Liquid-phase synthesis of 2-substituted benzimidazoles, benzoxazoles and benzothiazoles

A novel acid fluoride for use in the liquid-phase synthesis of substituted benzimidazoles, benzoxazoles and benzothiazoles was developed. Its synthetic utility is exemplified by a structurally diverse set of aromatic heterocycles. Final cleavage is achieved by treatment with sodium methoxide in methanol for 12 h. The corresponding benzimidazoles, benzoxazoles and benzothiazoles were obtained in good isolated yields (22-62%, four steps).     

Solid-phase combinatorial synthesis of benzothiazoles, benzimidazoles, and benzoxazoles using a traceless linker

New methodology for the solid-phase synthesis of benzothiazoles, benzimidazoles, and benzoxazoles has been developed by using a traceless 4-alkoxy-aniline linker. The desired products were released from the polymer support by imine-exchange process coupled with air oxidation. Combinatorial library consisting of 36 members has been synthesized using this linker. The yields are low to good, which highly depend on the building blocks. Recycling of the polymer support was also investigated.     

Diversity oriented synthesis of benzoxazoles and benzothiazoles

A combinatorial synthetic route yielding benzoxazoles and benzothiazoles is described. The use of o-halophenylisocyanides in the Ugi reaction (U-4CR) followed by a copper-catalyzed cyclization affords the benzoxazole as well as the benzothiazole moiety in good yield and high diversity.     

Metal free montmorillonite KSF clay catalyzed practical synthesis of benzoxazoles and benzothiazoles under aerobic conditions

An efficient method for the synthesis of benzoxazoles and benzothiazoles via montmorillonite KSF clay catalyzed condensation reaction between 2-aminophenols or 2-aminothiophenols and β-diketones is reported. The efficiency of the reaction reflects from the wide substrate scope with electronic differentiation on aryls. The reaction is metal free and proceeds without the exclusion of air or moisture, and further the catalyst can be recycled up to 3–5 catalytic cycles.     

One-pot tandem approach for the synthesis of benzimidazoles and benzothiazoles from alcohols

Propylphosphonic anhydride (®T3P) has been demonstrated to be an efficient and mild reagent for the one-pot synthesis of benzimidazoles and benzothiazoles from variety of alcohols. Mild conditions, short reaction time, broad functional group tolerance, low epimerization, easy and quick isolation of the products, excellent chemo selectivity, and excellent yields are main advantages of this procedure. Thus, the present method is utilizing alcohols instead of aldehydes.     

Solid-phase synthesis of benzothiazoles using an alkoxyamine linker

An alkoxyamine linker was applied for the solid-phase synthesis of benzothiazoles. The substrate was anchored by aldoxime linkage and products were cleaved from the solid-support by aldoxime-imine exchange coupled with air-oxidation under the weakly acidic conditions. The tether is highly robust under Mitsunobu reaction, nucleophilic substitution reaction, and Pd-catalyzed reaction conditions.     

Cerium‐catalyzed tandem synthesis of 2‐substituted benzothiazoles in PEG

An efficient and convenient condensation reaction of 2‐aminothiophenol with aldehydes catalyzed by a catalytic amount of ceric ammonium nitrate in polyethylene glycol was investigated. As a result, a set of diverse 2‐substituted benzothiazoles such as 2‐phenylbenzothiazole as well as its p‐Me, p‐NO₂, p‐F, p‐Cl, p‐Br, o‐OMe, p‐OMe and 2‐furyl, 2‐pyridyl and styryl derivatives were obtained in good to excellent yields for 5 h at room temperature. Additionally, the catalyst system was recovered and reused several times without evident loss in activity. Copyright © 2011 John Wiley & Sons, Ltd.     

Organocatalytic oxidative synthesis of C2-functionalized benzoxazoles,naphthoxazoles, benzothiazoles and benzimidazoles

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Iodine-mediated cyclisation of thiobenzamides to produce benzothiazoles and benzoxazoles

Synthesis of benzothiazoles by reaction of iodine with thiobenzamides, which do not possess an ortho alkoxy or ester group, is described. The unlikely synthesis of benzoxazoles from reaction of 2-alkoxythiobenzamides with iodine is also reported.     

