Conformation and tautomerism of meth­oxy-substituted 4-phenyl-4-thia­zoline-2-thio­nes: a combined crystallographic and ab initio investigation

4-Phenyl-4-thia­zoline-2-thiol is an active pharmaceutical compound, one of whose activities is as a human indole­namine di­oxy­genase inhibitor. It has been shown recently that in both the solid state and the gas phase, the thia­zoline­thione tautomer should be preferred. As part of both research on this lead compound and a medicinal chemistry program, a series of substituted aryl­thia­zoline­thio­nes have been synthesized. The mol­ecular conformations and tautomerism of 4-(2-meth­oxy­phen­yl)-4-thia­zoline-2-thione and 4-(4-meth­oxy­phen­yl)-4-thia­zoline-2-thione, both C₁₀H₉NOS₂, are reported and compared with the geometry deduced from ab initio calculations [PBE/6-311G(d,p)]. Both the crystal structure analyses and the calculations establish the thione tautomer for the two substituted aryl­thia­zoline­thio­nes. In the crystal structure of the 2-meth­oxy­phenyl regioisomer, the thia­zoline­thione unit was disordered over two conformations. Both isomers exhibit similar hydrogen-bond patterns [R₂²(8) motif] and form dimers. The crystal packing is further reinforced by short S...S inter­actions in the 2-meth­oxy­phenyl isomer. The conformations of the two regioisomers correspond to stable geometries calculated from an ab initio energy-relaxed scan.

S1. Introduction

4-Phenyl-1,3-thia­zole-2-thiol, (1) (see Scheme 1), is an active pharmaceutical compound acting, among other properties, as a human indole­namine di­oxy­genase inhibitor (Röhrig et al., 2010) with an inhibitory potency of about 40 µM, as deduced from our previous studies (Takagi et al., 2014). We have recently studied the solid-state polymorphism and tautomeric equilibrium of (1) (Carletta et al., 2015) and have shown that in both the solid state and the gas phase, the thia­zoline­thione tautomer should be preferred.

As part of our research on this lead compound, we have begun a medicinal chemistry program and synthesized a series of substituted aryl­thia­zoline­thio­nes. In the present report, we compare the conformation and tautomerism of 4-(2-meth­oxy­phenyl)-4-thia­zoline-2-thione, (2), and 4-(4-meth­oxy­phenyl)-4-thia­zoline-2-thione, (3) (see Scheme 1), both in their crystal structures and by ab initio optimized-geometry calculations.

S2. Experimental

S2.1. Synthesis and crystallization

The two title aryl­thia­zoline­thio­nes, (2) and (3), were synthesized from tri­ethyl­ammonium di­thio­carbamate (1 mmol) dissolved in ethanol (20 ml) to which the corresponding bromo­aceto­phenone (1 mmol) was added dropwise (Scheme 1). After 15 min of reaction, the solvent was evaporated and the corresponding solids were purified by flash chromatography (silica gel, cyclo­hexane/ethyl acetate eluant). The yields were over 90%. Crystals suitable for X-ray diffraction analysis were obtained by recrystallization in NMR tubes, by the slow evaporation of concentrated solutions in deuterated methanol.

S2.2. Refinement

Crystal data, data collection and structure refinement details for (2) and (3) are summarized in Table 1. A riding-model refinement was applied for all H atoms of (2) and (3). H atoms potentially involved in hydrogen bonds were first located in difference Fourier maps prior to calculation of their idealized positions. For (2), two disordered components were refined for the thia­zoline­thione ring. The occupancy of each part was first refined using an isotropic model for the atoms. The refined occupancies (65:35) were then fixed and the atoms were subsequently refined anisotropically. Distance restraints were applied to these groups. In particular, the bond linking the arene and disordered five-membered ring was restrained to 1.47 (2) Å, a value observed in regioisomer (3) and in the unsubstituted compound (1) (Carletta et al., 2015).

S2.3. Calculations

Calculations were performed using GAUSSIAN09 (Frisch et al., 2009), using the DFT Pbe method and 6-311G(d,p) basis set. Full geometry optimization was performed on the two possible tautomers (thione and thiol forms; see Scheme 2) for both regioisomers. In addition, a relaxed conformation scan was performed (360° rotation, 15° increment) around the torsion angle between the substituted arene ring and the heterocycle for the more stable thione tautomer of each regioisomer.

S3. Results and discussion

In the two observed polymorphs of 4-phenyl-1,3-thia­zole-2-thiol, (1) (Scheme 1), the thia­zoline­thione tautomer was observed in the crystal [Carletta et al., 2015; Cambridge Structural Database (CSD; Groom & Allen, 2014) refcodes FIKZOO11 and FIKZOO12]. A similar result was observed in the crystal structures of 4-(4-chloro­phenyl)-1,3-thia­zole-2-thiol (Nalini & Desiraju, 1987; CSD refcode DOPYAI) and 4-(3-nitro­phenyl)-1,3-thia­zole-2-thiol (Nalini & Desiraju, 1989; CSD refcode SEJLEY).

