Tandem Protocol for the Synthesis of 3‐Acyl Benzothiadiazine 1,1‐Dioxides

Abstract

A metal-free and efficient tandem synthesis of 3-acyl 3,4-dihydro-2H-1,2,4-benzothiadiazine-1,1-dioxides and 3-acyl-2H-1,2,4-benzothiadiazine-1,1-dioxides has been developed via CÀH functionalization of ethynylarenes and ethenylarenes followed by condensation with 2-aminobenzenesulfonamide. The reaction involves the formation of arylglyoxal as an intermediate from multiform substrates through Kornblum oxidation in the presence of iodine and DMSO. Use of simple and readily available starting materials, inexpensive reagent, broad substrate scope and a very simple operation are noteworthy features of this protocol. This method provides an easy access to pharmaceutically important 3-acyl-1,2,4-benzothiadiazine-1,1-dioxides in good yields.

Iodine and DMSO as Surrogate of Hazardous Metal and Non‐Metal Reagents in Organic Synthesis

“…[756,757] Sathe and group used a one-pot synthetic method where they stirred phenyl acetylene and styrene as model substrates with molecular iodine dissolved in DMSO at 110 °C for 1.0 hour in a sealed tube. [758] They have then . This group found that increasing the amounts of molecular iodine could increase the product yields.…”

“…Some of the synthetic routes for benzothiadiazine, involve the use of metal catalysts such as copper (Scheme 75 (a) and (b)) [756,757] . Sathe and group used a one‐pot synthetic method where they stirred phenyl acetylene and styrene as model substrates with molecular iodine dissolved in DMSO at 110 °C for 1.0 hour in a sealed tube [758] . They have then added 2‐aminobenzenesulfonamide to the reaction mixture, which lead to the formation of (1,1‐dioxido‐3,4‐dihydro‐2 H ‐benzo[e][1,2,4]thiadiazin–3‐yl)(phenyl)methanone when the reaction mixture was kept at room temperature for another 1.0 hour (Scheme 75 (c)).…”

I2/DMSO-mediated oxidative C–C and C–heteroatom bond formation: a sustainable approach to chemical synthesis

“…A new, metal-free, efficient, and scalable approach was devised for the production of 3-acyl-3,4-dihydro-2 H -1,2,4-benzothiadiazine-1,1-dioxides 44 and 3-acyl-2 H -1,2,4-benzothiadiazine-1,1-dioxide 45 ( Scheme 25 ). In their study, Chaskar et al 71 employed affordable ethynyl arenes 1 and ethenyl arenes 27, which are readily accessible, as starting materials. These compounds consist of sp 2 and sp 3 carbon–hydrogen (C–H) bonds, respectively.…”