Simple naphthalimide based anion sensors: Deprotonation induced colour changes and CO2 fixation

Article abstract of DOI:10.1016/j.tetlet.2003.09.148

The 4-amino-1,8-naphthalimide based chemosensors 2, 4 and 6 show striking green-to-purple colour changes due to the deprotonation of the 4-amino moiety on interaction with strongly basic anions such as F^-: these colour changes reverse gradually

Full text of DOI:10.1016/j.tetlet.2003.09.148

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 8909–8913
Simple naphthalimide based anion sensors: deprotonation induced
colour changes and CO2 fixation
Thorfinnur Gunnlaugsson,* Paul E. Kruger,* Paul Jensen, Frederick M. Pfeffer* and
Gillian M. Hussey
Department of Chemistry, Trinity College Dublin, Dublin 2, Ireland
Received 7 August 2003; revised 5 September 2003; accepted 12 September 2003
Abstract—The 4-amino-1,8-naphthalimide based chemosensors 2, 4 and 6 show striking green-to-purple colour changes due to the
deprotonation of the 4-amino moiety on interaction with strongly basic anions such as F−: these colour changes reverse gradually
with time due to the fixation of atmospheric CO2 (as HCO3−) yielding 1:1 adducts as demonstrated by X-ray crystallography.
© 2003 Elsevier Ltd. All rights reserved.
F− induced a blue colour change.7 Other colorimetric
sensors displaying similar effects have been reported by
Sessler et al. who used ‘off-the-shelf’ reagents possess-
ing aniline-like NH2 donors such as 1,2-diaminoan-
throquinone as ‘naked-eye’ colorimetric sensors for
anions.8 In order to fully elucidate the process leading
to the colour change that we observed for 1, and
potentially exploit this mechanism in the development
of chemo-sensors, we designed the 4-amino-1,8-naph-
thalimide derivatives 2, 4 and 6 (Fig. 1). These are
structurally simple naphthalimide systems that are eas-
ily synthesised and possess acidic protons that can
Currently, there is great interest within the field of
supramolecular chemistry in the development of recog-
nition units for the sensing of molecules and ions.1
Whilst numerous luminescent and colorimetric sensors/
chemosensors have been developed for cations,1 less
attention has been paid to the development of such
sensors for anions.2 Nevertheless, some excellent exam-
ples of compounds capable of anion recognition and
sensing have been reported.2,3 However, these
approaches have often involved the synthesis of struc-
turally complicated hosts.4
Our interest in this field has lead us to develop several
luminescent chemosensors for biologically important
anions using both cationic and charge neutral recep-
tors.5 To this end, we recently synthesised and evalu-
ated combined thiourea/naphthalimide based anion
sensors such as 1 (Fig. 1). Sensor 1, was designed as a
Photoinduced Electron Transfer (PET) chemosensor
for anions such as acetate and fluoride, where the
fluorescence emission of 1, which occurs in the green,
was quenched upon adding either of these ions (ꢀ1
equiv.) due to enhanced PET from the thiourea recep-
tor to the excited state of the fluorophore.6 We also
observed a significant green-to-purple colour change in
the presence of high concentrations of F− (>2.5 equiv.).
We suspected that F− might be sufficiently basic such
that it could deprotonate the NH and lead to the
observed long wavelength colour change. Recently,
Gale et al. have reported similar phenomena where
deprotonation of pyrrole 2,5-diamide anion sensors by
Figure 1. Structure of 1 and the simple naphthalimides 2–6.
* Corresponding author. Tel.: +353 1 609 3459; fax: +353 1 671 2628.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.09.148

8910
T. Gunnlaugsson et al. / Tetrahedron Letters 44 (2003) 8909–8913
participate in hydrogen bonding or be deprotonated by
basic anions, giving rise to the above mentioned green-
to-purple colour change. In this letter we discuss the
results of this work and the unexpected ability of 2 and
4, in the presence of F− to fix atmospheric CO2.