For both (2) and (3) only the thia­zoline­thione form is observed (Fig. 1). Moreover, for the 2-meth­oxy isomer, two disordered components were found for the thia­zoline­thione ring, with occupancies of 0.65 and 0.35.

Ab initio calculations [Pbe/6-311G(d,p)] performed on the two possible tautomers for each of the regioisomers show that the thia­zoline­thione tautomer is favoured over the thia­zole-2-thiol tautomer in the gas phase. The calculated ΔE values are 54.8 and 34.5 kJ mol^-1 in favour of the thia­zoline­thione tautomer for (2) and (3), respectively. This is in agreement with previous calculations carried out on unsubstituted 4-phenyl-1,3-thia­zole-2-thiol, (1) (Carletta et al., 2015).

The gas-phase results agree with the solid-state structures of (1) (Carletta et al., 2015), (2) and (3).

The addition of a meth­oxy group on the arene ring in both title compounds impacts the conformation of the molecules (Fig. 1). 4-Meth­oxy-substituted isomer (3) adopts an almost coplanar conformation [C2—C1—C7—N1 = 11.8 (3)°], while, as expected, for 2-meth­oxy-substitued isomer (2), steric hindrance involving the ortho-substitued arene group leads to a larger deviation from coplanarity of the two rings [C2—C1—C7/C7'—N1/N1' = 55.3 (9) and 44 (2)° for the two components].

The influence of the meth­oxy substituents on the arene rings was also studied by an ab initio [Pbe/6-311G(d,p)] relaxed-conformation scan (360° rotation, 15° step) around the C2—C1—C7—N1 torsion angle between the two rings (Fig. 2). In both compounds, conformations at ±90 and 180° are the least favoured. Disruption of the electronic delocalization between the arene and thia­zoline­thione fragments in the perpendicular conformation (±90°) leads to a large rotational barrier. Substitution at the ortho position, i.e. compound (2), leads to a rotational barrier of about 16 kJ mol^-1. Also for (2), steric contacts between the meth­oxy group and the C8—H8 group (180° conformation) destabilize the conformation by about 8 kJ mol^-1.

Isomers (2) and (3) both crystallize with one molecule in the asymmetric unit and form dimers stabilized by hydrogen bonds [R₂²(8) motif; Bernstein et al., 1995] (Fig. 3 and Tables 2 and 3). For compound (3), an extra C—H···S inter­action is observed that adds an R₂²(7) ring at each side of the N—H···S hydrogen bond (Fig. 3b).

In the crystal packing of (3), the almost planar molecules stack along the a axis. For compound (2), the crystal packing is stabilized by an inter­molecular S···S contact (S1···S2 < 3.5 Å; Table 4 and Fig. 4), as was also observed in the case of 4-chloro phenyl thia­zoline­thione [should this be the thiol form 4-(4-chloro­phenyl)-1,3-thia­zole-2-thiol as in paragraph 1?] (Nalini & Desiraju, 1986).

Structure description

4-Phenyl-1,3-thia­zole-2-thiol, (1) (see Scheme 1), is an active pharmaceutical compound acting, among other properties, as a human indole­namine di­oxy­genase inhibitor (Röhrig et al., 2010) with an inhibitory potency of about 40 µM, as deduced from our previous studies (Takagi et al., 2014). We have recently studied the solid-state polymorphism and tautomeric equilibrium of (1) (Carletta et al., 2015) and have shown that in both the solid state and the gas phase, the thia­zoline­thione tautomer should be preferred.

As part of our research on this lead compound, we have begun a medicinal chemistry program and synthesized a series of substituted aryl­thia­zoline­thio­nes. In the present report, we compare the conformation and tautomerism of 4-(2-meth­oxy­phenyl)-4-thia­zoline-2-thione, (2), and 4-(4-meth­oxy­phenyl)-4-thia­zoline-2-thione, (3) (see Scheme 1), both in their crystal structures and by ab initio optimized-geometry calculations.

Calculations were performed using GAUSSIAN09 (Frisch et al., 2009), using the DFT Pbe method and 6-311G(d,p) basis set. Full geometry optimization was performed on the two possible tautomers (thione and thiol forms; see Scheme 2) for both regioisomers. In addition, a relaxed conformation scan was performed (360° rotation, 15° increment) around the torsion angle between the substituted arene ring and the heterocycle for the more stable thione tautomer of each regioisomer.

