Hydrogen-Bonding Interactions in Crystalline Solids of Cyclic Thioureas Mary T.
McBride,†
Tzy-Jiun M. Luo, and G. Tayhas R. Palmore*
Department of Chemistry, University of California, Davis, California 95616
CRYSTAL GROWTH & DESIGN 2001 VOL. 1, NO. 1 39-46
Received September 1, 2000
ABSTRACT: The crystal structures of three cyclic thioureas (4,5-disubstituted benzimidazolene-2-thiones) are reported. Each compound forms a tape motif in the solid state. Two of the three compounds assemble into tapes via N-H- - -S hydrogen bonds. These tapes pack into planar sheets. The third compound assembles into tapes via C-H- - -Br hydrogen bonds. These tapes pack at angles relative to each other, generating puckered sheets. The patterns of packing of these three cyclic thioureas are compared to those observed in the crystalline solids of cyclic ureas that have analogous molecular structures. The patterns of packing adopted by cyclic thioureas are rationalized in terms of molecular structure, solvent of crystallization, and energies and efficiencies of packing. 1. Introduction In our effort to control the patterns of packing of molecules in crystalline solids, we use functional groups arranged in a manner that encourages molecules to assemble into hydrogen-bonded tapes (Figure 1).1-5 A tape is a supramolecular motif that results when each molecule forms hydrogen bonds to exactly two neighboring molecules and when the hydrogen bonds between any two molecules form a cyclic, eight-membered ring (i.e., R22(8)).6-8,35 Tapes are an attractive motif with which to engineer solid-state structures because they are stronger and more restrictive than chains or ribbons of hydrogen bonds and they often pack with their long axes parallel.9 These features limit the number of orientations available for molecules to pack in their crystalline solids, and therefore, molecules that can form tapes tend to be more predictable in terms of their packing.10 We report the crystal structures of three cyclic thioureas (i.e., 4,5-disubstituted derivatives of benzimidazolene-2-thiones labeled 1-SMe2-β, 2-SH2-β, and 1-SBr2) and compare them to crystalline solids of cyclic ureas with analogous molecular structure (labeled 1-Me2, 2-H2, and 1-Br2) (Figure 2).11 Note that β in the labels 1-SMe2-β and 2-SH2-β indicates that these solids are polymorphs to solids comprised of the same compounds that were reported previously.12 Similar to cyclic ureas, cyclic thioureas comprise two hydrogen-bond donors (N-H) and one hydrogen-bond acceptor (CdS) that can function as a double acceptor. Consequently, the pattern in which cyclic thioureas pack is expected to be similar to those observed in crystalline solids of cyclic ureas. The electronegativity of sulfur (2.4), however, is lower than that of oxygen (3.5), and therefore, the polar character of the CdS bond in thiourea is reduced relative to that of a CdO bond in urea. This decrease in polar character of the CdS bond in thiourea is expected to weaken the hydrogen-bonding interactions between thioureas as compared to ureas with analogous * To whom correspondence should be addressed. E-mail: palmore@ chem.ucdavis.edu. † Current address: Department of Chemistry and Materials Science, Lawrence Livermore National Laboratory, Livermore, CA 94550.
Figure 1. (a) Hydrogen-bonded tape that forms between thioureas related through a center of inversion. Each thiourea forms an R22(8) pattern of hydrogen bonds with two adjacent thioureas. (b) Schematic diagram of cyclic thioureas assembled into stepped tapes, where filled circles represent sulfur atoms. (c) Schematic diagram of stepped tapes viewed on edge to illustrate the 1 Å separation between parallel planes that contain molecules on opposite sides of the tape.
