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Volume 70 
Part 2 
Pages 241-249  
February 2014  

Received 20 December 2013
Accepted 20 January 2014
Online 31 January 2014

N-H...S and N-H...O hydrogen bonds: `pure' and `mixed' R22(8) patterns in the crystal structures of eight 2-thio­uracil derivatives

aInstitut für Organische Chemie und Chemische Biologie, Goethe-Universität Frankfurt, Max-von-Laue-Strasse 7, 60438 Frankfurt am Main, Germany
Correspondence e-mail: egert@chemie.uni-frankfurt.de

The preferred hydrogen-bonding patterns in the crystal structures of 5-propyl-2-thio­uracil, C7H10N2OS, (I), 5-meth­oxy-2-thio­uracil, C5H6N2O2S, (II), 5-meth­oxy-2-thio­uracil-N,N-di­methyl­acetamide (1/1), C5H6N2O2S·C4H9NO, (IIa), 5,6-dimethyl-2-thio­uracil, C6H8N2OS, (III), 5,6-dimethyl-2-thio­uracil-1-methyl­pyrrolidin-2-one (1/1), C6H8N2OS·C5H9NO, (IIIa), 5,6-dimethyl-2-thio­uracil-N,N-di­methyl­formamide (2/1), 2C6H8N2OS·C3H7NO, (IIIb), 5,6-dimethyl-2-thio­uracil-N,N-di­methyl­acetamide (2/1), 2C6H8N2OS·C4H9NO, (IIIc), and 5,6-dimethyl-2-thio­uracil-di­methyl ­sulfoxide (2/1), 2C6H8N2OS·C2H6OS, (IIId), were analysed. All eight structures contain R22(8) patterns. In (II), (IIa), (III) and (IIIa), they are formed by two N-H...S hydrogen bonds, and in (I) by alternating pairs of N-H...S and N-H...O hydrogen bonds. In contrast, the structures of (IIIb), (IIIc) and (IIId) contain `mixed' R22(8) patterns with one N-H...S and one N-H...O hydrogen bond, as well as R22(8) motifs with two N-H...O hydrogen bonds.

1. Introduction

Active pharmaceutical ingredients (APIs) are usually delivered as solid drugs containing a crystalline form of the API. Due to their higher stablility and reproducibility, the use of crystalline forms is favoured over amorphous forms (Shan & Zaworotko, 2008[Shan, N. & Zaworotko, M. J. (2008). Drug Discovery Today, 13, 440-446.]). Because of poor solubilities APIs may show a low bioavailability. New crystalline forms of APIs with higher solubility and therefore improved bioavailability can be obtained by synthesizing pharmaceutical cocrystals (Blagden et al., 2007[Blagden, N., De Matas, M., Gavan, P. T. & York, P. (2007). Adv. Drug Deliv. Rev. 59, 617-630.]; Schultheiss & Newman, 2009[Schultheiss, N. & Newman, A. (2009). Cryst. Growth Des. 9, 2950-2967.]; Vishweshwar et al., 2006[Vishweshwar, P., McMahon, J. A., Bis, J. A. & Zaworotko, M. J. (2006). J. Pharm. Sci. 95, 499-516.]). Since noncovalent inter­actions like hydrogen bonds play a dominant role in the mol­ecular recognition process during cocrystal formation, it is helpful to know the preferred hydrogen-bonding pattern of an API.

[Scheme 1]

2-Thio­uracil derivatives are potential candidates for the preparation of pharmaceutical cocrystals. They show anti­thyroid activity, since they inhibit the biosynthesis of the thyroid hormone thyroxine as well as its de-iodinative metabolism in peripheral tissues, whereby the relative antithyroid activity depends on the residues at atoms C5 and C6 of the pyrimidine ring (Hershman & Van Middlesworth, 1962[Hershman, J. M. & Van Middlesworth, L. (1962). Endocrinology, 71, 94-100.]; Hershman, 1964[Hershman, J. M. (1964). J. Clin. Endocrinol. Metab. 24, 173-179.]; Visser et al., 1979[Visser, T. J., Van Overmeeren, E., Fekkes, D., Docter, R. & Hennemann, G. (1979). FEBS Lett. 103, 314-318.]). In the crystal structures of 2-thio­uracil derivatives, R22(8) (Bernstein et al., 1995[Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555-1573.]) is the most abundant hydrogen-bonding pattern (Hützler & Bolte, 2013a[Hützler, W. M. & Bolte, M. (2013a). Acta Cryst. C69, 93-100.]); these patterns consist of either two N-H...S or two N-H...O hydrogen bonds [`pure' R22(8) patterns]. In an attempt to find also `mixed' R22(8) patterns consisting of one N-H...S and one N-H...O hydrogen bond, we investigated the three 2-thio­uracil derivatives 5-propyl-2-thio­uracil, 5-meth­oxy-2-thio­uracil and 5,6-dimethyl-2-thio­uracil crystallized alone with a variety of solvents.

