Conformational behaviour of medium-sized rings. Part 12. Tri-3-methyltrianthranilide

Abstract

The stepwise synthesis of the N,N′-di- and N,N′,N″-tri-substituted tri-3-methyltrianthranilides (13)–(19) are described. The amino-acid derivatives (34), (38), and (45), which are the key acyclic precursors in the synthesis of the tri-3-methyltrianthranilides, were all prepared from 2-amino-m-toluic acid (22) and 2-nitro-m-toluoyl chloride as starting materials.

Tri-3-methyltrianthranilide derivatives with three equivalent N,N′,N″-substituents can exist in either propeller or helical conformations. The N,N′,N″-trimethyl derivative (14) adopts enantiomeric helical conformations in solution and the barrier to ring inversion is 26.8 kcal mol^–1. The N,N′,N″-tribenzyl derivative (19) populates both propeller and helical conformations in solution: these two conformational diastereoisomers have been separated by chromatography and isolated as crystalline compounds.

Tri-3-methyltrianthranilide derivatives with two or three non-equivalent N,N′,N″-substituents can, in principle, exist in either propeller or three different helical conformations. One of these three helical conformations is specifically populated in deuteriochloroform solution by compounds (13) and (15)–(17). The N,N′-dibenzyl derivative (18) populates the propeller and one helical conformation in solution: two conformational diastereoisomers have been isolated, one as an oil and the other as a crystalline compound.

The N,N′-dimethyl-N″-benzyl derivative (15) undergoes spontaneous resolution when it crystallises as a 1 : 1 adduct from toluene. The N-methyl-N′-benzyl derivative (16) also forms a 1 : 1 inclusion compound on crystallisation from toluene. Although this derivative exists as only one conformational diastereoisomer of the helical type in deuteriochloroform solution, two different diastereoisomeric conformations undergo equilibration in hexadeuteriodimethyl sulphoxide with a barrier to interconversion of 16.1 kcal mol^–1.