In the two observed polymorphs of 4-phenyl-1,3-thia­zole-2-thiol, (1) (Scheme 1), the thia­zoline­thione tautomer was observed in the crystal [Carletta et al., 2015; Cambridge Structural Database (CSD; Groom & Allen, 2014) refcodes FIKZOO11 and FIKZOO12]. A similar result was observed in the crystal structures of 4-(4-chloro­phenyl)-1,3-thia­zole-2-thiol (Nalini & Desiraju, 1987; CSD refcode DOPYAI) and 4-(3-nitro­phenyl)-1,3-thia­zole-2-thiol (Nalini & Desiraju, 1989; CSD refcode SEJLEY).

For both (2) and (3) only the thia­zoline­thione form is observed (Fig. 1). Moreover, for the 2-meth­oxy isomer, two disordered components were found for the thia­zoline­thione ring, with occupancies of 0.65 and 0.35.

Ab initio calculations [Pbe/6-311G(d,p)] performed on the two possible tautomers for each of the regioisomers show that the thia­zoline­thione tautomer is favoured over the thia­zole-2-thiol tautomer in the gas phase. The calculated ΔE values are 54.8 and 34.5 kJ mol^-1 in favour of the thia­zoline­thione tautomer for (2) and (3), respectively. This is in agreement with previous calculations carried out on unsubstituted 4-phenyl-1,3-thia­zole-2-thiol, (1) (Carletta et al., 2015).

The gas-phase results agree with the solid-state structures of (1) (Carletta et al., 2015), (2) and (3).

The addition of a meth­oxy group on the arene ring in both title compounds impacts the conformation of the molecules (Fig. 1). 4-Meth­oxy-substituted isomer (3) adopts an almost coplanar conformation [C2—C1—C7—N1 = 11.8 (3)°], while, as expected, for 2-meth­oxy-substitued isomer (2), steric hindrance involving the ortho-substitued arene group leads to a larger deviation from coplanarity of the two rings [C2—C1—C7/C7'—N1/N1' = 55.3 (9) and 44 (2)° for the two components].

The influence of the meth­oxy substituents on the arene rings was also studied by an ab initio [Pbe/6-311G(d,p)] relaxed-conformation scan (360° rotation, 15° step) around the C2—C1—C7—N1 torsion angle between the two rings (Fig. 2). In both compounds, conformations at ±90 and 180° are the least favoured. Disruption of the electronic delocalization between the arene and thia­zoline­thione fragments in the perpendicular conformation (±90°) leads to a large rotational barrier. Substitution at the ortho position, i.e. compound (2), leads to a rotational barrier of about 16 kJ mol^-1. Also for (2), steric contacts between the meth­oxy group and the C8—H8 group (180° conformation) destabilize the conformation by about 8 kJ mol^-1.

Isomers (2) and (3) both crystallize with one molecule in the asymmetric unit and form dimers stabilized by hydrogen bonds [R₂²(8) motif; Bernstein et al., 1995] (Fig. 3 and Tables 2 and 3). For compound (3), an extra C—H···S inter­action is observed that adds an R₂²(7) ring at each side of the N—H···S hydrogen bond (Fig. 3b).

In the crystal packing of (3), the almost planar molecules stack along the a axis. For compound (2), the crystal packing is stabilized by an inter­molecular S···S contact (S1···S2 < 3.5 Å; Table 4 and Fig. 4), as was also observed in the case of 4-chloro phenyl thia­zoline­thione [should this be the thiol form 4-(4-chloro­phenyl)-1,3-thia­zole-2-thiol as in paragraph 1?] (Nalini & Desiraju, 1986).

Synthesis and crystallization

The two title aryl­thia­zoline­thio­nes, (2) and (3), were synthesized from tri­ethyl­ammonium di­thio­carbamate (1 mmol) dissolved in ethanol (20 ml) to which the corresponding bromo­aceto­phenone (1 mmol) was added dropwise (Scheme 1). After 15 min of reaction, the solvent was evaporated and the corresponding solids were purified by flash chromatography (silica gel, cyclo­hexane/ethyl acetate eluant). The yields were over 90%. Crystals suitable for X-ray diffraction analysis were obtained by recrystallization in NMR tubes, by the slow evaporation of concentrated solutions in deuterated methanol.

Refinement details

Crystal data, data collection and structure refinement details for (2) and (3) are summarized in Table 1. A riding-model refinement was applied for all H atoms of (2) and (3). H atoms potentially involved in hydrogen bonds were first located in difference Fourier maps prior to calculation of their idealized positions. For (2), two disordered components were refined for the thia­zoline­thione ring. The occupancy of each part was first refined using an isotropic model for the atoms. The refined occupancies (65:35) were then fixed and the atoms were subsequently refined anisotropically. Distance restraints were applied to these groups. In particular, the bond linking the arene and disordered five-membered ring was restrained to 1.47 (2) Å, a value observed in regioisomer (3) and in the unsubstituted compound (1) (Carletta et al., 2015).

