Two polymorphs of the title organic salt (a very effective medicinal preparation with the commercial name thiotriazoline), C4H10NO+·C5H6N3O2S-, were obtained. The cations and anions are connected by hydrogen bonds and extend into two-dimensional networks. The main packing motifs are an R44(12) cluster in the monoclinic form and a chain in the orthorhombic form.
Supporting information
CCDC references: 718125; 718126
Compound (I) was prepared from a mixture of
(5-methyl-1H-1,2,4-triazol-3-ylsulfanyl)acetic acid and morpholine in
an equimolar ratio. The reaction was carried out in water, ethanol or
isopropanol solution. Crystals of the monoclinic polymorph were obtained from
the organic alhocols and crystals of the orthorhombic polymorph were obtained
from aqueous solution.
All H atoms in both structures were located in electron density difference maps.
The C-bound H atoms in the structure of the monoclinic modification were
included in the refinement in the riding model approximation, with
Uiso constrained to be 1.5 times Ueq of the carrier atom for
the methyl group and 1.2 times Ueq of the carrier atom for the other
atoms. The N-bound H atoms were refined in isotropic approximation. In the
structure of the orthorhombic modification, all H atoms were refined in
isotropic approximation.
For both compounds, data collection: CrysAlis CCD (Oxford Diffraction, 2007); cell refinement: CrysAlis RED (Oxford Diffraction, 2007); data reduction: CrysAlis RED (Oxford Diffraction, 2007); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).
(monoclinic_I) morpholin-4-ium
2-(5-methyl-1
H-1,2,4-triazol-3-ylsulfanyl)acetate
top
Crystal data top
C4H10NO+·C5H6N3O2S− | F(000) = 552 |
Mr = 260.32 | Dx = 1.410 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2ybc | Cell parameters from 1840 reflections |
a = 12.0500 (11) Å | θ = 3–35° |
b = 7.0380 (8) Å | µ = 0.27 mm−1 |
c = 15.6547 (14) Å | T = 293 K |
β = 112.559 (11)° | Plate, colourless |
V = 1226.1 (2) Å3 | 0.20 × 0.20 × 0.20 mm |
Z = 4 | |
Data collection top
Oxford Diffraction Xcalibur 3 diffractometer | 1289 reflections with I > 2σ(I) |
Radiation source: Enhance (Mo) X-ray Source | Rint = 0.041 |
Graphite monochromator | θmax = 25.0°, θmin = 2.8° |
Detector resolution: 16.1827 pixels mm-1 | h = −14→12 |
ω–scans | k = −8→8 |
4942 measured reflections | l = −18→15 |
2086 independent reflections | |
Refinement top
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.051 | Hydrogen site location: difference Fourier map |
wR(F2) = 0.143 | H atoms treated by a mixture of independent and constrained refinement |
S = 0.96 | w = 1/[σ2(Fo2) + (0.086P)2] where P = (Fo2 + 2Fc2)/3 |
2086 reflections | (Δ/σ)max < 0.001 |
167 parameters | Δρmax = 0.62 e Å−3 |
0 restraints | Δρmin = −0.23 e Å−3 |
Crystal data top
C4H10NO+·C5H6N3O2S− | V = 1226.1 (2) Å3 |
Mr = 260.32 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 12.0500 (11) Å | µ = 0.27 mm−1 |
b = 7.0380 (8) Å | T = 293 K |
c = 15.6547 (14) Å | 0.20 × 0.20 × 0.20 mm |
β = 112.559 (11)° | |
Data collection top
Oxford Diffraction Xcalibur 3 diffractometer | 1289 reflections with I > 2σ(I) |
4942 measured reflections | Rint = 0.041 |
2086 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.051 | 0 restraints |