Compounds 1–4 and 6 are based on the 4-amino-1,8-
naphthalimide structure. Such compounds are highly
coloured, as well as being fluorescent, emitting typically
with umax ꢀ550 nm in CH2Cl2, as they possess large
excited state dipole moments due to their internal
charge transfer (ICT) excited state nature.9 The synthe-
sis of these compounds is straightforward and high
yielding. The synthesis of 2 and 3 was achieved in two
steps by first reacting one equivalent of n-ethylamine in
refluxing toluene with 4-bromo-1,8-naphthalic anhy-
dride, which after aqueous work-up gave the imide in
ca. 80% yield as an off-white powder.6 This was fol-
lowed by nucleophilic aromatic substitution using neat
n-butylamine or pyrrolidine to give 2 and 3, as yellow–
orange coloured powders in 74 and 86% yield, respec-
tively. The di-n-butyl derivative 4 was made in a single
step by refluxing the naphthalic anhydride in neat
n-butylamine followed by aqueous workup.6 For the
4-amino derivative 6, 4-nitro-1,8-naphthalic anhydride
and ethylamine were used to make 5, and subsequent
reduction of the nitro group using 10% Pd/C and
ammonium formate in MeOH afforded 6 in 78% over-
all yield. All new compounds were satisfactorily
analysed using conventional methods. We were able to
grow crystals of 2 suitable for X-ray crystal analysis,
which confirmed the structure10 (Fig. 2). We note that
adjacent molecules participate in p···p, CꢀH···p, and
weak hydrogen bond interactions, the strongest of these
being between the proton of the 4-amino moiety and
the imide oxygen of an adjacent molecule.
Figure 3. The changes in the (corrected) UV–vis spectra of 2
upon addition of F− in DMSO. [2]=5.8 mM. The intensities
of the bands at 446 and 287 nm are reduced upon deprotona-
tion of the 4-amino moiety of 2 with the formation of two
new bands at 535 and 341 nm, respectively. Insert: The
changes in the 535 nm band as a function of F−.
287 nm were substantially reduced with the formation
of new bands at ca. 535 and 341 nm and concomitant
formation of three isosbestic points at ca. 480, 380 and
300 nm. Although these isosbestic points were very
clear at lower concentrations, at higher concentrations
some broadening was observed (possibly due to aggre-
gation). We propose that these spectral changes are due
to the deprotonation of the amino moiety by F− rather
than hydrogen bonding. This would suggest that two
species were formed, namely the negatively charged
naphthalimide (Naph−) and HF. This causes a signifi-
cant increase in the charge density on the amino nitro-
gen with associated enhancement in the push–pull
character of the ICT transition, bathochromically shift-
ing the absorption. As demonstrated above, the absorp-
tion at 446 nm for 2 was almost ‘switched off’ upon
gradual addition of F−, and the 535 nm absorption was
‘switched on’. The F− recognition by 2 was also evident
in its fluorescence emission (umax=535 nm), which was
considerably quenched upon F− addition. Moreover,
upon excitation at 535 nm a new broad fluorescence
emission was observed between 580 and 800 nm, which
gradually increased in intensity as a function of [F−].
As discussed above, we predicted that the ICT state of
2 and 4 might be modulated by strongly basic anions
such as F− through strong hydrogen bonding to, or
deprotonation of, the electron donating amino moiety.
We first investigated these possibilities by observing the
changes in the UV–vis spectrum of DMSO solutions of
2 upon addition of AcO−, H2PO4 , Cl−, Br−, F− (as their
−
(C4H9)4N+ salts). Compound 2 has a strong absorption
band centred at 446 nm (log m=4.23 M−1 cm−1) due to
its ICT character and a second band at 287 nm (n“p*)
(Fig. 3). Upon addition of the above anions, only F−
gave rise to changes in these absorption bands (Fig. 3).
Upon titration of 2 with F− the absorptions at 446 and
When these measurements were repeated using 3, which
lacks the acidic proton, no such spectroscopic changes
were observed, whereas 4 and 6 displayed similar
behaviour as that observed for 2. These results clearly
indicate that 2, 4 and 6 have potential as colorimetric
sensors for F−, caused by the deprotonation of the
4-amino moiety of these compounds giving rise to large
colour changes at long wavelength as in the case of F−.
