(5S,6R)-5-Methyl-6-phenyl-4-propyl-1,3,4-oxadiazinane-2-thione

Joshua L Kocher; Kate L Edler; Barbara A Bohling; George P Nora; Carrie Stafford; Shawn R Hitchcock; Gregory M Ferrence

doi:10.1107/S1600536809019382

. 2009 May 29;65(Pt 6):o1421–o1422. doi: 10.1107/S1600536809019382

(5S,6R)-5-Methyl-6-phenyl-4-propyl-1,3,4-oxadiazinane-2-thione

Joshua L Kocher ^a, Kate L Edler ^a, Barbara A Bohling ^a, George P Nora ^a, Carrie Stafford ^a, Shawn R Hitchcock ^a, Gregory M Ferrence ^a,^*

PMCID: PMC2969751 PMID: 21583263

Abstract

The title molecule, C₁₃H₁₈N₂OS, is an oxadiazinanthione derived from (1R,2S)-norephedrine. There are two molecules in the asymmetric. Both adopt roughly half-chair conformations; however, the 5-position carbon orients out of opposite faces of the oxadiazinanthiones plane in the two molecules. In the crystal structure, they are oriented as a dimer linked by a pair of N—H⋯S hydrogen bonds. The absolute configuration has been established from anomalous dispersion and confirms the known stereochemistry based on the synthetic procedure.

Related literature

For background, see: Hitchcock et al. (2002 ▶, 2008 ▶); Trepanier et al. (1968 ▶). For related compounds, see: Burgeson et al. (2004 ▶); Casper, Blackburn et al. (2002 ▶); Casper, Burgeson et al. (2002 ▶); Cremer & Pople (1975 ▶); Ferrence et al. (2003 ▶); Hitchcock et al. (2001 ▶, 2004 ▶); Rodrigues et al. (2005 ▶, 2006 ▶); Squire et al. (2005 ▶); Szczepura et al. (2004 ▶). For structural analysis, see: Boeyens (1978 ▶); Bruno et al. (2004 ▶); Cremer & Pople (1975 ▶); Spek (2009 ▶).

Experimental

Crystal data

C₁₃H₁₈N₂OS
M _r = 250.36
Monoclinic,
a = 12.5888 (6) Å
b = 8.0648 (4) Å
c = 14.2862 (7) Å
β = 112.4488 (7)°
V = 1340.51 (11) Å³
Z = 4
Mo Kα radiation
μ = 0.23 mm⁻¹
T = 193 K
0.45 × 0.3 × 0.26 mm

Data collection

Bruker SMART 1000 CCD diffractometer
Absorption correction: multi-scan (SADABS in SAINT-Plus; Bruker, 1999 ▶) T _min = 0.812, T _max = 0.943
10254 measured reflections
5344 independent reflections
5154 reflections with I > 2σ(I)
R _int = 0.016

Refinement

R[F ² > 2σ(F ²)] = 0.028
wR(F ²) = 0.076
S = 1.03
5344 reflections
315 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.19 e Å⁻³
Absolute structure: Flack (1983 ▶)
Flack parameter: 0.03 (4)

Data collection: SMART (Bruker, 1999 ▶); cell refinement: SAINT (Bruker, 1999 ▶); data reduction: SAINT; program(s) used to solve structure: SIR2004 (Burla et al., 2005 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶) and Mercury (Macrae et al., 2008 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶) and publCIF (McMahon & Westrip, 2008 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809019382/fj2214sup1.cif

e-65-o1421-sup1.cif^{(24.1KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809019382/fj2214Isup2.hkl

e-65-o1421-Isup2.hkl^{(256.4KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Enhanced figure: interactive version of Fig. 3

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N3—H3⋯S67	0.86 (2)	2.48 (2)	3.3257 (14)	167 (2)
N53—H53⋯S17	0.82 (2)	2.56 (2)	3.3711 (15)	167 (2)

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Acknowledgments

This material is based upon work supported by the US National Science Foundation (CHE-0348158) (to GMF) and the American Chemical Society Petroleum Research Fund (grant No. 407771B) (to SRH). GMF thanks Dr Robert McDonald and the University of Alberta X-ray Crystallography Laboratory for the collection of low-temperature CCD X-ray data.

supplementary crystallographic information

Comment

The heterocyclic structure of 1,3,4-oxadiazinan-2-one compounds have been known for nearly forty years, however the related compound 3,4,5,6-tetrahydro-2H-1,3,4-oxadiazinan-2-thione has just within the last 10 years been synthesized and studied (Trepanier et al., 1968; Hitchcock et al., 2002). Other oxadiazinanones, but no oxadiazinanthiones, have been reported and studied. The oxadiazinanone structures previously reported by Hitchcock and co-workers all contain a carbonyl group attached at the N3 position, which is believed to have an impact on the ring conformation (Burgeson et al., 2004; Casper, Blackburn et al., 2002; Casper, Burgeson et al., 2002; Ferrence et al., 2003; Hitchcock et al., 2001, 2004, 2008; Squire et al., 2005; Szczepura et al., 2004).