Computing details

For both compounds, data collection: CrysAlis PRO (Rigaku Oxford Diffraction, 2014); cell refinement: CrysAlis PRO (Rigaku Oxford Diffraction, 2014); data reduction: CrysAlis PRO (Rigaku Oxford Diffraction, 2014); program(s) used to solve structure: SIR2004 (Burla et al., 2005); program(s) used to refine structure: SHELXL2015 (Sheldrick, 2015); molecular graphics: Please provide; software used to prepare material for publication: SHELXL2015 (Sheldrick, 2015).

Figures

	Fig. 1. Displacement ellipsoid plots (50% probability level) for (a) 4-(2-methoxyphenyl)-4-thiazoline-2-thione, (2), and (b) 4-(4-methoxyphenyl)-4-thiazoline-2-thione, (3). The two disordered components are shown for regioisomer (2).
	Fig. 2. Results from an ab initio relaxed conformation scan [Pbe/6–311 G(d,p), 360° rotation, 15° step] around the N1—C7—C1—C2 torsion angle between the substituted arene ring and the heterocyclic thiazolinethione ring for compounds (2) (dashed line) and (2) (solid line).
	Fig. 3. Hydrogen-bonded dimers [R2^2(8) motif] observed in the crystal structure of (a) (2), where the upper molecule is at (x, y, z) and the lower molecule is at (-x, -y + 2, -z + 1), and (b) (3), with the molecule at the right at (x, y, z) and that at the left at (-x, -y + 1, -z + 1). Only the main disorder component (occupancy 0.65) for the 2-methoxy regioisomer is presented. For regioisomer (3), an extra C—H···S interaction is observed, which adds a further R2^2(7) ring at each side of the N—H···S hydrogen bond.
	Fig. 4. View of the S···S close contact [3.478 (4) Å] observed in the crystal structure of (2). Only the main disordered component is shown. The molecule at the right is at (-x + 1/2, y - 1/2, -z + 3/2).

(2) 4-(2-Methoxyphenyl)-4-thiazoline-2-thione

Crystal data

C10H9NOS2	F(000) = 464
Mr = 223.30	Dx = 1.384 Mg m^−3
Monoclinic, P21/n	Cu Kα radiation, λ = 1.54184 Å
a = 8.4228 (1) Å	Cell parameters from 4159 reflections
b = 7.9082 (1) Å	θ = 2.7–67.1°
c = 16.2102 (3) Å	µ = 4.23 mm^−1
β = 97.152 (2)°	T = 293 K
V = 1071.35 (3) Å^3	Prism, colourless
Z = 4	0.60 × 0.40 × 0.30 mm

Data collection

Rigaku Gemini ultra Ruby diffractometer	1837 independent reflections
Mirror monochromator	1724 reflections with I > 2σ(I)
Detector resolution: 5.1856 pixels mm^-1	Rint = 0.020
ω scans	θmax = 66.5°, θmin = 6.2°
Absorption correction: multi-scan (CrysAlis PRO; Rigaku Oxford Diffraction, 2014))	h = −7→10
Tmin = 0.698, Tmax = 1.000	k = −9→9
5263 measured reflections	l = −18→19

Refinement

Refinement on F^2	3 restraints
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.028	H-atom parameters constrained
wR(F^2) = 0.075	w = 1/[σ^2(Fo^2) + (0.0415P)^2 + 0.1363P] where P = (Fo^2 + 2Fc^2)/3
S = 1.06	(Δ/σ)max < 0.001
1837 reflections	Δρmax = 0.14 e Å^−3
176 parameters	Δρmin = −0.14 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	Occ. (<1)
C1	0.26041 (15)	0.58504 (18)	0.48362 (10)	0.0510 (3)
C2	0.33418 (14)	0.66459 (18)	0.42106 (9)	0.0483 (3)
C3	0.35828 (17)	0.5774 (2)	0.34986 (10)	0.0614 (4)
H3	0.4039	0.6312	0.3075	0.074*
C4	0.3138 (2)	0.4088 (2)	0.34215 (14)	0.0764 (5)
H4	0.3304	0.3496	0.2944	0.092*
C5	0.2457 (2)	0.3279 (2)	0.40394 (15)	0.0832 (6)
H5	0.2184	0.2141	0.3986	0.100*
C6	0.21794 (19)	0.4164 (2)	0.47407 (13)	0.0699 (5)
H6	0.1701	0.3621	0.5155	0.084*
C10	0.4726 (2)	0.9107 (2)	0.38258 (12)	0.0698 (5)
H10A	0.5681	0.8464	0.3788	0.105*
H10B	0.5009	1.0217	0.4035	0.105*
H10C	0.4125	0.9200	0.3284	0.105*
O1	0.37858 (11)	0.82820 (13)	0.43719 (6)	0.0559 (3)
C7	0.2314 (11)	0.6911 (8)	0.5578 (4)	0.0377 (12)	0.65
C8	0.2815 (7)	0.6414 (8)	0.6403 (4)	0.0577 (12)	0.65
H8	0.3388	0.5440	0.6567	0.069*	0.65
S1	0.2165 (2)	0.7959 (2)	0.70743 (12)	0.0577 (3)	0.65
C9	0.1231 (10)	0.9144 (11)	0.6243 (4)	0.0382 (13)	0.65
N1	0.1468 (7)	0.8437 (6)	0.5531 (4)	0.0342 (9)	0.65
H1	0.1119	0.8892	0.5061	0.041*	0.65
S2	0.0317 (3)	1.0974 (7)	0.6356 (2)	0.0484 (4)	0.65
C7'	0.228 (3)	0.6491 (16)	0.5610 (10)	0.051 (3)	0.35
C8'	0.2364 (15)	0.614 (2)	0.6338 (9)	0.098 (5)	0.35
H8'	0.2774	0.5099	0.6523	0.118*	0.35
S1'	0.1782 (5)	0.7451 (5)	0.6990 (2)	0.0946 (12)	0.35
C9'	0.132 (2)	0.889 (2)	0.6223 (12)	0.059 (5)	0.35
N1'	0.1669 (16)	0.8071 (16)	0.5527 (9)	0.0342 (9)	0.35
H1'	0.1507	0.8549	0.5048	0.041*	0.35
S2'	0.0342 (8)	1.0711 (13)	0.6347 (5)	0.066 (2)	0.35

