2-Ethyl-1-[5-(4-methyl­phen­yl)pyrazol-3-yl]-3-(thio­phene-2-carbon­yl)iso­thio­urea: mol­ecular ribbons containing three types of hydrogen-bonded ring

The title compound, C₁₈H₁₈N₄OS₂, was prepared by reaction of S,S-diethyl 2-thenoylimidodi­thio­carbonate with 5-amino-3-(4-methyl­phen­yl)-1H-pyrazole using microwave irradiation under solvent-free conditions. In the mol­ecule, the thio­phene unit is disordered over two sets of atomic sites, with occupancies of 0.814 (4) and 0.186 (4), and the bonded distances provide evidence for polarization in the acyl­thio­urea fragment and for aromatic type delocalization in the pyrazole ring. An intra­molecular N—H...O hydrogen bond is present, forming an S(6) motif, and mol­ecules are linked by N—H...O and N—H...N hydrogen bonds to form a ribbon in which centrosymmetric R₂²(4) rings, built from N—H...O hydrogen bonds and flanked by inversion-related pairs of S(6) rings, alternate with centrosymmetric R₂²(6) rings built from N—H...N hydrogen bonds.

S1. Introduction

Iso­thio­urea derivatives exhibit a range of biological behaviour, including pharmacological activity on the central nervous system (Harada et al., 2004; Witkin & Nelson, 2004; Montes et al., 2005) and action as potent inhibitors of various enzyme systems (Di Giacomo et al., 2003; Witkin & Nelson, 2004), including nitric oxide synthase (Di Giacomo et al., 2003; Basaran et al., 2005; Oliveira et al., 2011). S-Alkyl­iso­thio­ureas, such as S-methyl­iso­thio­urea and S-(3-di­methyl­amino­propyl)­iso­thio­urea (dimaprit) are two of the inhibitors most commonly used against nitric oxide synthase (Basaran et al., 2005; Oliveira et al., 2011), while the N,S-di­alkyl­iso­thio­urea clobenpropit (Harada et al., 2004) can be used as an anti­convulsant. In synthesis, pyrazolyliso­thio­ureas have been used as inter­mediates in the preparation of pyrazolo­[1,5-a][1,3,5]triazines (Insuasty, Estrada, Cobo et al., 2006; Insuasty, Estrada, Cortés et al., 2006; Insuasty et al., 2012), which are important as analogues of known anti­depressant (Gilligan et al., 2009; Saito et al., 2011), anti-inflammatory (Raboisson et al., 2008), anti­tumoural (Popowycz et al., 2009) and anti­viral agents (Gudmundsson et al., 2009). With these considerations in mind, we have now prepared 2-ethyl-1-[5-(4-methyl­phenyl)­pyrazol-3-yl]-3-(thio­phen-2-carbonyl)­iso­thio­urea, (I) (see Scheme 1) whose structure we report here.

S2. Experimental

S2.1. Synthesis and crystallization

A mixture of S,S-di­ethyl 2-thenoylimido­thio­carbonate (0.015 mol) and 5-amino-3-(4-methyl­phenyl)-1H-pyrazole (0.015 mol) was subjected to microwave irradiation in the absence of solvent (maximum power 300 W, for 3 min at a temperature of 433 K), using a focused microwave reactor (CEM Discover). When the reaction was complete, as indicated by thin-layer chromatography, the crude product was dissolved in chloro­form (3.0 ml) and purified by column chromatography on silica gel, using a mixture of hexanes and ethyl acetate (4:1 v/v) as eluent to give the title compound, (I). After removal of the solvent under reduced pressure, crystallization from ethyl acetate, at ambient temperature and in the presence of air, provided colourless crystals suitable for single-crystal X-ray diffraction (yield 51%, m.p. 404 K).

