1-[4-(3-{[5-(4-Chlorophenyl)furan-2-yl]methylideneamino}-2,5-dioxoimidazolidin-1-yl)butyl]-4-methylpiperazine-1,4-diium dichloride hemihydrate

The title compound, C23H30ClN5O3 2+·2Cl−·0.5H2O, was synthesized by N-alkylation of 1-({[5-(4-chlorophenyl)-2-furanyl]methylene}amino)-2,4-imidazolidinedione with 1-bromo-4-chlorobutane, and N-methylpiperazine. In the crystal, the cations, anions and water molecules are linked by O—H⋯Cl and N—H⋯Cl hydrogen bonds.

All bond lengths and angles in (I) are within normal ranges (Allen et al., 1987) except for the N-H bonds involved in hydrogen bonds with charged donors N4-H4A (1.04 Å) and N5-H5A (1.05 Å)of piperazonia ring, and also chloride ions  (Table 1 and Fig. 2).

Experimental
The title compound was prepared according to the method of Matson et al. (1999). A three-neck 1 L flask fitted with a thermometer, mechanical stirrer, heating mantle, reflux condenser and addition funnel is charged with DMF (240 ml) and heated to 323 K. 1-[[[5-(4-Chlorophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidinedione (29 g) is added and heating is continued. When dissolution is completed, potassium carbonate (14 g) is charged to the flask and heating is continued to 353 K. After 20 minutes, 1-bromo-4-chlorobutane (18.5 g) is added, and heating is continued to approximately 373 K.
After 50 minutes, N-methylpiperazine (23.5 g) is added, and the mixture is allowed to stir for 2 h at 373 K. The reaction mixture is cooled to approximately 283 K and filtered to remove insolubles. The DMF is removed under reduced pressure at 338-341 K and replaced with absolute ethanol (175 ml). The mixture is heated to dissolve the free base and filtered to remove insolubles. The product is precipitated from ethanol (300 ml total) with the addition of 20 g of concentrated hydrochloric acid and then filtered to give 31 g of Azimilide dihydrochloride. The above dihydrochloride is suspended in 670 ml of refluxing ethanol and 150 ml of water are added to obtain complete solubilization. The mixture was standing under 298 K, then white crystals were grown slowly. The crystals were washed with cold ethanol, yield 25.6 g.

Refinement
The two water H atoms were located in a difference Fourier map and then refined as riding on the water O atom (0.85 and 0.86 Å). Other H atoms were positioned geometrically and refined using a riding model, with d(C-H) = 0.93 -0.97 Å and U iso (H) = 1.2U eq (C) or 1.5U eq (C methyl ).
supplementary materials sup-2 Figures Fig. 1. The molecular structure of (I) with the atom-numbering scheme and 30% probability displacement ellipsoids.