Benzylic Thio and Seleno Newman–Kwart Rearrangements

Abstract

The thermally induced O → S and O → Se migration reactions facilitate the rearrangement of O-benzyl thio- and selenocarbamates [BnOC(═X)NMe] (X = S or Se) into their corresponding S-benzyl thio- and Se-benzyl selenocarbamates [BnXC(═O)NMe] (X = S or Se). A series of substituted O-benzyl thio- and selenocarbamates were synthesized and rearranged in good yields of 33-88%. The reaction rates are higher for substrates with electron-donating groups in the 2 or 4 position of the aromatic ring, but the rearrangement also proceeds with electron-withdrawing substituents. The rearrangement follows first-order reaction kinetics and proceeds via a tight ion pair intermediate consisting of the benzylic carbocation and the thio- or selenocarbamate moiety. Computational studies support these findings.

Selenium‐NMR Spectroscopy in Organic Synthesis: From Structural Characterization Toward New Investigations

“…For instance, a benzylic thio-and seleno-Newman-Kwart rearrangement was studied to provide mechanistic insights. [149] In this recent work, Pittelkow and co-workers have observed a fundamental change in the rearrangement mechanism when altering the phenyl group of the benzylic species. [150] The reaction was carried using both elements (S or Se), and the reaction kinetic was discussed based on the substrate scope.…”

“…Despite of the profound intellectual challenge to develop rearrangement reactions, currently, a great amount of information is presented in the literature. For instance, a benzylic thio‐ and seleno‐Newman‐Kwart rearrangement was studied to provide mechanistic insights [149] . In this recent work, Pittelkow and co‐workers have observed a fundamental change in the rearrangement mechanism when altering the phenyl group of the benzylic species [150] .…”

Development of Acid-Mediated H2S/COS Donors That Respond to a Specific pH Window

“…Although analogous O -alkyl thiocarbamate donors have been prepared and are stable under ambient conditions, we found that the O -alkyl thiocarbamate with the imine trigger isomerized to the S -alkyl pH-sensitive thiocarbamate ( S - pHTCM ) isomer both in the solution and also in the solid state (Figure S1). Thione–thiol isomerization is well known to occur in thiocarbamates via the Newman–Kwart rearrangement , but typically requires high temperatures or catalysts. , Similarly, benzylic Newman–Kwart rearrangements have recently been reported to occur at elevated temperatures . We hypothesize that the electron-donating imine substituent aids in the stabilization of the benzylic carbocation intermediate formed in the thiocarbamate rearrangement and, thus, may facilitate this isomerization under more mild conditions.…”

“…31,32 Similarly, benzylic Newman−Kwart rearrangements have recently been reported to occur at elevated temperatures. 33 We hypothesize that the electron-donating imine substituent aids in the stabilization of the benzylic carbocation intermediate formed in the thiocarbamate rearrangement and, thus, may facilitate this isomerization under more mild conditions.…”

Understanding the Solid-State Assembly of Pharmaceutically-Relevant N,N-Dimethyl-O-Thiocarbamates in the Absence of Labile Hydrogen Bonds

“…Capped stick representation of the crystal structure of Tolnaftate 15, denoting π-π and CH-π interactions between adjacent naphthyl (in yellow) and phenyl (in blue) rings.Finally, Hirshfeld surface analysis (Figure S33-52)were performed on all 14 crystal structures, as well as selected O-thiocarbamate compounds namely ERIWEH,39 GIQDES,40 JELTUQ,41 JELVAY,41 VIVVUU,42 and ZAHHUO, 43 using CrystalExplorer.44 For most of the compounds analysed, the largest percentage contribution to the interatomic contacts of the Hirshfeld surfaces were mainly C-H/H-C (~ 20-30%), H-H/H-H (~ 15-65%) and H-S/S-H (10-20%) short-range contacts. Representative noteworthy close contacts are highlighted in Figure 7, specifically for 14, 15, and JELTUQ.…”