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

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posted on 19.04.2019, 00:00 by Agnieszka Bodzioch, Dominika Pomikło, Małgorzata Celeda, Anna Pietrzak, Piotr Kaszyński
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 1g via the Ruppert reaction with 1d 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 1f 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 π–π*(1) transition energy and good correlation of the 1H NMR chemical shift with the substituent constant σp. 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.