The synthesis of hydrophobic 1-alkyl-1H,1′H-2,2′-bibenzo[d]imidazoles

Introduction

New, selective extractants have been designed for recovery of metals from primary and secondary raw materials in hydrometallurgical processes. Owing to the presence of four nitrogen atoms in 1H,1′H-2,2′-bibenzo[d]imidazole (1), this compound can form various types of complexes with d-electron metal ions [1–4]. The limited solubility of 1H,1′H-2,2′-bibenzo[d]imidazole (1) in commercial hydrocarbon solvents makes it impractical to use the compound as an extractant. The introduction of hydrophobic substituents into the molecule of compound 1 increases solubility and enables the use of such derivatives in the extraction stage in technological processes. Our previous studies have shown that the complexing and extracting abilities of hydrophobic derivatives of 1H,1′H-2,2′-bibenzo[d]imidazole (1) and other heterocyclic compounds (e.g. hydrophobic amides and esters of pyridinecarboxylic acids) depend on the structure, position, and number of substituents in aromatic rings. To accurately investigate the usefulness of monoalkyl- (3) and dialkyl-1H,1′H-2,2′-bibenzo[d]imidazoles (4) in the extraction processes, it is necessary to obtain pure compounds with well-defined structures. There are some reports in the literature describing only disubstituted derivatives of 1 as the extractants of metal ions [5]. ACORGA ZNX 50, a reagent with a bis(alkoxycarbonyl) substitution of 1H,1′H-2,2′-bibenzo[d]imidazole (1) was proposed previously as a selective extractant for zinc(II) over iron(III) from chloride solutions [6, 7].

The objective of our work was the synthesis of 1-alkyl-1H,1′H-2,2′-bibenzo[d]imidazoles 3. Alkylation of disodium 2,2′-bibenzo[d]imidazole-1,1′-diide (2a) turned out to be a good method to obtain the desired compounds 3. To the best of our knowledge, this is the first work that shows how to obtain hydrophobic mono-substituted compounds 3. The literature describes alkylation of 1H,1′H-2,2′-bibenzo[d]imidazole (1) conducted in the presence of a base. Alkyl halides with highly hydrophobic (octadecyl) and less hydrophobic (methyl, ethyl) groups have been used to obtain 1,1′-disubstituted derivatives of 1 [8–11]. Furthermore, the reaction of compound 1 with an alkyl dihalide has been used for the synthesis of 1,1′-bridged derivatives 1 [12, 13]. The disubstituted derivatives 4 have also been obtained from 1-alkylbenzimidazoles as substrates [14–17].

There are two reports describing the preparation of 1-methyl-1H,1′H-2,2′-bibenzo[d]imidazole. Fieselmann and co-workers have described the synthesis of this compound by alkylation of 1 with methyl iodide in the presence of sodium methoxide. The alkylation reaction was conducted in a glass pressure vessel heated at 95°C at the pressure of 4 atm giving a mixture of both 1-methyl-1H,1′H-2,2′-bibenzo[d]imidazole and 1,1′-dimethyl-1H,1′H-2,2′-bibenzo[d]imidazole [18]. The mono-methylated derivative has also been obtained by Nguyen and co-workers by an iron sulfide-catalyzed condensation between 2-aminonitrobenzenes and 2-methylbenzimidazoles [19]. Neither of the two methods has been used to prepare more hydrophobic 1-alkyl-1H,1′H-2,2′-bibenzo[d]imidazoles 3.

