Phenylmagnesium Bromide Research Articles

In situ Grignard metalation method (iGMM) for the preparation of alkynyl magnesium and calcium compounds

In the in situ Grignard Metalation Method (iGMM), intermediately formed ethylmagnesium bromide as well as ethylcalcium and ethylstrontium iodide metalate trialkylsilylethyne in THF. For Me3SiCCMgBr (1a) a temperature-dependent Schlenk equilibrium is operative and this heteroleptic compound coexists with the homoleptic congeners Mg(CCSiMe3)2 (1b) and MgBr2. The reaction enthalpy ΔH and entropy ΔS adopt characteristic values. Initially formed Me3SiCCCaI (2a) is quantitatively converted to homoleptic Ca(CCSiMe3)2 (2b) and CaI2. With increasing size of the alkaline-earth metal increasing amounts of the degradation product Me3SiCCSiMe3 hamper isolation of analytically pure compounds of strontium and barium. The molecular structures of [(thf)3Mg(CCSiMe3)2] (1b) and [(thf)3Ca(µCCSiMe3)I]2 (2a) have been determined by single-crystal X-ray diffraction.

Synthesis of Vicinal anti-Amino Alcohols from N-tert-Butanesulfinyl Aldimines and Cyclopropanols.

The stereoselective synthesis of vicinal amino alcohols derivatives from 1-substituted cyclopropanols and chiral N-tert-butanesulfinyl imines is described. Cyclopropanols are easily prepared from carboxylic esters upon reaction with ethylmagnesium bromide in the presence of titanium tetraisopropoxide and undergo carbon-carbon bond cleavage by means of diethylzinc to produce, upon base deprotonation, enolized zinc homoenolates, which react with chiral sulfinyl imines in a highly regio- and stereoselective manner.

Regulation of ester contents enabled tunable thermal and mechanical properties of poly(ester amide)

AbstractPoly(ε‐caprolactone‐co‐ε‐caprolactam) was synthesized through ring‐opening copolymerization of ε‐caprolactone (CLO) and ε‐caprolactam catalyzed by ethylmagnesium bromide (EtMgBr) or sodium ε‐caprolactam. Varied ester contents were achieved from 0 to 100 mol%. EtMgBr enabled the copolymerization with high yield of over 95%. Thermal properties vary with different ester contents. With increasing CLO content, the onset decomposition temperature (273.36 to 240.97 °C) and glass transition temperature (52.1 to −56.3 °C) gradually decreased. The results of melting behavior of resultant poly(ester amide)s through differential scanning calorimetry and theoretical calculation indicated a eutectic temperature of 46.6 °C. The mechanical properties of obtained copolymers were systematically investigated. The enhancement of CLO incorporation led to a decrease in tensile strength (70.99 to 9.88 MPa) and Young's modulus (690.03 to 19.18 MPa). Copolymer with CLO incorporation of 70 mol% exhibited a eutectic temperature of 46.6 °C, and enabled a high elongation at break (658%) and enhanced impact strength (138.5 kJ m−2). © 2023 Society of Chemical Industry.

Molybdenum-Catalyzed Directed Activation of Aryl Chlorides and Fluorides

AbstractA low-valent molybdenum species generated by the reduction of a molybdenum precursor with phenylmagnesium bromide catalytically cleaves a C–Cl or C–F bond in an aromatic ketone under mild conditions, followed by cyclization to produce a hydroxyphthalan (1,3-dihydro-2-benzofuran-1-ol) derivative.

Ring-opening of 5,15-dioxaporphyrin into 1,9-diaryldipyrrin by a reaction with Grignard reagents

A ring-opening of nickel 10,20-dimesityl-5,15-dioxaporphyrin (NiDOP) proceeded in a reaction with aryl Grignard reagents to afford 1,9-diaryldipyrrins instead of demetallation reaction to form a free base form. A reagent scope for the ring-opening reaction revealed that reactions with less-sterically hindered aryl Grignard reagents, such as phenyl and para-substituted phenylmagnesium bromides, provided the dipyrrin products. In contrast, no reaction occurred, and unreacted NiDOP was recovered when alkyl, ethynyl, and 2-thienylmagnesium bromides and sterically hindered mesitylmagnesium bromide were used for the reactions. Herein, the unique ring-opening reactivity of NiDOP and characterization of the 1,9-diaryldipyrrin products are reported.

