Imidazo[1,2-a ]heterocyclic scaffolds are well-explored substrates in medicinal chemistry while
examples of their application in material science remain relatively scarce.[1 ] However, the intrinsic fluorescence of imidazopyridine (ImPy) and related fused
systems is quite intriguing and could be very promising for the development of novel
fluorophores.[2 ] ImPys are easily accessible through an isonitrile-based multicomponent reaction
(MCR), the Groebke–Blackburn–Bienaymé reaction (GBB-3CR).[3 ] The modular nature of MCRs would also allow for easy assembly, customization and
fine-tuning of the optoelectronic properties of these compounds.[4 ] However, possible applications of the GBB-3CR and its products for the design of
functional chromophores have not been explored thoroughly. One of the few examples
of the synthesis of chromophores based on the GBB-3CR was reported by Burchak et al. in 2011.[5 ] Shahrisa et al. reported a library of donor-acceptor fluorophores consisting of imidazo[1,2-a ]pyridines as donors in combination with tetrazole, dihydropyridine or dihydropyrimidones
acceptors via sequential GBB-3CR-Ugi-azide-4CR/Hantzsch-4CR/Biginelli-3CR synthesis.[6 ] Balijapalli and Iyer also designed imidazo[1,2-a ]pyridine fluorophores exhibiting excited-state intramolecular proton transfer (ESIPT)
properties, which were accessed in a copper-catalyzed three-component reaction rather
than a GBB-3CR.[7 ] Due to their luminescence properties, we targeted the exploration of imidazo[1,2-a ]heterocycles for different applications; e.g., pH sensing or DNA-staining.[8 ] To expand on these results, we envisioned imidazo[1,2-a ]heterocycles acting as donor motifs in donor-acceptor chromophores that would emit
via thermally activated delayed fluorescence (TADF).[9 ] In 2020, Lee et al. reported on the first series of TADF-emitters containing the imidazopyridine motif.[10 ] Nitrile groups were grafted onto the scaffold to enhance their electron-withdrawing
properties and it was combined as an acceptor with two different donors. As the secondary
amino substituent originating from the isonitrile employed in the GBB-3CR increases
the electron density of the imidazopyridine, we expected that this moiety would be
very well suited as a donor rather than an acceptor. We thus targeted the design of
donor-acceptor TADF-emitters featuring an ImPy-based donor.
Prior to synthesis, we assessed the feasibility of our design using density functional
theory by partnering the 3-(tert -butylamino) imidazo[1,2-a ]pyridine moiety with a range of electron-accepting groups that had previously been
studied in donor-acceptor TADF emitters. We first modelled a set of potential structures
with 3-tert -butyl imidazo[1,2-a ]pyridine as the donor, a 2,6-dimethylphenylene bridge that is coupled at the 4-position
to the acceptor motif (ImPy*). The results are listed in Table [1 ].
Table 1 Chemical Structures and DFT-Predicted Singlet-Triplet Energy Gaps and Vertical S1 Energy Levels of the ImPy* Donor with Different Acceptor Types using the PBE0/6-31G(d,p)
Method In Vacuuma
p -ImPy-CN
p -ImPy-NPI
p -ImPy-Ph.Bs.
p -ImPy-Baz
p -ImPy-Try
p -ImPy-Aq
0.92 eV
0.73 eV
0.65 eV
0.63 eV
0.40 eV
0.18 eV
3.95 eV (389 nm)
3.19 eV (389 nm)
3.62 eV (343 nm)
3.66 eV (339 nm)
3.43 eV (361 nm)
2.75 eV (450 nm)
a Top row: ΔE
ST , bottom row: S1 energy
According to the calculations, the dihedral angle between the ImPy* unit and the 2,6-dimethylphenylene
bridging unit is ca. 29°. The smallest ΔE
ST value was obtained for the combination of ImPy and anthraquinone (Aq). The ImPy-group
acts as a relatively weak donor, thus pairing it with the strong acceptor anthraquinone
was necessary to stabilize the S1 energy into the visible regime and decrease the singlet-triplet energy gap, ΔE
ST , to a value where TADF may be possible. Coupling ImPy to weaker electron acceptors
would yield a weaker charge-transfer state that would place the likely emission in
the UV region.