[Figure 1]
Figure 1
A perspective view of (I)[link], showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. Dashed lines indicate N-H...S hydrogen bonds.
[Figure 2]
Figure 2
A partial packing diagram for (I)[link]. N-H...S and N-H...O hydrogen bonds are shown as dashed lines. [Symmetry code: (i) x, y, z - 1.]
[Figure 3]
Figure 3
A perspective view of (II)[link], showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
[Figure 4]
Figure 4
A partial packing diagram for (II)[link], showing a layer parallel to ([\overline{1}]02). Hydrogen bonds are shown as dashed lines. [Symmetry codes: (i) x + 1, -y + [{3\over 2}], z + [{1\over 2}]; (ii) -x + 1, -y + 1, -z + 1.]
[Figure 5]
Figure 5
A perspective view of (IIa)[link], showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. Dashed lines indicate hydrogen bonds. The N,N-di­methyl­acetamide solvent mol­ecules X and Y are disordered and only the major occupied sites are shown.
[Figure 6]
Figure 6
A partial packing diagram for (IIa)[link], showing the dimers arranged parallel to (010). Hydrogen bonds are shown as dashed lines.
[Figure 7]
Figure 7
A perspective view of (III)[link], showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
[Figure 8]
Figure 8
A partial packing diagram for (III)[link]. Hydrogen bonds are shown as dashed lines. [Symmetry codes: (i) -x + 1, -y + 1, -z + 1; (ii) x - 1, y, z.]
[Figure 9]
Figure 9
A perspective view of (IIIa)[link], showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. The dashed line indicates an N-H...O hydrogen bond.
[Figure 10]
Figure 10
A partial packing diagram for (IIIa)[link]. Hydrogen bonds are shown as dashed lines. [Symmetry code: (i) -x + 2, -y + 1, -z + 1.]
[Figure 11]
Figure 11
A perspective view of (IIIb)[link], showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. Dashed lines indicate hydrogen bonds.
[Figure 12]
Figure 12
A partial packing diagram for (IIIb)[link]. Hydrogen bonds are shown as dashed lines. [Symmetry code: (i) -x, -y - 1, -z + 1.]
[Figure 13]
Figure 13
A perspective view of (IIIc)[link], showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. In (a) only site X and in (b) only site Y of the disordered DMAC mol­ecule is shown (site occupancy factors = 0.50). Dashed lines indicate hydrogen bonds.
[Figure 14]
Figure 14
A partial packing diagram for (IIIc)[link]. Hydrogen bonds are shown as dashed lines. The disordered DMAC mol­ecules are not shown. [Symmetry code: (i) -x + 1, -y + 2, -z + 1.]
[Figure 15]
Figure 15
A perspective view of (IIId)[link], showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. Dashed lines indicate hydrogen bonds.
[Figure 16]
Figure 16
A partial packing diagram for (IIId)[link]. Hydrogen bonds are shown as dashed lines. [Symmetry code: (i) -x + 2, - y + 1, -z.]

2. Experimental

2.1. Synthesis and crystallization

Isothermal solvent evaporation experiments under different conditions with commercially available 2-thio­uracil derivatives and various solvents in which they show an appropriate solubility yielded crystals of the eight title com­pounds, (I)[link]-(IIId)[link] (Table 1[link]), whose structures were analysed. All solvents were used as supplied without further purification. In order to optimize the crystal quality, experiments at different temperatures and with varied crystallization rates were carried out. However, for structures (IIa)[link], (IIIa)[link] and (IIId)[link] only moderate improvement of the crystal quality was observed.

