organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

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ISSN: 2414-3146

Meloxicam hydro­chloride

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aFacultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, 72570 Puebla, Pue., Mexico, and bInstituto de Física, Benemérita Universidad Autónoma de Puebla, 72570 Puebla, Pue., Mexico
*Correspondence e-mail: sylvain_bernes@hotmail.com

Edited by I. Brito, University of Antofagasta, Chile (Received 27 February 2023; accepted 2 March 2023; online 10 March 2023)

The title salt, C14H14N3O4S2+·Cl [systematic name: 2-(4-hy­droxy-2-methyl-1,1-dioxo-1,2-benzo­thia­zine-3-amido)-5-methyl-1,3-thia­zol-3-ium chloride] is the hydro­chloride derivative of meloxicam, a drug used to treat pain and inflammation in rheumatic disorders and osteoarthritis. Although its mol­ecular structure is similar to that previously reported for the hydro­bromide analogue, both salts are not isomorphous. Different crystal structures originate from a conformational modification, arising from a degree of rotational freedom for the thia­zolium ring in the cations. By taking as a reference the conformation of meloxicam, the thia­zolium ring is twisted by 10.96 and −16.70° in the hydro­chloride and hydro­bromide salts, while the 1,2-benzo­thia­zine core is a rigid scaffold. This behaviour could explain why meloxicam is a polymorphous compound.

3D view (loading...)
[Scheme 3D1]
Chemical scheme
[Scheme 1]

Structure description

Meloxicam [abbreviated hereafter as MX; systematic name: 4-hy­droxy-2-methyl-N-(5-methyl-1,3-thia­zol-2-yl)-2H-1,2-benzo­thia­zine-3-carboxamide 1,1-dioxide] is an achiral benzo­thia­zine drug, practically insoluble in water at physiological pH (Luger et al., 1996[Luger, P., Daneck, K., Engel, W., Trummlitz, G. & Wagner, K. (1996). Eur. J. Pharm. Sci. 4, 175-187.]). This mol­ecule was patented in 1977, and is currently classified as an anti­pyretic and non-steroidal anti-inflammatory medication, used for the management of pain and inflammation associated with rheumatoid arthritis and osteoarthritis, in adults and children. In some countries, it has also been approved for use in veterinary medicine. The crystallization of meloxicam is a `difficult art' (Śniechowska et al., 2021[Śniechowska, J., Paluch, P. & Dudek, M. K. (2021). Acta Cryst. A77, C897.]), since four neat polymorphic forms are known, along with one hydrated form (Coppi et al., 2003[Coppi, L., Bartra Sanmartí, M. & Closa Clavo, M. (2003). US patent 2003/0109701 A1.]; Freitas et al., 2017[Jacon Freitas, J. T., Santos Viana, O. M. M., Bonfilio, R., Doriguetto, A. C. & de Araújo, M. B. (2017). Eur. J. Pharm. Sci. 109, 347-358.]). So far, only the triclinic form I and the hydrated form were structurally characterized by X-ray diffraction (Luger et al., 1996[Luger, P., Daneck, K., Engel, W., Trummlitz, G. & Wagner, K. (1996). Eur. J. Pharm. Sci. 4, 175-187.]; Fabiola et al., 1998[Fabiola, G. F., Pattabhi, V., Manjunatha, S. G., Rao, G. V. & Nagarajan, K. (1998). Acta Cryst. C54, 2001-2003.]; Fedorov et al., 2019[Fedorov, A. Y., Drebushchak, T. N. & Tantardini, C. (2019). Comput. Theor. Chem. 1157, 47-53.]). Actually, the formula of MX·H2O is not well defined: for the reported structure, the water mol­ecule is disordered over two general positions, with occupancies reported as 0.53 (3) and 0.63 (3).

