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.     

Unexpected Formation of 5‐Nitro‐1H‐benzimidazoles by Nucleophilic Recyclization of 1‐Methyl‐5‐nitropyridinium Salts

The synthesis of substituted 5‐nitro‐2‐phenyl‐1H‐benzimidazoles has been described via domino anionic process rearrangement of 3‐benzoylamino‐1,2‐dimethyl‐5‐nitropyridinium salts in the presence of NaOH water–alcohol solution. Substituted N‐benzoyl‐o‐phenylenediamines was obtained via recyclization of 3‐benzoylamino‐1,2‐dimethyl‐5‐nitropyridinium salts in the presence of aqueous methylamine solution.     

Synthesis of 4,6-diarylpyrimidin-2(1H)-one derivatives from benzyl halides and (1-bromoethyl)benzene under solvent-free conditions

A facile synthesis of a series of pyrimidinone derivatives from the reaction of benzyl halides, (1-bromoethyl)benzene and urea in the presence of pyridine N-oxide (PNO) under solvent-free conditions is described. This transformation presumeably occurs via oxidation/cross-aldol condensation/Michael addition/intra molecular cyclization, domino sequence, involving the formation of one C–C bond and two C–N bonds in a single step.     

Convenient synthesis of heteroaryl-linked benzimidazoles via microwave-assisted boronate ester formation

N-Substituted 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzimidazoles were conveniently accessed via microwave-assisted synthesis. Subsequent Suzuki-Miyaura cross-coupling with heteroaryl halides proceeded to give a wide variety of heteroaryl-substituted benzimidazoles.     

Aqueous Titanium Trichloride Promoted Reductive Cyclization of o‐Nitrostyrenes to Indoles: Development and Application to the Synthesis of Rizatriptan and Aspidospermidine

Treatment of o‐nitrostyrenes with aqueous TiCl₃ solution at room temperature afforded indoles through a formal reductive C(sp²)–H amination process. A range of functions such as halides (Cl, Br), carbonyl (ester, carbamate), cyano, hydroxy, and amino groups were tolerated. From β,β‐disubstituted o‐nitrostyrenes, 2,3‐disubstituted indoles were formed by a domino reduction/cyclization/migration process. Mild conditions, simple experimental procedure, ready accessibility of the starting materials and good to excellent yields characterize the present transformation. The methodology was used as a key step in a concise synthesis of rizatriptan and a formal total synthesis of aspidospermidine.     

Reactions with hydrazidoyl halides. IV. Synthesis of thiazolo[3,2-a]benzimidazoles,imidazo[2,1-6]thiazoles and pyrazolo[4,3-b]thiazines

Hydrazidoyl halides were condensed with 2-mercaptobenzimidazole yielding 4a-c and 7a,b which were cyclized to the corresponding 2-arylhydrazonothiazolo[3,2-a]benzimidazol-3-ones 5a,b and 3-substituted 2-arylazo thiazolo[3,2-a]benzimidazoles 8a,b respectively. Imidazo[2,1-b]thiazoles were obtained by the reaction of hydrazidoyl halides with 2-mercapto-4,5-dihydroimidazole. Also, hydrazidoyl halides 6a,b were reacted with 3-amino-4-mercapto-5-phenylpyrazole to give pyrazolo[4,3-b]thiazines 15a,b . The structures of the products were assigned on the basis of their elemental analysis and spectral data.     

Synthesis of the complex bridged 1,5-oxazabicycles <Emphasis Type="Italic">via</Emphasis> one-pot reactions of 4,5-diazafluoren-9-one,alkyl halides,and cyclic 1,3-diketone

An efficient and practical procedure for the preparation of the complex bridged 1,5-oxazabicycles was developed via a one-pot domino reaction of 4,5-diazafluoren-9-one, reactive alkyl halides, and cyclic 1,3-dicarbonyl compounds.     

A Novel Approach to the Synthesis of [1,2-a]Fused Polymethylenebenzimidazoles

Abstract

The synthesis of 2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazoles and 7,8,9,10-tetrahydro-6H-azepino[1,2-a]benzimidazoles from cyclic amidines is described.     

Tuned C?H Functionalization to Construct Aza‐Podophyllotoxin/Aza‐Conidendrin Derivatives by Means of Domino Cyclization

An efficient domino cyclization method for the construction of aza‐podophyllotoxin/aza‐conidendrin derivatives has been established. Reactions of different dienes with aryl halides in the presence of a palladium catalytic system produced different kinds of podophyllotoxin derivatives through a highly regioselective C? H functionalization. Treatment of dienes with aryl halides that have electron‐withdrawing substituents on the phenyl ring created aza‐podophyllotoxin derivatives by means of the functionalization of the C? H bonds ortho to the C? halide bonds of the incoming aryl halides. The reaction of dienes with 1‐iodobenzene or aryl halides that incorporate electron‐donating groups produced aza‐conidendrin derivatives by means of the functionalization of both sp³ C? H and sp² C? H bonds. The regioselective C? H functionalization for the formation of different pseudo‐podophyllotoxin/‐conidendrin derivatives is proven by analyses of the ¹H NMR spectra of the products and selective X‐ray analyses of the structures of the products. Thus, the palladium‐catalyzed domino cyclization of 1,6‐dienes for the preparation of aza‐podophyllotoxin/aza‐conidendrin derivatives can be controlled by selectively controlling the C? H functionalization.     

