Novel naphthalimide derivatives with near-infrared emission: synthesis via photochemical cycloaromatization, fluorescence in solvents and living cell

Article abstract of DOI:10.1016/j.tetlet.2008.10.022

In this Letter, a pair of novel naphthalimide derivatives with long-wavelength emission (>600 nm) and larger Stokes shift (>140 nm) have been developed through the photochemical cycloaromatization, in which intramolecular radical-induced 1,3-aromatic hydr

Full text of DOI:10.1016/j.tetlet.2008.10.022

Tetrahedron Letters 50 (2009) 22–25
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Novel naphthalimide derivatives with near-infrared emission: synthesis via
photochemical cycloaromatization, fluorescence in solvents and living cell
*
Liping Duan, Yufang Xu, Xuhong Qian , Yexiang Zhang, Yang Liu
State Key Laboratory of Bioreactor Engineering and Shanghai Key Lab of Chemical Biology, School of Pharmacy, East China University of Science and Technology,
PO Box 544, Shanghai 200237, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 June 2008
Revised 30 September 2008
Accepted 7 October 2008
Available online 11 October 2008
In this Letter, a pair of novel naphthalimide derivatives with long-wavelength emission (>600 nm) and
larger Stokes shift (>140 nm) have been developed through the photochemical cycloaromatization, in
which intramolecular radical-induced 1,3-aromatic hydrogen transfer might be occurred. Cell uptake
experiments showed that dye 2 could be used as a potential NIR fluorescence imaging agent.
Ó 2008 Elsevier Ltd. All rights reserved.
The operational light input/output wavelengths of most current
biological indicators are in the range of 300–600 nm, which often
limits their use as biological sensors or as reagents for photo-
dynamic therapy, because this spectral region suffers from strong
interference due to the background absorbance and auto-fluores-
cence from biological environment or endogenous chromophores
in sample media. So, it has aroused much attention to develop
new near-infrared fluorescent dyes as powerful detecting or treat-
ing tools in biological systems.1,2
Many researchers have used heptamethine cyanine dyes as
fluorescent labels or sensors for biomolecules in vivo, because their
spectra can reach near-infrared (NIR) region. However, polyme-
thine cyanine dyes are not so easy to be synthesized and modified,
their photo-stabilities are relatively low and their Stokes shift is
usually less than 25 nm, which may cause self-quenching and
measurement error by the exciting and scattered light, and then
decreases the detection sensitivity to a great extent. Therefore,
NIR dyes with a larger Stokes shift are very promising for NIR fluo-
rescence bioassays. 1,8-Naphthalimide is a famous fluorophore
with high stability.3 It can be easily modified by interacting with
very few. Therefore, it motives us to prepare NIR dyes 1 and 2
through photosensitive radical cyclization.
Starting from compound 3, N-butyl-4-bromo-5-nitro-1,8-naph-
thalimide,9 dye 110 with methoxy group or dye 210 with N0,N-
dimethylamino-group were synthesized in four-step scheme,
respectively. The details for the syntheses are shown in Scheme 1.
Photo-irradiation of compounds 611 or 712 was carried out at a
wavelength of 300 nm in dry chloroform as well as in polar solvent
such as acetonitrile. In all cases, the same product was obtained
through the formation of five-membered fused carbocyclic struc-
tures. Peri-diacetylene 6 (or 7), a yellow (blue-black) fluorescent
solid, was prepared from N-butyl-4-bromo-5-iodo-1,8-naphthali-
mide 5,13 catalytic amounts of 2.5 mol % Pd(PPh3)4 and 5 mol %
CuI in triethylamine at 90 °C. The synthesis of 5 from 414 involved
two steps: diazotization of N-butyl-4-bromo-5-amino-1,8-naph-
thalimide 4 in dilute hydrochloric acid and decomposition of the
corresponding diazonium chloride in aqueous potassium iodide
(67% yield).
When 6 (or 7) was dissolved in dry chloroform and irradiated by
the light with wavelength of 300 nm, dyes 1 (or 2) was developed.