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0404 (6)	0.0550 (8)	0.0592 (9)	0.0063 (5)	0.0121 (6)	0.0048 (6)
C2	0.0396 (6)	0.0543 (7)	0.0519 (7)	0.0037 (5)	0.0089 (5)	−0.0024 (6)
C3	0.0535 (8)	0.0723 (10)	0.0601 (9)	0.0017 (7)	0.0140 (7)	−0.0103 (7)
C4	0.0628 (9)	0.0768 (12)	0.0910 (13)	−0.0021 (8)	0.0145 (9)	−0.0318 (10)
C5	0.0644 (10)	0.0579 (10)	0.1294 (18)	−0.0068 (8)	0.0204 (11)	−0.0197 (11)
C6	0.0566 (8)	0.0576 (9)	0.0993 (13)	0.0012 (7)	0.0251 (8)	0.0066 (8)
C10	0.0759 (10)	0.0713 (11)	0.0676 (10)	−0.0140 (8)	0.0301 (8)	0.0003 (8)
O1	0.0609 (6)	0.0548 (6)	0.0564 (6)	−0.0055 (4)	0.0249 (5)	−0.0037 (4)
C7	0.0418 (15)	0.033 (3)	0.0402 (18)	0.006 (2)	0.0130 (11)	0.0128 (17)
C8	0.055 (3)	0.0680 (18)	0.0520 (19)	0.0241 (17)	0.0126 (18)	0.0123 (15)
S1	0.0673 (6)	0.0740 (6)	0.0321 (4)	0.0211 (4)	0.0067 (3)	0.0091 (4)
C9	0.040 (3)	0.0536 (19)	0.020 (2)	0.0022 (15)	0.0023 (15)	0.0034 (13)
N1	0.0385 (17)	0.033 (3)	0.0310 (6)	0.0148 (14)	0.0053 (10)	0.0043 (17)
S2	0.0587 (8)	0.0520 (10)	0.0332 (6)	0.0125 (6)	0.0005 (5)	−0.0064 (5)
C7'	0.047 (4)	0.028 (5)	0.081 (6)	0.013 (4)	0.020 (3)	0.027 (3)
C8'	0.073 (8)	0.150 (11)	0.079 (7)	0.058 (7)	0.041 (6)	0.079 (7)
S1'	0.111 (3)	0.137 (3)	0.0389 (13)	0.0547 (19)	0.0225 (14)	0.0347 (17)
C9'	0.034 (4)	0.077 (8)	0.067 (8)	0.013 (4)	0.013 (4)	0.009 (5)
N1'	0.0385 (17)	0.033 (3)	0.0310 (6)	0.0148 (14)	0.0053 (10)	0.0043 (17)
S2'	0.094 (3)	0.067 (4)	0.0368 (13)	−0.0031 (17)	0.0074 (13)	−0.0118 (13)

Geometric parameters (Å, º)

