Bis{(R)-1-(3-amino­sulfonyl-4-meth­oxy­phen­yl)-N-[2-(2-eth­oxy­phen­oxy)eth­yl]propan-2-aminium} adipate tetra­hydrate

Zoran Ham; Anton Meden; Marta Kasunič

doi:10.1107/S1600536813005254

. 2013 Mar 9;69(Pt 4):o516–o517. doi: 10.1107/S1600536813005254

Bis{(R)-1-(3-aminosulfonyl-4-methoxyphenyl)-N-[2-(2-ethoxyphenoxy)ethyl]propan-2-aminium} adipate tetrahydrate

Zoran Ham ^a, Anton Meden ^b,^*, Marta Kasunič ^b

PMCID: PMC3629575 PMID: 23634062

Abstract

The title compound, 2C₂₀H₂₉N₂O₅S⁺·C₆H₈O₄ ²⁻·4H₂O, which was found to be optically active, is a relatively rare example of a chiral compound crystallizing in the triclinic crystal system. The dihedral angles between the phenyl rings of the cations are 60.03 (15) and 62.03 (16)°, while the C atoms of the anion are almost coplanar (r.m.s. deviation 0.085 Å) and all trans to each other. In the crystal, the components are connected by an extensive network of N—H⋯O and O—H⋯O hydrogen bonds. The sulfonamide groups link the cations into pairs via two N—H⋯O hydrogen bonds about the pseudo-inversion centre, leading to the formation of R ₂ ²(8) rings. The anions are stacked in between four cationic pairs. Pairs of water molecules bridge the larger building units, forming hydrogen bonds with the remaining two O atoms of the anion.

Related literature

(R)-5-(2-(2-(2-Ethoxyphenoxy)ethylamino)propyl)-2-methoxybenzenesulfonamide (generic name tamsulosin) has an α-adrenergic blocking action and possesses hypotensive activity and is used mainly for the treatment of benign prostatic hyperplasia, see: Abrams et al. (1995 ▶). graphic file with name e-69-0o516-scheme1.jpg

Experimental

Crystal data

2C₂₀H₂₉N₂O₅S⁺·C₆H₈O₄ ²⁻·4H₂O
M _r = 1035.21
Triclinic,
a = 10.4595 (2) Å
b = 11.9020 (3) Å
c = 12.6423 (3) Å
α = 69.439 (1)°
β = 70.466 (1)°
γ = 67.058 (1)°
V = 1320.95 (5) Å³
Z = 1
Mo Kα radiation
μ = 0.17 mm⁻¹
T = 293 K
0.25 × 0.25 × 0.20 mm

Data collection

Nonius KappaCCD diffractometer
Absorption correction: multi-scan (DENZO-SMN; Otwinowski & Minor, 1997 ▶) T _min = 0.933, T _max = 0.966
26272 measured reflections
10988 independent reflections
8651 reflections with I > 2σ(I)
R _int = 0.030

Refinement

R[F ² > 2σ(F ²)] = 0.047
wR(F ²) = 0.143
S = 1.00
10988 reflections
641 parameters
7 restraints
H-atom parameters constrained
Δρ_max = 0.42 e Å⁻³
Δρ_min = −0.36 e Å⁻³
Absolute structure: Flack (1983 ▶), 4978 Friedel pairs
Flack parameter: 0.10 (8)

Data collection: COLLECT (Nonius, 1998 ▶); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997 ▶); data reduction: DENZO-SMN; program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012 ▶) and Mercury (Macrae et al., 2006 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Click here for additional data file.^{(55.4KB, cif)}

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536813005254/ld2093sup1.cif

e-69-0o516-sup1.cif^{(55.4KB, cif)}

Click here for additional data file.^{(537.2KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813005254/ld2093Isup2.hkl

e-69-0o516-Isup2.hkl^{(537.2KB, hkl)}

Click here for additional data file.^{(19.4KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813005254/ld2093Isup3.cml

