Mesoporous silica supported ytterbium as catalyst for synthesis of 1,2‐disubstituted benzimidazoles and 2‐substituted benzimidazoles

The benzimidazole ring is an important pharmacophore in contemporary drug discovery. Thus, effort to identifying new compounds containing benzimidazole scaffolds have gained much attention in recent years. In the present study, MCM‐41 type mesoporous silica with large pore (l‐MSN) supported ytterbium was successfully prepared by wet impregnation method. Among rare earth metal salts, ytterbium triflate has already been widely investigated as a catalyst in organic synthesis but less toxic ytterbium oxide has yet to be explored. Relatively high abundance and low cost of ytterbium with respect to many catalytically active metals (e.g. Pd, Au, Ru, Ir, Pt) offer an opportunity to develop sustainable catalysts for organic conversions. The catalyst has been characterized by various techniques including nitrogen adsorption, FT‐IR, TEM, SEM, EDX technique and elemental mapping. The obtained materials exhibit high surface area and a narrow distribution of mesoporosity. The catalytic performance of the Yb@l–MSNs was tested by synthesis of 1,2‐disubstituted benzimidazoles and 2‐substituted benzimidazoles through the coupling of aldehydes with o‐phenylenediamine. The catalyst resulted in excellent yields in short reaction times and the reaction showed tolerance toward both electron‐donating and electron‐withdrawing functional groups at room temperature. A particularly interesting finding was the solvent selectivity of this reaction; namely, 1,2‐disubstituted benzimidazoles generated as major product in water‐ethanol, while the 2‐substituted benzimidazoles was generated exclusively in non‐polar solvents like toluene.     

New route for preparation of nitrosubstituted 1,2‐phenylenediamines

4‐Nitrobenzoselenadiazole was methylated with dimethylsulphate to give corresponding 1‐N‐methyl‐4‐nitrobenzoselenadiazolium methylsulphate which after alkaline ring‐opening afforded 1‐N‐methyl‐3‐nitro‐1,2‐phenylenediamine in 90% yield. This compound was also prepared from 3‐nitro‐1,2‐phenylenediamine by monomethylation through tosylation, methylation and detosylation and was confirmed and characterised as 1‐methyl‐4‐nitrobenzimidazole. Methylation of 5‐nitrobenzoselenadiazole and subsequent alkaline ring‐opening led to unseparable mixture of both methylated products.     

Synthesis of benzimidazoles by copper‐catalyzed aerobic oxidative domino reaction of 1,2‐diaminoarenes and arylmethyl halides

Arylmethyl halides are readily synthesized via halogenation from the basic raw materials, even in green processes. They are used to replace their downstream products to prepare medicinally important 2‐aryl benzimidazoles. CuBr‐catalyzed synthesis of 2‐aryl benzimidazoles from arylmethyl halides and 1,2‐diaminoarenes via a one‐pot domino reaction is developed. This new synthetic method is simple, practical and cost saving, and tolerates wide functional groups. A mechanism of CuBr‐catalyzed aerobic oxidative domino reaction via a one‐pot four‐step process is proposed. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis of 2‐amino‐s‐triazino[1,2‐a]benzimidazoles as potential antifolates from 2‐guanidino‐ and 2‐guanidino‐5‐methylbenzimidazoles

The syntheses of 2‐amino‐s‐triazino[1,2‐a]benzimidazoles from 2‐guanidinobenzimidazoles were successfully carried out by a ring annelation reaction. The regiochemistry of the ring closure of 5‐methyl‐2‐guanidinobenzimidazole with diethyl azodicarboxylate, aldehydes, acetone, diethyl ethoxymethylenemalonate and orthoesters, leading to the formation of s‐triazine ring was studied. High regioselectivity was not observed in any of these reactions. However, the synthesis of s‐triazino[1,2‐a]benzimidazole system was found to be more regioselective than its 3,4‐dihydro analogue. NOESY experiment indicated that the compound, 2‐amino‐4,4‐dimethyl‐3,4‐dihydro‐s‐triazino[1,2‐a]benzimidazole existed predominantly as the 3,4‐dihydro tautomer in dimethyl sulfoxide. It was found to inhibit bovine dihydrofolate reductase with IC₅₀ 10.9 μM.     

