D-Secoestrone derivatives. V. 3-Methoxy-17-oxo-17-phenyl-16,17-secoestra-1,3,5(10)-triene-16-nitrile and 17-hydroxy-3-methoxy-17-phenyl-16,17-secoestra-1,3,5(10)-triene-16-nitrile

The two title 16,17-secoestrone derivatives, 3-methoxy-17-oxo-17-phenyl-16,17-secoestra-1,3,5(10)-triene-16-nitrile, C₂₅H₂₇NO₂, (I) (17-oxo substituent), and 17-hydroxy-3-methoxy-17-phenyl-16,17-secoestra-1,3,5(10)-triene-16-nitrile, C₂₅H₂₉NO₂, (II) (17-hydroxy substituent), have quite different conformations in the solid state. These conformational differences can be minimized by molecular mechanics calculations. Thus, the remarkable difference in the biological activity of the two compounds, e.g. the strong oestrogenic characteristics of (I) and the moderate antioestrogenic action of (II), must be caused by the difference in substitution at C17. In (II), the mol­ecules are linked by O—H...N hydrogen bonds, forming spirals along the b direction.

S1. Comment

Within the framework of a broader project aimed at obtaining potential antioestrogens, a series of new 16,17-secoestrone derivatives has been reported by Petrović et al. (1990). While studying the structure-activity relationships of these derivatives (Stanković et al., 1992, 1993, 1994), we observed that the substituent at C17 has a remarkable influence on the biological properties of the synthesized compounds. Thus, to a great extent, 3-methoxy-17-hydroxy-17-methyl-16,17-secoestra-1,3,5(10)-trien-16-nitrile retained oestrogenic characteristics, while the corresponding 17-benzyl derivative showed a complete loss of oestrogenic activity, exhibiting a moderate antioestrogenic action (Medić-Mijačević, 1992).

With the aim of further investigations into the influence of C17 substituents on biological activity, the two new title 16,17-secoestrone derivatives, (I) and (II), were prepared. Since the starting materials were synthesized from the natural oestrone, the absolute stereochemistry of which is known (Fieser & Fieser, 1967), the X-ray structures of (I) and (II) are described for the appropriate enantiomer. \sch

Perspective views of the molecules of (I) and (II) are shown in Figs. 1 and 2. During the anisotropic refinement, it became evident from the displacement parameters of compound (I) that the phenyl ring is disordered; the phenyl ring atoms exibit large thermal displacements which are almost parallel with the plane containing them. The model that describes this disorder has at least two phenyl rings, denoted A and B. Since the phenyl ring plane practically coincides with the plane containing the C13—C17 and C17—C20 bonds, as seen from the C13—C17—C20(A,B)—C25(A,B) torsion angles (Table 1), these thermal displacements cause deformation of the C13—C17—C20(A,B) angles (Table 1), which is significant for conformer (A).

Molecular mechanics calculations (MMC) using PCMODEL (Serena Software, 1989) Query were also performed to define the conformation of the molecules in terms of energy minima. It was found that the molecule of (I) with an unsplit phenyl ring has an energy minimum conformation with respect to the molecule with disordered phenyl rings, so this model was used for MMC in the ring-conformation and molecular-energy analysis.

Ring puckering parameters (Cremer & Pople, 1975) and asymmetry parameters (Duax et al., 1976) define the ring conformations for both (I) and (II). Steroid ring B exhibits a 7α,8β-half chair conformation (³H₄) in both molecules, which is slightly distorted towards a 7α-envelope (³E) after MMC. Steroid ring C has an almost ideal 8β,12α-chair conformation in (I), but it is significantly distorted in (II). After MMC, the conformation of ring C in (I) also became significantly distorted and similar to (II). The orientation of the phenyl ring, defined by the C14—C13—C17—C20 and C13—C17—C20—C25 torsion angles, was changed, too, by about 26 and -75°, respectively. Rotation of the phenyl ring about the C17—C20 bond in the rigid-rotor approximation confirmed that, in the crystalline state, molecule (I) is in a shallow minimum, significantly removed from the absolute minimum. The orientation of atom O2 was also changed by about 10°, going from synperiplanar to synclinal in relation to atom C14. Since the conformations of the molecules became similar after MMC (Fig. 3), the difference in biological activity could be interpreted as being due to the different substituents at C17, as well as the fact that, in (II), a new chiral centre has been introduced.

In compound (II), there appears to be a short intramolecular contact of 1.96 Å between H17 and H151, which is much shorter than the relevant van der Waals sum of 2.4 Å. However, the corresponding value of 2.04 Å in the energy-minimized structure suggests that this shortness is simply a consequence of the minimum energy conformation of the molecule.

Also in compound (II), there is an O—H···N hydrogen bond (Table 3). In (I), there are only van der Waals separations between molecules. The non-bonded intramolecular O1···O2 distances (Tables 1 and 2), which could be responsible for biological activity, are shorter than the corresponding distance of 10.9 Å found in oestradiol (Fullerton, 1977; Duax et al., 1977).

S2. Experimental

The starting material was 3-methoxy-1,3,5(10)-triene-16,17-dione-16-oxime, (1), which was prepared from oestrone using the procedure of Miljković & Petrović (1977). Addition of phenyllithium to the C17 carbonyl function of (1) led to the formation of 3-methoxy-17α-phenyl-17β-hydroxyestra-1,3,5(10)-trien-16-one oxime, (2), in a 69.64% yield. The action of p-toluene sulfonyl chloride on (2) in dry pyridine resulted in a Beckmann fragmentation reaction and the formation of the 16,17-seco derivative, (I), in a high yield. Finally, sodium borohydride reduction of (I) afforded (II) as the sole product.

