Synthesis of 2-Thio- and 2-Oxoimidazoles via Cascade Addition−Cycloisomerization Reactions of Propargylcyanamides

Abstract

A methodology to generate 2-thio- and 2-oxoimidazoles through an addition-cyclization-isomerization reaction of propargylcyanamides with thiol and alcohol nucleophiles is described. In general, the reaction sequence allows for the rapid formation of highly substituted 2-thio- and 2-oxoimidazoles in good to excellent yields.

The Cyanamide Moiety, Synthesis and Reactivity

“…Nucleophilic additions of thiols to the nitrile group of cyanamides (as 44) have been reported under acidic 41 or ba-sic conditions. 42 As previously, the intermediate thioureas generated could be engaged in subsequent cycloisomerizations, providing 2-thioimidazoles in good yields (45, Scheme 16).…”

“…The alkoxides could be generated from alcohols in the presence of mild base such as potassium carbonate. 42 The oxygen of a β-dicarbonyl function could provide a similar reactivity. 43 An elegant strategy for the in situ generation of alkoxide nucleophiles derives from the ring opening of epoxides by sodium cyanamide.…”

Double Duty for Cyanogen Bromide in a Cascade Synthesis of Cyanoepoxides

“…[3] In the von Braun reaction, BrCN acts as an equivalent of both CN + and Br À by fragmenting tertiary amines into cyanamides and alkylbromides (Mode IV). [4,5] Herein, we report an unprecedented Mode V, in which cyanogen bromide works as an equivalent of Br + and CN À in a one-pot transformation of ketones into cyanoepoxide derivatives (Mode V).Our research group has recently demonstrated that alkynyl bromides can act as equivalents of both Br + and alkynyl anions in a highly efficient, one-pot conversion of ketones into alkynylepoxides. [6] We hypothesized that cyano-gen bromide could potentially be involved in a similar transformation as an equivalent of both Br + and CN À (Scheme 2).…”

“…Thus, BrCN was shown to serve as a donor of Br + in reactions with strongly nucleophilic organometallic reagents to provide the corresponding vinyl-or arylbromides (Mode I). [4,5] Herein, we report an unprecedented Mode V, in which cyanogen bromide works as an equivalent of Br + and CN À in a one-pot transformation of ketones into cyanoepoxide derivatives (Mode V). [2] When reacted with primary or secondary amines or alcohols, cyanogen bromide behaves as an equivalent of CN + , and gives rise to cyanamides or cyanates (Mode III).…”

“…[3] In the von Braun reaction, BrCN acts as an equivalent of both CN + and Br À by fragmenting tertiary amines into cyanamides and alkylbromides (Mode IV). [4,5] Herein, we report an unprecedented Mode V, in which cyanogen bromide works as an equivalent of Br + and CN À in a one-pot transformation of ketones into cyanoepoxide derivatives (Mode V).…”