Regioselective halogenation of biphenyls for preparation of valuable polyhydroxylated biphenyls and diquinones

Electron-rich biphenyls were selectively oxyfunctionalised through a halogenation-methoxylation sequence. The obtained biphenyl methyl ethers were then oxidised to the corresponding quinones. This strategy transforms commercially available biphenyls into both natural and bioactive oxidised compounds.     

Regioselective halogenation of aminopyrimidinyl-pyrrole carboxylic acid derivatives

The regioselective synthesis of halogenated aminopyrimidinyl-pyrroles as useful scaffolds for the preparation of diversified selective kinase inhibitors is described. The chemistry is simple and mostly based on the use of N-halosuccinimides under mild reaction conditions but the regioselectivity observed is partially unexpected.     

Visible-light-induced halogenation of aliphatic CH bonds

Alkyl halides are of particular interests in the areas of pharmaceutical, agrochemical, and material sciences. Direct CH halogenation has been recognized as the most efficient method for the introduction of halogen atoms into organic molecules. This Digest paper highlighted some of the most recent and significant developments in the visible light-promoted halogenation of aliphatic CH bonds.     

A mild and efficient method for halogenation of 3,5-dimethyl pyrazoles by ultrasound irradiation using N-halosuccinimides

The 4-halo-3,5-dimethyl pyrazoles have been synthetisized in good yields in short reaction times in the absence of a catalyst by reaction of 3,5-dimethyl pyrazoles with N-halosuccinimides (NBS, NCS and NIS) under ultrasound irradiation. Finally, the halogenation of pyrazoles with Br₂, ICl and I₂ was showed in similar conditions.     

Metal-free halogenation of arylboronate with N-halosuccinimide

Efficient bromination and chlorination of aryl pinacol boronates were accomplished without the addition of metal reagent. The reaction proceeded efficiently with electron-rich arylboronates or heteroarylboronates in DMF or acetonitrile, to afford mono-, di-, or trihalogenated aryl pinacol boronates.     

Regioselective vicinal-dichlorination of meso-aryl [26]hexaphyrin(1.1.1.1.1.1)

Two synthetic methods are developed for halogenations of meso-hexakis(pentafluorophenyl)-substituted [26]hexaphyrin(1.1.1.1.1.1); one is regioselective trans-vicinal-dichlorination with sulfuryl chloride and the other is acid-assisted hydrohalogenation followed by oxidation with DDQ.     

Ring B functionalization of scalarane sesterterpenes by radical relay halogenation

The functionalization of the B-ring of the scalarane framework has been achieved for the first time by a radical relay halogenation (RRH) synthetic method. The known scalaranic methyl ester, which was prepared by a procedure with an overall yield higher than those reported in the literature, has been used as the starting substrate. Some theoretical considerations explaining the course of RRH reaction are also presented.     

Mild electrophilic halogenation of chloropyridines using CCl4 or C2Cl6 under basic phase transfer conditions

Effective chlorination of 2,3,5,6-tetrachloropyridine to pentachloropyridine was realized under mild phase transfer conditions with carbon tetrachloride and 50% NaOH or solid K₃PO₄. Mechanistic study of this reaction indicated the possibility of an aromatic carbanionic intermediate. Hexachloroethane was established as a more selective electrophilic chlorination agent.     

The regioselective C5 halogenation of quinolines using sodium halides under transition metal-free conditions

An efficient and mild halogenation of 8-acylaminoquinoline at the C5 position was described. The reaction utilized easily available sodium halides as the halogen sources and proceeded smoothly under transition metal-free conditions. Various 8-aminoquinolines with a number of functional groups were compatible in this reaction to afford the corresponding halogenated products in moderate to good yields. Moreover, the reaction conditions also tolerated the substrates without the 8-aminoquinolyl auxiliary, such as N-phenyl amide and N-naphthyl amide.     

Synthesis,halogenation and structural characterization of (Z)-1-[2-(triphenylstannyl)vinyl]-1-cyclododecanol

Synthesis and characterisation of (Z)-1-[2(triphenylstannyl)vinyl]-l-cyclododecanol, c-(CH₂)₁₁C(OH)CH=CHSnPh₃, are reported, together with its halogenation by I₂, Br₂ and ICI to yield derivatives of the types c-(CH₂)₁₁C(OH)CH=CHSnPhs_?nX_n (n=1, 2; X=I, Br, Cl, respectively). The molecular structures of two compounds have been determined by X-ray diffraction analysis. The tin atom exhibits a distorted tetrahedral geometry in the crystal of (Z)-l-[2–(triphenylstannyI)vinyl]-l-cyclododecanol, but a trigonal bipyramidal geometry in the monoiodo-derivative (Z)-l-[2]-(diphenyliodo-stannyl)vinyl)-1-cyclododecanol and other derivatives, in which significant intramolecular coordinative interaction HO→Sn ia observed. And the formation of a five-membered tin containing ring is significant for their antitumour activities.     

