Presence Of Trimethylsilyl Chloride Research Articles

Synthesis of N-Alkyl-1,3-dihydro-2,1-benzisoxazoles.

We describe a practical method for the synthesis of various substituted N-alkyl-1,3-dihydro-2,1-benzisoxazoles and their 2,1-benzisoxazolone precursors starting from readily available methyl 2-nitrobenzoates. The method entails partial nitro reduction with hydrazine and rhodium on carbon to give the hydroxylamines, followed by base-mediated cyclization to give the corresponding benzisoxazol-3(1H)-ones. Subsequent alkylation is conducted under basic conditions and is followed by reduction to the target 1,3-dihydrobenzisoxazoles, achieved with lithium aluminum hydride in the presence of trimethylsilyl chloride.

Inhibition of cytotoxic self-assembly of HEWL through promoting fibrillation by new synthesized α-hydroxycarbamoylphosphinic acids.

The main objective of the present study is to investigate the potency of new synthesized hydroxycarbamoyl phosphinic acid derivatives in modulating cytotoxic fibrillogenesis of hen egg white lysozyme (HEWL), as a common model in protein aggregation studies. Hydroxycarbamoyl phosphinic acid derivatives were prepared by the reaction of α-hydroxyalkylphosphinic acids with isocyanates (or isothiocyanates) in the presence of trimethylsilyl chloride (TMSCl). The designed process involves the condensation reaction leading to formation of new C sp2-P bond formation. The synthesis and purity of novel designed compounds were confirmed by NMR, LC-MS, and HPLC techniques. A range of experiments, including thioflavin T (ThT) and 8-anilino-1-naphthalenesulfonic acid (ANS) fluorescence assays, Congo red binding measurement, atomic force microscopy imaging, MTT-based cell viability and hemolysis assays were employed to investigate anti-amyloidogenic effects of tested compounds. The obtained results demonstrate that these compounds are able to significantly modulate the self-assembly process of HEWL via shortening of nucleation phase leading to the acceleration of fibrillation and appearance of very large and thick fibrils with decreased surface hydrophobicity and cytotoxicity. Based on ANS binding data, we suggest that increased exposure of hydrophobic patches of oligomeric species is the possible mechanism by which tested compounds promote self-assembly process of HEWL. Fluorescence anisotropy and molecular docking studies indicate the interaction of both synthesized compounds with HEWL, and more specifically with residues that are situated in the highly aggregation-prone β-domain region of protein. This study unveils the potential of hydroxyalkylphosphinic acids as modulators of amyloid fibrillation highlighting these compounds as a promising approach for targeting protein aggregates associated with neurodegenerative diseases.

Iron(III)‐Catalyzed Difluoroalkylation of Aryl Alkynes with Difluoroenol Silyl Ether in the Presence of Trimethylsilyl Chloride

AbstractThe reaction of non‐fluorinated silyl enol ether with alkyne is useful for the synthesis of β,γ‐unsaturated carbonyl compounds. However, most of the existing methods for realizing such organic transformation usually employ stoichiometric amounts of relatively expensive Lewis acids/metallic salts. Herein, an iron(III)‐catalyzed difluoroalkylation of aryl alkynes with difluoroenol silyl ether was developed. The reactions proceeded smoothly in the presence of a catalytic amount of iron(III) chloride, stoichiometric amounts of trimethylsilyl chloride, and 4 Å molecular sieves in dichloroethane (DCE) to afford the corresponding α‐alkenyl‐α,α‐difluoroketones in modest to good yields. Remarkably, among the various metallic salts screened, cheap and less‐toxic iron(III) salt was found to be the most efficient Lewis acid catalyst for the present reaction. In addition, in the absence of iron(III) chloride or trimethylsilyl chloride, either no reaction occurred or considerably reduced reaction performance was observed. Moreover, the use of Brønsted acid to replace iron(III) chloride as reaction catalyst failed to promote the reaction. The reaction could be scaled up and the obtained difluoroalkylated carbonyl compound serves as a versatile building block which could be subjected to late‐stage diversification to be converted into useful organic molecules containing CF2H and CF2CF2 moieties. Deuterated experiments showed that the proton in the generated alkene product should originate from trace amounts of water present in the reaction system.magnified image

