3,3-Bis(2-hy­dr­oxy­eth­yl)-1-(4-nitro­benzo­yl)thio­urea: crystal structure, Hirshfeld surface analysis and computational study

In the title compound, C₁₂H₁₅N₃O₅S, a tris­ubstituted thio­urea derivative, the central CN₂S chromophore is almost planar (r.m.s. deviation = 0.018 Å) and the pendant hy­droxy­ethyl groups lie to either side of this plane. While to a first approximation the thione-S and carbonyl-O atoms lie to the same side of the mol­ecule, the S—C—N—C torsion angle of −47.8 (2)° indicates a considerable twist. As one of the hy­droxy­ethyl groups is orientated towards the thio­amide residue, an intra­molecular N—H⋯O hydrogen bond is formed which leads to an S(7) loop. A further twist in the mol­ecule is indicated by the dihedral angle of 65.87 (7)° between the planes through the CN₂S chromophore and the 4-nitro­benzene ring. There is a close match between the experimental and gas-phase, geometry-optimized (DFT) mol­ecular structures. In the crystal, O—H⋯O and O—H⋯S hydrogen bonds give rise to supra­molecular layers propagating in the ab plane. The connections between layers to consolidate the three-dimensional architecture are of the type C—H⋯O, C—H⋯S and nitro-O⋯π. The nature of the supra­molecular association has been further analysed by a study of the calculated Hirshfeld surfaces, non-covalent inter­action plots and computational chemistry, all of which point to the significant influence and energy of stabilization provided by the conventional hydrogen bonds.

1. Chemical context

In addition to accepting C—H⋯O inter­actions, nitro groups are known to form nitro-N—O⋯π(ar­yl) inter­actions (Huang et al., 2008) as well as participate as donors and acceptors in π-hole inter­actions (Bauzá et al., 2014). Hence, when the title nitro-containing compound, (I), became available, a crystallographic analysis was undertaken. Compound (I) is an example of a tri-substituted thio­urea mol­ecule, H₂NC(=S)NH₂, whereby three of the four hydrogen atoms have been substituted to yield 4-NO₂C₆H₄C(=O)N(H)C(=S)N(CH₂CH₂OH)₂. Such N,N′-di(alk­yl/ar­yl)-N′-benz­oyl­thio­urea derivatives have a carbonyl group connected to the thio­urea framework and offer opportunities for rich coordination chemistry as these mol­ecules feature both hard (oxygen) and soft (sulfur) donor atoms along with nitro­gen donors and indeed, a variety of coordination modes have been observed. The neutral mol­ecule has been observed to coordinate in a monodentate-S mode (Gunasekaran, Ng et al., 2012; Saeed et al., 2014). In its deprotonated form, O-,S- chelation is often observed (Saeed et al., 2014). There are a variety of motivations for investigating metal complexes of benzoyl­thio­urea derivatives such as for catalytic applications and for anion recognition (Zhang & Schreiner, 2009; Gunasekaran, Jerome et al., 2012; Nishikawa, 2018). Over and above these considerations, there are continuing investigations into their biological potential, such as anti-microbial (Gemili et al., 2017; Binzet et al., 2018; Saeed et al., 2018), anti-cancer (Peng et al., 2016; Barolli et al., 2017; Jeyalakshmi et al., 2019) and anti-mycobacterium tuberculosis (Plutín et al., 2016) agents. In a continuation of our on-going work on these mol­ecules and their metal complexes (Selvakumaran, Ng et al., 2011; Selvakumaran, Karvembu et al., 2011; Gunasekaran et al., 2017; Tan, Azizan et al., 2019), we now describe the synthesis, spectroscopic characterization and X-ray crystallographic investigation of (I). Further, an analysis of the calculated Hirshfeld surfaces, non-covalent inter­action plots as well as a computational chemistry study for (I) are described.

2. Structural commentary

Selected geometrical data for (I), Fig. 1, are given in Table 1. The key feature of the structure is that it is a tri-substituted thio­urea mol­ecule with one of the nitro­gen atoms having a benzoyl residue and the other bearing two hy­droxy­ethyl groups. An approximate syn relationship is established between the thione-S and carbonyl-O atoms. Even though they lie to the same side of the mol­ecule, the S1—C1—N2—C6 torsion angle of −47.8 (2)° is consistent with a significant twist in the mol­ecule about the C1—N2 bond; the O3—C6—N2—C1 torsion angle is −3.6 (2)°.

