research communications
of Brinzolamide: a carbonic anhydrase inhibitor
aDepartment of Chemistry and Chemical Engineering, Minjiang University, Fuzhou 350108, People's Republic of China
*Correspondence e-mail: lby@mju.edu.cn
In 12H21N3O5S3 [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 of the molecule in the crystal was determined by [Flack parameter = 0.01 (4)].
of the title compound, CKeywords: crystal structure; Brinzolamide; carbonic anhydrase inhibitor; sulfonamide; thiazine; absolute configuration; hydrogen bonding.
CCDC reference: 1473394
1. Chemical context
The crystal structures of organic solids are dominated mainly by hydrogen-bonding interactions (Steiner, 2002). Hydrogen bonding plays a crucial role in 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 of Brinzolamide and the hydrogen-bonding interactions present in the crystal packing.
2. Structural commentary
The molecular structure of the title compound is shown in Fig. 1. The six-membered thiazine ring has an 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.
3. Supramolecular features
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).
4. Database survey
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 P21, with four independent molecules in the 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 with the N atom as the flap.
5. Synthesis and crystallization
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).
6. Refinement
Crystal data, data collection and structure . 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 of the molecule in the crystal was determined by [Flack parameter = 0.01 (4)].
details are summarized in Table 2Supporting information
CCDC reference: 1473394
10.1107/S2056989016006022/su5292sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: 10.1107/S2056989016006022/su5292Isup2.hkl
Supporting information file. DOI: 10.1107/S2056989016006022/su5292Isup3.cml
The crystal structures of organic solids are dominated mainly by hydrogen-bonding interactions (Steiner, 2002). Hydrogen bonding plays a crucial role in
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 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
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 P21, with four independent molecules in the 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 with the N atom as the flap.
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).
Crystal data, data collection and structure
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 of the molecule in the crystal was determined by [Flack parameter = 0.01 (4)].The crystal structures of organic solids are dominated mainly by hydrogen-bonding interactions (Steiner, 2002). Hydrogen bonding plays a crucial role in
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 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
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 P21, with four independent molecules in the 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 with the N atom as the flap.
For related literature, see: March (2000); Steiner (2002) Vippagunta (2001);
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).
detailsCrystal data, data collection and structure
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 of the molecule in the crystal was determined by [Flack parameter = 0.01 (4)].Data collection: CrystalClear (Rigaku, 2000); cell