In this photo-chemical reaction process, we speculated that 3-
hydrocyclohexa-1,2,4-triene intermediate formed first through
photochemical cycloaromatization, followed by a very rapid radi-
cal-induced 1,3-hydrogen transfer and thus resulted in a stable
phenyl ring,15–17 which involved a geometry change and hydrogen
rearrangement as shown in Scheme 2. According to Balasubrama-
niyan’s points,18 this cyclization process may include the effects of
concerted, dipolar and more complex reaction mechanisms, too.
The other intermediates such as cyclobutadiene might also be
formed during the photochemical process. We attempted to isolate
the intermediates, but failed.
other biomolecules at their imide moiety. Many of their derivatives
3,4
have good photostability, high fluorescence quantum yield
and
have been widely used as labels or probes for proteins, cells, lyso-
somes and other acidic organelles.5,6 However, the emission bands
of most naphthalimide derivatives are in blue and green-yellow
regions.7 Although it was known that electron-donating groups
at the 4,5-positions of 1,8-naphthalimides usually increase the
fluorescence quantum yield of the compounds and shift the
emission to long wavelength,8 the reports on 1,8-naphthalimides
derivatives with emission wavelengths longer than 600 nm are
Radical-induced hydrogen migration was very common when
the hydrogen was originated from an aliphatic hydrocarbon or
from a heteroatom-bonded hydrogen, in which, unstable radical
* Corresponding author.
E-mail address: xhqian@ecust.edu.cn (X. Qian).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.10.022

L. Duan et al. / Tetrahedron Letters 50 (2009) 22–25
23
O
N
O
O
N
O
O
N
O
O
N
O
O
N
5
O
c
a
b
d
R
Br NO2
3
Br NH2
4
Br
I
R
R
R
1: R = OCH3
2: R = N(CH3)2
6: R = OCH3
7: R = N(CH3)2
Scheme 1. Synthetic procedures of 1 and 2. Reagents and conditions: (a) SnCl2ꢁ2H2O, AcOH, HCl (g), room temperature, 90%; (b) NaNO2, HCl, KI, 0–5 °C, 48%; (c) methoxy-
phenylethyne(4-N0,N-dimethylphenylethyne), Pd(PPh3)4, CuI, Et3N, N2, reflux, 85%; (d) h
m
, 30%.
O
N
O
O
N
O
O
N
O
O
N
H
O
O
N
O
hv
hv
R
R
R
R
H
R
R
R
R
1 or 2
6 or 7
R
R1= OCH3, R2=N(CH3)2
Scheme 2. Possible mechanism of the product formation for the photoreactions of 6 or 7.
R
formed initially, and then it rearranged rapidly to form a more sta-
ble aromatic compound. However, hydrogen migrations from an
aromatic hydrocarbon are very difficult because aromatic hydro-
gen cannot easily be abstracted by radicals. For this reason, benz-
ene is often used as solvent for free radical reactions. Up to now,
only a few examples of radical-induced aromatic hydrogen trans-
fer, for example, 1,5 or 1,6-hydrogen transfer were reported,19,20
while the reports on 1,3 or 1,4-aromatic hydrogen transfer have
not be found. This reaction process from compound 6 (or 7) to
dye 1 (or 2) might provided the first example of radical-induced
aromatic 1,3-hydrogen transfer.
Table 1 illustrates the photophysical data of dyes 1 and 2 in dif-
ferent solvents. It can be seen that when the polarity of solvent in-
creases, a larger Stokes shift will increase, while their fluorescence
quantum yields decrease. The largest Stokes shift and longest
emission wavelengths for 1 and 2 are 136 nm, 620 nm and
166 nm, 750 nm, respectively. It means that 1 and 2 have potential
application in biological environments.
In the case of 1, with a methoxy group attached to the para
position of the benzene ring, the absorption and emission peaks
in methanol were centred at 484 nm and 620 nm, respectively,
and a high fluorescence quantum yield was obtained. The Stokes
shift was in the range of 70–100 nm varied with solvent.
