Supra­molecular structures in three thio­uracil derivatives: 5,6-tri­methyl­ene-2-sulfan­yl­idene-1,2-di­hydro­pyrimidin-4(3H)-one, 2-(4-fluorobenzyl­sulfan­yl)-5,6-tri­methyl­ene­pyrimidin-4(3H)-one and methyl 2-{[2-(4-fluoro­benzyl­sulfan­yl)-5,6-tri­methyl­ene­pyrimidin-4-yl]­oxy}acetate

The mol­ecules of the title compounds, C₇H₈N₂OS, (1), C₁₄H₁₃FN₂OS, (2), and C₁₇H₁₇FN₂O₃S, (3), crystallize in the space groups C2/m, C2/c and Ia, respectively. Compounds (1) and (2), an S-alkyl­ated derivative of (1), consist of only one symmetry-independent mol­ecule, while (3), an O-alkyl­ated derivative of (2), contains two independent mol­ecules in the asymmetric unit. The molecules of (1) sit on crystallographic mirror planes. In the supra­molecular structure of (1), a combination of N-H...O and N-H...S hydrogen bonds creates a mol­ecular strap with C(6) and R₂²(8) motifs, which is further stabilized by an S...S contact. In the packing of (2), a one-dimensional mol­ecular column is made up of two kinds of dimers. One dimer, with an R₂²(18) motif, is formed by a pair of C-H...O soft hydrogen bonds and the other, with an R₂²(8) motif, is produced via a pair of N-H...O hard hydrogen bonds. In the packing of (3), mol­ecules A and B form two different types of one-dimensional chain by inter­molecular C-H...N hydrogen bonds, and by C...N and O...S contacts, respectively. Two such kinds of chain are connected alternately via inter­chain C-H...O hydrogen bonds, giving a two-dimensional sheet. Finally, a three-dimensional supra­molecular structure is formed through weak intersheet C-H...F hydrogen bonds. The study of the mol­ecular and supra­molecular structures of thio­uracil derivatives is significant in the development of lipoprotein-associated phospho­lipase A₂ inhibitors.

S1. Introduction

Thio­uracil and its derivatives have attracted considerable inter­est due to their important biological activities (Koppel et al., 1961; Furberg & Petersen, 1972). They have been widely utilized as tools to investigate biochemical system agents, some of which exhibit anti­cancer (Al-Safarjalani et al., 2005), anti­viral (Brunelle et al., 2007; Ding et al., 2006) and anti­bacterial (Al-Deeb et al., 2012; Al-Abdullah et al., 2011; Hawser et al., 2006) activities. The crystal structures of some thio­uracil derivatives have been described (El-Emam et al., 2012; Radi et al., 2009; Ji et al., 2007; Wang et al., 2007; Singh et al., 2006; Balalaie et al., 2006; Glidewell et al., 2003). Recently, 5,6-tri­methyl­ene­thio­uracil derivatives have shown potential lipoprotein-associated phospho­lipase A₂ inhibitive activities. However, to the best of our knowledge, no crystal structures of 5,6-tri­methyl­ene­thio­uracil nor its derivatives have yet been described. Thus, we synthesized 5,6-tri­methyl­ene-2-sulfanyl­idene-1,2-di­hydro­pyrimidin-4(3H)-one (Blackie et al., 2003), (1), and its derivatives by selectively incorporating 4-fluoro­benzyl and meth­oxy­carbonyl­meth­oxy at the S- and O-positions, respectively, viz. 2-(4-fluoro­benzyl­sulfanyl)-5,6-tri­methyl­enepyrimidin-4(3H)-one, (2), and methyl 2-{[2-(4-fluoro­benzyl­sulfanyl)-5,6-tri­methyl­enepyrimidin-4-yl]­oxy}acetate, (3).

S2. Experimental

S2.1. Synthesis and crystallization

The synthesis of (1) followed a previously described method (Blackie et al., 2003) by reacting ethyl cyclo­pentane­carboxyl­ate with thio­urea mediated by sodium ethoxide in absolute ethanol to give a white solid (yield 65%, m.p. 526–528 K). Spectroscopic analysis: ¹H NMR (DMSO-d₆, 600 MHz, δ, p.p.m.): 1.94–1.99 (m, 2H), 2.49 (t, 2H), 2.69 (t, 2H), 12.20 (s, 1H), 12.58 (s, 1H). Single crystals of (1) suitable for X-ray diffraction analysis were obtained by slow vapour diffusion of pentane into a solution of (1) in EtOH–CH₂Cl₂ [Solvent ratio?] at 298 K.

The synthesis of (2) followed a previously described method (Mulholland et al., 2003) by selective S-alkyl­ation of (1) with 4-fluoro­benzyl chloride in the presence of NaOH in a solution of propan-2-ol and H₂O [Solvent ratio?] to give a white solid (yield 88%, m.p. 483–485 K). Spectroscopic analysis: ¹H NMR (DMSO-d₆, 600 MHz, δ, p.p.m.): 1.93–1.98 (m, 2H), 2.58 (t, 2H), 2.76 (t, 2H), 4.38 (s, 2H), 7.14 (dd, 2H), 7.45 (dd, 2H), 12.54 (s, 1H). Single crystals of (2) suitable for X-ray diffraction analysis were obtained by slow vapour diffusion of pentane into a solution of (2) in EtOH–CH₂Cl₂ [Solvent ratio?] at 298 K.

For the synthesis of (3), methyl bromo­acetate (0.153 g, 1.00 mmol) was added to a suspension of (2) (0.276 g, 1.00 mmol) and anhydrous K₂CO₃ (0.414 g, 3.00 mmol) in dry aceto­nitrile (20 ml). The resulting mixture was stirred for 3 h at 353 K and then cooled to room temperature. After filtration, the filtrate was added to di­chloro­methane and washed with brine, and the organic layer was dried over anhydrous MgSO₄. The solvent was evaporated in vacuo to give a white solid (yield 95%, m.p. 325–327 K). Spectroscopic analysis: ¹H NMR (DMSO-d₆, 600 MHz, δ, p.p.m.): 2.04–2.09 (m, 2H), 2.77 (t, 2H), 2.85 (t, 2H), 3.64 (s, 3H), 4.32 (s, 2H), 4.98 (s, 2H), 7.13 (dd, 2H), 7.42 (dd, 2H). Single crystals of (3) suitable for X-ray diffraction analysis were obtained by slow evaporation of a solution of (3) in EtOAc at 298 K.

S2.2. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 1. H atoms attached to anisotropically refined atoms were placed in geometrically idealized positions and included as riding atoms, with C—H = 0.93 Å and U_iso(H) = 1.2U_eq(C) for aromatic, C—H = 0.96 Å and U_iso(H) = 1.5U_eq(C) for methyl, and C—H = 0.97 Å and U_iso(H) = 1.2U_eq(C) for methyl­ene H atoms, and N—H = 0.86–0.92 Å and U_iso(H) = 1.2U_eq(N). Atom C5 of (1) and atom C4 of (2) are each disordered over two positions, both with refined site-occupancy factors of 0.50:0.50.

S3. Results and discussion

Compound (1) crystallizes in the space group C2/m with one molecule in the asymmetric unit (Fig. 1). The molecule adopts a conformation in which the N1/C1/N2/C2/C3/C7 ring is fully coplanar with its conjoint atoms C4 and C6, while the C5 methyl­ene group is disordered over two positions, with refined site-occupancy factors of 0.50. The thio­uracil ring exists in a thione form, with C═O and C═S bond lengths of 1.229 (3) and 1.671 (3) Å, respectively. The C═S bond is shorter than the corresponding bond in the parent 2-thio­uracil [1.683 (3) Å; Tiekink, 1989]. In the crystal packing of (1), there are N—H···O and N—H···S hydrogen bonds (Hu et al., 2005; Long et al., 2005) (Table 2).

