Halogenating Reagents Research Articles

PBr3-Mediated Cyclization of 1,7-Diyn-3,6-bis(propargyl carbonate)s: Synthesis of 5-Bromotetracenes.

A new and straightforward method for the synthesis of 5-bromotetracenes through PBr3-mediated cyclization of 1,7-diyn-3,6-bis(propargyl carbonate)s has been developed. This method offers several advantages such as easily accessible starting materials, high efficiency, and wide functional group compatibility. In addition, chloro- and iodo-substituted tetracenes were also synthesized using appropriate halogenating reagents. The utility of the 5-bromotetracene products has been illustrated by their efficient transformations through various palladium-catalyzed cross-coupling reactions.

Palladium‐Catalyzed ortho‐Halogenation of Tertiary Benzamides

AbstractA general and efficient protocol for the synthesis of ortho‐halogenated tertiary benzamides under mild conditions is described. Benzamides with various functional groups underwent ortho‐iodination, bromination or chlorination with NXS using a cationic palladium catalyst generated in situ from Pd(OAc)2 and TfOH in DME. Given the generality, efficiency, mild conditions, and readily available catalyst and halogenation reagents, this method could provide a practical approach for the synthesis of ortho‐halogenated benzamides.

Reaction of 4-hydroxycoumarin or its O-substituted derivatives with diatomic interhalogens: ICl and IBr

ABSTRACTHerein, we present some aspects regarding the iodination/bromination of 4-hydroxycoumarin or its O-methyl or O-acetyl derivatives with iodine monochloride or iodine monobromide as halogenation reagents. Also, the investigation of photochemical transformation of the three 3-iodocoumarins was investigated for the first time.

ChemInform Abstract: PhI(OAc)2 Oxidative C5 Halogenation of Quinolines Using Copper Halides under Mild Conditions.

A concise and efficient protocol for PhI(OAc)2 oxidation halogenation of quinoline at the C5 position was developed, affording the desired remote C–H activation products in moderate to excellent yields. This reaction proceeds with copper halides as the halogenating reagent to afford the halogenated quinolines and features excellent substrate tolerance, providing a facile pathway for the C5 halogenation of quinoline.

Nitroxyl-Radical-Catalyzed Oxidative Coupling of Amides with Silylated Nucleophiles through N-Halogenation.

A nitroxyl-radical-catalyzed oxidative coupling reaction between amines with an N-protecting electron-withdrawing group (EWG) and silylated nucleophiles was developed to furnish coupling products in high yields, thus opening up new frontiers in organocatalyzed reactions. This reaction proceeded through the activation of N-halogenated amides by a nitroxyl-radical catalyst, followed by carbon-carbon coupling with silylated nucleophiles. Studies of the reaction mechanism indicated that the nitroxyl radical activates N-halogenated amides, which are generated from N-EWG-protected amides and a halogenation reagent, to give the corresponding imines.

Nitroxyl‐Radical‐Catalyzed Oxidative Coupling of Amides with Silylated Nucleophiles through N‐Halogenation

AbstractA nitroxyl‐radical‐catalyzed oxidative coupling reaction between amines with an N‐protecting electron‐withdrawing group (EWG) and silylated nucleophiles was developed to furnish coupling products in high yields, thus opening up new frontiers in organocatalyzed reactions. This reaction proceeded through the activation of N‐halogenated amides by a nitroxyl‐radical catalyst, followed by carbon–carbon coupling with silylated nucleophiles. Studies of the reaction mechanism indicated that the nitroxyl radical activates N‐halogenated amides, which are generated from N‐EWG‐protected amides and a halogenation reagent, to give the corresponding imines.

One-Pot Three-Component Synthesis of 2-Imino-1,3-Thiazolines on Soluble Ionic Liquid Support.

An efficient one-pot, three-component synthesis of 2-imino-1,3-thiazolidines and 2-imino-1,3-thiazolines using ionic liquid-tethered 2-aminobenzimidazoles was reported. The protocol includes reaction of ionic liquid attached 2-aminobenzimidazoles with isothiocyanates to afford isothioureas, followed by its base induced inter and intramolecular nucleophilic displacement reactions with 1,2-dichloroethane (EDC) which results in thiazolidine ring formation. In the next to the last step, the ionic liquid support was removed by methanolysis to deliver 2-imino-1,3-thiazolidines, which were sequentially oxidized with manganese(III) triacetate to yield 2-imino-1,3-thiazolines. The salient feature of this method is the use of 1,2-dichloroethane as a synthetic equivalent for α-haloketone to avoid the use of toxic halogenating reagents.

