Pseudo-five-component synthesis of indolone-3-aminopropenylidene merocyanine dimers and their attenuated aggregation-induced emission

Four indolone-3-aminopropenylidene merocyanine dimers and a reference  -indolonyl-  -amino merocyanine are readily synthesized in a consecutive multicomponent insertion-alkynylation-addition sequence in a one-pot fashion. The rotational barriers of the terminal amino moieties were estimated by variable temperature NMR measurements and the observed coalescence at room temperature to lie in the same margin as for  - pyrrolidinyl enoates. While the mono merocyanine, chosen as a reference, displays the expected 1300 fold increase in emission intensity upon induced aggregation, the merocyanine dimers, although intense in their absorption behavior and redshifted in their emission maxima, only show a 50-60 fold fluorescence increase. The considerable attenuation of emission of the merocyanine dimers in the amorphous solid state supports the finding that unimolecular symmetrical merocyanine dimers of this type are not intensive AIE systems.

The molecular structures of reference chromophore 1a and bichromophores 8 were assigned by 1 H and 13 C NMR spectroscopy and mass spectrometry.As anticipated, for the bichromophores 8 a reduced set of signals is observed, in accordance with the molecular symmetry.Furthermore, it can be deduced as for previously reported -indolonyl--amino merocyanines 1, that only a single diastereomer is formed. 35he rotational barrier of the merocyanine C-N-bond can be estimated from the coalescence temperature of the methylene protons adjacent to the nitrogen atom, of both the hexyl chain and the benzyl group.From room temperature proton NMR spectra (see Supporting Information) it can be estimated that the coalescence temperature Tc apparently is around room temperature (293 K) for the reference system 1a and the three consanguineous bichromophores 8a, 8b, and 8c.Upon increasing the temperature to 323 K, two signals at  3.15-3.23and  4.28-4.44evolve for the N-methylene protons of the hexyl side-chain and the benzylic protons.Lowering the temperature to 263 K causes a resolution into two sets of diastereotopic signals for these protons.These pairs of signals merge at the coalescence temperature Tc.The rate constant for the internal dynamic process, i.e. the C-N-bond rotation, is described for both signals by equation (1).
 = frequency in Hz.
Insertion of equation ( 1) into the Eyring equation, and rearranging, gives the free enthalpy of activation G ≠ (equation (2)) for the examined process.Scheme 2. Consecutive pseudo five-component synthesis of homo-bichromophores 8 by insertionalkynylation-addition sequence.
Insertion of constants in equation (2) finally gives G ≠ as function of Tc and  (equation (3)).
For a coalescence temperature Tc of 293 K (20 °C) and the frequency differences  the rotational barriers of the merocyanine C-N-bonds are estimated from G ≠ (Table 1).
Table 1.Rotational barriers of the merocyanine C-N-bonds G ≠ (293 K) at a coalescence temperature Tc = 293 K of reference system 1a and the three consanguineous bichromophores 8a, 8b, and 8c and the resolved diastereotopic sets of N-methylene and N-benzyl protons determined at 263 K from the proton NMR spectra The average of the free enthalpy of activation G ≠ can be determined for the merocyanines 1a and 8a, 8b, and 8c in a narrow range of 55.20.2 kJ/mol.This rational barrier is relatively low and lies at a comparable magnitude as recently determined for ethyl -pyrrolidino enoates. 46he reference chromophore 1a is an orange solid that luminesces under a hand-held UV lamp, in agreement with the photophysical behavior of many other -indolonyl--amino merocyanines 1. [35][36][37][38] As previously shown for merocyanines 1 with 3-piperazinyl donors, 37 we first recorded the UV/vis spectrum of reference chromophore 1a (Figure 1), showing an intense merocyanine typical broad absorption band at 490 nm with an absorption coefficient of 43500 L•mol -1 •cm -1 .The AIE measurements in 1,4-dioxane/water mixtures with increasing water fraction produce an emission signal upon inducing aggregation that is visible to the naked eye (Figure 2) and reaches a maximum of 568 nm at a water fraction of 80% (Figure 3).As would be expected, the homo-bichromophores 8 display superimposing UV/vis spectra in dichloromethane with broad intense longest wavelength absorption maxima max at 490-491 nm with absorption coefficients of 74600 (8b), 73300 (8c) and 63300 L•mol -1 •cm -1 (8d) (Figure 4), indicating that despite variation of substituents R 1 and R 2 , the chromophore is essentially the same and that in the electronic ground state, reflected by UV/vis absorptions, the two constituting merocyanine moieties are essentially electronically decoupled.In place of homo-bichromophores 8 the AIE measurements were performed for bichromophore 8d (Figure 5, however, in two polarity opposing solvent mixtures, i.e. 1,4-dioxane/water mixtures with increasing content of water (Figure 5, left) and dichloromethane/cyclohexane mixtures with increasing content of cyclohexane (Figure 5, right).While the former produce a 60-fold increase of the emission signal upon inducing aggregation with a maximum at 613 nm at a water fraction of 80% (Figure 4, left, bottom), the latter leads to a 50-fold emission increase of the band at 597 nm for a 95% fraction of cyclohexane (Figure 4, right, bottom).In comparison to the reference chromophore 1a the AIE of bichromophore 8d clearly redshifted in both solvent mixtures, indicating that the intramolecular merocyanine-merocyanine interaction obviously causes a lowering in the excited state energies in the bichromophore aggregates.However, in comparison to the reference chromophore 1a (1300-fold) the AIE enhancement of bichromophore 8d in both solvent systems is with 50-to 60-fold significantly lower.Therefore, it can be assumed that the anti-parallel molecular orientation of the merocyanine units in the aggregates of bichromophore 8d largely overcompensates for the AIE effect gained in the monochromophore system 1a.This effect is also visible to the naked eye for the amorphous powders under a handheld UV lamp (Figure 6).While merocyanine 1a brightly shines upon UV excitation, homo-bichromophore 8d is only very weakly emissive.