Similar phenomena were observed in other organic
solvents such as THF and CH2Cl2. In contrast, how-
ever, only a minor shift was observed in the naphthal-
imide ICT band in water.9
The above recognition process was highly visible to the
naked eye with a colour change from yellow/green-to-
red/purple upon addition of F− (Fig. 4). Similar results
Figure 2. Crystal and molecular structure of 2 showing H-
bond interaction between adjacent molecules.

T. Gunnlaugsson et al. / Tetrahedron Letters 44 (2003) 8909–8913
8911
to the proton at position three (see Fig. 1) of the
naphthalimide ring was monitored as the NꢀH signal
became significantly broadened after the addition of
only small quantities of F− and completely disappeared
after the addition of 0.5 equiv. We noted that for the
1
saturation to occur in the H NMR signals, approxi-
mately 2 equiv. of F− were needed (see Fig. 6), which
−
might suggest the formation of bifluride (HF2 ) as a
new signal was observed as a triplet at ca. 16 ppm.14
Even though we have been unable to prove this unam-
biguously, it is possible that full deprotonation of the
4-amino group occurs only after 2 equiv. of the anion
have been added; hence the first equivalent forms a
strong hydrogen bond to the amino hydrogen, and only
after the second equivalent of F− has been added is the
proton removed. We are currently investigating this
further.
Figure 4. Colour change observed upon the addition of F− to
a DMSO solution of 2. Left: 2; Right: 2+F−.
were obtained when strong bases such as TBAOH,
NaH, and LDA were specifically employed. In contrast,
no colour changes were observed upon addition of
NEt3 or DMAP. This further confirms our suspicion
that deprotonation of the amino moiety and not hydro-
gen bonding to it is responsible for the pronounced
colour changes.
During the course of the titration experiments we
observed that upon leaving the purple coloured solu-
tions of 2+F− open to the air for several hours, the
colour change reversed, i.e. the green colour was
returned. We originally surmised this to be due to the
absorption of water by the solution. To investigate this
further we attempted to grow crystals from 2+F− solu-
tion (or the deprotonated form of 2 after addition of
F−) under a dry atmosphere. Whilst a crystalline form
of 2+F− was obtained, the crystals were unsuitable for a
single crystal diffraction study. Nevertheless, exposure
of the mother liquor to air for even the briefest time
induced the formation of yellow/orange crystals. Fortu-
nately, these were suitable for a single-crystal X-ray
diffraction experiment. The structural determination
showed that these crystals are not the deprotonated
form of 2, but in fact the TBA salt of the 1:1 adduct
To investigate this deprotonation process further we
1
also monitored the changes in the H NMR spectra of
DMSO-d6 solutions of 2 upon addition AcO−, H2PO4 ,
−
Cl−, Br−, F− (as their (C4H9)4N+ salts) for F−. Of these
anions only F− gave rise to spectral changes, as seen in
1
Figure 5. The H NMR of 2 (Fig. 5) shows the aro-
matic region and a resonance at 7.76 ppm for the
4-amino proton. Upon addition of the anion, substan-
tial changes occur. The shift of the resonance assigned
−
−
formed between 2 and HCO3 , the HCO3 having
arisen following atmospheric CO2 fixation (Fig. 7).
Each molecule of 2 is strongly hydrogen bonded via its
−
−
amino proton to O3 of HCO3 . The HCO3 ion is also
involved in a self-complimentary hydrogen bonded
association with its nearest neighbour. In contrast with
the structure of 2, the naphthalimide moieties in
TBA[2·HCO3] do not participate in p-stacking interac-
tions with each other but interact through alkyl
CꢀH···p contacts with the TBA cations, whose alkyl
chains separate the aromatic units. Whilst the fixation
of CO2 (as carbamate) by aliphatic amines is well
known,11 the formation of bicarbonate with amines is
less so, with the structural characterisation of these
1
Figure 5. Stack plot of H NMR spectra (in DMSO-d6) of 2
and after addition of various quantities of TBA·F.
Figure 7. The structure of the 1:1 adduct formed between 2
−
Figure 6. Changes in the chemical shift of proton three within
2 upon addition of various anions in DMSO-d6.
and HCO3 showing H-bonded pairs (t-butylammonium
cations omitted for clarity).