Table 1
Selected geometric parameters (Å, °) for (I) determined experimentally (X-ray) and from theory (DFT)

Parameter	X-ray	Theory
C1=S1	1.6777 (16)	1.668
C1—N1	1.334 (2)	1.366
C1—N2	1.4038 (19)	1.410
C6—O3	1.2156 (18)	1.219
C6—N2	1.3771 (19)	1.388
S1—C1—N1	123.83 (12)	124.7
S1—C1—N2	121.89 (11)	121.8
N1—C1—N2	114.23 (13)	113.4
O3—C6—N2	123.57 (14)	124.3
O3—C6—C7	121.17 (13)	121.1
N2—C6—C7	115.20 (13)	114.5
S1—C1—N2—C6	−47.8 (2)	−44.6
S1—C1—N1—C2	173.80 (11)	167.8
S1—C1—N1—C4	−8.0 (2)	−7.2
O3—C6—N2—C1	−3.6 (2)	−16.5
O3—C6—C7—C8	163.29 (15)	152.7
N1—C2—C3—O1	−62.76 (17)	−69.3
N1—C4—C5—O2	57.76 (17)	68.4

Figure 1 The mol­ecular structure of (I) showing the atom-labelling scheme and displacement ellipsoids at the 70% probability level.

The hy­droxy­ethyl groups lie to either side of the CN₂S plane (r.m.s. deviation = 0.017 Å). Crucially, the O1-hydroxy­ethyl group is folded towards the thio­amide residue, which allows for the formation of an intra­molecular N2—H⋯O1 hydrogen bond and an S(7) loop, Table 2. That the mol­ecule is highly twisted is evidenced by the dihedral angle of 65.87 (7)° between the CN₂S atoms and the terminal C7–C12 aryl ring. From Table 1, it is apparent that the C1—N1 bond length is considerably shorter than C1—N2, indicating delocalization of π-electron density over the S1—C1—N1 atoms. However, the large twist for the C1—N2 bond mentioned above does not allow significant delocalization to extend to atoms C1, N1 and C6. The expected trends relating to the nature of the bonds about the quaternary-C1 atom are seen in the bond angles about that atom. Thus, the angles subtended by the formally doubly bonded S1 atom are appreciably wider. Finally, the nitro group is effectively co-planar with the aryl ring to which it is attached, as seen in the O4—N3—C10—C9 torsion angle of 5.2 (2)°.

Table 2
Hydrogen-bond geometry (Å, °)

Cg1 is the centroid of the (C7–C12) ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2N⋯O1	0.87 (1)	1.88 (1)	2.6749 (17)	151 (1)
O1—H1O⋯O2^i	0.84 (2)	1.87 (2)	2.7075 (17)	176 (2)
O2—H2O⋯S1^ii	0.84 (1)	2.33 (1)	3.1724 (12)	175 (2)
C2—H2B⋯O3^i	0.99	2.53	3.2305 (18)	127
C5—H5A⋯S1^iii	0.99	2.77	3.4915 (17)	130
C8—H8⋯O3^iv	0.95	2.36	3.2147 (19)	150
N3—O4⋯Cg1^v	1.22 (1)	3.63 (1)	3.6927 (16)	83 (1)
Symmetry codes: (i) ; (ii) x-1, y, z; (iii) -x+1, -y+1, -z+1; (iv) ; (v) -x+2, -y+1, -z+2.

3. Gas-phase theoretical structure

With the aid of a long-range corrected wB97XD density functional with Grimme's D2 dispersion model (Chai & Head-Gordon, 2008) and coupled with Pople's 6-311+G(d,p) basis set (Petersson et al., 1988), as implemented in Gaussian16 (Frisch et al., 2016), the gas-phase geometry-optimized structure of (I) was calculated. As confirmed through a frequency analysis with zero imaginary frequency, the local minimum structure in the gas-phase was located in this study. The experimental and theoretical structures are superimposed (Macrae et al., 2006) in Fig. 2. The analysis shows that there are only minor differences between the mol­ecules with the r.m.s. deviation between the conformations being only 0.015 Å. The derived inter­atomic data for the geometry-optimized structure are included in Table 1 from which it can be seen there is a close correlation between the experimental and calculated geometries.

Figure 2 Overlay diagram for the experimental (green image) and geometry-optimized (red) mol­ecules of (I). The mol­ecules have been overlapped so the S=C—N—C=O fragments are coincident.

It is evident that the only major differences between the experimental and geometry-optimized structures relate to some of the torsion angles. Thus, the most significant conformational difference is evidenced by a nearly 13° difference in the O3—C6—N2—C1 torsion angles, i.e. −3.6 (2)° (X-ray) versus −16.5° (calculation), indicating a greater deviation from the anti-disposition in the optimized structure. Also, the N1—C2—C3—O1 and N1—C4—C5—O2 torsion angles are close to symmetric in the optimized structure cf. the experimental structure. Similar trends were noted in analogous calculations performed on the 4-methyl analogue (Tan, Azizan et al., 2019).

