An Efficient and Expeditious Synthesis of Di- and Monosubstituted 2-Aminoimidazoles

Abstract

A microwave-assisted protocol was developed for the construction of di- and monosubstituted 2-aminoimidazoles. The two-step reaction involves the synthesis of N-(1H-imidazol-2-yl)acetamides from readily available alpha-haloketones and N-acetylguanidine, followed by deacetylation. Significant rate enhancement was observed for both steps of the protocol, and the overall reaction time was shortened to 20 min compared to 48 h of the conventional procedures. A representative set of di- and monosubstituted 2-aminoimidazoles was prepared using commercially available parallel reactors.

Acyl guanidine functional poly(2‐oxazoline)s as reactive intermediates and stimuli‐responsive materials

“…When the polymer is dissolved in acid media and titrated with base, only one equivalence point can be seen. However, when the polymer is dissolved in basic media and titrated with acid, a second equivalence point can be identified, which points toward the hydrolysis of the acyl group to the corresponding acid, which is in line with the literature . All polymers show a similar behavior as can be seen in Figure S11, with the respective pKa values around 9.52, 9.53, 9.23, and 9.50 for the copolymers modified with guanidine, TBD, metformine and acyl‐2‐amino‐5‐phenyl‐imidazole, respectively.…”

“…More specifically, we explored the possible synthesis of acyl‐2‐aminoimidazoles by reacting our functional polymers with α‐haloketones (Scheme ). This reaction was reported in the literature on small molecules where near quantitative conversions were reported . Inspired by this report, we explored the reaction conditions in order to facilitate this reaction on the acyl guanidine functionalized polymer.…”

“…Performing the reaction in the absence of solvent would also eliminate any effects of the solvent on the overall reaction as DMF has been reported to give lower yields compared to ACN. 51 In addition, we also demonstrated the possibility of performing the first step, the guanidinylation, via HSVM, resulting in a complete solvent-less postpolymerization modification protocol, with the exception of the purification steps, for the preparation of PAOx with acyl guanidine side chains. An overview of the synthetic scheme is given in Scheme 2.…”

“…This reaction was reported in the literature on small molecules where near quantitative conversions were reported. 51 Inspired by this report, we explored the reaction conditions in order to facilitate this reaction on the acyl guanidine functionalized polymer. However, as mentioned above, the highly polar acyl guanidine moieties limited the solubility of the polymer in ACN, the reported reaction solvent.…”

“…[48][49][50] These interesting features have led us to explore the utilization of methyl ester functional PAOx for the acylation of guanidines. Within this contribution, we show the successful synthesis and isolation of three acyl guanidine adducts, as well as their utility as a reactive moiety for the synthesis of acyl-2-aminoimidazoles, see Scheme 1, [51][52][53] which present a class of pharmacologically active substances. 54,55 Furthermore, the stimuli-responsive behavior of some of these polymers is demonstrated.…”