Green synthesis of methadone in eutectic solvent

Eutectic solvents (DES), have attracted much attention in the last decade. With the advantages of nonflammability, thermal and chemical stability, high solubility and partial vapor pressure, non-toxicity and reasonable prices, these solvents are suggested as useful solvents. On the other hand, the eutectic solvents developed by Abbott are the new generation of ionic liquids. The mixture of eutectics is from an ammonium salt and a hydrogen bonding compound such as urea, acid, amine, and non-toxic amines. Choline chloride and urea, are quite environmentally friendly and are known practically as green solvents. The purpose of the present research is to present the synthesis of diphenyl acetonitrile with 1-dimethylamino-2-chloropropane by a eutectic’s solvent. In addition, methadone is synthesized from the reaction of 2,2-Diphenyl-4-dimethylaminovaleronitrile with ethyl magnesium bromide in the presence of solvent eutectic, which is in optimal and environmentally compatible conditions and by principles of green chemistry.

Nickel(II) complexes with N,O‐donor thiopseudourea ligands: Syntheses, structures, and catalytic applications in Kumada–Corriu cross‐coupling reactions

Synthesis, characterization, and physical properties of benzyl‐N′‐(4‐R‐benzoyl)‐N‐(2,6‐diisopropylphenyl)carbamimidothioates, HL1 (R = H) and HL2 (R = Cl), and their nickel(II) complexes having the general molecular formula [Ni(L1/2)2] (1 and 2) have been reported. Elemental analysis, magnetic susceptibility, solution electrical conductivity, and various spectroscopic (IR, UV–Vis, and 1H NMR) measurements were used to characterize HL1, HL2, and the two complexes (1 and 2). The molecular structures of all four compounds were determined by single‐crystal X‐ray crystallographic studies. The structures of HL1 and HL2 showed the imino‐ketone form of both compounds. In each of 1 and 2, the six‐membered chelate ring forming iminolate‐O and azomethine‐N donor two (L1/2)− ligands form a square‐planar trans‐N2O2 coordination environment around the metal center. The spectroscopic characteristics of HL1, HL2, 1, and 2 are consistent with their molecular structures. Both complexes were successfully employed as efficient catalysts in Kumada–Corriu CC cross‐coupling reactions of aryl bromides with phenylmagnesium bromide. The reactions provided biaryl products in good to excellent yields with a good substrate scope.

Highly efficient approach to the total synthesis of flavoxate hydrochloride

An efficient and short approach to the total synthesis of flavoxate hydrochloride, a muscle relaxant in urinary bladder, is reported. The synthesis of flavoxate hydrochloride is accomplished from o -cresol in 5 steps with 60.3% overall yield using formylation with formaldehyde, Grignard reaction with ethylmagnesium bromide, oxidation with potassium permanganate, Kostanecki-Rabinson cyclization and esterification with thionyl chloride and piperidinoethanol as linear steps.

Computational Chemistry on Reactions of Ethylmagnesium Bromide with Diisopropyl Ketone

Computational Chemistry on Reactions of Ethylmagnesium Bromide with Diisopropyl Ketone

Accessing a key intermediate for sub(oxa)porphyrins from a sustainable raw-material—Cashew apple bagasse

Furan-2,5-diylbis(phenylmethanol) is a key intermediate to access sub(oxa)porphyrins. Previously, this key intermediate was accessible from fossil-derived furan using highly dangerous lithium reagents. Presently, we have produced this key intermediate from cashew apple bagasse (CAB), via the formation of 5-hydroxymethylfurfural (HMF). CAB is non-food biomass containing cellulose and hemicellulose. From the CAB, we have obtained the HMF in the yield of 310 mg/g of CAB. The Response Surface Methodology (RSM) optimized condition for efficient conversion of CAB to HMF is (i) temperature at 180 °C, (ii) 1:1 mol ratio of catalysts (ZnSO4/NaHSO4), and (iii) reaction duration of 3 h. CAB-derived HMF is treated with an oxidizing agent pyridinium chlorochromate (PCC) to obtain 2,5-diformylfuran (DFF). DFF is converted into furan-2,5-diylbis(phenylmethanol) in a reaction with phenylmagnesium bromide. Based on the TD-DFT analysis of sub(oxa)porphyrins, it is concluded that the absorption behavior of sub(oxa)porphyrins can be tuned by introducing electron-withdrawing groups into the phenyl ring of the sub(oxa)porphyrins.

