Abstract
The one-pot reaction of chlorosulfonyl isocyanate (CSI) with epoxides having phenyl, benzyl and fused cyclic alkyl groups in different solvents under mild reaction conditions without additives and catalysts was studied. Oxazolidinones and five-membered cyclic carbonates were obtained in ratios close to 1:1 in the cyclization reactions. The best yields of these compounds were obtained in dichloromethane (DCM). Together with 16 known compounds, two novel oxazolidinone derivatives and two novel cyclic carbonates were synthesized with an efficient and straightforward method. Compared to the existing methods, the synthetic approach presented here provides the following distinct advantageous: being a one-pot reaction with metal-free reagent, having shorter reaction times, good yields and a very simple purification method. Moreover, using the density functional theory (DFT) method at the M06-2X/6-31+G(d,p) level of theory the mechanism of the cycloaddition reactions has been elucidated. The further investigation of the potential energy surfaces associated with two possible channels leading to oxazolidinones and five-membered cyclic carbonates disclosed that the cycloaddition reaction proceeds via an asynchronous concerted mechanism in gas phase and in DCM.
Highlights
Oxazolidinones (1), five-membered heterocyclic rings containing an ester group adjacent to a nitrogen atom, are important compounds in synthetic and pharmaceutical chemistry because of their considerable use as antibiotics [1], immunomodulators [2], antibacterials [3], as well as synthetic intermediates and chiral auxiliaries for various organic conversions [4,5,6,7]
We synthesized various epoxides (7a–j) in the presence of meta-chloroperbenzoic acid (m-CPBA), from the corresponding alkenes dissolved in DCM at room temperature
For the synthesis of oxazolidinones and five-membered cyclic carbonates, the most effective solvent was determined based on the reaction of 8-oxabicyclo[5.1.0]octane (7b) with chlorosulfonyl isocyanate (CSI) (Table 1) which was the first reaction performed in this study
Summary
Oxazolidinones (1), five-membered heterocyclic rings containing an ester group adjacent to a nitrogen atom, are important compounds in synthetic and pharmaceutical chemistry because of their considerable use as antibiotics [1], immunomodulators [2], antibacterials [3], as well as synthetic intermediates and chiral auxiliaries for various organic conversions [4,5,6,7]. Linezolid [1,2,3] (3) and cytoxazone [8,9] (4) are oxazolidinone derivatives having significant biological activities. Linezolid (3) is the first oxazolidinone drug approved in 2000 by the Food and Drug Administration (FDA) for the treatment of multidrug resistant Gram-positive bacterial infections (Scheme 1) [10]. Cytoxazone is a microbial metabolite exhibiting potent cytokine-modulating activity. Tedizolid phosphate (trade name Sivextro), which exhibits antibiotic activity is another oxazolidinone drug approved by the FDA in 2014 [11]. Befloxatone and toloxatone, N-substituted phenyloxazolidinone derivatives, are reversible inhibitors of monoamine oxidase (MAO) [12,13]. N-Aryloxazolidinedione compounds, which are toloxatone derivatives, have been reported to exhibit good affinity for human MAO-A [14]
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