Synthesis , Characterization , and Application of Poly ( N , N-dibromo-N-ethylnaphthyl-2 , 7-disulfonamide ) as an Efficient Reagent for the Synthesis of 2-Arylbenzimidazole and 2-Aryl-1-arylmethyl-1 H-1 , 3-benzimidazole Derivatives

The condensation of O-phenylenediamine (OPD) with aryl aldehydes is carried out in acetonitrile using poly(N,N-dibromoN-ethylnaphthyl-2,7-disulfonamide) (PBNS) as a novel and heterogeneous catalyst. PBNS has some potential advantages which include ease of separation from the reactionmixture by simple filtration, easy preparation, recoverablility, convenience, and stability under normal condition and also is not dangerous as molecular bromine.


Introduction
Polymeric reagents are referred to as the reactive species which are tied or fastened to a polymeric backbone.These reagents have both the physical characteristics of the high polymer and the chemical characteristics of the attached reagent function.Their ease of separation from the reaction mixture and recovery are the most potential advantages of these reagents [1].Because of its poisonous nature and destroying qualities, molecular bromine in preparative chemistry can be considered as a main reason for worry and anxiety [2].Therefore, N-bromo reagents such as N-bromosuccinimide [3], N,N  -dibromo-N,N  -1,2ethanediylbis (benzene sulfonamide) [4], and 1,3-dibromo-5,5-dimethylhydantoin [5] have found widespread applications in organic reactions via in situ generation of Br + .N-Bromo compounds are inexpensive and nonhazardous reagents and also they are widely applicable in industrial processes for the synthesis of drugs, pharmaceuticals, and agrochemicals [6].In this presented work, we synthesize the novel polymer, namely, poly(N,N  -dibromo-N-ethylnaphthyl-2,7disulfonamide) (PBNS).The advantages of PBNS are as follows: (I) the preparation of PBNS is easy and convenient, (II) PBNS is inexpensive and nonhazardous reagent, (III) PBNS is stable for several months under normal condition, and (IV) after the reaction of PBNS with substrate, the polysulfonamide can be recycled and reused four times without decreasing the yield.
In recent years, preparation of benzimidazoles has been an interesting subject.Benzimidazole and its derivatives have been used as the antiulcerative esomeprazole [7,8] and in diverse human therapeutic areas as an antiulcer and antihistaminic [9].The condensation of an arylene diamine with a carboxylic acid or its derivative under harsh dehydrating reaction conditions is the most popular synthesis of these materials [10,11].Another method for synthesis of this compound is the condensation of arylene diamine with an aldehyde [11,12].Herein, in this work we have reported PBNS as a novel, heterogeneous, and reusable catalyst for the condensation of O-phenylenediamine (OPD) with aryl aldehydes to give corresponding 2-arylbenzimidazoles and 2aryl-1-arylmethyl-1H-1,3-benzimidazoles.

Experimental Sections
2.1.General Information.All chemicals were obtained commercially from Aldrich and/or Merck companies that were used without further purification.Melting points were measured on a SMPI apparatus. 1H and 13 C NMR spectra were recorded in DMSO-d 6 or CDCl 3 solvent on a Joel 90 MHz or a Bruker 400 spectrometer.Infrared measurements were performed on a PerkinElmer spectrometer.Molecular weight distribution (polydispersity index, PDI = Mw Mn −1 ) and number and weight average molecular weights (M  and M  ) of the poly(N-ethylnaphthyl-2,7-disulfonamide) were determined by GPC (gel permeation chromatography) measurements on a 150 Waters GPC system (mobile phase: THF, flow: 1.0 mL min −1 , and column temperature: 30 ∘ C) [13].The TGA thermograms of the poly(N-ethylnaphthyl-2,7-disulfonamide) and PBNS were obtained in nitrogen atmosphere, flow (200 mL min −1 ) ramping at a heating rate of 5.00 ∘ C min −1 , in the range 30-950 ∘ C.

Synthesis of Poly(N-ethylnaphthyl-2,7-disulfonamide).
Naphthalene-2,7-disulfonyl chloride (4.88 g, 15 mmol) was dissolved in CHCl 3 (25 mL).Excess of ethylenediamine (2 mL, 17 mmol) was added dropwise and the mixture was stirred at room temperature until the white precipitated solid appeared.The compound was then filtered and washed off with CHCl 3 and water.The product was dried in reduced pressure to afford white powder (85% yields).IR (KBr, cm

Synthesis of PBNS.
Poly(N-ethylnaphthyl-2,7-disulfonamide) (1.0 g) was dissolved in 2 mL NaOH 3 M.This solution was added to a flask equipped with magnetic stirrer.A solution of molecular bromine (2 mL, 58.4 mmol) was added to the previous mixture at 0 ∘ C. The orange precipitate was formed immediately.The functionalized polymer was separated by filtration, washed several times with cold distilled water (3 × 10 mL), and dried under reduced pressure (75% yields).PBNS was characterized by IR, 1 H NMR, 13 C NMR, and TGA analysis.