Compound (2), an S-alkyl­ated derivative of (1), crystallizes in the space group C2/c with one molecule in the asymmetric unit (Fig. 2). Similar to (1), the N1/C7/N2/C1/C2/C6 ring is almost coplanar with its conjoint atoms C3 and C5, with N2—C1—C2—C3 and C7—N1—C6—C5 torsion angles of -179.8 (2) and 179.3 (2)°, respectively. The C4 methyl­ene unit is also disordered over two positions, with refined site-occupancy factors of 0.50. The phenyl ring is nearly perpendicular to the N1/C7/N2/C1/C2/C6 ring, with a dihedral angle of 77.1 (7)°. The N1—C7 and N1—C6 bond lengths are typical for such types of double and single bonds. The extremely short N1—C7 [1.303 (3) Å] and N2—C7 [1.357 (3) Å] bonds illustrate the consequence of the electronic delocalization caused by the S atom, while the C2—C6 distance of 1.354 (3) Å is very long for a double bond of this type [mean value 1.326 (3) Å; standard reference?]. The C1—O1 distance of 1.245 (2) Å is longer than the corresponding value of 1.230 (4) Å of (1), which is typical for C═O. In its crystal packing, there are hard N—H···O and soft C—H···O hydrogen bonds (Zhang et al., 2007) (Table 3).

Compound (3), an O-alkyl­ated derivative of (2) or an O- and S-bis-alkyl­ated derivative of (1), crystallizes in the space group Ia with two independent molecules, A and B, in the asymmetric unit (Fig. 3). For both molecules, the pyrimidine ring is coplanar only with their conjoint C atoms (C10 and C12 for molecule A, C27 and C29 for molecule B). However, atoms C11 for molecule A and C28 for molecule B deviate from the pyrimidine ring by 21.3 (2) and 23.2 (2)°, respectively. [These would normally be distances, not angles. Please check.] Remarkably, very different dihedral angles of 50.7 (9)° for molecule A and 89.6 (9)° for molecule B are found between the phenyl ring and the pyrimidine ring. The phenyl ring lies to one side of the pyrimidine ring, with N2—C8—S1—C7 and N3—C25—S2—C24 torsion angles of 14.4 (2) and -6.5 (3)° for molecules A and B, respectively. In the crystal packing, C—H···N and C—H···F hydrogen bonds are observed (Table 4).

In the supra­molecular structure of (1), an infinite one-dimensional chain is firstly formed by a combination of inter­molecular N1—H1···O1(x, y, z - 1) hydrogen bonds, locally creating a C(6) motif (Bernstein et al., 1995) at each link in the chain. Two adjacent such chains run in opposing directions and produce a molecular strap through a pair of centrosymmetrically related N2—H2···S1(-x + 1, y, -z + 1) hydrogen bonds between donors N2—H2 and acceptor S1 atoms of neighbouring molecules, locally generating an R₂²(8) motif (Fig. 4). In addition, an S···S contact (Ksiażek et al., 2009; Nagy et al., 2002) exists between adjacent R₂²(8) motifs, with an S1···S1 separation of 3.342 (3) Å, which is less than the sum of the van der Waals radii for two S atoms (S = 1.80 Å, Bondi, 1964). This S···S contact further stabilizes the molecular strap.

In the packing of (2), two supra­molecular dimers are observed (Fig. 5). One dimer is formed centrosymmetrically by two co-operative C10—H10···O1(-x + 1/2, -y + 1/2, -z + 1) hydrogen bonds, locally creating an R₂²(18) motif in which C10—H10 acts as hydrogen-bond donor and the acceptor is the carbonyl O atom. Additionally, a π–π contact (Singh et al., 2006) occurs between two parallel N1/C7/N2/C1/C2/C6 rings, with a Cg···Cg(-x + 1/2, -y + 1/2, -z + 1) distance of 3.814 (9) Å (Cg is the centroid of the N1/C7/N2/C1/C2/C6 ring). Next, each dimer is centrosymmetrically linked to its neighbours to produce a one-dimensional supra­molecular column through a combination of two N2—H2···O1(-x + 1/2, -y + 3/2, -z + 1) hydrogen bonds, locally creating an R₂²(8) motif. In this case, N2—H2 is the hydrogen-bond donor, while the carbonyl O atom again acts as acceptor. Aromatic π-stacking forces are an important factor in the stabilization of such a supra­molecular column.

In the crystal structure of (3), for molecule A, a one-dimensional comb-like chain is formed by a combination of inter­molecular C15—H15A···N1(x, y + 1, z) hydrogen bonds, locally generating a C(7) motif at each link in the chain (Fig. 6). However, for molecule B, a similar chain is produced not by inter­molecular hydrogen bonds but through co-operative C33···N4(x, y + 1, z) and O5···S2(x, y + 1, z) contacts (Nagy et al., 2002; Griffith et al., 1997) (Fig. 7), with distances of 3.186 (4) and 3.260 (2) Å, respectively, which are less than the sums of the van der Waals radii for the corresponding pairs of atoms (C = 1.70, N = 1.55, O = 1.52 and S = 1.80 Å; Bondi, 1964). Two kinds of such chains connect alternately in reverse directions by inter­chain C34ⁱⁱ—H34Cⁱⁱ···O2 and C3—H3···O5ⁱⁱ [symmetry code: (ii) x, -y + 1/2, z - 1/2] hydrogen bonds, creating a zigzag two-dimensional plane (Fig. 8). Finally, a three-dimensional supra­molecular structure is formed by weak inter­planar C12—H12A···F1(x - 1/2, y + 1/2, z - 1/2) hydrogen bonds.

Related literature

For related literature, see: Al-Abdullah et al. (2011); Al-Deeb et al. (2012); Al-Safarjalani et al. (2005); Balalaie et al. (2006); Bernstein et al. (1995); Blackie et al. (2003); Bondi (1964); Brunelle et al. (2007); Ding et al. (2006); El-Emam et al. (2012); Furberg & Petersen (1972); Glidewell et al. (2003); Griffith et al. (1997); Hawser et al. (2006); Hu et al. (2005); Ji et al. (2007); Koppel et al. (1961); Ksiażek et al. (2009); Long et al. (2005); Mulholland et al. (2003); Nagy et al. (2002); Radi et al. (2009); Singh et al. (2006); Tiekink (1989); Wang et al. (2007); Zhang et al. (2007).

Computing details

Data collection: SMART (Bruker, 1999) for (1), (2); CrysAlis PRO (Agilent, 2012) for (3). Cell refinement: SMART (Bruker, 1999) for (1), (2); CrysAlis PRO (Agilent, 2012) for (3). Data reduction: SAINT (Bruker, 1999) for (1), (2); CrysAlis PRO (Agilent, 2012) for (3). For all compounds, program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXS97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures

	Fig. 1. The molecular structure of (1), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. The disordered entities (dashed lines) are shown. [Not as clear as in Fig. 2 - can they be made more distinct?]
	Fig. 2. The molecular structure of (2), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. The disordered entities (hollow lines) are shown.
	Fig. 3. The molecular structure of the two independent molecules of (3), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 4. The hydrogen-bonded supramolecular strap of (1), showing the S···S contacts and N—H···O interactions (dashed lines), and the C(6) and R2^2(8) motifs. H atoms not involved in these motifs and the disordered entities have been omitted for clarity. [Symmetry codes: (i) x, y, z - 1; (ii) -x + 1, y, -z + 1; (iii) -x + 1, y, -z.]
	Fig. 5. The hydrogen-bonded supramolecular column of (2), showing the π–π contacts (turquoise dashed lines) and C—H···O interactions (green dashed lines), and the R2^2(8) and R2^2(18) motifs. H atoms not involved in these motifs and the disordered entities have been omitted for clarity. [Symmetry codes: (i) -x + 1/2, -y + 1/2, -z + 1; (ii) -x + 1/2, -y + 3/2, -z + 1; (iii) x, y + 1, z.]
	Fig. 6. The hydrogen-bonded supramolecular chain of molecule A of (3), showing the C(7) motif. Dashed lines indicate C—H···N interactions. H atoms not involved in this motif have been omitted for clarity. [Symmetry code: (i) x, y + 1, z.]
	Fig. 7. The supramolecular chain of molecule B of (3), assembled by C—H···N and O···S contacts (dashed lines). H atoms have been omitted for clarity. [Symmetry code: (i) x, y + 1, z.]
	Fig. 8. The transect of the hydrogen-bonded two-dimensional plane of (3). Dashed lines indicate C—H···O interactions. H atoms not involved in the motif have been omitted for clarity. [Symmetry codes: (ii) x, -y + 1/2, z - 1/2; (iv) x - 1/2, y + 1/2, z - 1/2.]

