Bisphenol flukicides. I. Crystal structures of 2,2'-ethylidenebis(4-chloro-6-nitrophenol) and 2,2'-isopropylidenebis(4-chloro-6-nitrophenol)

Abstract

Abstract2,2'-Ethylidenebis (4-chloro-6-nitrophenol), ClaHIoC12N206, is monoclinic, space group P2~/c, with a = 9.859 (13), b = 12.557 (10), c = 12.451 (6) A, fl = 94.46 (7) °, Z = 4. 2,2'-Isopropylidenebis(4-chloro-6-nitrophenol), ClsHI2CI2N206, is monoclinic space group C2/c, with a = 13.785 (2), b = 13.077 (5), c = 9.291 (3) A, fl= 97.81 (3) °, Z = 4. Both structures were deduced from Mo Ka intensities measured on a diffractometer. The ethane structure was determined by direct methods and refined to an R of 0.065 for 1218 observed terms. The heavy-atom method was used to solve the isopropane structure, which was refined to an R of 0.049 for 1051 observed terms. In the ethane structure, the CI atoms lie on the same side of the molecular skeleton and the dihedral angle between the phenyl rings is 92.4 °. In the isopropane structure, however, the phenyl rings are mutually inclined at 77.4 ° and the CI atoms lie on opposite sides of the molecular skeleton which has twofold symmetry.Introduction 5,5'-Dichloro-3,3'-dinitro-2,2'-biphenyldiol (I), otherwise known as menichlopholan, is an effective curative 0567-7408/79/122952-06501.00for Fasciola hepatica (liver-fluke) infection in sheep and cattle (Burrows, 1973). Menichlopholan uncouples oxidative phosphorylation in warm-blooded animals (van Miert & Groeneveld, 1969) and it is probable that the effectiveness of the compound against liver-flukes is due to the same effect. The related compound, 2,2'-methylenebis(4-chloro-6-nitrophenol) (II), has been shown to be an effective fasciolicide; similarly, 2,2'-ethylidenebis(4-chloro-6-nitrophenol) hepatica, but 2,2'-isopropylidenebis(4-chloro-6-nitrophenol) (IV) possesses no effective fasciolicidal properties (information supplied by ICI Australia Ltd).It has been suggested that me variation of anthelmintic (worm-killing) properties of bisphenol analogues may be attributed to differing conformations in the molecules (ICI Australia Ltd). We are currently carrying out crystallographic studies of a number of bisphenols in an attempt to derive a possible relationship between their conformations and biological activity.The first two crystal structures determined in this series, (III) and (IV), are reported here and subsequently referred to as the ethane and isopropane respectively. ExperimentalWeissenberg photographs showed that yellow plate-like crystals of (III), grown from ethanol in a desiccator over sulphuric acid, were monoclinic, space group P21/c.Yellow needles of (IV), similarly grown from ethyl acetate, were also shown to be monoclinic, space group Cc or C2/c, subsequently confirmed as C2/c. Cell parameters were determined by least squares from 20 values for ten strong reflections for the ethane and 25 for the isopropane structure, measured on a diffractometer with Mo Ka radiation. The densities were determined by flotation in a mixture of o-xylene and bromoform and indicated Z = 4 for both structures. Crystal data are given in Table 1.For both compounds, intensities were recorded withMo Ka radiation on a Rigaku-AFC fo...

5,5'-Dichloro-3,3'-dinitro-2,2'-biphenyldiol

“…It is recognized that biphenol and bisphenol flukicides act by inhibiting ATP production in the flukes, and the active site is thought to be the succinate dehydrogenase complex (Metzger & Dfiwel, 1973). The molecular conformation of the biphenol reported here provides a comparison with those of several bisphenol flukicide structures reported earlier (Hay & Mackay, 1979Hay, DeMunk & Mackay, 1980). The latter, which contain a bridging C atom, have the same ring substitutents as niclofolan in which the phenyl rings are directly linked.…”

Molecular conformation of di-o-anisylcarbinol: an X-ray diffraction study

“…A considerable number of molecular structure determinations, theoretical calculations, and nmr spectra on bridged diphenyl con~pounds have been performed by several authors (4)(5)(6)(7)(8)(9)(10)(11)(12). A common purpose of these works was to study the effects of different bridging atoms and phenyl substituents on the bridged diphenyl conformation.…”