The Preparation of 2-Methyl-1-phenylbenzimidazole 3-Oxide

Fluorescent 6‐hydroxy‐ and 6,7‐dihydroxy‐4‐trifluoro‐methylcarbostyrils and formation of o‐carboxymethylated derivatives via o‐succinimide esters

“…We started the synthesis of N-alkylcarbostyrils 5a,b from dimethoxyanilines 4a,b, which were obtained from 166 G. Uray, N. S. Badgujar, S. Ková ková and W. Stadlbauer Vol 45 the commercially available 4-aminoveratrol 1 by a selective monoalkylation with the corresponding orthoformates 2 via a Chapman rearrangement [6]. In the first reaction step the formamides 3 were obtained, which gave on acidic hydrolysis N-alkyl-3,4-dimethoxyanilines 4 in good yields.…”

Product Class 4: Benzimidazoles

“…Typically, a 1-(acylamino)-or 1-(aroylamino)-2-aminoarene 31 is cyclized either by uncatalyzed thermolysis [192,193] or by treatment with aqueous or ethanolic acid [194] or phosphoryl chloride. [195] Hydrochloric, sulfuric, and phosphoric acids have been used successfully, but yields can vary considerably.…”

“…2-Methyl-1-phenyl-1H-benzimidazole (32, R 1 = Ph; R 2 = Me; R 5 = H): [193] A soln of N 1 -acetyl-N 2 -phenyl-1,2-phenylenediamine (2.26 g, 10 mmol) in dry xylene (10 mL) was heated for 16 h under reflux. Removal of the solvent in vacuo gave a yellow oil which was crystallized (benzene/hexane) as pale tan crystals; yield: 1.36 g (65%); mp 70.5±72.5 8C.…”

“…The organic extracts were dried (Na 2 SO 4 ), filtered, and the filtrate was evaporated in vacuo to give a residue, which was chromatographed (alumina, CHCl 3 ). [193] Methods of this type are especially recommended for making 1,2-disubstituted benzimidazole 3-oxides, and for the cyclization of 2-nitroanilides in which there is an electron-withdrawing group on the carbonyl group (e.g., 37, R 1 = H; R 2 = CF 3 ). [8,202,203] Scheme 24 Reductive Cyclization of N-Acyl-2-nitroanilines [8,202,203] Methods that involve catalytic hydrogenation in acidic medium have largely superseded earlier reductive processes.…”

“…Either or both of the arylamine and acyl moieties can be varied to give different products. [204,211] Scheme 25 Benzimidazole N-Oxides Made from N-Acyl-2-nitroanilines [193,204,208] [204] Me Me H 2 , Pd/C 84 [208] Ph Me H 2 , PtO 2 69 a [193] a Hydrochloride salt. By judicious choice of substrate substituents (i.e., R 1 and R 2 ), 1-and 2-substituted, and 1,2-disubstituted benzimidazoles can be made.…”