Determination of the PBNS Capacity by Iodometric
Method.The capacity of the polymeric reagent was determined by iodometric method [14].The PBNS suspension was prepared by stirring 100 mg of it in 20 mL of water for 12 h.Therefore, 10 mL of potassium iodide (10% w/v) and 10 mL sulfuric acid (10% w/v) were mixed with the suspension.The standard thiosulfate solution was used to titre liberated iodine with the starch as the indicator.The amount of available bromonium ion (Br + ) per gram in the polymer sample was achieved from the amount of titrant.The average capacity was measured as 5.5 mmol of bromonium ion (Br + ) per gram of PBNS reagent.

General
Procedure for the Synthesis of 2-Arylbenzimidazole Derivatives.PBNS (0.15 g) or 0.83 mmol of N-Br was added to a mixture of OPD (1 mmol) and aldehyde derivatives (1 mmol) in acetonitrile (10 mL).The mixture was stirred at room temperature for an appropriate time (Table 1).After disappearance of the reactant, monitored by TLC (7 : 3 nhexane : acetone), the solvent was evaporated.Then CH 2 Cl 2 (10 mL) was added to the residual solid mixture and stirred for 10 min.The mixture was filtered.The solvent was removed under reduced pressure to give the corresponding products in 70-90% yields.Further purification was carried out by the crystallization in ethanol 96% to afford crystalline products.

General Procedure for the Synthesis of 2-Aryl-1-arylmethyl-1H-1,3-benzimidazole Derivatives.
A mixture of OPD (1 mmol), aldehyde derivatives (2 mmol), and PBNS (0.055 g) or 0.304 mmol of N-Br in acetonitrile (10 mL) was placed in 50.0 mL single neck round-bottomed flask equipped with a magnetic stirrer.The reaction mixture was refluxed and stirred for the specific times (Table 2).The progress of the reaction was monitored by TLC (7 : 5 n-hexane : acetone).After completion of the reaction, monitored by TLC, solvent in the reaction mixture was evaporated and dichloromethane (10 mL) was added to the mixture; then, it was separated by the filtration.CH 2 Cl 2 was removed by reduced pressure to give corresponding benzimidazole compounds in 89-96% yields, which were recrystallized from hot water-ethanol (1 : 1).

