Synthesis of trans N-Substituted Pyrrolidine Derivatives Bearing 1,2,4-triazole Ring

Background: 1,2,4-triazoles scaffolds display significant biological activities due to hydrogen bonding, solubility, dipole character, and rigidity Objective: The core motif of 1,2,4-triazoles plays a vital role in clinical drugs such as Rizatriptan (anti-migraine), Ribavirin (antiviral), anastrozole (anticancer), etizolam (anxiolytic), estazolam (anticonvulsant), alprazolam (anti-hypnotic), letrozole (aromatase inhibitor), loreclezole (anticonvulsant), trazadone (antidepressant) etc Method: Epoxide ring opening of tert-butyl 6-oxa-3-azabicyclo [3.1.0] hexane-3-carboxylate followed by methylation under basic conditions and de-protection gave the corresponding trans 1-(4-methoxypyrrolidin-3-yl)-1H-1,2,4-triazole hydrochloride salt as the precursor. This precursor on reaction with substituted benzoyl chlorides and benzyl bromides gave the desired amide and amine products Results: A library of 14 N-substituted pyrrolidine derivatives i.e. trans3-methoxy-4-(1H-1,2,4-triazol-1-yl) pyrrolidin-1-yl) (phenyl)methanone and trans 1-benzyl-4-methoxypyrrolidin-3-yl)-1H-1,2,4-triazole were prepared Conclusion: Eight novel amides (6a-h) and six amines (8a-f) derivatives were synthesized using 1-(4-methoxypyrrolidin-3-yl)-1H-1,2,4-triazole 4 salt with substituted benzoyl chlorides and benzyl bromides.

Synthesis, antibacterial activities, binding mode analysis and predictive ADME studies of novel 1-(aryl)-2-(1H-imidazol-1-yl)methanones

Introduction: In the present study a novel series of twelve 1-(aryl)-2-(1H-imidazol-1-yl)methanones 3(a-l) were synthesized and characterised by physicochemical and spectral analysis,viz. elemental analysis, IR spectroscopy, NMR spectroscopy. The antibacterial property of the compounds were examined, in order to develop new broad spectrum antibiotics. Methods: The compounds 3(a-l) were synthesised by reacting the corresponding 2-(aryl)-1H-imidazoles 2 with substituted benzoyl chlorides. Binding mode analysis of the most active compound was carried out. Predictive ADME studies were carried out for all the compounds. Results and Discussions: Among the synthesized compounds, (2-(3-nitrophenyl) (2,4-dichlorophenyl) -1Himidazol-1-yl)methanone 3i exhibited highest antibacterial activity. Binding mode analysis of the highest active compound was carried out in the active site of glucosamine-6-phosphate synthase (2VF5).

The use of isoxazoline and isoxazole scaffolding in the design of novel thiourea and amide liquid-crystalline compounds

A series of novel thiourea and amide liquid crystals containing 5-membered isoxazoline and isoxazole rings were synthetized and the liquid crystal properties studied. Thioureas were obtained using a condensation reaction of benzoyl chlorides, arylamines and ammonium thiocyanate. The amides, on the other hand, were the byproduct of a quantitative reaction which used potassium cyanate as the starting material. Thiourea and amide derivatives were predominantly SmA mesophase inductors. A nematic mesophase was observed only for thioureas and amides containing an isoxazole ring. Additionaly, the liquid crystal behavior was also dependent on the relative position of nitrogen and oxygen atoms on the 5-membered heterocycle.

Facile Synthesis of Novel Benzoylthiophene C-Nucleoside Analogues via Coupling of Sugar Alkynes, Aroyl Chlorides, and 1,4-Dithiane-2,5-diol

Concise synthesis of novel benzoylthiophene C-nucleoside analogues has been achieved by the reaction of various terminal sugar alkynes with substituted benzoyl chlorides and 1,4-dithiane-2,5-diol, and subsequent dilute HCl-promoted dehydration in one pot. The sugar alkynes include pyranosides, furanosides, and acyclic sugar. The benzoyl chloride has various substituents. Twenty-eight examples are given. The desired products are obtained in 70–89% yields, and the mechanism has been clarified by isolation of the intermediate.

Friedel–Crafts approach to the one-pot synthesis of methoxy-substituted thioxanthylium salts

An efficient synthesis of methoxy-substituted thioxanthylium salts has been developed. The reaction of diaryl sulfides with benzoyl chlorides in the presence of TfOH smoothly proceeded to give the desired thioxanthylium salts in good yields. In their UV–vis spectra, the maximum absorption wavelengths of methoxy-functionalized thioxanthylium salts were observed at around 460 nm, which show a drastic red shift compared to the parent thioxanthylium salts. The present reaction provides a versatile access to functionalized thioxanthylium salts, and therefore it constitutes a promising tool for the synthesis of biologically and photochemically active molecules.

Friedel-Crafts approach to the one-pot synthesis of methoxy substituted thioxanthylium salts

An efficient synthesis of methoxy substituted thioxanthylium salts has been developed. The reaction of diaryl sulfides with benzoyl chlorides in the presence of TfOH smoothly proceeded to give the desired thioxanthylium salts in good yields. In their UV-vis spectra, the maximum absorption wavelengths of methoxy functionalized thioxanthylium salts were observed at around 460 nm, which show a drastic red shift compared to the parent thioxanthylium salts. The present reaction provides a versatile access to functionalized thioxanthylium salts, and therefore it constitutes a promising tool for the synthesis of biologically and photochemically active molecules.

Unexpected Migration of Benzoyl Group in the Synthesis of 3-Benzoyl-2-Phenylbenzofurans under Wittig Conditions

In the present work, we report the unexpected formation of isomeric 3-benzoyl-2-phenylbenzo[b]furans using triphenylphosphonium salt and benzoyl chlorides under Wittig conditions. In particular, we found that the o-[(benzoyloxy)benzyl]-triphenyl-phosphoranes constitute the key intermediate that reasonably undergoes benzoyl group migration.

Synthesis of 4-aryl-1,3,4a-Triazaphenanthrene-2-Selones via Three-Component Condensation of Quinolin-2-Amine, Potassium Selenocyanate and an Acyl Chloride

A three-component reaction between quinolin-2-amine, potassium selenocyanate and variously substituted benzoyl chlorides in acetone at room temperature provided a simple and efficient one-pot route for the synthesis of six 4-aryl-1,3,4a-triazaphenanthrene-2-selones in good yields.