S2.2. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1. H atoms were located in difference maps. H atoms bonded to C atoms were subsequently treated as riding atoms in geometrically idealized positions, with C—H = 0.95 (aromatic and heterocyclic), 0.98 (CH₃) or 0.99 Å (CH₂), and with U_iso(H) = kU_eq(C) where k = 1.5 for the methyl groups, which were permitted to rotate but not to tilt, and 1.2 for all other H atoms bonded to C atoms. For H atoms bonded to N atoms, the atomic coordinates were refined with U_iso(H) = 1.2U_eq(N), giving the N—H distances shown in Table 3. Four low-angle reflections (011, 110, 110 and 111), which had been attenuated by the beam stop, were omitted from the refinements. Examination of the refined structure at this stage revealed some unsatisfactory inter­atomic distances in the thio­phene unit: the two C—C double-bond distances were very different [1.511 (6) Å for C32—C33 and 1.357 (7) Å for C34—C35] and the former of these appeared to be significantly larger than the formal single-bond distance [C33—C34 = 1.490 (6) Å]. In addition, the largest peak in the difference map was close to atom C33 and the deepest hole was close to atom S31. Accordingly, the thio­phene unit was modelled using two sets of atomic sites, related to one another by a rotation of approximately 180° around the C31—C32 bond. For the minor-disorder component, the bonded distances and the one-angle non-bonded distances were restrained to be the same as the corresponding distances in the major component, subject to uncertainties of 0.005 Å and 0.01 Å, respectively. The H atoms of the minor component were included in the refinement in calculated positions, with C—H = 0.95 Å and U_iso(H) = 1.2U_eq(C), and the anisotropic displacement parameters for pairs of atoms occupying approximately the same regions of space were constrained to be identical. Subject to these conditions, the site occupancies of the two components refined to 0.814 (4) and 0.286 (4), respectively, with a dihedral angle between their mean planes of 4.4 (14)°.

S3. Results and discussion

The title iso­thio­urea, (I), was synthesized by the reaction between S,S-di­ethyl thenoylimidodi­thio­carbonate, (A) (see Scheme 1), and 5-amino-3-(4-methyl­phenyl)-1H-pyrazole, (B), using a brief period of microwave irradiation under solvent-free conditions. The reaction proceeds by elimination of ethane­thiol which is a gas under the reaction conditions employed (b.p. 308 K), and the formation of this volatile by-product and its loss from the reaction system undoubtedly provides an effective entropic driver for the formation of (I). The aims of this study were not only the confirmation of the molecular constitution of compound (I) but also the determination of its conformation and the mode of supra­molecular assembly. The structure analysis found no indication whatever of the presence of any of the other possible conformations, in particular the conformation (Ib) (see Scheme 2) or of any of its tautomers, which would be a necessary precursor for the formation of the potential condensation product, the pyrazolo­[1,5-a][1,3,5]triazine, (II), although such bicyclic products are readily obtained when solutions of N-substituted S,S-di­ethyl imidodi­thio­carbonates and 5-amino-1H-pyrazoles in N,N-di­methyl­formamide are heated under reflux (Insuasty, Estrada, Cobo et al., 2006; Insuasty, Insuasty et al., 2012).

The central spacer unit between atoms C13 and C32 is very nearly planar, as indicated by the relevant torsion angles (Table 2). For the atoms forming the spacer unit, the maximum deviation from their mean plane is 0.025 (2) Å for atom N1, with an r.m.s. deviation of 0.014 Å. Associated with this near planarity, the structure contains an intra­molecular N—H···O hydrogen bond (Table 3), forming an S(6) motif (Bernstein et al., 1995). The dihedral angles between the plane of the spacer unit and the pyrazole ring, and the major component of the disordered thio­phene ring are 58.82 (13) and 10.0 (6)°, respectively, while that between the pyrazole and phenyl rings is 19.96 (18)°. Accordingly, molecules of (I) exhibit no inter­nal symmetry and so they are conformationally chiral: the centrosymmetric space group accommodates equal numbers of the two conformational enanti­omers, although the conformational chirality has no chemical significance. It seems likely that the conformation is influenced by the presence of the intra­molecular hydrogen bond, as this is likely to be absent from conformations such as (Ib) (see Scheme 2).

