Dibenzo[b,f][1,4]thia­zepin-11-yl-diethyl-amine

Maria Altamura; Antonio Guidi; Loic Jierry; Paola Paoli; Patrizia Rossi

doi:10.1107/S1600536812042328

. 2012 Oct 13;68(Pt 11):o3133–o3134. doi: 10.1107/S1600536812042328

Dibenzo[b,f][1,4]thiazepin-11-yl-diethyl-amine

Maria Altamura ^a, Antonio Guidi ^a, Loic Jierry ^b, Paola Paoli ^c,^*, Patrizia Rossi ^c

PMCID: PMC3515236 PMID: 23284456

Abstract

In the title compound, C₁₇H₁₈N₂S, the thiazepine ring adopts a boat conformation and the dihedral angle between the benzene rings is 75.92 (5)°, resulting in a butterfly-like conformation. In the crystal, molecules are connected via weak C_aromatic—H⋯N contacts involving the imine N atom as acceptor and through a quite short C—H⋯π interaction. The resulting molecular chains propagate along the c-axis direction.

Related literature

For ‘privileged structures’, that is ‘structures able to provide high affinity ligands for more than one type of receptor’, see: Evans et al. (1988 ▶); Patchett & Nargund (2000 ▶); Fedi et al. (2008 ▶). For the clinical use of dibenzothiazepine derivatives, see: Ganesh et al. (2011 ▶); Pettersson et al. (2009 ▶); Riedel et al. (2007 ▶); Warawa et al. (2001 ▶). For structure–property relationships in (6,7,6)-tricyclic ring systems, see: Ravikumar & Sridhar (2005 ▶); Altamura et al. (2008 ▶, 2009 ▶, 2011 ▶). For geometrical data and descriptors, see: Duax et al. (1976 ▶); Bertolasi et al. (1982 ▶); Allen et al. (1987 ▶).

Experimental

Crystal data

C₁₇H₁₈N₂S
M _r = 282.40
Monoclinic,
a = 12.0137 (2) Å
b = 8.2257 (1) Å
c = 15.0513 (2) Å
β = 102.952 (1)°
V = 1449.54 (4) Å³
Z = 4
Cu Kα radiation
μ = 1.89 mm⁻¹
T = 150 K
0.20 × 0.18 × 0.03 mm

Data collection

Oxford Diffraction XcaliburPX diffractometer
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2006 ▶) T _min = 0.722, T _max = 0.945
6173 measured reflections
2364 independent reflections
1837 reflections with I > 2σ(I)
R _int = 0.019

Refinement

R[F ² > 2σ(F ²)] = 0.032
wR(F ²) = 0.086
S = 1.05
2364 reflections
181 parameters
H-atom parameters constrained
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.26 e Å⁻³

Data collection: CrysAlis CCD (Oxford Diffraction, 2006 ▶); cell refinement: CrysAlis CCD; data reduction: CrysAlis RED (Oxford Diffraction, 2006 ▶); program(s) used to solve structure: SIR92 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: PARST (Nardelli, 1995 ▶).

Supplementary Material

Click here for additional data file.^{(16.8KB, cif)}

Crystal structure: contains datablock(s) I, New_Global_Publ_Block. DOI: 10.1107/S1600536812042328/nc2296sup1.cif

e-68-o3133-sup1.cif^{(16.8KB, cif)}

Click here for additional data file.^{(113.8KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812042328/nc2296Isup2.hkl

e-68-o3133-Isup2.hkl^{(113.8KB, hkl)}

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

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

Cg is the centroid of the C8–C12 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C5—H5⋯N1ⁱ	0.95	2.70	3.576 (2)	154
C4—H4⋯Cg ⁱ	0.95	2.81	3.5759 (18)	139

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors acknowledge the CRIST (Centro di Cristallografia Strutturale, University of Firenze) where the data collection was performed.

supplementary crystallographic information

Comment

Many antidepressant drugs have a tricyclic structure with two aromatic rings fused to a central seven membered ring, on which one or more heteroatoms can be present. In this context, dibenzothiazepines are a class of heterocyclic scaffolds containing nitrogen and sulfur which belong to the class of the so-called "privileged structures", i.e. structures "able to provide high affinity ligands for more than one type of receptor" (Evans et al. 1988; Patchett & Nargund 2000; Fedi et al. 2008). In fact the dibenzothiazepine skeleton has a broad spectrum of medical applications; its derivatives are used to treat schizophrenia and also find applications as neuroleptics, antidepressants, antihistaminic, just to name a few (Ganesh et al. 2011; Pettersson et al. 2009; Riedel et al. 2007; Warawa et al. 2001). Within our programme research concerning the structural elucidation of tricyclic molecules in order to gain further insights into structure–property relationships (Altamura et al., 2008; Altamura et al., 2009; Altamura et al., 2011) we investigated the crystal and molecular structure of the title compound. The overall shape of the tricyclic skeleton is controlled both by the conformation of the central seven-membered ring and the relative arrangement of the aromatic rings bound to it. The central thiazepine ring adopts the usual boat conformation, with C1, C2, C8 and C9 as the basal plane, the S atom as the bow and the N1—C7 bond as the stern. The deviation from a pure boat conformation is quite small as can be seen from the asymmetry index ΔC_s which is 3.97°; the bow angle is 51.04 (8)° and the stern angle is 41.89 (8)°(Duax et al. 1976; Bertolasi et al. 1982; Ravikumar & Sridhar, 2005). Finally, the dihedral angle between the benzene rings is 104.08 (5)°. As a consequence the dibenzothiazepine tricyclic skeleton assumes an overall butterfly-like shape (Fig. 1). The N2—C7 bond is shorter than an usual N—C single bond [1.368 (2) Å compared to 1.416 Å (Allen et al. 1987)] and the sum of the bond angles about N2 is 358°; consequently, N2 has a partial sp² character. Molecular chains, which propagate along the c axis, are formed through intermolecular interactions (Fig. 2): a weak C—H_aromatic···N contact which involves the imine nitrogen atom as acceptor and a quite short C—H···π interaction (Table 1).

Experimental

The synthesis of the title compound started from the commercially available tricyclic lactam (dibenzo[b,f][1,4]thiazepin-11(10H)-one) (0.89 g, 3.91 mmol), that was dissolved into 10 ml of phosphorus oxychloride and refluxed for two hours under nitrogen atmosphere. After removal of excess POCl₃ under vacuum, the corresponding iminochloride (11-chlorodibenzo[b,f][1,4]thiazepine) was obtained as a yellow oil, that was dissolved in 20 ml of anhydrous toluene. An excess of diethylamine (20 ml, 191 mmol) was added and the mixture refluxed until complete conversion (monitored by HPLC; about 6 h were needed for complete conversion). After removal of the solvent in vacuo and purification by flash chromatography (eluent: gradient CH₂Cl₂/cyclohexane from 50:50 to 100% CH₂Cl₂), dibenzo[b,f][1,4]thiazepin-11-yl-diethyl-amine was obtained as a yellow oil (0.66 g, 60% yield), which became a white solid on standing at room temperature for several days. Crystals suitable for single-crystal X-ray diffraction analysis were obtained by slow evaporation of a water/DMSO solution of dibenzo[b,f][1,4]thiazepin-11-yl-diethyl-amine.