Parallel synthesis of a library of benzoxazoles and benzothiazoles using ligand-accelerated copper-catalyzed cyclizations of ortho-halobenzanilides

A general method for the formation of benzoxazoles via a copper-catalyzed cyclization of ortho-haloanilides is reported. This approach complements the more commonly used strategies for benzoxazole formation which require 2-aminophenols as substrates. The reaction involves an intramolecular C-O cross-coupling of the ortho-haloanilides and is believed to proceed via an oxidative insertion/reductive elimination pathway through a Cu(I)/Cu(III) manifold. The reaction is also applicable to the formation of benzothiazoles. A variety of ligands including 1,10-phenanthroline and N,N'-dimethylethylenediamine were shown to provide ligand acceleration/stabilization in the reaction. Optimal conditions for cyclization used a catalyst combination of CuI and 1,10-phenanthroline (10 mol %). The method was amenable to a parallel-synthesis approach, as demonstrated by the synthesis of a library of benzoxazoles and benzothiazoles substituted at various positions in the ring. Most examples utilized the cyclization of ortho-bromoanilides, but ortho-iodoanilides and ortho-chloroanilides also undergo a reaction under these conditions. The rate of reaction of the ortho-haloanilides follows the order I > Br > Cl, consistent with oxidative addition being the rate-determining step.     

Parallel synthesis of benzoxazoles via microwave-assisted dielectric heating

A facile route to benzoxazoles has been developed using microwave-assisted dielectric heating. The ease of synthesis and workup allowed the parallel synthesis of a 48-membered library of benzoxazoles quickly and efficiently.     

Synthesis of 2-pyranosyl benzothiazoles, benzimidazoles and benzoxazoles via nucleophilic addition reactions of pyranosyl nitrile oxides

Reaction of per-O-acetylated-β-d-pyranosyl nitrile oxides, generated by dehydrochlorination of the corresponding hydroximoyl chlorides, with 2-aminothiophenol afforded 2-(β-d-pyranosyl)benzothiazoles. 1,2-Diaminobenzene and 2-aminophenol reacted similarly to yield 2-(β-d-pyranosyl)benzimidazoles and 2-(β-d-pyranosyl)benzoxazoles, respectively. The structures of 2-β-d-glucopyranosylbenzimidazole (17), 2-(2,3,4-tri-O-acetyl-β-d-xylopyranosyl)benzimidazole (19) and the xylopyranosyl thiohydroximate 13 were established by X-ray crystallography.     

Organosilicon derivatives of 2-mercapto-substituted benzoxazoles,benzothiazoles and benzimidazoles

The interactions of sodium salts of 2-mercaptobenzoxazole, 2-mercaptobenzothiazole and 2-mercaptobenzimidazole with (chloromethyl)trimethyl-, chloromethyl(dimethoxy)methylor (chloromethyl)trimethoxysilanes have been shown to result in the corresponding previously unknown (2-heterylthiomethyl)triorganylsilanes. Transetherification of (2-heteryl-thiomethyl)trimethoxysilanes with triethanolamine gives 1-(2-benzoxazolylthiomethyl)-, 1-(2-benzothiazolylthiomethyl)- and 1-(2-benzimidazolylthiomethyl)silatranes. The reaction of the corresponding alkoxysilanes with boron trifluoride etherate leads to (2-benzoxazolylthiomethyl)- and (2-benzothiazolylthiomethyl)-substituted trifluorosilanes and methyldifluorosilanes having a dragonoid chelate structure. By the hydrolysis of (2-heterylthiomethyl)trimethoxysilanes, new organosilicon sorbents, poly(2-heteryl-thiomethyl)silsesquioxanes have been synthesized.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1965–1969, November, 1993.     

One-pot approach for the synthesis of 2-aryl benzothiazoles via a two-component coupling of gem-dibromomethylarenes and o-aminothiophenols

One-pot synthesis of 2-aryl benzothiazoles from gem-dibromomethylarenes using 2-aminoarylthiols is described. Benzothiazoles were obtained in high chemical yields under mild conditions. This transformation would facilitate synthesis by short reaction times, large-scale synthesis, easy and quick isolation of the products, which are the main advantages of this procedure.     

Bakers’ yeast catalyzed synthesis of benzothiazoles in an organic medium

The cyclocondensation of 2-aminothiophenol and aldehydes has been carried out in dichloromethane using bakers’ yeast as a catalyst for obtaining 2-aryl/heteryl benzothiazoles in good yields.     

Tungstate sulfuric acid as an efficient catalyst for the synthesis of benzoxazoles and benzothiazoles under solvent-free conditions

Tungstate sulfuric acid (TSA) has been found to be an efficient and reusable catalyst for the synthesis of benzoxazole and benzothiazole derivatives via reactions of orthoesters with o-aminophenols or o-aminothiophenols in high yields.     

Nano ceria catalyzed synthesis of substituted benzimidazole,benzothiazole, and benzoxazole in aqueous media

A series of substituted benzimidazoles, benzothiazoles, and benzoxazoles was synthesized by combining 1,2-phenylenediamine, 2-aminothiophenol, or 2-aminophenol with aryl, heteroaryl, aliphatic, α,β-unsaturated aldehydes in the presence of nano ceria (CeO₂) as an efficient heterogeneous catalyst.