Reaction Of Grignard Reagents Research Articles

Synthesis and Multifaceted Exploration of 4-Phenylpiperidin-4-ol Substituted Pyrazole: Photophysical Insights with Biological Activity

Abstract In this study, we successfully synthesized a pyrazole derivative, specifically 4-phenylpiperidin-4-ol substituted pyrazole (CHP), through the reaction of Grignard reagents in combination with pyrazole. This newly synthesized molecule was subjected to a comprehensive evaluation for both its photophysical and biological applications. Notably, CHP exhibited promising invitro antifungal and antibacterial activities, primarily attributed to the presence of the 4-phenylpiperidin-4-ol moiety and resulting component contributed to an enhanced absorption rate of lipids, thereby improving the pharmacological activity of CHP. This correlation between structure and function was further supported by the outcomes of structure-activity relationship studies. Additionally, we conducted in silico studies to examine the molecular interactions of the synthesized molecule with key proteins, including DNA Gyrase, Lanosterol 14 α-demethylase, and KEAP1-NRF2. The results unveiled robust binding interactions at specific sites within these proteins, indicating potential therapeutic relevance. Furthermore, the photophysical properties of the synthesized compounds were thoroughly investigated using the ab-initio technique. This involved the determination of ground state optimization and HOMO-LUMO energy levels, all calculated with the DFT-B3LYP-6-31G(d) basis set. The assessment of the theoretically estimated HOMO-LUMO value provided insights into the global chemical reactivity descriptors, revealing that the synthesized molecule boasts a highly electronegative and electrophilic index. Taken together, our findings suggest that pyrazole derivatives with 4-phenylpiperidin-4-ol substitutions exhibit promising applications in both photophysical and biological contexts.

Methylene bis(p-chlorobezodithioate): Synthesis, characterization and its use as analytical reagent for Silver ion

The study included the preparation and diagnosis of disulfur ligands (Dithiols) and the preparation of their complex with monovalent (Silver), which included the the following steps: First: preparation of the sulfur compound through the reaction of Grignard reagent (ClPhMgX), with carbon disulfide (CS2), this step form [ClPhCS2]- , an acidic liquid sulfur compound which was converted into a dimer compound by second step :- reacting with (Benzene tetra methyl ammonium hydroxyl) which produce a negatively charged compound [ClPhCS2]-, which is a viscous, hydrated compound with a strong sulfur smell. The product [ClPhCS2]- react with dichloromethane (DCM) which produce (methylene-bis (p-Chlorodithiobenzoate). Which is characterized with (IR,UV-VIS, 1H-NMR, 13C spectroscopy , mass spectrometry) then followed by Analytical study for the prepared compound were investigated by preparation of their complex with Monovalent (Silver), where the stability constants of the prepared complex were studied, which showed the stability of the complex at room temperature and at pH (PH = 8). The absorbance of the complex for UV-Vis. light was studied and the mole ratio (M: L) was studied. From the study of spectroscopic methods.

Transition‐Metal‐Free Chichibabin‐Type Coupling of Halo‐azaarenes with Grignard reagents

AbstractA Chichibabin‐type coupling of halo‐azaarenes with Grignard reagents under transition‐metal‐free conditions is developed. The alkylation and arylation of azaarenes can be achieved by the reaction of Grignard reagents with azaarenium salts mediated by BTC/DMAP/DCM system. It has practical value for preparing functionalized azaarenes.

An Efficient Route for the Synthesis of 1,5‐Disubstituted Tetrazoles and their Anti‐Microbial Activity Against Salmonella Paratyphi

AbstractCarbimidothioates were synthesized by the reaction of Grignard reagents with arylisothiocyanates followed by methylation with methyl iodide. Further, these carbimidothioates were cyclized with sodium azide in DMF at 120 °C to get 1,5‐disubstituted tetrazoles, which are important class of compounds in medicinal chemistry. Hence, we evaluated the antibacterial activity against Salmonella Paratyphi bacteria. Among the series, compounds 6 a, 6 c, 6 f and 6 i effectively inhibited Solamonella Paratyphi. Compound 6 f performed well in the agar well diffusion experiment. Compound 6 i outperformed the standard drug in micro dilution assay and biofilm inhibition experiment using Crystal violet at 1 mM concentration. These studies demonstrates that active molecules are the most promising options for reducing S. paratyphi biofilm. In order to know the binding mode of the synthesized molecules, we performed molecular docking studies with protein Salmonella Paratyphi A lipopolysaccharide acetyltransferase periplasmic domain (PDB ID‐6SE1). Among the series, compounds 6 f and 6 i exhibited the most significant affinity score with 6SE1 protein.