2.2. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. All H atoms except those of the disordered solvent mol­ecules were initially located by difference Fourier synthesis. Subsequently, all H atoms bonded to C atoms were placed at calculated positions and refined using a riding model, with methyl C-H = 0.98 Å, secondary C-H = 0.99 Å and aromatic C-H = 0.95 Å, and with Uiso(H) = 1.5Ueq(C) for methyl H atoms or 1.2Ueq(C) for secondary and aromatic H atoms. For all methyl groups, except those of the disordered solvent mol­ecules, free rotation about their local threefold axis was allowed.

In (II)[link], (IIa)[link], (IIIb)[link], (IIIc)[link] and (IIId)[link], isotropic refinement of N-bound H atoms resulted in the isotropic displacement parameters of the H atoms being smaller than the corresponding equivalent displacement parameters of the N atoms. Therefore, the isotropic displacement parameters of the H atoms were coupled to the equivalent displacement parameters of the parent N atoms, with Uiso(H) = 1.2Ueq(N). Additionally, in (II)[link], (IIa)[link], (III)[link], (IIIc)[link] and (IIId)[link], the N-H distances were restrained to 0.88 (2) Å.

In (IIa)[link], the two independent DMAC mol­ecules (X and Y) are disordered over a pseudo-mirror plane along O21(X/Y)...C32(X/Y) lying perpendicular to the plane through all non-H atoms of X/Y [site-occupancy factors for the major occupied orientation of 0.668 (12) for X and 0.759 (11) for Y]. For the solvent mol­ecules, similarity restraints for the 1,2 and 1,3 distances were applied, as well as the similar-ADP restraint and rigid-bond restraint (SIMU and DELU in SHELXL97; Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]).

In (III)[link], an isotropic extinction parameter was refined. In (IIIc)[link], the DMAC mol­ecule shows disorder over two equally occupied positions which do not lie in a common plane. Similarity restraints for the 1,2 and 1,3 distances were applied. The methyl groups at C5 of both 5,6-dimethyl-2-thio­uracil mol­ecules show a rotational disorder [site-occupancy factors for the major occupied orientation of 0.70 (2) for C51A and 0.58 (2) for C51B]. In each of (IIa)[link] and (IIId)[link], three reflections with bad Fo/Fc agreement were omitted.

3. Results and discussion

5-Propyl-2-thio­uracil, (I)[link], crystallizes in the triclinic space group P[\overline{1}] with two mol­ecules (A and B) in the asymmetric unit (Fig. 1[link]). The pyrimidine rings of both mol­ecules are planar [r.m.s. deviations for all non-H atoms of the rings = 0.029 (for A) and 0.022 Å (for B)] and are tilted towards each other, enclosing a dihedral angle of 30.59 (4)°. The propyl groups exhibit different conformations in A and B: whereas the side chain of mol­ecule A is twisted, with the planes through the ring and the propyl group enclosing a dihedral angle of 73.18 (8)°, it is extended in mol­ecule B, with a dihedral angle of 2.0 (3)°. The mol­ecules are connected by alternating R22(8) inter­actions consisting of either two N-H...S or two N-H...O hydrogen bonds, resulting in chains running along the c axis (Fig. 2[link] and Table 3[link]). In the crystal packing, adjacent chains show a tubular arrangement (see extra figure in the Supporting information ).

5-Meth­oxy-2-thio­uracil, (II)[link], crystallizes in the monoclinic space group P21/c with one planar mol­ecule in the asymmetric unit (r.m.s. deviation for all non-H atoms = 0.012 Å), whereby atoms C4A and C52A exhibit an antiperiplanar conformation (Fig. 3[link]). In the crystal packing, mol­ecules are connected into homodimers stabilized by R22(8) N-H...S hydrogen bonds. Adjacent homodimers are linked to each other by bifurcated R12(5) N-H...O hydrogen bonds and enclose a dihedral angle of 6.75 (7)°, resulting in layers parallel to ([\overline{1}]02) (Fig. 4[link] and Table 4[link]).