Synthesis and structures of amido-functionalized N-heterocyclic nickel(II) carbene complexes

A series of bis-bidentate nickel(II) complexes [Ni(R-bimy-CH2CONH)2] (bimyH = benzimidazole; R = Me (3), Et (4), Ph (5)) bearing amido-functionalized N-heterocyclic carbene ligands, and pincer-type nickel(II) complexes [Ni(Py-bimy-CH2CONH)X] (X = Cl (6), Br (7)) bearing an amido- and pyridyl-functionalized N-heterocyclic carbene ligand were prepared. These complexes were characterized by NMR (1D and 2D) and single-crystal X-ray diffraction. Complexes 3-5 possess cis configuration, and the carbene ligands bound to the nickel atom through C2 carbon and NH nitrogen in a bis-bidentate coordination mode. In complexes 6 and 7, the pyridyl substituent was also N-bound to the nickel metal center resulting in a pincer-type coordination mode. As observed from the proton NMR spectra, the six-membered chelate rings in complexes 3-5 rendered the protons of the methylene moieties diastereotopic, and the cis configuration made the free rotation of the ethyl substituent in 4 and the phenyl substituent in 5 hampered by the adjacent substituent. The catalytic activity of these nickel complexes in Kumada cross-coupling of phenylmagnesium bromide with aryl chlorides was also investigated. The results indicated that pincer-type complexes 6 and 7 displayed excellent to moderate catalytic activity depending on the aryl chloride used.

Gold(I)-catalyzed intramolecular [4 + 2] cycloaddition of ortho-(N-tethered 1,6-diynyl)benzaldehydes to 3,4-dihydrobenzo[f]isoquinolin-1(2H)-ones

An efficient synthetic method to prepare 3,4-dihydrobenzo[f]isoquinolin-1(2H)-ones through gold(I)-catalyzed intramolecular [4 + 2] benzannulation of o-(N-tethered 1,6-diynyl)benzaldehydes at a low catalyst loading of 2 mol% is described. The product of 3,4-dihydrobenzo[f]isoquinolin-1(2H)-ones can be easily transformed to benzo[f]isoquinolin-1-ols by simply treating with phenylmagnesium bromide under mild conditions. The structures of compounds 2o and 2w were also ascertained by X-ray crystallographic analysis.

Synthesis and catalytic application of cyclopentadienyl nickel(II) N-heterocyclic carbene complexes

A series of ester-functionalized benzimidazolium salts 2a–c were prepared by quaternization of 1-{(ethoxycarbonyl)methyl}benzimidazole (1) with 3,5-dimethylbenzyl bromide, 2,5-dimethylbenzyl chloride and 3-methoxybenzyl chloride, respectively. Refluxing 2a–c with nickelocene in THF yielded the neutral cyclopentadienyl NHC nickel(II) complexes 3a–c. Their structures were defined by NMR, IR and elemental analysis techniques. Molecular weights of 3a–c were affirmed by MALDI-TOF mass spectrometry. Catalytic tests of 3a–c were performed in Kumada coupling of some aryl chlorides with phenylmagnesium bromide at 25 °C.

General Route to Purin-2-ylmagnesium Halides by Metal–Halogen Exchange in Dichloromethane

Treatment of a solution of a 9-alkyl- or 9-aryl-2-iodopurine in dichloromethane with an ethereal solution of ethylmagnesium bromide at –5 °C generates the corresponding purin-2-ylmagnesium bromide, which reacts with aldehydes to give the corresponding 2-(hydroxyalkyl)purines in yields of 53–84%. The purin-2-yl Grignard reagents show good functional-group tolerance to ester and nitro groups, and the method permits the synthesis of the previously unknown 6-unsubstituted 2-magnesiopurines for the first time. Performing the same procedure in THF as solvent resulted either in extensive decomposition or rapid isomerization to give purin-8-ylmagnesium halides.

A molecular electron density theory study of the Grignard reagent‐mediated regioselective direct synthesis of 1,5‐disubstituted‐1,2,3‐triazoles

AbstractThe [3 + 2] cycloaddition (32CA) reaction of phenyl azide4with ethynylbenzene5in presence of ethyl magnesium bromide (EtMgBr) has been studied within the Molecular Electron Density Theory with the aim to rationalise the high‐yielding direct regioselective synthesis of 1,5‐disubstituted‐1,2,3‐triazoles. Topological analysis of the electron localisation function (ELF) of phenyl azide4indicates that it has azwitterionicstructure participating inzw‐type32CA reactions. Computed activation parameters along the two feasible reaction paths for this 32CA reaction makes the rationalisation of the experimental outcomes possible. Grignard reagent‐mediated processes have a polar character and complete regioselectivity, which is in line with the fast, clean, and high yielding reaction experimentally observed. The reaction follows aone‐stepmechanism involving a high asynchronous transition state structure. Topological analysis of the ELF and calculated quantum theory of atoms‐in‐molecule parameters indicate that formation of new C–N single bonds does not begin exactly at the corresponding transition state structure.