S3. Refinement

The crystals of (I) were very thin and their diffraction power very low, so the data collection was stopped at θ = 59.93°. For this reason, the calculated sin(θ_max)/wavelength (0.5613) is less than the required value of 0.575, and the required ratio of reflections to parameters of 8 has not been satisfied either (6.1094). The H atoms were generated and refined as riding, with isotropic displacement parameters fixed to 1.2U_eq or 1.3U_eq of the parent atoms, or 1.5U_eq for the methyl-H atoms. Refinement of the Flack (1983) parameter was not successful for either compound.

Computing details

For both compounds, data collection: CAD-4 Software (Enraf-Nonius, 1989); cell refinement: CAD-4 Software; data reduction: CAD-4 Software; program(s) used to solve structure: SHELXS86 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPII (Johnson, 1976); software used to prepare material for publication: CSU (Vicković, 1988).

Figures

	Fig. 1. A perspective view of (I) with the atomic labelling scheme. Displacement ellipsoids are shown at the 30% probability level and H atoms are drawn as spheres of arbitrary radii. The disordered phenyl ring is represented by two subgroups, C20A—C25A and C20B—C25B. The site occupancy factor of the subgroup A is 0.287 (6) and that of the subgroup B 0.713 (6).
	Fig. 2. A perspective view of (II) with the atomic labelling scheme. Displacement ellipsoids are shown at the 30% probability level and H atoms are drawn as spheres of arbitrary radii.
	Fig. 3. The superimposed fit for the energy minimized molecular structures of (I) (solid lines) and (II) (dashed lines).

(I) 3-methoxy-17-oxo-17-phenyl-16,17-secoestra-1,3,5(10)-triene-16-carbonitrile

Crystal data

C25H27NO2	F(000) = 400
Mr = 373.48	Dx = 1.207 Mg m^−3
Monoclinic, P21	Cu Kα radiation, λ = 1.54178 Å
a = 8.154 (1) Å	Cell parameters from 25 reflections
b = 8.602 (3) Å	θ = 10–20°
c = 15.005 (4) Å	µ = 0.59 mm^−1
β = 102.47 (2)°	T = 293 K
V = 1027.6 (5) Å^3	Prism, colourless
Z = 2	0.45 × 0.08 × 0.03 mm

Data collection

Enraf-Nonius CAD-4 diffractometer	Rint = 0.000
Radiation source: fine-focus sealed tube	θmax = 59.9°, θmin = 3.0°
Graphite monochromator	h = −9→8
ω/θ scans	k = 0→9
1616 measured reflections	l = 0→16
1616 independent reflections	3 standard reflections every 180 min
978 reflections with I > 2σ(I)	intensity decay: none

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.061	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.150	H-atom parameters constrained
S = 1.18	w = 1/[σ^2(Fo^2) + (0.0443P)^2 + 0.3945P] where P = (Fo^2 + 2Fc^2)/3
1616 reflections	(Δ/σ)max = 0.007
251 parameters	Δρmax = 0.11 e Å^−3
9 restraints	Δρmin = −0.14 e Å^−3

