Radical-mediated dehydrative preparation of cyclic imides using (NH₄)₂S₂O₈–DMSO: application to the synthesis of vernakalant

Abstract

SummaryAmmonium persulfate–dimethyl sulfoxide (APS–DMSO) has been developed as an efficient and new dehydrating reagent for a convenient one-pot process for the synthesis of miscellaneous cyclic imides in high yields starting from readily available primary amines and cyclic anhydrides. A plausible radical mechanism involving DMSO has been proposed. The application of this facile one-pot imide forming process has been demonstrated for a practical synthesis of vernakalant.

Synthesis of Succinimide Derivatives by NHC-Catalyzed Stetter Reaction of Aromatic Aldehydes with N-Substituted Itaconimides

“…Recently, our group developed an expedient protocol for the synthesis of maleimide and succinimide derivatives by using a new dehydrating agent (NH 4 ) 2 S 2 O 8 /dimethyl sulfoxide (DMSO). 10 In continuation of that, herein, we applied the same protocol in the synthesis of N -aryl itaconimide derivatives. The developed reaction condition worked very well and tolerated various electron-withdrawing and electron-donating substituents on primary aromatic amines (Scheme 1).…”

Ammonium persulfate activated DMSO as a one-carbon synthon for the synthesis of methylenebisamides and other applications

“…14 Probably, both the reactions followed the APS-DMSO mediated deaminative and desulfurative cyclization pathway respectively, and their mechanism may be similar to our previous report on dehydrative cyclization of amic acids to imides. 15 The suitability of symmetrical heteroaromatic methylenebisamides was studied. Thiophene-2-carboxamide provided bisamide 19 in high yield; however, quinoline-3-carboxamide did not furnish bisamide 20, plausibly due to oxidation of the highly basic quinoline nitrogen (Fig.…”

“…We have previously proved that APS oxidizes DMSO to form dimethyl sulfone (DMS) in 1,4-dioxane. 15 Taking that into consideration we envisaged formation of the sulfonyl compound 34 as a probable intermediate formed by the reaction of amide with DMSO/DMS radical species. Reaction of benzamide (1) using DMS instead of DMSO under the standard protocol also furnished the desired bisamide 2 (Scheme 7).…”

Cyclic imide derivatives: As promising scaffold for the synthesis of antimicrobial agents

“…The alkaloid phyllanthimide isolated from leaves of Phyllanthus sellowianus (Euphorbiaceae) has been used as a precursor for the synthesis of some of cyclic imides. [ 14 ] There are several approved drugs with cyclic imide structure such as phensuximide, buspirone, and thalidomide. [ 15 ]…”