Claisen type Condensation of Methyl Ketones with Carbimidothioates: A New Gateway for the Synthesis of β‐Enaminones

AbstractCarbimidothioates are synthesized by the reaction of Grignard reagents or heteroaryl lithium compounds with arylisothiocyanates followed by treatment with methyl iodide. Further, application of these intermediates in the synthesis of β‐enaminones by their condensation with methyl ketones in the presence of sodium hydride in DMF is reported. This method offers a new gateway for the synthesis of β‐enaminones, which are important building blocks in synthetic organic chemistry.

Synthesis of phospholes and 1,1′-biphospholes mediated by zirconacyclopentadienes and PBr3

The efficient synthesis of phospholes through the reactions of Grignard reagents with in situ-generated 1-bromophospholes has been developed. This method allows the easy substituent variation at the phosphorus atom of the phospholes. The 1,1′-biphospholes can also be conveniently prepared through Zn-promoted debromo-dimerization of 1-bromophospholes. The gold-phosphole complexes of LAuCl were also synthesized, which were found to act as efficient catalysts in gold-catalyzed [3+2] cycloaddition of ynamides with 4,5-dihydro-1,2,4-oxadiazoles.

Direct Reaction of Grignard Reagents with Isocyanates in Flow

Direct Reaction of Grignard Reagents with Isocyanates in Flow

A Practical and General Amidation Method from Isocyanates Enabled by Flow Technology

AbstractThe addition of carbon nucleophiles to isocyanates represents a conceptually flexible and efficient approach to the preparation of amides. This general synthetic strategy has, however, been relatively underutilized owing to narrow substrate tolerance and the requirement for less favourable reaction conditions. Herein, we disclose a high‐yielding, mass‐efficient, and scalable method with appreciable functional group tolerance for the formation of amides by reaction of Grignard reagents with isocyanates. Through the application of flow chemistry and the use of substoichiometric amounts of CuBr2, this process has been developed to encompass a broad range of substrates, including reactants found to be incompatible with previously published procedures.

A Practical and General Amidation Method from Isocyanates Enabled by Flow Technology.

The addition of carbon nucleophiles to isocyanates represents a conceptually flexible and efficient approach to the preparation of amides. This general synthetic strategy has, however, been relatively underutilized owing to narrow substrate tolerance and the requirement for less favourable reaction conditions. Herein, we disclose a high-yielding, mass-efficient, and scalable method with appreciable functional group tolerance for the formation of amides by reaction of Grignard reagents with isocyanates. Through the application of flow chemistry and the use of substoichiometric amounts of CuBr2 , this process has been developed to encompass a broad range of substrates, including reactants found to be incompatible with previously published procedures.

Novel syntheses of an aliphatic series of new dithiocarboxylates and perthiocarboxylates of copper (I) and some of their complexes with triphenylphosphine

ABSTRACTCopper(I) alkyldithiocarboxylates (1a), (1b) and (1c) of formula [RCS2Cu]4 [(1a) R = t-Bu, (1b) R = n-Bu, (1c) R = sec-Bu] and copper(I) alkylperthiocarboxylates (2a), (2b) and (2c) of formula [RCS3Cu]4 [(2a) R = t-Bu, (2b) R = n-Pr, (2c) R = cyclohexyl] were prepared from the reaction of Grignard reagents with carbon disulfide, in the presence of CuBr. Cu(I) Dithiocarboxylates (1a) and (1b) were treated with triphenylphosphine to give, respectively, complexes (3a) and (3b) of formula RCS2Cu(PPh3)2 [(3a) R = t-Bu, (3b) R = n-Bu]. The compounds obtained were characterized by various spectroscopic tools including NMR (1H, 13C, 31P) spectroscopy, and single crystal X-ray diffraction.

One-Pot Synthesis of Trisubstituted Triazenes from Grignard Reagents and Organic Azides.

