Mild Synthesis of Substituted 1,2,5-Oxadiazoles Using 1,1′-Carbonyldiimidazole as a Dehydrating Agent

Abstract

1,1'-Carbonyldiimidazole was found to induce the formation of a variety of 3,4-disubstituted 1,2,5-oxadiazoles (furazans) from the corresponding bisoximes at ambient temperature. This method enables these inherently energetic compounds to be prepared at temperatures well below their decomposition points and with improved functional group compatibility relative to prior methods. Conditions were developed that allowed for the first high-yielding synthesis of chlorofurazans from their amino counterparts, enabling the mild synthetic manipulation of these heterocycles.

Crystal structure of poly[(μ3-4-amino-1,2,5-oxadiazole-3-hydroxamato)thallium(I)]

“…However, the standard synthetic procedures for oxadiazolecontaining scaffolds usually utilizes the dehydrative cyclization of bis-oximes, which is performed at high temperatures (Fershtat & Makhova, 2016;Romeo & Chiacchio, 2011) and often includes the introduction of different activating reagents (Shaposhnikov et al, 2003;Telvekar & Takale, 2013). A convenient procedure for the synthesis of substituted 4-amino-1,2,5-oxadiazoles based on the formation of bis-oximes in situ from the hydroxylamine and cyano-oximes was recently proposed (Neel & Zhao, 2018). The introduction of dehydrating agents allows a significant decrease in the temperature during reaction, gave the possibility to synthesize substituted 1,2,5-oxadiazoles with various side functional groups.…”

“…The title compound was obtained according to a modification of the procedure reported by Neel & Zhao (2018) (Fig. 4).…”

N-Oxide-Controlled Chemoselective Reduction of Nitrofuroxans

“…IR spectra were recorded on a Bruker 'Alpha' spectrophotometer in the range 400-4000 cm -1 (resolution: 2 cm -1 ). 1 H, 13 C and 19 F NMR spectra were recorded on a Bruker AM-300 (300.13, 75.47 and 282.4 MHz, respectively) spectrometer and referenced to the residual solvent peak. 14 N NMR spectra were measured on a Bruker AM-300 (21.69 MHz) spectrometer using MeNO 2 (δ 14N = 0.0) as an external standard.…”

“…1 H NMR (300 MHz, DMSO-d 6 ): δ = 2.38 (s, 3 H, CH 3 ), 6.16 (br s, 2 H, NH 2 ), 7.36 (d, J = 7.4 Hz, 2 H, ArH), 7.67 (d,J = 7.4 Hz,2 H,ArH). 13 C NMR (75.5 MHz, DMSO-d 6 ): δ = 21.4, 123.1, 128.0, 130.1, 140.5, 147.3, 155.7.…”

“…Recently, 1,1′carbonyldiimidazole was utilized for the preparation of aminofurazans from the corresponding pre-synthesized aminoglyoximes at ambient temperature. 13 Aminoglyoximes can also be used for the synthesis of aminofuroxans via oxidation reactions. Oxidation of aminoglyoximes with Br 2 14 or K 3 Fe(CN) 6 14a results in the regioselective formation of 3-amino-4-arylfuroxans, which can be thermally isomerized into the corresponding 4-amino isomers on heating in toluene.…”