The bond distances in the molecule of (I) (Table 2) present some inter­esting features. In the central spacer unit, the distances for N1—C2 and C2—N3, which are formally single and double bonds, respectively, differ by less than 0.025 Å, while the formal single bond N3—C31 is somewhat shorted than the single bond N1—C13, and the carbonyl bond C31—O31 is typical of those in simple amides [mean value (Allen et al., 1987) 1.231 Å, upper quartile value 1.238 Å], where considerable electronic delocalization can occur. These observations, taken together, indicate that the polarized form (Ia) (see Scheme 1) is a significant contributor to the overall electronic structure in addition to the classical form (I), and that the intra­molecular N—H···O hydrogen bond should be regarded as charge-assisted (Gilli et al., 1994). Within the pyrazole ring, the distances (Table 2) for N11—C15 and N12—C1, which are formally single and double bonds, respectively, differ by less than 0.02 Å, as do those for C13—C14 and C14—C15, which again are formally single and double bonds. These observations indicate a significant degree of aromatic type delocalization within the pyrazole ring, cf. (Ia), although the large dihedral angle between the pyrazole ring and the central spacer unit effectively rules out the possibility of any more extended conjugation.

The supra­molecular assembly in compound (I) is fairly simple and depends upon only two hydrogen bonds, one each of the N—H···N and N—H···O types (Table 3). An inversion-related pair of molecules is linked by N—H···N hydrogen bonds to form a centrosymmetric dimer, centred at (1/2, 1/2, 1/2) and characterized by an R₂²(6) motif (Fig. 2). The N1—H1 bond participates in an almost-planar charge-assisted three-centre N—H···(O)₂ system, where one component is the intra­molecular hydrogen bond mentioned above and where the other component links an inversion-related pair of molecules in a centrosymmetric R₂²(4) motif centred at (1/2, 0, 1/2) and flanked by an inversion-related pair of S(6) rings (Fig. 2). The combination of these motifs generates a molecular ribbon, or chain of rings, in which the R₂²(4) centred at (1/2, n, 1/2) alternate with the R₂²(6) rings centred at (1/2, n+1/2, 1/2), where n represents an integer in each case (Fig. 2). One ribbon of this type passes through each unit cell, but there are no significant direction-specific inter­actions between adjacent ribbons.

There are, however, three inter­molecular C—H···π contacts in the structure of (I) (Table 3), but none of them can be regarded as structurally significant. One of them involves an aliphatic C—H bond of low acidity, while the C—H bonds in the other two contacts are components of the disordered thio­phene unit. The contacts involving atoms C21 and C44 have very long H···centroid and C···centroid distances, while that involving atom C32 has a very narrow C—H···centroid angle (cf. Wood et al., 2009).

It is of inter­est briefly to compare both the conformation and the supra­molecular assembly in compound (I) with the corresponding behaviour of the tris-substituted iso­thio­urea compound (III) (Sudha et al., 1996) (see Scheme 2). In compound (III), the orientation of both N-aryl substituents differs from the N-substituents in (I) and this may, in part, be a consequence of the intra­molecular N—H···N contact. However, in view of the rather small N—H···N angle here, 123 (2)°, this contact would probably not now be regarded as an effective hydrogen bond (cf. Wood et al., 2009). On the other hand, the structure of (III) contains a fairly short C—H···π(arene) hydrogen bond, unremarked in the original structure report (Sudha et al., 1996), with dimensions H···Cg = 2.68 (3) Å, C···Cg = 3.600 (3) Å and C—H···Cg 162 (3)° (Cg is the centroid of the arene ring [addition OK?]), which links molecules related by a 2₁ screw axis into chains running parallel to the [010] direction (Fig. 3). There are, however, no N—H···O hydrogen bonds or inter­molecular N—H···N hydrogen bonds in the structure of compound (III); neither (I) nor (III) contains and aromatic π–π stacking inter­actions, possibly because these are effectively prevented by the methyl substituents on the aryl rings.

