research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 72| Part 5| May 2016| Pages 692-695
doi:10.1107/S2056989016006022

Crystal structure of Brinzolamide: a carbonic anhydrase inhibitor

CROSSMARK_Color_square_no_text.svg
Huirong Zhenga and Benyong Loua*

aDepartment of Chemistry and Chemical Engineering, Minjiang University, Fuzhou 350108, People's Republic of China
*Correspondence e-mail: lby@mju.edu.cn

Edited by H. Stoeckli-Evans, University of Neuchâtel, Switzerland (Received 5 April 2016; accepted 11 April 2016; online 15 April 2016)

In crystal structure of the title compound, C12H21N3O5S3 [systematic name: (R)-4-ethyl­amino-2-(3-meth­oxy­prop­yl)-3,4-di­hydro-2H-thieno[3,2-e][1,2]thia­zine-6-sulfonamide 1,1-dioxide], there exist three kinds of hydrogen-bonding inter­actions. The sulfonamide group is involved in hydrogen bonding with the secondary amine and the meth­oxy O atom, resulting in the formation of layers parallel to the bc plane. The layers are linked by an N—H⋯O hydrogen bond involving a sulfonamide O atom as acceptor and the secondary amine H atom as donor, which gives rise to the formation of a unique bilayer structure. The absolute structure of the mol­ecule in the crystal was determined by resonant scattering [Flack parameter = 0.01 (4)].

CCDC reference: 1473394

1. Chemical context

The crystal structures of organic solids are dominated mainly by hydrogen-bonding inter­actions (Steiner, 2002[Steiner, T. (2002). Angew. Chem. Int. Ed. 41, 48-76.]). Hydrogen bonding plays a crucial role in polymorphism of active pharmaceutical ingredients (Vippagunta et al., 2001[Vippagunta, S. R., Brittain, H. G. & Grant, D. J. W. (2001). Adv. Drug Deliv. Rev. 48, 3-26.]). Brinzolamide (Conrow et al., 1999[Conrow, R. E., Dean, W. D., Zinke, P. W., Deason, M. E., Sproull, S. J., Dantanarayana, A. P. & DuPriest, M. T. (1999). Org. Process Res. Dev. 3, 114-120.]), is a carbonic anhydrase inhibitor used for the treatment of open-angle glaucoma or ocular hypertension (March & Ochsner, 2000[March, W. F. & Ochsner, K. I. (2000). Am. J. Ophthalmol. 129, 136-143.]). Herein,we report on the crystal structure of Brinzolamide and the hydrogen-bonding inter­actions present in the crystal packing.

[Scheme 1]

2. Structural commentary

The mol­ecular structure of the title compound is shown in Fig. 1[link]. The six-membered thia­zine ring has an envelope conformation with the N atom, N2, as the flap. The 3-meth­oxy­propyl chain has a twisted conformation with torsion angles N2—C7—C8—C9, C7—C8—C9—O5 and C8—C9—O5—C10 being 71.66 (18), 166.76 (14) and 82.04 (19)°, respectively. The ethyl­amino group (N3/C11/C12) is normal to the mean plane of the five planar atoms of the thia­zine ring (S3/C3–C6), making a dihedral angle of 84.4 (3)°. The three main functional groups (the sulfonamide, the secondary amine and the meth­oxy group) extend themselves in different directions, which facilitates the formation of a hydrogen-bonded network.

[Figure 1]
Figure 1
The mol­ecular structure of the title compound, showing the atom labelling and 30% displacement ellipsoids.

