Multi-step Redox Systems with NIR-Fluorescence Based on 4H-Imidazoles

A new class of 4H-imidazoles was synthesized starting from fused-ring aromatic dinitriles. Strong bathochromic shifts of the longest wavelength absorptions were observed in the corresponding UV/vis spectra due to a conversion of the merocyanine chromophores into cyanines/(aza)oxonoles upon protonation/deprotonation of the 4H-imidazoles. Novel boratetraazapentalenes were synthesized via a cyclization reaction with boron trifluoride. These mesoionic species bearing a cyanine chromophore not only show NIR-fluorescence, they also participate as part of a quasi-reversible multi-step redox system. Large calculated semiquinone formation constants KSEM (3x1010 to 5x1011) indicate a high thermodynamic stability of the corresponding radical anions (SEM).


Introduction
Over the last several years a great number of organic substances with extraordinary absorption, emission or electrochemical properties have been developed. In conjunction with materials science, many of these substances were employed in new materials such as displays, organic LED's or other, mostly electronic devices. Only a few organic systems combine all the desirable properties for all the mentioned application fields, thus making research on polyfunctional dyes very popular.
4H-Imidazoles 1 are well known for their long wavelength UV/vis absorptions and high extinction coefficients (log  ε > 4) [1]. As part of a two-electron redox system, the reduction of the deeply coloured 4H-imidazoles 1 (OX) leads to nearly colourless, fluorescent 1H-imidazoles 2 (RED) via radical-ion intermediates (SEM) (Scheme 1). Cyclization of derivatives 1 with boron compounds yields red fluorescent boratetraazapentalenes 3, which on the other hand may be regarded as electronpoor heterocycles. The radical anions of this new class of electrophores show unusual high K SEM values (up to 10 15 ) [2]. As part of a four-electron redox system, in which the radical state is replaced by more stable closed-shell moieties, bis-4H-imidazoles show almost identical properties as their monofunctional parent compounds [3]. Due to their long wavelength absorptions in the UV/vis spectra, correlated with high extinction coefficients, together with their interesting redox behaviour, 4H-imidazoles are promising candidates for the synthesis of functional dyes [4].
Therefore we sought to prepare 4H-imidazoles which are connected to other chromophores. The involvement of ring-fused aromatic systems such as anthracene or naphthalene, should lead to bathochromic shifts of the absorptions/emissions of the corresponding boratetraazapentalenes. Due to the switch between merocyanine and cyanine upon protonation of 4H-imidazoles, their application as acidochromic dyes also should be of interest.

Results and Discussion
As the starting material required for bis-4H-imidazoles, dinitriles of type 4 were synthesized via a condensation reaction of o-xylylenedicyanide with the corresponding 1,2-diketones in the presence of sodium ethoxide [5,6]. The naphthalene derivative 4d was obtained starting from 1,5-naphthalenediol [7,8]. All reported dinitriles are yellow-greenish fluorescent solids and, with the exception of derivative 4d, sparingly soluble in organic solvents. Reactions of the dinitriles 4 with lithium hexamethyldisilazide (LiHMDS) yielded the corresponding amidinates, which were converted into the persilylated amidines by heating with chlorotrimethylsilane under reflux. As depicted in Scheme 2, all attempts to interconvert both nitrile groups failed. This failure can be attributed to considerable delocalization of the negative charge over the aromatic system which significantly lowers the electrophilicity of the second cyano group. The observed decrease of reactivity is in accordance with the synthesis of a series of substituted aromatic amidines [9]. Unfortunately, the alternative Pinnersynthesis route was not successful, due to poor solubility of dinitriles 4 in ethanol.
The 4H-imidazoles of type 5 were synthesized by a deprotection-cyclization sequence using bisimidoylchlorides derived from oxalic acid in the presence of KF/18-crown-6-ether. The products 5 were purified by column chromatography of the reaction mixture in 15 up to 30% yield (Scheme 2).