Related literature

For related literature, see: Allen et al. (1987); Basaran et al. (2005); Bernstein et al. (1995); Di Giacomo, Sorrenti, Salerno, Cardile, Guerrera, Siracusa, Avitabile & Vanella (2003); Gilli et al. (1994); Gilligan et al. (2009); Gudmundsson et al. (2009); Harada et al. (2004); Insuasty et al. (2012); Insuasty, Estrada, Cobo, Low & Glidewell (2006); Insuasty, Estrada, Cortés, Quiroga, Insuasty, Abonía, Nogueras & Cobo (2006); Montes et al. (2005); Oliveira et al. (2011); Popowycz et al. (2009); Raboisson et al. (2008); Saito et al. (2011); Sudha et al. (1996); Witkin & Nelson (2004); Wood et al. (2009).

Computing details

Data collection: COLLECT (Hooft, 1999); cell refinement: DIRAX/LSQ (Duisenberg et al., 2000); data reduction: EVALCCD (Duisenberg et al., 2003); program(s) used to solve structure: SIR2011 (Burla et al., 2012); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2008, 2014); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2008, 2014) and PLATON (Spek, 2009).

Figures

	Fig. 1. The molecular structure of compound (I), showing the atom-labelling scheme and the intramolecular N—H···O hydrogen bond. The atomic coordinates for the C32 and C42 sites were constrained to be identical and the refined occupancies of the two disorder components are 0.814 (4) and 0,186 (4).
	Fig. 2. A stereoview of part of the crystal structure of compound (I), showing the formation of a chain of alternating R2^2(4) and R2^2(6) rings running parallel to the [010] direction. Hydrogen bonds are shown as dashed lines and H atoms bonded to C atoms have been omitted.
	Fig. 3. A stereoview of part of the crystal structure of compound (III), showing the formation of a chain built from C—H···π(arene) hydrogen bonds, depicted as dashed lines, running parallel to the [010] direction. The original atomic coordinates (Sudha et al., 1996) have been used and, for the sake of clarity, H atoms bonded to C or N atoms which are not involved in the motif shown have been omitted.

2-Ethyl-1-[5-(4-methylphenyl)pyrazol-3-yl]-3-(thiophen-2-carbonyl)isothiourea

Crystal data

C18H18N4OS2	Z = 2
Mr = 370.48	F(000) = 388
Triclinic, P1	Dx = 1.366 Mg m^−3
a = 7.998 (2) Å	Mo Kα radiation, λ = 0.71073 Å
b = 11.085 (3) Å	Cell parameters from 4118 reflections
c = 11.696 (2) Å	θ = 3.1–27.5°
α = 61.92 (2)°	µ = 0.31 mm^−1
β = 84.921 (18)°	T = 120 K
γ = 79.928 (19)°	Block, colourless
V = 900.8 (4) Å^3	0.36 × 0.32 × 0.22 mm

Data collection

Bruker–Nonius KappaCCD diffractometer	4114 independent reflections
Radiation source: Bruker-Nonius FR591 rotating anode	2350 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.097
Detector resolution: 9.091 pixels mm^-1	θmax = 27.5°, θmin = 3.5°
ϕ and ω scans	h = −10→10
Absorption correction: multi-scan (SADABS; Sheldrick, 2003)	k = −14→14
Tmin = 0.835, Tmax = 0.934	l = −14→15
12759 measured reflections

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)] = 0.057	Hydrogen site location: mixed
wR(F^2) = 0.119	H atoms treated by a mixture of independent and constrained refinement
S = 1.02	w = 1/[σ^2(Fo^2) + (0.0281P)^2 + 0.6991P] where P = (Fo^2 + 2Fc^2)/3
4114 reflections	(Δ/σ)max < 0.001
247 parameters	Δρmax = 0.30 e Å^−3
10 restraints	Δρmin = −0.37 e Å^−3

Special details

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.