As for compound 2, with dimethylamino group instead of
methoxy, the absorption and emission maxima in methanol shifted
to 584 nm and 750 nm, respectively. And its fluorescence quantum
yield was much lower than that of 1. The Stokes shift of 1 and 2
increases in the following order: dichloromethane ꢀ ethyl
acetate < methanol. It is explained that ICT dyes usually show an
increase in Stokes shift with increasing solvent polarity. Compared
with 1, the dimethyl-amino group affected the photophysical prop-
erties of 2 in two ways: its strong electron-donating ability stabi-
lized the highly polar excited state and the pre-twisted geometry
come from steric hindrance between the peri-proton and N-methyl
group favoured a further formation of the TICT state. The former
made both emission and absorption maxima shift to longer wave-
lengths, and the latter led to a remarkable lower fluorescence
quantum yield of 2 (less than 0.1). The photo-induced electron
transfer (PET) from the diaminophenyl group to the fluorophore
also quenched the fluorescence of 2.22 The remarkably large Stokes
shift (more than 140 nm) for compound 2 suggested the possible
occurrence of a TICT state from the donor moiety to the acceptor
unit. On the other hand, according to Joertners energy gap law,
when the energy of the emissive state is lowered, the non-radiative
de-excitation processes increase exponentially, which results in
the lower quantum yield of 2 (Fig. 1).
Table 1
Spectroscopic data of 1 and 2 in different solvents
Solvent
kabs (nm)
log
e
kflu (nm)
Uf
1
2
Dichloromethane
Ethylacetate
Methanol
485
480
484
4.84
4.80
4.71
555
561
620
0.406
0.400
0.145
Dichloromethane
Ethylacetate
Methanol
580
570
584
5.08
5.12
5.32
721
715
750
0.095
0.080
0.015
a Determined by comparison with rhodamine B in ethanol (
Ref. 21).
U = 0.49, according to

24
L. Duan et al. / Tetrahedron Letters 50 (2009) 22–25
350
300
250
200
150
100
50
0.5
0.4
0.3
0.2
0.1
0.0
800
700
600
500
400
300
200
100
0
0.5
0.4
0.3
0.2
0.1
0.0
CH3COOC2H5
CH3OH
CH2Cl2
CH2Cl2
CH3OH
CH3COOC2H5
0
900
300
400
500
600
700
800
300
400
500
600
700
800
Wavelength (nm)
Wavethlength (nm)
Figure 1. Absorption and emission spectra of 1 and 2 in different solvents (1: excited slit width 5 nm, emission slit width 5 nm; 2: excited slit width 10 nm, emission slit
width 10 nm).
Figure 2. Fluorescence microphotographs of V79 cells incubated with (c, d) or without (a, b) 10 lM of 2 at 37 °C. Scanning was taken after 2 h incubation. Magnification was
1000ꢃ. (a) Brightfield image of cells; (b) excited at 537 nm, no obvious fluorescence was observed; (c) scanning was taken on brightfield; (d) excited at 537 nm.
3. Ramachandram, B.; Saroja, G.; Sankaran, N. B.; Samanta, A. J. Phys. Chem. B
2000, 104, 11824–11832.
4. (a) Middleton, R. W. J. Heterocycl. Chem. 1986, 23, 849–854; (b) Li, Y.; Xu, Y.;
V79 379A Chinese hamster cells were used for the evaluation of
dye 2 as potential cell staining or imaging agent, which were main-
tained as exponentially growing suspension cultures in Eagle’s
minimal essential medium with Earle’s salts, modified for suspen-
sion cultures with 7.5% fetal calf serum. The dye was added to cell
Qian, X. Tetrahedron Lett. 2004, 45, 1247–1251; (c) Xu, Y.; Qu, B.; Qian, X. Bioorg.
Med. Chem. Lett. 2005, 15, 1139–1142; (d) Li, Y.; Xu, Y.; Qian, X. Bioorg. Med.
Chem. Lett. 2003, 13, 3513–3515; (e) Mao, P.; Qian, X.; Zhang, H. Dyes and
Pigments 2004, 60, 9–16.
suspensions to give the appropriate concentration at 10 lM. The
5. Xu, Z.; Qian, X.; Cui, J.; Zhang, R. Tetrahedron 2006, 62, 10117–10122.
6. (a) Kawai, K.; Kawabata, K.; Tojo, S.; Majima, T. Bioorg. Med. Chem. Lett. 2002,
12, 2363–2366; (b) Qian, X.; Li, Z.; Yang, Q. Bioorg. Med. Chem. Lett. 2007, 15,
6846–6851.