Synthesis,characterization, and biological activity of phosphorylated/thiophosphorylated compounds of 2‐substituted benzimidazoles

A series of phosphorylated and thiophosphorylated compounds of 2‐substituted benzimidazoles have been synthesized by the reaction of POCl₃ and PSCl₃ with 2‐substituted benzimidazoles in different molar ratios. The compounds have been characterized by elemental analyses, infrared, and ¹H NMR and ³¹P NMR spectral studies. These compounds were found to be insecticidal when tested against Periplenata americana. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:154–157, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20385     

Synthesis of 5,15-diarylporphyrins via orthoesters condensation with aryldipyrromethanes

General access to 5,15-diarylporphyrins in two steps is described. Generalization of this approach to tetra-substituted porphyrins allows the reproducible preparation of compounds, in some cases with high yields for porphyrins, which can be used in photodynamic therapy (PDT) in cancer today.     

One‐Pot Synthesis of Pyrimido[1,2‐a]benzimidazoles under Solvent‐Free Conditions

A series of pyrimido[1,2‐a]benzimidazoles were obtained from aldehydes, 2‐aminobenzimidazole and ethyl acetoacetate in good‐to‐excellent yields by a simple, mild, and efficient procedure utilizing N,N,N′,N′‐tetrabromobenzene‐1,3‐disulfonamide (TBBDA) and poly(N‐bromo‐N‐ethylbenzene‐1,3‐disulfonamide) (PBBS) as catalysts.     

Synthesis of multi‐functionalized quinolines and 1,2‐dihydroquinolines through FeCl3‐mediated reactions of carbonyl compounds with 2‐vinylanilines

A facile and efficient approach toward the synthesis of functionalized quinolines and 1,2‐dihydroquinolines from carbonyl compounds and 2‐vinylanilines is described. The protocol utilizes the nonhazardous and less expensive FeCl₃ as catalyst with wide functional group tolerance and avoiding heavy metal impurities in the products.     

Synthesis of thiazole,oxazole and heterocyclic ring‐substituted 1,2‐dioxanes

The reactions of 4‐bromoacetyl‐3‐methoxy‐3‐methyl‐6,6‐diphenyl‐1,2‐dioxane with thioureas or thioamides gave 3‐methoxy‐3‐methyl‐6,6‐diphenyl‐4‐(4‐thiazolyl)‐1,2‐dioxanes in 63–90% yields. The similar reaction of 4‐bromoacetyl‐3‐methoxy‐3‐methyl‐6,6‐diphenyl‐1,2‐dioxane with acetamide gave 3‐methoxy‐3‐methyl‐4‐(2‐methyl‐4‐oxazolyl)‐6,6‐diphenyl‐1,2‐dioxane in 39% yields. The reactions of 4‐bromoacetyl‐3‐methoxy‐3‐methyl‐6,6‐diphenyl‐1,2‐dioxane with 3‐alkyl‐4‐amino‐5‐mercaptot[1,2,4]triazoles yielded 3‐methoxy‐3‐methyl‐6,6‐diphenyl‐4‐[3‐(5‐alkyl[1,2,4]triazolo[3,4‐b]‐2,3‐dihydro‐6H‐[1,3,4]thiadiazinyl)]‐1,2‐dioxanes in moderate yields (43–46%).     

Selective Synthesis of 2‐Aryl‐1‐benzylated‐1H‐benzimidazoles

An efficient and simple procedure was developed for the green synthesis of various 2‐aryl‐1‐ben‐zylated‐1H‐benzimidazoles in high yields by condensation of o‐phenylenediamine with aldehydes with P₂O₅/SiO₂ as catalyst under solvent‐free and ambient conditions.     

Microwave‐mediated synthesis and antibacterial activity of some novel 2‐(substituted biphenyl) benzimidazoles via Suzuki‐Miyaura cross coupling reaction and their N‐substituted derivatives

A series of some novel 2‐(substituted biphenyl) benzimidazoles and their N‐substituted derivatives were synthesized via microwave‐mediated Suzuki‐Miyaura coupling of 2‐(4‐iodophenyl)‐1H‐benzimidazole or 2‐(4‐iodophenyl)‐6‐amino‐1H‐benzimidazole and arylboronic acids. The method reported herein offers advantageous shorter reaction times, higher yields and is applicable to a large set of substrates. All the synthesized compounds were screened for their antibacterial activity against Staphylococcus aureus and Salmonella typhimurium bacterial species. J. Heterocyclic Chem., (2011).     

Synthesis of 2‐(1‐methyl‐1,2,5,6‐tetrahydropyridin‐3‐yl)benzimidazoles

A useful approach for the synthesis of pharmacologically active tetrahydropyridinylbenzimidazoles is described. 2‐Pyridin‐3‐ylbenzimidazoles 3a‐d have been synthesized by condensation of 3‐pyridinecarbox‐aldehyde 1 with substituted 1,2‐phenylenediamines 2a‐d following oxidative cyclization with iodobenzene diacetate. Methylation of 3a‐d with iodomethane and potassium hydroxide, subsequent formation of methylpyridinium salts 4a‐d and 7a‐d and reduction thereafter afforded tetrahydropyridinylbenzimidazoles 5a‐d and 8a‐d .     