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
O1	0.0235 (7)	0.6513 (7)	0.6124 (3)	0.0923 (15)
O2	0.8038 (9)	0.6621 (10)	0.1508 (5)	0.133 (2)
N	0.4593 (11)	0.9987 (10)	0.0726 (5)	0.127 (3)
C1	0.3824 (9)	0.5628 (8)	0.5183 (4)	0.079 (2)
H1	0.4818	0.5072	0.5362	0.094*
C2	0.2731 (10)	0.5700 (8)	0.5752 (5)	0.079 (2)
H2	0.2987	0.5198	0.6314	0.095*
C3	0.1244 (10)	0.6515 (9)	0.5498 (5)	0.080 (2)
C4	0.0880 (9)	0.7269 (8)	0.4671 (5)	0.078 (2)
H4	−0.0116	0.7828	0.4503	0.094*
C5	0.1982 (10)	0.7206 (8)	0.4083 (4)	0.0708 (18)
C6	0.1493 (9)	0.8020 (9)	0.3185 (4)	0.090 (2)
H61	0.1059	0.9042	0.3282	0.117*
H62	0.0597	0.7441	0.2794	0.117*
C7	0.2962 (9)	0.8206 (8)	0.2692 (4)	0.081 (2)
H71	0.2531	0.8514	0.2063	0.105*
H72	0.3721	0.9011	0.2988	0.105*
C8	0.3902 (9)	0.6680 (8)	0.2719 (4)	0.0732 (18)
H8	0.3074	0.5865	0.2497	0.088*
C9	0.4739 (8)	0.6290 (8)	0.3710 (4)	0.0712 (18)
H9	0.5583	0.7098	0.3918	0.085*
C10	0.3479 (9)	0.6381 (8)	0.4327 (4)	0.0708 (18)
C11	0.5671 (10)	0.4761 (9)	0.3765 (5)	0.091 (2)
H111	0.4874	0.3925	0.3573	0.118*
H112	0.6238	0.4566	0.4393	0.118*
C12	0.6958 (10)	0.4777 (11)	0.3162 (4)	0.102 (3)
H121	0.7519	0.3777	0.3205	0.133*
H122	0.7800	0.5563	0.3385	0.133*
C13	0.6137 (10)	0.5118 (9)	0.2143 (5)	0.084 (2)
C14	0.5191 (8)	0.6671 (8)	0.2107 (4)	0.0711 (18)
H14	0.6026	0.7474	0.2341	0.085*
C15	0.4382 (10)	0.7101 (8)	0.1105 (4)	0.082 (2)
H151	0.4916	0.6490	0.0704	0.106*
H152	0.3205	0.6814	0.0983	0.106*
C16	0.4507 (11)	0.8713 (10)	0.0888 (5)	0.087 (2)
C17	0.7606 (12)	0.5317 (13)	0.1674 (5)	0.107 (3)
C18	0.4992 (12)	0.3829 (9)	0.1703 (6)	0.114 (3)
H181	0.5173	0.3634	0.1102	0.172*
H182	0.3845	0.4128	0.1663	0.172*
H183	0.5230	0.2903	0.2065	0.172*
C19	−0.1237 (11)	0.7452 (12)	0.5936 (6)	0.118 (3)
H191	−0.1791	0.7390	0.6439	0.177*
H192	−0.1981	0.7087	0.5391	0.177*
H193	−0.0933	0.8511	0.5853	0.177*
C20A	0.889 (5)	0.431 (6)	0.139 (3)	0.106 (6)	0.287 (6)
C21A	0.995 (7)	0.478 (6)	0.083 (4)	0.137 (7)	0.287 (6)
H21A	0.9895	0.5790	0.0608	0.164*	0.287 (6)
C22A	1.110 (7)	0.374 (7)	0.061 (4)	0.168 (10)	0.287 (6)
H22A	1.1816	0.4051	0.0235	0.202*	0.287 (6)
C23A	1.119 (6)	0.222 (7)	0.094 (5)	0.170 (12)	0.287 (6)
H23A	1.1958	0.1528	0.0792	0.204*	0.287 (6)
C24A	1.012 (9)	0.175 (7)	0.150 (6)	0.186 (14)	0.287 (6)
H24A	1.0179	0.0743	0.1723	0.223*	0.287 (6)
C25A	0.897 (8)	0.280 (7)	0.172 (4)	0.161 (9)	0.287 (6)
H25A	0.8258	0.2482	0.2096	0.194*	0.287 (6)
C20B	0.8545 (16)	0.387 (2)	0.1475 (9)	0.106 (6)	0.71
C21B	0.969 (2)	0.419 (2)	0.0936 (14)	0.137 (7)	0.71
H21B	0.9807	0.5207	0.0740	0.164*	0.713 (6)
C22B	1.066 (2)	0.301 (3)	0.0688 (15)	0.168 (10)	0.71
H22B	1.1425	0.3227	0.0327	0.202*	0.713 (6)
C23B	1.048 (2)	0.150 (2)	0.0980 (16)	0.170 (12)	0.71
H23B	1.1134	0.0702	0.0814	0.204*	0.713 (6)
C24B	0.934 (3)	0.117 (2)	0.1519 (19)	0.186 (14)	0.71
H24B	0.9223	0.0158	0.1714	0.223*	0.713 (6)
C25B	0.837 (3)	0.236 (2)	0.1767 (16)	0.161 (9)	0.71
H25B	0.7604	0.2138	0.2128	0.194*	0.713 (6)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.112 (4)	0.089 (3)	0.087 (3)	0.002 (4)	0.048 (3)	0.005 (3)
O2	0.138 (5)	0.149 (6)	0.129 (5)	0.005 (5)	0.066 (4)	0.021 (5)
N	0.195 (8)	0.097 (6)	0.099 (5)	0.020 (6)	0.052 (5)	0.025 (5)
C1	0.099 (6)	0.070 (4)	0.073 (5)	0.005 (4)	0.030 (4)	0.004 (4)
C2	0.106 (6)	0.063 (4)	0.072 (4)	0.007 (5)	0.028 (4)	0.008 (4)
C3	0.111 (6)	0.062 (4)	0.073 (5)	−0.007 (5)	0.036 (5)	−0.008 (4)
C4	0.094 (5)	0.064 (4)	0.078 (5)	0.013 (4)	0.025 (4)	0.003 (4)
C5	0.091 (5)	0.060 (4)	0.061 (4)	0.013 (4)	0.015 (4)	0.002 (3)
C6	0.109 (6)	0.085 (5)	0.079 (5)	0.033 (5)	0.030 (4)	0.012 (4)
C7	0.115 (6)	0.063 (4)	0.066 (4)	0.030 (4)	0.025 (4)	0.012 (3)
C8	0.100 (5)	0.062 (4)	0.060 (4)	0.006 (4)	0.020 (4)	0.000 (3)
C9	0.089 (5)	0.059 (4)	0.069 (4)	0.011 (4)	0.024 (4)	0.006 (3)
C10	0.098 (5)	0.054 (4)	0.061 (4)	−0.006 (4)	0.018 (4)	−0.003 (3)
C11	0.118 (6)	0.080 (5)	0.082 (5)	0.034 (5)	0.039 (4)	0.016 (4)
C12	0.123 (7)	0.114 (7)	0.082 (5)	0.038 (6)	0.050 (5)	0.019 (5)
C13	0.115 (6)	0.063 (5)	0.084 (5)	0.009 (5)	0.042 (5)	0.000 (4)
C14	0.094 (5)	0.062 (4)	0.058 (4)	0.006 (4)	0.019 (4)	−0.001 (4)
C15	0.124 (6)	0.068 (5)	0.058 (4)	0.010 (4)	0.029 (4)	−0.002 (3)
C16	0.130 (7)	0.075 (6)	0.061 (4)	0.018 (5)	0.032 (4)	0.005 (4)
C17	0.121 (8)	0.121 (8)	0.084 (6)	0.030 (7)	0.033 (5)	0.011 (6)
C18	0.171 (9)	0.068 (5)	0.119 (6)	0.004 (6)	0.065 (6)	−0.010 (5)
C19	0.115 (7)	0.130 (8)	0.124 (7)	0.006 (7)	0.060 (6)	0.004 (6)
C20A	0.106 (9)	0.155 (16)	0.061 (5)	0.045 (9)	0.031 (6)	0.024 (8)
C21A	0.085 (9)	0.22 (2)	0.111 (9)	0.010 (12)	0.041 (7)	−0.020 (13)
C22A	0.079 (14)	0.27 (3)	0.166 (11)	0.017 (16)	0.053 (10)	−0.037 (18)
C23A	0.15 (2)	0.24 (3)	0.113 (9)	0.10 (2)	0.019 (13)	−0.009 (17)
C24A	0.23 (3)	0.22 (2)	0.115 (9)	0.14 (2)	0.054 (18)	0.023 (16)
C25A	0.23 (2)	0.162 (18)	0.113 (8)	0.127 (16)	0.086 (12)	0.048 (10)
C20B	0.106 (9)	0.155 (16)	0.061 (5)	0.045 (9)	0.031 (6)	0.024 (8)
C21B	0.085 (9)	0.22 (2)	0.111 (9)	0.010 (12)	0.041 (7)	−0.020 (13)
C22B	0.079 (14)	0.27 (3)	0.166 (11)	0.017 (16)	0.053 (10)	−0.037 (18)
C23B	0.15 (2)	0.24 (3)	0.113 (9)	0.10 (2)	0.019 (13)	−0.009 (17)
C24B	0.23 (3)	0.22 (2)	0.115 (9)	0.14 (2)	0.054 (18)	0.023 (16)
C25B	0.23 (2)	0.162 (18)	0.113 (8)	0.127 (16)	0.086 (12)	0.048 (10)