Based on these results, we envisaged that incorporating multiple ImPy residues attached
to a central phenylene spacer would effectively increase the strength of the charge-transfer
S1 state, red-shifting the emission and decreasing further ΔE
ST . A series of target emitters with different configurations of donors and the Aq acceptor
was designed: o -, m -, and p -ImPyAq. The differing regiochemistry of the donor was expected to influence the exchange
energy of the emitter and thus ΔE
ST . The energy levels of the frontier orbitals of the three isomers and their localization
in the optimized structures are presented in Figure [1 ].
Figure 1 DFT-predicted HOMO and LUMO orbital distribution (isovalue 0.02) and singlet and
triplet energies of p -ImPyAq*, m -BisImPyAq, and o -BisImPyAq using the PBE0/6-31G(d,p) method in vacuum.
For all three proposed compounds, the estimated ΔE
ST values are moderately small, with p -ImPyAq* exhibiting the largest ΔE
ST of 0.18 eV while the bis-ImPyAq isomers both have predicted ΔE
ST of 0.10 eV. The LUMOs of each of the three structures are almost exclusively located
on the anthraquinone acceptor, while the HOMOs span over the imidazo[1,2-a ]pyridine moiety and the central phenylene ring. In the case of p -ImPyAq*, the greater extension of the LUMO onto the bridge explains the higher ΔE
ST for this compound. The HOMO-LUMO gaps were calculated to range from 2.78 to 3.11
eV. However, the singlet oscillator strength of all compounds is relatively low, reflecting
the poor overlap of the electron densities of the HOMO and LUMO in each molecule.
To access the proposed structures starting from a set of donors and acceptors, a modular
synthesis approach was developed by dissecting the emitters into individual building
blocks. The donor building blocks, comprising the ImPy moiety and the phenylene spacer,
were prepared via a GBB-3CR from the respective brominated benzaldehydes (Scheme [1 ]). For the para -emitter, the location of the methyl groups on the phenylene spacer was inverted because
the respective aldehyde component for the GBB-3CR synthesis of this building block
is more easily available. The yield of the mono-imidazo[1,2-a ]pyridine donor 4a was significantly better than for the bis-imidazo[1,2-a ]pyridines due to their additional reactive site and because of the steric congestion
in the case of 4c .
Scheme 1 Synthesis of the ImPy-donor building blocks 4a –c
via GBB-3CRs
The acceptor building block, anthraquinone pinacol borate was prepared via Miyaura borylation according to a procedure by Liu et al. using a Pd(dppf)Cl2 catalyst and potassium acetate as the base.[11 ] The desired product 6 was obtained in quantitative yield (Scheme [2 ]).
Scheme 2 Synthesis of anthraquinone pinacol borate 6
via Miyaura borylation
We next optimized the Suzuki–Miyaura conditions for the coupling of the individual
building blocks to form the targeted donor-acceptor compounds. To find the best reaction
conditions for this key step, we first optimized the synthesis of p -ImPyAq as a model system. The conversion of 4a into 7 was calculated from the 1 H NMR spectra of the crude products to identify the most effective reaction conditions.
For this, the ratio of the signals’ integrals corresponding to the methyl residues
of the phenyl spacer of both starting material and product were used. As no internal
standard was employed, the conversion does not reflect the actual isolated yield.
The results are displayed in Table [2 ]. Among the tested Pd sources, palladium(II) acetate performed the best. Potassium
acetate and potassium carbonate were used for the optimization of the Pd source and
the ligand. The best results were obtained using RuPhos and SPhos (entries 9 and 11);
without any ligand, only traces of the product could be detected (entry 12). Using
stronger bases like potassium tert -butoxide, potassium hydroxide or cesium carbonate led to a significantly improved
conversion as, in all three cases, no residual starting material was present (entries
13–15). Considering the overall purity of the product based on its 1 H NMR spectrum from each of the various entries, cesium carbonate was chosen. Using
these optimized conditions, the target ortho -, meta - and para -emitters were synthesized from the respective building blocks (Scheme [3 ]).
