Phenyl Halides Research Articles

Beryllium compounds for the carbon-halogen bond activation of phenyl halides: the role of non-innocent ligands.

Beryllium is a metallomimetic main-group element, i.e., it behaves similarly to transition metals (TMs) in some bond activation processes. To investigate the ability of Be compounds to activate C-X bonds (X = F-I), we have computationally investigated, using DFT methods, the reaction of (CAAC)2Be (CAAC = 1-(2,6-diisopropylphenyl)-3,3,5,5-tetramethylpyrrolidin-2-ylidene) and a series of five-membered heterocyclic beryllium bidentate ligands with phenyl halides. We have analysed all plausible reaction mechanisms and our results show that, after the initial C-X oxidative addition, migration of the phenyl group occurs towards the less electronegative heteroatom. Our theoretical study highlights the important role of bidentate non-innocent ligands in providing the required electrons for the initial Ph-X oxidative addition. In contrast, the monodentate ligand, CAAC, does not favour this oxidative addition.

Living Covalent-Anionic-Radical Polymerization via a Barbier Strategy.

The developments of the living alkene polymerization method have achieved great progress and enabled the precise synthesis of important polyalkenes with controlled molecular weight, molecular weight distribution, and architecture through an anionic, cationic or radical strategy. However, it is still challenging to develop a living alkene polymerization method through an all-in-one strategy where anionic and radical characteristics are merged into one polymerization species. Here, a versatile living polymerization method is reported by introducing a well-established all-in-one covalent-anionic-radical Barbier strategy into a living polymerization. Through this living covalent-anionic-radical Barbier polymerization (Barbier CARP), narrow distributed polystyrenes, with Đ as low as 1.05, are successfully prepared under mild conditions with a full monomer conversion by using wide varieties of organohalides, for example, alkyl, benzyl, allyl, and phenyl halides, as initiators with Mg in one pot. This living covalent-anionic-radical polymerization via a Barbier strategy expands the methodology library of polymer chemistry and enables living polymerization with an unconventional polymerization mode.

Halogen-Halogen Nonbonded Interactions.

Halogen–halogen nonbonded interactions were studied for methyl halides and phenyl halides using both B3LYP and MP2 along with 6-311+G* and aug-cc-pVTZ. With the methyl halides, the linear approach was found to lead to little stabilization, whereas the “90°” approach gave 1–2 kcal/mol. This modest stabilization was due to long-range electron correlation effects. The lowest-energy arrangement had the molecules side-by-side, with the major stabilization being derived from halogen–hydrogen interactions. The results for methyl bromide were quite similar. Chlorobenzene dimer with the 90° orientation gave a small stabilization energy, but the best arrangement had the two benzene rings oriented over each other. The meta orientation of the chlorines had a lower energy than ortho or para. The dimerization energy was larger than that for two benzene rings sitting directly above each other, suggesting that whereas Cl···Cl interaction is not very important, the effect of the halogen on the electron distribution does have an effect. This suggests that much of the crystallographic results for these compounds may not be due to halogen–halogen interactions but rather the interaction between the substituted benzene rings along with crystal forces.

Photocatalytic Carboxylation of Phenyl Halides with CO2 by Metal‐Organic Frameworks Materials

Main observation and conclusionIn this work, important commercial pharmaceutical intermediates, phenylpropionic acid compounds, are successfully obtained by catalyzing the reaction of carbon dioxide with phenyl halides using MOF‐5, a typical metal‐organic framework (MOF) material. The influence of temperature, pressure, catalyst type and light on the reaction is investigated, and a 90.3% selectivity towards fluorophenylpropionic acid is reached. Significantly, the catalysts are effective for varied benzyl compounds containing different substituent groups. The catalysts are stable and remain active after three cycles.

