Eine einfache Synthese des 1,2,4-Oxadiazol-Systems durch N-O-Verknüpfung

Increasing the index of covalent oxygen bonding at nitrogen attached to carbon

“…Oxidation of an acylenamine to create an isoxazole ring nitrogen-oxygen bond is apparently unknown; however, the closely related preparation of a 1,2,4-oxadiazole (eq 109) from .CR (109) an A/-acylamidine (141) and alkaline hypochlorite was recently reported. 129 Another oxadiazole ring closure was discovered on heating neat the A/'-benzoyl derivative 143 of /V-benzlmidoyl-S, S-dimethylsulfilimine (eq 111).130 N^> (111) CeH5…”

Synthesis of Aroylguanidines by an Unexpected Demethylation-Addition Cascade

“…18 Furthermore, several nitrogencontaining heterocycles, including highly bioactive guanosines, 19 can be prepared by using acylguanidines as starting materials. [20][21][22][23] Because of the importance of acylguanidines in various roles, several methods have been reported for their synthesis. 24 However, in comparison with N-polysubstituted acylguanidines, the routes to N-acyl-N′-arylguanidines are limited to several representative approaches, including reactions of acylcyanamides with aniline hydrochloride in refluxing toluene or xylenes, 25 acylation of guanidines with carbonic acid in the presence of 1,1′-carbonyldimidazole, 21 solid-phase synthesis of disubstituted acylguanidines; 26 and the reaction of acylthioureas with hexamethyldisilazane in the presence of 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide to give acylguanidines.…”

Acyl Amidines by Pd-Catalyzed Aminocarbonylation: One-Pot Cyclizations and 11C Labeling

“…1,2,4-Oxadiazoles are accessible from acyl amidines by reaction with hydroxylamine hydrochloride or sodium hypochlorite. , After some experimentation, we discovered that the former reagent was suitable for the two-step one-pot preparation of 1,2,4-oxadiazoles. Specifically, we utilized this strategy to prepare unsymmetrical diaryl-1,2,4-oxadiazoles 6a – 6d in 40–73% yield from the respective aryl iodide and 2a over two steps (Scheme ).…”

“…Building on the successful one-pot carbonylation/cyclization sequence developed using Mo­(CO) 6 , 11 C-6a was synthesized from 1a and 2a (Scheme ). The cyclization was tested with hydroxylamine hydrochloride and sodium hypochlorite, with only the former giving full consumption of the intermediate 11 C-3a (HPLC analysis). , Pleasingly, isotopically labeled 1,2,4-oxadiazole 11 C-6a could be isolated in a decay-corrected RCY of 25% and in 99% radiochemical purity. The RCY was based on the starting amount of [ 11 C]­CO and the decay-corrected, isolated amount of 11 C-6a .…”

“…Acyl amidines are useful intermediates in the synthesis of a number of heterocycles, such as 1,2,4-triazoles, , 1,3,5-triazines, 1,2-dihydro-3 H -pyrrol-3-ones, and 1,2,4-oxadiazoles. , They are also interesting motifs in drug discovery, and biologically active examples are found throughout the literature, including angiotensin II receptor ligands, thrombin (prodrug), β-secretase, cathepsin D, and renin inhibitors . The most straightforward synthesis of acyl amidines is by acylation of amidines and was indeed reported by Pinner already in 1889 from an acid anhydride .…”