6533b857fe1ef96bd12b5123

RESEARCH PRODUCT

Synthesis of 2-anilinobenzimidates, anthranilamides, and 2,3-dihydroquinazolin-4(1H)-ones from N-heterocyclic carbenes of indazole

Martin NiegerZong GuanKai HillrichsCemre ÜNlüKari RissanenAndreas Schmidt

subject

Indazole010405 organic chemistryCarbene dimerizationbenzamideOrganic Chemistryanthranilic acidFormaldehyde010402 general chemistry01 natural sciencesBiochemistryMedicinal chemistry0104 chemical sciencescarbenechemistry.chemical_compoundReaction temperaturechemistryDrug DiscoveryAnthranilic acidOrganic chemistryBenzamideCarbeneta116indazol-3-ylideneBond cleavagebenzenecarboximidic acid

description

N-Heterocyclic carbenes of indazole (indazol-3-ylidenes), which are substituted at N1 with aromatics were generated in situ from the corresponding indazolium salts. At 60 °C the indazol-3-ylidenes underwent a ring-opening under N–N bond cleavage to intermediary N-(6-methylenecyclohexa-2,4-dien-1-ylidene)anilines. Trapping of these intermediates by alcohols proved to be a convenient method for the preparation of 2-anilinobenzimidates, which have scarcely been described in the literature. The reaction temperature avoids carbene dimerization, which occurs at −80 °C or rearrangement of the ring-opened intermediate to acridines, which affords 100 °C. Water converted the ring-opened products into anthranilamides, which were cyclized on reaction with formaldehyde to 2,3-dihydroquinazolin-4(1H)-ones.

yearjournalcountryeditionlanguage
2015-01-01Tetrahedron
10.1016/j.tet.2014.11.054https://doi.org/10.1016/j.tet.2014.11.054