Synthesis, structure and reactivity of β-chalcocyclohexenals: Dichalcogenides and chalcogenides

The present work describes the synthesis and characterization of a series of organochalcogen compounds derived from β-chlorocyclohexenal (27a)/β-bromocyclohexenal (27b) which are stabilized by E⋯O (E = S, Se, Te) intramolecular secondary bonding interaction (IM-SBI). Di-(2-formylcyclohex-1-ene)sulfide (21) was prepared by treating 27b with disodium sulfide. Di-(2-formylcyclohex-1-ene)diselenide (28) was obtained by reacting 27a with disodium diselenide. The reaction always produced a mixture of di-(2-formylcyclohex-1-ene)diselenide (28) and di-(2-formylcyclohex-1-ene)selenide (29). Attempts to synthesize di-(2-formylcyclohex-1-ene)ditelluride 30 by the reaction of 27b with disodium ditelluride afforded a mixture of monotellurides; 3,4,5,6,7,8-hexahydro-2H-9-telluraanthracene-1-carbaldehyde (26), di-(2-formylcyclohex-1-ene)telluride (22) and 9-hydroxy-2,3,5,6,7,8,9,9a-octahydro-1H-telluroxanthene-4-carbaldehyde (31). Reactions of 28 with halogenating reagents afforded the corresponding organylselenenyl halides; selenenyl chloride 35, selenenyl bromide 36 and selenenyl iodide 37. Tellurides 26 and 22 were used as ligands for metal complexation reactions.

ChemInform Abstract: Four‐Component Electrophilic Difunctionalization of Olefins Using Sulfonic Acids, Cyclic Ethers, and NBS.

AbstractThe novel, highly regio‐ and diastereoselective four‐component reaction affords sulfonate ester derivatives.

Bromophosphoalkoxylation of olefins with organic phosphates, cyclic ethers and NBS

A variety of structurally novel phosphoalkoxy ester derivatives were prepared via highly regio- and diastereoselective four-component reaction involving olefin, cyclic ether, halogen reagent and organic phosphate. All components can be varied flexibly and moderate to excellent yields were obtained at room temperature. Several of these ester derivatives showed strong anticancer activity against human lung adenocarcinoma cells.

Four-component electrophilic difunctionalization of olefins using sulfonic acids, cyclic ethers, and NBS

A novel and highly regio- and diastereoselective four-component reaction involving an olefin, a cyclic ether, a halogen reagent, and a sulfonic acid has been developed to access alkoxyether derivatives. Moderate to excellent yields were obtained with a broad substrate scope without external catalyst. Several of these sulfonate ester derivatives showed strong anticancer activity against human lung adenocarcinoma cells.

ChemInform Abstract: Trihaloisocyanuric Acids as Atom‐Economic Reagents for Halogenation of Aromatics and Carbonyl Compounds in the Solid State by Ball Milling.

It is shown that both tribromoisocyanuric acid (TBCA) and trichloroisocyanuric acid (TCCA) are excellent reagents for direct halogenation of electron-rich aromatics under solvent-free, ball-milling conditions. The results are remarkable in light of the fact that chlorination of aromatics without any acid catalyst is heretofore unknown. The procedure is operationally simple, and the reactions occur within a few hours, affording high yields of halogenated products. Similarly, crystalline β-keto dicarbonyl compounds are shown to undergo direct α,α-dihalogenation with TBCA and TCCA with ball milling. Whereas monoketones are found to be unreactive with TBCA/TCCA, addition of 25 mol-% of p-toluenesulfonic acid as a solid catalyst catalyzes the reaction, leading to the formation of α-chloro/bromo ketones in very good isolated yields. The fact that each of the reagents, in principle, serves as a source of three halogen atoms should render solvent-free halogenation of aromatics and carbonyl compounds with TBCA/TCCA an invaluable synthetic protocol.

ChemInform Abstract: Harnessing the Versatile Reactivity of Propargyl Alcohols and Their Derivatives for Sustainable Complex Molecule Synthesis

AbstractReview: [72 refs.

ChemInform Abstract: Four‐Component Reaction Leading to Highly Functionalized Sulfoalkoxy Carbonyl Compounds.

AbstractA facile regio‐ and diastereoselective four‐component reaction of α,β‐unsaturated carbonyl compounds, a cyclic ether, a sulfonic acid, and a halogen reagent is developed under mild conditions to access α‐bromo‐β‐sulfoalkoxyl carbonyl derivatives with excellent trans‐selectivity.

ChemInform Abstract: Sodium Halides as Halogenating Reagents: Rhodium(III)‐Catalyzed Versatile and Practical Halogenation of Aryl Compounds.

We report a concise, versatile and practical method for the ortho-chlorination, ortho-bromination and ortho-iodination of aryl compounds. The significant advantage of this transformation is the creation of the carbon-halogen bond by use of readily available and cheap halide salts as formal nucleophilic halogenating reagents under mild reaction conditions.