An umpolung reaction of α-iminothioesters possessing a cyclopropyl group.

An umpolung N-alkylation reaction of α-cyclopropyl α-iminothioesters with diethylaluminum chloride or ethylmagnesium bromide affords the corresponding N-ethylated α-aminothioesters in good yields. Subsequent oxidation and reaction of the N-ethylated product with a thiolate or a chloride anion proceed effectively to give the ring-opened products in good yields. In contrast, relatively “hard” nucleophiles did not give the ring-opened products but gave the addition products to the iminium carbon.

A convenient approach for vinylation reaction in the synthesis of 5-vinyl-2-pyrrolidinone, a key intermediate of vigabatrin

A convenient, safe and cost-effective method for carrying out the key vinylation of 5-ethoxy-2-pyrrolidinone (8) in the preparation of 5-vinyl-2-pyrrolidinone (2) in the presence of potassium carbonate is described. This present procedure is developed by replacing inherently hazardous ethyl magnesium bromide with inexpensive and eco-friendly potassium carbonate. The reaction was performed on a multi-gram scale, with vinyl magnesium bromide as the vinylation reagent, in an 81% yield to give the 5-vinyl-2-pyrrolidinone with excellent purity and without the need for chromatography.

The asymmetric synthesis of (S,S)-methylphenidate hydrochloride via ring-opening of an enantiopure aziridinium intermediate with phenylmagnesium bromide

The key step in our synthetic strategy towards (S,S)-methylphenidate hydrochloride employs the ring-opening of an in situ formed aziridinium intermediate. Treatment of an α-hydroxy-β-amino ester with methanesulfonic anhydride promoted aziridinium formation and the subsequent addition of phenylmagnesium bromide resulted in stereospecific and regioselective ring-opening to give the corresponding α-phenyl-β-amino ester with overall retention of configuration. Subsequent functional group manipulation followed by N-deprotection and cyclisation generated the piperidine ring within the target compound, and transesterification gave (S,S)-methylphenidate hydrochloride, in only 8 steps from 1,5-pentanediol, in 15% overall yield. These results demonstrate the synthetic utility of enantiopure aziridinium intermediates as substrates for the generation of stereodefined C–C bonds, and crucially this methodology provides access to α-substituted-β-amino ester substrates that are not accessible via enolate alkylation chemistry. The strategy reported herein is potentially applicable to all possible stereoisomers of methylphenidate as well as differentially substituted analogues.

Electrophilic amination of Cu(I) catalyzed phenylmagnesium bromide with N,O-bis(trimethylsilyl)hydroxylamine in THF:N-donor solvent. Control of C–N and C–O chemoselectivity

Reaction of PhMgBr with (Me3Si)HNO(SiMe3)[TMSHA] in the presence of CuI or CuCN catalysis (10–20 mol %) in THF:cosolvent (cosolvent = HMPA or TMEDA) at room temperature can provide an atom-economic and step-economic access for arylamine synthesis starting from aryl Grignard reagents. Chemoselectivity to yield C–N or C–O coupling can be controlled by changing reaction parameters. Cu(I) catalyzed reaction of PhMgBr in THF or in THF:HMPA (or TMEDA) affords both C–N and C–O coupling products, i.e. aniline and phenol (mol ratio ≥ 7:3), whereas uncatalyzed reaction of PhMgBr gives phenol. Mechanisms were proposed for the solvent dependence of chemoselectivity in the coupling of both uncatalyzed and Cu(I) catalyzed Grignard reagent with (TMS)HNO(TMS).

Convenient and easy access to 2-hydroxycyclopent-2-enones from acylcyanohydrins

A convenient access to 2-hydroxycyclopentenones was designed from acylcyanohydrins, by using titanacyclopropane complexes as nucleophilic partners and an intramolecular aldol condensation in basic conditions. The development of a one-pot procedure allows a step- and atom-economic process, and the use of Grignard reagents other than ethylmagnesium bromide provided valuable 3,4-disubstituted 2-hydroxycyclopentenones. The utility of the hydroxy group was illustrated by further functionalization of the α-position using palladium-mediated cross-coupling reactions.