3. Supra­molecular features

There are three kinds of hydrogen-bonding inter­actions in the crystal of Brinzolamide (Table 1[link] and Figs. 2[link] and 3[link]). The sulfonamide group is involved in hydrogen bonding [N1⋯N3 = 2.886 (2) Å, Table 1[link]] with the secondary amine, forming a C(8) chain along the b-axis direction. The sulfonamide group is also involved in hydrogen bonding with the meth­oxy group [N1⋯O5 = 2.841 (2) Å, Table 1[link]], linking the chains to form sheets parallel to the bc plane (Fig. 2[link] and Table 1[link]). There also exists another hydrogen bond between the sulfonamide and the secondary amine [N3⋯O1 = 3.042 (2) Å, Table 1[link]], linking the sheets to form a unique bilayer structure (Fig. 3[link]).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A D⋯A D—H⋯A
N1—H1B⋯O5i 0.87 (1) 1.98 (1) 2.841 (2) 177 (2)
N1—H1A⋯N3ii 0.87 (1) 2.03 (1) 2.886 (2) 171 (2)
N3—H3⋯O1iii 0.86 (1) 2.26 (1) 3.042 (2) 151 (2)
Symmetry codes: (i) x, y+1, z-1; (ii) x, y+1, z; (iii) [-x, y-{\script{1\over 2}}, -z+1].
[Figure 2]
Figure 2
A view along the a axis of the two-dimensional hydrogen-bonded network in the crystal of the title compound. The hydrogen bonds are shown as dashed lines (see Table 1[link] for details).
[Figure 3]
Figure 3
A view along the c axis of the crystal packing of the title compound, showing the hydrogen bonded bilayer structure. The hydrogen bonds are shown as dashed lines (see Table 1[link] for details).

4. Database survey

A search of the Cambridge Structural Database (CSD, Version 5.37, last update February 2016; Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]) revealed no hits for Brinzolamide. A search for the fused six- and five-membered ring system, viz. 3,4-di­hydro-2λ2-thieno[3,2-e][1,2]thia­zine 1,1-dioxide, gave only two hits: 8b-bromo-2-(bromo­meth­yl)-4-methyl-3a-phenyl-1,3a,4,8b-tetra­hydro-2H-furo[2,3-c]thieno[3,2-e][1,2]thia­zine 5,5-dioxide (BUFQIE; Barange et al., 2014[Barange, D. K., Kavala, V., Kuo, C.-W., Wang, C.-C., Rajawinslin, R. R., Donala, J. & Yao, C.-F. (2014). Tetrahedron, 70, 7598-7605.]) and (S)-6,6-dimethyl-4a,5,6,7-tetra­hydro-4H-pyrrolo­[1,2-b]thieno[3,2-e][1,2]thia­zine 9,9-dioxide (BUXDEE; Zeng & Chemler, 2007[Zeng, W. & Chemler, S. R. (2007). J. Am. Chem. Soc. 129, 12948-12949.]). The latter crystallizes in the chiral monoclinic space group P21, with four independent mol­ecules in the asymmetric unit. However, in both compounds the six-membered thia­zine ring is also fused to a second five-membered ring; a tetra­hydro­furo ring in the case of BUFQIE, fused to the C—C bond, and a pyrrolo ring in the case of BUXDEE, fused to the N—C bond. The thia­zine ring in BUFQIE has a distorted twist-boat conformation, while in BUFQIE all four independent mol­ecules have half-chair conformations. This is in contrast to the situation in the title compound where the thia­zine ring has an envelope conformation with the N atom as the flap.

5. Synthesis and crystallization

The enanti­oselective synthesis of Brinzolamide has been reported by Conrow et al., (1999[Conrow, R. E., Dean, W. D., Zinke, P. W., Deason, M. E., Sproull, S. J., Dantanarayana, A. P. & DuPriest, M. T. (1999). Org. Process Res. Dev. 3, 114-120.]). It is marketed under the trade name of Azopt by Alcon Laboratories, Inc., Fort Worth, Texas 76134, USA. Colourless prismatic crystals of Brinzolamide (383 mg, 1 mmol) were obtained by slow evaporation of a solution in chloro­form (15 ml).

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. The NH and NH2 H atoms were located in difference Fourier maps and refined with distance restraints of N—H = 0.87 (1) Å for NH and 0.86 (1) Å for NH2 H atoms. The C-bound H atoms were included in calculated positions and treated as riding atoms: C—H = 0.95–1.00 Å with Uiso(H) = 1.5Ueq(C-meth­yl) and 1.2Ueq(C) for other H atoms. The absolute structure of the mol­ecule in the crystal was determined by resonant scattering [Flack parameter = 0.01 (4)].

