One-Pot Parallel Synthesis of Alkyl Sulfides, Sulfoxides, and Sulfones

Abstract

A simple and cost-effective one-pot parallel synthesis approach to sulfides, sulfoxides, and sulfones from thiourea was elaborated. The method combines two procedures optimized to the parallel synthesis conditions: alkylation of thiourea with alkyl chlorides and mono or full oxidation of in situ generated sulfides with H2O2 or H2O2-(NH4)2MoO4. The experimental set up required commonly used lab equipment: conventional oven and ultrasonic bath; the work up includes filtration or extraction with chloroform. The method was evaluated on an 81 member library of drug-like sulfides, sulfoxides, and sulfones yielding the compounds on a 30-300 mg scale. A small-scale synthesis of 2-(benzhydrylsulfinyl)acetamide (modafinil) utilizing our approach resulted in similar efficiency to the published procedures.

Design, synthesis, and bioactivities of novel pyridazinone derivatives containing 2‐phenylthiazole or oxazole skeletons

“…The synthetic routes of all target compounds and intermediates are shown in Figure 3. [ 26,31–33 ] The structures of all synthesized compounds were characterized by NMR, MS, and elemental analysis. The chemical structures, MS data, physical properties, and biological activities of all target compounds 12a ‐ l are illustrated in Table 1.…”

Alkyl Sulfides as Promising Sulfur Sources: Metal‐Free Synthesis of Aryl Alkyl Sulfides and Dialkyl Sulfides by Transalkylation of Simple Sulfides with Alkyl Halides

“…Alkyl sulfides have received considerable attention as important scaffolds in natural products, material chemistry, pharmaceuticals, food chemistry and ligands . The synthesis of sulfides with a saturated carbon skeleton receives increasing attention, especially in pharmaceutical areas, due in part to higher hydrophilic nature of alkyl groups than aromatic groups –. Conventional approaches for alkyl‐sulfur bond formation are mainly based on substitution reactions of nucleophilic sulfur reagents such as metal sulfides, thiosulfates, thiourea, thiol derivatives with electrophilic alkylating reagents.…”

Synthesis of (R)-Modafinil via Organocatalyzed and Non-Heme Iron-Catalyzed Sulfoxidation Using H2O2 as an Environmentally Benign Oxidant

“…The fact that there is a continued demand for novel synthetic methods to attain modafinil is further demonstrated by a recently published one-pot parallel synthetic approach [29] as well as another strategy, established by Cibulka and co-workers, employing electron-deficient heteroarenium salts for the activation of hydrogen peroxide [30].…”

“…After the first synthesis was developed in 1979 by Lafon [22], several methods have been envisioned for its racemic generation using hydrogen peroxide as an abundant, environmentally benign oxidant [23][24][25][26][27][28][29].…”