Geometric parameters (Å, º)

O1—O2	10.368 (1)	C14—C15	1.550 (8)
O1—C3	1.375 (8)	C14—H14	0.9800
O1—C19	1.424 (9)	C15—C16	1.433 (11)
O2—C17	1.218 (11)	C15—H151	0.9700
N—C16	1.128 (9)	C15—H152	0.9700
C1—C2	1.363 (9)	C17—C20A	1.49 (5)
C1—C10	1.410 (9)	C17—C20B	1.53 (2)
C1—H1	0.9300	C18—H181	0.9600
C2—C3	1.380 (9)	C18—H182	0.9600
C2—H2	0.9300	C18—H183	0.9600
C3—C4	1.375 (9)	C19—H191	0.9600
C4—C5	1.390 (8)	C19—H192	0.9600
C4—H4	0.9300	C19—H193	0.9600
C5—C10	1.391 (8)	C20A—C21A	1.3900
C5—C6	1.495 (9)	C20A—C25A	1.3900
C6—C7	1.546 (9)	C21A—C22A	1.3900
C6—H61	0.9700	C21A—H21A	0.9300
C6—H62	0.9700	C22A—C23A	1.3900
C7—C8	1.516 (9)	C22A—H22A	0.9300
C7—H71	0.9700	C23A—C24A	1.3900
C7—H72	0.9700	C23A—H23A	0.9300
C8—C9	1.534 (8)	C24A—C25A	1.3900
C8—C14	1.537 (8)	C24A—H24A	0.9300
C8—H8	0.9800	C25A—H25A	0.9300
C9—C11	1.512 (9)	C20B—C21B	1.3900
C9—C10	1.527 (9)	C20B—C25B	1.3900
C9—H9	0.9800	C21B—C22B	1.3900
C11—C12	1.527 (8)	C21B—H21B	0.9300
C11—H111	0.9700	C22B—C23B	1.3900
C11—H112	0.9700	C22B—H22B	0.9300
C12—C13	1.560 (10)	C23B—C24B	1.3900
C12—H121	0.9700	C23B—H23B	0.9300
C12—H122	0.9700	C24B—C25B	1.3900
C13—C18	1.506 (11)	C24B—H24B	0.9300
C13—C17	1.524 (11)	C25B—H25B	0.9300
C13—C14	1.538 (9)
C3—O1—C19	117.9 (6)	C13—C14—H14	107.2
C2—C1—C10	121.4 (7)	C8—C14—H14	107.2
C2—C1—H1	119.3	C15—C14—H14	107.2
C10—C1—H1	119.3	C16—C15—C14	114.6 (6)
C1—C2—C3	120.3 (7)	C16—C15—H151	108.6
C1—C2—H2	119.9	C14—C15—H151	108.6
C3—C2—H2	119.9	C16—C15—H152	108.6
O1—C3—C4	124.9 (8)	C14—C15—H152	108.6
O1—C3—C2	115.5 (7)	H151—C15—H152	107.6
C4—C3—C2	119.6 (7)	N—C16—C15	179.0 (9)
C3—C4—C5	120.7 (7)	O2—C17—C20A	103 (2)
C3—C4—H4	119.6	O2—C17—C13	119.3 (9)
C5—C4—H4	119.6	C20A—C17—C13	137 (2)
C10—C5—C4	120.2 (6)	O2—C17—C20B	122.2 (10)
C10—C5—C6	121.7 (6)	C20A—C17—C20B	19 (2)
C4—C5—C6	118.1 (7)	C13—C17—C20B	118.4 (10)
C5—C6—C7	113.3 (6)	C13—C18—H181	109.5
C5—C6—H61	108.9	C13—C18—H182	109.5
C7—C6—H61	108.9	H181—C18—H182	109.5
C5—C6—H62	108.9	C13—C18—H183	109.5
C7—C6—H62	108.9	H181—C18—H183	109.5
H61—C6—H62	107.7	H182—C18—H183	109.5
C8—C7—C6	109.7 (6)	O1—C19—H191	109.5
C8—C7—H71	109.7	O1—C19—H192	109.5
C6—C7—H71	109.7	H191—C19—H192	109.5
C8—C7—H72	109.7	O1—C19—H193	109.5
C6—C7—H72	109.7	H191—C19—H193	109.5
H71—C7—H72	108.2	H192—C19—H193	109.5
C7—C8—C9	109.4 (5)	C21A—C20A—C25A	120.0
C7—C8—C14	113.3 (6)	C21A—C20A—C17	125 (3)
C9—C8—C14	111.0 (5)	C25A—C20A—C17	115 (3)
C7—C8—H8	107.6	C20A—C21A—C22A	120.0
C9—C8—H8	107.6	C20A—C21A—H21A	120.0
C14—C8—H8	107.6	C22A—C21A—H21A	120.0
C11—C9—C10	114.0 (6)	C21A—C22A—C23A	120.0
C11—C9—C8	110.9 (5)	C21A—C22A—H22A	120.0
C10—C9—C8	111.1 (5)	C23A—C22A—H22A	120.0
C11—C9—H9	106.8	C24A—C23A—C22A	120.0
C10—C9—H9	106.8	C24A—C23A—H23A	120.0
C8—C9—H9	106.8	C22A—C23A—H23A	120.0
C5—C10—C1	117.7 (6)	C23A—C24A—C25A	120.0
C5—C10—C9	122.2 (6)	C23A—C24A—H24A	120.0
C1—C10—C9	120.1 (7)	C25A—C24A—H24A	120.0
C9—C11—C12	111.2 (6)	C24A—C25A—C20A	120.0
C9—C11—H111	109.4	C24A—C25A—H25A	120.0