7. (a) Mitschke, U.; Bäuerle, P. J. Mater. Chem. 2000, 10, 1471–1507; (b) Adachi, C.;
Tsutsui, T.; Saito, S. Appl. Phys. Lett. 1989, 55, 1489–1492; (c) Adachi, C.; Tsutsui,
T.; Saito, S. Appl. Phys. Lett. 1990, 56, 799–804.
8. (a) Li, Z.; Yang, Q.; Qian, X. Tetrahedron 2005, 61, 8711–8717; (b) Grabchev, I.;
Qian, X.; Bojinov, V. Polymer 2002, 43, 5731–5736; (c) Grabchev, I.; Qian, X.;
Xiao, Y. New Chem. 2002, 26, 920–925; (d) Zhang, W.; Qian, X.; Wu, Y.
Heterocycl. Commun. 2003, 9, 229–234; (e) Cui, D.; Qian, X.; Liu, F. Org. Lett.
2004, 6, 2757–2760.
9. Xu, Z. C.; Xiao, Y.; Qian, X. H.; Cui, J. N.; Cui, D. W. Org. Lett. 2005, 7, 3029–3032.
10. Preparation of 1 and 2: The solution of 6 or 7 (50 mg) in dry chloroform was
photo-irradiated by the light with wavelength of 300 nm for 10 min, then
removed the solvent in vacuo. The residual materials were purified by column
chromatography (SiO2, CHCl3: n-C6H12 = 1:1) to give 1 as a yellow-red solid
images were taken with Leica DMIRB imaging system. As shown
in Figure 2d, after incubation with dye 2 for 2 h at 37 °C, it showed
an intense intracellular red fluorescence with the excitation wave-
length at 537 nm (luminescence lifetimes 8 ms), which revealed
that 2 could be potentially used as a biological label.
In summary, we provided two novel naphthalimide derivatives
with near-infrared emission and large Stokes shift, which were
synthesized through photo-induced cyclization by radical-induced
1,3-aromatic hydrogen transfer. Cell uptake experiments with fluo-
rescence images implied the potentials of the long-wavelength
fluorescent dye 2 used as a NIR fluorescence imaging agent.
Acknowledgements
15 mg (30%) (2 as blue-black solid 12 mg (25%).1: mp 175–176 °C, IR (KBr)
m:
2918, 1691, 1654, 1632, 1606, 1502, 1450, 1350, 1220, 1175, 1027 cmꢂ1
.
1H
NMR (CDCl3, 400 MHz) d 0.97 (t, J = 7.2 Hz, 3H), 1.41–1.47 (m, 2H), 1.65–1.71
(m, 2H), 3.76 (s, 3H), 4.01 (s, 3H), 4.13 (t, J = 7.2 Hz, 2H), 6.94 (s, 1H), 7.20 (d,
J = 8.4 Hz, 3H), 7.41 (d, J = 7.8 Hz, 2H), 7.85 (d, J = 8.8 Hz, 1H), 7.95 (d, J = 7.8 Hz,
1H), 8.20 (d, J = 8.8 Hz, 2H), 8.49 (d, J = 7.8 Hz, 1H). 13C NMR (CDCl3, 100 MHz) d
13.85, 20.39, 30.48, 40.10, 55.29, 55.40, 107.15, 114.85, 118.75, 119.12, 121.26,
122.42, 122.50, 129.05, 129.54, 130.62, 130.74, 132.34, 134.03, 134.73, 135.64,
135.85, 137.03, 142.56, 142.92, 158.99, 159.67, 163.97, 164.09. HRMS (ESI+)
calcd. for C34H27NO4 [M+H+]: 514.2018, found: 514.2020. Compound 2: mp.
This work is supported by the National Natural Science Founda-
tion of China (20536010, 20746003) and Program of Shanghai Sub-
ject Chief Scientist and Shanghai Leading Academic Discipline
Project(B507) and the National High Technology Research and
Development Program of China (863 Program 2006AA10A201).
We also thank Dr. J. Qian for valuable discussions.