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).Fig. 1. The molecular structure of the title compound, showing the atom labelling and 30% displacement ellipsoids. | |
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). | |
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). |
C12H21N3O5S3 | F(000) = 404 |
Mr = 383.50 | Dx = 1.472 Mg m−3 |
Monoclinic, P21 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2yb | Cell parameters from 2619 reflections |
a = 9.698 (2) Å | θ = 2.1–27.5° |
b = 8.8127 (19) Å | µ = 0.46 mm−1 |
c = 10.133 (2) Å | T = 293 K |
β = 92.248 (3)° | Prism, colourless |
V = 865.4 (3) Å3 | 0.35 × 0.35 × 0.20 mm |
Z = 2 |
Rigaku Mercury CCD diffractometer | 3684 independent reflections |
Radiation source: fine-focus sealed tube | 3612 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.010 |
Detector resolution: 14.6306 pixels mm-1 | θmax = 27.5°, θmin = 2.0° |
CCD_Profile_fitting scans | h = −12→12 |
Absorption correction: multi-scan (CrystalClear; Rigaku, 2000) | k = −11→11 |
Tmin = 0.853, Tmax = 0.913 | l = −13→13 |
6608 measured reflections |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.022 | H 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 reflections | Δρmax = 0.21 e Å−3 |
222 parameters | Δρmin = −0.19 e Å−3 |
4 restraints | Absolute structure: 1595 Friedel pairs; Flack (1983) |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: 0.01 (4) |
C12H21N3O5S3 | V = 865.4 (3) Å3 |
Mr = 383.50 | Z = 2 |
Monoclinic, P21 | Mo Kα radiation |
a = 9.698 (2) Å | µ = 0.46 mm−1 |
b = 8.8127 (19) Å | T = 293 K |
c = 10.133 (2) Å | 0.35 × 0.35 × 0.20 mm |
β = 92.248 (3)° |
Rigaku Mercury CCD diffractometer | 3684 independent reflections |
Absorption correction: multi-scan (CrystalClear; Rigaku, 2000) | 3612 reflections with I > 2σ(I) |
Tmin = 0.853, Tmax = 0.913 | Rint = 0.010 |
6608 measured reflections |
R[F2 > 2σ(F2)] = 0.022 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.059 | Δρmax = 0.21 e Å−3 |
S = 1.03 | Δρmin = −0.19 e Å−3 |
3684 reflections | Absolute structure: 1595 Friedel pairs; Flack (1983) |
222 parameters | Absolute structure parameter: 0.01 (4) |
4 restraints |
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. |
x | y | z | Uiso*/Ueq | ||
S1 | 0.08557 (3) | 0.95125 (4) | 0.63688 (3) | 0.02705 (9) | |
S2 | 0.26509 (4) | 0.81437 (4) | 0.85525 (3) | 0.02964 (9) | |
S3 | 0.37674 (4) | 0.52417 (4) | 0.99143 (4) | 0.03230 (9) | |
O1 | −0.02692 (13) | 0.88932 (16) | 0.55817 (13) | 0.0482 (3) | |
O2 | 0.05935 (13) | 1.05211 (14) | 0.74416 (12) | 0.0409 (3) | |
O3 | 0.51842 (12) | 0.50532 (17) | 0.96186 (14) | 0.0482 (3) | |
O4 | 0.34354 (16) | 0.59370 (17) | 1.11319 (11) | 0.0504 (3) | |
O5 | 0.14543 (15) | 0.01552 (16) | 1.26375 (12) | 0.0472 (3) | |
N1 | 0.19095 (16) | 1.02862 (18) | 0.54219 (13) | 0.0365 (3) | |
N2 | 0.30128 (13) | 0.35864 (15) | 0.97875 (12) | 0.0310 (3) | |
N3 | 0.29017 (12) | 0.32938 (16) | 0.60656 (12) | 0.0285 (3) | |
C1 | 0.17016 (14) | 0.79352 (17) | 0.70936 (12) | 0.0241 (3) | |
C2 | 0.16170 (15) | 0.64755 (17) | 0.66712 (13) | 0.0262 (3) | |
H2 | 0.1130 | 0.6168 | 0.5884 | 0.031* | |
C3 | 0.29337 (15) | 0.62151 (18) | 0.85939 (14) | 0.0269 (3) | |
C4 | 0.23410 (14) | 0.54569 (18) | 0.75421 (13) | 0.0248 (3) | |
C5 | 0.23691 (15) | 0.37508 (18) | 0.73479 (14) | 0.0262 (3) | |
H5 | 0.1394 | 0.3386 | 0.7368 | 0.031* | |