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
N1	0.3279 (3)	0.2082 (3)	0.4701 (3)	0.0225 (6)
H1	0.368 (4)	0.135 (3)	0.461 (3)	0.027*
C2	0.1951 (4)	0.1888 (3)	0.5529 (3)	0.0213 (7)
N3	0.1319 (3)	0.0718 (3)	0.6188 (3)	0.0218 (6)
N11	0.5020 (3)	0.5098 (3)	0.3601 (2)	0.0206 (6)
H11	0.536 (4)	0.567 (3)	0.386 (3)	0.025*
N12	0.4531 (3)	0.3925 (3)	0.4597 (2)	0.0219 (6)
C13	0.3919 (4)	0.3340 (3)	0.3977 (3)	0.0202 (7)
C14	0.4022 (4)	0.4109 (3)	0.2628 (3)	0.0211 (7)
H14	0.3681	0.3892	0.1997	0.025*
C15	0.4728 (4)	0.5251 (3)	0.2411 (3)	0.0188 (6)
C151	0.5089 (4)	0.6473 (3)	0.1196 (3)	0.0210 (7)
C152	0.6171 (4)	0.7337 (3)	0.1179 (3)	0.0240 (7)
H152	0.6769	0.7104	0.1939	0.029*
C153	0.6378 (4)	0.8549 (3)	0.0045 (3)	0.0253 (7)
H153	0.7113	0.9132	0.0053	0.030*
C154	0.5537 (4)	0.8929 (3)	−0.1101 (3)	0.0239 (7)
C155	0.4511 (4)	0.8038 (3)	−0.1086 (3)	0.0297 (8)
H155	0.3959	0.8249	−0.1859	0.036*
C156	0.4272 (4)	0.6840 (4)	0.0040 (3)	0.0292 (8)
H156	0.3540	0.6258	0.0025	0.035*
C157	0.5691 (5)	1.0279 (3)	−0.2324 (3)	0.0321 (8)
H17A	0.6452	1.0786	−0.2163	0.048*
H17B	0.4567	1.0842	−0.2565	0.048*
H17C	0.6154	1.0077	−0.3030	0.048*
S21	0.10176 (10)	0.33474 (8)	0.57279 (9)	0.0270 (2)
C21	−0.0845 (4)	0.2748 (3)	0.6694 (3)	0.0296 (8)
H21A	−0.1734	0.3556	0.6521	0.035*
H21B	−0.1290	0.2145	0.6421	0.035*
C22	−0.0503 (5)	0.1948 (4)	0.8151 (3)	0.0372 (9)
H22A	0.0272	0.1087	0.8345	0.056*
H22B	−0.1576	0.1730	0.8622	0.056*
H22C	0.0013	0.2513	0.8420	0.056*
C31	0.1990 (4)	−0.0419 (3)	0.6018 (3)	0.0226 (7)
O31	0.3184 (3)	−0.0511 (2)	0.5300 (2)	0.0288 (6)
S31	−0.0260 (2)	−0.16440 (14)	0.80208 (15)	0.0293 (4)	0.814 (4)
C32	0.1148 (4)	−0.1636 (3)	0.6839 (3)	0.0220 (7)	0.814 (4)
C33	0.1415 (18)	−0.2895 (10)	0.6845 (11)	0.0244 (14)	0.814 (4)
H33	0.2155	−0.3091	0.6252	0.029*	0.814 (4)
C34	0.0486 (16)	−0.3870 (8)	0.7817 (13)	0.0351 (15)	0.814 (4)
H34	0.0508	−0.4784	0.7942	0.042*	0.814 (4)
C35	−0.0448 (8)	−0.3341 (5)	0.8557 (6)	0.0302 (16)	0.814 (4)
H35	−0.1121	−0.3852	0.9281	0.036*	0.814 (4)
S41	0.155 (2)	−0.3061 (11)	0.6610 (13)	0.0244 (14)	0.186 (4)
C42	0.1148 (4)	−0.1636 (3)	0.6839 (3)	0.0220 (7)	0.186 (4)
C43	−0.007 (4)	−0.179 (2)	0.778 (3)	0.0293 (4)	0.186 (4)
H43	−0.0481	−0.1090	0.8034	0.035*	0.186 (4)
C44	−0.065 (4)	−0.308 (2)	0.833 (3)	0.0302 (16)	0.186 (4)
H44	−0.1553	−0.3323	0.8944	0.036*	0.186 (4)
C45	0.024 (8)	−0.393 (3)	0.787 (6)	0.0351 (15)	0.186 (4)