Regioselective monobromination of substituted phenols in the presence of β-cyclodextrin

Cyclodextrin acts as a restricting nanovessel to enhance regioselectivity in bromination of substituted phenols such as 3-nitrophenol, 2-chlorophenol, 3-chlorophenol, and 4-chlorophenol. In contrast to solution bromination, cyclodextrin facilitates regioselective monobromination and formation of polybrominated products are substantially reduced. Selectivities in brominations are also observed in water and in the solid state. The observed results are rationalized on the basis of specific modes of inclusion of substituted phenols inside the cyclodextrin cavity and find strong support from energy minimization studies and ¹H-¹H NOESY.     

Efficient and economic halogenation of aryl amines via arenediazonium tosylate salts

Arenediazonium tosylate salts have been successfully employed as a new and efficient reagent in halogenation reactions. A novel and economic protocol has been developed for the bromination and chlorination of various anilines using arenediazonium tosylate salts. A wide variety of reaction conditions were studied in acetonitrile at either room temperature or 60 °C in the presence or absence of catalyst with good to excellent yields. A surprising result showed the formation of acetanilides as a major product of aniline and methyl-substituted aniline halogenations in high yields.     

Reactions of methyl 3-hydroxythiophene-2-carboxylate. Part 4. Synthesis of methyl 5-azolyl-3-hydroxythiophene-2-carboxylates

The indirect introduction of an azolyl group in position 5 of compound 1 by an easy two-step procedure taking place at room temperature is described. A similar procedure yields the 4-chloro derivatives of these 5-azolyl compounds. The same method is applied for the introduction of a 5-azido group and from the 5-azido compounds, 5-v-triazolyl derivatives are obtained by a known method.     

Selective trifluorination of alkyl aryl sulfides using IF5

In the reaction of IF₅ with alkyl aryl sulfides in heptane under reflux conditions, the arylthio group migrated once and three fluorine atoms were selectively introduced on the alkyl chain. In order to find the reason why the reaction stopped at the trifluorination step, we examined the oxidation potentials of the starting material, a reaction intermediate, and the product, and the time course of the reactions.     

Trihaloisocyanuric acids as convenient reagents for regioselective halogenation of β-dicarbonyl compounds

The reaction of β-dicarbonyl compounds (β-ketoesters and β-diketones) with 0.34 mol equiv of trichloro- and tribromoisocyanuric acids produced regioselectively the corresponding α-monohalo β-dicarbonyl compound. On the other hand, utilization of 0.68 mol equiv of the trihaloisocyanuric acid produced the α,α-dihalo β-dicarbonyl compound.     

Regioselective synthesis of 2-unsubstituted 1-aryl-4- and 1-aryl-5-acylimidazoles

An efficient and simple method for the synthesis of 2-unsubstituted 1-aryl-4- and 1-aryl-5-acylimidazoles has been developed. It consists in the condensation of α-diketone monooximes with aromatic amines and formaldehyde on the presence of boron trifluoride etherate, leading to the formation of stable boron trifluoride complexes of N-oxides. Further reduction of these complexes led to the corresponding imidazoles. This method permits broad variations of substituents in the aryl part of these compounds.     

Cyclization and halogenation of substituted o-allylphenols with diacetoxyiodobenzene in the presence of iodine or bromine

Substituted 2-halomethyl-2,3-dihydrobenzofurans were synthesized in one pot and in mild yield from substituted o-allylphenols with diacetoxyiodobenzene in the presence of 12 or Br2 in dry CH2Cl2 under reflux.     

Remote radical halogenation of aminoquinolines with aqueous hydrogen halide (HX) and oxone

Simple and halide-atom economical HX reagents (X?=?Cl, Br and I) were applied to the remote CH bond halogenation reaction of 8-aminoquinoline amides. This strategy features a broad substrate scope and good functional group tolerance. A series of C5-halogenated 8-aminoquinolines were obtained in moderate to good yields under mild conditions.