The zwitterion (23′E)-(23R,25S)-23-[1-(oxidoiminio)ethyl]-5β-spirostan-3β-yl acetate

The title steroidal compound, C31H49NO5, resulted from the selective oximation of (23R)-23-acetylsarsasapogenin acetate. One- and two-dimensional 1H and 13C NMR spectra, as well as IR data, are in agreement with the presence of a ketoxime group at C-23. However, recrystallization in slightly acidic media affords the title compound in the rare zwitterionic oxime form, as a consequence of migration of the hydroxy H atom to the N atom in the oxime group. This H atom is clearly detected and its position was refined from X-ray data. The geometry for the C=N+(H)—O− group features long C=N and short N—O bond lengths compared to non-zwitterionic oximes. The ketoxime is stabilized with the E configuration, avoiding steric hindrance between the oxime O atom and H atom at C-23. The sum of the angles around the oxime N atom is 359.6°, giving a planar configuration for that atom, as expected for sp 2 hybridization.

The title steroidal compound, C 31 H 49 NO 5 , resulted from the selective oximation of (23R)-23-acetylsarsasapogenin acetate. One-and two-dimensional 1 H and 13 C NMR spectra, as well as IR data, are in agreement with the presence of a ketoxime group at C-23. However, recrystallization in slightly acidic media affords the title compound in the rare zwitterionic oxime form, as a consequence of migration of the hydroxy H atom to the N atom in the oxime group. This H atom is clearly detected and its position was refined from X-ray data. The geometry for the C N + (H)-O À group features long C N and short N-O bond lengths compared to non-zwitterionic oximes. The ketoxime is stabilized with the E configuration, avoiding steric hindrance between the oxime O atom and H atom at C-23. The sum of the angles around the oxime N atom is 359.6 , giving a planar configuration for that atom, as expected for sp 2 hybridization.

Related literature
For the synthesis of (23R)-23-acetylsarsasapogenin acetate used as starting material, see: Meza-Reyes et al. (2005). For the full spectroscopic characterization of the tautomers of the title compound, see: Herná ndez-Linares (2005). For tautomerism between oximes and imine N-oxides, see: Ferná ndez et al. (1994). For related zwitterionic oximes and hydrochloride oximes characterized by X-ray diffraction, see: Witte et al.  Data collection: XSCANS (Siemens, 1994); cell refinement: XSCANS; data reduction: XSCANS; program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.  Synthetic routes are available for the large scale preparation of (23R)-23-acetylsarsasapogenin acetate (Meza-Reyes et al., 2005). During attempts to functionalize the 23 position in sarsasapogenin acetate, we have found that the oximation of (23R)-23-acetylsarsasapogenin acetate using NH 2 OH.HCl afforded the expected 23-hydroxyimino derivative. IR spectrum for that compound exhibits a strong vibration at 3400 cm -1 (ν O-H ), a weak vibration at 1636 cm -1 (ν C=N ), and a vibration at 951 cm -1 (ν N-O ), characteristics of ketoximes. One-dimensional and two-dimensional 1 H and 13 C NMR data are also in full agreement with that assignment (Hernández-Linares, 2005, and archived CIF). For instance, 31 signals are detected in 13 C-NMR, one of which, at 159.3 p.p.m., is characteristic of the C23 1 atom substituted by an hydroxyimino group.
However, recrystallization of the ketoxime in a slightly acidic medium (MeOH/CH 2 Cl 2 , 98:2) afforded a solid with a significantly different melting point (459 K for the oxime, 516 K for the recrystallized material). On the other hand, the high m.p. solid presents a new 1 H-NMR broad signal at 9.05 p.p.m., and the stretching vibration for OH group in the IR spectrum no longer appears, while a new strong vibration is observed at 2300 cm -1 . In order to rationalize these dramatic changes, the X-ray analysis of this material was carried out.
The molecular structure ( Fig. 1) resolves the above mentioned problem: a difference map shows a strong residual in the vicinity of atom N34, while no H atom is found bonded to O35. The oxime is thus stabilized in the solid-state in a rather rare zwittterionic form. The residual close to N34 refines well as an H atom. The N-H bond accounts for the IR vibration at 2300 cm -1 and H34 is detected in 1 H-NMR at 9.05 p.p.m..
Refinement of the proposed model was however not so straightforward. Alternative models assuming a non-zwitterionic oxime were probed, with disordered N and O sites, which resulted in oxime groups with geometry far from expectation and physically unreasonable intermolecular contacts. On the other hand, refinements carried out with a free H34 atom converged to a geometry where the oxime N atom deviates significantly from the expected planar trigonal arrangement, although the N34-H34 bond length lies in the expected range. Considering that the structure is based on room-temperature data, we eventually refined the structural model with a pair of soft restraints for non-bonding separations involving H34 (see Experimental). Finally, a supplementary concern is about the terminal O atom O35, which is separated by 2.757 (5) Å from the carbonyl O30 atom of a symmetry-related molecule (symmetry code: 2 -x, -1/2 + y, 1/2 -z). Such an arrangement would be suitable for a stabilizing hydrogen bond, which is not observed because of the migration of the oxime H atom to N34.
With the currently available data, it is however difficult to decide if this situation resulted from the actual migration of the H atom in the solid-sate. Definitively, more data are required in order to fully characterize this zwitterion, for example low temperature neutron diffraction data, and the X-ray structure of the non-zwitterionic title molecule.
The tautomerism between oximes and imine N-oxides seems to be poorly documented (Fernández et al., 1994). In the case of the title compound, the C═N bond length is long, 1.361 (6) Å, and the N-O bond length is short, 1.367 (5) Å, supplementary materials sup-2 compared to common non-zwitterionic oximes (ca. 1.28 and 1.41 Å, respectively). The sum of angles around N2 is very close to 360°, as expected for a sp 2 hybridized atom. Therefore, delocalization is extended on the whole hydroxyimino group, C32/N34/O35, which is almost planar. The imine group presents the E configuration, which avoids steric hindrance between the oxime O atom and methine H atom H23C. This geometry is close to that previously reported for the few zwitterionic oximes or hydrochloride oximes characterized by X-ray diffraction (Fernández et al., 1994;Gurkova et al., 1988;Laus et al., 2008). The imine N-oxide tautomer has also been used as a ligand (Witte et al., 1984;Forgan et al., 2008).

Refinement
H34 was found in a difference map and refined with free coordinates, although geometry around N34 was restrained through soft restraints in order to avoid significant deviations from trigonal geometry. The X-ray structure of acetone oxime hydrochloride was used as target (Gurkova et al., 1988): H34···C32 and H34···O35 separations were restrained to 2.10 (2) Å.
The isotropic displacement parameter for H34 was fixed to U iso (H34) = 1.5U eq (N34). Other H atoms were placed in idealized positions and refined using a riding model, with fixed C-H bond lengths: 0.96 (methyl), 0.97 (methylene) or 0.98 Å (methine). Isotropic displacement parameters were computed as U iso (H) = 1.5U eq (carrier C) for methyl groups and U iso (H) = 1.2U eq (carrier C) for other H atoms. Methyl groups were allowed to rotate about their C-C bonds. Fig. 1. The title molecule with displacement ellipsoids for non-H atoms shown at the 30% probability level.