One-Pot Synthesized Pd@N-Doped Graphene: An Efficient Catalyst for Suzuki–Miyaura Couplings

Nitrogen-doped graphene (NDG)-palladium (Pd)-based nanocatalysts (NDG@Pd) can be potentially applied as an efficient catalyst for the preparation of biaryls in a Suzuki–Miyaura coupling reaction. Herein, we report the one-pot facile synthesis of an NDG@Pd nanocatalyst, wherein the nanocatalyst was prepared by the simultaneous reduction of graphene oxide (GRO) and PdCl2 in the presence of hydrazine hydrate as a reducing agent, while ammonium hydroxide was used as a source of “N’’ on the surface of graphene. The as-synthesized NDG@Pd nanocatalyst, consisting of smaller-sized, spherical-shaped palladium nanoparticles (Pd-NPs) on the surface of NDG, was characterized by several spectroscopic and microscopic techniques, including high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), ultraviolet–visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), and Brunauer–Emmett–Teller (BET). The nanocatalyst displayed outstanding catalytic activity in the Suzuki–Miyaura cross-coupling reactions of phenyl halides with phenyl boronic acids under facile conditions in water. The catalytic activity of NDG@Pd was found to be a more efficient catalyst when compared to pristine highly reduced graphene oxide (HRG) based Pd nanocatalyst (HRG@Pd). Furthermore, the reusability of the catalyst was also tested by repeatedly performing the same reaction using the recovered catalyst. The N-doped catalyst displayed excellent reusability even after several reactions.

Plant Extract Mediated Eco-Friendly Synthesis of Pd@Graphene Nanocatalyst: An Efficient and Reusable Catalyst for the Suzuki-Miyaura Coupling

Suzuki-Miyaura coupling reaction catalyzed by the palladium (Pd)-based nanomaterials is one of the most versatile methods for the preparation of biaryls. However, use of organic solvents as reaction medium causes a big threat to environment due to the generation of toxic byproducts as waste during the work up of these reactions. Therefore, the use of water as reaction media has attracted tremendous attention due to its environmental, economic, and safety benefits. In this study, we report on the synthesis of green Pd@graphene nanocatalyst based on an in situ functionalization approach which exhibited excellent catalytic activity towards the Suzuki–Miyaura cross-coupling reactions of phenyl halides with phenyl boronic acids under facile conditions in water. The green and environmentally friendly synthesis of Pd@graphene nanocatalyst (PG-HRG-Pd) is carried out by simultaneous reduction of graphene oxide (GRO) and PdCl2 using Pulicaria glutinosa extract (PGE) as reducing and stabilizing agent. The phytomolecules present in the plant extract (PE) not only facilitated the reduction of PdCl2, but also helped to stabilize the surface of PG-HRG-Pd nanocatalyst, which significantly enhanced the dispersibility of nanocatalyst in water. The identification of PG-HRG-Pd was established by various spectroscopic and microscopic techniques, including, high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), ultraviolet–visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), and Raman spectroscopy. The as-prepared PG-HRG-Pd nanocatalyst demonstrated excellent catalytic activity towards the Suzuki-Miyaura cross coupling reactions under aqueous, ligand free, and aerobic conditions. Apart from this the reusability of the catalyst was also evaluated and the catalyst yielded excellent results upon reuse for several times with marginal loss of its catalytic performance. Therefore, the method developed for the green synthesis of PG-HRG-Pd nanocatalyst and the eco-friendly protocol used for the Suzuki coupling offers a mild and effective substitute to the existing protocols and may significantly contribute to the endeavors of green chemistry.

Robust Suzuki-Miyaura cross-coupling on DNA-linked substrates.

The Suzuki-Miyaura cross-coupling is one of the most widely employed reactions in medicinal chemistry. To apply this reaction to DNA-encoded library technology (ELT), an alternative approach in the discovery of small molecule hits and leads, we explored the Suzuki-Miyaura cross-coupling on DNA-linked aryl halides. Pd(PPh3)4 was demonstrated to be an effective catalyst for cross-coupling with on-DNA halide substrates under aqueous conditions. It efficiently catalyzes the coupling of phenyl halides (iodide or bromide) and pyridinyl bromides with various boronic acids/esters, including challenging heterocyclic boronic acids/esters.

Computed ligand effects on the oxidative addition of phenyl halides to phosphine supported palladium(0) catalysts.