H45	0.0139	−0.4874	0.8198	0.042*	0.186 (4)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0217 (14)	0.0204 (14)	0.0265 (15)	−0.0055 (11)	0.0088 (11)	−0.0126 (12)
C2	0.0187 (15)	0.0241 (17)	0.0220 (17)	−0.0037 (12)	0.0021 (13)	−0.0115 (14)
N3	0.0197 (13)	0.0194 (14)	0.0258 (15)	−0.0045 (10)	0.0038 (11)	−0.0103 (12)
N11	0.0242 (14)	0.0200 (14)	0.0201 (14)	−0.0081 (11)	0.0053 (11)	−0.0107 (12)
N12	0.0235 (13)	0.0204 (14)	0.0224 (14)	−0.0088 (11)	0.0085 (11)	−0.0099 (12)
C13	0.0156 (14)	0.0215 (17)	0.0263 (17)	−0.0049 (12)	0.0054 (13)	−0.0137 (14)
C14	0.0225 (15)	0.0254 (17)	0.0189 (16)	−0.0059 (13)	0.0026 (13)	−0.0127 (14)
C15	0.0157 (14)	0.0223 (17)	0.0196 (16)	−0.0041 (12)	0.0027 (12)	−0.0108 (13)
C151	0.0201 (15)	0.0263 (17)	0.0197 (16)	−0.0033 (12)	0.0045 (13)	−0.0140 (14)
C152	0.0253 (16)	0.0264 (18)	0.0213 (17)	−0.0067 (13)	−0.0008 (14)	−0.0108 (14)
C153	0.0267 (17)	0.0271 (18)	0.0239 (18)	−0.0103 (13)	0.0029 (14)	−0.0116 (15)
C154	0.0241 (16)	0.0284 (18)	0.0181 (16)	−0.0020 (13)	0.0036 (13)	−0.0112 (14)
C155	0.0327 (18)	0.036 (2)	0.0186 (17)	−0.0100 (15)	−0.0045 (14)	−0.0086 (15)
C156	0.0294 (18)	0.036 (2)	0.0278 (19)	−0.0176 (15)	0.0033 (15)	−0.0156 (16)
C157	0.039 (2)	0.030 (2)	0.0221 (18)	−0.0072 (15)	0.0002 (16)	−0.0074 (15)
S21	0.0248 (4)	0.0202 (4)	0.0355 (5)	−0.0048 (3)	0.0100 (4)	−0.0138 (4)
C21	0.0186 (16)	0.0303 (19)	0.038 (2)	−0.0041 (13)	0.0111 (15)	−0.0164 (16)
C22	0.037 (2)	0.043 (2)	0.038 (2)	−0.0151 (17)	0.0150 (17)	−0.0230 (19)
C31	0.0222 (16)	0.0235 (17)	0.0234 (17)	−0.0043 (13)	−0.0010 (14)	−0.0115 (14)
O31	0.0290 (12)	0.0270 (13)	0.0348 (14)	−0.0087 (10)	0.0134 (11)	−0.0187 (11)
S31	0.0265 (6)	0.0287 (6)	0.0332 (8)	−0.0109 (5)	0.0107 (5)	−0.0143 (5)
C32	0.0169 (15)	0.0246 (17)	0.0260 (18)	−0.0049 (12)	−0.0005 (13)	−0.0122 (14)
C33	0.024 (2)	0.024 (2)	0.034 (4)	−0.0034 (19)	0.007 (2)	−0.0220 (15)
C34	0.033 (5)	0.022 (2)	0.050 (3)	−0.0098 (16)	−0.003 (2)	−0.014 (2)
C35	0.028 (3)	0.020 (3)	0.030 (3)	−0.009 (2)	0.000 (3)	0.000 (3)
S41	0.024 (2)	0.024 (2)	0.034 (4)	−0.0034 (19)	0.007 (2)	−0.0220 (15)
C42	0.0169 (15)	0.0246 (17)	0.0260 (18)	−0.0049 (12)	−0.0005 (13)	−0.0122 (14)
C43	0.0265 (6)	0.0287 (6)	0.0332 (8)	−0.0109 (5)	0.0107 (5)	−0.0143 (5)
C44	0.028 (3)	0.020 (3)	0.030 (3)	−0.009 (2)	0.000 (3)	0.000 (3)
C45	0.033 (5)	0.022 (2)	0.050 (3)	−0.0098 (16)	−0.003 (2)	−0.014 (2)