Coupling/cyclization of 1,6-enynes with aryl halides: an efficient and general route for the synthesis of functionalized hexahydroindole and hexahydrobenzofuran derivatives

An efficient and general route for the synthesis of functionalized hexahydroindole and hexahydrobenzofuran derivatives has been developed via the palladium-catalyzed domino coupling/cyclization reaction of 1,6-enynes and aryl halides. The results indicated that the electronic properties of the aryl halides strongly affect the reaction yields.     

Ni‐Catalyzed Cross‐Coupling Reaction: The Direct Synthesis of Symmetrical Disulfanes from Aryl and Primary Alkyl Halides

A novel Ni‐catalyzed cross‐coupling reaction is introduced for the direct synthesis of diaryldisulfanes and dialkyldisulfanes from aryl halides and primary alkyl halides at normal atmospheric conditions, respectively. This one‐pot and domino protocol utilizes only 10 mol% of NiCl₂ as a catalyst and morpholin‐4‐ium morpholine‐4‐carbo‐dithioate as a new, stable, solid, and odorless sulfurating reagent in the presence of ethylene glycol as a cosolvent and bidentate ligand in dimethyl formamide (DMF) at 130°C with good to excellent yields and relatively short time reaction.     

Synthesis of pyrazolo[1′,5′:1,2]-1,3,5-triazino[5,6-a]benzimidazoles

The synthesis of a new class of tetracyclic bridgehead heterocycle pyrazolo[1′,5′:1,2]-1,3,5-triazino[5,6-a] benzimidazoles is reported. The key intermediate 2-(3-aminopyrazol-2-yl)benzimidazoles were prepared by the reaction of 2-hydrazinobenzimidazole with an appropriate reagent such as ethyl ethoxymethylenecyanoacetate, ethoxymethylenemalononitrile, β-cyanoacetophenone or α-formylphenylacetonitrile. The treatment of these key intermediates with triethylorthoesters afforded the corresponding pyrazolo[1′,5′:1,2]-1,3,5-triazino[5,6-a]benzimidazoles.     

Magnetic iron oxide nanoparticles/K<Subscript>2</Subscript>S: a simple and scale-up method for the direct synthesis of symmetrical disulfides from aryl halides

A simple, one-pot, efficient and novel protocol has been developed for direct synthesis of symmetrical organic disulfides by domino reaction of aryl halides and K₂S in the presence of magnetic Fe₃O₄ nanoparticles as a readily available, highly efficient and recyclable catalyst. A variety of diaryl disulfides can be obtained in good-to-excellent yields up to 98%.     

Cover Feature: Stereoselective Domino Semipinacol-Schmidt Reaction: Diastereoselective Synthesis of 7 a-epi-(+)-Lepadiformine C and Formal Synthesis of 7 a-epi-(−)-Lepadiformine A (Eur. J. Org. Chem. 19/2023)

A concise approach has been developed for the diastereoselective synthesis of the azatricyclic core of (−)-7 a-epi-lepadiformine A ( 8 a ) and (−)-7 a-epi-lepadiformine C ( 8 b ) using stereoselective domino semipinacol-Schmidt reaction as a key step. In presence of TiCl₄, the oxaspiropentane-azide derivatives underwent stereoselective domino cyclization to furnish the corresponding angularly fused azatricyclic cores in very good yields. Moreover, azatricyclic core of (−)-7 a-epi-lepadiformine A has also been realized, in a stepwise manner, through the intramolecular Schmidt reaction of azido-spirocyclobutanone intermediate. The synthetic utility of domino semipinacol-Schmidt reaction is further shown in the diastereoselective synthesis of (+)-7 a-epi-lepadiformine C ( 7 ).     

An efficient,one‐pot and CuCl‐catalyzed route to the synthesis of symmetric organic disulfides via domino reactions of thioacetamide and aryl (alkyl) halides

In this article, a simple, general and novel method for the synthesis of diaryl (dialkyl) disulfides from aryl (alkyl) halides is described. This is a convenient approach that involves the use of commercially available and inexpensive thioacetamide as a sulfur transfer reagent in the domino process for the synthesis of symmetric organic disulfides. Copyright © 2013 John Wiley & Sons, Ltd.     

Rapid and Cheap Synthesis of Benzimidazoles via Intermittent Microwave Promotion: A Simple and Potential Industrial Application of Air as Oxidant

Using inexpensive KI as the catalyst in the presence of ambient air, benzimidazoles were synthesized from aromatic aldehydes and o-phenylenediamine with excellent yields via intermittent microwave irradiation without reflux equipment. The synthesis process was mild and only needed only a short reaction time (7–10 min). As a simple example of the utilization of molecular oxygen under mild conditions, this method provides a novel way to synthesize benzimidazoles. The industrial synthesis of benzimidazoles may be realized by a cycle of microwave irradiation.     

