7-[(3-Chloro-6-methyl-6,11-dihydro­dibenzo[c,f][1,2]thia­zepin-11-yl)amino]­hepta­noic acid S,S-dioxide hydro­chloride

Anatoly Mishnev; Alvis Zvirgzdins; Andris Actins; Mara Delina

doi:10.1107/S1600536812042432

. 2012 Oct 13;68(Pt 11):o3136. doi: 10.1107/S1600536812042432

7-[(3-Chloro-6-methyl-6,11-dihydrodibenzo[c,f][1,2]thiazepin-11-yl)amino]heptanoic acid S,S-dioxide hydrochloride

Anatoly Mishnev ^a, Alvis Zvirgzdins ^b,^*, Andris Actins ^b, Mara Delina ^b

PMCID: PMC3515238 PMID: 23284458

Abstract

In the title compound, C₂₁H₂₆ClN₂O₄S^.Cl, also known as tianeptine hydrochloride, the seven-membered ring adopts a boat conformation. The dihedral angle between the mean planes of the benzene rings is 44.44 (7)°. There is an intramolecular hydrogen bond formed via S= O⋯H—N. In the crystal, molecules are connected via pairs of N—H.·O, N—H⋯Cl and O—H⋯Cl hydrogen bonds, forming inversion dimers, which are consolidated by C—H⋯O interactions. The dimers are linked by C—H⋯O and C—H⋯Cl interactions, forming a two-dimensional network lying parallel to (011).

Related literature

For general information about tianeptine and its preparation, see: Guzman et al. (2010 ▶). For related structures, see: Orola et al. (2012 ▶).

Experimental

Crystal data

C₂₁H₂₆ClN₂O₄S⁺·Cl⁻
M _r = 473.40
Triclinic,
a = 9.5439 (2) Å
b = 10.0910 (2) Å
c = 13.1802 (3) Å
α = 104.000 (1)°
β = 101.538 (1)°
γ = 105.018 (1)°
V = 1139.04 (4) Å³
Z = 2
Mo Kα radiation
μ = 0.41 mm⁻¹
T = 190 K
0.24 × 0.20 × 0.14 mm

Data collection

Nonius KappaCCD diffractometer
7552 measured reflections
4985 independent reflections
4015 reflections with I > 2σ(I)
R _int = 0.021

Refinement

R[F ² > 2σ(F ²)] = 0.040
wR(F ²) = 0.100
S = 1.03
4985 reflections
273 parameters
H-atom parameters constrained
Δρ_max = 0.76 e Å⁻³
Δρ_min = −0.34 e Å⁻³

Data collection: COLLECT (Hooft, 1998 ▶); cell refinement: HKL DENZO (Otwinowski & Minor, 1997 ▶); data reduction: SCALEPACK (Otwinowski & Minor, 1997 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: Mercury (Macrae et al., 2008 ▶); software used to prepare material for publication: SHELXL97 and publCIF (Westrip, 2010 ▶).

Supplementary Material

Click here for additional data file.^{(23.1KB, cif)}

Crystal structure: contains datablock(s) global. DOI: 10.1107/S1600536812042432/pv2586sup1.cif

e-68-o3136-sup1.cif^{(23.1KB, cif)}

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

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H3A⋯Cl2ⁱ	0.90	2.31	3.154 (2)	157
N2—H3B⋯O3ⁱⁱ	0.90	2.32	2.821 (2)	115
C16—H11B⋯O3ⁱⁱ	0.97	2.56	3.201 (2)	124
O4—H6⋯Cl2ⁱⁱⁱ	0.82	2.22	3.043 (2)	176
C4—H3⋯Cl2^iv	0.93	2.82	3.651 (2)	150
C18—H6A⋯O4^v	0.97	2.56	3.467 (2)	157
C7—H7⋯Cl2	0.98	2.59	3.534 (2)	162
N2—H3B⋯O2	0.90	2.02	2.802 (2)	144

Open in a new tab

Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) ; (v) .

Acknowledgments

This work was supported by the European Regional Development Fund (No. 2011/0014/2DP/2.1.1.1.0/10/APIA/VIAA/092).

supplementary crystallographic information

Comment

Tianeptine salts are of wide interest since they are crystalline. Although the synthesis of the title compound, tianeptine hydrochloride, has been described (Guzman et al., 2010) we describe in this article an improved method of its synthesis and its crystal structure.

In the title compound (Fig. 1), the seven-membered ring adopts a boat conformation with the values of torsion angles: C1—S1—N1—C13 = -78.4 (2) and C1—C6—C7—C8 = -56.3 (3)°. The dihedral angle between the mean planes of the two benzene rings (C1–C6 and C8–C13) is 44.44 (7)°. There is an intramolecular hydrogen bond in the title molecule which is formed via S1═O2···H3B—N2 that stabilizes the molecular structure. In the crystal, the molecules are connected via hydrogen bonds between carboxyl and amine groups and chloride anion, O4—H6···Cl2, N2—H3A···Cl2 and N2—H3B···O3. The crystal structure is further consolidated by intermolecular interactions, C18—H6A···O4, C4—H3···Cl2, C16—H11B···O3 and C7—H7···Cl2 (Table 1 and Fig. 2). The supramolecular structure of tianeptine hydrochloride consists of parallel oriented tricyclic fragment and parallel oriented carbon atom chains (heptanoic acid). Carbon atom chains are linked with hydrogen bonds via chloride anion, amine and carboxylgroup. The torsion angle C8—C7—N2—C15 is -168.4 (2)° so that the carbon atom chain C15—C20 is almost parallel to the benzene ring C8—C13.

The crystal structures of tianeptine polymorphs have been reported recently (Orola et al., 2012). The title structure is more similar with polymorph A structure in which tianeptine molecules are linked via hydrogen bonds between amine and carboxyl groups. The tianeptine molecules in the structure of tianeptine polymorph B are in a zwiterrion form.

Experimental

Tianeptine sodium salt (0.5 g;1.09 mmol) was dissolved in 20 ml deionized water in a Erlenmeyer flask and added ~3 mmol of hydrochloric acid. Mixture were stirred for 6 h. After 6 h suspension was filtered and washed with cold water. The product was dried and recrystallized from water by slow evaporation at room temperature.