Polymorphic equilibrium responsive thermal and mechanical stimuli in light-emitting crystals of N -methylaminonaphthyridine

Article abstract of DOI:10.1021/ol302963e

Crystal polymorphs of 1,8-naphthyridine derivative, being anti and syn conformers, show a reversible transformation from anti to syn by heating and from syn to anti by grinding with the alteration of emittance intensity, and notably, thermal transformation from anti to syn conformer took place in single-crystal-to-single-crystal (SC-to-SC) form, which was confirmed by a single crystal X-ray crystallography.

Full text of DOI:10.1021/ol302963e

ORGANIC
LETTERS
2012
Vol. 14, No. 24
6282–6285
Polymorphic Equilibrium Responsive
Thermal and Mechanical Stimuli in
Light-emitting Crystals of
N‑Methylaminonaphthyridine
Naomi Harada, Yuichiro Abe, Satoru Karasawa, and Noboru Koga*
Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi,
Higashi-ku, Fukuoka, 812-8582 Japan.
koga@fc.phar.kyushu-u.ac.jp
Received November 6, 2012
ABSTRACT
Crystal polymorphs of 1,8-naphthyridine derivative, being anti and syn conformers, show a reversible transformation from anti to syn by heating
and from syn to anti by grinding with the alteration of emittance intensity, and notably, thermal transformation from anti to syn conformer took
place in single-crystal-to-single-crystal (SC-to-SC) form, which was confirmed by a single crystal X-ray crystallography.
The solid-state emissions of organic molecules and metal
complexes in response to heat,1 pressure,2 light,3 etc.4 have
drawn attention and intensive study. Since the solid-state
emitting properties strongly depend on the molecular
structure and the molecular arrangements in crystals, the
alteration of molecular arrangements caused by external
stimuli (heat, pressure, light, etc.) manifests as changes
observed in emission color and intensity. In crystal poly-
morphs, transformation between them by external stimuli
produces alterationsofemitting color and intensity. There-
fore, many molecules and metal complexes showing
polymorph-dependent emission have been reported as
switchable molecules by taking advantage of crystal-to-
crystal (C-to-C) interconversion.5
However, the examples that single-crystal-to-single-crystal
(SC-to-SC) phase transition have been limited.6 Recently, we
reported the donorÀacceptor type of quinoline (TFMAQ)
derivatives showing an emission color change with exother-
mic SC-to-SC transformation.6b In the polymorphs of 1,8-
naphthyridine derivative, this time, endothermic SC-to-SC
transformation with alteration of the emission intensity was
observed. We report herein the solid-state (crystalline) emit-
ting properties of polymorphs of 1,8-naphthyridine fluoro-
phores in response to heat and grinding.
(1) (a) Zhao, Y.; Gao, H.; Fan, Y.; Zhou, T.; Su, Z.; Liu, Y.; Wang, Y.
Adv. Mater. 2009, 21, 3165–3169. (b) Chung, J. W.; An, B.-K.; Park, S. Y.
Chem. Mater. 2008, 20, 6750–6755. (c) Mutai, T.; Satou, H.; Araki, K.
Nat. Mater. 2005, 4, 685–687.
(2) (a) Zhang, G.; Lu, J.; Sabat, M.; Fraser, C. L. J. Am. Chem. Soc. 2010,
132, 2160–2162. (b) Ito, H.; Saito, T.; Oshima, N.; Kitamura, N.; Ishizuka, S.;
Hinatsu, Y.; Wakeshima, M.; Kato, M.; Tsuge, K.; Sawamura, M. J. Am.
Chem. Soc. 2008, 130, 10044–10045. (c) Sagara, Y.; Mutai, T.; Yoshikawa, I.;
Araki, K. J. Am. Chem. Soc. 2007, 129, 1520–1521.
(3) (a) Chung, J. W.; You, Y.; Huh, H. S.; An, B.-K.; Yoon, S.ÀJ.;
Kim, S. H.; Lee, S. W.; Park, S. Y. J. Am. Chem. Soc. 2009, 131, 8163–
8172. (b) Kumar, N. S. S.; Varghese, S.; Narayan, G.; Das, S. Angew.
Chem., Int. Ed. 2006, 45, 6317–6321.
A parent compound, 2,4-ditrifluoromethyl-7-amino-1,8-
naphthyridine, 1, was prepared in a manner similar to the
(4) Crenshaw, B. R.; Weder, C. Chem. Mater. 2003, 15, 4717–4724.
(5) (a) Mutai, T.; Tomoda, H.; Ohkawa, T.; Yabe, Y.; Araki, K.
Angew. Chem., Int. Ed. 2008, 47, 9522–9524. (b) Davis, R.; Rath, N. P.;
Das, R. Chem. Commun. 2004, 74–75.
(6) (a) Luo, X.; Li, J.; Li, C.; Heng, L.; Dong, Y. Q.; Liu, Z.; Bo, Z.;
Tang, B. Z. Adv. Mater. 2011, 23, 3261–3265. (b) Abe, Y.; Karasawa, S.;
Koga, N. Chem.;Eur. J. 2012, 18, 15038–15048.
r
10.1021/ol302963e
Published on Web 12/12/2012
2012 American Chemical Society