180–181 °C, IR (KBr) m: 3414, 2918, 1691, 1651, 1606, 1517, 1450, 1342, 1231,
1112. 1H NMR (CDCl3, 400 MHz) d 0.975 (t, J = 7.2 Hz, 3H), 1.43–1.47 (m, 2H),
1.66–1.75 (m, 2H), 2.96 (s, 6H), 3.11 (s, 6H), 4.14 (t, J = 7.2 Hz, 2H), 6.79 (m, 2H),
7.01 (d, J = 8.4 Hz, 2H), 7.12 (d, J = 8.4 Hz, 1H), 7.33 (d, J = 8 Hz, 2H), 7.78 (d,
J = 8.4 Hz, 1H), 7.91 (d, J = 7.8 Hz, 1H), 8.10 (s, 1 H), 8.18 (d, J = 7.8 Hz, 1H), 8.50
(d, J = 7.8 Hz, 1H). 13C NMR (CDCl3, 100 MHz) d 13.85, 20.41, 30.50, 40.04 40.67,
40.15, 48.59, 48.68, 113.00, 115.8, 118.29, 120.44, 122.30, 122.41, 125.66,
126.24, 127.27, 128.35, 129.30, 129.46, 129.58, 130.20, 130.30, 130.83, 131.05,
131.29, 132.36, 133.07, 133.43, 164.17, 164.28. HRMS (ESI+) calcd for
C36H33N3O2 [M+H+]: 540.2636, found: 540.2642.
References and notes
1. (a) Mustroph, H.; Stollenwerk, M.; Bressau, V. Angew. Chem., Int. Ed. 2006, 45,
2016–2035; (b) Rurack, K.; Kollmannsberger, M.; Daub, J. Angew. Chem., Int. Ed.
2001, 40, 385–387; (c) Shah, N.; Cerussi, A.; Eker, C.; Espinoza, J.; Butler, J.;
Fishkin, J.; Hornung, R.; Tromberg, B. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 4420–
4425; (d) Achilefu, S. Technol. Cancer. Res. Treat. 2004, 3, 393–409; (e)
Buschmann, V.; Weston, K. D.; Sauer, M. Bioconjugate Chem. 2003, 14, 195–204.
2. (a) Zen, J.-M.; Patonay, G. Anal. Chem. 1991, 63, 2934–2938; (b) Zhang, Z.;
Achilefu, S. Chem. Commun. 2005, 5887–5889; (c) Glunde, K.; Guggino, S. E.;
Ichikawa, Y.; Bhujwalla, Z. M. Mol. Imaging 2003, 2, 24–36; (d) Glunde, K.; Foss,
C. A.; Takagi, T.; Wildes, F.; Bhujwalla, Z. M. Bioconjugate Chem. 2005, 16, 843–
851.
11. Preparation of N-butyl-4,5-di(p-methoxy-phenylethynyl)-1.8-naphthalimide (6):
To a suspension of 5 (45 mg, 0.1 mmol) in triethylamine (10 mL) under N2
atmosphere, CuI (0.0013 g, 0.007 mmol), Pd(PPh3)4 (0.0046 g, 0.4 mmol) and p-
methoxyphenylethyne (40 mg, 0.3 mmol) were added. The reaction mixture
was stirred for 6 h at reflux temperature. The suspension was filtered and

L. Duan et al. / Tetrahedron Letters 50 (2009) 22–25
25
washed with ethyl acetate. The organic layer was washed with water, dried
over anhydrous MgSO4 and the solvent was removed in vacuo. The residual
material was purified by column chromatography (SiO2, CHCl3) to give 6 as a
chloride. The reaction mixture was stirred for 1 h. The precipitated solid was
collected by filtration and washed with water. Crystallization from acetic acid
gave 4 as yellow needles: 3.42 g (98.8%) mp 210.5–211.2 °C. IR (KBr) m: 3460,
yellow-red solid: 41 mg (80%) mp 155–156 °C. IR (KBr)
m
: 2946, 2177, 1580,
3370, 1700, 1650, 1630, 1560, 1420, 1280, 1150, 1030. 1H NMR (CDCl3,
400 MHz) d 0.975 (t, J = 7.2Hz, 3H), 1.43–1.45 (m, 2H), 1.70–1.75 (m, 2H), 4.14
(t, J = 7.2 Hz, 2H), 6.20–6.40 (br s, 2H), 6.85 (d, J = 8.0 Hz, 1H), 7.85 (d, J = 8.0 Hz,
1H), 8.34 (d, J = 8 Hz, 1H), 8.42 (d, J = 8.0 Hz, 1H). 13C NMR (CDCl3, 100 MHz) d
13.83, 20.38, 30.15, 40.12, 112.12, 112.16, 117.52, 122.74, 125.46, 131.56,
131.79, 132.49, 134.23, 150.52, 163.61, 164.01, HRMS (ESI+) calcd for
C16H16N2O2Br [M+H+]: 347.0395, found: 347.0386.