4. Supra­molecular features

In the crystal of (I), O1—H1O⋯O2 hydrogen bonds (Table 2) lead to a helical chain propagating along the b-axis direction, with adjacent mol­ecules related by the 2₁ screw axis. The O2—H2O⋯S1 hydrogen bonding serves to cross-link translationally related chains along the a axis to form a supra­molecular layer in the ab plane, Fig. 3(a). The layers are connected into a three-dimensional architecture by methyl­ene-C—H⋯O(carbon­yl), methyl­ene-C—H⋯S(thione) and comparatively rare nitro-O⋯π(ar­yl) contacts, Fig. 3(b).

Figure 3 Views of the mol­ecular packing in (I): (a) supra­molecular layer in the ab plane sustained by hy­droxy-O—H⋯O(hy­droxy) and hy­droxy-O—H⋯S(thione) hydrogen bonds and (b) view of the unit-cell contents in a projection down the a axis, highlighting the methyl­ene-C—H⋯O(carbon­yl), methyl­ene-C—H⋯S(thione) and nitro-O⋯π(ar­yl) connections between layers; one layer is represented in space-filling mode. The O—H⋯O, O—H⋯S, C—H⋯O, C—H⋯S and N—O⋯π inter­actions are shown as orange, blue, green, pink and purple dashed lines, respectively.

5. Hirshfeld surface analysis

Using Crystal Explorer 17 (Turner et al., 2017) and established procedures (Tan, Jotani et al., 2019), the Hirshfeld surfaces and two-dimensional fingerprint plots (full and decomposed) for (I) were calculated. In the Hirshfeld surface mapped over electrostatic potential in Fig. 4, the donors and acceptors of the conventional O—H⋯O and O—H⋯S hydrogen bonds and C—H⋯O contacts appear as blue (positive potential) and red (negative potential) regions, respectively. The bright-red spots near the participating atoms in the Hirshfeld surface mapped over d_norm in Fig. 5 also give indications of these inter­molecular inter­actions. Additional diminutive red spots near the methyl­ene-H2B and H5A, thione-S1 and carbonyl-O3 atoms are indicative of weaker C—H⋯S and C—H⋯O inter­actions, Table 2. Further, the presence of faint-red spots near the ethyl-C3 and nitro-O5 atoms on the surface indicate C—H⋯O contacts in the packing involving the nitro substit­uent. The other faint-red spots appearing in Fig. 5 indicate the presence of short inter­atomic contacts as summarized in Table 3. The influence of the nitro group is also seen in the nitro-O4⋯π(C7–C12) inter­action, illustrated through yellow dotted lines in Fig. 6.

Table 3
A summary of short inter­atomic contacts (Å) in (I)^a

Contact	Distance	Symmetry operation
H1O⋯H2O	2.23	1 − x,  + y,  − z
C1⋯C3	3.368 (2)	1 − x, − + y,  − z
C1⋯H3B	2.71	1 − x, − + y,  − z
C3⋯O3	3.0819 (19)	1 − x,  + y,  − z
C3⋯O5	3.168 (2)	2 − x, 1 − y, 1 − z
H3B⋯O5	2.65	2 − x, 1 − y, 1 − z
C5⋯H1O	2.61	1 − x, − + y,  − z
C6⋯O2	3.0924 (18)	1 + x, y, z
C6⋯H2O	2.81	1 + x, y, z
Note: (a) The inter­atomic distances are calculated in Crystal Explorer 17 (Turner et al., 2017) whereby the X—H bond lengths are adjusted to their neutron values.

Figure 4 A view of the Hirshfeld surface mapped over the calculated electrostatic potential for (I). The red and blue regions represent negative and positive electrostatic potentials, respectively. The potentials were calculated using the STO-3G basis set at Hartree–Fock level of theory over a range of ±0.18 atomic units.

Figure 5 Two views of the Hirshfeld surface mapped over dnorm for (I) in the range −0.127 to +1.259 arbitrary units.

Figure 6 A view of the Hirshfeld surfaces mapped with the shape-index property for (I), highlighting the inter­molecular N—O⋯π(ar­yl) inter­actions through yellow dotted lines.

The enrichment ratio (ER) descriptor, which is derived from the analysis of the Hirshfeld surface (Jelsch et al., 2014), was also employed to analyse the inter­molecular contacts in the crystal of (I). The ER(X, Y) reflects the relative likelihood of the formation of X-to-Y inter­actions in a crystal, i.e. the ratio between the proportion of actual contacts in a crystal to the theoretical proportion of random contacts. Data for (I) are given in Table 4. The enrichment ratios greater than unity for the atom pairs (O, H) and, in particular, (S, H), are consistent with the relatively high likelihood for the formation of the O—H⋯O and O—H⋯S hydrogen bonds in the crystal of (I). It is also evident that the value greater than unity for (C, O) arises from the nitro-O⋯π(ar­yl) contacts.