Among the many meloxicam salts characterized by X-ray diffraction, the hydro­bromide was deposited as a CSD communication (Tumanov et al., 2011[Tumanov, N., Dyakonova, M., Pankrushina, N. & Shahtshneider, T. P. (2011). CSD Communication (refcode XATJAF, CCDC 832082). CCDC, Cambridge, England.]; CSD refcode: XATJAF). MX·HBr crystallizes in space group P21/c. The thia­zole group is protonated, in such a way that a double-acceptor hydrogen bond is formed with the bromide ion accepting links from the thiazolium and amide NH groups, to form a common R21(6) ring motif with the thia­zolium and amide NH groups as donors. The conformation for HMX+ is close to that observed for neutral MX, owing to an intra­molecular hydrogen bond between the enol group in the 1,2-benzo­thia­zine core and the carbonyl group of the amide functionality, which gives the common S(6) motif. We have now determined the structure of the hydro­chloride salt, MX·HCl, which also crystallizes in space group P21/c, although with different unit-cell parameters. The mol­ecular structure of MX·HCl is similar to that of MX·HBr, including the same intramolecular O—H⋯O and intermolecular N—H⋯Cl hydrogen bonds (Fig. 1[link]; Table 1[link], entries 1–3). Mol­ecules are however packed in different ways in both salts, as corroborated by their simulated powder diffraction patterns, which are clearly different (Fig. 2[link]). If the nature of the anion, Cl or Br, is not taken into account, MX·HBr and MX·HCl can thus be described as polymorphic forms crystallizing in a single space group.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
O1—H1O⋯O2 0.84 (2) 1.85 (2) 2.5921 (18) 148 (2)
N1—H1N⋯Cl1 0.89 (2) 2.16 (2) 2.992 (2) 155.5 (19)
N2—H2N⋯Cl1 0.87 (2) 2.35 (2) 3.1185 (18) 147.8 (18)
C1—H1D⋯O4i 0.96 2.62 3.286 (3) 127
C14—H14C⋯O2ii 0.96 2.52 3.380 (3) 150
Symmetry codes: (i) x, y+1, z; (ii) [-x+1, y-{\script{1\over 2}}, -z+{\script{1\over 2}}].
[Figure 1]
Figure 1
Mol­ecular structure of the title compound, with displacement ellipsoids at the 50% probability level for non-H atoms. Dashed lines represent intra­molecular hydrogen bonds (Table 1[link], entries 1–3). The labelling scheme is that adopted for MX·HBr (Tumanov et al., 2011[Tumanov, N., Dyakonova, M., Pankrushina, N. & Shahtshneider, T. P. (2011). CSD Communication (refcode XATJAF, CCDC 832082). CCDC, Cambridge, England.]).
[Figure 2]
Figure 2
Simulated powder X-ray diffraction patterns for MX·HBr (top, pattern calculated using the deposited Cif file for XATJAF; Tumanov et al., 2011[Tumanov, N., Dyakonova, M., Pankrushina, N. & Shahtshneider, T. P. (2011). CSD Communication (refcode XATJAF, CCDC 832082). CCDC, Cambridge, England.]) and MX·HCl (bottom). Patterns were calculated with Mercury (Macrae et al., 2020[Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226-235.]), assuming the Cu Kα radiation. Mol­ecular structures are represented along with their patterns.

A close examination of the conformation of the cations, and a comparison with the neutral mol­ecule MX (Fabiola et al., 1998[Fabiola, G. F., Pattabhi, V., Manjunatha, S. G., Rao, G. V. & Nagarajan, K. (1998). Acta Cryst. C54, 2001-2003.]; CSD refcode: SEDZOQ) rationalizes this behaviour. Assuming that the 1,2-benzo­thia­zine core is a rigid moiety, an overlay between HMX+ in both salts and MX shows that the thia­zolium ring has some degree of rotational freedom. Taking MX as reference, the HMX+ cation has its thia­zolium ring twisted by 10.96° in MX·HCl and by −16.70° in MX·HBr (Fig. 3[link]). This rotation over a range of ca 25° is sufficient to enable the formation of distinct secondary inter­molecular contacts (Table 1[link], entries 4 and 5), which, in turn, alter the packing of the cations in the crystal. By widening this behaviour to meloxicam, for which the rotation of the thia­zole group is less restrained, since no R21(6) ring motif involving an halide ion is present, one would assume that the rich polymorphism observed for this drug is also associated to similar conformational modifications.

