Nirmalya Mukherjee

Solvent-free one-pot synthesis of 1,2,3-triazole derivatives by the ‘Click’ reaction of alkyl halides or aryl boronic acids, sodium azide and terminal alkynes over a Cu/Al2O3 surface under ball-milling

A one-pot procedure for the synthesis of 1,2,3-triazole derivatives by a three-component coupling of alkyl (benzyl) halides or aryl boronic acids, sodium azide and terminal alkynes over copper(II) sulfate supported on alumina (Cu/Al2O3) under ball-milling in the absence of any solvent and additive has been developed. The product was isolated by simple washing of the crude reaction residue with ethanol followed by evaporation of the solvent. No chromatographic purification is required. The catalyst is recycled for subsequent reactions. The azides are produced in situ and thus this procedure avoids the handling of hazardous azides. This protocol offers broad scope for access to a variety of diversely substituted 1,2,3-triazoles. The use of no hazardous organic solvent, the use of ball-milling, and cost efficiency, recyclability of the catalyst up to eight runs without appreciable loss of activity and high yields of products make this procedure greener.

Reaction under ball-milling: solvent-, ligand-, and metal-free synthesis of unsymmetrical diaryl chalcogenides.

A convenient, efficient, and general procedure for the synthesis of diaryl chalcogenides including sulfides, selenides and tellurides has been developed by the reaction of diazonium tetrafluoroborates and diaryl dichalcogenides on the surface of alumina under ball-milling without any solvent or metal. A wide range of functionalized diaryl chalcogenides are obtained in high purity by this procedure.

A general and green procedure for the synthesis of organochalcogenides by CuFe2O4 nanoparticle catalysed coupling of organoboronic acids and dichalcogenides in PEG-400

A general and efficient procedure has been developed for the synthesis of organochalcogenides (selenides and tellurides) by a simple reaction of organoboronic acids and dichalcogenides catalysed by CuFe2O4 nanoparticles in PEG-400 without any ligand. This protocol offers the scope for access to a wide spectrum of chalcogenides including diaryl, aryl–heteroaryl, aryl–styrenyl, aryl–alkenyl, aryl–allyl, aryl–alkyl and aryl–alkynyl versions. The catalyst is magnetically separable and recyclable eight times without any loss of appreciable catalytic activity. The products are obtained in high purities after evaporation of solvent followed by filtration column chromatography.

Heterogeneous CuII‐Catalysed Solvent‐Controlled Selective N‐Arylation of Cyclic Amides and Amines with Bromo‐iodoarenes

A selective N-arylation of cyclic amides and amines in DMF and water, respectively, catalysed by Cu(II) /Al2 O3 has been achieved. This protocol has been employed for the synthesis of a library of arenes bearing a cyclic amide and an amine moiety at two ends, including a few scaffolds of therapeutic importance. The mechanism has been established based on detailed electron paramagnetic resonance (EPR) spectroscopy, X-ray photoelectron spectroscopy (XPS), UV diffuse reflectance spectroscopy (DRS) and inductively coupled plasma-mass spectrometry (ICP-MS) studies of the catalyst at different stages of the reaction. The Cu(II) /Al2 O3 catalyst was recovered and recycled for subsequent reactions.

Mechanism of Inducible Nitric-Oxide Synthase Dimerization Inhibition by Novel Pyrimidine Imidazoles

Background: Overproduction of nitric oxide by dimeric inducible nitric-oxide synthase (iNOS) is physiologically harmful. Results: Pyrimidine imidazole derivative (PID) binds to both the iNOS dimer and monomer causing irreversible monomerization and inhibition of dimerization, respectively. Conclusion: PID can physiologically inhibit iNOS both during and after its assembly into active enzyme. Significance: Our study reveals PIDs dual ability to inhibit iNOS as well as their kinetic mechanisms. Overproduction of nitric oxide (NO) by inducible nitric-oxide synthase (iNOS) has been etiologically linked to several inflammatory, immunological, and neurodegenerative diseases. As dimerization of NOS is required for its activity, several dimerization inhibitors, including pyrimidine imidazoles, are being evaluated for therapeutic inhibition of iNOS. However, the precise mechanism of their action is still unclear. Here, we examined the mechanism of iNOS inhibition by a pyrimidine imidazole core compound and its derivative (PID), having low cellular toxicity and high affinity for iNOS, using rapid stopped-flow kinetic, gel filtration, and spectrophotometric analysis. PID bound to iNOS heme to generate an irreversible PID-iNOS monomer complex that could not be converted to active dimers by tetrahydrobiopterin (H4B) and l-arginine (Arg). We utilized the iNOS oxygenase domain (iNOSoxy) and two monomeric mutants whose dimerization could be induced (K82AiNOSoxy) or not induced (D92AiNOSoxy) with H4B to elucidate the kinetics of PID binding to the iNOS monomer and dimer. We observed that the apparent PID affinity for the monomer was 11 times higher than the dimer. PID binding rate was also sensitive to H4B and Arg site occupancy. PID could also interact with nascent iNOS monomers in iNOS-synthesizing RAW cells, to prevent their post-translational dimerization, and it also caused irreversible monomerization of active iNOS dimers thereby accomplishing complete physiological inhibition of iNOS. Thus, our study establishes PID as a versatile iNOS inhibitor and therefore a potential in vivo tool for examining the causal role of iNOS in diseases associated with its overexpression as well as therapeutic control of such diseases.

CHAPTER 1:Carbon–Heteroatom Bond Forming Reactions and Heterocycle Synthesis under Ball Milling

Ball-milling has received considerable attention in organic synthesis as reactions under ball milling can be performed in the absence of any solvent, at ambient temperature and under mild conditions, which are relevant for a green process. The carbon–heteroatom bond forming reactions and synthesis of heterocycles are of much importance in academia as well as pharmaceutical industry. The present chapter focuses on the carbon–heteroatom bond forming reactions (particularly C–N, C–O, C–S, C–Se, C–Te, C–F, C–Cl, C–I, etc.) and the synthesis of heterocycles (particularly N-, O- and B-containing heterocycles and macro-heterocycles) under ball-milling. Moreover, the oxygenation and cycloaddition reactions of fullerene leading to corresponding heterocycles are also included.

Synthesis of Bioactive Five- and Six-Membered Heterocycles Catalyzed by Heterogeneous Supported Metals

Abstract The synthesis of five- and six-membered heterocycles is of continued interest due to the potent bioactivity and application of these molecules as therapeutic drugs. On the other hand, heterogeneous catalysts have also gained tremendous attention in both industry and academia due to their environmentally benign character. The present chapter focuses on the synthesis of bioactive five- and six-membered heterocycles (particularly N-, O-, and S-containing molecules) by heterogeneous catalysts involving transition metals (Pd, Cu, Au, and Sn), bimetallic systems (Pt/Ir and Mg/Al), and metal oxides (PdO, CuO, ZnO and SnO 2 ). The five-membered N-containing heterocycles (such as indoles, oxindoles, and triazoles), O-containing heterocycles (such as furans and benzofurans) and S-containing compounds (benzothiazoles and thiophenes) have been included whereas among six-membered heterocycles, syntheses of quinilones, quinazolines, and quinoxalines, benzodioxanes, benzoxazines, and 4 H -pyrans have been demonstrated. The preparations of heterogeneous catalysts, their structures, recyclability, and function with reference to certain significant reactions are discussed in detail.