8912
T. Gunnlaugsson et al. / Tetrahedron Letters 44 (2003) 8909–8913
species remaining especially rare.12 It has been noted
previously by other researchers that melts of partially
hydrated tetra-alkylammonium salts of relatively basic
anions such as F−, readily and reversibly absorb CO2,
(1H, dd, J=7.6 and 8.8, Ar-H), 8.43 (1H, d, J=8.0,
Ar-H), 8.72 (1H, d, J=8.0, Ar-H), 8.76 (1H, d, J=7.5,
Ar-H), 8.86 (1H, d, J=8.5, Ar-H); lC (100 MHz,
CDCl3) 13.2, 36.0, 123.1, 123.7, 123.9, 127.0, 129.1,
129.3, 129.7, 129.9, 132.4, 149.5, 162.3, 163.1; m/z
(ESMS): 293 (M+Na)+.
−
giving bicarbonate and bifluoride (HF2 ) within the
melt.13 This process requires water to be present, which
is itself strongly hydrogen bonded to the anion, F−,
such that its basicity is enhanced making it more able
to react with CO2. However, when solution of 2 in the
presence of TBAOH was allowed to interact with air in
the same manner as above, the green colour also reap-
peared. It is thus possible that this hydroxide solution is
also able to fix CO2 and perhaps the deprotonated
amine (not F−) plays the key role in the CO2 fixation
process. We are currently investigating these features in
greater detail.
4-Amino-N%-ethyl-1,8-naphthalimide 6
Yield 150 mg (84%). Mp 275.8–276.5°C. Anal. calcd for
C14H12N2O2: C, 69.99; H, 5.03; N, 11.66%; Found: C,
69.78; H, 5.23; N, 11.37%; lH (400 MHz, DMSO-d6)
1.18 (3H, t, J=7.0, CH3), 4.05 (2H, q, J=7.0,
CH2CH3), 6.85 (1H, d, J=8.8, Ar-H), 7.43 (2H, brs,
NH2), 7.66 (1H, dd, J=7.6 and 7.9, Ar-H), 8.20 (1H, d,
J=8.8, Ar-H), 8.44 (1H, d, J=7.0, Ar-H), 8.61 (1H, d,
J=8.2, Ar-H); lC (100 MHz, DMSO-d6) 13.4, 34.3,
107.6, 108.2, 119.4, 121.8, 124.0, 129.3, 129.7, 131.0,
133.9, 152.7, 162.7, 163.6; m/z (ESMS): 241 [M+H]+.
In summary, we have confirmed that deprotonation is
responsible for the colour change observed upon F−
titration of 2 (and therefore 1) and demonstrated that
simple highly coloured ICT chromophores have poten-
tial as naked eye sensors for F− in DMSO. We are
currently examining the naphthalimide frameworks
with an eye to improving these simple colorimetric
sensors and assessing as to whether they might perform
as reporters of CO2.11
Acknowledgements
We thank Kinerton Ltd, Enterprise Ireland and IRC-
SET, Wexford County Council and TCD for financial
support, Drs. Hazel M. Moncrieff and Anthea C. Lees
for helpful discussion and Dr. John E. O’Brien for
NMR.
Experimental
4-N-Butyl N%-ethyl-1,8-naphthalimide 2
References
Yield 132 mg (74%). Mp 172.6–173.8°C. Anal. calcd for
C18H20N2O2: C, 72.95; H, 6.80; N, 9.45%. Found: C,
72.83; H, 7.17; N, 9.43%; lH (400 MHz, DMSO-d6):
0.95 (3H, t, J=7.6, CH3); 1.18 (3H, t, J=7.0, CH3);
1.41–1.46 (2H, m, CH2); 1.67–1.71 (2H, m, CH2); 3.37
(2H, q, J=6.9, CH2); 4.05 (2H, q, J=7.0, CH2); 6.78
(1H, d, J=8.0, H3 Naphth); 7.68 (1H, t, J=8.5, H6
Naphth); 7.76 (1H, brs, NH); 8.27 (1H, d, J=8.5, H2
Naphth); 8.44 (1H, d, J=7.6, HNaphth); 8.71 (1H, d,
J=8.5, HNaphth); lC (400 MHz, [D6]Acetone): 12.99,
13.42, 19.90, 30.61, 34.73, 42.98, 103.86, 109.91, 119.70,
122.84, 124.21, 125.20, 129.34, 130.58, 133.97, 148.92,
163.52, 164.06.
