Iodine-promoted ring-opening methylation of benzothiazoles with dimethyl sulfite

Abstract

A new methylation of N,S-atoms using dimethyl sulfite as a safe and cheap methylating reagent through halogen bond promoted ring-opening coupling of benzothiazoles is described.

Theoretical Study for Evaluating and Discovering Organic Hydride Compounds as Potential Novel Methylation Reagents

“…Then, T o , which refers to the temperature when ΔG°is zero, is calculated (T o = ΔH o /ΔS o ) according to the above hypothesis. From Table 1, it can be concluded that T o ranges from 38.76 to 80.02 °C when ΔG°R D (XH •+ ) increased 15 K are considered to be potential methyl radical reagents in organic synthesis (Figure 1). 33 Nine XH •+ s (5H •+ , 6H •+ , 9H •+ , 10H •+ , 12H •+ , 13H •+ , 15H •+ , 43H •+ , and 45H •+ , Scheme 3) in this work are found to be potential methyl radical reagents in organic synthesis, with ΔG°R D (XH •+ ) ranging from 2.67 (15H •+ ) to 4.81 kcal/mol (45H •+ ) and ΔG RD ≠ (XH •+ ) ranging from 15.84 (5H •+ ) to 18.91 kcal/mol (13H •+ ).…”

“…The introduction of the methyl group to drug molecules is helpful to improve their binding affinity, biological availability, and metabolic stability (called “magic methyl effect”), which greatly changes the pharmacological properties of bioactive molecules. − Methylation plays an important role in the modification of drug molecules, DNA, as well as proteins. − According to different reaction mechanisms, the methylation agents are divided into three classes, i.e., electrophilic methylation reagents, nucleophilic methylation reagents, and free radical methylation reagents . At present, great progress has been made in the methylation reaction. − Many chemists have made outstanding contributions in this field, and a large number of new methyl reagents − and new methylation reactions have been developed, − especially electrocatalytic, , visible-light-induced, or transition-metal-catalyzed − methylation, in recent years. In 2021, Dixon and co-workers published an important review about C–H methylation in chemical synthesis, which covered the various methylation reagents and diverse strategies employed to realize the selective installation of the C–Me bond in extensive chemical structures .…”

“…31 In 2021, we further evaluated the antioxidant reactivities of XRH •+ s with different substituents (Scheme 1b), 32 and in 2022, we have calculated the Gibbs free energy [denoted as ΔG°R D (X′H •+ ) (for 298 K) and ΔG°′ RD (X′H •+ ) (for 355 K)] and the activation free energy [denoted as ΔG RD ≠ (X′H •+ ) (for 298 K) and ΔG ≠ ′ RD (X′H •+ ) (for 355 K)] of 47 trifluoromethyl-substituted organic hydride compound radical cations (X′H •+ ) releasing the trifluoromethyl radical in MeCN at 298. 15 and 355 K with the density functional theory (DFT) method (Scheme 1c). 33 Fifteen XH •+ s with a 1,4-dihydropyridine structure and three XH •+ s with a 3,4-dihydropyrimidin-2one structure are identified to be novel excellent and potential trifluoromethylation reagents, respectively, according to their reactivity data.…”

Palladium-Catalyzed Methylsulfonylation of Alkyl Halides Using Dimethyl Sulfite as SO2 Surrogate and Methyl Source

“…Recently, sulfites have been found as versatile SO 2 donors in some sulfonylations . We also developed a methylation reaction using dimethyl sulfite as methylating reagent . Encouraged by these results, we envision whether dimethyl sulfite could be applied as both sulfur dioxide donor and methyl source in some methylsulfonylations.…”

“…13 We also developed a methylation reaction using dimethyl sulfite as methylating reagent. 14 Encouraged by these results, we envision whether dimethyl sulfite could be applied as both sulfur dioxide donor and methyl source in some methylsulfonylations. Herein, we report a Pd-catalyzed methylsulfonylation of aryl/alkyl iodides with dimethyl sulfite to directly produce methyl sulfone derivatives under ligand-and base-free reaction conditions (Scheme 2, eq c).…”