1506, 1387, 1354, 1250, 1086 cmꢂ1 1H NMR (CDCl3, 400 MHz) d 0.99 (t,
.
J = 7.2 Hz, 3H), 1.42–1.50 (m, 2H), 1.70–1.78 (m, 2H), 3.80 (s, 6H), 4.19 (t,
J = 7.2 Hz, 2H), 6.72 (d, J = 8.0 Hz, 4H), 7.34 (d, J = 8.0 Hz, 4H), 8.02 (d, J = 7.8 Hz,
2H), 8.57 (d, J = 7.8 Hz, 2H). 13C NMR (CDCl3, 100 MHz) d 13.93, 20.59, 30.20,
40.46, 55.9, 92.91, 113.12, 117.87, 122.99, 125.28, 131.36, 131.89, 133.48,
133.77, 134.87, 160.24, 162.86, HRMS (ESI+) calcd for C34H28NO4 [M+H+]:
514.2018, found: 514.2013.
15. (a) Blum, J.; Baidossi, W.; Badrieh, Y.; Hoffman, R. E. J. Org. Chem. 1996, 60,
4738–4742; (b) Bossenbroek, B.; Shechter, H. J. Am. Chem. Soc. 1967, 89, 7111–
7112; (c) Kandil, S. A.; Dessy, R. E. J. Am. Chem. Soc. 1966, 88, 3027–3034.
16. (a) White, E. H.; Sieber, A. F. Tetrahedron Lett. 1966, 7, 2473–2474; (b)
Bossenbroek, B. Ph.D. Dissertation, 1967, The Ohio State University.
17. (a) Roberts, T. D.; Ardemagni, L.; Shechter, H. J. Am. Chem. Soc. 1969, 91, 6185–
6186; (b) Muller, J.-F.; Muller, D.; Dewey, H. J.; Michl, J. J. Am. Chem. Soc. 1978,
100, 1629–1630.
12. Preparation of N-butyl-4,5-di(p-N0,N-dimethylphenylethynyl)-1,8-naphthalimide
(7): Compound 7 was obtained by the same procedure with 5 and 4-N0,N-
dimethylphenylethyne as raw material (85%). Mp: 162–163 °C, IR (KBr)
2925, 2200, 1688, 1651,1576, 1517, 1443, 1350, 1231, 1190, 1064 cmꢂ1
m:
.
1H
NMR (CDCl3, 400 MHz) d 0.99 (t, J = 7.2 Hz, 3H), 1.44–1.51 (m, 2H), 1.70–1.78
(m, 2H), 2.98 (s,12H), 4.18 (t, J = 7.2 Hz, 2H), 6.54 (d, J = 8.0 Hz, 4H), 7.33 (d,
J = 8.4 Hz, 4H), 7.97 (d, J = 8 Hz, 2H), 8.53 (d, J = 8.0 Hz, 2H). 13C NMR (CDCl3,
100 MHz) d 13.83, 20.40, 30.20, 40.29, 88.32, 111.67, 121.25, 129.07, 130.46,
133.36, 133.76, 163.93, HRMS (ESI+) calcd for C36H33N3O2 [M+H+]: 540.2651,
found: 540.2648.
18. Balasubramaniyan, V. Chem. Rev. 1966, 66, 567–641.
19. (a) Karady, S.; Lee, A. N.; Dolling, U.-H.; Douglas, A. W.; McManemin, G. J.;
Marcune, B. J. Am. Chem. Soc. 1995, 117, 5425–5426; (b) Clark, A. E.; Davidson,
E. R.; Zaleski, J. M. J. Am. Chem. Soc. 2001, 123, 2650–2657; (c) Abeywickrema,
A. N.; Beckwith, A. L. J. Chem. Commun. 1986, 464–465; (d) Beckwith, A. L. J.;
Meijs, G. F. J. Org. Chem. 1987, 52, 1922–1930.