C1—C6	1.384 (2)	C7—N1	1.399 (8)
C1—C2	1.403 (2)	C8—S1	1.767 (6)
C1—C7	1.511 (6)	C8—H8	0.9300
C2—O1	1.3631 (17)	S1—C9	1.746 (7)
C2—C3	1.381 (2)	C9—N1	1.320 (8)
C3—C4	1.386 (2)	C9—S2	1.660 (7)
C3—H3	0.9300	N1—H1	0.8600
C4—C5	1.373 (3)	C1—C7'	1.411 (14)
C4—H4	0.9300	C7'—C8'	1.20 (2)
C5—C6	1.380 (3)	C7'—N1'	1.351 (15)
C5—H5	0.9300	C8'—S1'	1.599 (17)
C6—H6	0.9300	C8'—H8'	0.9300
C10—O1	1.4183 (18)	S1'—C9'	1.694 (19)
C10—H10A	0.9600	C9'—N1'	1.36 (2)
C10—H10B	0.9600	C9'—S2'	1.683 (13)
C10—H10C	0.9600	N1'—H1'	0.8600
C7—C8	1.407 (11)
S1···S2^i	3.478 (4)	S1'···S2'^i	3.661 (9)
C6—C1—C2	118.86 (15)	N1—C7—C1	124.5 (6)
C6—C1—C7	124.0 (3)	C7—C8—S1	108.2 (5)
C2—C1—C7	117.2 (3)	C7—C8—H8	125.9
O1—C2—C3	124.68 (13)	S1—C8—H8	125.9
O1—C2—C1	115.00 (12)	C9—S1—C8	92.3 (4)
C3—C2—C1	120.31 (14)	N1—C9—S2	126.0 (5)
C2—C3—C4	119.30 (17)	N1—C9—S1	110.2 (5)
C2—C3—H3	120.3	S2—C9—S1	123.6 (4)
C4—C3—H3	120.3	C9—N1—C7	116.7 (6)
C5—C4—C3	121.02 (17)	C9—N1—H1	121.7
C5—C4—H4	119.5	C7—N1—H1	121.7
C3—C4—H4	119.5	C7'—C1—C6	111.7 (6)
C4—C5—C6	119.57 (17)	C7'—C1—C2	129.4 (6)
C4—C5—H5	120.2	C8'—C7'—N1'	106.5 (14)
C6—C5—H5	120.2	C8'—C7'—C1	142.6 (14)
C5—C6—C1	120.89 (17)	N1'—C7'—C1	110.9 (13)
C5—C6—H6	119.6	C7'—C8'—S1'	120.9 (13)
C1—C6—H6	119.6	C7'—C8'—H8'	119.5
O1—C10—H10A	109.5	S1'—C8'—H8'	119.5
O1—C10—H10B	109.5	C8'—S1'—C9'	90.6 (8)
H10A—C10—H10B	109.5	N1'—C9'—S2'	131.6 (14)
O1—C10—H10C	109.5	N1'—C9'—S1'	103.6 (11)
H10A—C10—H10C	109.5	S2'—C9'—S1'	124.0 (12)
H10B—C10—H10C	109.5	C9'—N1'—C7'	118.4 (14)
C2—O1—C10	118.57 (12)	C9'—N1'—H1'	120.8
C8—C7—N1	112.6 (5)	C7'—N1'—H1'	120.8
C8—C7—C1	122.8 (6)
C6—C1—C2—O1	−177.13 (13)	C8—S1—C9—S2	−177.7 (6)
C7—C1—C2—O1	3.2 (4)	S2—C9—N1—C7	178.0 (7)
C6—C1—C2—C3	2.4 (2)	S1—C9—N1—C7	2.8 (10)
C7—C1—C2—C3	−177.3 (4)	C8—C7—N1—C9	−1.7 (11)
O1—C2—C3—C4	177.28 (14)	C1—C7—N1—C9	175.5 (7)
C1—C2—C3—C4	−2.2 (2)	C7'—C1—C2—O1	−1.1 (11)
C2—C3—C4—C5	0.3 (3)	C7'—C1—C2—C3	178.5 (11)
C3—C4—C5—C6	1.3 (3)	C7'—C1—C6—C5	−177.5 (9)
C4—C5—C6—C1	−1.1 (3)	C6—C1—C7'—C8'	42 (3)
C2—C1—C6—C5	−0.7 (2)	C2—C1—C7'—C8'	−134 (2)
C7—C1—C6—C5	178.9 (4)	C6—C1—C7'—N1'	−139.3 (11)
C3—C2—O1—C10	−7.8 (2)	C2—C1—C7'—N1'	44 (2)
C1—C2—O1—C10	171.73 (13)	N1'—C7'—C8'—S1'	1 (2)
C6—C1—C7—C8	52.6 (9)	C1—C7'—C8'—S1'	180 (2)
C2—C1—C7—C8	−127.7 (6)	C7'—C8'—S1'—C9'	−1.5 (17)
C6—C1—C7—N1	−124.3 (7)	C8'—S1'—C9'—N1'	1.5 (14)
C2—C1—C7—N1	55.3 (9)	C8'—S1'—C9'—S2'	172.0 (14)
N1—C7—C8—S1	−0.2 (8)	S2'—C9'—N1'—C7'	−170.9 (16)
C1—C7—C8—S1	−177.5 (6)	S1'—C9'—N1'—C7'	−1 (2)
C7—C8—S1—C9	1.4 (6)	C8'—C7'—N1'—C9'	1 (2)
C8—S1—C9—N1	−2.4 (7)	C1—C7'—N1'—C9'	−178.8 (15)

Symmetry code: (i) −x+1/2, y−1/2, −z+3/2.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···S2^ii	0.86	2.46	3.269 (7)	157

Symmetry code: (ii) −x, −y+2, −z+1.