C12—C11—H111	109.4	C20A—C25A—H25A	120.0
C9—C11—H112	109.4	C21B—C20B—C25B	120.0
C12—C11—H112	109.4	C21B—C20B—C17	112.2 (10)
H111—C11—H112	108.0	C25B—C20B—C17	127.8 (10)
C11—C12—C13	112.2 (6)	C22B—C21B—C20B	120.0
C11—C12—H121	109.2	C22B—C21B—H21B	120.0
C13—C12—H121	109.2	C20B—C21B—H21B	120.0
C11—C12—H122	109.2	C21B—C22B—C23B	120.0
C13—C12—H122	109.2	C21B—C22B—H22B	120.0
H121—C12—H122	107.9	C23B—C22B—H22B	120.0
C18—C13—C17	110.8 (7)	C22B—C23B—C24B	120.0
C18—C13—C14	111.5 (6)	C22B—C23B—H23B	120.0
C17—C13—C14	109.0 (7)	C24B—C23B—H23B	120.0
C18—C13—C12	112.6 (7)	C25B—C24B—C23B	120.0
C17—C13—C12	105.0 (6)	C25B—C24B—H24B	120.0
C14—C13—C12	107.7 (6)	C23B—C24B—H24B	120.0
C13—C14—C8	112.7 (5)	C24B—C25B—C20B	120.0
C13—C14—C15	110.2 (5)	C24B—C25B—H25B	120.0
C8—C14—C15	112.1 (6)	C20B—C25B—H25B	120.0
C10—C1—C2—C3	0.3 (11)	C7—C8—C14—C15	−55.1 (8)
C19—O1—C3—C4	−4.9 (10)	C9—C8—C14—C15	−178.6 (6)
C19—O1—C3—C2	174.3 (7)	C13—C14—C15—C16	−139.1 (7)
C1—C2—C3—O1	−179.9 (7)	C8—C14—C15—C16	94.5 (8)
C1—C2—C3—C4	−0.7 (11)	C14—C15—C16—N	−58 (68)
O1—C3—C4—C5	179.9 (7)	C18—C13—C17—O2	136.8 (9)
C2—C3—C4—C5	0.7 (10)	C14—C13—C17—O2	13.8 (11)
C3—C4—C5—C10	−0.3 (10)	C12—C13—C17—O2	−101.3 (10)
C3—C4—C5—C6	178.6 (6)	C18—C13—C17—C20A	−49.6 (19)
C10—C5—C6—C7	−14.7 (10)	C14—C13—C17—C20A	−172.6 (16)
C4—C5—C6—C7	166.3 (6)	C12—C13—C17—C20A	72.3 (18)
C5—C6—C7—C8	46.2 (8)	C18—C13—C17—C20B	−46.4 (10)
C6—C7—C8—C9	−65.4 (7)	C14—C13—C17—C20B	−169.4 (7)
C6—C7—C8—C14	170.1 (5)	C12—C13—C17—C20B	75.5 (9)
C7—C8—C9—C11	179.2 (6)	O2—C17—C20A—C21A	−16 (3)
C14—C8—C9—C11	−55.1 (7)	C13—C17—C20A—C21A	169 (3)
C7—C8—C9—C10	51.3 (8)	C20B—C17—C20A—C21A	161 (6)
C14—C8—C9—C10	177.1 (6)	O2—C17—C20A—C25A	164 (3)
C4—C5—C10—C1	−0.1 (9)	C13—C17—C20A—C25A	−11 (3)
C6—C5—C10—C1	−179.0 (7)	C20B—C17—C20A—C25A	−19 (6)
C4—C5—C10—C9	−179.3 (7)	C25A—C20A—C21A—C22A	0.0
C6—C5—C10—C9	1.8 (10)	C17—C20A—C21A—C22A	−180.0 (9)
C2—C1—C10—C5	0.1 (10)	C20A—C21A—C22A—C23A	0.0
C2—C1—C10—C9	179.4 (7)	C21A—C22A—C23A—C24A	0.0
C11—C9—C10—C5	−146.3 (7)	C22A—C23A—C24A—C25A	0.0
C8—C9—C10—C5	−20.1 (9)	C23A—C24A—C25A—C20A	0.0
C11—C9—C10—C1	34.5 (9)	C21A—C20A—C25A—C24A	0.0
C8—C9—C10—C1	160.7 (6)	C17—C20A—C25A—C24A	180.0 (8)
C10—C9—C11—C12	−177.6 (6)	O2—C17—C20B—C21B	−11.8 (15)
C8—C9—C11—C12	56.1 (8)	C20A—C17—C20B—C21B	−15 (4)
C9—C11—C12—C13	−57.9 (9)	C13—C17—C20B—C21B	171.5 (10)
C11—C12—C13—C18	−67.1 (9)	O2—C17—C20B—C25B	168.1 (14)
C11—C12—C13—C17	172.2 (7)	C20A—C17—C20B—C25B	165 (5)
C11—C12—C13—C14	56.2 (9)	C13—C17—C20B—C25B	−8.6 (13)
C18—C13—C14—C8	68.5 (8)	C25B—C20B—C21B—C22B	0.0
C17—C13—C14—C8	−168.9 (6)	C17—C20B—C21B—C22B	179.9 (6)
C12—C13—C14—C8	−55.5 (8)	C20B—C21B—C22B—C23B	0.0
C18—C13—C14—C15	−57.6 (8)	C21B—C22B—C23B—C24B	0.0
C17—C13—C14—C15	65.0 (8)	C22B—C23B—C24B—C25B	0.0
C12—C13—C14—C15	178.5 (6)	C23B—C24B—C25B—C20B	0.0
C7—C8—C14—C13	179.9 (6)	C21B—C20B—C25B—C24B	0.0
C9—C8—C14—C13	56.4 (8)	C17—C20B—C25B—C24B	−179.9 (7)

