N-Methyl-2-thiocytisine

The rings of the three-ring cytisine system in the title compound [systematic name: (1R,5S)-1,2,3,4,5,6-hexahydro-1,5-methano-8H-pyrido[1,2-a][1,5]diazocine-8-thione], C12H16N2S, have planar [maximum deviation 0.0170 (7) Å], half-chair and chair conformations. In the crystal structure, relatively short and directional C—H⋯π interactions and weaker secondary C—H⋯S contacts join the molecules into helical chains along the [001] direction.


N-Methyl-2-thiocytisine
A. M. Owczarzak, A. K. Przybyl and M. Kubicki Comment (-)-Cytisine and its N-methyl derivative are toxic quinolizidine alkaloids, which are found in different plants from the Fabaceae (Leguminosae) family. They can cause nausea, convulsions and ultimately death by respiratory failure. Chemically, these compounds have a tricyclic skeleton, which can be characterized as a bispidine framework fused to 2-pyridone.
The absolute configuration of two chiral centers was established as 7R, 9S (Okuda et al., 1961), and the crystal structures of both cytisine and N-methylcytisine have been reported (Freer et al., 1987). Also the structure of 2-thiocytisine was determined (Imming et al., 2001), but this is the only structure of thioanalogue of cytisine in the CSD (Allen, 2002;Version 5.31 of Nov. 2009, updated Feb. 2010. During our studies on cytisine derivatives we have synthesized N-methyl-2-thiocytisine (1, Scheme 1), and here we present the results of its structural characterization.
The configuration 7R,9S is confirmed by the value of the Flack parameter. The overall conformation of 1 is similar to other cytisine derivatives (Fig. 1). The ring A is almost planar, maximum deviation from the least-squares plane is 0.0170 (7) Å, ring B has the half-chair conformation, with five atoms almost coplanar (maximum deviation of 0.0497 (7) Å) and the bridgehead C8 atom significantly out of this plane, by -0.7560 (15) Å, and ring C is close to ideal chair conformation. This might be also described using the description of the asymmetry parameters (Duax & Norton, 1975), which measure the deviation from the ideal symmetry of the certain conformation. The ideal half-chair should possess C s symmetry, and the appropriate asymmetry parameter for B, ΔC s N1 is relatively high, equal to 8.4°. Ring C is much closer to the ideal chair symmetry of D 3d , maximum values of the asymmetry parameters are ΔC s 9 =2.61°, and ΔC 2 8-9 =2.50°.
In the crystal structure -in absence of the possibility of stronger interactions -relatively short and directional, (Table 1) C-H···π interactions play quite an important role. Their geometrical characteristics fit quite well to the category of weak hydrogen bonds (cf. for instance Desiraju & Steiner, 1999, Braga et al., 1998. Together with longer, probably of secondary nature, but still directional C-H···S contacts (Table 1)  N-methylcytisine was prepared adequately to the procedure: cytisine (1, 0.38 g, 2 mmol) was dissolved in 4 ml of 10% KOH and dimethyl sulfate (1.3 ml, 14 mmol) was added. The mixture was refluxed for 3 h. To cold mixture 12 ml of CH 2 Cl 2 was added and the mixture was stirred for 20 min. Then organic layer was separated and washed with water, dried above tube that was placed in an alumina bath inside the microwave oven and irradiated twice for 2 min. The crude material was dissolved in CH 2 Cl 2 (40 ml) and filtered, the solvent was evaporated. The residue was purified by column chromatography (Al 2 O 3 , CH 2 Cl 2 ). The yield 25% of yellow crystals (55 mg), m.p. 147 o C.

Refinement
The positions of hydrogen atoms were found in the difference Fourier maps and both positional and isotropic displacement prameters were freely refined. Fig. 1. Anisotropic ellipsoid representation of molecule 1 together with atom labelling scheme. The ellipsoids are drawn at 50% probability level, hydrogen atoms are depicted as spheres with arbitrary radii.

Figures
(1R,5S)-1,2,3,4,5,6-hexahydro-  Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > 2σ(F 2 ) is used only for calculating Rfactors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.