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 (1 3)-(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 (1 4) adopts enantiomeric helical conformations in solution and the barrier to ring inversion is 26.8 kcal mol-l. The N,N',N"-tribenryl derivative (1 9) 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 (1 3) and (1 5)-(17). The N,N'-dibenzyl derivative (1 8) populatesthe propeller and one helicalconformation 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 (1 5) 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-l.PREVIOUSLY, we have demonstrated that the free energies of activation for ring inversion and interconversion processes 7 in solution for the trisalicylides (1)- (5) and trithiosalicylides (6)-(9) are raised dramatically by the introduction of alkyl substituents into the orthopositions of the aromatic rings. Subsequently, the conformational behaviour of a wide range of N,N'-diand N , N' ,N"-t ri-subs t it u t ed t riant hranilide derivatives l p 4 (10) in solution was studied by us in considerable detail. However, there was little or no incentive during our initial investigations reported in the preceding paper to incorporate alkyl substituents into the ortko-positions of the aromatic rings for two reasons: (i) the substituents associated with the nitrogen atoms of the trans-amide linkages provided the necessary n.m.r. probes with which to investigate the conformational behaviour of the trianthranilide derivatives in solution, and (ii) the barriers to ring inversions and interconversions involving enantiomeric pairs of diastereoisomeric propeller and helical conformations were generally in excess of 20 kcal mol-l. In some instanc...

Observation of Diastereomers of the Hydrogen-Bonded Aggregate Hub(M)3·3CA Using 1H Nuclear Magnetic Resonance Spectroscopy When CA Is an Optically-Active Isocyanuric Acid

“…Similar geometric isomers have been observed in other systems: initial investigations of medium-sized rings based on tri- o -thymotide in solution by Stoddard − and the support of these findings using single-crystal X-ray diffraction , and 13 C NMR spectroscopy revealed the presence of isomers. Recently, conformational diastereomers of a related trianthranilide have been isolated …”

Study on the Solubilities of Mononitro-Substituted Products of Nitration of m-Toluic Acid in Several Solvents at Temperatures between 297.65 and 351.75 K

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Cyclophanes in Host-Guest Chemistry

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