The synthesis and fluorescence properties of macromolecular components based on 1,8-naphthalimide derivatives and dimers

Article abstract of DOI:10.1016/j.tetlet.2011.12.009

A series of novel 1,8-naphthalimide derivatives and dimers possessing reactive carboxylic acid, nitro, amine, or bromide functionality is prepared and their photophysical properties are studied. Those derivatives that contain amine substituents attached d

Full text of DOI:10.1016/j.tetlet.2011.12.009

Tetrahedron Letters 53 (2012) 808–810
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
The synthesis and fluorescence properties of macromolecular components
based on 1,8-naphthalimide derivatives and dimers
Alaa M.M. El-Betany a,b, Neil B. McKeown a,
⇑
a School of Chemistry, Cardiff University, Cardiff CF10 3AT, UK
b Chemistry Department, Faculty of Science, Damietta Branch, Mansoura University, New Damietta City 34517, Egypt
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of novel 1,8-naphthalimide derivatives and dimers possessing reactive carboxylic acid, nitro,
amine, or bromide functionality is prepared and their photophysical properties are studied. Those deriv-
atives that contain amine substituents attached directly to the 1,8-naphthalimide unit display intense
yellow-green fluorescence.
Received 19 October 2011
Revised 21 November 2011
Accepted 2 December 2011
Available online 8 December 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
1,8-Naphthalimide
Fluorescence
Dendrimer
Dimer
Derivatives of 1,8-naphthalimide are of interest due to their use-
ful photophysical and biological properties that offer promise for
medical applications as free radical scavengers,1 potential photore-
dox anticancer agents,2 fluorescent labels,3 photosensitizers,4 and
imaging agents.5–8 Many of these properties are related to their pla-
nar shape and optimal size that makes them efficient DNA intercala-
tors.9–11 In addition, they are particularly attractive as fluorophores
as they can demonstrate high quantum yields, good photo-stability
and their fluorescence can be tuned throughout a wide spectral
range from blue to red.12 These properties also make 1,8-naphthal-
imide derivatives ideal for many non-biological applications such as
fluorescent pigments and dyes13 and as components in fluorescent
sensors for specific metal cations,14,15 or pH determination,16 and
within optical switches17 or organic luminescent devices.18–20 The
attractive properties of the 1,8-naphthalimide chromophore have
led to its incorporation into numerous polymeric21,22 and den-
dritic5,23–29 structures so as to tailor solubility, self-association,
and molecular size to suit a particular application. Here we describe
the synthesis and photophysical properties of 1,8-naphthalimide
derivatives that are suitable as building blocks for such macromolec-
ular structures due to additional reactive functionality such as
amine, carboxylic acid, or aryl bromide, which is activated toward
substitution by amine or aryloxy nucleophiles.30 Previous reports
demonstrate that such substitution at the 4-position can induce a
large red-shift to the kmax of the 1,8-naphthalimide chromophore
and enhance fluorescence strongly.30–35
The novel N-phenyl-1,8-naphthalimide derivatives 1–9 were
synthesized using conventional methodology by refluxing equimo-
lar quantities of 1,8-naphthalic anhydride, 4-bromo-1,8-naphthalic
anhydride, or 3,6-dinitro-1,8-naphthalic anhydride with 4-amino-
benzoic acid, 5-aminoisophthalic acid or 3,5-diaminobenzoic acid,
respectively, in the presence of glacial acetic acid and sodium ace-
tate (Scheme 1, Table 1). Reduction of the nitro substituents of
N-phenyl-1,8-naphthalimides 2, 5, and 8 by a palladium-catalyzed
hydrogenation gave amino-containing derivatives 10–12 (Scheme
1, Table 1). N-Phenyl-1,8-naphthalimide derivatives 1–6 were ob-
tained in good yields in high purity by simple flash chromatogra-
phy or recrystallisation, whereas compounds 7–9 were obtained
in low yield following chromatographic isolation from by-prod-
ucts, including modest quantities of the 1,3-naphthalimide dimers
13–15. Alternatively, dimers 13–15 could be prepared in much
higher yield by reacting
a
twofold excess of 1,8-naphthalic
R1
R1
R3
R5
O
O
N
O
ii
R3
R5
i
R4
O
O
+
R4
H2N
R2
R2
R1
R1
R1 = NO2
R1 = NH2
Scheme 1. The synthesis of 1,8-naphthalimides 1–12. Reagents and conditions: (i)
AcOH, NaOAc, reflux, 8–14 h; (ii) H2, 1 bar, 10% Pd/C, DMF, 25 °C. Table 1 gives
substituents R1–R5.
⇑
Corresponding author. Tel.: +44 2920 875851.
E-mail address: mckeownnb@cardiff.ac.uk (N.B. McKeown).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.12.009