The manifold of reaction pathways for the oxidative addition of phenyl bromide and phenyl chloride substrates to phosphine-modified palladium(0) complexes has been investigated with dispersion-corrected density functional theory (B3LYP-D2) for a range of synthetically relevant ligands, permitting the evaluation of ligand, substrate and method effects on calculated predictions. Bulky and electron-rich ligands P(t)Bu3 and SPhos can access low-coordinate complexes more easily, facilitating formation of the catalytically active species throughout the cycle. While the bisphosphine oxidative addition step is reasonably facile for the smaller PCy3 and PPh3 ligands, the dissociation of these ligands to generate reactive palladium complexes becomes more important and the catalyst is more likely to become trapped in unreactive intermediates. This study demonstrates the feasibility of exploring the catalytic manifold for synthetically relevant ligands with computational chemistry, but also highlights the remaining challenges.

Application of an air-and-moisture-stable diphenylphosphinite cellulose-supported nanopalladium catalyst for a Heck reaction

A diphenylphosphinite cellulose-supported nanopalladium (Cell–OPPh2-Pd0) was conveniently prepared from cellulose and chlorodiphenylphosphine in pyridine, followed by treatment of an ethanol solution of palladium chloride. The prepared catalysis was found to be air- and moisture-stable and have significant catalytic activities in Heck coupling under mild operating conditions. Various phenyl halides were coupled with alkenes in DMF under air, to afford the corresponding products in good yields. Furthermore, the catalyst can be easily recovered by simple filtration and reused for up to six cycles without losing its activity.

Influence of the Formation of the Halogen Bond ArX- - -N on the Mechanism of Diketonate Ligated Copper-Catalyzed Amination of Aromatic Halides

The mechanism of cross-coupling reactions of aryl halides PhX (X = I, Br, Cl) with cyclohexylamine catalyzed by CuI associated with a diketonate ligand (ket = 2-acetylcyclohexanoate) has been investigated via DFT. Phenyl halides which can be involved in halogen-bond formation (X = I, Br) with the anionic nitrogen of the intermediate [(ket)Cu-NHCy]− can undergo intramolecular oxidative addition, which is in competition with the classical oxidative addition three-centered pathway, whereas those which cannot (X = Cl) undergo a classical oxidative addition, leading to the common complex (ket)CuIIIPh(NHCy). The latter is involved in a faster reductive elimination, leading to PhNHCy. C6F5I, which involves the strongest C6F5I- - -N halogen bond, generates the anion C6F5– and consequently not the expected C–N cross-coupling product by substitution at the C–I bond, as evidenced experimentally.

Singlet/triplet phenyl cations and benzyne from the photodehalogenation of some silylated and stannylated phenyl halides

The photodehalogenation of fluoro or chlorobenzene derivatives smoothly generates triplet and singlet phenyl cations (3,1Ar+) and potentially benzyne. These intermediates lead to different products, which warrants exploring the direct effect of substituents. SiMe3 and SnMe3 groups have been found to be convenient probes since they affect neither the photophysics nor the primary dehalogenation of 4-chloroanisole and 4-chloro (or 4-fluoro) N,N-dimethylaniline (except for the case of 4-fluoro-3-(trimethylstannyl)aniline, which was preferentially demetallated). The stabilization by these groups (with SnMe3ca. 10 kcal mol−1 for the triplets and 20 kcal mol−1 for the singlets, as computed by using (U)B3LYP DFT method with LANL2DZ basis set) made 1Ar+ the lowest state with stannylated and silylated anisoles and solvolysis the main process. On the other hand, donating substituents and an acidic solvent favored the triplet cation chemistry, a quite general process leading to reduction or (in the presence of π bond nucleophiles) to arylation. Noteworthily, the stannylated 4-N,N-dimethylaminophenyl cation eliminated the Me3Sn+ group, opening an unprecedented path to the corresponding benzyne. Apart from the control of the chemical output, the photostabilizing effect found with a silyl group may be useful for designing less phototoxic fluorinated drugs.