A simple and versatile method for the preparation of linear, trisubstituted triazenes is reported. The procedure is based on the reaction of Grignard reagents with 1-azido-4-iodobutane or 4-azidobutyl-4-methylbenzenesulfonate. These organic azides enable the regioselective formation of triazenes via an intramolecular cyclization step. The new method can be used for the preparation of aryl, heteroaryl, vinyl, and alkyl triazenes. The synthetic utility of vinyl triazenes is demonstrated by acid-induced C-N, C-O, C-F, C-P, and C-S bond-forming reactions.

Long sought synthesis of quaternary phosphonium salts from phosphine oxides: inverse reactivity approach

Quaternary phosphonium salts (QPS), a key class of organophosphorus compounds, have previously only been available by routes involving nucleophilic phosphorus. We report the realisation of the opposite approach to QPS utilising phosphine oxides as the electrophilic partner and Grignard reagents as nucleophiles. The process is enabled through the crucial intermediacy of the derived halophosphonium salts. The route does not suffer from the slow kinetics and limited availability of many parent phosphines and a broad range of QPS were prepared in excellent yields.

Stereoselective synthesis of isoindolinones and tert-butyl sulfoxides

A reaction of Grignard reagents with an optically pure N-sulfinylimine derived from methyl 2-formylbenzoate yields enantioenriched isoindolinones and tert-butyl sulfoxides. The products are formed by the addition of the nucleophile to N-sulfinylimine followed by cyclization to form N-tert-butylsulfinylisoindolinone, which readily undergoes substitution with a second equivalent of Grignard reagent. The reaction can be carried out in dichloromethane at room temperature or at elevated temperatures without any loss of stereoselectivity. The use of nucleophiles other than Grignard reagents has also been investigated.

Copper‐Catalyzed Synthesis of Tetrasubstituted Allenes from Quaternary Ammonium Salts and Grignard Reagents

AbstractAlthough the synthesis of allenes has made considerable progress, methods for tetrasubstituted allenes are still limited. In this paper, the CuBr2‐catalyzed cross‐coupling reaction of Grignard reagents and propargylic ammonium salts in tetrahydrofuran at 60 °C under argon delivered tetrasubstituted allenes in good to excellent yields. The reaction is thought to proceed by an SN2′ pathway.

Fluorographene Modified by Grignard Reagents: A Broad Range of Functional Nanomaterials.

Fluorographene is the youngest stoichiometric derivative of graphene; hence, its reactivity is only poorly explored. Compared to graphene, the significantly higher reactivity of C-F bonds makes this material a suitable platform for a large number of chemical modifications. Fluorographene is also the only member of the halographene family that can be prepared in the stoichiometric composition (C1 F1 ). Herein, the chemical modification of fluorographene with Grignard reagents, which are well known in organic synthesis for the formation of new C-C bonds, is presented. The reaction with alkyl magnesium bromides led to successful modification of fluorographene with ethyl, vinyl, ethynyl and propargyl groups. Chemical characterisation showed the presence of covalently bonded functional groups in a high concentration exceeding one functional group per C6 motif. The reactivity of Grignard reagents with fluorographene decreased from ethyl to ethynyl. The terminal carbon-carbon triple bonds were used for click reactions with organic azides leading to the formation of triazole rings. These findings open up a broad spectrum of opportunities for simple and robust modification of graphene by chemical reactions proceeding at room temperature under mild conditions. These results have major application potential in sensing, biomedical and energy-related applications.

Fabrication of Polyethylene/MoS2 nanocomposites using a novel exfoliated-MoS2–MgCl Bi-supported Ziegler-Natta catalyst via in-situ polymerization

A novel exfoliated-MoS2 (EMoS2)–MgCl bi-supported Ziegler-Natta catalyst was synthesized by the reaction of Grignard reagent and EMoS2, followed by anchoring with TiCl4. The tendency of the individual EMoS2 layers to aggregate was prevented by covering them with solid-state Ziegler-Natta catalyst. The resultant catalyst was applied to ethylene polymerization, forming polyethylene (PE)/EMoS2 organic-inorganic hybrid nanocomposites. The resultant products had a flake-shape morphology, with EMoS2 well dispersed in the PE matrix. In addition, the thermal stability and mechanical properties of PE were significantly enhanced by the introduction of EMoS2.

Association and Dissociation of Grignard Reagents RMgCl and Their Turbo Variant RMgCl⋅LiCl.

