N-Alkyl Carbamoylimidazoles as Isocyanate Equivalents: Exploration of the Reaction Scope for the Synthesis of Ureas, Hydantoins, Carbamates, Thiocarbamates, and Oxazolidinones

Abstract

The reaction of the HCl or trifluoroacetic acid salts of primary amines with carbonyldiimidazole (CDI) is shown to be a preparatively useful method for forming monosubstituted carbamoylimidazoles (28 examples) without the formation of symmetrical urea side products. The utility of these air-and water-stable crystalline carbamoylimidazole reagents was demonstrated by their reactions as blocked or masked isocyanate equivalents. Reaction with various classes of nucleophiles provides access to useful functional groups including ureas, carbamates, thiocarbamates, hydantoins, and oxazolidinones. A parallel synthesis library of 30 ureas was generated by the reaction of 6× carbamoylimidazole intermediates with 5× amines and triethylamine. The unsymmetrical urea-containing natural products macaurea A and pygmaniline A were also prepared in good yields (95% over four steps and 79% over three steps, respectively) using this approach. The reaction of carbamoylimidazoles with amino acid methyl esters followed by microwave irradiation in aqueous media gives hydantoins in high yields, further demonstrating the ability of carbamoylimidazoles as isocyanate surrogates. Three hydantoin-containing natural products including macahydantoin D and meyeniihydantoin A were prepared in nearly quantitative yields from proline methyl ester and carbamoylimidazoles. The reaction of carbamoylimidazoles with alcohols and thiols under basic conditions affords carbamates and thiocarbamates, respectively, in good yields. Lastly, a method for the preparation of chiral oxazolidinone heterocycles from chiral epoxy alcohols is demonstrated using a double displacement approach. The reactions occur with high regio-and stereoselectivity (dr ≥ 15:1 by 1 H NMR) via a domino attack of the corresponding alkoxides with carbamoylimidazoles followed by an intramolecular attack of the in situ generated urea anion at the proximal position of the epoxide group.

Synthesis of Molsidomine and Mesocarb Analog via Mechanochemistry

“…Similar results were obtained when increasing the milling frequency from 25 to 30 Hz (Table 2, entries 3 and 4). The group of Batey reported that, for primary aliphatic amines, using the hydrochloride form instead of the free amine allowed to suppress the formation of symmetrical urea [16a] . However, in our case, the use of aniline hydrochloride in solvent‐free conditions resulted in a larger proportion of urea (Table 2, entries 5 and 6).…”

Depolymerizing Polyethylene Terephthalate (PET) via “Imidazolysis” for Obtaining a Diverse Array of Intermediates from Plastic Waste

“…The transacylation activity of imidazolides or carbonyl diimidazolides has been extensively investigated by previous researchers. ,, Following this, our upcycling study aimed to explore the reactivity of TBIs in aminolysis reactions with excess n -butylamine under reflux. It was observed that all three TBIs (1b, 2b, and 3b) exhibited sufficient reactivity to form the symmetric 2° terephthalamide (compound c) in Scheme a, with moderate to high yields, as the imidazoles were displaced in favor of amide formation with amines.…”

Functionalization of Polydimethylsiloxane with Diazirine-Based Linkers for Covalent Protein Immobilization

“…The target compounds 3 and 4 were readily synthesized from ethylene glycol diazirine 6 in one step, as illustrated in Scheme . To achieve a rapid and clean protein immobilization in subsequent steps, efficient electrophilic groups on linkers have been selected: imidazole carbamate , and benzyl bromide, where the latter has been widely used for polymer grafting − and small molecular functionalization, and the former is known to react efficiently with amine-containing nucleophiles.…”