A new synthetic method for the construction of benzoazepine analogues has been developed employing ortho-arylmethylbenzyl azide derivatives as precursors using an azide rearrangement reaction. In this work, 14 benzoazepine compounds were successfully synthesized in moderate to excellent yields. All synthetic benzoazepines were evaluated for their cytotoxicity against normal human kidney cell line (HEK cell). The results showed that compound 18c had the lowest cytotoxicity (IC50 = 65.68 μM) among tested compounds, which was comparable with the antianxiety drug diazepam (IC50 = 87.90 μM). Based on the cytotoxicity results, five benzoazepine analogues (compounds 18c, 18h, 18j, 18n, and 18p) were selected to determine the antianxiety effect on stressed rats using elevated plus maze (EPM) and open field test (OFT) methods. Interestingly, compound 18c showed better anxiolytic activity than diazepam without a sedative effect by showing superior hyperlocomotor activity. Therefore, this discovery could pave the way for drug development to treat patients with anxiety disorder.

ortho-Arylcyclopropanecarbonyl carboxaldehydes were utilized common substrates for the synthesis of furanodibenzocycloheptenes and dibenzocycloheptenes. Excess amount of (+)-camphorsulfonic acid ((+)-CSA) could lead to acid-promoted cyclopropane ring opening/cyclization reaction of the common substrates to give dibenzocycloheptene products in up to 87% yield. Alternatively, when the common precursors were treated with catalytic amount of super acid (NHTf 2 ) resulting in the formation of furanodibenzocycloheptenes as a mixture of two regioisomeric products.