[Figure 3]
Figure 3
Overlay between meloxicam (grey), MX·HBr (red) and MX·HCl (green), calculated with Mercury (Macrae et al., 2020[Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226-235.]). The fits were carried out using atoms belonging to the 1,2-benzo­thia­zine core (14 atoms), while the amide and thia­zole groups were kept free. The r.m.s. deviations for the fits are better than 0.04 Å. For the structure of the neutral mol­ecule MX, which has been reported three times, refcode SEDZOQ was retained (Fabiola et al., 1998[Fabiola, G. F., Pattabhi, V., Manjunatha, S. G., Rao, G. V. & Nagarajan, K. (1998). Acta Cryst. C54, 2001-2003.]), in order to have all models at room temperature. For clarity, halide anions are omitted, as well as H atoms bonded to C atoms. Note that in MX, the thia­zole ring is not protonated.

Synthesis and crystallization

Meloxicam hydro­chloride was unintentionally crystallized while screening slurry co-crystallizations using derivatives of (S)-α-methyl­benzyl­amine or L-proline as coformers. In some experiments, an amount of a 0.02 N HCl solution was added to the slurry, for the purpose of modifying the pH of the medium. Single crystals of the MX·HCl salt were recovered from these slurries.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link].

Table 2
Experimental details

Crystal data
Chemical formula C14H14N3O4S2+·Cl
Mr 387.85
Crystal system, space group Monoclinic, P21/c
Temperature (K) 295
a, b, c (Å) 11.3380 (6), 10.7346 (5), 14.5503 (10)
β (°) 109.430 (5)
V3) 1670.05 (17)
Z 4
Radiation type Ag Kα, λ = 0.56083 Å
μ (mm−1) 0.26
Crystal size (mm) 0.23 × 0.09 × 0.07
 
Data collection
Diffractometer Stoe Stadivari
Absorption correction Multi-scan X-AREA 1.88 (Stoe & Cie, 2019[Stoe & Cie (2019). X-AREA and X-RED32, Stoe & Cie, Darmstadt, Germany.])
Tmin, Tmax 0.407, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections 40949, 3902, 2285
Rint 0.088
(sin θ/λ)max−1) 0.653
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.032, 0.074, 0.83
No. of reflections 3902
No. of parameters 234
H-atom treatment H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.26, −0.24
Computer programs: X-AREA 1.88 (Stoe & Cie, 2019[Stoe & Cie (2019). X-AREA and X-RED32, Stoe & Cie, Darmstadt, Germany.]), SHELXT2018/2 (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL2018/3 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]), XP in SHELXTL-Plus (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), Mercury (Macrae et al., 2020[Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226-235.]) and publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Structural data


Computing details top

Data collection: X-AREA 1.88 (Stoe & Cie, 2019); cell refinement: X-AREA 1.88 (Stoe & Cie, 2019); data reduction: X-AREA 1.88 (Stoe & Cie, 2019); program(s) used to solve structure: SHELXT2018/2 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015b); molecular graphics: XP in SHELXTL-Plus (Sheldrick, 2008) and Mercury (Macrae et al., 2020); software used to prepare material for publication: publCIF (Westrip, 2010).

2-(4-Hydroxy-2-methyl-1,1-dioxo-1,2-benzothiazine-3-amido)-5-methyl-1,3-thiazol-3-ium chloride top
Crystal data top
C14H14N3O4S2+·ClF(000) = 800
Mr = 387.85Dx = 1.543 Mg m3
Monoclinic, P21/cAg Kα radiation, λ = 0.56083 Å
a = 11.3380 (6) ÅCell parameters from 19546 reflections
b = 10.7346 (5) Åθ = 2.2–26.5°
c = 14.5503 (10) ŵ = 0.26 mm1
β = 109.430 (5)°T = 295 K
V = 1670.05 (17) Å3Block, yellow
Z = 40.23 × 0.09 × 0.07 mm
Data collection top
Stoe Stadivari
diffractometer
3902 independent reflections
Radiation source: Sealed X-ray tube, Axo Astix-f Microfocus source2285 reflections with I > 2σ(I)
Graded multilayer mirror monochromatorRint = 0.088
Detector resolution: 5.81 pixels mm-1θmax = 21.5°, θmin = 2.2°
ω scansh = 1414
Absorption correction: multi-scan
X-AREA 1.88 (Stoe & Cie, 2019)
k = 1414
Tmin = 0.407, Tmax = 1.000l = 1919
40949 measured reflections
Refinement top
Refinement on F2Primary atom site location: dual
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.032Hydrogen site location: mixed
wR(F2) = 0.074H atoms treated by a mixture of independent and constrained refinement
S = 0.83 w = 1/[σ2(Fo2) + (0.0329P)2]
where P = (Fo2 + 2Fc2)/3
3902 reflections(Δ/σ)max = 0.001
234 parametersΔρmax = 0.26 e Å3
0 restraintsΔρmin = 0.24 e Å3
0 constraints
Special details top