Conclusions
The synthetic one-pot insertion-alkynylation-addition concept of the three-component synthesis of indolonyl--amino merocyanines can be readily expanded to the formation of merocyanine dimers in the sense of a pseudo-five-component fashion.While the absorption characteristics of these homobichromophores behave essentially in an additive manner, as expected for non-interacting multichromophores in the electronic ground state, the excited state behavior deviates significantly from the reference monomerocyanine.While the latter displays a significant enhancement of emission upon induced aggregation in solvent mixtures, the model homo-bichromophore only reveals a very modest increase of emission, although with distinct redshift.This indicates that the monomerocyanine typical gain of fluorescence in the series of -indolonyl--amino merocyanines is significantly attenuated as a consequence of a potential symmetrical anti-parallel alignment of the merocyanines upon aggregation.This finding also holds true in the solid state, as supported by comparison of reference monomerocyanine with homo-bichromophore under the handheld UV lamp.As a consequence, for the design of unimolecular multichromophore AIE systems, either breaking the structural or electronic symmetry might give a trade-off.Just very recently we could show that indolonyl--amino merocyanines are well-suited for designing donor-acceptor bichromophores showing aggregation induced dual emission (AIDE) operated by partial energy transfer. 40Further studies to enhance multichromophore AIE by donor-acceptor patterns are currently under investigation.

