A new synthetic route to 1,3,4‐oxadiazoles. Pharmacological study of some new derivatives

Abstract

2‐Substituted 1,3,4‐oxadiazoles have been examined as possible prodrugs of antidepressant hydrazides. A new method of synthesis of this heterocycle from thionoester and five new oxadiazoles substituted at the 2‐position by a 4‐pyridyl or 4‐aminophenyl group and at the 5‐position by a phenyl group are described.

Microwave-Accelerated Solvent-Free Synthesis of Thioketones, Thiolactones, Thioamides, Thionoesters, and Thioflavonoids

“…The synthesis of thio analogues of ketones, flavones, isoflavones, lactones, amides, and esters has received considerable attention due to the biological importance of these molecules, their rich photochemistry, and their usefulness as precursors for the synthesis of a variety of organic compounds. − This basic transformation has been accomplished by several reagents, namely, phosphorus pentasulfide, 7a,b hydrogen sulfide in the presence of acid,7c bis(tricyclohexyltin) sulfide with boron trifluoride,7d bis(trimethylsilyl) sulfide with CoCl 2 ·6H 2 O,7e and thiation of gem -dichlorides with sodium hydrogen sulfide,7f thioacetic acid 7g or potassium xanthate 7h. Most of these lengthy procedures, however, require an excess of reagents and involve the use of aromatic hydrocarbon solvents such as toluene, xylene, benzene, or triethylamine and pyridine under dry conditions, affording only moderate yields of products.…”

“…Thionoesters are useful building blocks for the assembly of a variety of organic compounds. , They can be readily desulfurized with Raney nickel to produce the corresponding ethers . The synthesis of 1,3,4-oxadiazoles, which possess significant activity as herbicides, fungicides, and plant cell growth factors, require thionoesters as precursors. , Consequently, we have broadened the scope of this solvent-free protocol by preparing valuable thionoesters (Table ) . In this case, our process requires 0.8 equiv of the Lawesson's reagent for complete conversion to the corresponding thioesters, which is a dramatic improvement over existing methods.…”

“…Thionoesters are useful building blocks for the assembly of a variety of organic compounds. 13,14 They can be readily desulfurized with Raney nickel to produce the corresponding ethers. 13 The synthesis of 1,3,4-oxadiazoles, 14 which possess significant activity as herbicides, fungicides, and plant cell growth factors, require thionoesters as precursors.…”

An efficient and straightforward approach for accessing thionoesters via palladium-catalyzed C–N cleavage of thioamides

“…It is common and important that α,α-difluoroethers exist in liquid crystal materials. 19–22 More significantly, thionoesters are utilized for the synthesis of some drug intermediates such as 1,3,4-oxadiazoles, possible prodrugs of antidepressant hydrazides, 23,24 and1,4,2-oxathiazoles, 25 a potential fragment of the drugs. Furthermore, the Pluth group have recently demonstrated that thionoesters could function as cysteine-selective H 2 S donors.…”

A General and Efficient Route to Thionoesters via Thionoacyl Nitrobenzotriazoles

“…Thionoesters, unlike their oxoester counterparts of lesser electrophilicity of the carbonyl system, react readily with DAST under mild conditions to provide cleanly and in good yield the corresponding α,α-difluoroethers, compounds of current interest. Thionoesters are also considered as suitable starting materials for the synthesis of 1,3,4-oxadiazoles of considerable activity , as plant cell growth factors, herbicides, and fungicides. Recently, the influence of thionoesters as effective chain transfer agents in the polymerization of styrene, methyl acrylate, and related olefins was reported .…”