wR(F2) = 0.143 | H atoms treated by a mixture of independent and constrained refinement |
S = 0.96 | Δρmax = 0.62 e Å−3 |
2086 reflections | Δρmin = −0.23 e Å−3 |
167 parameters | |
Special details top
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes)
are estimated using the full covariance matrix. The cell e.s.d.'s are taken
into account individually in the estimation of e.s.d.'s in distances, angles
and torsion angles; correlations between e.s.d.'s in cell parameters are only
used when they are defined by crystal symmetry. An approximate (isotropic)
treatment of cell e.s.d.'s is used for estimating e.s.d.'s 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 >
σ(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 | x | y | z | Uiso*/Ueq | |
N1 | 0.1964 (2) | 0.2898 (4) | 0.39636 (19) | 0.0428 (7) | |
H1N | 0.220 (3) | 0.279 (5) | 0.448 (3) | 0.064 (13)* | |
N2 | 0.2684 (2) | 0.2885 (4) | 0.34647 (15) | 0.0403 (7) | |
C3 | 0.1873 (2) | 0.3056 (4) | 0.26168 (18) | 0.0349 (7) | |
N4 | 0.0718 (2) | 0.3171 (4) | 0.25484 (16) | 0.0477 (7) | |
C5 | 0.0815 (2) | 0.3058 (5) | 0.3416 (2) | 0.0409 (8) | |
S6 | 0.22105 (6) | 0.31335 (14) | 0.16276 (5) | 0.0474 (3) | |
C7 | 0.3827 (2) | 0.3114 (5) | 0.21725 (19) | 0.0392 (8) | |
H7B | 0.4094 | 0.4181 | 0.2594 | 0.047* | |
H7A | 0.4088 | 0.1956 | 0.2530 | 0.047* | |
C8 | 0.4397 (3) | 0.3233 (4) | 0.14635 (19) | 0.0377 (7) | |
O9 | 0.55028 (19) | 0.3319 (4) | 0.17809 (15) | 0.0728 (9) | |
O10 | 0.37335 (18) | 0.3288 (3) | 0.06226 (13) | 0.0465 (6) | |
C11 | −0.0174 (3) | 0.3091 (6) | 0.3765 (2) | 0.0628 (11) | |
H11C | −0.0638 | 0.1946 | 0.3582 | 0.094* | |
H11B | −0.0682 | 0.4169 | 0.3511 | 0.094* | |
H11A | 0.0162 | 0.3180 | 0.4428 | 0.094* | |
N12 | 0.6517 (2) | 0.3438 (4) | 0.05237 (19) | 0.0429 (7) | |
H12B | 0.640 (2) | 0.465 (5) | 0.020 (2) | 0.051 (9)* | |
H12A | 0.617 (3) | 0.345 (4) | 0.090 (2) | 0.041 (9)* | |
C13 | 0.7814 (2) | 0.3062 (5) | 0.10850 (19) | 0.0426 (8) | |
H13B | 0.7895 | 0.1912 | 0.1445 | 0.051* | |
H13A | 0.8154 | 0.4108 | 0.1509 | 0.051* | |
C14 | 0.8474 (3) | 0.2843 (5) | 0.0448 (2) | 0.0491 (9) | |
H14B | 0.8437 | 0.4029 | 0.0122 | 0.059* | |
H14A | 0.9313 | 0.2564 | 0.0810 | 0.059* | |
O15 | 0.79727 (19) | 0.1363 (3) | −0.02043 (15) | 0.0518 (6) | |
C16 | 0.6757 (3) | 0.1787 (5) | −0.0769 (2) | 0.0474 (8) | |
H16B | 0.6433 | 0.0790 | −0.1225 | 0.057* | |
H16A | 0.6723 | 0.2972 | −0.1095 | 0.057* | |
C17 | 0.6008 (3) | 0.1955 (5) | −0.0192 (2) | 0.0486 (8) | |
H17B | 0.5189 | 0.2284 | −0.0585 | 0.058* | |
H17A | 0.5995 | 0.0746 | 0.0102 | 0.058* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
N1 | 0.0415 (15) | 0.0611 (19) | 0.0305 (15) | −0.0002 (13) | 0.0191 (12) | −0.0017 (14) |
N2 | 0.0348 (13) | 0.0602 (18) | 0.0284 (13) | −0.0009 (12) | 0.0147 (10) | −0.0003 (12) |
C3 | 0.0320 (15) | 0.0446 (19) | 0.0301 (15) | −0.0044 (13) | 0.0143 (12) | −0.0005 (13) |
N4 | 0.0307 (13) | 0.077 (2) | 0.0350 (14) | 0.0036 (13) | 0.0127 (10) | 0.0026 (14) |
C5 | 0.0322 (15) | 0.055 (2) | 0.0388 (17) | −0.0034 (14) | 0.0170 (13) | −0.0018 (15) |
S6 | 0.0338 (4) | 0.0817 (7) | 0.0268 (4) | −0.0008 (4) | 0.0119 (3) | 0.0018 (4) |
C7 | 0.0337 (15) | 0.059 (2) | 0.0280 (15) | 0.0042 (14) | 0.0152 (12) | −0.0001 (14) |