Grignard reagents RMgCl and their so-called turbo variant, the highly reactive RMgCl⋅LiCl, are of exceptional synthetic utility. Nevertheless, it is still not fully understood which species these compounds form in solution and, in particular, in which way LiCl exerts its reactivity-enhancing effect. A combination of electrospray-ionization mass spectrometry, electrical conductivity measurements, NMR spectroscopy (including diffusion-ordered spectroscopy), and quantum chemical calculations is used to analyze solutions of RMgCl (R=Me, Et, Bu, Hex, Oct, Dec, iPr, tBu, Ph) in tetrahydrofuran and other ethereal solvents in the absence and presence of stoichiometric amounts of LiCl. In tetrahydrofuran, RMgCl forms mononuclear species, which are converted into trinuclear anions as a result of the concentration increase experienced during the electrospray process. These trinuclear anions are theoretically predicted to adopt open cubic geometries, which remarkably resemble structural motifs previously found in the solid state. The molecular constituents of RMgCl and RMgCl⋅LiCl are interrelated via Schlenk equilibria and fast intermolecular exchange processes. A small portion of the Grignard reagent also forms anionic ate complexes in solution. The abundance of these more electron-rich and hence supposedly more nucleophilic ate complexes strongly increases upon the addition of LiCl, thus rationalizing its beneficial effect on the reactivity of Grignard reagents.

ChemInform Abstract: The Influence of Main Group Metallic Lewis Acids on the Formation and Reactivity of Grignard Reagents

The significance of main group metallic Lewis acids such as LiCl, MgCl2, AlCl3 on the formation and reactivities of Grignard reagents are best demonstrated by recent quick development of their diverse synthetic techniques and versatile reactivities towards various electrophiles. Although substantial progress has been made especially on the selective formation of carbon-metal bonds employing lithium chloride as the activator, novel protocols especially these for regioselective metalation of highly functionalized substrates are continuously developed and thus occupy a hot research spot in organometallic chemistry. This mini-review provides a concise overview mainly on the behavior of main group metallic salts derived from lithium, magnesium and aluminum as a powerful tool for regioselective metalation of C-X ( X = Cl, Br, I) and C-H bonds. The diverse functions of these metallic salts on the reactivities of Grignard reagents are exemplified primarily choosing aldehyde as the electrophile.

The Influence of Main Group Metallic Lewis Acids on the Formation and Reactivity of Grignard Reagents

The significance of main group metallic Lewis acids such as LiCl, MgCl2, AlCl3 on the formation and reactivities of Grignard reagents are best demonstrated by recent quick development of their diverse synthetic techniques and versatile reactivities towards various electrophiles. Although substantial progress has been made especially on the selective formation of carbon-metal bonds employing lithium chloride as the activator, novel protocols especially these for regioselective metalation of highly functionalized substrates are continuously developed and thus occupy a hot research spot in organometallic chemistry. This mini-review provides a concise overview mainly on the behavior of main group metallic salts derived from lithium, magnesium and aluminum as a powerful tool for regioselective metalation of C-X (X = Cl, Br, I) and C-H bonds. The diverse functions of these metallic salts on the reactivities of Grignard reagents are exemplified primarily choosing aldehyde as the electrophile. Keywords: Grignard reagent, metallic Lewis acids, main group.

Reactions of Grignard Reagents with Tin-Corrole Complexes: Demetalation Strategy and σ-Methyl/Phenyl Complexes

An efficient, mild, and one-step methodology for the conversion of tin-corroles to the corresponding free base corroles has been developed. The Grignard reagent, namely, methylmagnesium chloride, is responsible for the facile demetalation of tin-corroles. In an optimized reaction, almost complete destannation is observed using methylmagnesium chloride in a representative corrolato-Sn(IV)-chloride complex. This particular protocol has also been proven to be versatile on a wide variety of corrolato-Sn(IV)-chloride substrates. Similar Grignard reagents, namely, methyl/phenylmagnesium bromides, however, failed to perform the desired demetalation reaction and rather resulted in the usual σ-methyl/phenyl complexes in good yields. In addition to two novel σ-phenyl complexes and three novel σ-methyl complexes, one new A3-corrole and one new corrolato Sn(IV)chloride have also been synthesized. All the complexes have been thoroughly characterized by various spectroscopic techniques, including single-crystal X-ray s...