Table 2
Experimental details

Crystal data
Chemical formula C12H21N3O5S3
Mr 383.50
Crystal system, space group Monoclinic, P21
Temperature (K) 293
a, b, c (Å) 9.698 (2), 8.8127 (19), 10.133 (2)
β (°) 92.248 (3)
V (Å3) 865.4 (3)
Z 2
Radiation type Mo Kα
μ (mm−1) 0.46
Crystal size (mm) 0.35 × 0.35 × 0.20
 
Data collection
Diffractometer Rigaku Mercury CCD
Absorption correction Multi-scan (CrystalClear; Rigaku, 2000[Rigaku (2000). CrystalClear. Rigaku Corporation, Tokyo, Japan.])
Tmin, Tmax 0.853, 0.913
No. of measured, independent and observed [I > 2σ(I)] reflections 6608, 3684, 3612
Rint 0.010
(sin θ/λ)max (Å−1) 0.649
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.022, 0.059, 1.04
No. of reflections 3684
No. of parameters 222
No. of restraints 4
H-atom treatment H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.21, −0.19
Absolute structure 1595 Friedel pairs; Flack (1983[Flack, H. D. (1983). Acta Cryst. A39, 876-881.])
Absolute structure parameter 0.01 (4)
Computer programs: CrystalClear (Rigaku, 2000[Rigaku (2000). CrystalClear. Rigaku Corporation, Tokyo, Japan.]), SHELXS97 and SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), X-SEED (Barbour, 2001[Barbour, L. J. (2001). J. Supramol. Chem. 1, 189-191.]) and PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]).

Supporting information

CCDC reference: 1473394

Crystal structure: contains datablocks I, global. DOI: 10.1107/S2056989016006022/su5292sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S2056989016006022/su5292Isup2.hkl

Supporting information file. DOI: 10.1107/S2056989016006022/su5292Isup3.cml

checkCIF report


Chemical context top

The crystal structures of organic solids are dominated mainly by hydrogen-bonding inter­actions (Steiner, 2002). Hydrogen bonding plays a crucial role in polymorphism of active pharmaceutical ingredients (Vippagunta et al., 2001). Brinzolamide (Conrow et al., 1999), is a carbonic anhydrase inhibitor used for the treatment of open-angle glaucoma or ocular hypertension (March & Ochsner, 2000). Herein,we report on the crystal structure of Brinzolamide and the hydrogen-bonding inter­actions present in the crystal packing.

Structural commentary top

The molecular structure of the title compound is shown in Fig. 1. The six-membered thia­zine ring has an envelope conformation with the N atom, N2, as the flap. The 3-meth­oxy­propyl chain has a twisted conformation with torsion angles N2—C7—C8—C9, C7—C8—C9—O5 and C8—C9—O5—C10 being 71.66 (18), 166.76 (14) and 82.04 (19)°, respectively. The ethyl­amino group (N3/C11/C12) is normal to the mean plane of the five planar atoms of the thia­zine ring (S3/C3–C6), making a dihedral angle of 84.4 (3)°. The three main functional groups (the sulfonamide, the secondary amine and the meth­oxy group) extend themselves in different directions, which facilitates the formation of a hydrogen-bonded network.

Supra­molecular features top

There are three kinds of hydrogen-bonding inter­actions in the crystal of Brinzolamide (Table 1 and Figs. 2 and 3). The sulfonamide group is involved in hydrogen bonding [N1···N3 = 2.886 (2) Å, Table 1] with the secondary amine, forming a C(8) chain along the b-axis direction. The sulfonamide group is also involved in hydrogen bonding with the meth­oxy group [N1···O5 = 2.841 (2) Å, Table 1], linking the chains to form sheets parallel to the bc plane (Fig. 2 and Table 1). There also exists another hydrogen bond between the sulfonamide and the secondary amine [N3···O1 = 3.042 (2) Å, Table 1], linking the sheets to form a unique bilayer structure (Fig. 3).

Database survey top

\ A search of the Cambridge Structural Database (CSD, Version 5.37, last update February 2016; Groom et al., 2016) revealed no hits for Brinzolamide. A search for the fused six- and five-membered ring system, viz. 3,4-di­hydro-2λ2-thieno[3,2-e][1,2]thia­zine 1,1-dioxide, gave only two hits: 8b-bromo-2-(bromo­methyl)-4-methyl-3a-phenyl-1,3a,4,8b-tetra­hydro-2H-\ furo[2,3-c]thieno[3,2-e][1,2]thia­zine 5,5-dioxide (BUFQIE; Barange et al., 2014) and (S)-6,6-di­methyl-4a,5,6,7-tetra­hydro-4H-pyrrolo­[1,2-b]\ thieno[3,2-e][1,2]thia­zine 9,9-dioxide (BUXDEE; Zeng & Chemler, 2007). The latter crystallizes in the chiral monoclinic space group P21, with four independent molecules in the asymmetric unit. However, in both compounds the six-membered thia­zine ring is also fused to a second five-membered ring; a tetra­hydro­furo ring in the case of BUFQIE, fused to the C—C bond, and a pyrrolo ring in the case of BUXDEE, fused to the N—C bond. The thia­zine ring in BUFQIE has a distorted twist-boat conformation, while in BUFQIE all four independent molecules have half-chair conformations. This is in contrast to the situation in the title compound where the thia­zine ring has an envelope conformation with the N atom as the flap.