Copper‐Catalyzed Domino Synthesis of 2‐Imino‐1H‐imidazol‐5(2H)‐ones and Quinoxalines Involving CC Bond Cleavage with a 1,3‐Dicarbonyl Unit as a Leaving Group

Although 2‐imino‐1H‐imidazol‐5(2H)‐ones have important biological activities in metabolism, their synthesis has rarely been investigated. Quinoxalines as “privileged scaffolds” in medicinal chemistry have been extensively investigated, but the development of novel and efficient synthetic methods remains very attractive. Herein, we have developed two copper‐catalyzed domino reactions for the synthesis of 2‐imino‐1H‐imidazol‐5(2H)‐ones and quinoxalines involving C?C bond‐cleavage with a 1,3‐dicarbonyl unit as a leaving group. The domino sequence for the synthesis of 2‐imino‐1H‐imidazol‐5(2H)‐ones includes aza‐Michael addition, intramolecular cyclization, C?C bond‐cleavage, 1,2‐rearrangement, and aerobic dehydrogenation reaction, whereas the domino sequence for the synthesis of quinoxalines includes aza‐Michael addition, intramolecular cyclization, elimination reaction, and C?C bond‐cleavage reaction. The two domino reactions have significant advantages including high efficiency, mild reaction conditions, and high tolerance of various functional groups.     

Palladium‐Catalyzed Domino CH/NH Functionalization: An Efficient Approach to Nitrogen‐Bridged Heteroacenes

Palladium‐catalyzed domino C?H/N?H functionalization for the synthesis of novel nitrogen‐bridged thienoacenes and 10H‐benzo[4,5]thieno[3,2‐b]indole derivatives from dihaloarene is reported. This domino sequence consists of initial C?H functionalization of the benzo[b]thiophene moiety, followed by Buchwald–Hartwig coupling. This transformation is also useful for the synthesis of highly π‐extended compounds.     

1,2,3-benzotriazines. I. The synthesis of some benzimidazo [1,2-c][1,2,3]-benzotriazines and naphth[1′,2,(2′,1′):4,5]imidazo[1,2-c][1,2,3]benzotriazine

A number of substituted benzimidazo[1, 2-c][1,2,3]benzotriazines were prepared by the diazotization of the appropriate 2-(o-aminophenyl)benzimidazoles. Diazotization of 2-(o-aminophenyl)naphth[1,2-d]imidazole yielded a new heterocyclic ring system. Various methods of preparation of 2 - (o-aminophenyl)benzimidazoles were investigated. The condensation of o-phenylenediamines with anthranilic acids, in the presence of polyphosphoric acid, provided a convenient route to 2-(o-aminophenyl)benzimidazoles but in several cases the products were contaminated with considerable amounts of 6-(o-aminophenyl)benzimidazo[1,2 -c]quinazolines. 2 - (o-Aminophenyl)benzimidazoles were also obtained by the catalytic hydrogenation of 2-(o-nitrophenyl)benzimidazoles which resulted from the condensation of an o-phenylenediamine with an o-nitrobenzaldehyde in ethanol, nitrobenzene or acetic acid. When the condensation was carried out in nitrobenzene, small amounts of 2-(o-aminophenyl)benzimidazoles were also formed. The Weidenhagen synthesis, which involves the reaction of an aromatic diamine with an aldehyde in the presence of copper acetate and subsequent decomposition of the cuprous salt of the benzimidazole, yielded 2-(o-aminophenyl)benzimidazoles instead of the expected 2-(o-nitrophenyl)benzimidazoles when the decomposition was carried out in ethanol. When the cuprous salt was treated with hydrogen sulfide in dilute hydrochloric acid, a mixture of amino- and nitrobenzimidazoles resulted. The ultraviolet and infrared spectra of all the compounds prepared were examined.     

Synthesis and domino reactions of polymethylene-3-cyanopyridine-2(1Н)-thiones

A new and facile three-component method was developed for the synthesis of polymethylene-3-cyanopyridine-2(1Н)-thiones by the domino Knoevenagel → Michael → heterocyclization → dehydrogenation reaction from cycloalkanones, cyanothioacetamide, and polymethoxy-substituted benzaldehydes. The final dehydrogenation step was found to involve arylidenecyanothioacetamide. The resulting pyridinethiones and 4-chloroacetoacetic ester were introduced into the domino S_N2 → Thorpe-Ziegler → Guareschi-Thorpe reaction to synthesize tetracyclic dipyridothiophenes. Starting from these compounds, 8,9-polymethylenepyranothienodipyridines were also synthesized by the domino Knoevenagel → Michael → hetero-Thorpe-Ziegler reaction. Furthermore, a method for the synthesis of thienodipyridine annulated to the steroid skeleton is proposed.