Applications of low temperature gradient sublimation in vacuo: Rapid production of high quality crystals. The first solvent-free crystals of ethinyl estradiol

Abstract

A sublimation method based on the use of a conventional vacuum oven has been developed to extend the method's range of applications. The use of a small, externally controlled heater has increased the temperature range from 80- 200 to 80-500 °C and provides high-quality crystals of compounds ranging from oxalic acid to metal-free phthalocyanine. Some unique benefits of the method are relatively rapid crystal production, provision of crystals of compounds that are known only as solvates, simple optical detection of crystals that are likely to bend, and crystal habit control. The inability of ethynyl estradiol (EE) to form solvent-free crystals is explained on the basis of the structure of vapor-grown crystals, and three new solvate structures are reported. The visual detection of bending crystals of naftazone and 1,3-dinitrobenzene is described. The crystal morphologies of 1,4-naphthaquinone, metal-free phthalocyanine, and benzoic acid are controlled by the temperature gradient in the oven. © 2013 American Chemical Society.