Organic Letters
Letter
precipitate from the strongly acidic solution in 24% yield, while
1-Cl was isolated in 42% yield by substantial dilution of the
filtrate (supernatant after isolation of 2-Cl) with ice water and
subsequent crystallization of the obtained precipitate from
cyclohexane.
Scheme 3. Transformations of 2-R Derivatives and
Synthesis of Target Qbtz-R Fluorophores
Similarly, we prepared rare 2-H (25% yield) upon direct
iodination of btz-H with I2/KMnO4/H2SO4 and subsequent
workup of the reaction mixture with the exact amount of ice.
Although 6-iodobenzothiazole (1-H) was identified as the
major product of the reaction, its isolation in pure form turns
out to be problematic due to the higher content of other
monoiodinated regioisomers. Therefore, we developed an
alternative route, where 1-H is prepared by a reductive
hydrodehalogenation of 1-Cl with KI/H3PO2 (97% yield),
while 1-Cl can be obtained easily by direct iodination of btz-Cl
or by chlorination of 6-iodobenzothiazol-2(3H)-one (1-OH)
with POCl3 (Scheme 2). This procedure affords 1-H from btz-
OH in the overall 72% yield.
Furthermore, iodination experiments in H2SO4 can be easily
adjusted to provide 4,5,6,7-tetraiodobenzothiazoles (4-R, R =
Me, H, Cl), as potential building blocks for S,N-doped
nanographenes, with I2/KMnO4 system providing the highest
yields (75% for 4-Me).
4,7-Diiodobenzothiazoles, 2-R (easily separable from
concomitant 1-R) represent an expedient and more reactive
alternative to 4,7-dibromo-2-methylbenzothiazole,29 which
serves as an intermediate in the synthesis of dyes with
potential application in dye-sensitized solar cells30 and metal-
ion sensing,31 but its preparation requires a 5-step synthetic
route. Having a rapid and facile one-step access to valuable 2-R
in reasonable yields, we wondered whether these substrates can
be employed in the construction of a new class of D-π-A-π-D
benzothiazole-cored TPA fluorophores with reactive C-2
position available for modulation of linear and nonlinear
optical properties (Scheme 3). This was not possible in the
previously characterized quadrupolar dyes with the C-2
position occupied by one of the two electron-donating
branches (cf. Qbtz-2,6 in Scheme 1).
Computer-aided study of 4,7-bis(triphenylamine-ethynyl)-2-
R-benzothiazoles (Qbtz-R) by means of the quadratic
response time-dependent DFT method32 at the CAM-
B3LYP/6-311++G** level revealed large TPA cross sections
(400−1800 GM) for this series, which are comparable or
higher than that of Qbtz-2,6 with C-2/C-6 disubstitution (685
GM), but with a possibility to achieve TPA enhancement and
red-shift of absorption/emission peaks upon introduction of
auxiliary electron-withdrawing substituents to the C-2 position
and electron-donating substituents to the periphery of
triphenylamine units (Scheme 3 and Table S8 in SI). On the
contrary, derivatives with three or four triarylamine arms linked
to the benzothiazole core (products of coupling reactions with
3-R and 4-R) are computed to display smaller TPA activities
than Qbtz-R due to lower transition dipole moments between
the excited states (cf. Table S8 in SI).
Structures of all target chromophores Qbtz-R were
confirmed spectroscopically, while Qbtz-H was also charac-
terized by single crystal X-ray diffraction (Figure 1d).
Qbtz-R dyes were subjected to measurements of UV−vis
absorption and emission spectra, as well as to TPA cross
sections, δTPA, via a two-photon excited fluorescence (TPEF)
method with femtosecond laser excitation at wavelengths of
730−850 nm (Figure 2). One-photon and two-photon spectral
characteristics are summarized in Table 1.
Following the trends computed by quantum-chemical
calculations (Tables S8, S9 and Figure S18 in SI), the
absorption spectra of Qbtz-R dyes feature an intense
intramolecular charge-transfer (ICT) band in the visible region
with maxima λabs in the range of 388−458 nm, which are
generally red-shifted for derivatives with stronger electron
acceptors. The fluorescence is observed in the blue spectral
region for derivatives with electron-donating (R = NH2, OH,
Me) and neutral (R = H) substituents, while electron-
withdrawing groups (EWGs) cause a substantial bathochromic
shift of emission into green (Qbtz-CN), yellow (Qbtz′-CN),
and orange (Qbtz-CHO) region.
Most importantly, Qbtz-R chromophores exhibit high TPA
cross sections (540−1374 GM)roughly an order of
magnitude higher than most of the conventional one-photon
fluorophores, with TPEF maxima λTPA positioned at 740−820
nm. These positions are less than twice that of the single-
photon absorption λabs (S0 → S1), implying a deeper (S0 → S2
or S0 → S3) transition as expected for quadrupolar dyes due to
parity selection rules (Table S8 and Figure S6 in SI). While
already Qbtz-H exhibits somewhat higher activity than
regioisomeric Qbtz-2,6, the introduction of small EWG
substituents to the C-2 position of Qbtz-R leads to further
TPA enhancement and red-shift of TPA maxima beyond 800
nm, both effects being reinforced upon introduction of
pendant alkoxy groups to triphenylamine moieties. These
changes, together with only a moderate drop of emission
Encouraged by this finding, we prepared a set of 4,7-
bis(triphenylamine-ethynyl)benzothiazoles with D-π-A-π-D
setup by Sonogashira-type cross-coupling of 2-R with 4-
(N,N-diphenylamino)phenylacetylene (6a) and its congener
end-capped with two methoxy groups (6b). Since the C-2
position in 2-Cl is prone to nucleophilic substitutions, we
employed this derivative in the synthesis of 2-NH2, 2-OH and
2-CN, while 2-CHO was prepared by formylation of the
heteroaryllithium salt derived from 2-H (Scheme 3).
3462
Org. Lett. 2021, 23, 3460−3465