Synthesis and crystallization top

The enanti­oselective synthesis of Brinzolamide has been reported by Conrow et al., (1999). It is marketed under the trade name of Azopt by Alcon Laboratories, Inc., Fort Worth, Texas 76134, USA. Colourless prismatic crystals of Brinzolamide (383 mg, 1 mmol) were obtained by slow evaporation of a solution in chloro­form (15 ml).

Refinement top

Crystal data, data collection and structure refinement details are summarized in Table 2. The NH and NH2 H atoms were located in difference Fourier maps and refined with distance restraints of N—H = 0.87 (1) Å for NH and 0.89 (1) Å for NH2 H atoms. The C-bound H atoms were included in calculated positions and treated as riding atoms: C—H = 0.95–1.00 Å with Uiso(H) = 1.5Ueq(C-methyl) and 1.2Ueq(C) for other H atoms. The absolute structure of the molecule in the crystal was determined by resonant scattering [Flack parameter = 0.01 (4)].

Related literature top

For related literature, see: March (2000); Steiner (2002) Vippagunta (2001);

Structure description top

The crystal structures of organic solids are dominated mainly by hydrogen-bonding inter­actions (Steiner, 2002). Hydrogen bonding plays a crucial role in polymorphism of active pharmaceutical ingredients (Vippagunta et al., 2001). Brinzolamide (Conrow et al., 1999), is a carbonic anhydrase inhibitor used for the treatment of open-angle glaucoma or ocular hypertension (March & Ochsner, 2000). Herein,we report on the crystal structure of Brinzolamide and the hydrogen-bonding inter­actions present in the crystal packing.

The molecular structure of the title compound is shown in Fig. 1. The six-membered thia­zine ring has an envelope conformation with the N atom, N2, as the flap. The 3-meth­oxy­propyl chain has a twisted conformation with torsion angles N2—C7—C8—C9, C7—C8—C9—O5 and C8—C9—O5—C10 being 71.66 (18), 166.76 (14) and 82.04 (19)°, respectively. The ethyl­amino group (N3/C11/C12) is normal to the mean plane of the five planar atoms of the thia­zine ring (S3/C3–C6), making a dihedral angle of 84.4 (3)°. The three main functional groups (the sulfonamide, the secondary amine and the meth­oxy group) extend themselves in different directions, which facilitates the formation of a hydrogen-bonded network.

There are three kinds of hydrogen-bonding inter­actions in the crystal of Brinzolamide (Table 1 and Figs. 2 and 3). The sulfonamide group is involved in hydrogen bonding [N1···N3 = 2.886 (2) Å, Table 1] with the secondary amine, forming a C(8) chain along the b-axis direction. The sulfonamide group is also involved in hydrogen bonding with the meth­oxy group [N1···O5 = 2.841 (2) Å, Table 1], linking the chains to form sheets parallel to the bc plane (Fig. 2 and Table 1). There also exists another hydrogen bond between the sulfonamide and the secondary amine [N3···O1 = 3.042 (2) Å, Table 1], linking the sheets to form a unique bilayer structure (Fig. 3).

\ A search of the Cambridge Structural Database (CSD, Version 5.37, last update February 2016; Groom et al., 2016) revealed no hits for Brinzolamide. A search for the fused six- and five-membered ring system, viz. 3,4-di­hydro-2λ2-thieno[3,2-e][1,2]thia­zine 1,1-dioxide, gave only two hits: 8b-bromo-2-(bromo­methyl)-4-methyl-3a-phenyl-1,3a,4,8b-tetra­hydro-2H-\ furo[2,3-c]thieno[3,2-e][1,2]thia­zine 5,5-dioxide (BUFQIE; Barange et al., 2014) and (S)-6,6-di­methyl-4a,5,6,7-tetra­hydro-4H-pyrrolo­[1,2-b]\ thieno[3,2-e][1,2]thia­zine 9,9-dioxide (BUXDEE; Zeng & Chemler, 2007). The latter crystallizes in the chiral monoclinic space group P21, with four independent molecules in the asymmetric unit. However, in both compounds the six-membered thia­zine ring is also fused to a second five-membered ring; a tetra­hydro­furo ring in the case of BUFQIE, fused to the C—C bond, and a pyrrolo ring in the case of BUXDEE, fused to the N—C bond. The thia­zine ring in BUFQIE has a distorted twist-boat conformation, while in BUFQIE all four independent molecules have half-chair conformations. This is in contrast to the situation in the title compound where the thia­zine ring has an envelope conformation with the N atom as the flap.