Table 4
Enrichment ratios for (I)

Parameter	Ratio
H⋯H	0.88
C⋯H	0.85
O⋯H	1.26
S⋯H	1.66
C⋯O	1.34

The overall fingerprint plots for (I) and those delineated into H⋯H, O⋯H/H⋯O, C⋯H/H⋯C, S⋯H/H⋯S and C⋯O/O⋯C contacts are illustrated in Fig. 7(a)–(f), respectively, with a summary of the percentage contributions from the various contacts given in Table 5. The greatest contribution to the overall surface is from H⋯H contacts and this is closely followed by O⋯H/H⋯O contacts, as viewed by the pair of long spikes at d_e + d_i ∼1.8 Å in Fig. 7(c). The prominent features in Fig. 7(d) reflect the significant C⋯H/H⋯C contacts evident in the packing, Tables 2 and 3. The significant percentage contribution from S⋯H/H⋯S contacts reflects the presence of O—H⋯S hydrogen bonding and is apparent through the appearance of asymmetric spikes of different shapes at d_e + d_i ∼2.1 Å in the fingerprint plot of Fig. 7(e). The 5.8% contribution from C⋯O/O⋯C contacts and the aforementioned ER value of 1.66 clearly indicate the significance of the nitro-N—O⋯π inter­action upon the packing; this inter­action is reflected in the pair of short spikes d_e + d_i ∼3.0 Å, Fig. 7(f).

Table 5
Percentage contributions of inter­atomic contacts to the Hirshfeld surface for (I)

Contact	Percentage contribution
H⋯H	31.8
O⋯H/H⋯O	30.7
C⋯H/H⋯C	10.3
S⋯H/H⋯S	13.9
C⋯O/O⋯C	5.8
N⋯H/H⋯N	1.9
O⋯O	1.6
C⋯N/N⋯C	1.5
C⋯C	1.3
N⋯O/O⋯N	0.9
N⋯N	0.3

Figure 7 (a) A comparison of the full two-dimensional fingerprint plot for (I) and those delineated into (b) H⋯H, (c) O⋯H/H⋯O, (d) C⋯H/H⋯C, (e) S⋯H/H⋯S and (f) C⋯O/O⋯C contacts.

6. Computational chemistry

The energy calculations were performed using DFT-wB97XD/aug-cc-pVTZ (Woon & Dunning, 1993) to evaluate the strength of the inter­molecular O—H⋯O, O—H⋯S and C—H⋯O inter­actions between the respective pairs of mol­ecules. The BSSE corrected inter­action energies (E^BSSE_int) are listed in Table 6. From these data, it is clear the O—H⋯O hydrogen bond has the greatest inter­action energy, followed by C—H⋯O and O—H⋯S. These results reflect those reported recently for the 4-methyl analogue (Tan, Azizan et al., 2019).

Table 6
Summary of inter­action energies (kcal mol⁻¹) calculated for several directional contacts in (I)

Contact	Etot
O1—H1O⋯O2	−14.04
O2—H2O⋯S1	−5.60
C8—H8⋯O3	−10.05

The non-covalent inter­action plots generated by calculations performed with NCIPLOT (Johnson et al., 2010) provide complementary results for the inter­action energies. Thus, the pairs of mol­ecules associated with each of the energies tabulated in Table 6 were subjected to calculation as this provides a useful visualization index corresponding to the strength of any non-covalent inter­actions through a red–blue–green colour scheme on the isosurface. Thus, a blue coloration is indicative of a strong attractive inter­action, green indicates a weak inter­action while red is indicative of a strong repulsive inter­action (Contreras-García et al., 2011). As seen from Fig. 8, the O—H⋯O inter­action is clearly strong and attractive, while each of O—H⋯S and C—H⋯O are less so.

Figure 8 The non-covalent inter­action (NCI) plots for the dimeric aggregates in (I) sustained by (a) O—H⋯O, (b) O—H⋯S and (c) C—H⋯O inter­actions (highlighted in boxes) and (d) plot of RDG versus sign(λ^2)ρ(r). The gradient cut-off is set at 0.4 and the colour scale is −0.03 < ρ < 0.03 atomic units.

From the aforementioned, the mol­ecular packing is clearly governed by directional hydrogen bonding between mol­ecules. The simulated energy frameworks (Turner et al., 2017) were calculated to compare the topology of the inter­molecular inter­actions in the crystal of (I). An analysis of the resultant energy frameworks is shown in Fig. 9 and reveals the crystal of (I) is mainly stabilized by electrostatic and dispersive forces. The total electrostatic energy (E_{electrostatic}) of all pairwise inter­actions sums to −45.89 kcal/mol, while the total dispersion energy term (E_dispersion) computes to −51.51 kcal/mol.

Figure 9 The energy framework diagrams for (I) showing (a) Eelectrostatic (red cylinders), (b) Edispersion (green cylinders) and (c) Etotal (blue cylinders), viewed along the a axis. The frameworks were adjusted to the same scale factor of 50 with a cut-off value of 2.39 kcal/mol within 2 × 2 × 2 unit cells. The corresponding cylinder radii are proportional to the relative magnitude of the energies.

