Conformational behaviour of medium-sized rings. Part 11. Dianthranilides and trianthranilides

Abstract

Two approaches to the stepwise syntheses of N,N′-di- and N,N′,N″-tri-substituted trianthranilide derivatives (5)–(20) are described. In the shorter synthetic route, the key acyclic intermediate, N-[2-(o-nitrobenzamido)benzoyl]anthranilic acid (26) is prepared in a stepwise manner from anthranilic acid, isatoic anhydride (23), followed by o-nitrobenzoyl chloride. Alkylations of the amide functions at nitrogen, reductions of the aromatic nitro-groups, and cyclisations of the acyclic amino-acid derivatives provide a direct route to N,N′-dimethyl-(5) and N,N′-dibenzyl-(14) trianthranilides. Further alkylations or acylations of either (5) or (14) afford (i)N,N′,N″-trimethyltrianthranilide (7) and its trideuteriomethyl analogue (8), (ii)N,N′-dimethyl-N″-acetyl-(10), -N″-benzoyl-(11), and -N″-benzyl-(12) trianthranilides, (iii)N,N′,N″-tribenzyltrianthranilide (15), and (iv)N,N′-dibenzyl-N″-methyltrianthranilide (16). In the longer synthetic route, the key acyclic intermediate, methyl N-methyl-N-[2-(o-nitrobenzamido)benzoyl]anthranilate (42) is prepared in a stepwise manner from anthranilic acid and two molar equivalents of o-nitrobenzoyl chloride. Alkylations of the unsubstituted amide functions at nitrogen, reductions of the aromatic nitro-groups, and cyclisations of the acyclic amino-acid derivatives provide, not only an alternative route to N,N′-dimethyltrianthranilide (5) but also, a general route to the N-methyl-N′-trideuteriomethyl-(6), N-methyl-N′-benzyl-(17), and N-methyl-N′-ethyl-(19) analogues. Further alkylations of these N,N′-disubstituted derivatives afford N-methyl-N′,N″-di(trideuteriomethyl)-(9), N-methyl-N′-trideuteriomethyl-N″-benzyl-(13), N-methyl-N′-benzyl-N″-ethyl-(18), and N-methyl-N′-ethyl-N″-benzyl-(20) trianthranilides.