Crystallization in Polymorphic Systems:  The Solution-Mediated Transformation of β to α Glycine

Abstract

The crystallization and subsequent polymorphic transformation from the β to the R form of glycine has been studied using optical microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy techniques. The crystal structure and morphology of β glycine have been determined, and the influence of solvent, solubility, and process scale on its solvent-mediated transformation to the R form was quantified. It is concluded that for the low solubility environments used in this study, the rate-determining step in the transformation process is the dissolution rate of the metastable β polymorph.

Solid state linear-dichroic infrared (IR-LD) spectroscopic characterization of α-and β-glycine polymorphs

“…Crystals of β-glycine were grown by a liquid diffusion method described in [1,10]. Ethanol (5 ml) was carefully added dropwise to 10 ml of a saturated aqueous solution of α-glycine at 25 • C, forming small crystals of the β-form.…”

“…1.1) shows a broad absorption maximum with the highest NH stretching peak at 3093 cm −1 , characteristic of the α−modification [1,10]. According to theory [18] [24] or to (δ CCO + ν CC ) [18].…”

“…Assignment and confirmation of the experimental IR bands is carried out by IR-LD spectral analysis below and compared with the crystallographic structure for α-glycine [1][2][3][4][5][6][7][8][9][10]. [4]).…”

“…Crystallography [1,7,9,10] shows the monoclinic β-polymorph to be very similar to α, also forming head-to-tail chains of zwitterions linked by NH. .…”

“…O II distances are 2.758, 3.002 and 2.833, 3.022Å, respectively [4]). In the β-form individual parallel polar layers are linked via hydrogen bonds in a threedimensional network [1,7,9,10] (see Schemes 1a and 1b). However, the departure of the N-atom from the plane containing the COO − -fragment is larger in the β-polymorph (Scheme 1b).…”