procedure for TFMAQ using 2,6-diaminopyridine in
place of 1,3-diaminobenzene.6b Amino moiety of 1 was
converted to chloride, via hydroxy derivative,7 followed
by reaction with methylamine in the presence of copper
catalyst to afford 2 in 59% yield (4 steps, Scheme S1,
Supporting Information). From recrystallization with a
mixture of n-hexane and CH2Cl2 for 2, single crystals
were obtained as yellowish plates. In solution, fluoro-
phores 1 and 2 showed emission depending on the solvent
polarity. Fluorescence emission at λfmax (Φf) = 392 (0.04),
406 (0.14), 416 (0.19), and 435 (0.40) nm for 1 and at
λfmax (Φf) = 389 (0.09), 432 (0.36), 436 (0.50), and 444
(0.33) nm for 2 in n-hexane, chloroform, ethyl acetate,
and methanol, respectively, were observed under irradia-
tion at 380 nm (Figure S1, Supporting Information). In
solid states, on the other hand, 1 and 2 showed weak
blueish emission. Interestingly, the emission intensity of
the crystalline sample of 2 increased by heating at 200 °C.
Photographs of a single crystal taken under a microscope
are shown in Figure 1.
Since the observed thermal emitting behavior suggested
a SC-to-SC transformation between the polymorphs,
X-ray crystallography was carried out. By heating a large
sized crystal (5 Â 3 Â 3 mm) of pale yellow plate, 2b, at
200 °C, the crystal was partially destroyed. The obtained
crystal was cut and used as sample of 2a for X-ray crystal-
lography. The single crystal of 2a was also obtained by
sublimation of crystal 2b at over 150 °C. X-ray crystal-
lography (monoclinic, P21/c, and Z = 4) indicated that 2b
and 2a were polymorphous and that the a, b, and c axes for
crystal 2b corresponded to the b, a, and c axes for crystal 2a
(Figure S2, Supporting Information). The molecular and
crystal structures for 2b and 2a revealed by X-ray crystal-
lography are shown in Figure 2. In the molecular structure,
the molecule of 2b was an antiperiplanar (anti) conformer
in relation to the methyl moiety, while that of 2a was a
synperiplanar (syn) conformer. Interestingly, the observed
thermal transformation from 2b (anti) to 2a (syn) was
opposite to that for the corresponding TFMAQ-NHMe,
in which thermal SC-to-SC transformation took place
from the syn to anti conformer. In the molecular packings
Figure 2. (a) ORTEP drawings of molecular structures of 2b
(left) and 2a (right) and (b) molecular packings for 2b (left) and
2a (right) in a ball and stick model, In (b), H atoms and CF3
groups are omitted. Dotted lines indicate hydrogen bonds.
8-positions of naphthyridine belonging to the other mole-
cule were observed and expected to form the hydrogen
bonds. In 2b, the molecules formed the head-to-tail dimer
through the hydrogen bonds in the distance (rNÀN8) of
2.99 A. In contrast, the molecules of 2a formed one-
dimensional hydrogen bonding in the distances of
rNÀN1 = 3.14 and rNÀN8 = 3.15 A along the c axis. The
molecular arrangements for 2b and 2a showed different
types of herringbone (HB) structures along the c and a
axes, respectively. 2b was classified as γ-HB structure from
the length of the shortest axis (Figure S3, Supporting
Information).8 The differences of the packing arrange-
ments with different hydrogen bonding in 2b and 2a might
affect the emitting properties.
The fluorescence spectra of the crystal (crushed) sample
of 2b showed the weak emission at λfmax of 459 nm with
Φf(cry) of 0.03, while 2ashowed a blue shift by 10 nm and a
increase in Φf(cry), and values of λfmax of 444 nm and
Φf(cry) of 0.15, were obtained . The spectral changes are
shown in Figure 3a together with the absorption spectra.
The blue shift of the emission with the increase of the
fluorescence intensity for 2a might be due to the alteration
from a strong hydrogen bonded dimer to weak hydrogen
bond chains. Subsequently, when the obtained 2a (ca.
1 mg) was ground with an agate mortar and a pestle for
10 min, the emission intensity decreased and the wavelength
returned to 463 nm (Figure S4, Supporting Information),
suggesting that 2a returned to 2b by a mechanical stimulus.
The formation of 2b was also supported by IR spectra, in
which the absorption at 3301 cmÀ1 due to the NH stretch-
ing for 2a shifted to ∼3200 cmÀ1 for 2b by grinding
(Figure 3b). It is noted that the observed shift to the low
wavenumber indicated the phase transition to a species
having strong hydrogen bond. By repeating the cycle of
for 2b and 2a, the short distances (rNÀN1 and rNÀN8
)
between the nitrogen of amine and that at the 1- and
(7) Newkome, G. R.; Garbis, S. J.; Majestic, V. K.; Fronczek, F. R.;
Chiari, G. J. Org. Chem. 1981, 46, 833–839.
(8) (a) Hunter, C. A.; Lawson, K. R.; Perkins, J.; Urch, C. J. J. Chem.
Soc., Perkin Trans. 2 2001, 651–669. (b) Gavezzotti, A.; Desiraju, G. R.
Acta Crystallogr., Sect. B 1989, 45, 473–482.
Figure 1. Photographs of a single crystal of 2 before (left) and
after (right) heating at 200 °C for 10 min. Upper and lower show
under the irradiation at 365 nm and the room light, respectively.
Org. Lett., Vol. 14, No. 24, 2012
6283