C8 | 0.0410 (17) | 0.046 (2) | 0.0287 (15) | 0.0017 (14) | 0.0166 (13) | −0.0002 (14) |
O9 | 0.0363 (13) | 0.149 (3) | 0.0386 (13) | −0.0040 (13) | 0.0203 (10) | 0.0042 (14) |
O10 | 0.0490 (12) | 0.0671 (17) | 0.0240 (10) | −0.0031 (11) | 0.0146 (9) | 0.0039 (10) |
C11 | 0.0458 (19) | 0.095 (3) | 0.057 (2) | −0.0040 (19) | 0.0302 (16) | 0.000 (2) |
N12 | 0.0374 (14) | 0.059 (2) | 0.0377 (15) | 0.0038 (13) | 0.0208 (12) | 0.0070 (14) |
C13 | 0.0360 (16) | 0.055 (2) | 0.0351 (16) | 0.0074 (14) | 0.0113 (13) | −0.0003 (15) |
C14 | 0.0368 (17) | 0.064 (2) | 0.0476 (19) | 0.0009 (15) | 0.0174 (14) | 0.0003 (18) |
O15 | 0.0496 (13) | 0.0649 (17) | 0.0445 (13) | 0.0094 (11) | 0.0222 (10) | −0.0037 (11) |
C16 | 0.0454 (18) | 0.056 (2) | 0.0369 (17) | −0.0019 (16) | 0.0116 (13) | −0.0033 (16) |
C17 | 0.0380 (16) | 0.055 (2) | 0.0501 (19) | −0.0009 (15) | 0.0142 (14) | −0.0039 (17) |
Geometric parameters (Å, º) top
N1—C5 | 1.325 (4) | N12—C17 | 1.481 (4) |
N1—N2 | 1.371 (3) | N12—C13 | 1.493 (4) |
N1—H1N | 0.74 (4) | N12—H12B | 0.98 (3) |
N2—C3 | 1.317 (3) | N12—H12A | 0.85 (3) |
C3—N4 | 1.356 (4) | C13—C14 | 1.503 (4) |
C3—S6 | 1.746 (3) | C13—H13B | 0.9700 |
N4—C5 | 1.320 (4) | C13—H13A | 0.9700 |
C5—C11 | 1.490 (4) | C14—O15 | 1.421 (4) |
S6—C7 | 1.802 (3) | C14—H14B | 0.9700 |
C7—C8 | 1.515 (4) | C14—H14A | 0.9700 |
C7—H7B | 0.9700 | O15—C16 | 1.422 (3) |
C7—H7A | 0.9700 | C16—C17 | 1.507 (5) |
C8—O9 | 1.232 (3) | C16—H16B | 0.9700 |
C8—O10 | 1.251 (3) | C16—H16A | 0.9700 |
C11—H11C | 0.9600 | C17—H17B | 0.9700 |
C11—H11B | 0.9600 | C17—H17A | 0.9700 |
C11—H11A | 0.9600 | | |
| | | |
C5—N1—N2 | 111.3 (2) | C13—N12—H12B | 111.7 (16) |
C5—N1—H1N | 125 (3) | C17—N12—H12A | 111 (2) |
N2—N1—H1N | 123 (3) | C13—N12—H12A | 106 (2) |
C3—N2—N1 | 100.8 (2) | H12B—N12—H12A | 110 (3) |
N2—C3—N4 | 115.3 (2) | N12—C13—C14 | 109.2 (2) |
N2—C3—S6 | 124.2 (2) | N12—C13—H13B | 109.8 |
N4—C3—S6 | 120.6 (2) | C14—C13—H13B | 109.8 |
C5—N4—C3 | 103.4 (2) | N12—C13—H13A | 109.8 |
N4—C5—N1 | 109.2 (3) | C14—C13—H13A | 109.8 |
N4—C5—C11 | 127.5 (3) | H13B—C13—H13A | 108.3 |
N1—C5—C11 | 123.2 (3) | O15—C14—C13 | 111.4 (3) |
C3—S6—C7 | 99.05 (13) | O15—C14—H14B | 109.4 |
C8—C7—S6 | 111.36 (19) | C13—C14—H14B | 109.4 |
C8—C7—H7B | 109.4 | O15—C14—H14A | 109.4 |
S6—C7—H7B | 109.4 | C13—C14—H14A | 109.4 |
C8—C7—H7A | 109.4 | H14B—C14—H14A | 108.0 |
S6—C7—H7A | 109.4 | C14—O15—C16 | 110.2 (2) |
H7B—C7—H7A | 108.0 | O15—C16—C17 | 110.8 (2) |
O9—C8—O10 | 125.3 (3) | O15—C16—H16B | 109.5 |
O9—C8—C7 | 115.5 (2) | C17—C16—H16B | 109.5 |
O10—C8—C7 | 119.1 (2) | O15—C16—H16A | 109.5 |
C5—C11—H11C | 109.5 | C17—C16—H16A | 109.5 |
C5—C11—H11B | 109.5 | H16B—C16—H16A | 108.1 |
H11C—C11—H11B | 109.5 | N12—C17—C16 | 109.8 (3) |
C5—C11—H11A | 109.5 | N12—C17—H17B | 109.7 |
H11C—C11—H11A | 109.5 | C16—C17—H17B | 109.7 |
H11B—C11—H11A | 109.5 | N12—C17—H17A | 109.7 |
C17—N12—C13 | 110.9 (3) | C16—C17—H17A | 109.7 |
C17—N12—H12B | 106.4 (17) | H17B—C17—H17A | 108.2 |
| | | |
C5—N1—N2—C3 | 0.3 (4) | N4—C3—S6—C7 | 175.7 (3) |
N1—N2—C3—N4 | −0.1 (4) | C3—S6—C7—C8 | −178.3 (2) |
N1—N2—C3—S6 | 180.0 (2) | S6—C7—C8—O9 | 176.7 (3) |
N2—C3—N4—C5 | −0.2 (4) | S6—C7—C8—O10 | −1.4 (4) |
S6—C3—N4—C5 | 179.8 (2) | C17—N12—C13—C14 | 53.9 (4) |