molecular structure. Thus, depending on the chemistry of the substituents present, or the solvent used for crystallization, tapes that form in crystalline solids of cyclic ureas may be absent in the crystalline solids of cyclic thioureas that are structurally analogous. Additionally, in comparison to ureas, the weaker dipole moment of thioureas may result in the inclusion of solvent within the solid or the formation of threedimensional networks instead of tapes.8,11 2. Experimental Section Derivatives of 4,5-disubstituted benzimidazolene-2-thione (1-SMe2-β, 2-SH2-β, and 1-SBr2) were prepared using the synthetic methodology reported previously.12 Crystals were
10.1021/cg0000060 CCC: $20.00 © 2001 American Chemical Society Published on Web 11/15/2000
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Figure 2. Molecular structure of cyclic thioureas (Y ) S: 1-SMe2-β(a), (b), 2-SH2-β (b), and 1-SBr2 (c)) and cyclic ureas (Y ) O: 1-Me2 (a), 2-H2 (b), and 1-Br2 (c)). obtained by slow evaporation of solvent from a hot solution of pure cyclic thiourea. Crystals obtained by this method of crystallization often were clusters of twinned needles. Crystals marginally suitable for single-crystal X-ray diffraction were harvested from the end of a single needle where polarized light was extinguished uniformly. X-ray data for the compounds 1-SMe2-β and 1-SBr2 were collected on a Siemens P21 diffractometer. X-ray data for the compound 2-SH2-β were collected on a Siemens P4/RA diffractometer equipped with a rotating anode generator. All X-ray data were collected at 130 K using 2θ scans (λ ) 1.541 78 Å) over the range 3-57°. Lattice parameters were determined from least-squares analysis of 29 reflections. Two standard reflections were measured every 198 reflections. Structures were solved by direct methods and refined by full-matrix least squares on F2 using SHELXTL (version 5.03).13 All non-hydrogen atoms were refined anisotropically. Hydrogen atoms involved in hydrogen bonding were refined after location on a difference map with isotropic temperature factors, except for the amide hydrogen atoms in the compound 1-SBr2, which could not be located on the difference map. Other hydrogen atoms were placed in idealized positions with assigned isotropic thermal parameters. The packing fraction (Ck*) for each solid was calculated with the program PLATON14 using the relationship Ck* ) Vm/Vc, where Vm is the volume of the molecules in the unit cell and Vc is the total volume of the unit cell. The Minimizer and Crystal Packer modules in the program Cerius2 from MSI (version 3.8) were used to locate the molecular conformation with lowest energy and to determine the energy and efficiency of packing of molecules in each solid. All calculations were performed using a DREIDING force field.15 Atomic charges were calculated using the charge equilibrium method.16 Prior to calculation of the energy of packing, both cell parameters and conformation of molecules were optimized with the Minimizer module. The energy of the conformation with the best geometry was minimized until the rms of the energy was less than 0.1 kcal mol-1 Å-1. Minimization of molecular conformation was performed on 1-SCl2 and 1-SBr2 in both crystal structures with A-tapes and B-tapes before optimizing the energy of packing. After the atomic charges were recalculated, the structures were transferred to the Crystal Packer module and their packing energies minimized. Minimization of energy was performed in the absence of cell constraints with all molecules in the packed structure treated as rigid bodies. Iterative calculations of the total energy and the packing energy were performed until convergence was achieved.
3. Results Crystalline Solid of 1-SMe2-β (4,5-Dimethylbenzimidazolene-2-thione). The thiourea fragment in each molecule of 1-SMe2-β forms two hydrogen bonds (NH- - -S: 3.303 Å, 176.3°) to each of two adjacent molecules, generating a hydrogen-bonded tape (Figure 3). The nonpolar benzene rings form the outer edges of the tape. Molecules alternate on opposite sides of the tape and are related through a center of inversion. Molecules
Figure 3. Crystal structure of 1-SMe2-β (4,5-dimethylbenzimidazolene-2-thione): (a) view down the a axis, with molecules on opposite sides of the hydrogen-bonded (dashed lines) tape lying in two planes, separated by 1 Å; (b) parallel tapes packed into sheets (light and dark lines), separated by 3.558 Å; (c) two sheets rotated 90° to illustrate parallel packing of tapes and the resultant planar sheets.