The title compound, I, whose molecular structure is shown in Fig. 1, crystallizes with two independent molecules in the asymmetric unit with the two residues forming N–H···S intermolecularly H-bonded dimers with N3—H3···S67 = 2.48 (2) Å and N53—H53···S17 = 2.56 (2) Å. This H-bonding motif is similar to the N–H···O H-bonded dimers observed in the analogous oxadiazinaneone (Szczepura et al., 2004). A Mogul (Bruno et al. 2004) geometry check showed all non-H bond angles and distances to be normal. X-ray crystal structural data obtained for the oxadiazinan-2-thione proved to be interesting in the context of comparing it to related oxadiazinanone structures (Casper, Burgeson et al., 2002).

In fact, the two independent molecules in the asymmetric unit possess the two most common conformations for oxadiazine rings. Both molecules adopt roughly half-chair conformations with the most dramatic difference being whether the C5 (or C55) carbon resides above or below the respective mean O1—C2—N3—N4—C6 (or O51—C52—N53—N54—C56) plane. Ring puckering analysis using PLATON (Spek, 2009; Cremer & Pople, 1975; Boeyens, 1978) indicates θ = 129.9 (2)° and Φ = 55.1 (2)° for the O1—C2—N3—N4—C5—C6 ring. This is consistent with a formal conformational assignment close to an idealized envelope. Such a conformation possesses a pseudo-axial C5-methyl group, a typical pseudo-equatorial C6-phenyl ring, and a typical pseudo-axial N4-methyl group. Analysis of the O51—C52—N53—N54—C55—C56 ring indicates θ = 58.4 (2)° and Φ = 255.8 (2)°. This is consistent with a formal conformational assignment halfway between envelope (⁵E) and half-chair (⁵H₆). In contrast, this conformation includes a pseudo-equatorial C55-methyl, the typical pseudo-axial C56-phenyl ring, and interestingly, a pseudo-equatorial N54-methyl group. This conformation represents a departure from the previously obtained X-ray crystal structures for the related ephedrine based oxadiazinanone wherein the N4-methyl group has always been observed in a pseudo-axial position (Szczepura et al., 2004). The differences in conformation are more clearly illustrated in Fig. 2 which depicts a variety of overlays of the crystallographically independent molecules in the title compound and those found in the closely related oxadiazinanone, molecule II, 3,4,5,6-tetrahydro-2H-1,3,4-oxadiazinan-2-one. Fig. 2A shows the overlay of both independent molecules found in I and clearly shows their differing conformations. Fig. 2B shows the overlay of both independent molecules found in II and clearly shows the ring conformations to be essentially equivalent with the difference between the molecules being only the orientation of the terminal methyl group of the N4 propyl group. Figs. 2C and 2D show the nearly identical ring conformations of one of the independent molecules of I and either of the independent molecules of II. Figs. 2E and 2F clearly show the distinct conformation of the other independent molecule of I when compared with either independent molecule of II. All of these overlays were prepared in Mercury using a three point least-squares fit of the O(1), C(2), and N(3) atoms only. The existence of multiple conformers for oxadiazinanones has been observed before by Rodrigues and coworkers (Rodrigues et al., 2005; 2006). The conformational flexibility of these systems is believed to be due to the nature of the substituents on the ring system. In the case of the oxadiazinan-2-thione, the source of the conformational flexibility is not clear and remains to be determined by further experimentation.

A Jmol enhanced figure (Fig. 3) accompanies this article. This enhanced figure is designed to illustrate the 2₁ screw axis present in the monoclinic space group P21. Selecting appropriate radio buttons will highlight crystallographically identical molecules which are related by propagation along the 2₁ screw axis parallel to the b axis.

Experimental

The title compound was synthesized by Hitchcock et al. (Hitchcock et al., 2002).