(II) 17-hydroxy-3-methoxy-17-phenyl-16,17-secoestra-1,3,5(10)-triene-16-carbonitrile

Crystal data

C25H29NO2	F(000) = 404
Mr = 375.49	Dx = 1.196 Mg m^−3
Monoclinic, P21	Cu Kα radiation, λ = 1.54178 Å
a = 9.8063 (5) Å	Cell parameters from 25 reflections
b = 6.697 (1) Å	θ = 22.0–30.5°
c = 16.201 (1) Å	µ = 0.58 mm^−1
β = 101.455 (5)°	T = 293 K
V = 1042.8 (2) Å^3	Prism, colourless
Z = 2	0.38 × 0.18 × 0.15 mm

Data collection

Enraf-Nonius CAD-4 diffractometer	Rint = 0.000
Radiation source: fine-focus sealed tube	θmax = 74.0°, θmin = 2.8°
Graphite monochromator	h = −12→11
ω/θ scans	k = 0→8
2305 measured reflections	l = 0→20
2305 independent reflections	3 standard reflections every 120 min
2134 reflections with I > 2σ(I)	intensity decay: none

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.039	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.100	H-atom parameters constrained
S = 0.96	w = 1/[σ^2(Fo^2) + (0.052P)^2 + 0.2489P] where P = (Fo^2 + 2Fc^2)/3
2305 reflections	(Δ/σ)max < 0.001
257 parameters	Δρmax = 0.12 e Å^−3
1 restraint	Δρmin = −0.19 e Å^−3