on one side of the tape occupy a different plane than molecules on the other side of the tape; these two planes are parallel relative to each other and are separated by ∼1 Å to give what is referred to as a stepped tape (Figure 1c).12 The periodicity of molecules on the same side of the tape is 8.320 Å. Tapes align in parallel and pack into sheets with a periodicity of 16.527 Å between adjacent tapes. Due to the size of the dimethylbenzene ring of 1-SMe2-β, adjacent tapes within a sheet do not interdigitate. Close contacts (3.469 Å) within a sheet exist between aromatic hydrogen atoms (C-H- - -HC) of molecules that reside on the same side of a tape. The periodicity of sheets in the crystal is 3.558 Å, with an offset between adjacent sheets of 3.953 Å. Close contacts between sheets exist between methyl substituents (C-H- - -H-C: 2.336 Å). 1-SMe2-β is a polymorph of 1-SMe2.12 Both data sets were obtained from crystals of marginal quality, a property reflected in the poor refinement statistics. The two data sets are nearly identical in terms of unit cell parameters, patterns of packing (including the formation of tapes and molecular periodicity), and hydrogenbond distances and angles. The significant differences between the two structures are the temperature at which data were collected (143 K for 1-SMe2-β compared to 273 K for 1-SMe2) and the space group (P21/m for 1-SMe2-β compared to P21 for 1-SMe2). Data for 1-SMe2-β do not converge in the space group of lower symmetry (P21), and the hydrogen atoms were located easily on the difference map. Crystalline Solid of 2-SH2-β (2,3-Naphthimidazolene-2-thione). Similar to the crystalline solid of 1-SMe2-β, the thiourea fragment in each molecule of 2-SH2-β forms two hydrogen bonds (N-H- - -S: 3.345 Å, 161.80°) to each of two adjacent molecules, generating the tape motif (Figure 4). This molecule crystallizes in a centrosymmetric space group with molecules alternating on opposite sides of the tape through a center of inversion. Molecules on one side of the tape occupy a different plane than molecules on the other side of the
Crystalline Solids of Cyclic Thioureas
Figure 4. Crystal structure of 2-SH2-β (2,3-naphthimidazolene-2-thione): (a) view down the c-axis, with N-H- - -S interactions (dashed lines) resulting in the formation of tapes; (b) parallel tapes packing into sheets (light and dark lines), where molecules of solvent minimize void space by filling channels that form between adjacent tapes; (c) two sheets rotated 90°, with parallel packing of tapes resulting in planar sheets.
tape; these two planes are parallel relative to each other and are separated by ∼1 Å. The periodicity of molecules on the same side of the tape is slightly larger than that of 1-SMe2-β (i.e., 8.455 Å for 2-SH2-β vs. 8.320 Å for 1-SMe2-β). All tapes align parallel and pack into twodimensional sheets with a periodicity of 19.703 Å between adjacent tapes, 3.176 Å greater than that of the crystalline solid of 1-SMe2-β. The closest contact within a sheet occurs between naphthylene rings of 2-SH2-β (C-H- - -H-C, 2.601 Å). Adjacent tapes are out of register along the c axis by a single molecule, creating channels between tapes that are filled by molecules of solvent (i.e., disordered acetone). The value for Ck* in 2-SH2-β is 69.3 or 59.4 in the presence or absence of solvent, respectively. The presence of solvent in the crystalline lattice of 2-SH2-β does not disrupt the formation of N-H- - -S hydrogen bonds. Sheets pack 3.251 Å apart with an offset between adjacent sheets of 4.805 Å along the c axis. The closest contact between sheets occurs between amide groups (N1-H1- - -H1N1: 3.083 Å). The crystalline solid of 2-SH2-β is a polymorph of 2-SH2.12 Crystals were obtained from different solvents (2-SH2-β from acetone, 2-SH2 from THF), and data were collected at different temperatures (2-SH2-β at 143 K, 2-SH2 at 273 