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

#### **Leo Štefan 1,\*, Dubravka Matkovi´c-Calogovi´c ˇ <sup>2</sup> , Darko Fili´c <sup>3</sup> and Miljenko Dumi´c <sup>4</sup>**


Received: 13 July 2020; Accepted: 28 July 2020; Published: 3 August 2020

**Abstract:** The spontaneous *S*-alkylation of the thyreostatic drug methimazole (1-methyl-1,3-dihydro-1*H*-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-1*H*-imidazole-2-yl)thio]ethane, C10H14N4S<sup>2</sup> (**2a**), primarily isolated in the form of dihydrochloride tetrahydrate [C10H16N4S2]Cl2·4(H2O) (**2b**), which crystallized in the monoclinic *P*21/c space group. Neutralization of **2b,** followed by crystallization from the acetone/water mixture, produced dihydrate C10H14N4S2·2(H2O) (**2c**), which crystallized in the trigonal *R*-3 space group. Six water molecules in **2c** are H-bonded mutually and to the nitrogen atoms of six molecules of **2a.** DSC and TGA showed that **2c** melts at 65 ◦C and loses water up to 120 ◦C. By cooling to room temperature, anhydrous **2a** was obtained. Single crystals of **2a** that are suitable for X-ray structure analysis were obtained by neutralization of **2b,** followed by crystallization from dry dichloromethane. Anhydrous **2a** crystallizes in the monoclinic *P*21/c space group. The dehydration of **2c** led to the formation of the anhydrous product **2a,** 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 of **2c** via 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.

**Keywords:** methimazole; 1,2-bis[(1-methyl-1*H*-imidazole-2-yl)thio]ethane; solid-state forms; hydrates; dehydration