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement on F² for ALL reflections except for 50 with very negative F² or flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The observed criterion of F² > σ(F²) is used only for calculating -R-factor-obs etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
C1	−0.1651 (3)	0.2509 (5)	0.51905 (15)	0.0636 (7)
H1	−0.1081	0.1397	0.5194	0.076*
C2	−0.2664 (3)	0.2896 (5)	0.44843 (16)	0.0685 (8)
H2	−0.2770	0.2043	0.4023	0.082*
C3	−0.3516 (2)	0.4532 (5)	0.44593 (14)	0.0582 (7)
C4	−0.3357 (3)	0.5779 (5)	0.51486 (14)	0.0583 (6)
H4	−0.3936	0.6884	0.5138	0.070*
C5	−0.2332 (3)	0.5394 (4)	0.58647 (14)	0.0557 (6)
C6	−0.2231 (3)	0.6806 (6)	0.66030 (17)	0.0749 (9)
H61	−0.3162	0.7178	0.6664	0.097*
H62	−0.1753	0.8012	0.6488	0.097*
C7	−0.1460 (3)	0.5896 (5)	0.74251 (15)	0.0626 (7)
H71	−0.2038	0.4885	0.7613	0.081*
H72	−0.1271	0.6924	0.7854	0.081*
C8	−0.0093 (2)	0.4958 (4)	0.73078 (13)	0.0450 (5)
H8	0.0410	0.5972	0.7051	0.054*
C9	−0.0399 (2)	0.3217 (4)	0.66851 (14)	0.0484 (5)
H9	−0.0816	0.2157	0.6971	0.058*
C10	−0.1461 (2)	0.3746 (4)	0.58975 (14)	0.0506 (6)
C11	0.0963 (2)	0.2384 (5)	0.65113 (14)	0.0564 (6)
H111	0.1436	0.3406	0.6249	0.073*
H112	0.0770	0.1267	0.6125	0.073*
C12	0.1902 (2)	0.1695 (4)	0.73294 (14)	0.0507 (5)
H121	0.2768	0.1203	0.7202	0.066*
H122	0.1455	0.0589	0.7557	0.066*
C13	0.2240 (2)	0.3329 (3)	0.80088 (12)	0.0394 (4)
C14	0.0858 (2)	0.4313 (3)	0.81380 (13)	0.0395 (4)
H14	0.0352	0.3320	0.8404	0.047*
C15	0.1166 (2)	0.6125 (4)	0.87453 (14)	0.0450 (5)
H151	0.2085	0.5958	0.9094	0.059*
H152	0.1182	0.7328	0.8414	0.059*
C16	0.0167 (2)	0.6392 (4)	0.92895 (13)	0.0462 (5)
C17	0.2993 (2)	0.2347 (3)	0.88560 (13)	0.0448 (5)
H17	0.3029	0.3341	0.9304	0.067*
C18	0.3203 (2)	0.4899 (4)	0.77390 (15)	0.0502 (5)
H181	0.3953	0.4242	0.7546	0.075*
H182	0.3574	0.5740	0.8210	0.075*
H183	0.2686	0.5697	0.7292	0.075*
C19	−0.5366 (3)	0.6472 (6)	0.36771 (17)	0.0779 (9)
H191	−0.5933	0.6382	0.4095	0.117*
H192	−0.5952	0.6531	0.3127	0.117*
H193	−0.4804	0.7656	0.3772	0.117*
C20	0.4465 (2)	0.1687 (3)	0.88570 (13)	0.0436 (5)
C21	0.5583 (3)	0.2929 (4)	0.91538 (15)	0.0579 (6)
H21	0.5428	0.4174	0.9372	0.070*
C22	0.6928 (3)	0.2345 (5)	0.91305 (18)	0.0691 (8)
H22	0.7663	0.3215	0.9320	0.083*
C23	0.7190 (3)	0.0499 (6)	0.88322 (17)	0.0683 (8)
H23	0.8095	0.0114	0.8817	0.082*
C24	0.6096 (3)	−0.0778 (5)	0.85558 (18)	0.0656 (7)
H24	0.6263	−0.2043	0.8361	0.079*
C25	0.4743 (3)	−0.0184 (4)	0.85671 (16)	0.0557 (6)
H25	0.4011	−0.1058	0.8377	0.067*
N	−0.0595 (2)	0.6586 (4)	0.97240 (13)	0.0650 (6)
O1	−0.44920 (19)	0.4769 (4)	0.37312 (10)	0.0712 (6)
O2	0.2201 (2)	0.0691 (3)	0.90528 (12)	0.0638 (5)
H1O2	0.1806	0.0999	0.9436	0.096*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0653 (14)	0.077 (2)	0.0491 (12)	0.0078 (15)	0.0117 (11)	−0.0219 (14)
C2	0.0705 (15)	0.090 (2)	0.0452 (12)	0.0045 (17)	0.0122 (11)	−0.0229 (15)
C3	0.0518 (12)	0.0831 (19)	0.0411 (11)	−0.0064 (14)	0.0122 (9)	−0.0075 (13)
C4	0.0572 (13)	0.0707 (17)	0.0466 (12)	0.0063 (14)	0.0095 (10)	−0.0074 (13)
C5	0.0581 (13)	0.0643 (17)	0.0444 (11)	0.0057 (13)	0.0097 (10)	−0.0130 (12)
C6	0.0799 (17)	0.080 (2)	0.0576 (14)	0.0309 (18)	−0.0037 (13)	−0.0240 (16)
C7	0.0593 (13)	0.0772 (19)	0.0499 (12)	0.0211 (14)	0.0076 (10)	−0.0220 (13)
C8	0.0514 (11)	0.0428 (12)	0.0428 (10)	0.0037 (10)	0.0142 (9)	−0.0092 (10)
C9	0.0529 (11)	0.0507 (14)	0.0435 (11)	0.0020 (11)	0.0140 (9)	−0.0143 (10)
C10	0.0504 (11)	0.0586 (15)	0.0443 (11)	0.0011 (12)	0.0129 (9)	−0.0129 (12)
C11	0.0586 (13)	0.0658 (16)	0.0456 (11)	0.0123 (13)	0.0126 (10)	−0.0192 (12)
C12	0.0584 (12)	0.0455 (13)	0.0498 (11)	0.0090 (11)	0.0145 (10)	−0.0128 (11)
C13	0.0483 (10)	0.0358 (10)	0.0371 (9)	0.0005 (9)	0.0159 (8)	−0.0003 (9)
C14	0.0456 (10)	0.0350 (10)	0.0412 (10)	−0.0021 (9)	0.0164 (8)	−0.0074 (9)
C15	0.0495 (11)	0.0413 (12)	0.0467 (11)	−0.0021 (10)	0.0155 (9)	−0.0113 (10)
C16	0.0524 (11)	0.0445 (12)	0.0419 (10)	0.0055 (10)	0.0098 (9)	−0.0073 (9)
C17	0.0617 (12)	0.0356 (11)	0.0411 (10)	−0.0019 (10)	0.0194 (9)	0.0006 (9)
C18	0.0524 (11)	0.0500 (13)	0.0531 (11)	−0.0003 (11)	0.0222 (10)	0.0108 (11)
C19	0.0698 (16)	0.106 (3)	0.0551 (14)	0.008 (2)	0.0069 (12)	0.0041 (18)
C20	0.0562 (12)	0.0371 (11)	0.0369 (9)	0.0030 (10)	0.0075 (9)	0.0018 (9)
C21	0.0684 (15)	0.0468 (13)	0.0516 (12)	0.0003 (12)	−0.0050 (11)	−0.0059 (11)
C22	0.0524 (14)	0.072 (2)	0.0735 (17)	−0.0015 (14)	−0.0111 (12)	0.0004 (16)
C23	0.0567 (14)	0.080 (2)	0.0645 (15)	0.0119 (15)	0.0037 (12)	0.0020 (16)
C24	0.0667 (15)	0.0576 (17)	0.0711 (16)	0.0150 (14)	0.0099 (13)	−0.0091 (14)
C25	0.0606 (13)	0.0414 (13)	0.0653 (14)	0.0014 (12)	0.0127 (11)	−0.0093 (12)
N	0.0706 (13)	0.0733 (16)	0.0566 (12)	0.0075 (13)	0.0264 (10)	−0.0106 (12)
O1	0.0641 (10)	0.1052 (17)	0.0415 (8)	0.0040 (12)	0.0040 (7)	−0.0068 (11)
O2	0.0857 (12)	0.0448 (9)	0.0729 (11)	−0.0028 (10)	0.0447 (10)	0.0111 (9)

Geometric parameters (Å, º)