For related literature, see: March (2000); Steiner (2002) Vippagunta (2001);

Synthesis and crystallization top

The enanti­oselective synthesis of Brinzolamide has been reported by Conrow et al., (1999). It is marketed under the trade name of Azopt by Alcon Laboratories, Inc., Fort Worth, Texas 76134, USA. Colourless prismatic crystals of Brinzolamide (383 mg, 1 mmol) were obtained by slow evaporation of a solution in chloro­form (15 ml).

Refinement details top

Crystal data, data collection and structure refinement details are summarized in Table 2. The NH and NH2 H atoms were located in difference Fourier maps and refined with distance restraints of N—H = 0.87 (1) Å for NH and 0.89 (1) Å for NH2 H atoms. The C-bound H atoms were included in calculated positions and treated as riding atoms: C—H = 0.95–1.00 Å with Uiso(H) = 1.5Ueq(C-methyl) and 1.2Ueq(C) for other H atoms. The absolute structure of the molecule in the crystal was determined by resonant scattering [Flack parameter = 0.01 (4)].

Computing details top

Data collection: CrystalClear (Rigaku, 2000); cell refinement: CrystalClear (Rigaku, 2000); data reduction: CrystalClear (Rigaku, 2000); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: X-SEED (Barbour, 2001); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound, showing the atom labelling and 30% displacement ellipsoids.
[Figure 2] Fig. 2. A view along the a axis of the two-dimensional hydrogen-bonded layer in the crystal of the title compound. The hydrogen bonds are shown as dashed lines (see Table 1 for details).
[Figure 3] Fig. 3. A view along the c axis of the crystal packing of the title compound, showing the hydrogen bonded bilayer structure. The hydrogen bonds are shown as dashed lines (see Table 1 for details).
(5R)-5-ethylamino-3-(3-methoxypropyl)-2,2-dioxo-2,9-dithia-3-azabicyclo[4.3.0]nona-1(6)7-diene-8-sulfonamide top
Crystal data top
C12H21N3O5S3F(000) = 404
Mr = 383.50Dx = 1.472 Mg m−3
Monoclinic, P21Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ybCell parameters from 2619 reflections
a = 9.698 (2) Åθ = 2.1–27.5°
b = 8.8127 (19) ŵ = 0.46 mm−1
c = 10.133 (2) ÅT = 293 K
β = 92.248 (3)°Prism, colourless
V = 865.4 (3) Å30.35 × 0.35 × 0.20 mm
Z = 2
Data collection top
Rigaku Mercury CCD
diffractometer		3684 independent reflections
Radiation source: fine-focus sealed tube3612 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.010
Detector resolution: 14.6306 pixels mm-1θmax = 27.5°, θmin = 2.0°
CCD_Profile_fitting scansh = −12→12
Absorption correction: multi-scan
(CrystalClear; Rigaku, 2000)		k = −11→11
Tmin = 0.853, Tmax = 0.913l = −13→13
6608 measured reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.022H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.059 w = 1/[σ2(Fo2) + (0.0403P)2 + 0.0611P]
where P = (Fo2 + 2Fc2)/3
S = 1.03(Δ/σ)max = 0.001
3684 reflectionsΔρmax = 0.21 e Å−3
222 parametersΔρmin = −0.19 e Å−3
4 restraintsAbsolute structure: 1595 Friedel pairs; Flack (1983)
Primary atom site location: structure-invariant direct methodsAbsolute structure parameter: 0.01 (4)
Crystal data top
C12H21N3O5S3V = 865.4 (3) Å3
Mr = 383.50Z = 2
Monoclinic, P21Mo Kα radiation
a = 9.698 (2) ŵ = 0.46 mm−1
b = 8.8127 (19) ÅT = 293 K
c = 10.133 (2) Å0.35 × 0.35 × 0.20 mm
β = 92.248 (3)°