Refinement. All H atoms bonded to heteroatoms (H1O, H1N and H2N) were refined with free coordinates, and remaining H atoms were placed in idealized positions, with C—H bond lengths constrained to 0.96 (methyl groups) or 0.93 Å (aromatic CH). All H atoms were refined with calculated isotropic displacement parameters.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
Cl10.97139 (5)0.37304 (6)0.36101 (5)0.05872 (19)
S10.78018 (5)0.80065 (5)0.39329 (4)0.04065 (15)
S20.63352 (4)0.19526 (5)0.43965 (4)0.03731 (14)
O10.39766 (12)0.51274 (13)0.39149 (12)0.0416 (4)
H1O0.441 (2)0.576 (2)0.3941 (18)0.062*
O20.59216 (11)0.64257 (12)0.39574 (11)0.0402 (4)
O30.67314 (12)0.23387 (14)0.53969 (11)0.0463 (4)
O40.68678 (13)0.08624 (14)0.41315 (13)0.0544 (5)
N10.94397 (15)0.64715 (18)0.38545 (14)0.0421 (5)
H1N0.9763 (19)0.572 (2)0.3827 (16)0.050*
N20.76883 (14)0.54411 (16)0.39712 (14)0.0355 (4)
H2N0.8075 (18)0.4746 (19)0.3955 (16)0.043*
N30.65464 (13)0.31354 (15)0.37489 (13)0.0338 (4)
C10.9370 (2)0.9923 (2)0.3668 (2)0.0715 (9)
H1B0.8861681.0174680.3024910.107*
H1C1.0234511.0071470.3751310.107*
H1D0.9138491.0393110.4142360.107*
C20.91763 (19)0.8566 (2)0.37994 (18)0.0474 (6)
C30.9929 (2)0.7626 (2)0.37786 (18)0.0503 (6)
H31.0713200.7736850.3718230.060*
C40.83125 (16)0.65175 (18)0.39320 (15)0.0336 (5)
C50.64622 (16)0.54299 (19)0.39282 (15)0.0329 (5)
C60.58544 (16)0.42257 (18)0.38367 (15)0.0314 (5)
C70.46600 (16)0.41332 (18)0.38478 (15)0.0315 (5)
C80.40231 (15)0.29411 (18)0.38082 (14)0.0304 (4)
C90.27306 (16)0.28810 (19)0.35974 (15)0.0362 (5)
H90.2261260.3609350.3504800.043*
C100.21526 (17)0.1742 (2)0.35270 (16)0.0399 (5)
H100.1292130.1709950.3394330.048*
C110.28195 (18)0.0647 (2)0.36485 (17)0.0420 (5)
H110.2406670.0114040.3572890.050*
C120.41100 (18)0.06833 (19)0.38842 (16)0.0384 (5)
H120.4572020.0049760.3976690.046*
C130.46958 (16)0.18279 (18)0.39791 (15)0.0314 (4)
C140.6498 (2)0.2839 (2)0.27407 (17)0.0482 (6)
H14A0.6993230.2111300.2748640.072*
H14B0.6823180.3529420.2479560.072*
H14C0.5647800.2686290.2341860.072*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0481 (3)0.0530 (4)0.0799 (5)0.0108 (3)0.0278 (3)0.0043 (4)
S10.0437 (3)0.0326 (3)0.0513 (4)0.0087 (2)0.0233 (3)0.0037 (3)
S20.0316 (2)0.0271 (3)0.0530 (4)0.0024 (2)0.0138 (2)0.0052 (3)
O10.0363 (7)0.0272 (8)0.0634 (11)0.0046 (6)0.0194 (7)0.0013 (8)