Table 2 Optimization of the Reaction Condition for the Suzuki–Miyaura Coupling of 4a and 6
Entry
Catalyst
mol%
Ligand
mol%
Base
Conversion (%)b
1
Pd(dba)2
5
XPhos
10
K2 CO3
53
2
Pd2 (dba)3
5
XPhos
10
K2 CO3
44
3
Pd(PPh3 )4
5
XPhos
10
K2 CO3
62
4
Pd-Peppsi-iPr
5
XPhos
10
K2 CO3
24
5
Pd(OAc)2
5
XPhos
10
K2 CO3
64
6
Pd(OAc)2
10
XPhos
20
K2 CO3
55
7
Pd(OAc)2
2
XPhos
4
K2 CO3
25
8
Pd(OAc)2
5
XPhos
10
KOAc
39
9
Pd(OAc)2
5
SPhos
10
KOAc
51
10
Pd(OAc)2
5
CataCXium A
10
KOAc
36
11
Pd(OAc)2
5
RuPhos
10
KOAc
51
12
Pd(OAc)2
5
–
–
KOAc
3
13
Pd(OAc)2
5
RuPhos
10
KOt Bu
>99
14
Pd(OAc)2
5
RuPhos
10
KOH
>99
15
Pd(OAc)2
5
RuPhos
10
Cs2 CO3
>99
a Conditions: 4a (1.00 equiv), 6 (1.10 equiv), catalyst, ligand, base (3.00 equiv), solvent: toluene/water (4:1),
110 °C, 16 h.
b The conversion was calculated using the ratio of the 1 H NMR signals’ integrals of 4a and 7 .
After flash chromatography, p -ImPyAq (7 ) was obtained in a yield of 61%.[12 ] The notable difference between the quantitative conversion of 4a into 7 (see Table [2 ]) and the isolated yield of 7 is due to losses during the compound’s purification. For m -BisImPyAq (8 ), the yield was even higher, at 95%, likely due to the reduced steric hindrance of
the bromide.[13a ] The structure of 8 was confirmed unambiguously through single-crystal X-ray crystallography (Figure
[2 ]).[13b ]
Scheme 3 Synthesis of the ortho -, meta -, and para -ImPyAq through Suzuki–Miyaura coupling of the donor and acceptor building blocks
Figure 2 Molecular structure of one crystallographic independent molecule of 8 (displacement parameters are drawn at 50% probability level)
On the other hand, o -BisImPyAq (9 ) could not be obtained. Instead, protodeboronation of the anthraquinone pinacol borate
was observed while the ImPy building block remained unconverted. Addressing positions
between sterically hindered residues is quite challenging and only a few procedures
have been reported; e.g., using AntPhos as a ligand. While this catalytic system is
feasible for adjacent phenyl substituents, no reaction was observed for imidazo[1,2-a ]pyridines. Hence, o -BisImPyAq needed to be accessed via a different route. Therefore, the acceptor unit was attached to the bridging aldehyde
prior to the synthesis of the imidazo[1,2-a ]pyridine moieties. The synthetic approach is depicted in Scheme [4 ].
Scheme 4 Synthesis of (a) 10 and (b) 9 and 9′ . a The reaction was performed in MeOH at r.t. for 3 days.
2-Bromoisophthalaldehyde 2c was coupled to anthraquinone pinacol borate 6 in a Suzuki–Miyaura reaction. The desired coupling product 10 was obtained in a yield of 19%. Presumably, the losses are due to side reactions
like decarbonylation of the neighboring formyl groups as a significant evolution of
gas was observed during the reaction. Subsequently, the formyl groups were transformed
into 3-aminoimidazo[1,2-a ]pyridines in a GBB-3CR. Initially, standard conditions were applied. However, even
after a prolonged reaction time of ten days, the conversion remained incomplete. Thus,
the solvent was changed to chloroform and the temperature was increased to 60 °C to
accelerate the reaction. Through this modification to the reaction conditions, an
excellent yield of 92% for 9 could be achieved.[14 ]
Figure 3 (a–c) Absorption (black, obtained in toluene (1 × 10–5 M) at 300 K) and normalized emission spectra (red, obtained in toluene (1 × 10–4 M) at 300 K) of 9 (λexc = 350 nm), 8 and 7 (λexc = 340 nm for both) (from left to right) measured at r.t.; (d–f) Normalized emission
spectra of 9 , 8 and 7 (from left to right) measured in toluene (10 μM, λexc = 343 nm) at different time scales and temperatures: 1–100 ns at 77 K (black), 1–9
ms at 77 K (blue), 1–100 ns at r.t. (green).