(3) 4-(4-Methoxyphenyl)-4-thiazoline-2-thione

Crystal data

C10H9NOS2	F(000) = 464
Mr = 223.30	Dx = 1.461 Mg m^−3
Monoclinic, P21/n	Mo Kα radiation, λ = 0.71073 Å
a = 4.7187 (3) Å	Cell parameters from 2131 reflections
b = 12.0438 (7) Å	θ = 3.6–28.4°
c = 17.8972 (11) Å	µ = 0.49 mm^−1
β = 93.752 (6)°	T = 293 K
V = 1014.94 (11) Å^3	Prism, colourless
Z = 4	0.30 × 0.07 × 0.05 mm

Data collection

Rigaku Gemini ultra Ruby diffractometer	1792 independent reflections
Graphite monochromator	1506 reflections with I > 2σ(I)
Detector resolution: 5.1856 pixels mm^-1	Rint = 0.023
ω scans	θmax = 25.0°, θmin = 2.8°
Absorption correction: multi-scan (CrysAlis PRO; Rigaku Oxford Diffraction, 2014)	h = −5→5
Tmin = 0.864, Tmax = 1.000	k = −14→12
4344 measured reflections	l = −21→15

Refinement

Refinement on F^2	0 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F^2 > 2σ(F^2)] = 0.034	H-atom parameters constrained
wR(F^2) = 0.084	w = 1/[σ^2(Fo^2) + (0.0353P)^2 + 0.3259P] where P = (Fo^2 + 2Fc^2)/3
S = 1.06	(Δ/σ)max < 0.001
1792 reflections	Δρmax = 0.22 e Å^−3
136 parameters	Δρmin = −0.17 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
C1	0.4018 (4)	0.34780 (17)	0.31843 (11)	0.0372 (5)
C2	0.5465 (4)	0.44649 (18)	0.33252 (11)	0.0428 (5)
H2	0.5248	0.4839	0.3772	0.051*
C3	0.7223 (5)	0.49027 (18)	0.28128 (12)	0.0454 (5)
H3	0.8153	0.5572	0.2914	0.054*
C4	0.7607 (4)	0.43506 (17)	0.21489 (11)	0.0402 (5)
C5	0.6234 (5)	0.33600 (18)	0.20042 (12)	0.0476 (5)
H5	0.6510	0.2975	0.1564	0.057*
C6	0.4447 (5)	0.29387 (19)	0.25137 (12)	0.0483 (5)
H6	0.3500	0.2275	0.2406	0.058*
C7	0.2102 (4)	0.29915 (17)	0.37128 (11)	0.0377 (5)
C8	0.0972 (5)	0.19723 (18)	0.37034 (12)	0.0482 (5)
H8	0.1303	0.1436	0.3345	0.058*
C9	−0.0507 (4)	0.30928 (17)	0.47739 (11)	0.0391 (5)
C10	0.9916 (5)	0.4296 (2)	0.09993 (12)	0.0573 (6)
H10A	1.0680	0.3573	0.1115	0.086*
H10B	1.1255	0.4715	0.0732	0.086*
H10C	0.8175	0.4221	0.0695	0.086*
N1	0.1244 (3)	0.35970 (14)	0.43200 (9)	0.0388 (4)
H1	0.1813	0.4267	0.4401	0.047*
O1	0.9376 (3)	0.48585 (13)	0.16756 (8)	0.0532 (4)
S1	−0.11714 (13)	0.17739 (5)	0.44348 (3)	0.05114 (19)
S2	−0.19443 (14)	0.36229 (5)	0.55262 (3)	0.0547 (2)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0369 (10)	0.0349 (11)	0.0395 (11)	0.0038 (9)	0.0001 (8)	−0.0004 (9)
C2	0.0501 (12)	0.0398 (12)	0.0390 (11)	−0.0008 (10)	0.0066 (9)	−0.0064 (9)
C3	0.0535 (12)	0.0357 (12)	0.0478 (12)	−0.0059 (10)	0.0094 (10)	−0.0063 (9)
C4	0.0460 (11)	0.0365 (12)	0.0383 (11)	0.0056 (9)	0.0037 (9)	0.0033 (9)
C5	0.0592 (13)	0.0444 (13)	0.0396 (11)	0.0011 (10)	0.0075 (10)	−0.0103 (10)
C6	0.0554 (13)	0.0384 (13)	0.0515 (13)	−0.0065 (10)	0.0061 (10)	−0.0095 (10)
C7	0.0373 (10)	0.0355 (12)	0.0399 (11)	0.0036 (9)	−0.0015 (8)	−0.0012 (8)
C8	0.0574 (13)	0.0366 (12)	0.0512 (13)	−0.0057 (10)	0.0077 (10)	−0.0063 (10)
C9	0.0423 (11)	0.0319 (11)	0.0425 (11)	−0.0016 (9)	−0.0010 (9)	0.0056 (9)
C10	0.0728 (15)	0.0567 (15)	0.0440 (13)	0.0067 (12)	0.0167 (11)	0.0006 (11)
N1	0.0442 (9)	0.0308 (9)	0.0413 (9)	−0.0051 (7)	0.0033 (7)	−0.0003 (7)
O1	0.0714 (10)	0.0451 (9)	0.0453 (9)	−0.0027 (8)	0.0211 (7)	−0.0011 (7)
S1	0.0625 (4)	0.0350 (3)	0.0569 (4)	−0.0109 (3)	0.0117 (3)	−0.0008 (2)
S2	0.0785 (4)	0.0380 (3)	0.0500 (3)	−0.0045 (3)	0.0231 (3)	0.0024 (3)

