An Eco-friendly, Hantzsch-Based, Solvent-Free Approach to 2-Aminothiazoles and 2-Aminoselenazoles

Abstract

We report a simple, fast, and eco-friendly solvent-free protocol for the synthesis of 2-aminothiazoles and 2-amino-1,3-selenazoles (16 examples) through Hantzsch condensation without the use of a catalyst. It is noteworthy that this type of procedure is unprecedented for the synthesis of 1,3-selenazoles. Reactions proceed to completion in a few seconds and products are obtained in moderate to excellent yields after easy workup. Moreover, the synthesis of 4-(2-amino-1,3selenazol-4-yl)benzonitrile hydrobromide is reported for the first time.

Methyl 2-Amino-4-[1-(tert-butoxycarbonyl)azetidin-3-yl]-1,3-selenazole-5-carboxylate

“…The 77 Se NMR spectra contained a singlet at 581.4 ppm. The observed 15 N and 77 Se chemical shifts are consistent with data reported in the literature for 1,3-selenazoles possessing similar structures [18].…”

“…The multiplicity-edited 1 H- 13 C HSQC spectrum revealed a cross-peak correlating a methine proton at 4.67 ppm with the 13 C signal at 28.1 ppm from the azetidine ring (Figure 3). The connectivity of the 2-amino-1,3-selenazole-5-carboxylate moiety and the N-Bocprotected azetidine fragment could be confirmed based on long-range 1 H- 13 C and 1 H- 15 N correlations, obtained from gs-HMBC spectra of the aforementioned protons. The 1 H- 15 N HMBC experiment revealed a strong three-bond correlation between the 1,3-selenazole N-3 nitrogen, which resonated at −128.1 ppm, and the protons from the 2-amino functional group.…”

“…The connectivity of the 2-amino-1,3-selenazole-5-carboxylate moiety and the N-Bocprotected azetidine fragment could be confirmed based on long-range 1 H- 13 C and 1 H- 15 N correlations, obtained from gs-HMBC spectra of the aforementioned protons. The 1 H- 15 N HMBC experiment revealed a strong three-bond correlation between the 1,3-selenazole N-3 nitrogen, which resonated at −128.1 ppm, and the protons from the 2-amino functional group. In the case of 3-H from the azetidine ring system, it showed a strong correlation with the selenazole N-3, and additionally revealed data for azetidine N-1 at −309.0 ppm.…”

“…Selenazoles can be obtained using analogous synthetic strategies similar to the ones used for thiazoles. Among a variety of ring construction reactions, the most widely used approach is Hantzsch synthesis and its variations [15][16][17]. This methodology reliably leads to the formation of diverse heterocyclic rings in good yields.…”

“…The final structure of compound 4 was easily deduced after a detailed analysis of spectral data (Figures S1-S8). The 1 H- 15 N HSQC experiment revealed that the most downfield protons at 7.25 ppm belong to the NH 2 group, which resonates at −294.6 ppm. The multiplicity-edited 1 H- 13 C HSQC spectrum revealed a cross-peak correlating a methine proton at 4.67 ppm with the 13 C signal at 28.1 ppm from the azetidine ring (Figure 3).…”