Experimental Section (E)-3-((E)-3-(Benzyl(hexyl)amino)-3-(4-methoxyphenyl)-1-phenylallylidene)-1-tosylindolin-2-one (1a).
In an oven-dried Schlenk tube with magnetic stir bar, Pd(PPh3)2Cl2 (6.79 mg, 0.01 mmol, 2 mol%) and CuI (3.70 mg, 0.02 mmol, 4 mol%) were placed under nitrogen and dry acetonitrile (3 mL) was added.Amide 4 (227 mg, 0.50 mmol) was added to the suspension, which dissolved at 50 °C (oil bath) after 4 min.After cooling to room temp dry triethylamine (52.9 mg, 0.52 mmol) was added and the mixture was stirred at rt for 20 min.Then, 1ethynyl-4-methoxybenzene (5a) (73.0 mg, 0.55 mmol) was added to the reaction mixture and stirring at rt was continued for 10 min before the mixture was heated at 50 °C (oil bath) for 17 h.After cooling to rt, N-benzyl hexan-1-amine (6) (191 mg, 1.00 mmol) was added and the reaction mixture was stirred at 80 °C (oil bath) for 24 h.After cooling to rt, CH2Cl2 (10 mL) was added and the organic phase was extracted with saturated aq NH4Cl solution (10 mL).The aq layer was extracted with CH2Cl2 (3 x 10 mL).The combined organic layers were washed with brine (20 mL), dried (anhydrous MgSO4) and the organic solvents were removed under reduced pressure.The residue was adsorbed on Celite® and purified by flash chromatography on silica gel (nhexane/Me2CO, 15:1) and after crystallization from hexane/Me2CO, compound 1a (107 mg, 31%) was isolated as an orange fluorescent solid, mp 118 °C, Rf (n-hexane/EtOAc, = 0.38. General procedure (GP) for the pseudo five-component synthesis of merocyanine dimers 8.In an oven-dried Schlenk tube with magnetic stir bar, Pd(PPh3)2Cl2 (7.0 mg, 10 mol, 2 mol%) and CuI (3.8 mg, 20 mol, 4 mol%) were placed under N2 and dry MeCN (3 mL) was added.Amide 4 (227 mg, 0.50 mmol) was added to the suspension, which dissolved at 50 °C (oil bath) after 4 min.After cooling to rt, alkyne 5 (0.55 mmol) and dry Et3N (52.9 mg, 0.52 mmol) were added to the reaction mixture, which turned from yellow to brown (for experimental details, see Table 2).Then the mixture was heated at 50 °C (oil bath) for 16-18 h.After cooling to rt, compound 7 (0.23 mmol) was added and the reaction mixture turned red.The reaction mixture was stirred at 80 °C (oil bath) for 22-24 h and the product precipitated from solution.After cooling to rt, CH2Cl2 (20 mL) was added and the organic phase was extracted with saturated aq NH4Cl solution (15 mL).The aq layer was extracted with CH2Cl2 (3 x 10 mL).The combined organic layers were washed with brine (20 mL), dried (anhydrous MgSO4) and the organic solvents were removed under reduced pressure.The residue was adsorbed on Celite® and purified by flash chromatography on silica gel (n-hexane/Me2CO).For removing solvent inclusions, the purified products were dissolved in a minimum of CH2Cl2, n-hexane was added to the solution for precipitation and placed in the ultrasound bath for 10 min.After decantation the residual solvents were removed under reduced pressure and the pure products 8 were obtained as orange to red solids.

Figure 6 .
Figure 6.Amorphous powders of merocyanine 1a and homo-bichromophore 8d on a microscope slide under daylight (top) and under UV light upon excitation with a handheld UV-lamp (exc = 365 nm) (bottom).

Table 2 .
Experimental details of the pseudo-five-component synthesis of merocyanine dimers 8 The two methylene groups adjacent to the amino nitrogen atom coalesce; at 323 K two broad signals at  3.16and 4.32 form, at 263 K the methylene protons resolve into four diastereotopic signals at  2.82 and 3.42, and  4.08 and 4.72.The two methylene groups of adjacent to the amino nitrogen atom coalesce; at 323 K two broad signals at  3.15 and 4.28 form, at 263 K the methylene protons resolve into four diastereotopic signals at  2.84 and 3.46, and  4.04 and 4.78.Corresponds to [M] + calcd.m/z = 1254.5363.The two methylene groups of adjacent to the amino nitrogen atom coalesce; at 323 K two broad signals at  3.16 and 4.44 form, at 263 K the methylene protons resolve into four diastereotopic signals at  2.88 and 3.44, and  4.10 and 4.77.The two methylene groups of adjacent to the amino nitrogen atom coalesce; at 323 K two broad signals at  3.23 and 4.32 form, at 263 K the methylene protons resolve into four diastereotopic signals at  2.90 and 3.55, and  4.04 and 4.60.