Crystallographic studies of piperazine derivatives of 5,5-dimethylhydantoin in the search for structural features of A1-adrenoreceptors antagonists

A number of piperazine derivatives of hy­dan­toin display high affinity for $α_{1}$-adrenoreceptors and antagonistic properties, which make them potent hypotensive agents. In order to study the correlations between affinity for $α_{1}$-adrenoreceptors and mol­ecular structures, the crystal structures of six piperazine derivatives of 5,5-di­methyl­hy­dan­toin were determined by X-ray diffraction, namely, 4-(3-{3-[(2,4-di­chloro­phen­yl)meth­yl]-5,5-dimethyl-2,4-dioxoimidaz­oli­din-1-yl}-2-hy­droxy­prop­yl)-1-phenyl­piperazine-1,4-diium dichloride monohy­drate ethyl acetate hemisolvate, $C_{25}H_{32}Cl_{2}N_{4}O_{3}$$^{2+}·2Cl^{−}·H_{2}O·0.5C_{4}H_{8}O_{2}$ (1), 4-(2-cyano­phen­yl)-1-(3-{3-[(2,4-di­chloro­phen­yl)meth­yl]-5,5-dimethyl-2,4-dioxo­imidazolidin-1-yl}-2-hy­droxy­prop­yl)piperazin-1-ium chloride aceto­nitrile monosolvate, $C_{26}H_{30}Cl_{2}N_{5}O_{3}$$^{+}·Cl^{−}·C_{2}H_{3}N$ (2),1-(3-{3-[(2,4-di­chloro­phen­yl)meth­yl]-5,5-dimethyl-2,4-dioxoimidazolidin-1-yl}-2-hy­droxy­prop­yl)-4-(3,4-di­methyl­phen­yl)piperazin-1-ium chloride, $C_{27}H_{35}Cl_{2}N_{4}O_{3}$$^{+}·Cl^{−}$ (3), 1-(3-{3-[(2,4-di­chloro­phen­yl)meth­yl]-5,5-dimethyl-2,4-dioxoimidazolidin-1-yl}-2-hy­droxy­prop­yl)-4-(3-meth­oxy­phen­yl)piperazin-1-ium chloride, $C_{26}H_{33}Cl_{2}N_{4}O_{4}$$^{+}·Cl^{−}$ (4), 4-(2,3-di­chloro­phen­yl)-1-(3-{3-[(2,4-di­chloro­phen­yl)meth­yl]-5,5-dimethyl-2,4-dioxo­imidazolidin-1-yl}-2-hy­droxy­prop­yl)piperazin-1-ium chloride 0.2-hydrate, $C_{25}H_{29}Cl_{4}N_{4}O_{3}$$^{+}·Cl^{−}·0.2H_{2}O$ (5), and 3-[(2,4-di­chloro­phen­yl)meth­yl]-1-{3-[4-(3,4-di­chloro­phen­yl)piperazin-1-yl]-2-hy­droxy­prop­yl}-5,5-di­methyl­imidazolidine-2,4-di­one, $C_{25}H_{28}Cl_{4}N_{4}O_{3}$ (6). The com­pounds crystallize in the centrosymmetric triclinic space group, except for 2, which crystallizes in the monoclinic space group $P2_{1}/c$. For all six com­pounds, one mol­ecule is ob­served in the asymmetric unit. The mol­ecule of 1 is doubly protonated at both N atoms of the piperazine ring, whereas 2, 3, 4 and 5 are only protonated at one ring N atom. The protonated N atoms are engaged in charge-assisted hy­dro­gen bonds with the chloride anions, and in 1 the N atom inter­acts with the chloride anion via the water mol­ecule. The crystal packing in the protonated mol­ecules (1–5) is in each case dominated by a network of $N—H^{+}⋯Cl^{−}, O—H⋯Cl^{−} and C—H⋯Cl^{−}$ hy­dro­gen bonds, while in the base mol­ecule of 6, O—H⋯O hy­dro­gen bonds dominate.