7. Database survey

There are three literature precedents to (I), i.e. mol­ecules of the general formula 4-YC₆H₄C(=O)N(H)C(=S)N(CH₂CH₂OH)₂, namely Y = H, which has been reported twice (Koch et al., 1995; Cornejo et al., 2005), Y = F (Hennig et al., 2009) and Y = Me (Tan, Azizan et al., 2019). As seen in the overlay diagram of Fig. 10, whereby the central CN₂S residues are overlapped, there is a very close coincidence in the mol­ecular structures. The differences in conformation are most conveniently expressed in terms of the dihedral angles formed between the central CN₂S chromophore and pendant aryl ring, i.e. 65.92 (12), 68.96 (12), 69.51 (8) and 72.15 (10)° for (I) and Y = H, F and Me, respectively.

Figure 10 An overlay diagram of the four known structures of general formula 4-YC6H4C(=O)N(H)C(=S)N(CH2CH2OH)2: Y = NO2 (I) red image, Y = H (green), Y = F (blue) and Y = Me (pink). The mol­ecules are overlapped so the central CN2S residues are coincident.

The mol­ecular packing in the crystals is also very similar with the formation of the intra­molecular thio­amide-N—H⋯O(hy­droxy) hydrogen bond as well as the inter­molecular hy­droxy-O—H⋯O(hy­droxy) hydrogen and hy­droxy-O—H⋯S(thione) hydrogen bonding, leading to a supra­molecular layer in each case.

8. Synthesis and crystallization

Synthesis of (I): an excess of thionyl chloride (Merck) was mixed with 4-nitro­benzoic acid (Merck, 1 mmol) and the resulting solution was refluxed until a pale-yellow solution was obtained. The excess thionyl chloride was removed on a water bath, leaving only 4-nitro­benzoyl chloride, which is a yellow, viscous liquid. Ammonium thio­cyanate (Fisher, 1 mmol) was added to an acetone (30 ml) solution of 4-nitro­benzoyl chloride (1 mmol). The solution turned yellow after stirring for 2 h. The white precipitate (ammonium chloride) was isolated upon filtration and to the yellow filtrate, bis­(hy­droxy­eth­yl)amine (Acros, 1 mmol) was carefully added followed by stirring for 1 h. Upon the addition of di­chloro­methane (50 ml), a yellow precipitate was obtained, which was collected by filtration. Recrystallization was from its hot acetone solution yielding pale-yellow blocks of (I) after slow evaporation. Yield 69%. M.p. (Hanon MP-450 melting point apparatus): 411.5–413.7 K. IR (Bruker Vertex 70v FT–IR spectrophotometer, cm⁻¹): 3277 (br, νOH), 3170 (br, νNH), 3077 (w, νCH_aro), 2973–2882 (w, νCH), 1692 (s, νC=O), 1538 (s, νN=O_asym), 1524 (s, νC=C), 1343 (s, νN=O_sym), 1270 (s, νC—N), 1053 (s, νC=S), 734 (s, δCH). UV (Shimadzu UV 3600 Plus UV–vis spectrophotometer; ethanol:aceto­nitrile (1/1): λ_max nm (log ∊) 366.4 (4.16), 301.6 (4.88), 271.2 (5.00), 205.8 (5.14).

The pyrolytic process (Perkin Elmer STA 6000 Simultaneous Thermogravimetric Analyzer) for (I) showed the liberation of NO₂, equivalent a 15% weight loss, in the first stage in the range 194 and 222°C. This was followed by the liberation of a benzene mol­ecule, corresponding to 29% weight loss, between 222 and 282°C, whereas the subsequent stages involve the pyrolysis of CO (282 to 360°C) and OH (360 to 496°C) corresponding to 15 and 11% weight loss, respectively. Gradual weight loss continued beyond 800°C.

9. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 7. Carbon-bound H atoms were placed in calculated positions (C—H = 0.95–0.99 Å) and were included in the refinement in the riding-model approximation, with U_iso(H) set to 1.2U_eq(C). The O- and N-bound H atoms were located from a difference map and refined with O—H and N—H = 0.84±0.01 and 0.88±0.01 Å, respectively, and with U_iso(H) = 1.5U_eq(O) and 1.2U_eq(N).