Data collection top
Rigaku Mercury CCD
diffractometer		3684 independent reflections
Absorption correction: multi-scan
(CrystalClear; Rigaku, 2000)		3612 reflections with I > 2σ(I)
Tmin = 0.853, Tmax = 0.913Rint = 0.010
6608 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.022H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.059Δρmax = 0.21 e Å−3
S = 1.03Δρmin = −0.19 e Å−3
3684 reflectionsAbsolute structure: 1595 Friedel pairs; Flack (1983)
222 parametersAbsolute structure parameter: 0.01 (4)
4 restraints
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
S10.08557 (3)0.95125 (4)0.63688 (3)0.02705 (9)
S20.26509 (4)0.81437 (4)0.85525 (3)0.02964 (9)
S30.37674 (4)0.52417 (4)0.99143 (4)0.03230 (9)
O1−0.02692 (13)0.88932 (16)0.55817 (13)0.0482 (3)
O20.05935 (13)1.05211 (14)0.74416 (12)0.0409 (3)
O30.51842 (12)0.50532 (17)0.96186 (14)0.0482 (3)
O40.34354 (16)0.59370 (17)1.11319 (11)0.0504 (3)
O50.14543 (15)0.01552 (16)1.26375 (12)0.0472 (3)
N10.19095 (16)1.02862 (18)0.54219 (13)0.0365 (3)
N20.30128 (13)0.35864 (15)0.97875 (12)0.0310 (3)
N30.29017 (12)0.32938 (16)0.60656 (12)0.0285 (3)
C10.17016 (14)0.79352 (17)0.70936 (12)0.0241 (3)
C20.16170 (15)0.64755 (17)0.66712 (13)0.0262 (3)
H20.11300.61680.58840.031*
C30.29337 (15)0.62151 (18)0.85939 (14)0.0269 (3)
C40.23410 (14)0.54569 (18)0.75421 (13)0.0248 (3)
C50.23691 (15)0.37508 (18)0.73479 (14)0.0262 (3)
H50.13940.33860.73680.031*
C60.31904 (17)0.29191 (18)0.84604 (15)0.0312 (3)
H6A0.28950.18440.84730.037*
H6B0.41820.29390.82640.037*
C70.15834 (18)0.3485 (2)1.02768 (17)0.0410 (4)
H7A0.09160.37770.95570.049*
H7B0.14860.42121.10120.049*
C80.12434 (19)0.1893 (2)1.07530 (16)0.0409 (4)
H8A0.02370.18181.08720.049*
H8B0.14890.11491.00690.049*
C90.2000 (2)0.1493 (2)1.20395 (16)0.0414 (4)
H9A0.29880.13291.18730.050*
H9B0.19350.23551.26610.050*
C100.1941 (2)−0.1233 (3)1.2128 (2)0.0497 (5)
H10A0.1556−0.13811.12290.074*
H10B0.1652−0.20721.26900.074*
H10C0.2950−0.12091.21140.074*
C110.42904 (19)0.3825 (3)0.57763 (18)0.0499 (5)
H11A0.49820.32340.63050.060*
H11B0.43860.49050.60330.060*
C120.4563 (3)0.3657 (5)0.4339 (2)0.0923 (12)
H12A0.44800.25860.40870.138*
H12B0.54970.40160.41750.138*
H12C0.38900.42580.38160.138*
H30.2359 (17)0.369 (2)0.5477 (16)0.038 (5)*
H1A0.228 (2)1.1141 (16)0.566 (2)0.044 (6)*
H1B0.174 (2)1.024 (3)0.4577 (10)0.046 (5)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
S10.03112 (17)0.02019 (17)0.02929 (17)0.00014 (14)−0.00565 (13)0.00508 (14)
S20.04226 (19)0.01977 (18)0.02583 (16)−0.00143 (14)−0.01218 (13)−0.00112 (14)
S30.0398 (2)0.0277 (2)0.02842 (17)0.00293 (16)−0.01163 (13)0.00436 (15)
O10.0434 (7)0.0388 (7)0.0599 (8)−0.0078 (6)−0.0284 (6)0.0154 (6)
O20.0534 (7)0.0300 (7)0.0398 (6)0.0094 (5)0.0096 (5)0.0022 (5)
O30.0345 (6)0.0476 (8)0.0612 (8)0.0005 (6)−0.0145 (5)0.0135 (7)
O40.0838 (10)0.0383 (7)0.0280 (6)0.0073 (7)−0.0134 (6)−0.0016 (5)
O50.0716 (9)0.0387 (7)0.0326 (6)0.0081 (7)0.0188 (6)0.0074 (6)
N10.0563 (8)0.0259 (8)0.0274 (6)−0.0088 (7)0.0012 (5)0.0046 (6)
N20.0382 (6)0.0250 (7)0.0297 (6)0.0047 (5)0.0010 (5)0.0062 (5)
N30.0306 (6)0.0254 (7)0.0291 (6)−0.0013 (5)−0.0040 (4)−0.0020 (5)
C10.0283 (6)0.0219 (8)0.0216 (6)−0.0007 (5)−0.0055 (5)0.0033 (5)
C20.0324 (7)0.0211 (7)0.0246 (6)−0.0015 (5)−0.0064 (5)0.0004 (6)
C30.0328 (7)0.0196 (8)0.0276 (7)0.0021 (6)−0.0074 (5)0.0031 (6)