Efficient synthesis of novel 2‐(2‐chloroquinolin‐3‐yl)imidazo[1,2‐a]pyridin‐3‐amine derivatives

AbstractAn efficient method is applied for the synthesis of novel 2‐(2‐chloroquinolin‐3‐yl)‐N‐alkylimidazo[1,2‐a]pyridin‐3‐amine derivatives. The method is based on a two‐step approach from acetanilide, 2‐chloro‐3‐formyl quinoline, 2‐aminopyridine, and isocyanide under mild reaction conditions. In the first step, acetanilide forms 2‐chloroquinoline‐3‐carbaldehyde in the presence of phosphoryl chloride. The synthesized 2‐chloroquinoline‐3‐carbaldehyde takes part in a multicomponent reaction with 2‐aminopyridine, and isocyanide in the presence of trimethylsilyl chloride. The reaction is facile and the products are synthesized in high isolated yields under mild reaction conditions.

Efficient and chemoselective hydroboration of organic nitriles promoted by TiIV catalyst supported by unsymmetrical acenaphthenequinonediimine ligand

We report the synthesis, characterization, and utilization of a titanium (IV) complex [(η5-C5H5){L}TiCl2] (1) supported by a monoanionic ligand (L), N-(2, 6-diisopropyl)acenaphthenequinonediimido, as a molecular pre-catalyst for the hydroboration of nitriles. The unsymmetrical N-silylated N-(2, 6-diisopropyl)-N-(trimethylsilyl)-acenaphthenequinonediimine ligand (LSiMe3) was obtained upon the completion of a one-pot reaction between N-(2, 6-diisopropyl)iminoacenaphthenone and lithium hexamethyldisilazide in the presence of trimethylsilyl chloride in 1:1:1 M ratio at 90 °C. The reaction of LSiMe3 with {η5-(C5H5)TiCl3) in equal proportion (1:1) at 60 °C afforded the titanium complex [(η5-C5H5){L}TiCl2] (1) in good yield. The molecular structures of the N-silyl ligand (LSiMe3) and Ti(IV) complex 1 were established by single-crystal X-ray analysis. Complex 1 was tested as a pre-catalyst for hydroboration of nitriles with pinacolborane (HBpin) and catecholborane (HBcat) to afford diboryl amines at ambient temperature. Titanium complex 1 exhibited high conversion, superior selectivity, and broad functional group tolerance during hydroboration of nitriles with both HBpin and HBcat under mild conditions.

Metal‐Free Transamidation of Primary Amides using Trimethylsilyl Chloride

AbstractA metal‐free transamidation of primary amides was developed. Trimethylsilyl chloride (TMSCl) acted as the activator in transamidation. In the presence of TMSCl, primary amides reacted with primary amines to yield transamidated secondary amides in NMP solvent. The transamidation of benzamide with secondary amines for the formation of tertiary amides succeeds in an NMP/CHCl3 solvent mixture.

Nickel/Briphos-Catalyzed Direct Transamidation of Unactivated Secondary Amides Using Trimethylsilyl Chloride.

Direct transamidation of secondary amides was developed via nickel catalysis. In the presence of trimethylsilyl chloride and manganese, Ni(diglyme)Cl2 with a Briphos ligand efficiently promoted the transamidation of N-aryl benzamide derivatives with primary amines to afford the corresponding secondary amides in moderate to good yields. Primary amines bearing electron-donating groups gave higher yields of the transamidation products.