A. M. M. El-Betany, N. B. McKeown / Tetrahedron Letters 53 (2012) 808–810
809
Table 1
Synthetic yields and photophysical properties of 1,8-naphthalimides 1–12 (prepared as shown in Scheme 1) and dimers 12–16 (prepared as shown in Scheme 2)
Product R1
R2 R3
R4
R5
Yield (%) kmax absa (nm) Extinction coefficienta (MÀ1 cmÀ1
)
kmax emissiona,b (nm) RFIc Quantum yieldd (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
H
NO2
H
H
NO2
H
H
NO2
H
NH2
NH2
NH2
H
NO2
H
H
H
Br
H
H
H
H
H
CO2H
CO2H
CO2H
CO2H
CO2H
H
H
H
H
H
H
CO2H
H
H
H
H
92
93
68
334
270
342
334
273
342
335
270
342
440
438
432
335
272
342
435
1.4 Â 104
4.4 Â 104
1.7 Â 104
1.7 Â 104
3.2 Â 104
1.6 Â 104
1.3 Â 104
1.2 Â 104
1.9 Â 104
0.5 Â 104
0.4 Â 104
0.7 Â 104
2.8 Â 104
7.6 Â 104
3.4 Â 104
1.4 Â 104
383
341
402
410
419
408
422
455
428
518
518
521
405
342
401
518
1.7
3.6
1.8
4.4
88
5.6
1.3
2.2
1.6
198
215 10.3
299 16.7
2.0
1.0
1.7
—
—
—
—
—
—
—
—
—
CO2H 92
CO2H 95
CO2H 85
CO2H 43
CO2H 12
CO2H 11
Br CO2H
H
H
NH2
NH2
Br NH2
H
H
H
H
H
Br
H
H
H
91
7.4
CO2H
NH2
—
—
—
CO2H 92
CO2H 94
—
—
—
—
H
—
—
—
75
71
67
89
—
—
—
NH2
—
—
406 22.9
a
b
c
From DMF solution.
Excitation at 438 nm.
RFI = Relative fluorescence intensity normalized with respect to 14.
d
Relative to fluoroscein.
CO2H
R1
O
CO2H
NH2
O
O
R1
R2
R1
R2
i
O
O
+
H2N
N
N
R2
O
O
R1
R1
R1 = NO2
R1
R1 = NH2
ii
Scheme 2. The synthesis of 1,8-naphthalimide dimers 13–16. Reagents and conditions: (i) AcOH, NaOAc, reflux, 8–14 h; (ii) H2, 1 bar, 10% Pd/C, DMF, 25 °C. Table 1 gives
substituents R1–R2.
anhydride, 4-bromo-1,8-naphthalic anhydride or 3,6-dinitro-1,8-
naphthalic anhydride with 3,5-diaminobenzoic acid (Scheme 2, Ta-
ble 1). Hydrogenation of dimer 14 gave the amine-containing di-
mer 16. All of the compounds demonstrated good solubility in
polar aprotic solvents such as DMF or DMSO, but poor solubility
in other common solvents including water at pH 7.
the amine groups at the 3,6-positions of the 1,8-naphthalimide
units if the intense fluorescence that they induce is to be retained.
This could be achieved by attachment of the 1,8-naphthalimide
component via the amine or carboxylic acid substituents on the
N-phenyl unit (e.g., for 1–12: R3–R5 = NH2/CO2H, or for dimers
13–16: CO2H). Reactions of the amine substituents on the 1,8-
naphthalimide unit derived from monomers 10–12 or dimer 16
that will maintain their electron-donating ability (e.g., Michael
addition) could also be employed for their incorporation into a
dendritic structure. Alternatively, the post-synthetic reduction of
the nitro substituents of the 1,8-naphthalimide units derived from
components 2, 5, 8, and 14 or aromatic nucleophilic substitution of
the bromo-substituent of components derived from 1,8-naphthal-
imides 3, 6, 9, or 15 could provide amine functionality and able to
induce enhanced fluorescence. Preparative studies to explore these
strategies are in progress.
The basic photophysical properties of N-phenyl-1,8-naphthali-
mides 1–12 and those of the dimers 13–16 are listed in Table 1.
Of particular note is that the introduction of an electron-donating
amine functionality at the 3,6-positions of the naphthalimide unit
induces a significant red-shift of ꢀ100 nm in the position of the
longest wavelength band (kmax ꢀ520 nm) as demonstrated for
N-phenyl-1,8-naphthalimides 10–12 and dimer 16 (See Supple-
mentary data, Fig. S1). Solutions of these four compounds in DMF
also display conspicuous yellow-green fluorescence on excitation
at 439 nm (See Supplementary data, Fig. S2). The effect of substitu-
tion of the 1,8-naphthalimide core on the relative fluorescence
intensity (RFI) of these compounds can be summarized as
NH2 >> Br > H > NO2. Compounds 10–12 and dimer 16 possess
clear potential as fluorescent building units for dendritic molecules
and polymers, hence, the fluorescence quantum yields UF, for these
compounds were measured and found to be in the range 7–23%
(Table 1). The red-shifted values for kmax and the intense fluores-
cence demonstrated by these compounds can be attributed to
the presence of the two amines on the 1,8-naphthalimide unit,
which can interact with the imide functionality only through
Acknowledgments
A.E.B. would like to acknowledge the Egyptian Culture Affairs
and Missions Sector for financial support. We thank Mr. Ghaith
Al-Jayyouss for assistance in obtaining fluorescence data.
Supplementary data
p
system.36–38
Supplementary data (full experimental details for the prepara-
tion of compounds 1–16 and the collection of photophysical data
from these materials. UV–vis absorption spectra of these
compounds are shown in SI Fig. S1 and the emission spectra of
cross-conjugation via the
For the application of these compounds as building units for
dendritic molecules, as cores, branching units or terminal groups,
it will be important to maintain the electron-donating ability of

810
A. M. M. El-Betany, N. B. McKeown / Tetrahedron Letters 53 (2012) 808–810
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