C3—N4—C5—N1 | 0.4 (4) | N12—C13—C14—O15 | −57.5 (4) |
C3—N4—C5—C11 | −179.4 (4) | C13—C14—O15—C16 | 61.6 (3) |
N2—N1—C5—N4 | −0.5 (4) | C14—O15—C16—C17 | −61.1 (4) |
N2—N1—C5—C11 | 179.4 (3) | C13—N12—C17—C16 | −54.2 (4) |
N2—C3—S6—C7 | −4.4 (3) | O15—C16—C17—N12 | 57.6 (4) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1N···O10i | 0.74 (4) | 2.16 (4) | 2.782 (3) | 142 (4) |
N12—H12A···O9 | 0.85 (3) | 1.84 (4) | 2.687 (3) | 175 (3) |
N12—H12B···O10ii | 0.98 (3) | 1.90 (4) | 2.864 (4) | 168 (3) |
C14—H14A···N4iii | 0.97 | 2.63 | 3.370 (4) | 133 |
Symmetry codes: (i) x, −y+1/2, z+1/2; (ii) −x+1, −y+1, −z; (iii) x+1, y, z. |
(orthorhombic_I) morpholin-4-ium
2-(5-methyl-1
H-1,2,4-triazol-3-ylsulfanyl)acetate
top
Crystal data top
C4H10NO+·C5H6N3O2S− | F(000) = 1104 |
Mr = 260.32 | Dx = 1.410 Mg m−3 |
Orthorhombic, Pbca | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2ac 2ab | Cell parameters from 5833 reflections |
a = 9.6912 (2) Å | θ = 3–35° |
b = 8.3829 (2) Å | µ = 0.27 mm−1 |
c = 30.1907 (8) Å | T = 293 K |
V = 2452.70 (10) Å3 | Parallelepiped, colourless |
Z = 8 | 0.40 × 0.10 × 0.10 mm |
Data collection top
Oxford Diffraction Xcalibur 3 diffractometer | 2183 reflections with I > 2σ(I) |
Radiation source: Enhance (Mo) X-ray Source | Rint = 0.041 |
Graphite monochromator | θmax = 30.0°, θmin = 3.3° |
Detector resolution: 16.1827 pixels mm-1 | h = −13→8 |
ω–scans | k = −11→10 |
18044 measured reflections | l = −42→39 |
3481 independent reflections | |
Refinement top
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.034 | Hydrogen site location: difference Fourier map |
wR(F2) = 0.087 | All H-atom parameters refined |
S = 0.92 | w = 1/[σ2(Fo2) + (0.0484P)2] where P = (Fo2 + 2Fc2)/3 |
3481 reflections | (Δ/σ)max = 0.006 |
218 parameters | Δρmax = 0.23 e Å−3 |
0 restraints | Δρmin = −0.21 e Å−3 |
Crystal data top
C4H10NO+·C5H6N3O2S− | V = 2452.70 (10) Å3 |
Mr = 260.32 | Z = 8 |
Orthorhombic, Pbca | Mo Kα radiation |
a = 9.6912 (2) Å | µ = 0.27 mm−1 |
b = 8.3829 (2) Å | T = 293 K |
c = 30.1907 (8) Å | 0.40 × 0.10 × 0.10 mm |
Data collection top
Oxford Diffraction Xcalibur 3 diffractometer | 2183 reflections with I > 2σ(I) |
18044 measured reflections | Rint = 0.041 |
3481 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.034 | 0 restraints |
wR(F2) = 0.087 | All H-atom parameters refined |
S = 0.92 | Δρmax = 0.23 e Å−3 |
3481 reflections | Δρmin = −0.21 e Å−3 |
218 parameters | |
Special details top
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes)
are estimated using the full covariance matrix. The cell e.s.d.'s are taken
into account individually in the estimation of e.s.d.'s in distances, angles
and torsion angles; correlations between e.s.d.'s in cell parameters are only
used when they are defined by crystal symmetry. An approximate (isotropic)
treatment of cell e.s.d.'s is used for estimating e.s.d.'s 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 >
σ(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 | x | y | z | Uiso*/Ueq | |
N1 | 0.26645 (13) | 0.24052 (15) | 0.50982 (4) | 0.0346 (3) | |
H1N | 0.3419 (18) | 0.2653 (19) | 0.4999 (5) | 0.036 (4)* | |
N2 | 0.25287 (13) | 0.14007 (15) | 0.54554 (4) | 0.0349 (3) | |
