3-Substituted Benzo[e][1,2,4]triazines: Synthesis and Electronic Effects of the C(3) Substituent

A series of 19 structurally diverse C(3)-substituted derivatives of benzo[e] [1,2,4]triazine were synthesized from 3-chloro- (1c) and 3-iodobenzo[e][1,2,4]triazine (1d) obtained in three steps from 2-nitroaniline in 37-55% yields. Nucleophilic aromatic substitution and metal-catalyzed (Pd, Cu) reactions led to functional derivatives that include alkyl (C5H11), (het)aryl (Ph, 2-thienyl, ferrocenyl), ArC C, amine (NHPh and morpholine), PO(OEt)(2), sulfanyl (SBu-t), alkoxide (OEt, OMe), and CN. The synthesis of C(3)-CF3 derivative lg via the Ruppert reaction with ld and its 1-oxide analogue 2d led to the substitution followed by formal addition of HCF3 to the C=N bond. Pd-catalyzed carbonylation reactions of 1d and 2d did not give the corresponding C(3)-carboxylic acids. Therefore, acid if was obtained through hydrolysis of the CN. The substituent effect on the electronic structure of the benzo[e][1,2,4]triazine ring was investigated by spectroscopic methods (UV-vis and NMR) augmented with density functional theory calculations. Results show significant effect of the C(3) substituent on the pi-pi*(1) transition energy and good correlation of the H-1 NMR chemical shift with the substituent constant sigma(p). Molecular and crystal structures of six derivatives were established with the single-crystal X-ray diffraction method, and the substituent impact on the molecular geometry was investigated.