C40.0279 (6)0.0205 (7)0.0257 (6)0.0010 (5)−0.0037 (5)0.0025 (6)
C50.0280 (6)0.0202 (7)0.0301 (7)0.0013 (5)−0.0034 (5)0.0005 (6)
C60.0394 (7)0.0217 (8)0.0322 (7)0.0059 (6)−0.0008 (6)0.0026 (6)
C70.0414 (8)0.0419 (11)0.0402 (8)0.0084 (7)0.0087 (6)0.0116 (7)
C80.0458 (9)0.0453 (11)0.0317 (7)−0.0054 (8)0.0035 (6)0.0066 (8)
C90.0549 (10)0.0368 (10)0.0327 (8)0.0009 (8)0.0042 (7)0.0026 (7)
C100.0651 (12)0.0380 (10)0.0462 (10)0.0054 (9)0.0051 (8)−0.0013 (9)
C110.0390 (9)0.0666 (13)0.0444 (9)−0.0152 (9)0.0070 (7)−0.0117 (10)
C120.0653 (15)0.153 (4)0.0599 (14)−0.0316 (19)0.0227 (11)−0.0246 (18)
Geometric parameters (Å, º) top
S1—O11.4338 (12)C4—C51.517 (2)
S1—O21.4346 (13)C5—C61.540 (2)
S1—N11.5834 (14)C5—H51.0000
S1—C11.7600 (15)C6—H6A0.9900
S2—C11.7205 (13)C6—H6B0.9900
S2—C31.7219 (16)C7—C81.524 (3)
S3—O41.4256 (14)C7—H7A0.9900
S3—O31.4274 (14)C7—H7B0.9900
S3—N21.6349 (15)C8—C91.513 (2)
S3—C31.7592 (14)C8—H8A0.9900
O5—C101.416 (2)C8—H8B0.9900
O5—C91.436 (2)C9—H9A0.9900
N1—H1A0.866 (10)C9—H9B0.9900
N1—H1B0.866 (9)C10—H10A0.9800
N2—C61.484 (2)C10—H10B0.9800
N2—C71.493 (2)C10—H10C0.9800
N3—C111.466 (2)C11—C121.497 (3)
N3—C51.4731 (19)C11—H11A0.9900
N3—H30.856 (9)C11—H11B0.9900
C1—C21.357 (2)C12—H12A0.9800
C2—C41.4245 (19)C12—H12B0.9800
C2—H20.9500C12—H12C0.9800
C3—C41.365 (2)
O1—S1—O2120.25 (9)N2—C6—H6A108.9
O1—S1—N1108.78 (8)C5—C6—H6A108.9
O2—S1—N1109.28 (8)N2—C6—H6B108.9
O1—S1—C1105.28 (7)C5—C6—H6B108.9
O2—S1—C1105.47 (7)H6A—C6—H6B107.7
N1—S1—C1106.95 (8)N2—C7—C8112.05 (14)
C1—S2—C389.70 (7)N2—C7—H7A109.2
O4—S3—O3118.92 (9)C8—C7—H7A109.2
O4—S3—N2109.63 (8)N2—C7—H7B109.2
O3—S3—N2108.14 (8)C8—C7—H7B109.2
O4—S3—C3109.63 (8)H7A—C7—H7B107.9
O3—S3—C3108.34 (8)C9—C8—C7112.58 (16)
N2—S3—C3100.62 (7)C9—C8—H8A109.1
C10—O5—C9114.96 (14)C7—C8—H8A109.1
S1—N1—H1A118.3 (14)C9—C8—H8B109.1
S1—N1—H1B118.6 (15)C7—C8—H8B109.1
H1A—N1—H1B112 (2)H8A—C8—H8B107.8
C6—N2—C7114.80 (13)O5—C9—C8112.38 (16)
C6—N2—S3110.94 (10)O5—C9—H9A109.1
C7—N2—S3116.48 (11)C8—C9—H9A109.1
C11—N3—C5116.46 (13)O5—C9—H9B109.1
C11—N3—H3105.9 (14)C8—C9—H9B109.1
C5—N3—H3106.0 (14)H9A—C9—H9B107.9
C2—C1—S2113.32 (10)O5—C10—H10A109.5
C2—C1—S1126.55 (10)O5—C10—H10B109.5
S2—C1—S1119.95 (9)H10A—C10—H10B109.5
C1—C2—C4112.31 (12)O5—C10—H10C109.5
C1—C2—H2123.8H10A—C10—H10C109.5
C4—C2—H2123.8H10B—C10—H10C109.5
C4—C3—S2113.72 (11)N3—C11—C12111.18 (16)
C4—C3—S3121.46 (12)N3—C11—H11A109.4
S2—C3—S3124.60 (9)C12—C11—H11A109.4
C3—C4—C2110.94 (13)N3—C11—H11B109.4
C3—C4—C5125.25 (13)C12—C11—H11B109.4
C2—C4—C5123.73 (13)H11A—C11—H11B108.0
N3—C5—C4113.21 (12)C11—C12—H12A109.5
N3—C5—C6109.05 (12)C11—C12—H12B109.5
C4—C5—C6112.84 (13)H12A—C12—H12B109.5
N3—C5—H5107.1C11—C12—H12C109.5
C4—C5—H5107.1H12A—C12—H12C109.5
C6—C5—H5107.1H12B—C12—H12C109.5
N2—C6—C5113.55 (12)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1B···O5i0.87 (1)1.98 (1)2.841 (2)177 (2)
N1—H1A···N3ii0.87 (1)2.03 (1)2.886 (2)171 (2)
N3—H3···O1iii0.86 (1)2.26 (1)3.042 (2)151 (2)
Symmetry codes: (i) x, y+1, z−1; (ii) x, y+1, z; (iii) −x, y−1/2, −z+1.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1B···O5i0.87 (1)1.975 (10)2.841 (2)177 (2)
N1—H1A···N3ii0.87 (1)2.027 (11)2.886 (2)171 (2)
N3—H3···O1iii0.86 (1)2.262 (13)3.042 (2)151 (2)
Symmetry codes: (i) x, y+1, z−1; (ii) x, y+1, z; (iii) −x, y−1/2, −z+1.