Synthesis of 2‐phosphoro‐1,2‐thiazetidine 1,1‐dioxide

The reactions of phosphorochloridites 5a–c with an equimolar amount of 1,2‐thiazetidine 1,1‐dioxide (2) or L(−)‐3‐carboethoxy‐1,2‐thiazetidine 1,1‐dioxide (7) in the presence of triethylamine, affords the N‐phosphitylated β‐sultams 6a–b and L(−)‐8a,c. Their oxidation by addition of oxygen, sulfur, or selenium results in formation of stable organophosphorus β‐sultams 10a–b, L(−)‐11a,c, 12a, 13a, L(−)‐14c, and L(−)‐15c. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 61–67, 1999     

Synthesis of novel 3‐ and 5‐substituted indole‐2‐carboxamides

The preparation of several novel 3,5‐substituted‐indole‐2‐carboxamides is described. A 5‐nitro‐indole‐2‐carboxylate was elaborated to the 3‐benzhydryl ester, N‐substituted ester, and carboxylic acid intermedi ates, followed by conversion to the amide and then reduction of the 5‐nitro group to the amine. Indole‐2‐carboxamides with 3‐benzyl and 3‐phenyl substituents were prepared in four steps from either a 3‐bromo indole ester using the Suzuki reaction or from a 3‐keto substituted indole ester. N‐Alkylation of ethyl indole‐2‐carboxylate, followed by amidation and catalytic addition of 9‐hydroxyxanthene gave a 3‐xanthyl‐indole‐2‐carboxamide analog and a spiropyrrolo indole as a side product.     

Synthesis of poly(quinoxaline‐2,3‐diyl)s with alkoxy side chains by aromatizing polymerization of 4,5‐dialkoxy‐substituted 1,2‐ diisocyanobenzenes

Poly(quinoxaline‐2,3‐diyl)s bearing alkoxy pendants was synthesized by living polymerization of 4,5‐dialkoxy‐3,6‐dimethyl‐1,2‐diisocyanobenzenes, which were easily accessible from 3,6‐dimethylcatechol, using organonickel complexes as initiators. Thermal properties of the obtained polymers were fully determined by thermogravimetric analysis and differential scanning calorimetry, exhibiting strong dependence on their side chains. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Synthesis of quinoxaline derivatives through condensation of 1,2-diaminobenzenes with β-keto sulfoxides

The reaction of o-phenylenediamine with α-methylsulfinylcyclohexanone and α-methylsulfinylcyclopentanone in the presence of acetic acid afforded 1,2,3,4-tetrahydrophenazine and 2,3-dihydro-1H-cyclopenta[b]-quinoxaline, respectively. 3,4-Diaminotoluene and 3,4-diaminochlorobenzene were reacted with α-methyl-sulfinylacetophenone to give a mixture of the corresponding 6- and 7-substituted 2-phenylquinoxaline. Condensation of 3,4-diaminomethoxybenzene with α-methylsulfinylacetophenone gave 7-methoxy-2-phenylacetophenone, whereas, the same reaction between 3,4-diaminonitrobenzene and α-methylsulfinylacetophenone yielded 6-nitro-2-phenylquinoxaline.     

Synthesis and properties of new halogen‐substituted polyamides from 5‐halo‐m‐phenylenediamines and both aliphatic and aromatic dicarboxylic acids

New halogen‐substituted aromatic–aliphatic and wholly aromatic polyamides with high inherent viscosities were synthesized by the direct polycondensation of 5‐halo‐m‐phenylenediamines, where the halogens were Cl, Br, and I, with both aliphatic and aromatic dicarboxylic acids in N‐methyl‐2‐pyrrolidone with a mixture of triphenyl phosphite and pyridine as a condensing agent. The solubility of the halogen‐substituted polyamides was much higher than that of the parent polyamides derived from m‐phenylenediamine. The glass‐transition temperatures of the substituted aromatic–aliphatic polyamides increased in the order Cl < Br < I, whereas the temperatures of 10% weight loss in air decreased in the reverse order. The limiting oxygen index values, as an indication of flammability, increased for the substituted aromatic–aliphatic polyamides in the order Cl < Br < I. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 3911–3918, 2000