Harnessing the Versatile Reactivity of Propargyl Alcohols and their Derivatives for Sustainable Complex Molecule Synthesis

One of the major challenges faced in modern synthetic chemistry is the efficient and selective assembly of complex molecular structures, especially carbo- and heterocycles, from readily accessible starting materials. With this has arisen the development of tandem reaction processes, which permit multiple transformations in a single synthetic step and that have often provided elegant routes to complex target scaffolds from simple precursors. Propargyl alcohols and their derivatives have become increasingly attractive starting materials for such processes owing to their reactivity in the presence of a Brønsted or Lewis acid catalyst as well as halogenation reagents. This account describes our recent efforts in the field, and demonstrates how propargyl alcohols and their derivatives can be transformed into a diverse range of highly functionalized acyclic, carbocyclic and heterocyclic structures, which are of importance as synthetic building blocks and as motifs in functional materials and bioactive compounds. 1 Introduction 2 Acyclic Conjugated Enynes 3 Carbocycles 3.1 Indenes 3.2 Dihydrofluorenes 3.3 Cyclopentenes, Cyclobutenes and Cyclopenta[<i>b</i>]naphthalenes 3.4 <i>ortho</i>-Phenolic Esters 4 Heterocycles with One Heteroatom 4.1 Indoles 4.2 Piperidines, Azepines and Pyrrolidines 4.3 Pyrroles 4.4 Furans 4.5 Benzo[<i>b</i>]oxepines and Benzo[<i>b</i>]azepines 5 Heterocycles with Two Heteroatoms 5.1 Thiazoles and Oxazoles 5.2 Dioxolanes 6 Conclusion

Cu-catalyzed aryl C-H halogenation using N-halosuccinimides via assistance of benzoic acid

Aryl halides are a kind of extremely valuable compounds used in transition-metal-catalyzed coupling reactions,as well as important structure motifs in many natural products and manufactured drugs[1,2].The classical approach for preparation of haloarenes is electrophilic aromatic substitution(EAS) using various halogenating reagents or oxidative halogenations with halogenating reagent generated in situ from halides and oxidants,such as peroxide,oxygen and meta-cholorperoxybenzoic acid(mCPBA)[3,4].However,harsh reaction conditions are required for halogenation of less active aromatics.orthoMetalation followed by halogen quenching is another approach for halogenation of aromatics[5].However,there are obvious drawbacks for these methods,such as low regioselectivity,harsh conditions and even dangerous procedures.Therefore,the development of an alternative and practical way remains challenge in organic synthesis.

Trihaloisocyanuric Acids as Atom‐Economic Reagents for Halogenation of Aromatics and Carbonyl Compounds in the Solid State by Ball Milling

AbstractIt is shown that both tribromoisocyanuric acid (TBCA) and trichloroisocyanuric acid (TCCA) are excellent reagents for direct halogenation of electron‐rich aromatics under solvent‐free, ball‐milling conditions. The results are remarkable in light of the fact that chlorination of aromatics without any acid catalyst is heretofore unknown. The procedure is operationally simple, and the reactions occur within a few hours, affording high yields of halogenated products. Similarly, crystalline β‐keto dicarbonyl compounds are shown to undergo direct α,α‐dihalogenation with TBCA and TCCA with ball milling. Whereas monoketones are found to be unreactive with TBCA/TCCA, addition of 25 mol‐% of p‐toluenesulfonic acid as a solid catalyst catalyzes the reaction, leading to the formation of α‐chloro/bromo ketones in very good isolated yields. The fact that each of the reagents, in principle, serves as a source of three halogen atoms should render solvent‐free halogenation of aromatics and carbonyl compounds with TBCA/TCCA an invaluable synthetic protocol.

Sodium Halides as Halogenating Reagents: Rhodium(III)‐Catalyzed Versatile and Practical Halogenation of Aryl Compounds

AbstractWe report a concise, versatile and practical method for the ortho‐chlorination, ortho‐bromination and ortho‐iodination of aryl compounds. The significant advantage of this transformation is the creation of the carbon‐halogen bond by use of readily available and cheap halide salts as formal nucleophilic halogenating reagents under mild reaction conditions.magnified image

Gold-catalyzed dearomative spirocyclization of aryl alkynoate esters.

Aryl alkynoate esters undergo gold-catalyzed spirocyclization under mild conditions, affording spirolactones in high yields. This approach obviates the need for stoichiometric halogenating reagents typically employed for alkyne activation in related transformations. Water was found to play a critical role in governing the product selectivity. Anhydrous conditions lead selectively to coumarin products, as has previously been observed for aryl alkynoate esters, while the addition of 1 equiv of water leads selectively to spirocycle formation.