K). The unit cell parameters for the two compounds are similar; however, the molecules in these two polymorphs exhibit different patterns of packing. Molecules of 2-SH2-β form tapes, which pack into planar sheets with a slip in the registry between tapes in adjacent sheets that creates a space (channel) occupied by molecules of solvent (Figure 4). Tapes also form in the solid 2-SH2. Tapes in this solid pack with their long axes in parallel; however, the angle between adjacent tapes is 85°, thus creating Z-shaped sheets. Consequently, void space is created between adjacent tapes, which is filled by molecules of solvent. The difference
Crystal Growth & Design, Vol. 1, No. 1, 2001 41
in values for Ck* (69.3 for 2-SH2-β vs 65.7 for 2-SH2) illustrates a general trend observed in solids comprised of tapes: that is, planar sheets of parallel tapes pack more efficiently (minimize void space) than nonplanar sheets of tapes. Crystalline Solid of 1-SBr2 (4,5-Dibromobenzimidazolene-2-thione). The crystalline solid of 1-SBr2 is a solvate, including both dimethyl sulfoxide (DMSO) and water. On the basis of Etter’s rules for hydrogen bonding, the strongest donors (nitrogen atoms of thiourea) should form a hydrogen bond with the strongest acceptors (oxygen atom of DMSO). The solvatochromic parameter, β, measures the ability of a molecule to accept a proton in a solute-to-solvent hydrogen bond and is 0.76 for DMSO.17,18 Due to the high β value for DMSO, the N-H donor of 1-SBr2 forms hydrogen bonds with the oxygen acceptor of DMSO (N-H- - -ODMSO: 2.768 Å, 155.0°). This pattern of hydrogen bonding interferes with the formation of the N-H- - -S hydrogen bonds observed in crystalline solids of 1-SMe2-β and 2-SH2-β. In addition to the N-H- - -ODMSO interactions, 1-SBr2 forms two C-H- - -Br hydrogen bonds to each of two adjacent molecules, which by definition creates a tape motif in this solid (Figure 5).19-23 These C-H- - -Br interactions do not involve the best hydrogen-bond donors and acceptors and, therefore, are expected to be less influential in the packing of 1-SBr2 than the interaction between the N-H donor of 1-SBr2 and the oxygen acceptors in the molecules of solvent. It is interesting to note that the sulfur atom of 1-SBr2 does not participate in hydrogen bonding.24 In a manner similar to the crystalline solids of 1-SMe2-β and 2-SH2-β, adjacent molecules in the solid of 1-SBr2 are related to one another through a center of inversion. The periodicity between molecules on the same side of the C-H- - -Br tape is 13.747 Å. All tapes align with their long axis parallel and pack at an angle relative to each other that measures 141.5° between the planes of adjacent tapes to form Z-shaped sheets (Figure 5c). The periodicity of adjacent sheets is 3.362 Å; the closest contact between adjacent sheets is 3.054 Å (CBr- - -H-C). 4. Discussion General Trends in the Patterns of Packing of Cyclic Thioureas and Cyclic Ureas. Crystallographic data for the three cyclic thioureas are summarized in Table 1. Distances for hydrogen bonds and close contacts are given in Table 2. Similar to the solids of cyclic ureas that have analogous structures (1-Me2, 2-H2, 1-Br2), the molecular solids of 1-SMe2-β, 2-SH2-β, and 1-SBr2 are composed of planar molecules that crystallize in monoclinic, centrosymmetric space groups. All six compounds form tapes in their crystalline solids; however, molecules of 1-SBr2 assemble into tapes using C-H- - -Br interactions. The patterns of packing in four solids (1-SMe2-β, 1-Me2, 2-SH2-β, and 1-Br2) are similar: tapes pack in parallel to form planar sheets, and nonpolar substituents are clustered together but not interdigitated (Table 3). The range of values of Ck* for these four solids is 0.69-0.72 (when solvent is included in 2-SH2-β). In all four solids, the molecules form hydrogen bonds with adjacent molecules in the manner in which these
