Betaines of pyridinium benzimidazolate containing polymethylene interannular spacers

We report the first synthesis and relevant structural aspects of some simple examples of the betaines 5 - 7 and their immediate precursors 8 - 10 . Inner salts 5b , 6b and 7b were isolated, whereas compounds 5a , 6a and 7a were transformed to dihydropyridine derivatives. Their liquid-crystal behavior was examined and for benzimidazolyl pyridinium bromide 8a the second-order hyperpolarizability ( β ) was measured.


Introduction
The betaine pool comprises a vast array of highly dipolar chemical entities with a low molecular weight, and their properties depend on their dipolar nature.This ensemble of compounds offers the possibility of the coexistence of two terminal rings joined through different spacers with opposite characteristics within heteroaromatic systems: a π-deficient nucleus (cation, an acceptor group) and a π-excessive nucleus (anion, donor group). 1,2he study of azolium(pyridinium) azolate inner salts with a variety of spacers 1 together with their protonated counterparts 2, has been part of our research in the field, dealing with their synthesis, structure, reactivity and applications within heterocyclic advanced materials and supramolecular chemistry. 2,3RKAT USA, Inc.Initially, we focused our attention on the pyridinium azolate 3 4a inner salts with a C-N' direct bond together with molecules with a betaine character with a C-C' direct bond 4; 4b subsequently, we extended our study to their heterocyclic betaine homologues with different spacers. 2 Among these, we have focused our attention on the pyridinium benzimidazolate inner salts with an ethylene linker 5, together with pyridinium benzimidazolate betaines 6 and 7 with a pentamethylene and undecamethylene spacer, respectively.The dipolar nature of these compounds together with flexible interannular chains provides potential switch behavior, according to whether the medium is acidic or basic.On the other hand, related systems with pyridinium nuclei have demonstrated their application as new materials in liquid crystals 5a,b and in second and quadratic-order nonlinear optics materials (NLO).5c-e In the present paper, we report the first synthesis and relevant structural aspects of some examples of the betaines 5-7 and their key precursors 8-10.
Alternatively, a versatile procedure to access a range of benzimidazolylpyridinium salts with an ethylidene linker was studied and the pyridinium salts 8a,b were obtained from 4pyridylacrylic acid 11 in three steeps (Scheme 1).Alkylation of pyridine 11 with 1-iododecane yields pyridinium salt 14 that was reduced with Pd-C 10% at 120 psi to propionic acid 15.In parallel, benzimidazolylpyridinium salts 9a,b and 10a,b were prepared in a two-step protocol as shown in Scheme 2. Quaternization of pyridine was carried out with bromoalkyl acid 17-18 to obtain pyridinium derivatives 19-20, which were then efficiently transformed into targeted salts 9a,b and 10a,b by reaction with phenylenediamine 16a,b by Hein's modified benzimidazole synthesis. 6ransformation of the aforementioned pyridinium salts 8b, 9b and 10b into the corresponding inner salts 5b, 6b and 7b was carried out exploiting our standard protocol, [1][2][3][4] by the use of the anion-exchange Amberlite IRA-401 resin (OH -form).

