Ekiz, MakbuleTutar, AhmetÖkten, Salih2020-04-302020-04-3020160040-4020https://doi.org/10.1016/j.tet.2016.07.012https://hdl.handle.net/20.500.12684/3236Okten, Salih/0000-0001-9656-1803; Tutar, Ahmet/0000-0001-5524-8001WOS: 000381530900009The bromination of 2-aminobenzonitrile (2) with molecular bromine (2 equiv) furnished 2-amino-3,5-dibromobenzonitrile (7) in 98% yield. One-pot syntheses are described for dibromotacrine derivatives (6,14-18) utilizing Friedlander reactions. A convenient route is described for disubstituted derivatives of tacrines from dibromotacrine 6 and 15 by various substitution reactions. Several disubstituted tacrines were synthesized by treatment of dibromo 6 and 15 derivatives with n-BuLi followed by trapping with an electrophile [Si(Me)(3)Cl, S-2(Me)(2)]. Both were converted to the corresponding cyano derivatives (21-23) via copper-assisted nucleophilic substitution reactions in moderate yields (30%, 50%, and 60%, respectively). Copper-induced nucleophilic substitution of dibromide 15 with NaOMe afforded mono methoxide 31 in 25% yield. (C) 2016 Elsevier Ltd. All rights reserved.en10.1016/j.tet.2016.07.012info:eu-repo/semantics/closedAccessTacrineBromotacrineCyanotacrineLithium-bromine exchangeThiomethyltacrineMethoxytacrineArticle723553235330WOS:000381530900009Q2Q2