54083-74-8Relevant academic research and scientific papers
Conformational Behaviour of Medium-sized Rings. Part 11. Dianthranilides and Trianthranilides
Hoorfar, Alireza,Ollis, W. David,Price, Jennifer A.,Stephanatou, Julia Stephanidou,Stoddart, J. Fraser
, p. 1649 - 1700 (2007/10/02)
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-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 nitrogroups, 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-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.The constitutionally symmetrical N,N',N''-trimethyl- (7) and N,N',N''-tribenzyl- (15) trianthranilides exist in solution as an equilibrium mixture of propeller and helical conformations.In the case of the N,N',N''-trimethyl derivative (7), the predominant diastereoisomer with the helical conformation has been isolated as a pure compound.In the case of the N,N',N''-tribenzyl derivative (15), the propeller and helical conformational diastereoisomers have both been characterised as crystalline compounds.For both these compounds, the free-energy barriers to conformational inversion and interconversion processes in solution have been obtained from (i) direct equilibration experiments and (ii) dynamic 1H n.m.r. spectroscopy.Constitutionally unsymmetrical N,N'-di- and N,N',N''-tri-substituted trianthranilide derivatives can adopt three helical conformations in addition to a propeller conformation.Assignments have been made to conformations and conformational diastereoisomers of the N,N'-dimethyl- (5), N,N'-dimethyl-N''-benzyl- (12), N,N'-dibenzyl- (14), N,N'-dibenzyl-N''-methyl- (16), N-methyl-N'-benzyl- (17), N-methyl-N'-benzyl-N''-ethyl- ...