The DMAC solvate, (IIa)[link], crystallizes in the monoclinic space group P21/m. The asymmetric unit consists of two mol­ecules of 5-meth­oxy-2-thio­uracil (A and B) and two disordered DMAC mol­ecules, whereby all four mol­ecules lie on a mirror plane. Mol­ecules A and B are connected by R22(8) N-H...S hydrogen bonds and show further N-H...O hydrogen bonds with the solvent mol­ecules (Fig. 5[link] and Table 5[link]). In the crystal packing, the A-B homodimers are arranged parallel to (010) (Fig. 6[link]).

5,6-Dimethyl-2-thio­uracil, (III)[link], crystallizes in the monoclinic space group P21/c with one planar mol­ecule in the asymmetric unit (r.m.s. deviation for all non-H atoms = 0.037 Å) (Fig. 7[link]). The mol­ecules show R22(8) N-H...S hydrogen-bonding inter­actions stabilizing the homodimers, which are further connected by N-H...O hydrogen bonds, yielding R44(16) patterns and thus forming ribbons running along the a axis (Fig. 8[link] and Table 6[link]).

The NMP solvate, (IIIa)[link], crystallizes in the ortho­rhom­bic space group Pbca with one planar 5,6-dimethyl-2-thio­uracil mol­ecule (A; r.m.s. deviation for all non-H atoms = 0.015 Å) and one NMP mol­ecule (X) in the asymmetric unit, which are connected by an N-H...O hydrogen bond (Fig. 9[link]). The planes through all the non-H atoms of molecules A and X, respectively, form a dihedral angle of 55.49 (6)°. In the crystal packing, the 5,6-dimethyl-2-thio­uracil mol­ecules form dimers parallel to (010) stabilized by R22(8) N-H...S hydrogen bonds (Fig. 10[link] and Table 7[link]).

The DMF solvate, (IIIb)[link], crystallizes in the triclinic space group P[\overline{1}] with two 5,6-dimethyl-2-thio­uracil mol­ecules (A and B) and one solvent mol­ecule (X) in the asymmetric unit; all three mol­ecules lie in a common plane (r.m.s. deviation for all non-H atoms = 0.048 Å). This time mol­ecules A and B are linked by one N-H...S and one N-H...O hydrogen bond, thus forming a `mixed' R22(8) pattern, and mol­ecule B is further connected to the solvent mol­ecule by an N-H...O hydrogen bond (Fig. 11[link]). In the crystal packing, the 5,6-di­methyl-2-thio­uracil mol­ecules form tetra­mers through two additional R22(8) N-H...O hydrogen bonds. The tetra­mers are arranged parallel to ([\overline{2}]13) and show only van der Waals inter­actions between each other (Fig. 12[link] and Table 8[link]).

The asymmetric unit of the DMAC solvate, (IIIc)[link], which also crystallizes in the space group P[\overline{1}], consists of two 5,6-di­methyl-2-thio­uracil mol­ecules (A and B) and one DMAC mol­ecule. This latter is disordered over two positions (X and Y), whereby only X lies in a common plane with A and B (Fig. 13[link]a; r.m.s. deviation for all non-H atoms of A, B and X = 0.096 Å). The planes through X and Y form a dihedral angle of 70.71 (16)° (Fig. 13[link]b). As in (IIIb)[link], mol­ecules A and B are connected by a `mixed' R22(8) pattern consisting of one N-H...S and one N-H...O hydrogen bond, and mol­ecule B forms one additional N-H...O hydrogen bond with the solvent mol­ecule. Stabilized by two further R22(8) N-H...O hydrogen bonds, the 5,6-dimethyl-2-thio­uracil mol­ecules are connected into tetra­mers that are arranged parallel to (2[\overline{1}]0) (Fig. 14[link] and Table 9[link]).

Compound (IIId)[link] crystallizes in the monoclinic space group P21/n with two coplanar 5,6-dimethyl-2-thio­uracil mol­ecules, A and B (r.m.s. deviation for all non-H atoms = 0.062 Å), and one DMSO mol­ecule, X, in the asymmetric unit (Fig. 15[link]). The planes through mol­ecules A and B and through all the non-H atoms of X, respectively, are almost perpendicular [dihedral angle = 78.93 (17)°]. Mol­ecules A and B are again connected to each other via a `mixed' R22(8) pattern, and mol­ecule B is further connected to X by an N-H...O hydrogen bond. Similar to (IIIc)[link], in the crystal structure, one additional R22(8) N-H...O hydrogen-bonding inter­action is formed between mol­ecules A, yielding tetra­mers that are arranged alternately parallel to (221) and (2[\overline{2}]1), respectively (Fig. 16[link] and Table 10[link]).