(1) 2-Sulfanylidene-1,2,3,4,6,7-hexahydro-5H-cyclopenta[d]pyrimidin-4-one

Crystal data

C7H8N2OS	Z = 4
Mr = 168.21	F(000) = 352
Monoclinic, C2/m	Dx = 1.468 Mg m^−3
a = 16.158 (15) Å	Mo Kα radiation, λ = 0.71073 Å
b = 6.986 (6) Å	µ = 0.36 mm^−1
c = 6.810 (6) Å	T = 293 K
β = 97.935 (13)°	Block, colourless
V = 761.4 (12) Å^3	0.50 × 0.32 × 0.30 mm

Data collection

Bruker SMART CCD area-detector diffractometer	810 independent reflections
Radiation source: fine-focus sealed tube	550 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.090
ϕ and ω scans	θmax = 26.0°, θmin = 2.6°
Absorption correction: multi-scan (SADABS; Bruker, 1999)	h = −19→16
Tmin = 0.870, Tmax = 0.897	k = −8→6
2052 measured reflections	l = −8→8

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)] = 0.042	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.105	H-atom parameters constrained
S = 0.96	w = 1/[σ^2(Fo^2) + (0.0409P)^2] where P = (Fo^2 + 2Fc^2)/3
810 reflections	(Δ/σ)max < 0.001
70 parameters	Δρmax = 0.21 e Å^−3
0 restraints	Δρmin = −0.25 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.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
C1	0.36128 (17)	0.0000	0.2918 (4)	0.0437 (7)
C2	0.27896 (18)	0.0000	0.5751 (4)	0.0451 (7)
C3	0.20538 (17)	0.0000	0.4320 (4)	0.0426 (7)
C4	0.11486 (17)	0.0000	0.4659 (5)	0.0525 (8)
H4A	0.1033	0.1025	0.5519	0.063*	0.50
H4B	0.0993	−0.1196	0.5198	0.063*	0.50
C6	0.12991 (18)	0.0000	0.1049 (5)	0.0618 (9)
H6A	0.1197	−0.1195	0.0363	0.074*	0.50
H6B	0.1263	0.1030	0.0108	0.074*	0.50
C7	0.21200 (17)	0.0000	0.2368 (4)	0.0433 (7)
C5	0.0678 (3)	0.028 (4)	0.2531 (6)	0.060 (4)	0.50
H5A	0.0408	0.1500	0.2371	0.072*	0.50
H5B	0.0261	−0.0708	0.2289	0.072*	0.50
N1	0.28795 (14)	0.0000	0.1689 (3)	0.0485 (7)
H1	0.2891	0.0000	0.0430	0.058*
N2	0.35355 (14)	0.0000	0.4900 (3)	0.0477 (7)
H2	0.3993	0.0000	0.5712	0.057*
O1	0.28256 (15)	0.0000	0.7566 (3)	0.0689 (7)
S1	0.45269 (5)	0.0000	0.20321 (12)	0.0657 (4)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0347 (15)	0.068 (2)	0.0282 (15)	0.000	0.0042 (12)	0.000
C2	0.0473 (17)	0.0581 (19)	0.0314 (16)	0.000	0.0104 (14)	0.000
C3	0.0388 (15)	0.0577 (19)	0.0333 (16)	0.000	0.0114 (13)	0.000
C4	0.0445 (17)	0.063 (2)	0.054 (2)	0.000	0.0215 (15)	0.000
C6	0.0383 (17)	0.097 (3)	0.048 (2)	0.000	−0.0009 (15)	0.000
C7	0.0313 (14)	0.0618 (19)	0.0373 (17)	0.000	0.0065 (12)	0.000
C5	0.0403 (18)	0.073 (13)	0.068 (3)	0.008 (4)	0.0080 (17)	−0.006 (4)
N1	0.0365 (13)	0.0856 (18)	0.0237 (13)	0.000	0.0056 (11)	0.000
N2	0.0370 (13)	0.0782 (18)	0.0266 (13)	0.000	0.0002 (11)	0.000
O1	0.0723 (16)	0.1128 (19)	0.0232 (12)	0.000	0.0126 (11)	0.000
S1	0.0341 (5)	0.1235 (9)	0.0404 (6)	0.000	0.0088 (4)	0.000

Geometric parameters (Å, º)

C1—N1	1.353 (4)	C6—C7	1.496 (4)
C1—N2	1.373 (4)	C6—C5	1.531 (6)
C1—S1	1.671 (3)	C6—C5^i	1.531 (6)
C2—O1	1.229 (3)	C6—H6A	0.9600
C2—N2	1.407 (3)	C6—H6B	0.9600
C2—C3	1.430 (4)	C7—N1	1.370 (3)
C3—C7	1.348 (4)	C5—C5^i	0.38 (6)
C3—C4	1.512 (4)	C5—H5A	0.9600
C4—C5^i	1.553 (6)	C5—H5B	0.9600
C4—C5	1.553 (6)	N1—H1	0.8600
C4—H4A	0.9600	N2—H2	0.8600
C4—H4B	0.9600
N1—C1—N2	114.7 (2)	C5^i—C6—H6A	97.3
N1—C1—S1	121.2 (2)	C7—C6—H6B	111.6
N2—C1—S1	124.1 (2)	C5—C6—H6B	111.1
O1—C2—N2	119.3 (3)	C5^i—C6—H6B	123.3
O1—C2—C3	127.2 (3)	H6A—C6—H6B	109.7
N2—C2—C3	113.5 (2)	C3—C7—N1	122.0 (3)
C7—C3—C2	120.0 (2)	C3—C7—C6	114.1 (3)
C7—C3—C4	111.1 (3)	N1—C7—C6	124.0 (3)
C2—C3—C4	128.8 (3)	C5^i—C5—C6	82.8 (10)
C3—C4—C5^i	102.6 (2)	C5^i—C5—C4	82.9 (10)
C3—C4—C5	102.6 (2)	C6—C5—C4	108.5 (5)
C5^i—C4—C5	14 (2)	C5^i—C5—H5A	153.1
C3—C4—H4A	111.6	C6—C5—H5A	111.5
C5^i—C4—H4A	123.4	C4—C5—H5A	111.9
C5—C4—H4A	111.4	C5^i—C5—H5B	44.3
C3—C4—H4B	111.6	C6—C5—H5B	107.8
C5^i—C4—H4B	97.4	C4—C5—H5B	108.2
C5—C4—H4B	110.1	H5A—C5—H5B	108.7
H4A—C4—H4B	109.4	C1—N1—C7	122.7 (2)
C7—C6—C5	102.3 (3)	C1—N1—H1	118.7
C7—C6—C5^i	102.3 (3)	C7—N1—H1	118.7
C5—C6—C5^i	14 (2)	C1—N2—C2	127.2 (2)
C7—C6—H6A	111.7	C1—N2—H2	116.4
C5—C6—H6A	110.3	C2—N2—H2	116.4
O1—C2—C3—C7	180.0	C5^i—C6—C7—N1	172.6 (11)
N2—C2—C3—C7	0.0	C7—C6—C5—C5^i	−91.6 (2)
O1—C2—C3—C4	0.0	C7—C6—C5—C4	−11.6 (16)
N2—C2—C3—C4	180.0	C5^i—C6—C5—C4	80.0 (14)
C7—C3—C4—C5^i	7.3 (11)	C3—C4—C5—C5^i	91.6 (2)
C2—C3—C4—C5^i	−172.7 (11)	C3—C4—C5—C6	11.7 (16)
C7—C3—C4—C5	−7.3 (11)	C5^i—C4—C5—C6	−79.9 (14)
C2—C3—C4—C5	172.7 (11)	N2—C1—N1—C7	0.0
C2—C3—C7—N1	0.0	S1—C1—N1—C7	180.0
C4—C3—C7—N1	180.0	C3—C7—N1—C1	0.0
C2—C3—C7—C6	180.0	C6—C7—N1—C1	180.0
C4—C3—C7—C6	0.0	N1—C1—N2—C2	0.0
C5—C6—C7—C3	7.4 (11)	S1—C1—N2—C2	180.0
C5^i—C6—C7—C3	−7.4 (11)	O1—C2—N2—C1	180.0
C5—C6—C7—N1	−172.6 (11)	C3—C2—N2—C1	0.0

Symmetry code: (i) x, −y, z.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1^ii	0.86	1.94	2.797 (4)	176
N2—H2···S1^iii	0.86	2.66	3.516 (4)	175

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

(2) 2-[(4-Fluorobenzyl)sulfanyl]-3,4,6,7-tetrahydro-5H-cyclopenta[d]pyrimidin-4-one