Geometric parameters (Å, º)

N1—C2	1.347 (4)	C157—H17A	0.9800
N1—H1	0.87 (3)	C157—H17B	0.9800
C2—N3	1.323 (4)	C157—H17C	0.9800
C2—S21	1.768 (3)	S21—C21	1.811 (3)
N3—C31	1.377 (4)	C21—C22	1.530 (5)
C31—O31	1.238 (3)	C21—H21A	0.9900
N1—C13	1.408 (4)	C21—H21B	0.9900
N11—N12	1.368 (3)	C22—H22A	0.9800
N11—H11	0.91 (3)	C22—H22B	0.9800
N12—C13	1.343 (4)	C22—H22C	0.9800
C13—C14	1.399 (4)	C31—C32	1.477 (4)
C14—C15	1.381 (4)	S31—C32	1.701 (3)
C15—N11	1.357 (4)	C32—C33	1.370 (8)
C14—H14	0.9500	C33—C34	1.410 (10)
C15—C151	1.480 (4)	C33—H33	0.9500
C151—C152	1.392 (4)	C34—C35	1.364 (5)
C151—C156	1.402 (5)	C35—S31	1.710 (5)
C152—C153	1.397 (4)	C34—H34	0.9500
C152—H152	0.9500	C35—H35	0.9500
C153—C154	1.399 (5)	S41—C45	1.711 (7)
C153—H153	0.9500	C43—C44	1.410 (11)
C154—C155	1.384 (4)	C43—H43	0.9500
C154—C157	1.522 (4)	C44—C45	1.365 (7)
C155—C156	1.390 (4)	C44—H44	0.9500
C155—H155	0.9500	C45—H45	0.9500
C156—H156	0.9500
C2—N1—C13	125.3 (3)	H17A—C157—H17B	109.5
C2—N1—H1	113 (2)	C154—C157—H17C	109.5
C13—N1—H1	122 (2)	H17A—C157—H17C	109.5
N3—C2—N1	125.5 (3)	H17B—C157—H17C	109.5
N3—C2—S21	118.9 (2)	C2—S21—C21	101.66 (15)
N1—C2—S21	115.5 (2)	C22—C21—S21	113.5 (2)
C2—N3—C31	120.0 (2)	C22—C21—H21A	108.9
C15—N11—N12	113.5 (3)	S21—C21—H21A	108.9
C15—N11—H11	132 (2)	C22—C21—H21B	108.9
N12—N11—H11	114 (2)	S21—C21—H21B	108.9
C13—N12—N11	102.9 (2)	H21A—C21—H21B	107.7
N12—C13—C14	112.6 (3)	C21—C22—H22A	109.5
N12—C13—N1	119.5 (3)	C21—C22—H22B	109.5
C14—C13—N1	127.9 (3)	H22A—C22—H22B	109.5
C15—C14—C13	105.2 (3)	C21—C22—H22C	109.5
C15—C14—H14	127.4	H22A—C22—H22C	109.5
C13—C14—H14	127.4	H22B—C22—H22C	109.5
N11—C15—C14	105.9 (3)	O31—C31—N3	127.6 (3)
N11—C15—C151	122.8 (3)	O31—C31—C32	119.7 (3)
C14—C15—C151	131.3 (3)	N3—C31—C32	112.7 (2)
C152—C151—C156	117.9 (3)	C32—S31—C35	92.3 (2)
C152—C151—C15	121.2 (3)	C33—C32—C31	127.9 (5)
C156—C151—C15	120.9 (3)	C33—C32—S31	110.8 (4)
C151—C152—C153	120.1 (3)	C31—C32—S31	121.3 (2)
C151—C152—H152	119.9	C32—C33—C34	113.4 (5)
C153—C152—H152	119.9	C32—C33—H33	123.3
C152—C153—C154	122.0 (3)	C34—C33—H33	123.3
C152—C153—H153	119.0	C35—C34—C33	111.7 (5)