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
N1—H1B⋯O21ⁱ	0.96	2.11	3.028 (5)	160
N11—H11B⋯O11ⁱⁱ	0.86	2.23	3.029 (5)	155
N2—H2C⋯O3W	0.96	1.84	2.755 (4)	160
N12—H12B⋯O1W	0.96	1.87	2.797 (4)	160
N2—H2D⋯O1ⁱⁱⁱ	0.96	1.98	2.854 (4)	151
N12—H12A⋯O3^iv	0.96	1.83	2.746 (4)	159
N1—H1A⋯O3	0.95	1.84	2.790 (5)	173
N11—H11A⋯O1	0.78	2.03	2.798 (6)	169
O1W—H1WB⋯O2W ^v	0.95	1.80	2.746 (5)	174
O3W—H3WB⋯O4W ^vi	0.96	1.82	2.747 (5)	161
O2W—H2WA⋯O2	0.95	1.75	2.690 (6)	175
O4W—H4WA⋯O4^iv	0.89	1.77	2.658 (5)	175
O1W—H1WA⋯O24	0.90	2.33	2.899 (4)	121
O1W—H1WA⋯O25	0.90	2.08	2.963 (4)	165
O3W—H3WA⋯O14	0.92	2.39	2.920 (4)	116
O3W—H3WA⋯O15	0.92	2.03	2.935 (4)	166

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

Acknowledgments

The financial support of Ministry of Education, Science, Culture and Sport of the Republic of Slovenia via grant X-2000 is acknowledged.

supplementary crystallographic information

Comment

(R)-5-(2-(2-(2-ethoxyphenoxy)ethylamino)propyl)-2-methoxybenzenesulfonamide, designated with the generic pharmaceutical name tamsulosin, has an alpha-adrenergic blocking action and possesses a hypotensive activity and is used mainly for the treatment of benign prostatic hyperplasia (BPH) (Abrams et al., 1995). It has been used in the form of the hydrochloride salt of the pure R-enantiomer. Our attempts to prepare new salts of tamsulosin with improved solubility lead to the formation of yet unpublished tamsulosin adipate tetrahydrate (I). In this article, we report the absolute structure of (I). The asymmetric unit contains two protonated molecules of tamsulosin, adipate anion and four water molecules of solvation. All building units are connected with an extensive network of hydrogen bonds of N–H···O and O–H···O types. The former are donored by sulfonamide and amine N atoms from the cations: the shortest N···O distances and thus the strongest bonds lead towards water and anionic O atoms and are of lengths between 2.746 (4) and 2.854 (4) Å. As expected, intercationic N–H···O hydrogen bonds are somewhat weaker with N···O distances of 3.028 (5) and 3.029 (5) Å, respectively. O–H···O hydrogen bonds are donored by water molecules while the acceptors are anions, water molecules and cations, respectively. The shortest O···O distances are between water and anion (2.658 (5) and 2.690 (6) Å) while O(water)···O(water) distances are prolonged (2.746 (5) and 2.747 (5) Å, respectively). The building units are accommodated so that the O···O distances between water and cations are the longest (from 2.899 (4) to 2.963 (4) Å). The reason for significantly longer O···O aforementioned contacts are two pairs of bifurcated hydrogen bonds, donored by O1w and O3w. The details about hydrogen bonding can be seen in Table 1.

When considering the hydrogen bond topology, firstly, the sulfonamide groups link cations into pairs via two N–H···O hydrogen bonds around the pseudo inversion centre that leads to the formation of R₂²(8) rings. The cationic pairs are spatially arranged one above the other, i.e. there are columns of the cationic pairs in the structure. In between four of such pairs, anions are stacked, forming a larger structural segment (i.e. an anion in between four cationic pairs, 'A+4C'). This building unit is held together by N–H···O hydrogen bonds in which the anionic O atoms O1 and O3 are acceptors of two H-bonds being donnored by two neighbouring cationic columns. The other two anionic O atoms, i.e. O2 and O4, are in charge for further connections of the aforementioned larger structural segment 'A+4C', each via two water molecules, e.g. by a sequence of O–H···O hydrogen bonds which link together a cationic pair from one unit with the anion of the neighbouring unit. The described connections are depicted in Fig. 3.

Experimental

Tamsulosin adipate was prepared by mixing tamsulosin base and adipic (hexanedioic) acid in acetone at reflux temperature. The solution was cooled, concentrated and filtered. Obtained tamsulosin adipate was dried and dissolved in water at 25 °C to obtain a clear solution. The solution was left to stand at 25 °C for 7 days. Precipitated crystals of the title compound were separated from mother solution. The starting base was optically pure R enantiomer as well as the final product were optically active ([α]_Na^{20 °C}=-6°, conc. in methanol = 4 mg ml^-1), which proves that the chirality was preserved during synthesis.