Crystal data

C14H13FN2OS	F(000) = 1152
Mr = 276.32	Dx = 1.359 Mg m^−3
Monoclinic, C2/c	Mo Kα radiation, λ = 0.71073 Å
a = 25.381 (7) Å	Cell parameters from 1746 reflections
b = 5.8848 (18) Å	θ = 2.3–23.6°
c = 19.738 (6) Å	µ = 0.24 mm^−1
β = 113.626 (4)°	T = 293 K
V = 2701.1 (14) Å^3	Block, colourless
Z = 8	0.15 × 0.10 × 0.10 mm

Data collection

Bruker SMART CCD area-detector diffractometer	2371 independent reflections
Radiation source: fine-focus sealed tube	1689 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.029
ϕ and ω scans	θmax = 25.0°, θmin = 2.2°
Absorption correction: multi-scan (SADABS; Bruker, 1999)	h = −30→22
Tmin = 0.971, Tmax = 0.976	k = −5→6
6236 measured reflections	l = −21→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)] = 0.039	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.112	H-atom parameters constrained
S = 1.03	w = 1/[σ^2(Fo^2) + (0.0528P)^2 + 1.0457P] where P = (Fo^2 + 2Fc^2)/3
2371 reflections	(Δ/σ)max = 0.001
182 parameters	Δρmax = 0.23 e Å^−3
10 restraints	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.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq	Occ. (<1)
C1	0.31801 (9)	0.5332 (4)	0.53415 (12)	0.0441 (6)
C2	0.36216 (9)	0.3693 (4)	0.55138 (12)	0.0460 (6)
C3	0.41660 (10)	0.3517 (5)	0.61971 (14)	0.0621 (7)
H3A	0.4086	0.3114	0.6623	0.075*
H3B	0.4378	0.4938	0.6297	0.075*
C5	0.40815 (10)	0.0446 (4)	0.53084 (14)	0.0605 (7)
H5A	0.4249	0.0279	0.4948	0.073*
H5B	0.3974	−0.1042	0.5422	0.073*
C6	0.35732 (9)	0.2002 (4)	0.50272 (13)	0.0468 (6)
C7	0.27228 (9)	0.3250 (4)	0.41989 (11)	0.0416 (5)
C8	0.22252 (10)	0.0762 (4)	0.29126 (13)	0.0559 (7)
H8A	0.2511	0.1080	0.2714	0.067*
H8B	0.2364	−0.0482	0.3262	0.067*
C9	0.16623 (9)	0.0126 (4)	0.22965 (12)	0.0474 (6)
C10	0.13309 (12)	−0.1554 (4)	0.24030 (14)	0.0649 (7)
H10	0.1454	−0.2270	0.2861	0.078*
C11	0.08225 (12)	−0.2206 (5)	0.18530 (15)	0.0757 (9)
H11	0.0605	−0.3371	0.1931	0.091*
C12	0.06413 (11)	−0.1129 (5)	0.11954 (14)	0.0628 (7)
C13	0.09479 (11)	0.0557 (5)	0.10627 (14)	0.0695 (8)
H13	0.0814	0.1275	0.0605	0.083*
C14	0.14636 (11)	0.1199 (5)	0.16177 (14)	0.0623 (7)
H14	0.1678	0.2361	0.1534	0.075*
F1	0.01371 (7)	−0.1792 (3)	0.06450 (9)	0.0978 (6)
N1	0.31233 (8)	0.1712 (3)	0.43524 (10)	0.0470 (5)
N2	0.27354 (7)	0.4991 (3)	0.46552 (9)	0.0430 (5)
H2	0.2443	0.5950	0.4526	0.052*
O1	0.31596 (7)	0.6956 (3)	0.57347 (8)	0.0546 (5)
S1	0.21090 (3)	0.32567 (10)	0.33700 (3)	0.0506 (2)
C4'	0.4502 (6)	0.162 (4)	0.6010 (11)	0.081 (5)	0.41 (3)
H4'1	0.4823	0.2254	0.5926	0.098*	0.41 (3)
H4'2	0.4650	0.0540	0.6414	0.098*	0.41 (3)
C4	0.4373 (8)	0.111 (2)	0.6128 (5)	0.081 (4)	0.59 (3)
H4A	0.4266	0.0055	0.6429	0.097*	0.59 (3)
H4B	0.4788	0.1088	0.6292	0.097*	0.59 (3)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0457 (14)	0.0434 (14)	0.0410 (13)	0.0008 (11)	0.0151 (11)	0.0018 (11)
C2	0.0395 (13)	0.0489 (14)	0.0448 (13)	0.0035 (11)	0.0118 (10)	0.0015 (11)
C3	0.0476 (15)	0.0665 (18)	0.0570 (15)	0.0060 (13)	0.0050 (12)	−0.0013 (13)
C5	0.0500 (15)	0.0603 (17)	0.0677 (17)	0.0134 (12)	0.0199 (13)	0.0036 (13)
C6	0.0428 (14)	0.0467 (14)	0.0508 (13)	0.0037 (11sf3223)	0.0186 (11)	0.0028 (11)
C7	0.0434 (13)	0.0421 (13)	0.0400 (12)	−0.0002 (11)	0.0175 (10)	−0.0002 (10)
C8	0.0474 (14)	0.0627 (16)	0.0508 (14)	0.0070 (12)	0.0126 (12)	−0.0131 (12)
C9	0.0461 (13)	0.0490 (14)	0.0435 (13)	0.0051 (11)	0.0141 (11)	−0.0079 (11)
C10	0.0723 (19)	0.0577 (17)	0.0475 (14)	−0.0036 (14)	0.0061 (13)	0.0079 (12)
C11	0.072 (2)	0.075 (2)	0.0629 (18)	−0.0242 (15)	0.0092 (15)	0.0061 (15)
C12	0.0480 (16)	0.0771 (19)	0.0498 (15)	−0.0074 (14)	0.0054 (12)	−0.0085 (14)
C13	0.0636 (18)	0.093 (2)	0.0424 (14)	−0.0084 (16)	0.0109 (13)	0.0088 (14)
C14	0.0578 (17)	0.0744 (18)	0.0512 (15)	−0.0148 (14)	0.0182 (13)	0.0009 (13)
F1	0.0675 (11)	0.1311 (17)	0.0658 (10)	−0.0294 (10)	−0.0037 (8)	−0.0089 (10)
N1	0.0416 (11)	0.0488 (12)	0.0474 (11)	0.0038 (9)	0.0146 (9)	−0.0031 (9)
N2	0.0415 (10)	0.0440 (11)	0.0376 (10)	0.0069 (8)	0.0096 (8)	−0.0003 (8)
O1	0.0576 (11)	0.0524 (11)	0.0419 (9)	0.0086 (8)	0.0076 (7)	−0.0075 (8)
S1	0.0478 (4)	0.0534 (4)	0.0427 (3)	0.0064 (3)	0.0099 (3)	−0.0059 (3)
C4'	0.047 (6)	0.081 (7)	0.091 (6)	0.018 (5)	0.000 (5)	−0.014 (6)
C4	0.061 (5)	0.079 (5)	0.078 (4)	0.023 (4)	0.002 (3)	−0.001 (4)

Geometric parameters (Å, º)