Study on Reactions of Long-Lived Phenoxathiin Radical Cation with Aliphatic Alcohols, Phenol and Phenyl Halides in Ambient Condition by Fused-Droplet Electrospray Ionization Mass Spectrometry

he reactions of phenoxathiin radical cations with diverse organic compounds in ambient conditions were realized by using fused-droplet electrospray ionization mass spectrometry. In the investigation, the phenoxathiin radical cation was prepared by electrospray ionization. The reactants included aliphatic alcohols, phenol and phenyl halides and the reaction studies showed the unique reactivity the of phenoxathiin radical cation towards neutral organic compounds in ambient conditions, which has not been revealed in previous studies.

ChemInform Abstract: Synthesis and Catalytic Properties of a Heterocyclic—Carbene Complex of Palladium.

AbstractThe complex is catalytically highly active in the cross‐coupling reaction of phenyl halides (I) with phenylthiol.

Transfer of a Disilenyl Moiety to Aromatic Substrates and Lateral Functional Group Transformation in Aryl Disilenes

The reaction of 1 equiv of the disilenide Tip2Si═Si(Tip)Li (5; Tip = 2,4,6-(i)Pr3C6H2) with para-substituted phenyl iodides, 4-X-PhI, transfers the Tip2Si═Si(Tip) moiety with elimination of lithium iodide to yield the laterally functionalized disilenes Tip2Si═Si(Tip)(4-X-Ph) [X = H (6a), F (6b), Cl (6c), Br (6d), I (6e)]. The UV-vis absorptions of 6a-d suggest a linear correlation with electronic Hammett parameters. In addition, X-ray structural analyses of 6a-d verified the theoretically predicted linear dependence of the Si═Si bond length and trans-bent angles. The p-bromophenyl-substituted disilene 6d undergoes a metal-halogen exchange reaction to give 6f (X = Li), which was trapped with Me3SiCl to afford 6g (X = SiMe3). In the case of simple phenyl halides PhX without additional functionality, the reaction with 5 proceeded smoothly for X = Br, but phenyl chlorides and fluorides did not react at room temperature even after one week, hinting at an S(N)2-type aromatic substitution mechanism. Reactions of p- and m-diiodobenzene with 5 afford the corresponding phenylene-bridged tetrasiladienes p-7 and m-7. While red p-7 (λ(max) = 508 nm) exhibits efficient conjugation of the two Si═Si bonds with the phenylene linker, the conjugation in yellow m-7 (λ(max) = 449 nm) is much less effective. Electrochemical studies of m-7 and p-7 as well as density functional theory calculations and electron paramagnetic resonance studies of their respective radical anions provided further support for the notion of conjugation.

Effect of N1-substituted pyrazolic hybrid ligands on palladium catalysts for the Heck reaction

In this paper we have explored the influence of several linkers present on the [PdCl 2(L)] complexes, where L is 3,5-dimethylpyrazolic hybrid ligand N1-substituted by polyether chains and/or phenyl groups. These complexes have been used as pre-catalysts in the Heck reaction between phenyl halides and tert-butyl acrylate. The corresponding complexes efficiently catalyze the Heck olefination and provide good yields under phosphine-free conditions, even for aryl chlorides. Different reaction conditions were investigated and it was found that the nature of the ligand has an important influence on the effectiveness of the catalytic system. Ligand 1,8-bis(3,5-dimethyl-1 H-pyrazol-1-yl)-3,6-dioxaoctane ( L1), which has previously shown to be the most flexible and versatile, achieved high turnover numbers within very short reaction times and low catalyst loadings.

A Self-Supported Palladium-Bipyridyl Catalyst for the Suzuki-Miyaura Coupling in Water

A self-supported palladium catalyst (PdCl 2 BPy-Cu) was prepared via construction of a metal-organic framework (MOF) of a bipyridyl-palladium complex bearing carboxylic groups and a copper(II) linker. PdCl 2 BPy-Cu efficiently catalyzed the Suzuki-Miyaura coupling of phenyl halides with arylboronic acids in water under atmospheric conditions to afford the corresponding biaryl products in high yield. The catalyst was reused four times without loss of catalytic activity.