Table 7
Experimental details

Crystal data
Chemical formula	C12H15N3O5S
Mr	313.33
Crystal system, space group	Monoclinic, P21/c
Temperature (K)	100
a, b, c (Å)	7.4203 (2), 10.3241 (3), 18.4191 (6)
β (°)	95.471 (2)
V (Å^3)	1404.62 (7)
Z	4
Radiation type	Mo Kα
μ (mm^−1)	0.26
Crystal size (mm)	0.12 × 0.11 × 0.09
Data collection
Diffractometer	Bruker SMART APEX diffractometer
Absorption correction	Multi-scan (SADABS; Sheldrick, 1996)
Tmin, Tmax	0.970, 0.977
No. of measured, independent and observed [I > 2σ(I)] reflections	13082, 3233, 2621
Rint	0.041
(sin θ/λ)max (Å^−1)	0.650
Refinement
R[F^2 > 2σ(F^2)], wR(F^2), S	0.037, 0.093, 1.04
No. of reflections	3233
No. of parameters	200
No. of restraints	3
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å^−3)	0.33, −0.25
Computer programs: SMART and SAINT (Bruker, 2008), SHELXS97 (Sheldrick, 2015a), SHELXL2014/7 (Sheldrick, 2015b), ORTEP-3 for Windows (Farrugia, 2012), DIAMOND (Brandenburg, 2006) and publCIF (Westrip, 2010).

Supporting information

Computing details

Data collection: SMART (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014/7 (Sheldrick, 2015b); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012), DIAMOND (Brandenburg, 2006); software used to prepare material for publication: publCIF (Westrip, 2010).

(I)

Crystal data

C12H15N3O5S	F(000) = 656
Mr = 313.33	Dx = 1.482 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 7.4203 (2) Å	Cell parameters from 2434 reflections
b = 10.3241 (3) Å	θ = 2.3–25.8°
c = 18.4191 (6) Å	µ = 0.26 mm^−1
β = 95.471 (2)°	T = 100 K
V = 1404.62 (7) Å^3	Block, pale yellow
Z = 4	0.12 × 0.11 × 0.09 mm

Data collection

Bruker SMART APEX diffractometer	3233 independent reflections
Radiation source: fine-focus sealed tube	2621 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.041
φ and ω scans	θmax = 27.5°, θmin = 2.2°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −9→9
Tmin = 0.970, Tmax = 0.977	k = −13→13
13082 measured reflections	l = −23→23

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.037	Hydrogen site location: mixed
wR(F^2) = 0.093	H atoms treated by a mixture of independent and constrained refinement
S = 1.04	w = 1/[σ^2(Fo^2) + (0.042P)^2 + 0.3083P] where P = (Fo^2 + 2Fc^2)/3
3233 reflections	(Δ/σ)max = 0.001
200 parameters	Δρmax = 0.33 e Å^−3
3 restraints	Δρmin = −0.25 e Å^−3