Geometric parameters (Å, º)

C1—C2	1.386 (3)	C7—C8	1.338 (3)
C1—C6	1.391 (3)	C7—N1	1.391 (2)
C1—C7	1.472 (3)	C8—S1	1.722 (2)
C2—C3	1.381 (3)	C8—H8	0.9300
C2—H2	0.9300	C9—N1	1.342 (2)
C3—C4	1.384 (3)	C9—S2	1.673 (2)
C3—H3	0.9300	C9—S1	1.722 (2)
C4—O1	1.372 (2)	C10—O1	1.425 (2)
C4—C5	1.374 (3)	C10—H10A	0.9600
C5—C6	1.379 (3)	C10—H10B	0.9600
C5—H5	0.9300	C10—H10C	0.9600
C6—H6	0.9300	N1—H1	0.8600
C2—C1—C6	117.36 (19)	C8—C7—C1	128.18 (19)
C2—C1—C7	122.72 (18)	N1—C7—C1	121.05 (18)
C6—C1—C7	119.91 (18)	C7—C8—S1	111.78 (17)
C3—C2—C1	121.14 (19)	C7—C8—H8	124.1
C3—C2—H2	119.4	S1—C8—H8	124.1
C1—C2—H2	119.4	N1—C9—S2	127.78 (16)
C2—C3—C4	120.3 (2)	N1—C9—S1	108.01 (15)
C2—C3—H3	119.8	S2—C9—S1	124.17 (12)
C4—C3—H3	119.8	O1—C10—H10A	109.5
O1—C4—C5	124.71 (18)	O1—C10—H10B	109.5
O1—C4—C3	115.79 (19)	H10A—C10—H10B	109.5
C5—C4—C3	119.50 (19)	O1—C10—H10C	109.5
C4—C5—C6	119.75 (19)	H10A—C10—H10C	109.5
C4—C5—H5	120.1	H10B—C10—H10C	109.5
C6—C5—H5	120.1	C9—N1—C7	117.27 (17)
C5—C6—C1	121.9 (2)	C9—N1—H1	121.4
C5—C6—H6	119.0	C7—N1—H1	121.4
C1—C6—H6	119.0	C4—O1—C10	117.54 (17)
C8—C7—N1	110.77 (18)	C9—S1—C8	92.15 (10)
C6—C1—C2—C3	1.1 (3)	C6—C1—C7—N1	−168.62 (18)
C7—C1—C2—C3	−179.32 (19)	N1—C7—C8—S1	0.8 (2)
C1—C2—C3—C4	−1.0 (3)	C1—C7—C8—S1	−179.63 (16)
C2—C3—C4—O1	179.51 (18)	S2—C9—N1—C7	−178.17 (15)
C2—C3—C4—C5	−0.3 (3)	S1—C9—N1—C7	−0.1 (2)
O1—C4—C5—C6	−178.43 (19)	C8—C7—N1—C9	−0.5 (2)
C3—C4—C5—C6	1.3 (3)	C1—C7—N1—C9	179.90 (16)
C4—C5—C6—C1	−1.2 (3)	C5—C4—O1—C10	−2.6 (3)
C2—C1—C6—C5	0.0 (3)	C3—C4—O1—C10	177.62 (19)
C7—C1—C6—C5	−179.61 (19)	N1—C9—S1—C8	0.42 (15)
C2—C1—C7—C8	−167.8 (2)	S2—C9—S1—C8	178.60 (14)
C6—C1—C7—C8	11.8 (3)	C7—C8—S1—C9	−0.69 (17)
C2—C1—C7—N1	11.8 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···S2^i	0.86	2.55	3.374 (2)	162
C2—H2···S2^i	0.93	2.77	3.569 (2)	144

Symmetry code: (i) −x, −y+1, −z+1.