Highly effectual synthesis of 4,6-diarylpyrimidin-2(1H)-ones using N,N,N′,N′-tetramethylethylenediaminium-N,N′-disulfonic acid hydrogen sulfate as a dual-functional catalyst

Abstract The highly effectual synthesis of 4,6-diarylpyrimidin-2(1H)-ones via the one-pot multicomponent reaction of acetophenones with arylaldehydes and urea in the presence of trimethylsilyl chloride and a catalytic amount of the ionic liquid N,N,N′,N′-tetramethylethylenediaminium-N,N′-disulfonic acid hydrogen sulfate ([TMEDSA][HSO4]2) under solvent-free conditions has been described. The reaction results and conditions of the catalytic system have been compared with previously reported catalysts. [TMEDSA][HSO4]2 afforded better results in comparison with the reported catalysts in terms of one or more of these factors: yield, temperature, the reaction media, time, and generality. Moreover, a plausible reaction mechanism based on dual functionality of the catalyst has been proposed.

A general method for interconversion of boronic acid protecting groups: trifluoroborates as common intermediates.

We have developed a general protocol for the interconversion of diverse protected boronic acids, via intermediate organotrifluoroborates. N-Methyliminodiacetyl boronates, which have been hitherto resistant to direct conversion to trifluoroborates, have been shown to undergo fluorolysis at elevated temperatures. Subsequent solvolysis of organotrifluoroborates in the presence of trimethylsilyl chloride and a wide range of bis-nucleophiles enables the generation of a variety of protected boronic acids.

TMSCl-catalysed condensation of α-diketone compounds with urea/thiourea derivatives under solvent-free conditions

An efficient, rapid and green synthesis of glycoluril, imidazolidine-2-one, imidazole-2-one and imidazole-2-thiol derivatives have been accomplished by the reaction of urea/thiourea derivatives and α-diketone at 100°C in the presence of trimethylsilyl chloride (TMSCl) as Lewis acid catalyst under solvent-free conditions. This approach offers many advantages such as good product yields, various products, short reaction time, easy isolation of products, facile purification and environmentally benign reaction conditions. Synthesis of some glycoluril, imidazolidine-2-one, imidazole-2-one and imidazole-2-thiol derivatives was carried out by condensation reaction of urea derivatives with α-diketone compounds in the presence of trimethylsilyl chloride (TMSCl) catalyst under solvent-free conditions.

ChemInform Abstract: Trimethylsilyl Chloride Promoted Synthesis of α‐Branched Amines by Nucleophilic Addition of Organozinc Halides to Nitrones.

AbstractThe present new method proceeds in the presence of trimethylsilyl chloride which acts as an essential reaction promoter and a protection reagent for the sensitive N‐hydroxylamine group.

ChemInform Abstract: 4‐Chloro‐3‐(trifluoroacetyl)‐ and 4‐Chloro‐3‐(methoxalyl)coumarins as Novel and Efficient Building Blocks for the Regioselective Synthesis of 3,4‐Fused Coumarins.

Abstract 4-Chloro-3-(trifluoroacetyl)- and 4-chloro-3-(methoxalyl)coumarins react with electron-rich aminoheterocycles, dimethyl 1,3-acetonedicarboxylate, hydrazines, alkyl thioglycolates, and methyl sarcosinate to give a variety of 3,4-heteroannulated coumarins. The starting materials were prepared by the reaction of 4-hydroxycoumarin with trifluoroacetic anhydride and methyl 2-chloro-2-oxoacetate in the presence of trimethylsilylchloride. An NMR study and X-ray crystallographic analysis are reported.

Trimethylsilyl chloride promoted synthesis of α-branched amines by nucleophilic addition of organozinc halides to nitrones

A general procedure for the nucleophilic addition of organozinc halides with nitrones in the presence of trimethylsilyl chloride has been developed. Trimethylsilyl chloride was found to be both an indispensable reaction promoter and a ready hydroxylamine protective agent in these reactions. The produced O-(trimethylsilyl)hydroxylamines can be easily reduced into corresponding amines just by a zinc-copper couple in saturated aqueous NH(4)Cl solution.