Results and discussion

1-Alkyl-1H,1′H-2,2′-bibenzo[d]imidazoles 3 were obtained from 1 in a two-step synthesis through the intermediary of product 2 (Scheme 1) that was generated by the reaction of 1 with sodium or potassium hydroxide. The analysis of the literature suggests that methanol is the most suitable solvent for the deprotonation reaction, and the next choices are dichloromethane, acetonitrile, or dimethylformamide (DMF) [20]. First reactions were attempted in methanol under reflux conditions. It was observed that an increase in the reaction time above 16 h (Table 1, entries 2, 3 and 8, 9) and an increase in the molar ratio of hydroxide to the substrate 1 from 2 to 4 (Table 1, entries 1–3 and 7–9, 4 and 10, 5 and 11) had no significant impact on the yield of salt 2. Slightly lower yields of 2 are observed in cases where potassium hydroxide is used instead of sodium hydroxide (Table 1, entries 4 and 5, 10 and 11). The yields in methanol are increased with increasing the temperature (Table 1, entries 2 and 4, 8 and 10). On the other hand, the superior solubility of compound 1 in DMF results in a reduced yield because isolation of salt 2a from the remaining starting material is difficult (Table 1, entry 6). Spectral analyses confirmed that crude salts 2a,b could be used for the subsequent alkylation reaction without further purification. The ¹H NMR spectra of sodium salt 2a and potassium salt 2b indicate the absence of a singlet at 13.5 ppm assigned to the N-H protons in substrate 1.

Scheme 1

Alkylation of salt 2 was carried out at the reflux temperature of the reaction mixture using DMF or methanol as a solvent. When DMF was used in the alkylation reaction, 1-alkyl derivative of 1 was obtained as the main product (Table 2, entry 2) and no formation of 1,1′-dialkyl derivative of 1 was observed. Molecular modeling was used to analyze the reaction outcome. The Becke-style three-parameter density functional theory (DFT) and the Lee-Yang-Parr correlation functional B3LYP/6-31G(d,p) basis set were used to optimize molecules and compare their stability. The planar conformer s-trans of 1H,1′H-2,2′-bibenzo[d]imidazole was found to be definitely more stable (at 11.6 kcal/mol) than the nonplanar s-cis conformer because of the steric hindrance of (N)H atoms, causing the system to lose its planarity and resonance. The calculations showed also that 1-methyl-substituted s-trans-1H,1′H-2,2′-bibenzo[d]imidazole is a planar molecule. However, benzimidazole moieties of s-trans conformer of 1,1′-dimethyl-1H,1′H-2,2′-bibenzo[d]imidazole are not positioned in the same plane (Figure 1). One can expect that, for the extensive substituents (isobutyl, octyl, and decyl), the stability of such structures without coupling will be limited. The effective resonance-stabilization of planar s-trans-1-alkyl-1H,1′H-2,2′-bibenzo[d]imidazole is the cause of its great stability that protects it against further substitution reaction.

Figure 1

B3LYP/6-31G(d,p) optimized structures of the s-trans conformers for 1-methyl-1H,1′H-2,2′-bibenzo[d]imidazole (A) and 1,1′-dimethyl-1H,1′H-2,2′-bibenzo[d]imidazole (B).

Increasing the molar ratio of the alkyl halide to sodium salt 2a from 2:1 to 4:1 significantly increases the yield of the formation of a monoalkyl derivative 3 (Table 2, entries 2–4, 8 and 9). On the other hand, increasing the reaction time enhances the formation of a dialkyl derivative 4, which makes the purification of the main products 3 difficult. It is important that byproduct 4 is formed in a yield of <5%.

Byproduct 4a, 1,1′-didecyl-1H,1′H-2,2′-bibenzo[d]imidazole, was isolated from the reaction mixture and its structure was confirmed by ¹H NMR, ¹³C NMR, and HRMS.

Conclusion

New 1-alkyl-1H,1′H-2,2′-bibenzo[d]imidazoles 3a–c were synthesized by alkylation of substrate 1. The alkylation does not produce a significant amount of disubstituted byproduct 4.

Experimental

Melting points were determined using a Boetius hot stage apparatus. The low- and high-resolution mass spectra were recorded on a Intectra Mass AMD 402 spectrometer with electron-impact ionization and 70 eV energy. The ¹H NMR and the ¹³C NMR spectra were measured on a Varian Gemini 400 spectrometer (400 and 100 MHz, respectively) in CDCl₃, using tetramethylsilane (TMS) as an internal standard. Elemental analysis was performed on a Vario EL III (Elementar) instrument. All reagents were of analytical grade. Reaction progress and purity of the compounds were monitored by thin layer chromatography (TLC) using aluminum plates coated with silica gel (E. Merck). Silica gel 60 (E. Merck 70–230 mesh) was used for flash chromatography. Synthesis of 1H,1′H-2,2′-bibenzo[d]imidazole (1) has been described in our previous work [21].