Scheme 3
Nevertheless, pyridinium benzimidazolate betaines 5a, 6a and 7a were not isolated when the same procedure was used with benzimidazolylpyridinium salts 8a, 9a and 10a (see Schemes 4  and 5).When a solution of pyridinium cations was treated with an anion-exchange resin (OH - form) an intense purple color appeared that turned pale when acid was added.Elimination of solvent under vacuum provided colored solid compounds.
In order to study this transformation, 1 H NMR spectra in DMSO-d 6 of 8a was registered, and then a drop of tetrabutylamonium hydroxide was added to the solution.Chemical shifts of the new spectrum indicated that 1,4-dihydropyridine 21 was formed in basic solution (See Figure 2), and decomposition compounds were formed in 24 hours at room temperature.If TFAA was added to the initial basic solution, pyridinum salt 8a was recovered.An 1 H NMR spectrum in DMSO-d 6 of solid compound obtained from fast treatment (less than 1 minute) with Amberlite IRA-401 resin (OH -form) showed that dihydropyridine 21 was the main component.
Probably, betaine 5a was obtained, but the strong basicity of benzimidazolate anion is enough to form stabilized 1,4-dihydropyridine derivative 21.It is known that in a strong basic medium, 4-alkylpyridinium salts react to give an inner salt that is stabilized in 1,4dihydropyridine form. 8n addition, experimental deuteration in CD 3 OD confirmed that betaine 5a had been obtained, since H was immediately exchanged for D in the methylene bound at position 4 of the pyridine ring.H/D exchange was also observed at positions 2 and 6 of the pyridinium ring.
Similarly, treatment of both pyridinium salts 9a and 10a with anion-exchange Amberlite IRA-401 resin (OH -form) afforded colored solid.Formation of decomposition or alteration compounds was observed in their 1 H NMR spectra in DMSO-d 6.Data obtained in CD 3 OD showed the fast exchange H/D in positions 2 an 6 of pyridinium ring.
ARKAT USA, Inc.Thus, these results proved the high basicity of 5,6-dimethylbenzimidazolate in comparison with 5-nitrobenzimidazolate.Their basic character had been shown when N-benzimidazolylethylpyridinium salts were treated with an anion-exchange resin (OH -form).All new compounds were characterized on the basis of their 1 H and 13 C NMR data whereas only the 1 H NMR parameters were available for the title inner salt 5b, and individual assignments were made using the appropriate NMR experiments (see Tables 2 and 3, and Figure 2).Table 2. Selected 1 H NMR spectroscopic data of (pyridinio)benzimidazolate 5-7b inner salts and (benzimidazolyl)pyridinium tetrafluoroborates 8-10a,b at 200 MHz    Thus, the chemical shifts of the CH protons in the benzimidazole ring in 5-7b moved to lower frequencies, especially H-7 and H-6 (see ∆δ H-4, H-6 and H-7 in Table 2), indicating the change of electron density on the π-excessive nucleus and the anionic nature of the title compounds, in agreement with data reported for anionic species within benzimidazole systems. 1 Furthermore, a shielding effect was observed for the methyl protons close to the benzimidazole ring.With regard to the π-deficient moiety of all compounds, the δH values correspond to quaternary pyridinium structures.
On the other hand, in dihydropyridine derivative 21 signals corresponding to the pyridine ring were found upfield with respect to their precursor 8a together with CH 2 -N (see Figure 2).Moreover, the chemical shifts, multiplicity and integration changed in the ethylidene linker, according to the dihydropyridine structure.As mentioned, the structural characteristics of the compounds reported made them attractive from the advanced materials point of view.2c Some of these structures have an elongated geometry similar to ionic liquid crystals reported in the literature.5a,10 Likewise, the push-pull systems of the betaines and their immediate precursors are closely related to structures successfully studied in nonlinear optics which show high second order parameters (β and/or X (2) ).Their application in second-order nonlinear optic materials (NLO) has confirmed the value of these dipolar molecular structures and they manifest extremely large first hyperpolarisability in both theoretical 5a studies and experimental measurements.5e Pyridinium benzimidazolate inner salts 6-7b, and benzimidazolylpyridinium salts 8-10a,b were selected for a study of the mesogenic behavior.Surprisingly, none of them showed a clear liquid-crystal behavior.11a However, in order to study their properties in NLO, the second-order hyperpolarizability (β) of compound 8a revealed a value between 457 and 1441•10 -30 esu in chloroform, 11b depending on the concentration (Figure 3). 11The significance of self-association of these compounds were shown again 2 and high dilution is necessary to study their properties.In summary, new benzimidazolylpyridinium salts 8-10a,b were efficiently prepared and their transformation in basic media were studied.Inner salts 5-7b were isolated, whereas 5-7a evolved to dihydropyridine derivatives.Furthermore, the second-order hyperpolarizability (β) of compound 8a was measured, and promising values were obtained.The dipolar nature of these compounds together with a flexible interannular chain provides potential switch behavior, according to the acidic or basic media.TLC was performed on Merck precoated 60 F 254 silica gel plates in the solvent system methanol-ammonium chloride 2Mnitrometane (6:3:1) as developing solvent; and the spots were located with UV light and developed with a 10% aqueous solution of potassium iodide or 3% aqueous solution of hexachloroplatinic acid.Chromatography: neutral aluminum oxide 90 activity II-III (Merck).A standard protocol was applied for counteranion exchange using a strongly basic anion exchange resin (hydroxide form). 4When a rotary evaporator was used, the bath temperature was 25 °C.In general, the compounds were dried overnight at 25 °C in a vacuum oven.Microanalyses were performed on a Carlo Erba 1106 analyzer.

Method A. General procedure for the preparation of betaines (5-7b) (Table 1)
A solution of pyridinium salts 8b, 9b or 10b (ca.200 mg) in 96% ethanol (50mL) was passed through a column packed with a strongly basic anion exchange resin (Amberlite IRA 401, hydroxide form).The neutral eluates were evaporated to dryness and then the residue was triturated with diethylether (20 mL) to give the corresponding betaines 5b, 6b or 7b.

Figure 2 .
Figure 2. Selected chemical shift data of pyridinium salt 8a and dihydropyridine derivative 21.

Table 1 (
see Experimental Section), and all gave satisfactory elemental analysis.
9Pyridinium β-elimination was observed and vinylbenzimidazole was formed through the benzimidazolate intermediate.Physical data of benzimidazolylpyridinium salts 7-10a,b together with pyridinum benzimidazolate inner salts 5-7b are listed in

Table 1 .
Physical data of compounds 5

-7b and 8-10a,b
a See Experimental Section.b Yields were not optimized.c Satisfactory analytical data (±0.4% for C, H, N). d Oily compound.e Not analyzed.