All eight structures contain R22(8) homodimers, which is in agreement with the result of a previous Cambridge Structural Database (CSD; Allen, 2002[Allen, F. H. (2002). Acta Cryst. B58, 380-388.]) substructure search for 2-thio­uracil derivatives (Hützler & Bolte, 2013a[Hützler, W. M. & Bolte, M. (2013a). Acta Cryst. C69, 93-100.]). In (I)[link], (II)[link], (IIa)[link], (III)[link] and (IIIa)[link], the R22(8) motifs consist of two N-H...S hydrogen bonds, and (I)[link] shows additional R22(8) motifs consisting of two N-H...O hydrogen bonds. In (IIIb)[link], (IIIc)[link] and (IIId)[link], `mixed' R22(8) patterns containing one N-H...S and one N-H...O hydrogen bond are formed, as well as R22(8) motifs with two N-H...O hydrogen bonds. These three structures show the same hydrogen-bonding pattern between the 5,6-dimethyl-2-thio­uracil mol­ecules and the respective solvent mol­ecules, while the crystal packing of the tetra­mers is clearly different.

In structures (IIa)[link] and (IIIa)[link], the O atoms of the 2-thio­uracil group do not form hydrogen bonds but participate only in van der Waals inter­actions. Comparing (I)[link] with the structure of the isomeric compound 6-propyl-2-thio­uracil (CSD refcode UXIXUV01; Tutughamiarso & Egert, 2011[Tutughamiarso, M. & Egert, E. (2011). Acta Cryst. C67, o439-o445.]), equal hydrogen-bonding patterns are found in both structures but differences are observed for the conformation of the propyl side chains. Whereas the dihedral angle between the planes through the propyl group and the pyrimidine ring is similar for both mol­ecules in UXIXUV01 [26.0 (2) and 29.8 (2)°, respectively], it is clearly different in (I)[link] [73.18 (8) and 2.0 (3)°]. A search of the CSD (Version 5.34 of November 2012, plus three updates; Allen, 2002[Allen, F. H. (2002). Acta Cryst. B58, 380-388.]) yielded one further structure of each of the two isomers, namely the structure of the dioxane monosolvate of 5-propyl-2-thio­uracil (Hützler & Bolte, 2013b[Hützler, W. M. & Bolte, M. (2013b). Private communication (deposition number CCDC 968014). CCDC, Cambridge, England.]) and the dioxane hemisolvate of 6-propyl-2-thio­uracil (refcode BUW­YOH; Okabe et al., 1983[Okabe, N., Fujiwara, T., Yamagata, Y. & Tomita, K. (1983). Bull. Chem. Soc. Jpn, 56, 1543-1544.]). In both structures, R22(8) N-H...O homodimers are formed and the propyl side chains are coplanar with the pyrimidine rings, whereas the S atoms do not participate in hydrogen bonds.

In summary, and in agreement with our previous work on 2-thio­uracil derivatives, R22(8) is the favoured hydrogen-bonding pattern in all eight structures (I)[link]-(IIId)[link]. In five of the structures, R22(8) N-H...S hydrogen bonds are formed, and three structures contain `mixed' R22(8) patterns with one N-H...S and one N-H...O hydrogen bond. Additional R22(8) N-H...O hydrogen bonds are observed in four of these structures.

Table 1
Crystallization of 5-propyl-2-thio­uracil, (I)[link], 5-meth­oxy-2-thio­uracil, (II)[link] and (IIa)[link], and 5,6-dimethyl-2-thio­uracil, (III)[link]-(IIId)[link]

Apart from (III)[link], which was crystallized at 323 K, all crystallization experiments were performed at 295 K. DMF is N,N-dimethylformamide, DMAC is N,N-dimethylacetamide, NMP is 1-methylpyrrolidin-2-one and DMSO is dimethyl sulfoxide (see Scheme[link]).