Scheme 2.
Synthesis of 4H-imidazoles 5.  The newly synthesized 4H-imidazoles have essentially the same properties as the phenylsubstituted derivatives [1]. Their longest wavelength absorption in the UV/vis spectra is approximately 515 to 540 nm, with log(ε) values higher than 4.0; the infrared spectra show two characteristic bands at about 3400 cm -1 (NH-group) and 2220 cm -1 for the cyano-group. In the NMR spectra two doublets were detected between 7 and 8 ppm, which are characteristic for the aromatic protons of the arylamino/arylimino moieties.
Usually the cyanines 8 and the oxonoles 7 display bathochromic shifts of approximately 100 nm and 20 nm, respectively, with regards to the merocyanine 5 ( Figure 1). The isosbestic point in the UV/vis spectra during protonation or deprotonation of the 4H-imidazole 5c indicates a first order reaction ( Figure 2). Thus, 4H-imidazoles are well suited for the application as acidochromic dyes, especially in sensor systems.  The mesoionic boracycles 9 were obtained in about 50% yield by cyclization of 4H-imidazoles 5 with boron trifluoride diethyl ether complex in the presence of triethylamine. These deep blue reaction products were purified by column chromatography and identified by MS-, IR-, NMR-and UV/vis spectroscopy. Cyclic voltammetric measurements showed the quasi-reversibility of the reduction step. The very large calculated semiquinone formation constants K SEM (3x10 10 to 5x10 11 ) indicate a high thermodynamic stability of the radicalanions (SEM) ( Table 3). Compared with the phenylogous boracycles 3, the absorptions of 1,3,2-diazaborolidines 9 are shifted bathochromically (between 600 and 620nm). An unusually high stokes-shift of about 250 to 300 nm leads to the longest wavelength emissions in the area of NIR (Φ < 20%), exemplified by derivative 9d which is emitting at 870 nm ( Figure 3).

Conclusions
We have prepared the new 4H-imidazoles 5 and mesoionic 1,3,2-diazaborolidines 9, and have characterized them by elemental analysis, MS and NMR. Strong bathochromic shifts of the longest wavelength absorptions were observed in the corresponding UV/vis spectra due to a conversion of the merocyanine chromophores into cyanines/(aza)oxonoles upon protonation/deprotonation. The mesoionic boracycles 9 bearing a cyanine chromophore not only show NIR-fluorescence with an unusually high Stokes-shift, but they also participate as part of a quasi-reversible multi-step redox system. Large calculated semiquinone formation constants indicate a high thermodynamic stability of the corresponding radical anions. Thus, derivatives of 4H-imidazole are well suited for the applications in the functional dyes field.

General
All reactions were monitored by TLC, carried out on 0.25 mm Merck silica gel plates (60F 254 ) using UV light for visualization. 1 H-and 13 C-NMR spectra were recorded with a Bruker DRX 400 or Bruker AC 250 spectrometer. Melting points are measured with a Galen TM 3 apparatus and are uncorrected. UV/vis spectra were recorded on a Perkin-Elmer Lambda 19 spectrophotometer. MS spectra were taken from measurements on a Finnigan MAT SAQ 710 mass spectrometer. Elemental analyses were carried out in-house with an automatic analyzer LECO CHNS 932. Electrochemical measurements were carried out in dichloromethane with a Metrohm 663VA Stand using mercury or platinum electrodes (reference electrode SCE) and tetrabutylammonium hexafluorophosphate as conductive salt. The fluorescence spectra were recorded with a JASCO P-6500 instrument. Dinitriles 4a, 4b [5], 4c [6] and 4d [7,8] were prepared according to the published literature procedures. General procedure for the synthesis of 4H-imidazoles 5: Dinitrile 4 (1 mmol) was dissolved or suspended in dry THF (25 mL). After the addition of 1.0M Li-HMDS solution in THF or n-hexane (5 mL, 5 mmol), the reaction mixture was stirred at room temperature for 4 days and then evaporated to dryness in vacuo. The residue was dissolved in dry toluene (20 mL) and of chlorotrimethylsilane (0.75 mL, 6.0 mmol) was added. The reaction mixture was heated to 110 °C for 12 h and then the solvent was removed in vacuo. The silylated amidine was dissolved in dry THF (20 mL) and cyclized by addition of KF (0.35 g, 6.0 mmol), 18-crown-6-ether (1.58 g, 6.0 mmol) and the appropriate bis-imidoylchloride (1.5 mmol; Ar = 4-tol, 4-n-C 4 H 9 -C 6 H 4 -, 4t-C 4 H 9 -C 6 H 4 - [11]), whereby the colour changed from yellow to deep red. The mixture was stirred for 3-4 hours at about 40 to 50 °C to ensure completion of the reaction. The 4H-imidazoles 5 were obtained by filtration and column chromatography of the crude product (SiO 2 , toluene/acetone 50:1).   Boratetraazapentalenes 9 were prepared according to literature [2].