Synthesis of Benzimidazoles by Phosphine‐Mediated Reductive Cyclisation of ortho‐Nitro‐anilides

Abstract

Heating ortho‐nitro‐anilides 1–3 and 2‐methyl‐N‐(3‐nitropyridin‐2‐yl)propanamide (5) with 4 equiv. of a phosphine led to the 2‐substituted benzimidazoles 6–8 and to the imidazo[4,5‐b]pyridine 10, respectively, in yields between 45 and 85%. Heating 1 with (EtO)3P effected cyclisation and N‐ethylation, leading to the 1‐ethylbenzimidazole 6b. The slow cyclisation of the N‐pivaloylnitroaniline 2b allowed isolation of the intermediate phosphine imide 11 that slowly transformed into the 1H‐benzimidazole 7b. The structure of 11 was established by crystal‐structure analysis. While the N‐methylated ortho‐nitroacetanilide 3 cyclised to the 1,2‐dimethyl‐1H‐benzimidazole (8), the 2‐methylpropananilide 4 was transformed into 1‐methyl‐3‐(1‐methylethyl)‐2H‐benzimidazol‐2‐one (9).

Revealing the unusual role of bases in activation/deactivation of catalytic systems: O–NHC coupling in M/NHC catalysis

“…The physical and spectral characteristics of the product obtained are identical to those described in the literature. 38 …”

Pd‐Catalyzed Reductive Carbonylation‐Ring Closure of Aryl Halides: A Direct Approach for Synthesis of Benzimidazoles

“…However, in case of o-nitroaniline, the presence of different reducing agents in the reaction mixture such as Fe(CO) 5 , released CO, Pd(0) and also P(III) are responsible for the reduction of nitro group to the intermediate V which is in accordance with literature. [16,18,21] After that, the ring closure of this intermediate takes place to produce species (VI). In the presence of the produced iron oxides form Fe(CO) 5 , dehydrogenation of species (VI) takes place to deliver the desired benzimidazole.…”

“…[18] There are also few reports in the literature using substrates bearing -NO 2 functional group for benzimidazole formation in which reduction of the nitro group takes place under variety of catalytic systems such as selenium under basic conditions, [19] Ru 3 (CO) 12 , [20] and phosphines or phosphites (Ph 3 P, DPPE, P(OEt) 3 ). [21] Due to the probability of reduction of the -NO 2 group in the presence of Fe(CO) 5 and also investigating the diversity of nucleophiles for benzimidazole formation, we turned our attention to use o-nitroaniline instead of o-diaminobenzene as the nucleophilc partner toward the in situ generated aryl aldehydes. To find suitable conditions for promoting the Pd-catalyzed benzimidazole formation in the presence of o-nitroaniline, we performed the reaction of o-nitroaniline (1.5 mmol) and iodobenzene (1 a) (1.0 mmol) in the presence of PdCl 2 (5.0 mol%) and Fe(CO) 5 (1.2 mmol) in DMF at 110 8C under atmosphere of Ar for 24 h. Astonishingly, the desired benzimidazole (2 a) was obtained in 50 % yield along with the moderate amount of unreacted benzaldehyde and o-nitroaniline (Table 2, entry 1).…”

Folding Patterns in a Family of Oligoamide Foldamers

“…The solution was stirred at room temperature for 8h and concentrated in vacuo. The residue was purified by flash chromatography (hexane/EtOAc 8:2) to afford the nitro-amide 12 e. Procedure B: [21] Similar to procedure A, but am ixture of dichloromethane and pyridine (1:1) was used as as olvent, 4-dimethylaminopyridine (DMAP) was used (5 mol %) instead of Et 3 N, and the reaction was carried out at 0 8Cf or 2h,a llowed to warm to room temperature, and stirred for 4hat room temperature. The solution was washed with 1 m HCl (4 50mL), saturated NaHCO 3 (50 mL), and brine (50 mL) and dried over Na 2 SO 4 ,f iltered, and concentrated in vacuo.…”

“…[19] General procedure for the nitro-amide preparation:T hree different reported procedures were used. [20][21][22] Procedure A: [20] Et 3 N (130 mol %) was added to as tirred solution of ortho-nitroaniline (11)i nT HF at room temperature. Acyl chloride 9 was added dropwise through ad ropping funnel.…”