Synthesis of immobilized nanopalladium on polymer-supported Schiff base, and study of its catalytic activity in the Suzuki–Miyaura reaction

Nanopalladium particles immobilized on a matrix of poly(vinyl chloride) (PVC)-supported Schiff base were prepared from PVC with sequential attachment of ethylenediamine and salicylaldehyde, followed by treatment with an ethanolic solution of palladium chloride. The as-prepared catalyst was found to be air and moisture-stable and to have significant catalytic activity in Suzuki–Miyaura reactions under mild operating conditions. Various phenyl halides were coupled with phenylboronic acid in aqueous ethanol, under air, to afford the corresponding cross-coupled products in good yields. Furthermore, the catalyst can be easily recovered by simple filtration and reused for up to five cycles without losing its activity.

Solvation of benzene and phenyl halides in supercritical CO 2 studied by the interaction-induced CO 2 bending Raman band

To study solvation in supercritical (SC) CO 2, Raman spectra of SC CO 2 and its solutions with benzene or phenyl halides were studied based on the CO 2 bending vibrations, which become weakly Raman active upon interaction between CO 2 and other molecules. The bending band was as broad as 87 cm − 1 in neat SC CO 2 at 15 MPa. The addition of solute molecules resulted in steep decreases in band wavenumber and width in the region of solute molar fraction x < 0.03, and in an almost linear increase in intensity up to x of about 0.1. Solvation of the aromatic molecules in SC CO 2 was discussed based on preliminary ab initio calculations, which suggested that the CO 2 molecule interacts more strongly with the solute π-electrons than with the halogen substituent.

Direct Arylation Mediated by Palladium Complexes with Rigid Phosphine-Functionalized N-Heterocyclic Carbenes

New phosphine-functionalized N-heterocyclic carbene ligand precursors (L1H·I and L2H·I) were prepared. The former compound contains a PPh2 moiety, whereas the latter one has a more electron-donating PCy2 group. A reaction of L1H···I with PdCl2 in the presence of base afforded the complex PdL1ClI. An interconversion process between the two structural isomers of PdL1ClI was observed by variable-temperature NMR. The coalescence temperature (Tc) is at 368 K with the free energy of activation (ΔG⧧) found to be 68.9 kJ mol−1. A similar reaction of L2H·I with PdCl2 produced a mixture of PdL2ClI, PdL2Cl2, and PdL2I2. Unlike PdL1ClI, PdL2ClI undergoes a much faster exchange between the two structural isomers. Pure PdLI2 (L = L1 and L2) can be obtained by adding NaI in the reaction mixture to facilitate ligand exchange. [PdL(CH3C≡N)2](BF4)2 were also prepared straightforwardly by salt metathesis reactions. In total, seven new palladium complexes of L were structurally characterized, and in each of these structures an anagostic interaction exists between the palladium center and one of the diastereotopic methylene protons. The interaction also exists in solution, as evidenced by the downfield NMR shift of the proton. The new complexes PdLI2 and [PdL(CH3C≡N)2](BF4)2 show mediocre activities in benchmark Suzuki coupling reactions under conventional and microwave heating. They are, however, highly promising in mediating direct arylation of phenyl halides and diphenylacetylene, affording 9-benzylidene-9H-fluorene in good yields.

Recent Developments in the Organic Chemistry of Calcium – An Element with Unlimited Possibilities in Organometallic Chemistry?

AbstractThe organocalcium chemistry developed vastly during the last decade. The preparation of the organocalcium compounds via direct synthesis (insertion of Ca into a C‐X bond of phenyl halides, Grignard reaction) affords skilful procedures due to the inertia of the calcium metal and the extreme reactivity of the organocalcium derivatives. Further suitable preparative methods include metathesis reactions of CaX2 with KR or LiR, metallation reactions of H‐acidic substrates, metal‐halogen exchange reactions, and transmetallation of heavy main group atoms in their compounds with calcium metal. Possibilities to stabilize organocalcium compounds include steric shielding by bulky ligands at the periphery and electronic reduction of the nucleophilicity of the calcium‐bound carbanions. Selected applications in catalysis such as hydrophosphination are also mentioned. Very recent developments and challenges in the preparation of alkaline earth metal(I) compounds are presented as well. Concepts to overcome the rather large atomization energies of the metals are discussed.