C1—O1	1.245 (3)	C8—S1	1.808 (2)
C1—N2	1.387 (3)	C8—H8A	0.9700
C1—C2	1.413 (3)	C8—H8B	0.9700
C2—C6	1.354 (3)	C9—C10	1.368 (3)
C2—C3	1.498 (3)	C9—C14	1.381 (3)
C3—C4	1.535 (7)	C10—C11	1.367 (3)
C3—C4'	1.537 (9)	C10—H10	0.9300
C3—H3A	0.9700	C11—C12	1.349 (4)
C3—H3B	0.9700	C11—H11	0.9300
C5—C6	1.496 (3)	C12—C13	1.350 (4)
C5—C4'	1.533 (9)	C12—F1	1.362 (3)
C5—C4	1.536 (7)	C13—C14	1.381 (3)
C5—H5A	0.9700	C13—H13	0.9300
C5—H5B	0.9700	C14—H14	0.9300
C6—N1	1.374 (3)	N2—H2	0.8852
C7—N1	1.303 (3)	C4'—H4'1	0.9700
C7—N2	1.356 (3)	C4'—H4'2	0.9700
C7—S1	1.750 (2)	C4—H4A	0.9700
C8—C9	1.506 (3)	C4—H4B	0.9700
O1—C1—N2	119.9 (2)	H8A—C8—H8B	108.4
O1—C1—C2	126.9 (2)	C10—C9—C14	118.1 (2)
N2—C1—C2	113.1 (2)	C10—C9—C8	119.9 (2)
C6—C2—C1	119.5 (2)	C14—C9—C8	122.0 (2)
C6—C2—C3	112.1 (2)	C11—C10—C9	121.6 (2)
C1—C2—C3	128.3 (2)	C11—C10—H10	119.2
C2—C3—C4	102.0 (4)	C9—C10—H10	119.2
C2—C3—C4'	103.5 (5)	C12—C11—C10	118.8 (3)
C4—C3—C4'	21.0 (11)	C12—C11—H11	120.6
C2—C3—H3A	111.1	C10—C11—H11	120.6
C4—C3—H3A	92.8	C11—C12—C13	122.1 (2)
C4'—C3—H3A	111.1	C11—C12—F1	118.8 (3)
C2—C3—H3B	111.1	C13—C12—F1	119.1 (2)
C4—C3—H3B	129.2	C12—C13—C14	119.0 (3)
C4'—C3—H3B	111.1	C12—C13—H13	120.5
H3A—C3—H3B	109.0	C14—C13—H13	120.5
C6—C5—C4'	104.1 (5)	C9—C14—C13	120.4 (3)
C6—C5—C4	102.4 (4)	C9—C14—H14	119.8
C4'—C5—C4	21.0 (11)	C13—C14—H14	119.8
C6—C5—H5A	110.9	C7—N1—C6	114.02 (19)
C4'—C5—H5A	110.9	C7—N2—C1	123.47 (19)
C4—C5—H5A	129.1	C7—N2—H2	119.7
C6—C5—H5B	110.9	C1—N2—H2	116.8
C4'—C5—H5B	110.9	C7—S1—C8	101.70 (11)
C4—C5—H5B	92.8	C5—C4'—C3	107.0 (7)
H5A—C5—H5B	108.9	C5—C4'—H4'1	110.3
C2—C6—N1	125.7 (2)	C3—C4'—H4'1	110.3
C2—C6—C5	111.5 (2)	C5—C4'—H4'2	110.3
N1—C6—C5	122.8 (2)	C3—C4'—H4'2	110.3
N1—C7—N2	124.2 (2)	H4'1—C4'—H4'2	108.6
N1—C7—S1	122.58 (17)	C3—C4—C5	106.9 (5)
N2—C7—S1	113.23 (16)	C3—C4—H4A	110.3
C9—C8—S1	108.26 (16)	C5—C4—H4A	110.3
C9—C8—H8A	110.0	C3—C4—H4B	110.3
S1—C8—H8A	110.0	C5—C4—H4B	110.3
C9—C8—H8B	110.0	H4A—C4—H4B	108.6
S1—C8—H8B	110.0
O1—C1—C2—C6	178.9 (2)	F1—C12—C13—C14	−178.9 (3)
N2—C1—C2—C6	−0.9 (3)	C10—C9—C14—C13	−0.9 (4)
O1—C1—C2—C3	−0.5 (4)	C8—C9—C14—C13	179.4 (2)
N2—C1—C2—C3	179.7 (2)	C12—C13—C14—C9	0.2 (4)
C6—C2—C3—C4	−13.1 (9)	N2—C7—N1—C6	−0.4 (3)
C1—C2—C3—C4	166.3 (9)	S1—C7—N1—C6	179.58 (16)
C6—C2—C3—C4'	8.3 (14)	C2—C6—N1—C7	0.0 (3)
C1—C2—C3—C4'	−172.2 (13)	C5—C6—N1—C7	−179.3 (2)
C1—C2—C6—N1	0.6 (4)	N1—C7—N2—C1	0.1 (3)
C3—C2—C6—N1	−179.9 (2)	S1—C7—N2—C1	−179.88 (16)
C1—C2—C6—C5	180.0 (2)	O1—C1—N2—C7	−179.2 (2)
C3—C2—C6—C5	−0.5 (3)	C2—C1—N2—C7	0.5 (3)
C4'—C5—C6—C2	−7.6 (14)	N1—C7—S1—C8	0.7 (2)
C4—C5—C6—C2	13.9 (9)	N2—C7—S1—C8	−179.36 (16)
C4'—C5—C6—N1	171.8 (13)	C9—C8—S1—C7	163.62 (17)
C4—C5—C6—N1	−166.7 (9)	C6—C5—C4'—C3	12 (2)
S1—C8—C9—C10	−98.4 (2)	C4—C5—C4'—C3	−75.4 (16)
S1—C8—C9—C14	81.3 (3)	C2—C3—C4'—C5	−13 (2)
C14—C9—C10—C11	1.4 (4)	C4—C3—C4'—C5	75.8 (16)
C8—C9—C10—C11	−178.8 (3)	C2—C3—C4—C5	21.2 (14)
C9—C10—C11—C12	−1.2 (5)	C4'—C3—C4—C5	−75.3 (17)
C10—C11—C12—C13	0.5 (5)	C6—C5—C4—C3	−21.6 (14)
C10—C11—C12—F1	179.4 (3)	C4'—C5—C4—C3	75.6 (17)
C11—C12—C13—C14	0.0 (5)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C10—H10···O1^i	0.93	2.55	3.381 (3)	149
N2—H2···O1^ii	0.89	1.87	2.753 (2)	178

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

(3) Methyl 2-({2-[(4-fluorobenzyl)sulfanyl]-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl}oxy)acetate

Crystal data

C17H17FN2O3S	F(000) = 1456
Mr = 348.39	Dx = 1.430 Mg m^−3
Monoclinic, Ia	Mo Kα radiation, λ = 0.71073 Å
a = 17.1673 (12) Å	Cell parameters from 4673 reflections
b = 8.1187 (5) Å	θ = 3.6–28.1°
c = 23.7393 (16) Å	µ = 0.23 mm^−1
β = 102.045 (7)°	T = 100 K
V = 3235.8 (4) Å^3	Block, colourless
Z = 8	0.27 × 0.10 × 0.09 mm

Data collection

Agilent SuperNova Dual diffractometer (Cu at zero) with Eos detector	4963 independent reflections
Radiation source: SuperNova (Mo) X-ray Source	4626 reflections with I > 2σ(I)
Mirror monochromator	Rint = 0.041
Detector resolution: 16.0793 pixels mm^-1	θmax = 25.0°, θmin = 3.1°
ω scans	h = −20→20
Absorption correction: multi-scan (SADABS; Bruker, 1999)	k = −9→9
Tmin = 0.941, Tmax = 0.980	l = −24→28
11191 measured reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.036	H-atom parameters constrained
wR(F^2) = 0.086	w = 1/[σ^2(Fo^2) + (0.035P)^2 + 1.9371P] where P = (Fo^2 + 2Fc^2)/3
S = 1.05	(Δ/σ)max = 0.001
4963 reflections	Δρmax = 0.22 e Å^−3
435 parameters	Δρmin = −0.20 e Å^−3
2 restraints	Absolute structure: Flack (1983), with 2105 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.10 (6)

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.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > 2sigma(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

