Crystal structure and physical characterization of neotame methanol solvate

The crystal structure of the methanol solvate (empirical formula: 2C(20)H(30)N(2)O(5). 3CH(3)OH) of a new dipeptide sweetener, neotame (N-(3,3-dimethylbutyl)-L-alpha-aspartyl-L-phenylalanine 1-methyl ester), has been determined. Crystal data: a = 9.8989(1), b = 18.1331(1), c = 27.5725(1) Angstrom, orthorhombic, space group P2(1)2(1)2(1), with Z = 4. Each unit cell includes 8 neotame and 12 methanol molecules. Disorder exists in one neotame molecule and one methanol molecule. The crystals were characterized by the following techniques: hot-stage microscopy (HSM), Karl-Fischer titrimetry (KFT), powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), thermogravimetry (TGA),C-13 solid-state nuclear magnetic resonance (SSNMR) spectroscopy. Under HSM at a heating rate of 10 degrees C/min in silicone oil, the sample melts at 64-84 degrees C and liberates bubbles at 71-86 degrees C. DSC in open pans shows two overlapping endotherms at 56 and 71 degrees C, probably due to melting and desolvation, respectively. TGA in open pans shows 5.9% weight loss due to desolvation below 70 degrees C. Under house vacuum (23 mm Hg) over phosphorus pentoxide at 23 degrees C, the methanol solvate produces pure amorphous anhydrate, which converts to crystalline neotame monohydrate in the presence of moisture.