C3 | 0.11792 (13) | 0.12647 (15) | 0.54825 (4) | 0.0271 (3) | |
N4 | 0.04565 (12) | 0.21012 (14) | 0.51724 (4) | 0.0323 (3) | |
C5 | 0.14480 (14) | 0.27961 (16) | 0.49350 (4) | 0.0305 (3) | |
S6 | 0.03219 (4) | 0.00659 (4) | 0.586796 (12) | 0.03460 (11) | |
C7 | 0.17827 (16) | −0.0493 (2) | 0.62038 (5) | 0.0355 (3) | |
H7B | 0.252 (2) | −0.092 (2) | 0.6014 (6) | 0.064 (5)* | |
H7A | 0.209 (2) | 0.039 (2) | 0.6362 (6) | 0.055 (5)* | |
C8 | 0.14342 (14) | −0.18070 (16) | 0.65299 (4) | 0.0289 (3) | |
O9 | 0.23464 (11) | −0.21273 (12) | 0.68103 (3) | 0.0405 (3) | |
O10 | 0.03083 (11) | −0.25095 (13) | 0.64936 (4) | 0.0427 (3) | |
C11 | 0.1249 (2) | 0.3850 (2) | 0.45446 (6) | 0.0437 (4) | |
H11C | 0.069 (3) | 0.472 (3) | 0.4627 (7) | 0.082 (8)* | |
H11B | 0.081 (3) | 0.329 (3) | 0.4323 (7) | 0.080 (7)* | |
H11A | 0.210 (2) | 0.420 (3) | 0.4436 (6) | 0.076 (7)* | |
N12 | 0.47658 (14) | −0.04594 (16) | 0.68622 (4) | 0.0344 (3) | |
H12B | 0.4645 (17) | 0.052 (2) | 0.6744 (5) | 0.044 (5)* | |
H12A | 0.399 (2) | −0.095 (2) | 0.6855 (6) | 0.061 (6)* | |
C13 | 0.57932 (19) | −0.1300 (2) | 0.65842 (6) | 0.0451 (4) | |
H13A | 0.586 (2) | −0.236 (2) | 0.6694 (6) | 0.050 (5)* | |
H13B | 0.547 (2) | −0.132 (2) | 0.6311 (6) | 0.059 (6)* | |
C14 | 0.71394 (18) | −0.0426 (2) | 0.66022 (6) | 0.0456 (4) | |
H14A | 0.7002 (19) | 0.066 (2) | 0.6464 (6) | 0.053 (5)* | |
H14B | 0.786 (2) | −0.100 (2) | 0.6441 (6) | 0.061 (5)* | |
O15 | 0.76199 (11) | −0.02759 (14) | 0.70427 (4) | 0.0477 (3) | |
C16 | 0.66446 (17) | 0.0580 (2) | 0.73056 (6) | 0.0445 (4) | |
H16B | 0.6500 (16) | 0.169 (2) | 0.7184 (5) | 0.041 (4)* | |
H16A | 0.7015 (18) | 0.060 (2) | 0.7588 (6) | 0.052 (5)* | |
C17 | 0.52916 (18) | −0.0286 (2) | 0.73221 (5) | 0.0421 (4) | |
H17C | 0.5378 (19) | −0.136 (2) | 0.7428 (6) | 0.061 (5)* | |
H17A | 0.462 (2) | 0.022 (2) | 0.7487 (6) | 0.057 (6)* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
N1 | 0.0224 (6) | 0.0414 (7) | 0.0399 (7) | −0.0024 (5) | 0.0039 (5) | 0.0106 (5) |
N2 | 0.0237 (6) | 0.0404 (7) | 0.0406 (6) | −0.0012 (5) | 0.0002 (5) | 0.0114 (5) |
C3 | 0.0225 (7) | 0.0300 (7) | 0.0287 (6) | −0.0004 (6) | 0.0008 (5) | 0.0019 (5) |
N4 | 0.0235 (6) | 0.0376 (6) | 0.0358 (6) | −0.0015 (5) | −0.0011 (5) | 0.0085 (5) |
C5 | 0.0268 (7) | 0.0329 (7) | 0.0320 (7) | −0.0017 (6) | −0.0010 (6) | 0.0019 (6) |
S6 | 0.02316 (17) | 0.0430 (2) | 0.03765 (18) | −0.00426 (16) | −0.00057 (15) | 0.01264 (15) |
C7 | 0.0305 (8) | 0.0376 (8) | 0.0386 (8) | −0.0095 (7) | −0.0086 (6) | 0.0112 (7) |
C8 | 0.0286 (7) | 0.0268 (7) | 0.0312 (7) | 0.0003 (6) | 0.0015 (6) | 0.0006 (5) |
O9 | 0.0384 (6) | 0.0408 (6) | 0.0424 (5) | −0.0071 (5) | −0.0106 (5) | 0.0129 (5) |
O10 | 0.0300 (6) | 0.0440 (6) | 0.0541 (6) | −0.0114 (5) | −0.0036 (5) | 0.0174 (5) |
C11 | 0.0416 (10) | 0.0508 (10) | 0.0387 (9) | −0.0067 (9) | −0.0027 (8) | 0.0156 (8) |
N12 | 0.0238 (6) | 0.0327 (7) | 0.0468 (7) | −0.0028 (6) | −0.0032 (5) | 0.0082 (5) |
C13 | 0.0464 (10) | 0.0429 (10) | 0.0461 (9) | 0.0027 (8) | −0.0041 (8) | −0.0074 (8) |
C14 | 0.0355 (9) | 0.0563 (11) | 0.0452 (9) | 0.0059 (8) | 0.0057 (7) | −0.0044 (8) |
O15 | 0.0247 (5) | 0.0678 (8) | 0.0506 (6) | 0.0072 (5) | −0.0045 (5) | 0.0011 (5) |
C16 | 0.0351 (9) | 0.0595 (11) | 0.0389 (9) | −0.0014 (8) | −0.0059 (7) | −0.0038 (8) |