20. (a) Curran, D. P.; Fairweather, N. J. Org. Chem. 2003, 68, 2972–2974; (b) Smart,
R. P.; Peelen, T. J.; Blankespoor, R. L.; Ward, D. L. J. Am. Chem. Soc. 1997, 119,
461–465; (c) Qian, X.; Cui, J.; Zhang, R. Chem. Commun. 2001, 2656–2657; (d)
Qian, X.; Mao, P.; Yao, W.; Guo, X. Tetrahedron Lett. 2002, 43, 2995–2998; (e)
Curran, D. P.; Somayajulu, K. V.; Yu, H. Tetrahedron Lett. 1992, 33, 2295–2296;
(f) Sengupta, S.; Bhattacharyya, S. Tetrahedron Lett. 2001, 42, 2035–2037; (g)
Cioslowski, J.; Piskorz, P.; Mocrieff, D. J. Org. Chem. 1998, 63, 4052–4054; (h)
Chandler, S. A.; Hanson, P.; Taylor, A. B.; Walton, P. H.; Timms, A. W. J. Chem.
Soc., Perkin Trans. 2 2001, 214–228.
21. Casey, K. G.; Quitevis, E. L. J. Phys. Chem. 1988, 92, 6590–6594.
22. (a) Yoon, S.; Miller, E. W.; He, Q.; Do, P. H.; Chang, C. J. Angew. Chem., Int. Ed.
2007, 46, 6658–6661; (b) He, Q.; Miller, E. W.; Wong, A. P.; Chang, C. J. J. Am.
Chem. Soc. 2006, 128, 9316–9317; (c) Yoon, S.; Albers, A. E.; Wong, A. P.; Chang,
C. J. J. Am. Chem. Soc. 2005, 127, 16030–16031; (d) Meng, X.; Liu, L.; Hu, H.; Zhu,
M.; Wang, M.; Shi, J.; Guo, Q. Tetrahedron Lett. 2006, 47, 7961–7964.
13. Preparation of N-butyl-4-bromo-5-iodo-1.8-naphthalimide (5): 30 mL of NaNO2
(1.6 g, 0.023 mmol) aqueous solution was dropwise added to the HCl (22%,
25 mL) aqueous solution of 4 (3.5 g, 0.01 mol) at 0 °C. The reaction mixture was
stirred for 2 h at this temperature. The resulting precipitate was added to
40 mL of KI (8.85 g, 0.05 mol) aqueous solution and the mixture reacted for 1 h,
after which added NaHSO3 to destroy excessive Iꢂ. The resulted solid was
collected by filtration and then purified by column chromatography (SiO2,
CHCl3) to give (5) as a white solid in 60% Yield (2.7 g), mp 165.1–166.4 °C, IR
(KBr) m .
: 2950, 1695, 1647, 1630, 1560, 1430, 1280, 1150, 1035 cmꢂ1 1H NMR
(CDCl3, 400 MHz) d 0.985 (t, J = 7.2 Hz, 3H), 1.42–1.47 (m, 2H), 1.69–1.75 (m,
2H), 4.16 (t, J = 7.2 Hz, 2H), 8.18 (d, J = 8.0 Hz, 1H), 8.25 (d, J = 8.0 Hz, 1H), 8.41
(d, J = 8 Hz, 1H), 8.72 (d, J = 8.0 Hz, 1H). 13C NMR (CDCl3, 100 MHz) d 13.83,
20.29, 30.20, 40.36, 107.12, 125.87, 126.67, 128.99, 135.28, 136.66, 136.87,
139.15, 139.87, 141.65, 161.56, 163.86, HRMS (ESI+) calcd for C16H14NO2BrI
[M+H+]: 457.9253, found: 457.9264.
14. Preparation of N-butyl-4-bromo-5-amino-1.8-naphthalimide (4): Compound 3
(3.76 g, 0.01 mol) was added to a previously prepared solution of glacial acetic
acid (40 ml) containing 15.3 g of SnCl2 (0.08 mmol) and aerated with hydrogen