7 (CH), 162.9
(C=O). IR (KBr): 2252, 1703, 1667, 1585, 1437, 1377, 1323,
1
1
6
7
K. Matsubayashi, Y. Kubo, J. Org. Chem. 2008, 73, 4915.
K. Matsubayashi, C. Kajimura, H. Shiratori, Y. Kubo, T.
¹
1
+
1
239, 1181, 778 cm . MS (70 eV): m/z 236 (M , 67), 182
(74), 154 (100), 127 (27), 126 (64), 63 (36), 50 (15). Found: C,
Yoshihara, S. Tobita, Bull. Chem. Soc. Jpn. 2010, 83, 1067.
V. Wintgens, P. Valat, J. Kossanyi, L. Biczók, A. Demeter,
T. Bérces, J. Chem. Soc., Faraday Trans. 1994, 90, 411.
T. Yoshihara, H. Shimada, H. Shizuka, S. Tobita, Phys.
7
3
0.92; H, 3.44; N, 11.70%. Calcd for C H N O : C, 71.18; H,
14 8 2 2
.41; N, 11.86%.
1
8
1
9
References
a) M. F. Brana, A. Ramos, Curr. Med. Chem.: Anti-Cancer
Agents 2001, 1, 237. b) C. Bailly, C. Carrasco, A. Joubert, C. Bal,
N. Wattez, M.-P. Hildebrand, A. Lansiaux, P. Colson, C. Houssier,
M. Cacho, A. Ramos, M. F. Braña, Biochemistry 2003, 42, 4136.
Chem. Chem. Phys. 2001, 3, 4972.
20 R. W. Taft, Jr., N. C. Deno, P. S. Skell, Annu. Rev. Phys.
Chem. 1958, 9, 287.
1
21 a) A. Pardo, J. M. L. Poyato, E. Martin, J. Photochem.
1987, 36, 323. b) A. Pardo, E. Martin, J. M. L. Poyato, J. J.
Camacho, M. F. Braña, J. M. Castellano, J. Photochem. Photobiol.,
A 1987, 41, 69. c) A. Pardo, J. M. L. Poyato, E. Martin, J. J.
Camacho, D. Reyman, J. Photochem. Photobiol., A 1989, 46, 323.
22 a) M. S. Alexiou, V. Tychopoulos, S. Ghorbanian, J. H. P.
Tyman, R. G. Brown, P. I. Brittain, J. Chem. Soc., Perkin Trans. 2
1990, 837. b) D. Yuan, R. G. Brown, J. Phys. Chem. A 1997, 101,
3461.
2
V. K. Malviya, P. Y. Liu, D. S. Alberts, E. A. Surwitt, J. B.
Craig, E. V. Hanningan, Am. J. Clin. Oncol. 1992, 15, 41.
J. A. Spicer, S. A. Gamage, G. J. Finlay, W. A. Denny,
Bioorg. Med. Chem. 2002, 10, 19.
T. Takada, K. Kawai, S. Tojo, T. Majima, J. Phys. Chem. B
004, 108, 761.
a) I. Saito, M. Takayama, H. Sugiyama, K. Nakatani, A.
3
4
2
5
Tsuchida, M. Yamamoto, J. Am. Chem. Soc. 1995, 117, 6406. b) I.
Saito, M. Takayama, S. Kawanishi, J. Am. Chem. Soc. 1995, 117,
23 a) A. Samanta, B. Ramachandran, G. Saroja, J. Photochem.
Photobiol., A 1996, 101, 29. b) S. Banthia, A. Samanta, Chem.
Lett. 2005, 34, 722.
5
590. c) B. M. Aveline, S. Matsugo, R. W. Redmond, J. Am.
Chem. Soc. 1997, 119, 11785. d) J. E. Rogers, S. J. Weiss, L. A.
Kelly, J. Am. Chem. Soc. 2000, 122, 427. e) J. E. Rogers, B.
Abraham, A. Rostkowski, L. A. Kelly, Photochem. Photobiol.
24 O. V. Prezhdo, B. V. Uspenskii, V. V. Prezhdo, W.
Boszczyk, V. B. Distanov, Dyes Pigm. 2007, 72, 42.
25 C. Somich, P. H. Mazzocchi, H. L. Ammon, J. Org. Chem.
1987, 52, 3614.
2
001, 74, 521.