Synthesis, Crystal Structure and Solid State Transformation of 1,2-Bis[(1-methyl-1H-imidazole-2-yl)thio]ethane

The spontaneousS-alkylation of the thyreostatic drug methimazole (1-methyl-1,3-dihydro-1H-imidazole-2-thione,1) with 1,2-dichloroethane at room temperature, in dark or light conditions, led to the formation of its related substance 1,2-bis[(1-methyl-1H-imidazole-2-yl)thio]ethane, C10H14N4S2(2a), primarily isolated in the form of dihydrochloride tetrahydrate [C10H16N4S2]Cl-2 center dot 4(H2O) (2b), which crystallized in the monoclinicP2(1)/c space group. Neutralization of2b,followed by crystallization from the acetone/water mixture, produced dihydrate C10H14N4S2 center dot 2(H2O) (2c), which crystallized in the trigonalR-3 space group. Six water molecules in2care H-bonded mutually and to the nitrogen atoms of six molecules of2a.DSC and TGA showed that2cmelts at 65 degrees C and loses water up to 120 degrees C. By cooling to room temperature, anhydrous2awas obtained. Single crystals of2athat are suitable for X-ray structure analysis were obtained by neutralization of2b,followed by crystallization from dry dichloromethane. Anhydrous2acrystallizes in the monoclinicP2(1)/c space group. The dehydration of2cled to the formation of the anhydrous product2a,which is identical to the one obtained by crystallization, as was found by complementary solid-state techniques. No intermediate monohydrate or hemihydrate phases were detected. Powder diffraction showed the same pattern of2cvia both preparation procedures. The structures of all the forms were elucidated by spectroscopy, microscopy and thermal methods and confirmed by single crystal X-ray analysis.