1. (a) Rurack, K.; Resch-Genger, U. Chem. Soc. Rev. 2002,
116–127; (b) Rurack, K. Spectrochem. Acta A 2001, 57,
2161–2195; (c) Gunnlaugsson, T.; Nieuwenhuyzen, M.;
Richard, L.; Thoss, V. J. Chem. Soc., Perkin Trans. 2
2002, 141–159; (d) Gunnlaugsson, T.; MacDo´naill, D. A.;
Parker, D. J. Am. Chem. Soc. 2001, 123, 12866–12876; (e)
de Silva, A. P.; Fox, D. B.; Huxley, A. J.; Moody, T. S.
Coord. Chem. Rev. 2000, 205, 41–57; (f) Gunnlaugsson,
T. Tetrahedron Lett. 2001, 42, 8901–8905; (g)
Gunnlaugsson, T.; MacDo´naill, D. A.; Parker, D. Chem.
Commun. 2000, 93–95; (h) de Silva, A. P.; Gunaratne, H.
Q. N.; Gunnlaugsson, T.; Huxley, A. J. M.; McCoy, C.
P.; Rademacher, J. T.; Rice, T. E. Chem. Rev. 1997, 97,
1515–1566.
4-N-Pyrolidinyl N%-ethyl 1,8 naphthalimide 3
Yield 78 mg (86%). Mp 157.7–159.2°C. Anal. calcd for
C18H18N2O2·0.1 H2O: C, 72.97; H, 6.12; N, 9.51%.
Found: C, 72.80; H, 6.12; N, 9.49%; lH (400 MHz,
CDCl3): 1.34 (3H, t, J=7.0, CH3); 2.10–2.14 (4H, m,
2×CH2 pyrolidine); 3.79–3.82 (4H, m, 2×CH2 pyro-
lidine); 4.26 (2H, q, J=7.0, CH2); 6.83 (1H, d, J=8.5,
H3 Naphth); 7.55 (1H, t, J=7.8, H6 Naphth); 8.44
(1H, d, J=8.5, H2 Naphth); 8.59-8.61 (2H, m, H5, H7
Naphth); lC (400 MHz, CDCl3): 13.36, 26.04, 35.10,
53.11, 108.03, 110.41, 122.17, 122.21, 122.56, 130.51,
131.40, 132.87, 152.16, 163.47.
2. (a) Suksai, C.; Tuntulani, T. Chem. Soc. Rev. 2003, 32,
192–202; (b) Lee, D. H.; Lee, H. Y.; Hong, J.-I. Tetra-
hedon Lett. 2002, 43, 7273–7276; (c) Gale, P. A. Coord.
Chem. Rev. 2001, 213, 79–128; (d) Gale, P. A. Coord.
Chem. Rev. 2000, 199, 181–233; (e) Beer, P. D.; Gale, P.
A. Angew. Chem., Int. Ed. 2001, 40, 486–516; (f) Beer, P.
D. Chem. Commun. 1996, 689–696; (g) Schmidtchen, F.
P.; Berger, M. Chem. Rev. 1997, 97, 1609–1646; (h) Beer,
P. D.; Smith, D. K. Prog. Inorg. Chem. 1997, 46, 1–96; (i)
Atwood, J. L.; Holman, K. T.; Steed, J. W. Chem.
Commun. 1996, 1401–1407.
3. (a) Keegan, J.; Kruger, P. E.; Nieuwenhuyzen, M.;
O’Brien, J.; Martin, N. M. Chem. Commun. 2002, 2192–
2193; (b) Liao, J. H.; Chen, C. T.; Fang, J. M. Org. Lett.
