Greener synthesis using hydrogen peroxide in ethyl acetate of alicyclic ring-fused benzimidazoles and anti-tumour benzimidazolequinones

Incorporating Morpholine and Oxetane into Benzimidazolequinone Antitumor Agents: The Discovery of 1,4,6,9-Tetramethoxyphenazine from Hydrogen Peroxide and Hydroiodic Acid-Mediated Oxidative Cyclizations

“…14 1,8,9, [1,2-a]benzimidazole (5e) (0.224 g, 91%); brown oil; spectral data consistent with the literature. 14 [1,4]oxazino [4,3-a]benzimidazole (5a) (9 mg, 4%); Rf 0.35 (EtOAc). 7-Chloro-6,9-dimethoxy-3,4-dihydro-1H- [1,4]oxazino [4,3a] At the end of the reaction, the mixture was filtered, and the precipitate washed with water (30 mL) to give 6 (1.02 g, 34%) as an orange solid.…”

“…5,8-Dimethoxy-2,3-dihydro-1H-pyrrolo [1,2-a]benzimidazole (5d) (0.201 g, 92%); off-white solid; spectral data and melting point consistent with the literature. 14 General Procedure for the Synthesis of Quinones 1 and 2. Benzimidazole (0.26 mmol) and PIFA (0.447 g, 1.04 mmol) in H2O (29 mL) and MeOH (0.75 mL) were stirred at room temperature for 2 h. The mixture was extracted with CH2Cl2…”

Greener synthesis of chemical compounds and materials

“…Hybrid regioisomers of 2-(3,3 ' -diindolylmethylphenyl)-1 H -benzimidazole were obtained without catalysts and solvents under microwave treatment in short time (3–8 min) and with good yields, as a result of combination of several green chemistry principles. Also, important recent small molecules, prepared via greener processes, and comparative advantages of applications of greener methods for obtaining N- and O-containing compounds are as follows: a series of five, six, seven and eight-membered pyrrolo[1,2-a]benzimidazoles , prepared [67] using hydrogen peroxide in ethyl acetate from commercial o -(pyrrolidin-1-yl)anilines as precursors without further steps such as chromatography or organic-aqueous extraction;tetra-substituted pyrrole derivatives , synthesized with good yields (88–93%) in one step under ultrasound-assisted standard Knoevenagel condensation in water as a solvent and without catalyst followed by the reaction of Michael type [68];for 1,3,5-triazine, the use of silica supported Lewis acids (TiCl 4 , ZnCl 2 and AlEt 2 Cl supported on silica gel) under microwave conditions leads to tris-pyrazolyl-1,3,5-triazines , where triazine and pyrazole rings are connected with C–C bonds [69];synthesis of adipic acid from cyclohexene as precursor by oxidation with H 2 O 2 in a microemulsion system in the presence of stearyldimethylbenzylammonium chloride without N 2 O emissions (as in a conventional method), extreme reaction time, pressure, mixing and temperature, applying non-dangerous ultrafiltration instead evaporation;synthesis of soluble polyphenol via a simple formaldehyde-free route by direct oxidation of phenol by potassium ferricyanide in alkaline water; compared with classic routes, the use of dimethyl carbonate as an alternative reagent under solid/liquid phase conditions at 90°C for 5 h led to final products, methyl eugenol and veratraldehyde, in 95–96% yield, avoiding toxic compounds [70];higher-yield synthesis of propylene carbonate (PC) in solvent-free conditions by exothermic cycloaddition reaction of CO 2 and propylene oxide in a Parr high-pressure reactor using some heterogeneous catalysts (Ce–La–Zr–O) [71]; andsynthesis of hydroquinone by several steps (benzene-cumene-phenolhydroquinone) from petroleum-derived benzene as a precursor, using the Rh on Al 2 O 3 catalyst with 59% yield [72]. Other recently developed greener techniques deal with compounds such as poly(tannin-hexamethylendiamine), which can be used as an effective adsorbent for Cr(VI) [73], a lipophilic cantharidine-like model compound for pharmacological probe [74], thalidomide and some of its derivatives [75], 3,4-dihydropyrimidin-2(1H)-ones [76], biologically important spiro-2-oxindole derivatives [77], methyl nitroacetate [78].…”

One-Pot Synthesis of Dihalogenated Ring-Fused Benzimidazolequinones from 3,6-Dimethoxy-2-(cycloamino)anilines Using Hydrogen Peroxide and Hydrohalic Acid

“…9 Recently, methanesulfonic acid (0.5-1 equiv) has replaced TFA in H2O2mediated cyclizations to give alicyclic ring-fused benzimidazoles. 10 In comparison, the H2O2/HX system is relatively underutilized in the synthesis of heterocycles with H2O2/HBr used to catalyze the aziridination of alkenes with chloramine T. 11 One-pot H2O2/HXmediated oxidative cyclization of o-cyclic amine substituted anilines with selective dichlorination and dibromination gave a series of five to eight-membered ring-fused benzimidazoles, generally in >80% yield (Scheme 2a). 8…”