Acid-Catalyzed Hydrolysis and Intramolecular Cyclization of N-Cyano Sulfoximines for the Synthesis of Thiadiazine 1-Oxides

Abstract

Herein, we describe a novel approach for the practical synthesis of thiadiazine 1-oxides 10. The first example of an intramolecular cyclization with 2-N-cyano-sulfonimidoyl amides 9 to form the desired thiadiazine 1-oxides 10 was developed. One-pot acid-induced hydrolysis of the cyano group and the intramolecular cyclocondensation protocol readily provided various heterocyclic frameworks in good to moderate yields. Notably, the crystal structures of N-urea sulfoximine 11 and thiadiazine 1-oxide 10i have been determined using X-ray crystallography.

Synthesis of 3-amino-substituted benzothiadiazine oxides by a palladium-catalysed cascade reaction

“…Despite the pharmaceutical interest in 3-amino-substituted benzothiadiazine oxides, state-of-the-art methodologies to access these compounds are limited. Existing methods to access the backbone of these heterocycles include both metal-free 10 and metal-catalysed C–H amidations of non-activated sulfoximines, 11 or a copper-catalysed multicomponent reaction of 2-bromo sulfoximines, 12 yet the synthesis of the 3-amino-substituted derivatives is not described in either of these reports. In other studies, the synthesis of 3-amino-substituted benzothiadiazine oxides was achieved by multiple-step syntheses of pre-functionalised sulfoximines.…”

N-Cyano sulfilimine functional group as a nonclassical amide bond bioisostere in the design of a potent analogue to anthranilic diamide insecticide

“…More recently, we successfully developed a practical and scalable method for introduction of an N -cyano sulfilimine moiety into reactive functional group-substituted thioanisols. 51,52 Following our thionium-mediated reaction method, the desired N -cyano sulfilimine chlorantraniliprole 1 was successfully synthesized (Scheme 2). 65 It should be highlighted that this practical synthetic method of N -cyano sulfilimine 1 is column chromatography-free, with high yield, and performed on a 10 g scale.…”

“…N -Cyano sulfilimines have generally been applied as building blocks in the synthesis of biologically active N -cyano and NH-sulfoximines. 25–28,30,46–54 The SN bond of S( iv ) functional group is stabilized by electron-withdrawing groups and can be considered as a sulfur–nitrogen ylide in its ionic form (Fig. 1B).…”

“…In order to apply the aforementioned approach in our discovery program, we decided to study the N -cyano sulfilimine group-substituted chlorantraniliprole analog 1 based on our previous research. 49–52 As the reference molecule, chlorantraniliprole has captured a significant market share in the insect control business. This insecticide belong to the anthranilic diamide class of chemistry and provides excellent crop protection.…”

Intramolecular cyclization ofN-cyano sulfoximines by N–CN bond activation

“…However, despite the impressive progress made in the development of synthetic routes in recent decades, the introduction of a sulfoximinoyl moiety into a heterocyclic ring system remains challenging owing to the requirement for harsh reaction conditions, expensive transition-metal catalysts, and noncommercial amination reagents. 26,28 To establish highly efficient intramolecular cyclization under mild conditions, our study focused on the N–CN bond activation approach ( Fig. 2 ).…”