C154—C153—H153	119.0	C35—C34—H34	124.2
C155—C154—C153	117.4 (3)	C33—C34—H34	124.2
C155—C154—C157	120.2 (3)	C34—C35—S31	111.7 (4)
C153—C154—C157	122.4 (3)	C34—C35—H35	124.1
C154—C155—C156	121.2 (3)	S31—C35—H35	124.1
C154—C155—H155	119.4	C44—C43—H43	123.4
C156—C155—H155	119.4	C45—C44—C43	111.6 (8)
C155—C156—C151	121.3 (3)	C45—C44—H44	124.2
C155—C156—H156	119.3	C43—C44—H44	124.2
C151—C156—H156	119.3	C44—C45—S41	111.3 (8)
C154—C157—H17A	109.5	C44—C45—H45	124.3
C154—C157—H17B	109.5	S41—C45—H45	124.3
N1—C2—N3—C31	−2.4 (5)	C14—C15—C151—C156	19.5 (5)
C2—N3—C31—O31	0.7 (5)	C156—C151—C152—C153	1.8 (4)
C2—N3—C31—C32	179.3 (3)	C15—C151—C152—C153	−174.5 (3)
N3—C2—N1—C13	178.2 (3)	C151—C152—C153—C154	−0.6 (5)
C13—N1—C2—S21	−2.0 (4)	C152—C153—C154—C155	−1.6 (5)
C2—N1—C13—N12	61.4 (4)	C152—C153—C154—C157	177.1 (3)
N3—C31—C32—S31	−9.3 (4)	C153—C154—C155—C156	2.5 (5)
N11—C15—C151—C152	18.3 (4)	C157—C154—C155—C156	−176.2 (3)
N1—C2—S21—C21	172.1 (3)	C154—C155—C156—C151	−1.3 (5)
C2—S21—C21—C22	85.9 (3)	C152—C151—C156—C155	−0.9 (5)
S21—C2—N3—C31	177.9 (2)	C15—C151—C156—C155	175.4 (3)
C15—N11—N12—C13	0.2 (3)	N3—C2—S21—C21	−8.1 (3)
N11—N12—C13—C14	0.4 (3)	O31—C31—C32—C33	−6.3 (9)
N11—N12—C13—N1	−179.9 (2)	N3—C31—C32—C33	175.0 (8)
C2—N1—C13—C14	−118.9 (4)	O31—C31—C32—S31	169.4 (3)
N12—C13—C14—C15	−0.8 (3)	C35—S31—C32—C33	1.6 (7)
N1—C13—C14—C15	179.5 (3)	C35—S31—C32—C31	−174.7 (4)
N12—N11—C15—C14	−0.7 (3)	C31—C32—C33—C34	175.6 (9)
N12—N11—C15—C151	177.3 (3)	S31—C32—C33—C34	−0.4 (14)
C13—C14—C15—N11	0.8 (3)	C32—C33—C34—C35	−1.4 (18)
C13—C14—C15—C151	−176.9 (3)	C33—C34—C35—S31	2.6 (15)
C14—C15—C151—C152	−164.3 (3)	C32—S31—C35—C34	−2.5 (9)
N11—C15—C151—C156	−158.0 (3)	C43—C44—C45—S41	−9 (7)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O31	0.87 (4)	1.93 (4)	2.632 (4)	137 (3)
N1—H1···O31^i	0.87 (4)	2.51 (3)	3.052 (4)	121 (3)
N11—H11···N12^ii	0.91 (4)	2.07 (3)	2.857 (4)	145 (3)
C21—H21A···Cg1^iii	0.99	2.90	3.879 (4)	169
C33—H33···Cg1^i	0.95	2.80	3.481 (14)	129
C44—H44···Cg2^iv	0.95	3.00	3.82 (3)	147

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