The synthesized compounds were studied to assess their photophysical properties and
to evaluate whether the emitters exhibit TADF properties. For this, absorption and
emission spectra of the compounds were recorded at ambient temperature (Figure [3a ], Table [3 ]), and emission at 77 K over different time scales (Figure [3b ]). The absorption spectra of all derivatives show similar profiles, with the highest
intensity bands located at 290 nm, followed by lower intensity shoulders at 320–370
nm and a varying intensity low-energy band at >380 nm. Isomeric differences among
the derivatives are most notably reflected in the energy and intensity of this lowest
energy absorption band, with 9 showing the highest intensity. The DFT-predicted absorption spectra follow a similar
trend (Figure S19), except that they are considerably red-shifted compared to the
experimental results. The molar absorptivity values, ε, of the band located at 320–370
nm for 9 , 8 and 7 are 13,664, 15,717 and 11,424 M–1 cm–1 , respectively. Turning to emission in toluene, the spectra were acquired at a considerably
high concentration (1 × 10–4 M) due to their weak fluorescence intensity. Hence, all the samples showed weak,
broad emission bands in the sky-blue region, with peak maxima, λPL , of 463, 460, and 455 nm for 9 , 8 and 7 , respectively. The weak emission correlates with DFT-predicted low oscillator strength
values. In o -ImPyAq 9 , we noticed what appears to be dual emission with the second higher-energy peak at
394 nm. We have excluded its origin as being due to solvent Raman scattering as the
scattering peak appeared at a higher energy, therefore this high-energy peak could
be attributed to LE emission from one of the chromophores. There is a progressing
bathochromic shift of the λPL from para - to meta - to ortho -isomers that is consistent with the trends predicted by TD-DFT; however, the experimentally
observed emission red-shift is rather moderate (max. 8 nm). Low-temperature measurements
were performed to investigate the fundamental luminescent mechanisms of the samples.
For o -ImPyAq 9 , the signal-to-noise ratio remained poor, showing almost no emission at all. For
m -ImPyAq 8 , a bathochromic shift was observed for the prompt fluorescence at 77 K. No delayed
luminescence was observed.
Table 3 Photophysical Properties of the Synthesized Emittersa
entry
λabs (nm)
εmax (M–1 cm–1 )
λPL (nm)
o -BisImPyAq 9
285 / 335
27,828 / 13,780
394, 463
m -BisImPyAq 8
285 / 340
32,545 / 15,727
460
p -ImPyAq 7
283 / 332
18,432 / 11,414
455
a Measured in toluene. λexc = 343 nm.
In contrast to this, the emission intensity of p -ImPyAq 7 was significantly increased upon cooling to 77 K. While at room temperature the compound
was barely emissive, an intense green-yellowish prompt emission was observed at 77
K. Aside from the prompt fluorescence, a delayed luminescence was also observed. Surprisingly,
the maximum emission wavelength of the delayed fluorescence showed a hypsochromic
shift. A potential reason might be that the sample was flash-frozen, thus the conformations
of the individual molecules are not in equilibrium.[15 ] The broad and structureless singlet emission shape hints at emission occurring from
a charge-transfer state, while the structured phosphorescence is consistent with a
locally excited emission from anthraquinone individual chromophores.[16 ] Similar behavior in flash-freeze luminescence experiments was also observed in other
donor–acceptor systems.[15a ]
In summary, a series of donor–acceptor chromophores bearing a 3-aminoimidazo[1,2-a ]pyridine donor motif was synthesized through a GBB-3CR/Suzuki–Miyaura coupling sequence.
While multicomponent methods are still underrepresented in the synthesis of functional
materials, this study showcases the advantages of such modular approaches. The GBB-3CR
offers facile access to the imidazo[1,2-a ]scaffold, which can easily be derivatized through combinatorial variation of the
individual components. This way, a series of ImPy-based building blocks with different
geometries and substitution patterns were synthesized in overall good yields. Subsequently,
these ImPy-building blocks can be coupled to a variety of acceptor moieties. With
the optic of designing new TADF emitters, DFT calculations were used to assess a family
of ImPy-acceptor compounds possessing different acceptors. This study revealed that
in combination with an anthraquinone acceptor moiety, the calculated ΔE
ST values of the ImPy-based compounds were in a range suitable for TADF. However, spectroscopic
and optoelectronic characterization only show very weak emission at ambient temperatures
for the series of synthesized ImPyAq emitters. This is likely due to a combination
of very low oscillator strength and competing non-radiative deactivation pathways.
The detailed origin of this behavior is the subject of further studies. Thus, adjustments
and optimizations of the structures are necessary to improve the optoelectronic properties
of this class of emitters. Therefore, our modular approach lends itself perfectly
to assess different combinations of donor and acceptor motifs. Overall, the ImPy-donor
motive and the MCR-based synthesis concept provide a versatile synthetic platform
for the development of new types and architectures of fluorescent emitters.