2002, 4, 561–564; (c) Fabbrizzi, L.; Licchelli, M.; Mancin,
F.; Pizzeghello, M.; Rabaioli, G.; Taglietti, A.; Tecilla, P.;
Tonellato, U. Chem. Eur. J. 2002, 8, 94–101; (d) Miyaji,
4-Nitro-N%-ethyl-1,8-naphthalimide 5
Yield 510 mg (93%). Mp 187.6–188.9°C. Anal. calcd for
C14H10N2O4: C, 62.22; H, 3.73; N, 10.37%; Found: C,
62.18; H, 3.68; N, 10.15%; lH (400 MHz, CDCl3) 1.37
(3H, t, J=7.0, CH3), 4.28 (2H, q, J=7.0, CH2), 8.01

T. Gunnlaugsson et al. / Tetrahedron Letters 44 (2003) 8909–8913
8913
H.; Anzenbacher, P., Jr.; Sessler, J. L.; Bleasdale, E. R.;
Gale, P. A. Chem. Commun. 1999, 1723–1724; (e)
Cooper, C. R.; Spencer, N.; James, T. D. Chem. Com-
mun. 1998, 1365–1366; (f) Kubo, Y.; Tsukahara, M.;
Ishihara, S.; Tokita, S. Chem. Commun. 2000, 653–654;
(g) Xie, H.; Yi, S.; Yang, X.; Wu, S. New J. Chem. 1999,
23, 1105–1108.
163–164; (b) de Silva, A. P.; Gunaratne, H. Q. N.;
Gunnlaugsson, T. Tetrahedron Lett. 1998, 39, 5077–5080;
(c) de Silva, A. P.; Gunaratne, H. Q. N.; Habib-Jiwan, J.
L.; McCoy, C. P.; Rice, T. E.; Soumillion, J. P. Angew.
Chem., Int. Ed. Engl. 1995, 34, 1728–1731.
10. SMART and SAINT-NT, Bruker-AXS, Madison, WI,
1998; G. M. Sheldrick, SHELXTL Version 5.1, Bruker-
AXS, Madison, WI, 1998. Crystallographic data for the
structures in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplemen-
tary publication numbers CCDC: Compound 2 (Fig. 2):
204241; Compound 2 and HCO3 adduct (Fig. 7): 204242.
Copies of the data can be obtained, free of charge, on
application to CCDC, 12 Union Road, Cambridge CB2
1EZ, UK [fax: +44(0)-1223-336033 or e-mail: deposit@
ccdc.cam.ac.uk].
11. Hampe, E. M.; Rudkevich, D. M. Chem. Commun. 2002,
1450–1451 and references cited therein.
12. Mak, T. C. W.; Xue, F. J. Am. Chem. Soc. 2000, 122,
9860–9861.
13. Quinn, R.; Appleby, J. B.; Pez, G. P. J. Am. Chem. Soc.
1995, 117, 329–335.
14. Shenderovich, I. G.; Tolstoy, P. M.; Golubev, N. S.;
Smirnov, S. N.; Denisov, G. S.; Limbach, H.-H. J. Am.
Chem. Soc. 2003, 11710.
4. (a) Davis, A. P.; Lawless, L. J. Chem. Commun. 1999,
9–10; (b) Davis, A. P.; Perry, J. J.; Williams, R. P. J. Am.
Chem. Soc. 1997, 119, 1793–1794.
5. (a) Gunnlaugsson, T.; Harte, A. J.; Leonard, J. P.;
Nieuwenhuyzen, M. Chem. Commun. 2002, 2134–2135;
(b) Gunnlaugsson, T.; Davis, A. P.; O’Brien, J. E.;
Glynn, M. Org. Lett. 2002, 4, 2449–2452; (c)
Gunnlaugsson, T.; Davis, A. P.; Glynn, M. Chem. Com-
mun. 2001, 2556–2557; (d) Kruger, P. E.; Mackie, P. R.;
Nieuwenhuyzen, M. J. Chem. Soc., Perkin Trans. 2 2001,
1079–1083.
6. Gunnlaugsson, T.; Kruger, P. E.; Lee, T. C.; Parkesh, R.;
Pfeffer, F. M.; Hussey, G. M. Tetrahedron Lett. 2003, 43,
6575–6578.
7. Camiolo, S.; Gale, P.; Hursthouse, M. B.; Light, M. E.
Org. Biomol. Chem. 2003, 1, 741–744.
8. Miyaji, H.; Sessler, J. L. Angew. Chem., Int. Ed. 2001, 40,
154–157.
9. (a) de Silva, A. P.; Rice, A. Chem. Commun. 1999,