Role of sulphur-heterocycles in medicinal chemistry: An update

An efficient, general, and unprecedented methodology for the synthesis of 2-methylene-2,3-dihydro-1,4-thiazepines from N-propargylic β-enaminones is described. Initially, N-propargylic β-enaminones were thionated with Lawesson’s reagent in good to high yields, and then the resulting N-propargylic β-enaminothiones were subjected to electrophilic cyclization. When treated with zinc chloride in refluxing chloroform, N-propargylic β-enaminothiones underwent electrophilic cyclization to yield 2-methylene-2,3-dihydro-1,4-thiazepines in good to high yields. A general trend was observed for all N-propargylic β-enaminothiones, and the cyclization proceeded with high efficiency and large functional group tolerance. This process is also applicable to the cyclization of internal alkyne-tethered N-propargylic β-enaminothiones. This operationally simple and facile method may represent a very rapid entry to a library of functionalized 1,4-thiazepines in the area of pharmaceuticals.

Synthesis of 1,4-Thiazepines

Iodine‐Catalyzed, Ethyl‐Lactate‐Mediated Synthesis of 1,4‐Benzothiazines via Metal‐Free Cascade Enaminone Transamination and C−H Sulfenylation

A facile and highly efficient one-pot synthesis of novel thiazepine and benzothiazepine derivatives was established by ring expansion. With a greener methodology (ultrasonication), a polysubstituted ring system with the thiazepine core moiety can be easily synthesized from simple and easily available reactants in good yields. Moreover, the synthesized compounds show fluorescence and also antioxidant activity.

Synthesis and Characterization of Thiazepine/Benzothiazepine Derivatives Through Intramolecular C‐2 Ring Expansion Pathway

Organosulfur compounds have a pivotal role in the functionalities of many natural products, pharmaceuticals and organic materials. For these reasons, the search for new methodologies for the formation of carbon–sulfur bonds has been the object of intensive work for organic chemists. However, the proposed strategies suffer from various drawbacks, such as volatility, toxicity, and instability of the sulfur sources or the use of VOC solvents. In this review, we summarise the recent protocols which have the goal of obtaining sulfones, thioethers, thiazines, thiazepines and sulfonamides in an unconventional and/or sustainable way. The use of starting materials less invasive and toxic with respect to the traditional reagents, alternative solvents such as water, ionic liquids or deep eutectic solvents, the exploitation of ultrasound and electrochemistry, increasing the efficiency of the process, are reported. Moreover, representative reaction mechanisms are also discussed.

Unconventional approaches for the introduction of sulfur-based functional groups

A one pot synthesis of 1,4-benzothiazines from 1,3-benzothiazolium cations and α-haloketones through ring expansion under ultrasonication was carried out by employing optimal 5% sodium hydroxide and characterization was done with the help of various spectroscopic techniques viz. NMR, IR and mass spectrometry. Single crystal X-ray diffraction and computational studies of (4-bromophenyl)(4-methyl-4H-benzo[b][1,4]thiazin-2-yl)methanone (3c) were also performed. Different concentrations of different bases (NaOH, Na2CO3, NaHCO3 solutions etc.) were used to obtain 1,4-benzothiazine derivatives. But, the best results were obtained with 5% NaOH solution (3.7 equivalents) for the synthesis of single product 1,4-benzothiazine derivatives while, with other concentrations, the reaction did not proceed to a single product. Quantum chemical calculations were done to find the optimized geometry and to correlate the experimental and calculated values of the bond parametres and 13C NMR chemical shifts of the synthesized compound. The optimized geometry was obtained using density functional theory (DFT) with the basis set 6-31G(d). The theoretical values of the 1H NMR chemical shifts were in agreement with the experimental values. The photophysical properties of some of the synthesized compounds were studied with the help of ultraviolet-visible and fluorescence spectroscopy.

Base induced synthesis of 4H-1,4-benzothiazines and their computational studies

The title thiazines are obtained in one-pot from benzothiazolium cations and α-haloketones by ring expansion under ultrasonication.

Damanjt Singh Cannoo

Papers

Synthesis and Characterization of Thiazepine/Benzothiazepine Derivatives Through Intramolecular C‐2 Ring Expansion Pathway

Base induced synthesis of 4H-1,4-benzothiazines and their computational studies

Base Induced Synthesis of 4H‐1,4‐Benzothiazines and Their Computational Studies.