Compound Amount (mg, mmol) Solvent
(I)[link] 1.6, 0.009 DMF (20 µl)
(II)[link] 2.0, 0.013 DMF (40 µl)
(IIa)[link] 2.0, 0.013 DMAC (80 µl)
(III)[link] 2.7, 0.017 H2O (400 µl)
(IIIa)[link] 2.7, 0.017 NMP (80 µl)
(IIIb)[link] 3.2, 0.020 DMF (40 µl)
(IIIc)[link] 2.6, 0.017 DMAC (40 µl)
(IIId)[link] 2.3, 0.015 DMSO (40 µl)

Table 2
Experimental details

  (I) (II) (IIa) (III)
Crystal data
Chemical formula C7H10N2OS C5H6N2O2S C5H6N2O2S·C4H9NO C6H8N2OS
Mr 170.23 158.18 245.30 156.20
Crystal system, space group Triclinic, P[\overline{1}] Monoclinic, P21/c Monoclinic, P21/m Monoclinic, P21/c
Temperature (K) 173 173 173 173
a, b, c (Å) 8.6637 (10), 10.3098 (13), 10.7255 (13) 4.3141 (6), 16.9101 (18), 8.9965 (12) 13.225 (3), 6.4726 (8), 13.867 (3) 6.8295 (10), 15.2624 (18), 7.0948 (11)
[alpha], [beta], [gamma] (°) 76.253 (10), 71.401 (9), 70.983 (9) 90, 93.593 (10), 90 90, 97.170 (15), 90 90, 112.336 (11), 90
V3) 848.81 (18) 655.02 (14) 1177.7 (4) 684.04 (17)
Z 4 4 4 4
Radiation type Mo K[alpha] Mo K[alpha] Mo K[alpha] Mo K[alpha]
[mu] (mm-1) 0.33 0.43 0.27 0.40
Crystal size (mm) 0.30 × 0.22 × 0.10 0.32 × 0.11 × 0.06 0.30 × 0.18 × 0.12 0.50 × 0.25 × 0.20
 
Data collection
Diffractometer Stoe IPDS II two-circle diffractometer Stoe IPDS II two-circle diffractometer Stoe IPDS II two-circle diffractometer Stoe IPDS II two-circle diffractometer
Absorption correction Multi-scan (X-AREA; Stoe & Cie, 2001[Stoe & Cie (2001). X-AREA. Stoe & Cie, Darmstadt, Germany.]) Multi-scan (X-AREA; Stoe & Cie, 2001[Stoe & Cie (2001). X-AREA. Stoe & Cie, Darmstadt, Germany.]) Multi-scan (X-AREA; Stoe & Cie, 2001[Stoe & Cie (2001). X-AREA. Stoe & Cie, Darmstadt, Germany.]) Multi-scan (X-AREA; Stoe & Cie, 2001[Stoe & Cie (2001). X-AREA. Stoe & Cie, Darmstadt, Germany.])
Tmin, Tmax 0.909, 0.968 0.876, 0.975 0.923, 0.968 0.827, 0.925
No. of measured, independent and observed [I > 2[sigma](I)] reflections 6626, 3163, 2609 5186, 1228, 1072 9319, 2470, 1767 5187, 1285, 1212
Rint 0.062 0.077 0.116 0.083
(sin [theta]/[lambda])max-1) 0.608 0.609 0.617 0.609
 
Refinement
R[F2 > 2[sigma](F2)], wR(F2), S 0.040, 0.105, 1.00 0.043, 0.112, 1.06 0.077, 0.190, 1.12 0.057, 0.149, 1.07
No. of reflections 3163 1228 2470 1285
No. of parameters 217 98 227 102
No. of restraints 0 2 260 2
H-atom treatment H atoms treated by a mixture of independent and constrained refinement H atoms treated by a mixture of independent and constrained refinement H atoms treated by a mixture of independent and constrained refinement H atoms treated by a mixture of independent and constrained refinement
[Delta][rho]max, [Delta][rho]min (e Å-3) 0.28, -0.27 0.39, -0.22 0.50, -0.42 0.28, -0.33
  (IIIa) (IIIb) (IIIc) (IIId)
Crystal data
Chemical formula C6H8N2OS·C5H9NO 2C6H8N2OS·C3H7NO 2C6H8N2OS·C4H9NO 2C6H8N2OS·C2H6OS
Mr 255.34 385.50 399.53 390.54
Crystal system, space group Orthorhombic, Pbca Triclinic, P[\overline{1}] Triclinic, P[\overline{1}] Monoclinic, P21/n
Temperature (K) 173 173 173 173
a, b, c (Å) 15.2437 (6), 6.8275 (17), 23.555 (2) 8.5895 (13), 8.6241 (14), 15.350 (2) 8.0876 (14), 11.1034 (17), 11.9115 (17) 8.1597 (14), 22.612 (3), 10.5576 (17)
[alpha], [beta], [gamma] (°) 90, 90, 90 100.404 (13), 95.341 (12), 119.496 (11) 80.017 (12), 70.979 (12), 75.575 (13) 90, 105.459 (13), 90
V3) 2451.5 (7) 951.2 (3) 974.4 (3) 1877.5 (5)
Z 8 2 2 4
Radiation type Mo K[alpha] Mo K[alpha] Mo K[alpha] Mo K[alpha]
[mu] (mm-1) 0.26 0.30 0.30 0.42
Crystal size (mm) 0.60 × 0.25 × 0.20 0.45 × 0.35 × 0.25 0.38 × 0.24 × 0.22 0.55 × 0.15 × 0.10
 
