Iron(III) Chloride/l-Proline as an Efficient Catalyst for the Synthesis of 3-Substituted 1,2,4-Oxadiazoles from Amidoximes and Triethyl Orthoformate

Abstract

A general, facile, and efficient method is presented for the synthesis of 3-substituted 1,2,4-oxadiazoles from amidoximes and triethyl orthoformate. The procedure employs an iron(III) chloride/L-proline catalytic system and the 3-substituted 1,2,4-oxadiazole products are obtained in moderate to good yields.

Applications of alkyl orthoesters as valuable substrates in organic transformations, focusing on reaction media

“…In 2016, Kaboudin et al investigated iron(III) chloride/L-proline as an efficient catalytic system for the synthesis of 3-substituted 1,2,4-oxadiazoles (224) from amidoximes (223) and TEOF (5) (Scheme 60). 217 Polshettiwar and Varma performed the solvent-free synthesis of 1,3,4-oxadiazoles (226) 218-223 and 1,3,4-thiadiazoles (227) by the condensation of acid hydrazide (225) and triethyl orthoalkanates (5) under microwave irradiation (40-140 W). According to Scheme 61, the condensation of hydrazide and TEOF were successfully undertaken in two catalytic systems which were solid supported Naon® NR50 and P 4 S 10 /Al 2 O 3 .…”

“…In 2016, Kaboudin et al investigated iron( iii ) chloride/ l -proline as an efficient catalytic system for the synthesis of 3-substituted 1,2,4-oxadiazoles (224) from amidoximes (223) and TEOF (5) ( Scheme 60 ). 217 …”

Discovery of Small-Molecule Cyclic GMP-AMP Synthase Inhibitors

“…The solid was purified by column chromatography (1−20% MeOH/CH 2 Cl 2 ) to afford a white yellow solid (14.3 mg, 96% pure) in 20% yield: 1 H NMR (DMSO-d 6 , 400 MHz) δ 7.85 (s, 1H), 7.69 (d, J = 9.3 Hz, 2H), 7.24 (br, 2H), 3.84 (s, 3H); 13 N-2-(4-Iodophenyl)-6-(1,3,4-oxadiazol-2-yl)-1,3,5-triazine-2,4-diamine (27). 34,35 Triethyl orthofomate (0.216 mL) was added to a mixture of FeCl 3 (1.8 mg, 0.011 mmol), Lproline (1.2 mg, 0.011 mmol), and Et 3 N (3 μL, 0.022 mmol), and the resulting solution was stirred for 1 h at rt. The hydrazide substrate was added, and the mixture was stirred at 80 °C for 12 h. After it cooled, the reaction mixture was washed with Et 2 O (3 × 0.5 mL).…”

“…The mixture was cooled to rt, and the crude product was collected by filtration and washed with cold MeOH. The crude solid was triturated with MeOH to afford a white solid (7.3 g, 94% pure) in 73% yield: mp = 256−249 °C; 1 H NMR (DMSO-d 6 , 400 MHz) δ 10.17 (br, 1H), 7.84 (d, J = 8.5 Hz, 2H), 7.70 (br, 1H), 7.56 (br, 1H), 7.34 (d, J = 8.9 Hz, 2H), 3.84 (s, 3H); 13 Methyl 4-amino-6-((4-bromophenyl)amino)-1,3,5-triazine-2-carboxylate (35). After the general free base procedure C, a mixture of N-(4-bromophenyl)-1-carbamimidamidomethanimidamide hydrochloride i (12.4 g, 42.5 mmol) and NaOEt (2.9 g, 42.5 mmol) was stirred in EtOH (70 mL) at rt for 22 h. After the general procedure D, a mixture of dimethyloxalate (9.1 g, 76.9 mmol) and the arylbiguanide base (9.9 g, 38.5 mmol) in anhydrous MeOH (0.21 M) was stirred at 35 °C for 1 h and then refluxed overnight for ∼2.5 d. After 28 h at −20 °C, the precipitate was collected by filtration and washed with cold MeOH to afford a white solid (8.6 g) in 69% (crude).…”

Phosphite–imidazole catalyzed N-formylation and N-acylation of amines

“…41 Recently, the multifaceted reactivity of diethyl phosphite (DEP), which exists as a tautomeric mixture of tetravalent form I and trivalent form II (Scheme 2), has been reported and its applications in organic synthesis have been explored. 45 In continuation of our efforts in developing new synthetic methods for N-formyl compounds and benzimidazoles, [46][47][48] we decided to study the N-formylation reaction of aromatic amines with DMF in the presence of DEP. Herein, we report that DMF can work as an effective formyl donor to yield the corresponding formamides including formanilides in the presence of a mixture of DEP and imidazole.…”