C17 | 0.0351 (9) | 0.0531 (11) | 0.0380 (8) | 0.0006 (8) | 0.0062 (7) | 0.0076 (7) |
Geometric parameters (Å, º) top
N1—C5 | 1.3191 (17) | N12—C13 | 1.481 (2) |
N1—N2 | 1.3746 (16) | N12—C17 | 1.486 (2) |
N1—H1N | 0.816 (17) | N12—H12B | 0.905 (18) |
N2—C3 | 1.3154 (17) | N12—H12A | 0.86 (2) |
C3—N4 | 1.3633 (16) | C13—C14 | 1.497 (2) |
C3—S6 | 1.7478 (13) | C13—H13A | 0.948 (18) |
N4—C5 | 1.3328 (17) | C13—H13B | 0.882 (18) |
C5—C11 | 1.486 (2) | C14—O15 | 1.415 (2) |
S6—C7 | 1.8032 (15) | C14—H14A | 1.014 (18) |
C7—C8 | 1.5155 (19) | C14—H14B | 0.98 (2) |
C7—H7B | 0.98 (2) | O15—C16 | 1.428 (2) |
C7—H7A | 0.926 (19) | C16—C17 | 1.500 (2) |
C8—O10 | 1.2447 (16) | C16—H16B | 1.013 (17) |
C8—O9 | 1.2531 (16) | C16—H16A | 0.925 (18) |
C11—H11C | 0.94 (3) | C17—H17C | 0.96 (2) |
C11—H11B | 0.92 (2) | C17—H17A | 0.92 (2) |
C11—H11A | 0.94 (2) | | |
| | | |
C5—N1—N2 | 111.08 (12) | C17—N12—H12B | 108.8 (10) |
C5—N1—H1N | 126.9 (11) | C13—N12—H12A | 110.0 (13) |
N2—N1—H1N | 121.9 (11) | C17—N12—H12A | 111.9 (12) |
C3—N2—N1 | 101.36 (11) | H12B—N12—H12A | 108.5 (17) |
N2—C3—N4 | 115.06 (11) | N12—C13—C14 | 109.41 (14) |
N2—C3—S6 | 124.32 (10) | N12—C13—H13A | 107.0 (11) |
N4—C3—S6 | 120.58 (10) | C14—C13—H13A | 112.8 (12) |
C5—N4—C3 | 102.93 (11) | N12—C13—H13B | 107.6 (12) |
N1—C5—N4 | 109.57 (12) | C14—C13—H13B | 110.6 (13) |
N1—C5—C11 | 124.05 (13) | H13A—C13—H13B | 109.3 (17) |
N4—C5—C11 | 126.39 (13) | O15—C14—C13 | 111.38 (14) |
C3—S6—C7 | 98.66 (7) | O15—C14—H14A | 110.5 (10) |
C8—C7—S6 | 112.28 (10) | C13—C14—H14A | 108.2 (11) |
C8—C7—H7B | 106.0 (12) | O15—C14—H14B | 106.0 (10) |
S6—C7—H7B | 109.8 (11) | C13—C14—H14B | 111.4 (11) |
C8—C7—H7A | 108.4 (11) | H14A—C14—H14B | 109.3 (15) |
S6—C7—H7A | 109.4 (12) | C14—O15—C16 | 110.45 (12) |
H7B—C7—H7A | 111.0 (17) | O15—C16—C17 | 110.74 (15) |
O10—C8—O9 | 125.21 (13) | O15—C16—H16B | 110.7 (9) |
O10—C8—C7 | 118.82 (12) | C17—C16—H16B | 109.7 (9) |
O9—C8—C7 | 115.93 (12) | O15—C16—H16A | 105.3 (11) |
C5—C11—H11C | 109.1 (14) | C17—C16—H16A | 108.4 (11) |
C5—C11—H11B | 109.3 (14) | H16B—C16—H16A | 111.9 (14) |
H11C—C11—H11B | 109 (2) | N12—C17—C16 | 108.43 (13) |
C5—C11—H11A | 110.4 (13) | N12—C17—H17C | 104.4 (11) |
H11C—C11—H11A | 111 (2) | C16—C17—H17C | 112.9 (11) |
H11B—C11—H11A | 108.5 (18) | N12—C17—H17A | 108.0 (12) |
C13—N12—C17 | 110.22 (13) | C16—C17—H17A | 114.1 (11) |
C13—N12—H12B | 107.3 (10) | H17C—C17—H17A | 108.4 (15) |
| | | |
C5—N1—N2—C3 | −0.33 (15) | N4—C3—S6—C7 | −174.01 (12) |
N1—N2—C3—N4 | −0.07 (15) | C3—S6—C7—C8 | −169.46 (11) |
N1—N2—C3—S6 | 177.82 (10) | S6—C7—C8—O10 | 10.35 (19) |
N2—C3—N4—C5 | 0.43 (16) | S6—C7—C8—O9 | −171.77 (11) |
S6—C3—N4—C5 | −177.55 (10) | C17—N12—C13—C14 | −55.96 (19) |
N2—N1—C5—N4 | 0.62 (17) | N12—C13—C14—O15 | 57.3 (2) |
N2—N1—C5—C11 | −179.22 (15) | C13—C14—O15—C16 | −59.87 (19) |
C3—N4—C5—N1 | −0.61 (15) | C14—O15—C16—C17 | 61.11 (19) |
C3—N4—C5—C11 | 179.23 (16) | C13—N12—C17—C16 | 56.95 (19) |
N2—C3—S6—C7 | 8.21 (14) | O15—C16—C17—N12 | −59.27 (19) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1N···N4i | 0.816 (17) | 2.052 (18) | 2.8566 (17) | 168.4 (16) |
N12—H12A···O9 | 0.86 (2) | 1.88 (2) | 2.7344 (17) | 176.3 (19) |
