Organic Crystal Engineering with 1,4-Piperazine-2,5-diones. 6. Studies of the Hydrogen-Bond Association of Cyclo[(2-methylamino-4,7-dimethoxyindan-2-carboxylic acid)(2-amino-4,7-dimethoxyindan-2-carboxylic acid)]

The title 1,4-piperazine-2,5-dione was synthesized in 23% yield over six steps from ethyl 2-amino-4,7-dimethoxyindan-2-carboxylate. Crystallization by slow diffusion of ether into a chloroform
solution and by slow evaporation of an ethanol−chloroform−benzene solution produced polymorphic
crystalline forms as determined by single-crystal X-ray analysis. The polymorphs exhibited different
hydrogen-bonding networks. The association of this piperazinedione in solution was studied using
mass spectrometric and nuclear magnetic resonance spectroscopic techniques. The MS and NMR
data were interpreted using the solid-state structures as models for solution aggregation. Association
constants extracted from the NMR data are in line with those of other cyclic cis amides in chloroform
solvent.