4-Chloro-3-(trifluoroacetyl)- and 4-chloro-3-(methoxalyl)coumarins as novel and efficient building blocks for the regioselective synthesis of 3,4-fused coumarins

4-Chloro-3-(trifluoroacetyl)- and 4-chloro-3-(methoxalyl)coumarins react with electron-rich aminoheterocycles, dimethyl 1,3-acetonedicarboxylate, hydrazines, alkyl thioglycolates, and methyl sarcosinate to give a variety of 3,4-heteroannulated coumarins. The starting materials were prepared by the reaction of 4-hydroxycoumarin with trifluoroacetic anhydride and methyl 2-chloro-2-oxoacetate in the presence of trimethylsilylchloride. An NMR study and X-ray crystallographic analysis are reported.

Highly chemoselective reductive amination by one pot reaction of aldehydes, amines and Dihydropyridine Catalyzed by TMSCl

More efficient, cost effective and metal free DHP/TMSCl system for one pot reductive amination of aldehydes was developed. The method allows the efficient one pot synthesis of structurally diverse amines with Hantzsch ester as the hydrogen source in the presence of trimethylsilyl chloride as a catalyst in high to quantitative yields under mild conditions.

Ionic liquid: an efficient and recyclable medium for the synthesis of octahydroquinazolinone and biscoumarin derivatives

A facile and environmentally benign procedure for the synthesis of octahydroquinazolinone and biscoumarin derivatives in ionic liquids is reported. Octahydroquinazolinones were synthesized in the presence of trimethylsilyl chloride (TMSCl) while the synthesis of biscoumarins required no additive. The ability to reuse the ionic liquid, the high yields, and ease of purification are the important features of this process.

H6P2W18O62-18H2O, a Green and Reusable Catalyst for the Three-Component, One-Pot Synthesis of 4,6-Diarylpyrimidin-2(1H)-ones Under Solvent-Free Conditions

Three-component, one-pot synthesis of 4,6-diarylpyrimidin-2(1H)-ones and 9-phenyl-8-oxa-10,12-diaza-tricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-11-one by condensing acetophenone derivatives, aldehydes, and urea in the presence of trimethylsilyl chloride using a catalytic amount of H6P2W18O62-18H2O under solvent-free conditions is reported.

H 3PMo 12O 40 catalyzed three-component one-pot synthesis of 4,6-diarylpyrimidin-2(1 H)-ones under solvent-free conditions

4,6-Diarylpyrimidin-2(1 H)-one derivatives have been synthesized from three-component one-pot condensation of acetophenone derivatives, aldehydes and urea in the presence of trimethylsilyl chloride and a catalytic amount of H 3PMo 12O 40 under solvent-free conditions.

A Modified and Green Procedure for the Synthesis of β‐Amido Ketones Using a Br?nsted‐Acidic Ionic Liquid as Novel and Reusable Catalyst

AbstractA green and improved method for the synthesis of β‐amido ketones through one‐pot multi‐component reaction of an enolizable ketone, aryl aldehyde, acetonitrile or benzonitrile in the presence of trimethylsilyl chloride using 3‐methyl‐1‐(4‐sulfonic acid)butylimidazolium hydrogen sulfate [(CH2)4SO3HMIM][HSO4], a Br?nsted‐acidic ionic liquid, as an effective and recyclable catalyst is described. The present methodology offers several advantages such as simple procedure with an easy work‐up, relatively short reaction time, and good to excellent yields.

TMSCl‐mediated one‐pot, three‐component synthesis of 2H‐indazolo[2,1‐b]phthalazine‐triones

Abstract magnified imageA simple, efficient, and cost‐effective method for the synthesis of 2H‐indazolo[2,1‐b]phthalazine‐1,6,11(13H)‐trione derivatives by a one‐pot, three‐component condensation reaction of phthalazide, dimedone, or 1,3‐cyclohexanedione and aromatic aldehydes under CH3CN/DMF (8:2) media at 80°C for 30–60 min in the presence of trimethylsilyl chloride (TMSCl) is described. J. Heterocyclic Chem., (2009).