N12—H12B···O10ii | 0.905 (18) | 1.815 (18) | 2.7127 (17) | 171.1 (16) |
Symmetry codes: (i) x+1/2, −y+1/2, −z+1; (ii) −x+1/2, y+1/2, z. |
Experimental details
| (monoclinic_I) | (orthorhombic_I) |
Crystal data |
Chemical formula | C4H10NO+·C5H6N3O2S− | C4H10NO+·C5H6N3O2S− |
Mr | 260.32 | 260.32 |
Crystal system, space group | Monoclinic, P21/c | Orthorhombic, Pbca |
Temperature (K) | 293 | 293 |
a, b, c (Å) | 12.0500 (11), 7.0380 (8), 15.6547 (14) | 9.6912 (2), 8.3829 (2), 30.1907 (8) |
α, β, γ (°) | 90, 112.559 (11), 90 | 90, 90, 90 |
V (Å3) | 1226.1 (2) | 2452.70 (10) |
Z | 4 | 8 |
Radiation type | Mo Kα | Mo Kα |
µ (mm−1) | 0.27 | 0.27 |
Crystal size (mm) | 0.20 × 0.20 × 0.20 | 0.40 × 0.10 × 0.10 |
|
Data collection |
Diffractometer | Oxford Diffraction Xcalibur 3 diffractometer | Oxford Diffraction Xcalibur 3 diffractometer |
Absorption correction | – | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 4942, 2086, 1289 | 18044, 3481, 2183 |
Rint | 0.041 | 0.041 |
(sin θ/λ)max (Å−1) | 0.594 | 0.703 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.051, 0.143, 0.96 | 0.034, 0.087, 0.92 |
No. of reflections | 2086 | 3481 |
No. of parameters | 167 | 218 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement | All H-atom parameters refined |
Δρmax, Δρmin (e Å−3) | 0.62, −0.23 | 0.23, −0.21 |
Selected bond lengths (Å) for (monoclinic_I) topN1—C5 | 1.325 (4) | S6—C7 | 1.802 (3) |
N1—N2 | 1.371 (3) | C7—C8 | 1.515 (4) |
N2—C3 | 1.317 (3) | C8—O9 | 1.232 (3) |
C3—N4 | 1.356 (4) | C8—O10 | 1.251 (3) |
C3—S6 | 1.746 (3) | N12—C17 | 1.481 (4) |
N4—C5 | 1.320 (4) | N12—C13 | 1.493 (4) |
C5—C11 | 1.490 (4) | | |
Hydrogen-bond geometry (Å, º) for (monoclinic_I) top
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1N···O10i | 0.74 (4) | 2.16 (4) | 2.782 (3) | 142 (4) |
N12—H12A···O9 | 0.85 (3) | 1.84 (4) | 2.687 (3) | 175 (3) |
N12—H12B···O10ii | 0.98 (3) | 1.90 (4) | 2.864 (4) | 168 (3) |
C14—H14A···N4iii | 0.97 | 2.63 | 3.370 (4) | 133 |
Symmetry codes: (i) x, −y+1/2, z+1/2; (ii) −x+1, −y+1, −z; (iii) x+1, y, z. |
Selected bond lengths (Å) for (orthorhombic_I) topN1—C5 | 1.3191 (17) | S6—C7 | 1.8032 (15) |
N1—N2 | 1.3746 (16) | C7—C8 | 1.5155 (19) |
N2—C3 | 1.3154 (17) | C8—O10 | 1.2447 (16) |
C3—N4 | 1.3633 (16) | C8—O9 | 1.2531 (16) |
C3—S6 | 1.7478 (13) | N12—C13 | 1.481 (2) |
N4—C5 | 1.3328 (17) | N12—C17 | 1.486 (2) |
C5—C11 | 1.486 (2) | | |
Hydrogen-bond geometry (Å, º) for (orthorhombic_I) top
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1N···N4i | 0.816 (17) | 2.052 (18) | 2.8566 (17) | 168.4 (16) |
N12—H12A···O9 | 0.86 (2) | 1.88 (2) | 2.7344 (17) | 176.3 (19) |
N12—H12B···O10ii | 0.905 (18) | 1.815 (18) | 2.7127 (17) | 171.1 (16) |
Symmetry codes: (i) x+1/2, −y+1/2, −z+1; (ii) −x+1/2, y+1/2, z. |
Derivatives of thiotriazole represent a class of organic compounds with a wide range of biological activity (Kim et al., 1994; Gilbert et al., 1995; Davydov & Shvets, 2002; Meinhardt et al., 2002). The title complound, (I), is known (Mazur et al., 2007) as a very effective medicinal preparation with the commercial name thiotriazoline. It shows antioxidant, membrane-stabilizing, anti-ischemic, anti-arrhythmic, immunomodulatory, antiphlogistic, hepatoprotector, cardioprotector, tread and nephroprotector activities. It is well known also that polymorphism is very important for medical products that are produced as pills (Bernstein, 2002). In this paper we report the results of an investigation of the molecular and crystal structure of two polymorphic modifications of the medical product thiotriazoline.