O20.0383 (7)0.0267 (8)0.0571 (11)0.0007 (6)0.0179 (7)0.0027 (7)
O30.0430 (7)0.0456 (9)0.0426 (10)0.0028 (7)0.0039 (7)0.0088 (8)
O40.0467 (8)0.0310 (8)0.0918 (14)0.0089 (7)0.0316 (9)0.0046 (9)
N10.0338 (9)0.0423 (11)0.0521 (13)0.0032 (8)0.0169 (8)0.0026 (10)
N20.0326 (8)0.0290 (9)0.0457 (12)0.0017 (7)0.0141 (8)0.0003 (9)
N30.0342 (8)0.0279 (9)0.0428 (11)0.0000 (7)0.0173 (8)0.0012 (8)
C10.0752 (17)0.0440 (16)0.110 (3)0.0216 (13)0.0501 (18)0.0070 (16)
C20.0467 (11)0.0437 (14)0.0579 (17)0.0157 (11)0.0254 (12)0.0081 (12)
C30.0397 (11)0.0536 (15)0.0611 (17)0.0186 (11)0.0215 (11)0.0060 (13)
C40.0311 (9)0.0348 (12)0.0344 (13)0.0046 (8)0.0101 (9)0.0015 (10)
C50.0323 (9)0.0318 (11)0.0341 (13)0.0008 (9)0.0104 (9)0.0034 (10)
C60.0315 (9)0.0251 (10)0.0378 (13)0.0008 (8)0.0116 (9)0.0023 (9)
C70.0341 (9)0.0270 (10)0.0333 (13)0.0031 (8)0.0111 (9)0.0021 (9)
C80.0316 (9)0.0291 (11)0.0320 (12)0.0015 (8)0.0125 (8)0.0000 (9)
C90.0330 (9)0.0365 (12)0.0414 (13)0.0008 (9)0.0156 (9)0.0027 (10)
C100.0321 (9)0.0445 (13)0.0448 (14)0.0055 (9)0.0152 (10)0.0001 (11)
C110.0443 (11)0.0367 (13)0.0475 (15)0.0123 (10)0.0186 (11)0.0026 (11)
C120.0431 (10)0.0294 (12)0.0437 (14)0.0011 (9)0.0156 (10)0.0015 (10)
C130.0305 (8)0.0298 (11)0.0350 (12)0.0012 (8)0.0123 (8)0.0013 (9)
C140.0536 (12)0.0463 (14)0.0492 (15)0.0053 (11)0.0232 (11)0.0096 (12)
Geometric parameters (Å, º) top
S1—C41.700 (2)C1—H1D0.9600
S1—C21.740 (2)C2—C31.328 (3)
S2—O41.4275 (15)C3—H30.9300
S2—O31.4343 (16)C5—C61.450 (3)
S2—N31.6455 (17)C6—C71.363 (2)
S2—C131.7580 (17)C7—C81.461 (3)
O1—C71.341 (2)C8—C131.395 (3)
O1—H1O0.84 (2)C8—C91.395 (2)
O2—C51.240 (2)C9—C101.375 (3)
N1—C41.321 (2)C9—H90.9300
N1—C31.377 (3)C10—C111.376 (3)
N1—H1N0.89 (2)C10—H100.9300
N2—C41.366 (2)C11—C121.388 (3)
N2—C51.371 (2)C11—H110.9300
N2—H2N0.87 (2)C12—C131.382 (3)
N3—C61.438 (2)C12—H120.9300
N3—C141.484 (3)C14—H14A0.9600
C1—C21.495 (3)C14—H14B0.9600
C1—H1B0.9600C14—H14C0.9600
C1—H1C0.9600
C4—S1—C290.37 (10)O2—C5—C6123.12 (16)
O4—S2—O3119.55 (10)N2—C5—C6117.12 (17)
O4—S2—N3108.82 (10)C7—C6—N3121.01 (17)
O3—S2—N3107.58 (9)C7—C6—C5120.50 (17)
O4—S2—C13109.75 (9)N3—C6—C5118.49 (15)
O3—S2—C13108.11 (9)O1—C7—C6122.89 (18)
N3—S2—C13101.50 (9)O1—C7—C8114.19 (16)
C7—O1—H1O107.9 (16)C6—C7—C8122.91 (17)
C4—N1—C3113.59 (19)C13—C8—C9118.14 (18)
C4—N1—H1N117.6 (14)C13—C8—C7120.63 (15)
C3—N1—H1N128.8 (14)C9—C8—C7121.23 (17)