Special details

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
S1	0.74915 (5)	0.45567 (4)	0.59498 (2)	0.02217 (12)
O1	0.72148 (15)	0.75229 (11)	0.77993 (8)	0.0313 (3)
H1O	0.760 (3)	0.8221 (13)	0.7992 (11)	0.047*
O2	0.16441 (15)	0.47542 (11)	0.65347 (6)	0.0219 (3)
H2O	0.0554 (16)	0.466 (2)	0.6367 (12)	0.051 (7)*
O3	0.88241 (15)	0.29890 (10)	0.73714 (6)	0.0221 (3)
O4	1.35804 (19)	0.56698 (14)	1.06330 (7)	0.0407 (4)
O5	1.3728 (2)	0.35951 (15)	1.07036 (8)	0.0538 (4)
N1	0.52846 (17)	0.57554 (12)	0.67890 (7)	0.0168 (3)
N2	0.80071 (17)	0.51231 (12)	0.73839 (7)	0.0174 (3)
H2N	0.801 (2)	0.5824 (12)	0.7648 (8)	0.021*
N3	1.3235 (2)	0.45902 (16)	1.03874 (8)	0.0300 (4)
C1	0.6860 (2)	0.51602 (14)	0.67325 (8)	0.0167 (3)
C2	0.4669 (2)	0.61682 (14)	0.74939 (8)	0.0181 (3)
H2A	0.5141	0.5555	0.7879	0.022*
H2B	0.3330	0.6135	0.7461	0.022*
C3	0.5291 (2)	0.75230 (15)	0.77061 (10)	0.0232 (4)
H3A	0.4853	0.8146	0.7320	0.028*
H3B	0.4800	0.7783	0.8166	0.028*
C4	0.4055 (2)	0.60787 (16)	0.61391 (8)	0.0211 (3)
H4A	0.4779	0.6236	0.5723	0.025*
H4B	0.3402	0.6889	0.6232	0.025*
C5	0.2690 (2)	0.50167 (17)	0.59362 (9)	0.0224 (3)
H5A	0.1876	0.5288	0.5506	0.027*
H5B	0.3329	0.4220	0.5807	0.027*
C6	0.89516 (19)	0.40521 (14)	0.76552 (8)	0.0163 (3)
C7	1.0107 (2)	0.42635 (14)	0.83615 (8)	0.0172 (3)
C8	1.0674 (2)	0.54755 (15)	0.86196 (9)	0.0205 (3)
H8	1.0348	0.6228	0.8340	0.025*
C9	1.1712 (2)	0.55922 (16)	0.92821 (9)	0.0229 (4)
H9	1.2105	0.6417	0.9463	0.027*
C10	1.2160 (2)	0.44763 (17)	0.96720 (9)	0.0225 (4)
C11	1.1652 (2)	0.32570 (16)	0.94236 (9)	0.0249 (4)
H11	1.2000	0.2507	0.9702	0.030*
C12	1.0628 (2)	0.31546 (15)	0.87614 (9)	0.0222 (3)
H12	1.0275	0.2325	0.8576	0.027*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
S1	0.0180 (2)	0.0320 (2)	0.0167 (2)	0.00001 (16)	0.00252 (15)	−0.00347 (16)
O1	0.0161 (6)	0.0216 (6)	0.0562 (9)	−0.0018 (5)	0.0031 (6)	−0.0148 (6)
O2	0.0150 (6)	0.0302 (6)	0.0202 (6)	−0.0025 (5)	0.0007 (5)	0.0039 (5)
O3	0.0206 (6)	0.0177 (6)	0.0274 (6)	0.0012 (4)	−0.0010 (5)	−0.0045 (5)
O4	0.0425 (8)	0.0469 (8)	0.0303 (7)	−0.0041 (7)	−0.0090 (6)	−0.0105 (6)
O5	0.0680 (11)	0.0522 (9)	0.0356 (8)	−0.0006 (8)	−0.0231 (8)	0.0156 (7)
N1	0.0158 (6)	0.0181 (6)	0.0166 (6)	0.0005 (5)	0.0015 (5)	0.0018 (5)
N2	0.0171 (7)	0.0172 (6)	0.0177 (6)	0.0020 (5)	0.0000 (5)	−0.0032 (5)
N3	0.0241 (8)	0.0442 (10)	0.0212 (7)	−0.0019 (7)	−0.0010 (6)	0.0024 (7)
C1	0.0150 (7)	0.0157 (7)	0.0190 (8)	−0.0025 (6)	0.0003 (6)	0.0011 (6)
C2	0.0167 (8)	0.0183 (7)	0.0198 (7)	0.0008 (6)	0.0035 (6)	−0.0007 (6)
C3	0.0162 (8)	0.0208 (8)	0.0324 (9)	0.0023 (6)	0.0009 (7)	−0.0043 (7)
C4	0.0178 (8)	0.0258 (8)	0.0191 (8)	0.0014 (6)	−0.0007 (6)	0.0069 (7)
C5	0.0169 (8)	0.0334 (9)	0.0167 (8)	−0.0003 (7)	0.0010 (6)	0.0013 (7)
C6	0.0125 (7)	0.0175 (7)	0.0193 (7)	−0.0003 (6)	0.0041 (6)	−0.0001 (6)
C7	0.0136 (7)	0.0198 (8)	0.0187 (8)	0.0012 (6)	0.0038 (6)	0.0008 (6)
C8	0.0188 (8)	0.0194 (8)	0.0228 (8)	−0.0006 (6)	0.0003 (6)	0.0034 (6)
C9	0.0215 (8)	0.0223 (8)	0.0243 (8)	−0.0039 (6)	−0.0001 (7)	−0.0029 (7)
C10	0.0174 (8)	0.0329 (9)	0.0169 (8)	0.0008 (7)	−0.0005 (6)	0.0005 (7)
C11	0.0257 (9)	0.0238 (8)	0.0248 (8)	0.0049 (7)	0.0004 (7)	0.0077 (7)
C12	0.0224 (8)	0.0185 (8)	0.0254 (8)	0.0027 (6)	0.0008 (7)	−0.0001 (6)

Geometric parameters (Å, º)