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

	x	y	z	Uiso*/Ueq
C1	0.21470 (19)	0.1380 (4)	0.20284 (14)	0.0225 (7)
H1	0.2045	0.0588	0.2287	0.027*
C2	0.28026 (19)	0.2388 (4)	0.21629 (14)	0.0222 (8)
C3	0.29961 (19)	0.3535 (4)	0.17877 (14)	0.0220 (7)
H3	0.3460	0.4157	0.1883	0.026*
C4	0.24740 (18)	0.3724 (4)	0.12634 (14)	0.0218 (7)
H4	0.2583	0.4512	0.1006	0.026*
C5	0.17961 (18)	0.2774 (4)	0.11113 (13)	0.0182 (7)
C6	0.16405 (19)	0.1582 (4)	0.14935 (13)	0.0218 (7)
H6	0.1194	0.0913	0.1391	0.026*
C7	0.1210 (2)	0.3136 (4)	0.05605 (13)	0.0248 (8)
H7A	0.1391	0.4081	0.0374	0.030*
H7B	0.0698	0.3410	0.0648	0.030*
C8	0.03745 (18)	0.2199 (4)	−0.05020 (13)	0.0167 (7)
C9	−0.05422 (17)	0.1735 (4)	−0.13121 (13)	0.0167 (7)
C10	−0.10355 (18)	0.0763 (4)	−0.17947 (13)	0.0223 (7)
H10A	−0.1253	−0.0215	−0.1651	0.027*
H10B	−0.0723	0.0438	−0.2073	0.027*
C11	−0.17036 (19)	0.1973 (4)	−0.20645 (15)	0.0262 (8)
H11A	−0.2186	0.1741	−0.1927	0.031*
H11B	−0.1819	0.1880	−0.2481	0.031*
C12	−0.13894 (18)	0.3723 (4)	−0.18759 (13)	0.0195 (7)
H12A	−0.1176	0.4261	−0.2176	0.023*
H12B	−0.1806	0.4405	−0.1778	0.023*
C13	−0.07442 (18)	0.3377 (4)	−0.13544 (13)	0.0160 (7)
C14	−0.03054 (17)	0.4400 (4)	−0.09388 (13)	0.0156 (7)
C15	0.00792 (19)	0.7034 (4)	−0.05520 (13)	0.0199 (7)
H15A	−0.0013	0.8185	−0.0655	0.024*
H15B	0.0625	0.6779	−0.0571	0.024*
C16	−0.00156 (18)	0.6804 (4)	0.00579 (14)	0.0205 (7)
C17	−0.0822 (2)	0.5838 (5)	0.06712 (16)	0.0402 (10)
H17A	−0.0333	0.5459	0.0909	0.060*
H17B	−0.1229	0.5022	0.0664	0.060*
H17C	−0.0981	0.6849	0.0824	0.060*
C18	0.40573 (18)	0.5883 (4)	0.55432 (14)	0.0238 (8)
H18	0.4576	0.5581	0.5530	0.029*
C19	0.3522 (2)	0.6309 (4)	0.50363 (14)	0.0276 (8)
H19	0.3677	0.6292	0.4684	0.033*
C20	0.27613 (19)	0.6754 (4)	0.50697 (14)	0.0252 (8)
C21	0.25058 (19)	0.6796 (4)	0.55778 (14)	0.0234 (7)
H21	0.1986	0.7097	0.5587	0.028*
C22	0.30419 (18)	0.6377 (4)	0.60767 (14)	0.0217 (7)
H22	0.2880	0.6408	0.6427	0.026*
C23	0.38193 (18)	0.5909 (4)	0.60669 (13)	0.0181 (7)
C24	0.43988 (18)	0.5524 (4)	0.66213 (13)	0.0199 (7)
H24A	0.4828	0.4835	0.6548	0.024*
H24B	0.4132	0.4953	0.6886	0.024*
C25	0.54640 (18)	0.6922 (4)	0.75604 (13)	0.0170 (7)
C26	0.64246 (18)	0.7711 (4)	0.83052 (13)	0.0169 (7)
C27	0.69764 (18)	0.8875 (4)	0.86910 (14)	0.0223 (7)
H27A	0.6692	0.9519	0.8927	0.027*
H27B	0.7238	0.9614	0.8468	0.027*
C28	0.75793 (19)	0.7705 (4)	0.90623 (14)	0.0228 (7)
H28A	0.7729	0.8114	0.9454	0.027*
H28B	0.8056	0.7610	0.8905	0.027*
C29	0.71609 (18)	0.6010 (4)	0.90521 (13)	0.0181 (7)
H29A	0.7527	0.5112	0.9032	0.022*
H29B	0.6929	0.5863	0.9388	0.022*
C30	0.65276 (17)	0.6128 (4)	0.85085 (12)	0.0149 (6)
C31	0.60214 (17)	0.4957 (4)	0.81968 (12)	0.0155 (6)
C32	0.54546 (18)	0.2293 (3)	0.80889 (13)	0.0172 (7)
H32A	0.4937	0.2775	0.8087	0.021*
H32B	0.5486	0.1266	0.8301	0.021*
C33	0.55050 (18)	0.1914 (4)	0.74823 (13)	0.0181 (7)
C34	0.6332 (2)	0.1560 (5)	0.68240 (15)	0.0320 (9)
H34A	0.6188	0.0420	0.6767	0.048*
H34B	0.6874	0.1708	0.6790	0.048*
H34C	0.5989	0.2215	0.6538	0.048*
F1	0.32910 (12)	0.2242 (2)	0.26924 (8)	0.0339 (5)
F2	0.22359 (12)	0.7157 (3)	0.45756 (8)	0.0388 (6)
N1	0.00167 (15)	0.1080 (3)	−0.08859 (11)	0.0179 (6)
N2	0.02476 (14)	0.3824 (3)	−0.05073 (10)	0.0161 (5)
N3	0.54940 (14)	0.5329 (3)	0.77156 (10)	0.0146 (5)
N4	0.58912 (15)	0.8169 (3)	0.78335 (11)	0.0187 (6)
O1	−0.04463 (12)	0.6041 (2)	−0.09712 (8)	0.0188 (5)
O2	0.04824 (13)	0.7258 (3)	0.04617 (9)	0.0275 (6)
O3	−0.07075 (12)	0.6113 (3)	0.00919 (9)	0.0267 (5)
O4	0.60580 (12)	0.3390 (2)	0.83909 (8)	0.0170 (5)
O5	0.49369 (12)	0.1472 (3)	0.71212 (9)	0.0211 (5)
O6	0.62454 (12)	0.2068 (3)	0.73917 (9)	0.0208 (5)
S1	0.10930 (4)	0.13797 (9)	0.00721 (3)	0.02091 (18)