phase transition suggested that an enantiotropic transition
between two polymorphs took place.9 In the second and
the third cycles, noadditionalpeakat177 °C was observed,
suggesting that 2a formed after melting. In contrast, the
corresponding peak for TFMAQ-NHMe was exothermic,
suggesting a monotropic transition.10 To determine the
exothermic peak due to the transition from 2a to 2b, the
cooling processes after heating at 200 °C and after melting
at 228 °C were carefully investigated until 0 °C (2 °C/min).
In both measurements, no exothermic peak was observed.
The lack of a peak due to the transition from 2a to 2b
indicated that the crystal polymorph 2a formed after
heating at 200 °C and melting was thermally stable and
did not spontaneously return to 2b above 0 °C. Polymorph
2a also showed DSC curves similar those in the second and
third cycles for 2b (Figure S6, Supporting Information).
Figure 3. (a) Emission (solid line) and absorption (dotted line)
spectra before (black) and after (red) heating 2b and (b) change
of IR spectra of 2a before (red), after grinding for 5 min (sky
blue), 10 min (green), 15 min (purple), and 2b (blue). Solid-line
bars indicate the absorption due to 2a (red) and 2b (blue).
Figure 5. DSC curves of 2b. (Inset) the range of 135À220 °C
indicated by the arrow is expanded.
The XRD measurements using one sample of 2b were
continuallycarried outinorderof(i) the sampleof powder,
(ii) after heating the powder at 200 °C for 10 min, (iii) after
melting and cooling to rt and (iv) after grinding for 60 min.
The changes of XRD patterns of 2b are shown in Figure 6.
Before heating, the XRD pattern of the powder sample
(Figure 6i) was consistent with that simulated from the
result of single crystal X-ray analysis. After heating at
200 °C, the XRD pattern was changed and new peaks were
observed (Figure 6ii) which were consistent with that for
2a. After melting and cooling to rt, the XRD pattern was
also consistent with that for 2a (Figure 6iii), indicating that
2a formed after melting. This result might be because the
solidifying temperature (217 °C) was higher than the
phase-transfer one (177 °C). Interestingly, the XRD pat-
ternafter grindingthe sample at(iii) wasclose to that for 2b
(Figure 6iv), indicating that 2a returned to 2b by grinding.
The results of DSC and XRD suggested that the trans-
formation from 2b to 2a above 200 °C took place.
Furthermore, XRD in addition to the alteration of emis-
sion and IR absorption indicated that 2a obtained by
heating returned to 2b in response to mechanical stimulus
Figure 4. Change of λfmax value after heating at 200 °C (O) and
grinding (b) in the heat-grinding cycles.
heatingÀgrinding, the alteration of emission could be
representative (Figure 4).
To investigate the thermal properties and the structural
alterations after heating and grinding, differential scan
calorimetry (DSC) and X-ray diffraction (XRD) measure-
ments of 2b and 2a were carried out. DSC were measured
in the temperature range 25À250 °C for three cycles of
heating and cooling (10 °C/min for heating and cooling
rate, Figure 5). In the first cycle for 2b, DSC curves showed
weak and strong endothermic peaks at 177 and 228 °C,
respectively, on heating and a strong exothermic peak at
217 °C on cooling. The peaks at 228 and 217 °C were due to
the melting and the solidification, respectively. Interest-
ingly, a weak peak at 177 °C indicating as endothermic
(9) Mehta, G.; Sen, S. Chem. Commun. 2009, 5981–5983.
ꢀ
ꢀ
(10) Ceolin, R.; Tamarit, J.-L.; Barrio, M.; Lopez, D. O.; Nicolaı, B.;
¨
Veglio, N.; Perrin, M.-A.; Espeau, P. J. Pharm. Sci. 2008, 97, 3927–3941.
6284
Org. Lett., Vol. 14, No. 24, 2012