Data collection
Diffractometer Stoe IPDS II two-circle diffractometer Stoe IPDS II two-circle diffractometer Stoe IPDS II two-circle diffractometer Stoe IPDS II two-circle diffractometer
Absorption correction Multi-scan (X-AREA; Stoe & Cie, 2001[Stoe & Cie (2001). X-AREA. Stoe & Cie, Darmstadt, Germany.]) Multi-scan (X-AREA; Stoe & Cie, 2001[Stoe & Cie (2001). X-AREA. Stoe & Cie, Darmstadt, Germany.]) Multi-scan (X-AREA; Stoe & Cie, 2001[Stoe & Cie (2001). X-AREA. Stoe & Cie, Darmstadt, Germany.]) Multi-scan (X-AREA; Stoe & Cie, 2001[Stoe & Cie (2001). X-AREA. Stoe & Cie, Darmstadt, Germany.])
Tmin, Tmax 0.860, 0.950 0.875, 0.928 0.895, 0.937 0.804, 0.960
No. of measured, independent and observed [I > 2[sigma](I)] reflections 17581, 2319, 2081 7421, 3558, 3064 7639, 3730, 3106 13972, 3518, 2772
Rint 0.110 0.051 0.037 0.116
(sin [theta]/[lambda])max-1) 0.610 0.611 0.614 0.611
 
Refinement
R[F2 > 2[sigma](F2)], wR(F2), S 0.058, 0.129, 1.12 0.043, 0.119, 1.06 0.035, 0.094, 1.02 0.071, 0.180, 1.11
No. of reflections 2319 3558 3730 3518
No. of parameters 165 244 313 235
No. of restraints 0 0 26 4
H-atom treatment H atoms treated by a mixture of independent and constrained refinement H atoms treated by a mixture of independent and constrained refinement H atoms treated by a mixture of independent and constrained refinement H atoms treated by a mixture of independent and constrained refinement
[Delta][rho]max, [Delta][rho]min (e Å-3) 0.35, -0.31 0.36, -0.25 0.25, -0.21 0.43, -0.34
Computer programs: X-AREA (Stoe & Cie, 2001[Stoe & Cie (2001). X-AREA. Stoe & Cie, Darmstadt, Germany.]), SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), Mercury (Macrae et al., 2008[Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466-470.]), XP in SHELXTL-Plus (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]) and publCIF (Westrip, 2010[Westrip, S. P. (2010). J. Appl. Cryst. 43, 920-925.]).

Table 3
Hydrogen-bond geometry (Å, °) for (I)[link]

D-H...A D-H H...A D...A D-H...A
N1A-H1A...S21B 0.87 (3) 2.44 (3) 3.3030 (18) 170 (2)
N3A-H3A...O41Bi 0.85 (3) 1.99 (3) 2.835 (2) 175 (3)
N1B-H1B...S21A 0.87 (3) 2.42 (3) 3.2715 (18) 168 (2)
N3B-H3B...O41Aii 0.88 (3) 1.94 (3) 2.811 (2) 168 (2)
Symmetry codes: (i) x, y, z+1; (ii) x, y, z-1.