Results and Discussion
In continuation of our studies on application of N-halo compounds in organic synthesis [3][4][5]21] and also to explore new approaches toward the heterocyclic compounds, we have used an efficient protocol for the preparation of benzimidazoles catalyzed by PBNS as a novel reagent (Scheme 1).PBNS was synthesized by covalent attachment of poly(Nethylnaphthyl-2,7-disulfonamide) and molecular bromine (Scheme 2).
The molecular weight and polydispersity of the poly(Nethylnaphthyl-2,7-disulfonamide) were 108107 gmol −1 and 2.683, respectively.In the IR spectrum of this polymer and PBNS peaks due to the asymmetric and symmetric S=O stretching bands appeared at 1157, 1323, 1159, and 1324 cm −1 , respectively.In the poly(N-ethylnaphthyl-2,7-disulfonamide) N-H bound was observed at 3167 cm −1 .It was considerable that bonds corresponding to N-H in poly(N-ethylnaphthyl-2,7-disulfonamide) did not disappear in PBNS entirely.Therefore, the bond corresponding to the amino groups appeared at 3277 cm −1 (weak) (Figure 1).In 1 H NMR spectrum of poly(N-ethylnaphthyl-2,7disulfonamide), broad peaks at 7.7, 8.6, and 1.96-3.11ppm were related to the aromatic protons and methylene groups, respectively.The chemical shift of NH also appeared at 5.71 ppm (Figure 2(a)).In 13 C NMR spectrum of this polymer, signals at 139.64, 123.71, and 44.31-39.31ppm were related to the aromatic C=C and methylene group, respectively (Figure 2(b)).In the 1 H NMR spectrum of the PBNS peaks related to aromatic protons were observed at 7-9 ppm and the corresponding peaks related to methylene protons appeared between 2.5 and 4.5 ppm (Figure 2(c)).In 13 C NMR spectrum, peaks for the aromatic carbons appeared between 139.56 and 123.68 ppm and signals for the methylene groups were recorded between 42.88 and 39.32 ppm (Figure 2(d)).
In this paper, we have developed synthesis of 2arylbenzimidazoles and 1,2-disubstituted benzimidazoles by treating OPD with aryl aldehydes in the presence of PBNS.Under the optimized reaction condition, in the absence of PBNS, the synthesis of benzimidazoles did not proceed.The results clearly confirmed that PBNS played an important role in the synthesis of benzimidazoles and therefore the reaction rate and yields were increased.PBNS was used under the heterogeneous condition and could be separated from the reaction mixture by simple filtration.As it is shown in Scheme 3, by the reaction of 1 mmol substituted aldehydes with OPD at room temperature, 3 was produced and, in the reflux condition, 2 mmol of the substituted aldehydes was   reacted with OPD in the presence of the catalyst to produce 4.All of the products were isolated in high yields (75-96%) and confirmed by 1 H NMR and IR spectroscopy.The results are summarized in Tables 1 and 2. First, we compared the application of the catalyst in the different solvents for the synthesis of benzimidazoles.Among some solvents such as N,N-dimethylformamide (DMF), dichloromethane, acetone, n-hexane, and acetonitrile, acetonitrile was the best.Also, the results clearly indicated that 0.055 g or 0.304 mmol of N-Br of the PBNS for 2arylbenzimidazoles and 0.15 g or 0.83 mmol of N-Br of the PBNS for 2-disubstituted benzimidazoles were sufficient to catalyze the reaction.
As it is shown in Table 1, aryl aldehydes without substituent gave the desired benzimidazole in excellent yield (Table 1, entry 1) and aryl aldehydes with electronwithdrawing substituents were given the corresponding benzimidazoles in short reaction times and gave high to excellent yields (Table 1, entries 6-7).On the other hand, electronwithdrawing substituents on the aryl aldehydes did not do any noticeable changes in the reaction.
From the results summary in Table 2, it can be concluded that the absence of substituent on the aromatic ring may be responsible for the synthesis of 1,2-disubstituted benzimidazoles in shorter time and the highest yield (90%) (Table 2, entry 1).Aryl aldehydes with electron-withdrawing substituents (Table 2, entries 2-5) were given the corresponding 1,2-disubstituted benzimidazoles in good yields.The results clearly indicated that aryl aldehydes with electronwithdrawing substituents reacted quickly and in short reaction times in comparison with aryl aldehydes bearing electron-donating substituents (Table 2, entries 6).
Recyclability of the reagent was also studied in the synthesis of 2-arylbenzimidazoles and 1,2-disubstituted benzimidazoles by the reaction of aryl aldehydes and OPD.After completion of the reaction at the first run, acetonitrile was added to the mixture, stirred for 2 min to solve the product, and then filtered.The precipitated polymer was washed with CH 2 Cl 2 to solve the probabilistic residuals of reactants as well and dried to give polysulfonamide.The regeneration of PBNS from poly(N-ethylnaphthyl-2,7disulfonamide) was performed according to the method  mentioned at Section 2.3.The PBNS was reused for similar reaction.This process was repeated for four runs.Table 3 shows the results of this recyclability.Per run, the products 2arylbenzimidazoles and/or 1,2-disubstituted benzimidazoles were prepared without reducing the yield.The bromine atoms of PBNS are attached to nitrogen atoms of the polymer molecule.It is possible that Br + is to be released in situ condition from this catalyst.In this case, it can act as an oxidant in the reaction media.For the synthesis of 2-arylbenzimidazoles in the presence of PBNS, we suggest a mechanism for these reactions as follows [22].This proposed mechanism is shown in Scheme 4. In a plausible mechanism that is shown in Scheme 5, reaction mechanism for the condensation of OPD with aryl aldehydes in the presence of PBNS as catalyst to prepare 1,2-disubstituted benzimidazoles is proposed on the basis of the production of Br + .Probably the responsibility for generation of Br + ion causes activation of the aldehyde in this reaction.Condensation of aldehydes with OPD generates an intermediate in the first step.In the first condensation step that provides the intermediate reaction, the Br + ion is most likely involved as a more strong Lewis acid [23].Since Bronsted acid (HBr) or hydrogen bonding donor (-SO 2 NH-) is capable of performing condensation at the continuing our research, the reaction using poly(N-ethylnaphthyl-2,7-disulfonamide) instead of PBNS was investigated.Since in the presence of poly(N-ethylnaphthyl-2,7-disulfonamide) reaction failed, the hydrogen bonding donor (-SO 2 NH-) in the polymer is not so strong that it can perform the condensation reaction.Thus, since the reaction was not performed in the presence of the polymer, it can be concluded that bromonium ion (Br + ) is required for the reaction.

Conclusions
In summary, this work describes an efficient method for the synthesis of benzimidazole derivatives utilizing PBNS.The reactions proceed selectively under mild condition at room temperature or in the reflux condition in the presence of acetonitrile as a solvent to afford the corresponding 2arylbenzimidazoles and 2-aryl-1-arylmethyl-1H-1,3-benzimidazoles, respectively, in high to excellent yields.Finally, heterogeneous conditions, convenient method for workup, recoverability, and ease of the preparation of the catalyst are some advantages of this method.

Table 1 :
Synthesis of 2-arylbenzimidazoles in the presence of PBNS.
a All products were identified by their IR and 1 H NMR spectra.b Isolated yields.

Table 2 :
Synthesis of 1,2-disubstituted benzimidazoles in the presence of PBNS.All products were identified by their IR and 1 H NMR spectra.
a b Isolated yields.