the resulting 2a returned to 2b by grinding. The observed
reversibility might be due to the thermal phase transition,
in which 2b and 2a were enthalpically and entropically
stable, respectively. At room temperature, 2a was entropi-
cally unstable, and a subtle stimulus such as grinding might
be a sufficient trigger to induce transformation to the
enthalpically stable 2b.
In conclusion, crystal polymorphs, 2b and 2a, emitting
different intensities, reversibly transformed from 2b to 2a
by heating and from 2a to 2b by grinding. Especially,
thermal conversion from 2b to 2a took place in SC-to-
SC. The emitting intensity for 2a was 5 times larger than
that for 2b, and the accompanying thermal and mechanical
phase transitions could be regard as a switchable emission.
Supporting Information Available. Experimental de-
tails, absorption and emission spectra of 1 and 2 in various
solvents and solid state, the molecular packings for 2,
photographs for the powders of 2b and 2a, and other data
mentioned in this paper. This material is available free of
charge via the Internet at http://pubs.acs.org.
Figure 6. XRD pattern changes for powder sample of 2b; (i) the
sample of powder, (ii) after heating at 200 °C for 10 min and
cooling to rt, (iii) after melting and cooling to rt, and (iv) after
grinding for 60 min.
of grinding. Therefore the polymorphs 2b and 2a showed
the reversibility in that 2b converted to 2a by heating, while
The authors declare no competing financial interest.
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