C6 | 0.31904 (17) | 0.29191 (18) | 0.84604 (15) | 0.0312 (3) | |
H6A | 0.2895 | 0.1844 | 0.8473 | 0.037* | |
H6B | 0.4182 | 0.2939 | 0.8264 | 0.037* | |
C7 | 0.15834 (18) | 0.3485 (2) | 1.02768 (17) | 0.0410 (4) | |
H7A | 0.0916 | 0.3777 | 0.9557 | 0.049* | |
H7B | 0.1486 | 0.4212 | 1.1012 | 0.049* | |
C8 | 0.12434 (19) | 0.1893 (2) | 1.07530 (16) | 0.0409 (4) | |
H8A | 0.0237 | 0.1818 | 1.0872 | 0.049* | |
H8B | 0.1489 | 0.1149 | 1.0069 | 0.049* | |
C9 | 0.2000 (2) | 0.1493 (2) | 1.20395 (16) | 0.0414 (4) | |
H9A | 0.2988 | 0.1329 | 1.1873 | 0.050* | |
H9B | 0.1935 | 0.2355 | 1.2661 | 0.050* | |
C10 | 0.1941 (2) | −0.1233 (3) | 1.2128 (2) | 0.0497 (5) | |
H10A | 0.1556 | −0.1381 | 1.1229 | 0.074* | |
H10B | 0.1652 | −0.2072 | 1.2690 | 0.074* | |
H10C | 0.2950 | −0.1209 | 1.2114 | 0.074* | |
C11 | 0.42904 (19) | 0.3825 (3) | 0.57763 (18) | 0.0499 (5) | |
H11A | 0.4982 | 0.3234 | 0.6305 | 0.060* | |
H11B | 0.4386 | 0.4905 | 0.6033 | 0.060* | |
C12 | 0.4563 (3) | 0.3657 (5) | 0.4339 (2) | 0.0923 (12) | |
H12A | 0.4480 | 0.2586 | 0.4087 | 0.138* | |
H12B | 0.5497 | 0.4016 | 0.4175 | 0.138* | |
H12C | 0.3890 | 0.4258 | 0.3816 | 0.138* | |
H3 | 0.2359 (17) | 0.369 (2) | 0.5477 (16) | 0.038 (5)* | |
H1A | 0.228 (2) | 1.1141 (16) | 0.566 (2) | 0.044 (6)* | |
H1B | 0.174 (2) | 1.024 (3) | 0.4577 (10) | 0.046 (5)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
S1 | 0.03112 (17) | 0.02019 (17) | 0.02929 (17) | 0.00014 (14) | −0.00565 (13) | 0.00508 (14) |
S2 | 0.04226 (19) | 0.01977 (18) | 0.02583 (16) | −0.00143 (14) | −0.01218 (13) | −0.00112 (14) |
S3 | 0.0398 (2) | 0.0277 (2) | 0.02842 (17) | 0.00293 (16) | −0.01163 (13) | 0.00436 (15) |
O1 | 0.0434 (7) | 0.0388 (7) | 0.0599 (8) | −0.0078 (6) | −0.0284 (6) | 0.0154 (6) |
O2 | 0.0534 (7) | 0.0300 (7) | 0.0398 (6) | 0.0094 (5) | 0.0096 (5) | 0.0022 (5) |
O3 | 0.0345 (6) | 0.0476 (8) | 0.0612 (8) | 0.0005 (6) | −0.0145 (5) | 0.0135 (7) |
O4 | 0.0838 (10) | 0.0383 (7) | 0.0280 (6) | 0.0073 (7) | −0.0134 (6) | −0.0016 (5) |
O5 | 0.0716 (9) | 0.0387 (7) | 0.0326 (6) | 0.0081 (7) | 0.0188 (6) | 0.0074 (6) |
N1 | 0.0563 (8) | 0.0259 (8) | 0.0274 (6) | −0.0088 (7) | 0.0012 (5) | 0.0046 (6) |
N2 | 0.0382 (6) | 0.0250 (7) | 0.0297 (6) | 0.0047 (5) | 0.0010 (5) | 0.0062 (5) |
N3 | 0.0306 (6) | 0.0254 (7) | 0.0291 (6) | −0.0013 (5) | −0.0040 (4) | −0.0020 (5) |
C1 | 0.0283 (6) | 0.0219 (8) | 0.0216 (6) | −0.0007 (5) | −0.0055 (5) | 0.0033 (5) |
C2 | 0.0324 (7) | 0.0211 (7) | 0.0246 (6) | −0.0015 (5) | −0.0064 (5) | 0.0004 (6) |
C3 | 0.0328 (7) | 0.0196 (8) | 0.0276 (7) | 0.0021 (6) | −0.0074 (5) | 0.0031 (6) |
C4 | 0.0279 (6) | 0.0205 (7) | 0.0257 (6) | 0.0010 (5) | −0.0037 (5) | 0.0025 (6) |
C5 | 0.0280 (6) | 0.0202 (7) | 0.0301 (7) | 0.0013 (5) | −0.0034 (5) | 0.0005 (6) |
C6 | 0.0394 (7) | 0.0217 (8) | 0.0322 (7) | 0.0059 (6) | −0.0008 (6) | 0.0026 (6) |
C7 | 0.0414 (8) | 0.0419 (11) | 0.0402 (8) | 0.0084 (7) | 0.0087 (6) | 0.0116 (7) |
C8 | 0.0458 (9) | 0.0453 (11) | 0.0317 (7) | −0.0054 (8) | 0.0035 (6) | 0.0066 (8) |
C9 | 0.0549 (10) | 0.0368 (10) | 0.0327 (8) | 0.0009 (8) | 0.0042 (7) | 0.0026 (7) |
C10 | 0.0651 (12) | 0.0380 (10) | 0.0462 (10) | 0.0054 (9) | 0.0051 (8) | −0.0013 (9) |
C11 | 0.0390 (9) | 0.0666 (13) | 0.0444 (9) | −0.0152 (9) | 0.0070 (7) | −0.0117 (10) |
C12 | 0.0653 (15) | 0.153 (4) | 0.0599 (14) | −0.0316 (19) | 0.0227 (11) | −0.0246 (18) |
S1—O1 | 1.4338 (12) | C4—C5 | 1.517 (2) |