C4—N2—C5122.49 (17)C10—C9—C8119.81 (19)
C4—N2—H2N116.9 (13)C10—C9—H9120.1
C5—N2—H2N120.3 (13)C8—C9—H9120.1
C6—N3—C14114.85 (17)C9—C10—C11121.45 (17)
C6—N3—S2112.92 (13)C9—C10—H10119.3
C14—N3—S2115.87 (14)C11—C10—H10119.3
C2—C1—H1B109.5C10—C11—C12119.80 (19)
C2—C1—H1C109.5C10—C11—H11120.1
H1B—C1—H1C109.5C12—C11—H11120.1
C2—C1—H1D109.5C13—C12—C11118.80 (19)
H1B—C1—H1D109.5C13—C12—H12120.6
H1C—C1—H1D109.5C11—C12—H12120.6
C3—C2—C1127.9 (2)C12—C13—C8121.86 (16)
C3—C2—S1110.25 (17)C12—C13—S2121.34 (15)
C1—C2—S1121.73 (18)C8—C13—S2116.68 (14)
C2—C3—N1113.77 (19)N3—C14—H14A109.5
C2—C3—H3123.1N3—C14—H14B109.5
N1—C3—H3123.1H14A—C14—H14B109.5
N1—C4—N2120.09 (18)N3—C14—H14C109.5
N1—C4—S1112.01 (15)H14A—C14—H14C109.5
N2—C4—S1127.88 (14)H14B—C14—H14C109.5
O2—C5—N2119.75 (18)
O4—S2—N3—C6169.71 (13)N2—C5—C6—N33.0 (3)
O3—S2—N3—C659.40 (14)N3—C6—C7—O1179.05 (19)
C13—S2—N3—C654.01 (15)C5—C6—C7—O11.9 (3)
O4—S2—N3—C1434.30 (16)N3—C6—C7—C82.3 (3)
O3—S2—N3—C14165.18 (13)C5—C6—C7—C8176.80 (19)
C13—S2—N3—C1481.41 (15)O1—C7—C8—C13164.08 (19)
C4—S1—C2—C31.0 (2)C6—C7—C8—C1314.7 (3)
C4—S1—C2—C1175.5 (2)O1—C7—C8—C916.1 (3)
C1—C2—C3—N1175.5 (2)C6—C7—C8—C9165.1 (2)
S1—C2—C3—N10.7 (3)C13—C8—C9—C102.5 (3)
C4—N1—C3—C20.1 (3)C7—C8—C9—C10177.4 (2)
C3—N1—C4—N2177.2 (2)C8—C9—C10—C110.8 (3)
C3—N1—C4—S10.9 (2)C9—C10—C11—C122.5 (4)
C5—N2—C4—N1171.6 (2)C10—C11—C12—C130.9 (3)
C5—N2—C4—S16.2 (3)C11—C12—C13—C82.5 (3)
C2—S1—C4—N11.08 (18)C11—C12—C13—S2173.43 (17)
C2—S1—C4—N2176.9 (2)C9—C8—C13—C124.2 (3)
C4—N2—C5—O27.8 (3)C7—C8—C13—C12175.7 (2)
C4—N2—C5—C6171.4 (2)C9—C8—C13—S2171.96 (16)
C14—N3—C6—C795.1 (2)C7—C8—C13—S28.2 (3)
S2—N3—C6—C740.8 (2)O4—S2—C13—C1229.6 (2)
C14—N3—C6—C585.8 (2)O3—S2—C13—C12102.42 (19)
S2—N3—C6—C5138.34 (16)N3—S2—C13—C12144.58 (18)
O2—C5—C6—C74.7 (3)O4—S2—C13—C8154.31 (16)
N2—C5—C6—C7176.1 (2)O3—S2—C13—C873.71 (18)
O2—C5—C6—N3176.19 (19)N3—S2—C13—C839.29 (18)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1O···O20.84 (2)1.85 (2)2.5921 (18)148 (2)
N1—H1N···Cl10.89 (2)2.16 (2)2.992 (2)155.5 (19)
N2—H2N···Cl10.87 (2)2.35 (2)3.1185 (18)147.8 (18)
C1—H1D···O4i0.962.623.286 (3)127
C14—H14C···O2ii0.962.523.380 (3)150
Symmetry codes: (i) x, y+1, z; (ii) x+1, y1/2, z+1/2.
 

Funding information

Funding for this research was provided by: Consejo Nacional de Ciencia y Tecnología (grant No. 268178).

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