S2	0.47869 (5)	0.75022 (9)	0.69228 (3)	0.01879 (17)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0290 (18)	0.0184 (17)	0.0214 (17)	0.0046 (14)	0.0082 (14)	0.0016 (13)
C2	0.0250 (18)	0.0188 (17)	0.0191 (17)	0.0081 (14)	−0.0037 (14)	−0.0025 (13)
C3	0.0146 (15)	0.0191 (17)	0.031 (2)	−0.0012 (13)	0.0014 (14)	−0.0007 (14)
C4	0.0221 (17)	0.0190 (17)	0.0256 (18)	0.0047 (14)	0.0081 (14)	0.0061 (14)
C5	0.0173 (16)	0.0194 (16)	0.0184 (17)	0.0065 (13)	0.0048 (13)	−0.0053 (13)
C6	0.0185 (16)	0.0238 (18)	0.0231 (17)	−0.0003 (14)	0.0046 (14)	−0.0036 (14)
C7	0.0297 (18)	0.0188 (17)	0.0236 (19)	0.0051 (15)	0.0002 (15)	−0.0016 (14)
C8	0.0161 (15)	0.0147 (16)	0.0195 (17)	0.0025 (13)	0.0040 (13)	0.0008 (13)
C9	0.0150 (15)	0.0191 (17)	0.0171 (16)	0.0002 (13)	0.0060 (13)	0.0008 (13)
C10	0.0240 (17)	0.0175 (17)	0.0241 (18)	−0.0020 (13)	0.0019 (14)	−0.0012 (13)
C11	0.0219 (17)	0.0218 (18)	0.031 (2)	−0.0043 (15)	−0.0023 (15)	0.0008 (16)
C12	0.0207 (16)	0.0171 (16)	0.0212 (18)	0.0045 (14)	0.0051 (14)	−0.0009 (13)
C13	0.0182 (16)	0.0150 (16)	0.0163 (16)	−0.0012 (13)	0.0074 (13)	0.0023 (13)
C14	0.0208 (16)	0.0129 (16)	0.0150 (16)	0.0012 (13)	0.0081 (13)	0.0042 (12)
C15	0.0290 (18)	0.0134 (16)	0.0175 (17)	−0.0021 (13)	0.0055 (14)	−0.0012 (12)
C16	0.0252 (18)	0.0136 (16)	0.0219 (18)	0.0035 (14)	0.0029 (15)	0.0020 (14)
C17	0.045 (2)	0.048 (3)	0.037 (2)	−0.013 (2)	0.0316 (19)	−0.0068 (18)
C18	0.0213 (17)	0.0235 (18)	0.0263 (19)	−0.0028 (14)	0.0047 (15)	−0.0029 (14)
C19	0.039 (2)	0.0278 (19)	0.0170 (18)	−0.0081 (16)	0.0071 (16)	−0.0040 (14)
C20	0.031 (2)	0.0181 (18)	0.0219 (19)	−0.0049 (15)	−0.0060 (16)	0.0018 (14)
C21	0.0193 (16)	0.0188 (16)	0.0297 (19)	−0.0016 (14)	−0.0008 (14)	−0.0033 (14)
C22	0.0229 (17)	0.0215 (18)	0.0220 (18)	−0.0044 (14)	0.0079 (14)	−0.0027 (13)
C23	0.0222 (16)	0.0127 (16)	0.0180 (17)	−0.0020 (13)	0.0009 (13)	−0.0015 (12)
C24	0.0218 (16)	0.0140 (16)	0.0229 (17)	−0.0018 (13)	0.0023 (14)	−0.0011 (13)
C25	0.0173 (16)	0.0170 (16)	0.0176 (16)	−0.0003 (14)	0.0059 (13)	−0.0002 (13)
C26	0.0170 (16)	0.0160 (16)	0.0180 (17)	−0.0004 (13)	0.0046 (13)	−0.0028 (13)
C27	0.0229 (17)	0.0199 (17)	0.0220 (17)	−0.0052 (14)	−0.0003 (14)	−0.0031 (14)
C28	0.0209 (17)	0.0235 (18)	0.0226 (18)	−0.0036 (14)	0.0013 (14)	−0.0057 (14)
C29	0.0174 (15)	0.0197 (17)	0.0169 (16)	0.0009 (13)	0.0025 (13)	−0.0003 (13)
C30	0.0135 (15)	0.0174 (16)	0.0153 (16)	−0.0004 (12)	0.0064 (13)	−0.0044 (12)
C31	0.0187 (15)	0.0146 (15)	0.0149 (15)	0.0012 (13)	0.0074 (13)	−0.0004 (12)
C32	0.0206 (16)	0.0102 (15)	0.0201 (16)	−0.0018 (13)	0.0023 (13)	0.0012 (12)
C33	0.0207 (17)	0.0087 (15)	0.0247 (18)	0.0026 (13)	0.0040 (15)	0.0015 (13)
C34	0.0272 (18)	0.044 (2)	0.0274 (19)	−0.0014 (17)	0.0107 (16)	−0.0130 (16)
F1	0.0445 (12)	0.0253 (11)	0.0238 (11)	0.0005 (9)	−0.0116 (9)	0.0018 (8)
F2	0.0481 (13)	0.0299 (12)	0.0280 (12)	−0.0036 (10)	−0.0160 (10)	0.0066 (9)
N1	0.0192 (13)	0.0149 (14)	0.0186 (14)	0.0012 (11)	0.0019 (11)	0.0039 (11)
N2	0.0201 (13)	0.0142 (13)	0.0143 (13)	0.0002 (11)	0.0047 (11)	0.0011 (10)
N3	0.0169 (13)	0.0093 (12)	0.0180 (14)	−0.0010 (10)	0.0041 (11)	−0.0014 (10)
N4	0.0182 (13)	0.0165 (14)	0.0208 (14)	−0.0024 (11)	0.0024 (11)	−0.0016 (11)
O1	0.0276 (12)	0.0118 (11)	0.0159 (11)	0.0033 (9)	0.0017 (9)	−0.0001 (9)
O2	0.0311 (13)	0.0297 (14)	0.0198 (13)	−0.0088 (11)	0.0011 (11)	−0.0001 (10)
O3	0.0230 (12)	0.0318 (14)	0.0267 (13)	−0.0027 (10)	0.0086 (10)	−0.0040 (10)
O4	0.0211 (11)	0.0131 (11)	0.0152 (11)	−0.0030 (9)	0.0001 (9)	−0.0001 (8)
O5	0.0169 (11)	0.0220 (12)	0.0231 (12)	−0.0023 (9)	0.0010 (10)	−0.0033 (9)
O6	0.0177 (11)	0.0249 (12)	0.0191 (12)	−0.0001 (9)	0.0023 (9)	−0.0045 (9)
S1	0.0237 (4)	0.0163 (4)	0.0203 (4)	0.0049 (3)	−0.0010 (3)	0.0016 (3)
S2	0.0204 (4)	0.0142 (4)	0.0195 (4)	−0.0002 (3)	−0.0010 (3)	0.0001 (3)