S1—O2 | 1.4346 (13) | C5—C6 | 1.540 (2) |
S1—N1 | 1.5834 (14) | C5—H5 | 1.0000 |
S1—C1 | 1.7600 (15) | C6—H6A | 0.9900 |
S2—C1 | 1.7205 (13) | C6—H6B | 0.9900 |
S2—C3 | 1.7219 (16) | C7—C8 | 1.524 (3) |
S3—O4 | 1.4256 (14) | C7—H7A | 0.9900 |
S3—O3 | 1.4274 (14) | C7—H7B | 0.9900 |
S3—N2 | 1.6349 (15) | C8—C9 | 1.513 (2) |
S3—C3 | 1.7592 (14) | C8—H8A | 0.9900 |
O5—C10 | 1.416 (2) | C8—H8B | 0.9900 |
O5—C9 | 1.436 (2) | C9—H9A | 0.9900 |
N1—H1A | 0.866 (10) | C9—H9B | 0.9900 |
N1—H1B | 0.866 (9) | C10—H10A | 0.9800 |
N2—C6 | 1.484 (2) | C10—H10B | 0.9800 |
N2—C7 | 1.493 (2) | C10—H10C | 0.9800 |
N3—C11 | 1.466 (2) | C11—C12 | 1.497 (3) |
N3—C5 | 1.4731 (19) | C11—H11A | 0.9900 |
N3—H3 | 0.856 (9) | C11—H11B | 0.9900 |
C1—C2 | 1.357 (2) | C12—H12A | 0.9800 |
C2—C4 | 1.4245 (19) | C12—H12B | 0.9800 |
C2—H2 | 0.9500 | C12—H12C | 0.9800 |
C3—C4 | 1.365 (2) | ||
O1—S1—O2 | 120.25 (9) | N2—C6—H6A | 108.9 |
O1—S1—N1 | 108.78 (8) | C5—C6—H6A | 108.9 |
O2—S1—N1 | 109.28 (8) | N2—C6—H6B | 108.9 |
O1—S1—C1 | 105.28 (7) | C5—C6—H6B | 108.9 |
O2—S1—C1 | 105.47 (7) | H6A—C6—H6B | 107.7 |
N1—S1—C1 | 106.95 (8) | N2—C7—C8 | 112.05 (14) |
C1—S2—C3 | 89.70 (7) | N2—C7—H7A | 109.2 |
O4—S3—O3 | 118.92 (9) | C8—C7—H7A | 109.2 |
O4—S3—N2 | 109.63 (8) | N2—C7—H7B | 109.2 |
O3—S3—N2 | 108.14 (8) | C8—C7—H7B | 109.2 |
O4—S3—C3 | 109.63 (8) | H7A—C7—H7B | 107.9 |
O3—S3—C3 | 108.34 (8) | C9—C8—C7 | 112.58 (16) |
N2—S3—C3 | 100.62 (7) | C9—C8—H8A | 109.1 |
C10—O5—C9 | 114.96 (14) | C7—C8—H8A | 109.1 |
S1—N1—H1A | 118.3 (14) | C9—C8—H8B | 109.1 |
S1—N1—H1B | 118.6 (15) | C7—C8—H8B | 109.1 |
H1A—N1—H1B | 112 (2) | H8A—C8—H8B | 107.8 |
C6—N2—C7 | 114.80 (13) | O5—C9—C8 | 112.38 (16) |
C6—N2—S3 | 110.94 (10) | O5—C9—H9A | 109.1 |
C7—N2—S3 | 116.48 (11) | C8—C9—H9A | 109.1 |
C11—N3—C5 | 116.46 (13) | O5—C9—H9B | 109.1 |
C11—N3—H3 | 105.9 (14) | C8—C9—H9B | 109.1 |
C5—N3—H3 | 106.0 (14) | H9A—C9—H9B | 107.9 |
C2—C1—S2 | 113.32 (10) | O5—C10—H10A | 109.5 |
C2—C1—S1 | 126.55 (10) | O5—C10—H10B | 109.5 |
S2—C1—S1 | 119.95 (9) | H10A—C10—H10B | 109.5 |
C1—C2—C4 | 112.31 (12) | O5—C10—H10C | 109.5 |
C1—C2—H2 | 123.8 | H10A—C10—H10C | 109.5 |
C4—C2—H2 | 123.8 | H10B—C10—H10C | 109.5 |
C4—C3—S2 | 113.72 (11) | N3—C11—C12 | 111.18 (16) |
C4—C3—S3 | 121.46 (12) | N3—C11—H11A | 109.4 |
S2—C3—S3 | 124.60 (9) | C12—C11—H11A | 109.4 |
C3—C4—C2 | 110.94 (13) | N3—C11—H11B | 109.4 |
C3—C4—C5 | 125.25 (13) | C12—C11—H11B | 109.4 |
C2—C4—C5 | 123.73 (13) | H11A—C11—H11B | 108.0 |
N3—C5—C4 | 113.21 (12) | C11—C12—H12A | 109.5 |
N3—C5—C6 | 109.05 (12) | C11—C12—H12B | 109.5 |
C4—C5—C6 | 112.84 (13) | H12A—C12—H12B | 109.5 |
N3—C5—H5 | 107.1 | C11—C12—H12C | 109.5 |
C4—C5—H5 | 107.1 | H12A—C12—H12C | 109.5 |
C6—C5—H5 | 107.1 | H12B—C12—H12C | 109.5 |
N2—C6—C5 | 113.55 (12) |
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−1/2, −z+1. |
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1B···O5i | 0.87 (1) | 1.975 (10) | 2.841 (2) | 177 (2) |
N1—H1A···N3ii | 0.87 (1) | 2.027 (11) | 2.886 (2) | 171 (2) |
N3—H3···O1iii | 0.86 (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 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) |
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, 1.03 |
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) |
Absolute structure parameter | 0.01 (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.
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