Chichibabin-Type Condensation of Cyclic Ketones with 3-R-1,2,4-triazin-5(4H)-ones

Abstract

Reactions between substituted 1,2,4-triazines and ketones were investigated. General procedures for one-pot synthesis of hydrogenated derivatives of such polycyclic systems as benzo[c][1,2,4]triazino[1,6-a][2]azecine, [1,2,4]triazino[1,6-f]phenantridine, and dicyclopenta[b,d]pyrido[1,2-f][1,2,4]triazine are described.

[3 + 3]-Cycloaddition Reactions of α-Acidic Isocyanides with 1,3-Dipolar Azomethine Imines

“…On the basis of the above experimental results (Table and Scheme ) and related reports, ,,,,,, a possible mechanism for the [3 + 3]-cyclo­addition of α-metalated isocyanides 2 with azo­methine imines 1 is proposed (Scheme , with the reaction of iso­cyano­acetate 2a with imine 1a as an example). The reaction starts with the formation of α-cuprio­iso­cyanide A or its tautomer A ′ from iso­cyano­acetate 2a in the presence of CuI and DBU. ,, Then, the nucleophilic addition of α-cuprio­iso­cyanide A on the imine 1a takes place to form intermediate B .…”

“…In principle, α-metalated isocyanides are ambivalent reagents because both contain nucleophilic and electrophilic centers. − Consequently, we envisioned that the [3 + 3]-cyclo­addition reaction of α-acidic isocyanides with certain 1,3-dipoles should happen to form six-membered heterocycles. As part of our ongoing interest in developing cyclo­addition reactions based on α-acidic isocyanides, we present herein the first example of [3 + 3]-cyclo­addition reactions based on α-acidic isocyanides, including CuI-catalyzed [3 + 3]-cross-cyclo­addition of α-acidic isocyanides with azomethine imines and the AgOTf-catalyzed one-pot [3 + 3]-cycloaddition of ethyl iso­cyano­acetate with N -imino­isoquino­linium ylides, generated in situ from ( E )- N ′-(2-alkynyl­benzylidene)-4-methyl­benzene­sulfono­hydrazides, to deliver di- and tricyclic 1,2,4-triazine compounds (Scheme , eq 3). , Triazine derivatives have been identified as pharmaco­logically important heterocycles with diverse biological activities, − found in natural products, , and applied in organic synthesis. − …”

“…The [3 + 3]-cyclo­addition of α-acidic isocyanides with 1,3-dipoles described above represents a simple and efficient protocol for the direct synthesis of the six-membered heterocycles, [1,2,4]triazine derivatives 4 . , Encouraged by the successful application of α-acidic isocyanides 2 in the [3 + 3]-cross-cyclo­addition with azomethine imines 1 , next, we examined the one-pot reaction of ethyl iso­cyano­acetate 2a with ( E )- N ′-(2-alkynyl­benzyl­idene)-4-methyl­benzene­sulfono­hydrazides 5 as the precursors of N -imino­iso­quinolinium ylides 6 (Scheme ) . Fortunately, [1,2,4]triazino[6,1- a ]iso­quinoline 7a was obtained in 94% isolated yield when N ′-(2-alkynyl­benzyl­idene)hydrazide 5a was treated with AgOTf (10 mol %) in DCE (DCE = 1,2-dichloro­ethane) at 60 °C for 2 h followed by the addition of 2a and DBU (20 mol %).…”