Geometric parameters (Å, º)

C1—C2	1.374 (5)	C18—C23	1.387 (4)
C1—C6	1.391 (4)	C18—C19	1.397 (4)
C1—H1	0.9300	C18—H18	0.9300
C2—F1	1.363 (4)	C19—C20	1.373 (5)
C2—C3	1.376 (5)	C19—H19	0.9300
C3—C4	1.382 (4)	C20—F2	1.362 (4)
C3—H3	0.9300	C20—C21	1.367 (5)
C4—C5	1.380 (4)	C21—C22	1.382 (4)
C4—H4	0.9300	C21—H21	0.9300
C5—C6	1.390 (4)	C22—C23	1.392 (4)
C5—C7	1.504 (4)	C22—H22	0.9300
C6—H6	0.9300	C23—C24	1.508 (4)
C7—S1	1.822 (3)	C24—S2	1.826 (3)
C7—H7A	0.9700	C24—H24A	0.9700
C7—H7B	0.9700	C24—H24B	0.9700
C8—N2	1.337 (4)	C25—N4	1.336 (4)
C8—N1	1.342 (4)	C25—N3	1.343 (4)
C8—S1	1.766 (3)	C25—S2	1.769 (3)
C9—N1	1.350 (4)	C26—N4	1.343 (4)
C9—C13	1.376 (4)	C26—C30	1.371 (4)
C9—C10	1.499 (4)	C26—C27	1.506 (4)
C10—C11	1.544 (4)	C27—C28	1.540 (4)
C10—H10A	0.9700	C27—H27A	0.9700
C10—H10B	0.9700	C27—H27B	0.9700
C11—C12	1.552 (4)	C28—C29	1.550 (4)
C11—H11A	0.9700	C28—H28A	0.9700
C11—H11B	0.9700	C28—H28B	0.9700
C12—C13	1.505 (4)	C29—C30	1.507 (4)
C12—H12A	0.9700	C29—H29A	0.9700
C12—H12B	0.9700	C29—H29B	0.9700
C13—C14	1.386 (4)	C30—C31	1.392 (4)
C14—N2	1.328 (4)	C31—N3	1.336 (4)
C14—O1	1.353 (3)	C31—O4	1.350 (4)
C15—O1	1.442 (3)	C32—O4	1.439 (3)
C15—C16	1.502 (4)	C32—C33	1.493 (4)
C15—H15A	0.9700	C32—H32A	0.9700
C15—H15B	0.9700	C32—H32B	0.9700
C16—O2	1.202 (4)	C33—O5	1.211 (3)
C16—O3	1.331 (4)	C33—O6	1.339 (4)
C17—O3	1.447 (4)	C34—O6	1.446 (4)
C17—H17A	0.9600	C34—H34A	0.9600
C17—H17B	0.9600	C34—H34B	0.9600
C17—H17C	0.9600	C34—H34C	0.9600
C2—C1—C6	117.9 (3)	C18—C19—H19	120.7
C2—C1—H1	121.1	F2—C20—C21	118.5 (3)
C6—C1—H1	121.1	F2—C20—C19	118.7 (3)
F1—C2—C1	118.6 (3)	C21—C20—C19	122.8 (3)
F1—C2—C3	118.1 (3)	C20—C21—C22	118.1 (3)
C1—C2—C3	123.3 (3)	C20—C21—H21	121.0
C2—C3—C4	117.3 (3)	C22—C21—H21	121.0
C2—C3—H3	121.3	C21—C22—C23	121.5 (3)
C4—C3—H3	121.3	C21—C22—H22	119.3
C5—C4—C3	121.8 (3)	C23—C22—H22	119.3
C5—C4—H4	119.1	C18—C23—C22	118.8 (3)
C3—C4—H4	119.1	C18—C23—C24	121.0 (3)
C4—C5—C6	119.0 (3)	C22—C23—C24	120.1 (3)
C4—C5—C7	119.6 (3)	C23—C24—S2	106.3 (2)
C6—C5—C7	121.3 (3)	C23—C24—H24A	110.5
C5—C6—C1	120.6 (3)	S2—C24—H24A	110.5
C5—C6—H6	119.7	C23—C24—H24B	110.5
C1—C6—H6	119.7	S2—C24—H24B	110.5
C5—C7—S1	111.4 (2)	H24A—C24—H24B	108.7
C5—C7—H7A	109.3	N4—C25—N3	127.7 (3)
S1—C7—H7A	109.3	N4—C25—S2	114.2 (2)
C5—C7—H7B	109.3	N3—C25—S2	118.1 (2)
S1—C7—H7B	109.3	N4—C26—C30	124.7 (3)
H7A—C7—H7B	108.0	N4—C26—C27	124.5 (3)
N2—C8—N1	127.7 (3)	C30—C26—C27	110.8 (3)
N2—C8—S1	117.7 (2)	C26—C27—C28	102.9 (3)
N1—C8—S1	114.6 (2)	C26—C27—H27A	111.2
N1—C9—C13	124.4 (3)	C28—C27—H27A	111.2
N1—C9—C10	124.4 (3)	C26—C27—H27B	111.2
C13—C9—C10	111.1 (3)	C28—C27—H27B	111.2
C9—C10—C11	103.6 (3)	H27A—C27—H27B	109.1
C9—C10—H10A	111.0	C27—C28—C29	106.5 (2)
C11—C10—H10A	111.0	C27—C28—H28A	110.4
C9—C10—H10B	111.0	C29—C28—H28A	110.4
C11—C10—H10B	111.0	C27—C28—H28B	110.4
H10A—C10—H10B	109.0	C29—C28—H28B	110.4
C10—C11—C12	106.2 (2)	H28A—C28—H28B	108.6
C10—C11—H11A	110.5	C30—C29—C28	101.9 (2)
C12—C11—H11A	110.5	C30—C29—H29A	111.4
C10—C11—H11B	110.5	C28—C29—H29A	111.4
C12—C11—H11B	110.5	C30—C29—H29B	111.4
H11A—C11—H11B	108.7	C28—C29—H29B	111.4
C13—C12—C11	102.6 (2)	H29A—C29—H29B	109.3
C13—C12—H12A	111.2	C26—C30—C31	115.6 (3)
C11—C12—H12A	111.2	C26—C30—C29	112.2 (3)
C13—C12—H12B	111.2	C31—C30—C29	132.1 (3)
C11—C12—H12B	111.2	N3—C31—O4	118.7 (3)
H12A—C12—H12B	109.2	N3—C31—C30	122.5 (3)
C9—C13—C14	115.9 (3)	O4—C31—C30	118.8 (3)
C9—C13—C12	111.8 (3)	O4—C32—C33	115.3 (2)
C14—C13—C12	132.1 (3)	O4—C32—H32A	108.4
N2—C14—O1	118.8 (3)	C33—C32—H32A	108.4
N2—C14—C13	122.2 (3)	O4—C32—H32B	108.4
O1—C14—C13	119.0 (3)	C33—C32—H32B	108.4
O1—C15—C16	114.7 (3)	H32A—C32—H32B	107.5
O1—C15—H15A	108.6	O5—C33—O6	124.4 (3)
C16—C15—H15A	108.6	O5—C33—C32	122.9 (3)
O1—C15—H15B	108.6	O6—C33—C32	112.6 (3)
C16—C15—H15B	108.6	O6—C34—H34A	109.5
H15A—C15—H15B	107.6	O6—C34—H34B	109.5
O2—C16—O3	125.2 (3)	H34A—C34—H34B	109.5
O2—C16—C15	121.9 (3)	O6—C34—H34C	109.5
O3—C16—C15	112.9 (3)	H34A—C34—H34C	109.5
O3—C17—H17A	109.5	H34B—C34—H34C	109.5
O3—C17—H17B	109.5	C8—N1—C9	113.3 (3)
H17A—C17—H17B	109.5	C14—N2—C8	116.3 (3)
O3—C17—H17C	109.5	C31—N3—C25	115.6 (3)
H17A—C17—H17C	109.5	C25—N4—C26	113.9 (3)
H17B—C17—H17C	109.5	C14—O1—C15	115.6 (2)
C23—C18—C19	120.3 (3)	C16—O3—C17	115.0 (2)
C23—C18—H18	119.9	C31—O4—C32	115.8 (2)
C19—C18—H18	119.9	C33—O6—C34	114.1 (2)
C20—C19—C18	118.6 (3)	C8—S1—C7	99.34 (14)
C20—C19—H19	120.7	C25—S2—C24	102.84 (14)
C6—C1—C2—F1	178.0 (3)	N4—C26—C30—C31	−1.2 (4)
C6—C1—C2—C3	−2.6 (5)	C27—C26—C30—C31	177.4 (3)
F1—C2—C3—C4	−176.9 (3)	N4—C26—C30—C29	−178.9 (3)
C1—C2—C3—C4	3.6 (5)	C27—C26—C30—C29	−0.4 (4)
C2—C3—C4—C5	−1.9 (5)	C28—C29—C30—C26	−14.0 (3)
C3—C4—C5—C6	−0.8 (5)	C28—C29—C30—C31	168.8 (3)
C3—C4—C5—C7	174.3 (3)	C26—C30—C31—N3	3.0 (4)
C4—C5—C6—C1	1.9 (5)	C29—C30—C31—N3	−179.8 (3)
C7—C5—C6—C1	−173.1 (3)	C26—C30—C31—O4	−176.2 (3)
C2—C1—C6—C5	−0.3 (5)	C29—C30—C31—O4	0.9 (5)
C4—C5—C7—S1	119.5 (3)	O4—C32—C33—O5	−156.1 (3)
C6—C5—C7—S1	−65.6 (3)	O4—C32—C33—O6	25.9 (4)
N1—C9—C10—C11	166.4 (3)	N2—C8—N1—C9	−1.4 (4)
C13—C9—C10—C11	−12.5 (3)	S1—C8—N1—C9	178.5 (2)
C9—C10—C11—C12	20.5 (3)	C13—C9—N1—C8	−0.9 (4)
C10—C11—C12—C13	−20.8 (3)	C10—C9—N1—C8	−179.6 (3)
N1—C9—C13—C14	3.1 (4)	O1—C14—N2—C8	−178.7 (3)
C10—C9—C13—C14	−178.0 (3)	C13—C14—N2—C8	1.6 (4)
N1—C9—C13—C12	−179.8 (3)	N1—C8—N2—C14	1.0 (5)
C10—C9—C13—C12	−0.9 (4)	S1—C8—N2—C14	−178.9 (2)
C11—C12—C13—C9	13.8 (3)	O4—C31—N3—C25	177.2 (3)
C11—C12—C13—C14	−169.8 (3)	C30—C31—N3—C25	−2.1 (4)
C9—C13—C14—N2	−3.5 (4)	N4—C25—N3—C31	−0.8 (4)
C12—C13—C14—N2	−179.8 (3)	S2—C25—N3—C31	179.3 (2)
C9—C13—C14—O1	176.8 (3)	N3—C25—N4—C26	2.5 (5)
C12—C13—C14—O1	0.5 (5)	S2—C25—N4—C26	−177.7 (2)
O1—C15—C16—O2	163.6 (3)	C30—C26—N4—C25	−1.3 (4)
O1—C15—C16—O3	−18.6 (4)	C27—C26—N4—C25	−179.7 (3)
C23—C18—C19—C20	0.2 (5)	N2—C14—O1—C15	5.3 (4)
C18—C19—C20—F2	−179.4 (3)	C13—C14—O1—C15	−175.0 (3)
C18—C19—C20—C21	−0.1 (5)	C16—C15—O1—C14	−68.2 (3)
F2—C20—C21—C22	179.7 (3)	O2—C16—O3—C17	−3.3 (4)
C19—C20—C21—C22	0.3 (5)	C15—C16—O3—C17	179.0 (3)
C20—C21—C22—C23	−0.6 (5)	N3—C31—O4—C32	−6.6 (4)
C19—C18—C23—C22	−0.4 (5)	C30—C31—O4—C32	172.7 (2)
C19—C18—C23—C24	−177.3 (3)	C33—C32—O4—C31	67.3 (3)
C21—C22—C23—C18	0.7 (5)	O5—C33—O6—C34	−3.6 (4)
C21—C22—C23—C24	177.6 (3)	C32—C33—O6—C34	174.4 (3)
C18—C23—C24—S2	94.8 (3)	N2—C8—S1—C7	14.5 (3)
C22—C23—C24—S2	−82.1 (3)	N1—C8—S1—C7	−165.5 (2)
N4—C26—C27—C28	−166.8 (3)	C5—C7—S1—C8	179.0 (2)
C30—C26—C27—C28	14.7 (4)	N4—C25—S2—C24	173.6 (2)
C26—C27—C28—C29	−22.8 (3)	N3—C25—S2—C24	−6.5 (3)
C27—C28—C29—C30	22.4 (3)	C23—C24—S2—C25	−179.2 (2)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C15—H15A···N1^i	0.97	2.42	3.375 (4)	170
C3—H3···O5^ii	0.93	2.53	3.260 (4)	135
C34—H34C···O2^iii	0.96	2.52	3.307 (4)	139
C12—H12A···F1^iv	0.97	2.58	3.046 (4)	109

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