Experimental details

Crystal data
Chemical formulaC12H21N3O5S3
Mr383.50
Crystal system, space groupMonoclinic, P21
Temperature (K)293
a, b, c (Å)9.698 (2), 8.8127 (19), 10.133 (2)
β (°) 92.248 (3)
V (Å3)865.4 (3)
Z2
Radiation typeMo Kα
µ (mm−1)0.46
Crystal size (mm)0.35 × 0.35 × 0.20
Data collection
DiffractometerRigaku Mercury CCD
Absorption correctionMulti-scan
(CrystalClear; Rigaku, 2000)
Tmin, Tmax0.853, 0.913
No. of measured, independent and
observed [I > 2σ(I)] reflections		6608, 3684, 3612
Rint0.010
(sin θ/λ)max (Å−1)0.649
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.022, 0.059, 1.03
No. of reflections3684
No. of parameters222
No. of restraints4
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)0.21, −0.19
Absolute structure1595 Friedel pairs; Flack (1983)
Absolute structure parameter0.01 (4)

Computer programs: CrystalClear (Rigaku, 2000), SHELXS97 (Sheldrick, 2008), X-SEED (Barbour, 2001), SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).

 

Acknowledgements

The authors are grateful for a grant (No. 2015 J01599) from the Natural Science Foundation of Fujian Province.

References

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Journal logoCRYSTALLOGRAPHIC
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ISSN: 2056-9890
Volume 72| Part 5| May 2016| Pages 692-695
doi:10.1107/S2056989016006022
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