DMSO/I2 Metal-Free Oxidative α-Nitration of Ketones: A Route to One-Pot Synthesis of Thiohydroximic Acids from Acetophenones

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Recently, Batra et al. have reported another new DMSO/I2 metal-free route to functionalize ketones at the α-position.1 Their previous work had demonstrated a DMSO/I2/NaNO2-mediated route to the synthesis of highly substituted isoxazoles.2 Building on this work, they have developed a metal-free route using DMSO/I2/NaNO2 to nitrate the alpha position of ketones. Optimization indicated that, while [...]

DMSO as a Methylene Synthon: Synthesis of Bisimidazopyridinylmethanes

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Instances of synthetic methods using DMSO as a reagent/synthon have grown in recent years.  Review articles in 2016 highlight the many functional units that may be installed from DMSO   (-O, -SMe, -CH2SMe, -SO2Me, -Me, -CN, -CHO, and –CH2- ).1,2  Among these recent reports are reactions using DMSO to provide a one-carbon methylene linker between imidazo[1,2-a]heterocycles.3-5  [...]

One-Pot Copper(I)-Catalyzed Synthesis of Quinazolinones in DMSO from Aldehydes, Benzyl Alcohols or Methyl Arenes

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Work toward the efficient synthesis of quinazolin-4-(3H)-ones has continued to garner much attention.  Quinazolin-4-(3H)-ones are the core structural components in a variety of drugs and drug candidates and are known to convey numerous pharmacological and biological activities.  Routes to quinazolinones with substitution at the 2-position (1 in Equation 1) are especially important.   Interestingly, many of [...]

Two new DMSO/I2 catalyzed synthetic routes to 3-Thioindoles

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In 2014, Silveira and Braga reported the eco-friendly synthesis of 3-chalcogenyl-indoles using the DMSO/I2 catalytic system (Equation 1).1   These researchers used diselenides or disulfides as the chalcogen source.  The I2 catalyst and the dichalcogenide produced the electrophilic species RY-I (Y = Se or S) which underwent electrophilic substitution at the 3 position of the indole.  [...]

DMSO/ Superbase a-vinylation of ketones

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The Trofimov group (A.E. Favorsky Irkutsk Institute) has recently published a general synthesis of β,γ – unsaturated ketones which uses arylacetylenes and ketone starting materials.  This provides the  synthetic chemist yet another option for the nonobvious homoenolate synthon /  d3  reagent. α-vinylation reaction of Trofimov et Al (1) The authors provide a considerable list of existing routes to β,γ enones, which […]

Direct C-H activation and C-S bond formation catalyzed by DMSO/I2

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The DMSO/I2 catalytic system has made many formerly challenging reactions practical, inexpensive and much greener.1-5  This is the case in a recent paper by Peddinti and Parumala.6  They have reported the DMSO/I2 catalyzed direct C(sp2)-H activation of aryls containing electron-donating substituents, resulting in C-S bond formation and access to aryl sulfides Equation 1:  DMSO/I2 catalyzed [...]

A greener route to high-value bromohydrins using DMSO as solvent, oxidant, and oxygen source

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Bromohydrins are important building blocks and are widely used in the synthesis of azidoalcohols, epoxides, aminoalcohols, aziridines and hydroxyl acids.1  Due to the ease of conversion of bromohydrins to so many of the above building blocks, they are often used in the synthesis of pharmaceuticals.   Unfortunately, bromohydrins are traditionally synthesized using N-bromosuccinimide which always produces [...]

DMSO/I2 system for the synthesis of quinazolinones and pyrazolo[4,3-d]pyrimidin-7(6H)-ones

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A recent report by Vishwakarma and Bharate in the Journal of Organic Chemistry establishes a metal-free route to quinazolinones and pyrazolo-pyrimidinones using a DMSO/I2 catalytic system (Equation 1).1 DMSO acts as more than just a solvent in the reaction—it serves as an active participant in the reaction mechanism. DMSO/I2 catalytic systems have been used previously [...]

Metal-free Aerobic Oxidation to Synthesize Quinazolinones in DMSO

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Cheon, et al., have demonstrated a highly environmentally benign route to the synthesis of quinazolinones using readily-available aldehydes and anthranilimide (Equation 1).1 This route proceeds through a metal-free aerobic oxidation in wet DMSO. Equation 1: Metal-free protocol for the synthesis of quinazolinones in DMSO They additionally demonstrated that the protocol also works well with substituents [...]