During crystallization of thiotriazoline it was found that crystals of (I) grown from water and organic alcohols differ in shape. The X-ray diffraction study demonstrates that these represent two polymorphic modifications of thiotriazoline, namely an orthorhombic modification (OM) crystallized from aqueous solution and a monoclinic modification (MM) obtained from alcohol solution.
The analysis of the molecular structure of (I) in both modifications demonstrates that this compound represents organic salts (Fig. 1 and 2). Two H atoms on the N atom of the morpholine ring were located from electron density difference maps, and the Csp3—N bond lengths are very close (Tables 1 and 3) to the mean value 1.494 Å (Bürgi & Dunitz, 1994) for (Csp3)2—NH2+ bonds (the corresponding bond length in the nonprotonated morpholine ring is 1.473 Å). Thus it is possible to conclude that the positive charge is located on the protonated N atom of the morpholine ring. The C—O bond lengths of the carboxylate group are almost equal and they are very close to the mean value of the bond length in the carboxylate anion (1.250 Å). This indicates the localization of the negative charge within the carboxylate group. It is noted also that the bond lengths of the cation and anion are very close for both polymorphic modifications.
The morpholine ring adopts a chair conformation in both modifications [the puckering parameters (Zefirov et al., 1990) are S = 1.19, θ = 2.8°, ψ = 2.9° for MM, and S = 1.20, θ = 1.6°, ψ = 23.5° for OM]. The deviations of atoms N12 and O15 from the mean-square plane of the remaining atoms of the ring are 0.644 (3) and -0.667 (2) Å, respectively, in MM, and -0.669 (1) and 0.659 (1) Å, respectively, in OM. The anion is planar, in contrast to the neutral molecule of (5-methyl-1H-1,2,4-triazol-3-ylsulfanyl)acetate (Zubatyuk et al., 2008).
Analysis of the crystal structure of the two polymorphic modifications demonstrates the existence of hydrogen-bonded two-dimensional-networks in both modifications. However, the organization of these networks differs in the two polymorphs. In the crystal structure of MM, two pairs of cations and anions form an R44(12) cluster (Fig. 3) based on the N12—H12A···O9 and N12—H12B···O10(-x + 1, -y + 1, -z) strong hydrogen bonds (Table 2). The clusters are organized in layers (Fig. 4) that are parallel to the (100) plane. The molecules within the layer are connected by weaker N1—H1N···O10(x, -y + 1/2, z + 1/2) and C14—H14A···N4(x + 1, y, z) hydrogen bonds (Table 3). In the crystal structure of OM, the cations and anions form infinite zigzag chains (Fig. 5) along the [010] crystallographic direction owing to the formation of intermolecular N12—H12A···O9 and N12—H12B···O10(-x + 1/2, y + 1/2, z) hydrogen bonds (Table 4). Neighbouring chains are linked by an N1—H1N···N4(x + 1/2, -y + 1/2, -z + 1) hydrogen bond, forming layers parallel to (001) (Fig. 6).