S1—C1	1.6777 (16)	C3—H3A	0.9900
O1—C3	1.4218 (19)	C3—H3B	0.9900
O1—H1O	0.843 (10)	C4—C5	1.515 (2)
O2—C5	1.4331 (19)	C4—H4A	0.9900
O2—H2O	0.844 (10)	C4—H4B	0.9900
O3—C6	1.2156 (18)	C5—H5A	0.9900
O4—N3	1.221 (2)	C5—H5B	0.9900
O5—N3	1.220 (2)	C6—C7	1.504 (2)
N1—C1	1.334 (2)	C7—C8	1.389 (2)
N1—C4	1.4723 (19)	C7—C12	1.396 (2)
N1—C2	1.4796 (19)	C8—C9	1.385 (2)
N2—C6	1.3771 (19)	C8—H8	0.9500
N2—C1	1.4038 (19)	C9—C10	1.381 (2)
N2—H2N	0.871 (9)	C9—H9	0.9500
N3—C10	1.479 (2)	C10—C11	1.379 (2)
C2—C3	1.512 (2)	C11—C12	1.378 (2)
C2—H2A	0.9900	C11—H11	0.9500
C2—H2B	0.9900	C12—H12	0.9500
C3—O1—H1O	110.5 (15)	C5—C4—H4B	109.1
C5—O2—H2O	108.2 (16)	H4A—C4—H4B	107.8
C1—N1—C4	121.38 (13)	O2—C5—C4	110.21 (13)
C1—N1—C2	123.19 (13)	O2—C5—H5A	109.6
C4—N1—C2	115.41 (12)	C4—C5—H5A	109.6
C6—N2—C1	125.31 (13)	O2—C5—H5B	109.6
C6—N2—H2N	119.3 (11)	C4—C5—H5B	109.6
C1—N2—H2N	115.1 (11)	H5A—C5—H5B	108.1
O5—N3—O4	123.33 (16)	O3—C6—N2	123.57 (14)
O5—N3—C10	118.05 (15)	O3—C6—C7	121.17 (13)
O4—N3—C10	118.63 (15)	N2—C6—C7	115.20 (13)
N1—C1—N2	114.23 (13)	C8—C7—C12	119.91 (14)
N1—C1—S1	123.83 (12)	C8—C7—C6	123.75 (14)
N2—C1—S1	121.89 (11)	C12—C7—C6	116.34 (14)
N1—C2—C3	112.40 (13)	C9—C8—C7	120.31 (15)
N1—C2—H2A	109.1	C9—C8—H8	119.8
C3—C2—H2A	109.1	C7—C8—H8	119.8
N1—C2—H2B	109.1	C10—C9—C8	118.14 (15)
C3—C2—H2B	109.1	C10—C9—H9	120.9
H2A—C2—H2B	107.9	C8—C9—H9	120.9
O1—C3—C2	108.01 (12)	C11—C10—C9	122.97 (15)
O1—C3—H3A	110.1	C11—C10—N3	118.37 (15)
C2—C3—H3A	110.1	C9—C10—N3	118.66 (15)
O1—C3—H3B	110.1	C12—C11—C10	118.26 (15)
C2—C3—H3B	110.1	C12—C11—H11	120.9
H3A—C3—H3B	108.4	C10—C11—H11	120.9
N1—C4—C5	112.61 (13)	C11—C12—C7	120.37 (15)
N1—C4—H4A	109.1	C11—C12—H12	119.8
C5—C4—H4A	109.1	C7—C12—H12	119.8
N1—C4—H4B	109.1
C4—N1—C1—N2	169.47 (13)	O3—C6—C7—C12	−16.0 (2)
C2—N1—C1—N2	−8.8 (2)	N2—C6—C7—C12	161.02 (14)
C4—N1—C1—S1	−8.0 (2)	C12—C7—C8—C9	−1.8 (2)
C2—N1—C1—S1	173.80 (11)	C6—C7—C8—C9	178.89 (14)
C6—N2—C1—N1	134.76 (15)	C7—C8—C9—C10	0.1 (2)
C6—N2—C1—S1	−47.8 (2)	C8—C9—C10—C11	1.4 (3)
C1—N1—C2—C3	89.24 (17)	C8—C9—C10—N3	−178.75 (15)
C4—N1—C2—C3	−89.11 (16)	O5—N3—C10—C11	4.8 (2)
N1—C2—C3—O1	−62.76 (17)	O4—N3—C10—C11	−174.96 (16)
C1—N1—C4—C5	91.30 (17)	O5—N3—C10—C9	−175.05 (17)
C2—N1—C4—C5	−90.33 (16)	O4—N3—C10—C9	5.2 (2)
N1—C4—C5—O2	57.76 (17)	C9—C10—C11—C12	−1.1 (3)
C1—N2—C6—O3	−3.6 (2)	N3—C10—C11—C12	179.10 (15)
C1—N2—C6—C7	179.39 (13)	C10—C11—C12—C7	−0.8 (2)
O3—C6—C7—C8	163.29 (15)	C8—C7—C12—C11	2.2 (2)
N2—C6—C7—C8	−19.7 (2)	C6—C7—C12—C11	−178.47 (14)

Hydrogen-bond geometry (Å, º)

Cg1 is the centroid of the (C7–C12) ring.

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2N···O1	0.87 (1)	1.88 (1)	2.6749 (17)	151 (1)
O1—H1O···O2^i	0.84 (2)	1.87 (2)	2.7075 (17)	176 (2)
O2—H2O···S1^ii	0.84 (1)	2.33 (1)	3.1724 (12)	175 (2)
C2—H2B···O3^i	0.99	2.53	3.2305 (18)	127
C5—H5A···S1^iii	0.99	2.77	3.4915 (17)	130
C8—H8···O3^iv	0.95	2.36	3.2147 (19)	150
N3—O4···Cg1^v	1.22 (1)	3.63 (1)	3.6927 (16)	83 (1)

Symmetry codes: (i) −x+1, y+1/2, −z+3/2; (ii) x−1, y, z; (iii) −x+1, −y+1, −z+1; (iv) −x+2, y+1/2, −z+3/2; (v) −x+2, −y+1, −z+2.