O1—O2	10.119 (2)	C13—C14	1.558 (3)
C1—C2	1.383 (4)	C13—C17	1.568 (3)
C1—C10	1.396 (3)	C14—C15	1.553 (3)
C1—H1	0.9300	C14—H14	0.9800
C2—C3	1.373 (4)	C15—C16	1.454 (3)
C2—H2	0.9300	C15—H151	0.9700
C3—O1	1.373 (3)	C15—H152	0.9700
C3—C4	1.378 (4)	C16—N	1.131 (3)
C4—C5	1.400 (3)	C17—O2	1.426 (3)
C4—H4	0.9300	C17—C20	1.509 (3)
C5—C10	1.390 (4)	C17—H17	0.9800
C5—C6	1.513 (4)	C18—H181	0.9600
C6—C7	1.522 (4)	C18—H182	0.9600
C6—H61	0.9700	C18—H183	0.9600
C6—H62	0.9700	C19—O1	1.419 (4)
C7—C8	1.526 (3)	C19—H191	0.9600
C7—H71	0.9700	C19—H192	0.9600
C7—H72	0.9700	C19—H193	0.9600
C8—C9	1.532 (3)	C20—C25	1.384 (3)
C8—C14	1.539 (3)	C20—C21	1.384 (3)
C8—H8	0.9800	C21—C22	1.384 (4)
C9—C10	1.520 (3)	C21—H21	0.9300
C9—C11	1.525 (3)	C22—C23	1.370 (5)
C9—H9	0.9800	C22—H22	0.9300
C11—C12	1.527 (3)	C23—C24	1.375 (4)
C11—H111	0.9700	C23—H23	0.9300
C11—H112	0.9700	C24—C25	1.389 (4)
C12—C13	1.541 (3)	C24—H24	0.9300
C12—H121	0.9700	C25—H25	0.9300
C12—H122	0.9700	O2—H1O2	0.8200
C13—C18	1.534 (3)
C2—C1—C10	121.6 (3)	C12—C13—C14	109.09 (17)
C2—C1—H1	119.2	C18—C13—C17	109.12 (18)
C10—C1—H1	119.2	C12—C13—C17	108.93 (18)
C3—C2—C1	120.5 (2)	C14—C13—C17	109.31 (16)
C3—C2—H2	119.8	C8—C14—C15	110.03 (18)
C1—C2—H2	119.8	C8—C14—C13	113.19 (16)
O1—C3—C2	115.7 (2)	C15—C14—C13	110.53 (17)
O1—C3—C4	125.0 (3)	C8—C14—H14	107.6
C2—C3—C4	119.3 (2)	C15—C14—H14	107.6
C3—C4—C5	120.4 (3)	C13—C14—H14	107.6
C3—C4—H4	119.8	C16—C15—C14	114.25 (19)
C5—C4—H4	119.8	C16—C15—H151	108.7
C10—C5—C4	120.9 (2)	C14—C15—H151	108.7
C10—C5—C6	121.5 (2)	C16—C15—H152	108.7
C4—C5—C6	117.6 (2)	C14—C15—H152	108.7
C5—C6—C7	112.6 (3)	H151—C15—H152	107.6
C5—C6—H61	109.1	N—C16—C15	178.8 (3)
C7—C6—H61	109.1	O2—C17—C20	109.55 (17)
C5—C6—H62	109.1	O2—C17—C13	109.85 (19)
C7—C6—H62	109.1	C20—C17—C13	114.06 (17)
H61—C6—H62	107.8	O2—C17—H17	107.7
C6—C7—C8	110.6 (2)	C20—C17—H17	107.7
C6—C7—H71	109.5	C13—C17—H17	107.7
C8—C7—H71	109.5	C13—C18—H181	109.5
C6—C7—H72	109.5	C13—C18—H182	109.5
C8—C7—H72	109.5	H181—C18—H182	109.5
H71—C7—H72	108.1	C13—C18—H183	109.5
C7—C8—C9	109.46 (19)	H181—C18—H183	109.5
C7—C8—C14	113.69 (17)	H182—C18—H183	109.5
C9—C8—C14	111.58 (18)	O1—C19—H191	109.5
C7—C8—H8	107.3	O1—C19—H192	109.5
C9—C8—H8	107.3	H191—C19—H192	109.5
C14—C8—H8	107.3	O1—C19—H193	109.5
C10—C9—C11	114.18 (18)	H191—C19—H193	109.5
C10—C9—C8	112.8 (2)	H192—C19—H193	109.5
C11—C9—C8	109.60 (18)	C25—C20—C21	117.8 (2)
C10—C9—H9	106.6	C25—C20—C17	121.2 (2)
C11—C9—H9	106.6	C21—C20—C17	121.0 (2)
C8—C9—H9	106.6	C22—C21—C20	120.9 (3)
C5—C10—C1	117.3 (2)	C22—C21—H21	119.5
C5—C10—C9	122.0 (2)	C20—C21—H21	119.5
C1—C10—C9	120.5 (2)	C23—C22—C21	120.7 (3)
C9—C11—C12	110.47 (18)	C23—C22—H22	119.6
C9—C11—H111	109.6	C21—C22—H22	119.6
C12—C11—H111	109.6	C22—C23—C24	119.2 (3)
C9—C11—H112	109.6	C22—C23—H23	120.4
C12—C11—H112	109.6	C24—C23—H23	120.4
H111—C11—H112	108.1	C23—C24—C25	120.2 (3)
C11—C12—C13	114.4 (2)	C23—C24—H24	119.9
C11—C12—H121	108.7	C25—C24—H24	119.9
C13—C12—H121	108.7	C20—C25—C24	121.1 (2)
C11—C12—H122	108.7	C20—C25—H25	119.4
C13—C12—H122	108.7	C24—C25—H25	119.4
H121—C12—H122	107.6	C3—O1—C19	117.1 (2)
C18—C13—C12	109.90 (18)	C17—O2—H1O2	109.5
C18—C13—C14	110.47 (19)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H1O2···N^i	0.82	2.01	2.829 (3)	171

Symmetry code: (i) −x, y−1/2, −z+2.