Structural comparison of a gem-dichlorodiarylcyclopropane antiestrogen and three of its derivatives

Abstract

The pure antiestrogenic activity of compound (1) gave the impetus to synthesize a series of its derivatives (2)-(4). Structural features of these compounds are compared. Compound (1): 1,1-dichloro-cis-2,3-diphenylcyclopropane, C15H12Cl2, Mr = 263.2, orthorhombic, Pbca, a = 19.627 (7), b = 19.460 (6), c = 6.670 (2) A, V = 2547.5 A3, Z = 8, D chi = 1.372 g cm-3, lambda (MoK alpha) = 0.71069 A, mu (Mo K alpha) = 4.3 cm-1, F(000) = 1088, T = 138 K, R = 0.026 for 1923 observed reflections. Compound (2): 1,1-dichloro-cis-2,3-bis(4-methoxyphenyl)cyclopropane, C17H16Cl2O2, Mr = 323.2, monoclinic, P2(1)/C, a = 16.540(1), b = 7.4749(7), c = 12.333 (3) A, beta = 91.53 (2) degrees, V = 1524.2 A3, Z = 4, D chi = 1.408 g cm-3, lambda (Cu K alpha) = 1.54178 A, mu (Cu K alpha) = 37.0 cm-1, F(000) = 672, T = 163 K, R = 0.031 for 2919 observed reflections. Compound (3): 1,1-dichloro-cis-2-(4-benzyloxyphenyl)-3-phenylcyclopropane, C22H18Cl2O, Mr = 369.3, monoclinic, P2(1)/alpha, a = 21.064 (3), b = 14.749 (2), c = 5.8222 (8) A, beta = 95.48 (2) degrees, V = 1800.5 A3, Z = 4, D chi = 1.362 g cm-3, lambda (Cu K alpha) = 1.54178 A, mu (CuK alpha) = 31.5 cm-1, F(000) = 768, T = 163 K, R = 0.032 for 3256 observed reflections. Compound (4): 1,1-dichloro-trans-2-(4-acetoxyphenyl)-3-phenylcyclopropane, C17H14Cl2O2, Mr = 321.2, monoclinic, P2(1)/n, a = 16.555 (4), b = 12.297 (2), c = 7.439 (1) A, beta = 98.31 (2) degrees, V = 1498.5 A3, Z = 4, D chi = 1.423 g cm-3, lambda (Mo K alpha) = 0.71069 A, mu (Mo K alpha) = 3.8 cm-1, F(000) = 664, T = 163 K, R = 0.034 for 2474 observed reflections. The crystal structure determinations show that the relative conformation of the two aryl rings in all four structures are quite similar. In this conformation one of the phenyl rings is in a bisecting position with respect to the cyclopropane ring, while the other is in a perpendicular position. In each of the four molecules the cyclopropane ring shows significant bond-length asymmetry with d[C(2)-C(3)] greater than d [C(1)-C(3)] greater than d[C(1)-C(2)].(ABSTRACT TRUNCATED AT 400 WORDS)