Table 4
Hydrogen-bond geometry (Å, °) for (II)[link]

D-H...A D-H H...A D...A D-H...A
N1A-H1A...O51Ai 0.86 (2) 2.32 (2) 3.176 (3) 170 (3)
N1A-H1A...O41Ai 0.86 (2) 2.45 (3) 2.975 (3) 120 (2)
N3A-H3A...S21Aii 0.87 (2) 2.49 (2) 3.337 (2) 167 (3)
Symmetry codes: (i) [x+1, -y+{\script{3\over 2}}, z+{\script{1\over 2}}]; (ii) -x+1, -y+1, -z+1.

Table 5
Hydrogen-bond geometry (Å, °) for (IIa)[link]

D-H...A D-H H...A D...A D-H...A
N1A-H1A...O21X 0.86 (2) 1.89 (4) 2.658 (6) 147 (6)
N3A-H3A...S21B 0.87 (2) 2.55 (2) 3.420 (5) 172 (5)
N1B-H1B...O21Y 0.89 (2) 1.84 (3) 2.681 (6) 157 (6)
N3B-H3B...S21A 0.87 (2) 2.49 (2) 3.354 (5) 171 (5)

Table 6
Hydrogen-bond geometry (Å, °) for (III)[link]

D-H...A D-H H...A D...A D-H...A
N1A-H1A...O41Ai 0.86 (2) 2.09 (2) 2.920 (3) 160 (3)
N3A-H3A...S21Aii 0.87 (2) 2.51 (2) 3.368 (2) 173 (3)
Symmetry codes: (i) x-1, y, z; (ii) -x+1, -y+1, -z+1.

Table 7
Hydrogen-bond geometry (Å, °) for (IIIa)[link]

D-H...A D-H H...A D...A D-H...A
N1A-H1A...O21X 0.89 (4) 1.86 (4) 2.745 (2) 171 (3)
N3A-H3A...S21Ai 0.84 (3) 2.48 (3) 3.306 (2) 170 (3)
Symmetry code: (i) -x+2, -y+1, -z+1.

Table 8
Hydrogen-bond geometry (Å, °) for (IIIb)[link]

D-H...A D-H H...A D...A D-H...A
N1A-H1A...O41B 0.81 (3) 1.95 (3) 2.744 (2) 168 (3)
N3A-H3A...O41Ai 0.89 (3) 1.91 (3) 2.799 (2) 176 (2)
N1B-H1B...O11X 0.84 (3) 1.87 (3) 2.702 (3) 173 (3)
N3B-H3B...S21A 0.88 (3) 2.42 (3) 3.295 (2) 176 (2)
Symmetry code: (i) -x, -y-1, -z+1.

Table 9
Hydrogen-bond geometry (Å, °) for (IIIc)[link]

D-H...A D-H H...A D...A D-H...A
N1A-H1A...O41B 0.88 (2) 1.83 (2) 2.7111 (19) 175 (2)
N3A-H3A...O41Ai 0.88 (2) 1.96 (2) 2.8327 (18) 175 (2)
N1B-H1B...O21X 0.86 (2) 1.85 (2) 2.687 (15) 165 (2)
N1B-H1B...O21Y 0.86 (2) 2.06 (2) 2.910 (14) 171 (2)
N3B-H3B...S21A 0.85 (2) 2.56 (2) 3.4058 (15) 170 (2)
Symmetry code: (i) -x+1, -y+2, -z+1.

Table 10
Hydrogen-bond geometry (Å, °) for (IIId)[link]

D-H...A D-H H...A D...A D-H...A
N1A-H1A...O41B 0.87 (2) 1.90 (2) 2.776 (4) 176 (4)
N3A-H3A...O41Ai 0.88 (2) 1.96 (2) 2.837 (4) 174 (4)
N1B-H1B...O21X 0.88 (2) 1.88 (2) 2.746 (5) 168 (5)
N3B-H3B...S21A 0.88 (2) 2.39 (2) 3.258 (3) 171 (4)
Symmetry code: (i) -x+2, -y+1, -z.

Supporting information for this paper is available from the IUCr electronic archives (Reference: EG3147 ).


Acknowledgements

The authors thank Dr Michael Bolte and Valeska Gerhardt for helpful discussions.

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Acta Cryst (2014). C70, 241-249   [ doi:10.1107/S2053229614001387 ]