Korotaev Vladislav Y, Zimnitskiy Nikolay S, Kochnev Ivan A, Gomzikova Elizaveta M, Milchenko Anastasia D, Tverdokhlebov Nikolay A, Eltsov Oleg S, Barkov Alexey Y, Sosnovskikh Vyacheslav Y
Institute of Natural Sciences and Mathematics, Ural Federal University, 620000 Ekaterinburg, Russian Federation.
Institute of Chemical Engineering, Ural Federal University, 620062 Ekaterinburg, Russian Federation.
ACS Omega. 2025 Aug 27;10(35):40601-40624. doi: 10.1021/acsomega.5c06843. eCollection 2025 Sep 9.
Chemoselective methods for the synthesis of 1,5-benzodiazepine derivatives have been developed from 1-polyfluoroalkyl-3-styryl-1,3-diketones and -arylenediamines or 2-aminothiophenol. When the reaction was carried out in MeOH or MeCN at room temperature, 2,3,4,5-tetrahydro-1-1,5-benzodiazepines were obtained in 36-90% yields as a result of the addition of 1,2-diamine to the α,β-unsaturated ketone fragment of the enedione. A similar reaction of 1-CF-3-styryl-1,3-diketones in MeOH at -18 °C led to 2-hydroxy-4-styryl-2,3-dihydro-1-1,5-benzodiazepines in 57-87% yields as a result of the addition of 1,2-diamine to the 1,3-dicarbonyl fragment of the enedione. Dehydration of 2-hydroxy-4-styryl-2,3-dihydro-1-1,5-benzodiazepines with trifluoroacetic acid in CHCl at room temperature gave the corresponding 3-1,5-benzodiazepines in 73-96% yields. 2-Difluoromethyl-substituted 3-1,5-benzodiazepines can be synthesized directly from the corresponding enediones and -arylenediamines in MeOH at room temperature in one step in 76-95% yields. 2-Aminothiophenol reacts with 1-polyfluorolalkyl-3-styryl-1,3-diketones at reflux in EtOH to form 2,3,4,5-tetrahydro-1,5-benzothiazepines in 24-36% yields, whereas the reaction with aminophenol stops at the enaminone stage.
已开发出从1-多氟烷基-3-苯乙烯基-1,3-二酮与芳二胺或2-氨基硫酚合成1,5-苯并二氮杂卓衍生物的化学选择性方法。当反应在室温下于甲醇或乙腈中进行时，由于1,2-二胺加成到烯二酮的α,β-不饱和酮片段上，可得到产率为36-90%的2,3,4,5-四氢-1,5-苯并二氮杂卓。1-三氟甲基苯乙烯基-1,3-二酮在-18℃的甲醇中进行类似反应，由于1,2-二胺加成到烯二酮的1,3-二羰基片段上，可得到产率为57-87%的2-羟基-4-苯乙烯基-2,3-二氢-1,5-苯并二氮杂卓。2-羟基-4-苯乙烯基-2,3-二氢-1,5-苯并二氮杂卓在室温下于氯仿中用三氟乙酸脱水，可得到产率为73-96%的相应3,5-苯并二氮杂卓。2-二氟甲基取代的3,5-苯并二氮杂卓可在室温下于甲醇中由相应的烯二酮和芳二胺一步直接合成，产率为76-95%。2-氨基硫酚在乙醇中回流时与1-多氟烷基-3-苯乙烯基-1,3-二酮反应，形成产率为24-36%的2,3,4,5-四氢-1,5-苯并噻氮杂卓，而与氨基酚的反应则停留在烯胺酮阶段。