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Figure 5. Crystal structure of 1-SBr2 (4,5-dibromobenzimidazolene-2-thione): view of the packing; (b) two parallel sheets (light and dark lines) with molecules of solvent incorporated between adjacent tapes; (c) two sheets rotated 90° to illustrate the packing of adjacent tapes into Z-shaped sheets. Table 1. Crystallographic Data for the Cyclic Thioureas 1-SMe2-β chem formula
C9H10N2S
2-SH2-β
C11H8N2S‚ 0.5C3H6O mol wt 178.25 226.27 cryst syst monoclinic monoclinic space group P21/m C2/m cryst size (mm) 0.20 × 0.14 × 0.54 × 0.12 × 0.02 0.10 cryst color yellow yellow a (Å) 5.319(1) 25.052(3) b (Å) 8.320(2) 8.455(2) c (Å) 10.433(2) 5.184(1) R (deg) 90 90 β (deg) 103.32(3) 91.54(1) γ (deg) 90 90 3 V (Å ) 449.3(2) 1097.6(3) Z 2 4 dcalcd (g cm-3) 1.318 1.369 µ (cm-1) 2.730 2.404 GOF 1.160 1.059 R(all) 0.102 0.044 Rw(all) 0.277 0.122 no. of rflns 614 743
1-SBr2 C7H4Br2N2S‚ C2H6OS‚H2O 403.14 monoclinic P21/c 0.76 × 0.12 × 0.10 yellow 6.330(1) 29.496(6) 7.449(2) 90 98.16(3) 90 1376.7(5) 4 1.945 10.259 1.178 0.054 0.162 1592
molecules were designed: that is, interactions occur between the strongest hydrogen-bond donors (i.e., N-H) and the strongest hydrogen-bond acceptors (i.e., CdO or CdS). All hydrogen-bond donors and acceptors of each molecule are occupied. Competing hydrogen-bond donors or acceptors, introduced by the choice of solvent used during crystallization (i.e., ethyl acetate, dimethylformamide, acetone, methanol) do not interfere with the hydrogen-bonding interactions between N-H donors and CdS or CdO acceptors. The energies of the N-H- - -S hydrogen bonds in tapes of thioureas have been reported and compared to those in tapes of ureas using several ab initio methods.25,26 The results from these studies show that the N-H- - -S interaction between thioureas is lower in energy than that between ureas. For example, the energy reported for the “last H-bond” for thioureas ranges between -10.17 and -11.48 kcal mol-1 compared to between -11.58 and -13.73 kcal mol-1 for ureas, indicating that the hydrogen-bonding interaction between thioureas is weaker than that of ureas by ∼2 kcal mol-1.26 In addition to being a weaker interaction, N-H- - -S hydrogen bonds between cyclic thioureas force
molecules on one side of a tape to reside in a plane that is parallel to but separated from (∼1 Å) the plane occupied by molecules on the other side of the tape. This type of tape is referred to as a stepped tape,12 as opposed to a planar tape, and occurs to relieve steric crowding around the sulfur atoms and perhaps to reduce π-π repulsion between aromatic rings in adjacent sheets (Figure 6a,b).27 The covalent radius of a sulfur atom is larger than that of an oxygen atom by 0.38 Å, which results in hydrogen-bond angles for N-H- - -S interactions that are ∼6° smaller than those of N-H- - -O interactions. This difference in hydrogen-bond angles is manifested as stepped tapes (Figure 6b) in solids of cyclic thioureas or as puckered tapes (Figure 6c) in the calculated geometry of a tape comprised of four cyclic thioureas.11 In contrast, interactions that involve N-H- - -O hydrogen bonds between cyclic ureas allow molecules to reside either in the same plane on both sides of the tape (i.e., planar tape) or in planes that lie at angles relative to one another (i.e., puckered tape), both of which are observed experimentally. The puckered tape is not observed in the calculated geometry of a tape comprised of four cyclic ureas. The puckering of tapes in solids of cyclic ureas, in which the distance between molecules is less than that in tapes of cyclic thioureas (i.e., 6 Å vs 8.3 Å, respectively) relieves steric interactions between substituents. The range of values for Ck* is narrow for the cyclic ureas reported previously (0.71-0.72)11 and is at the upper limit expected for organic crystals.28 Consequently, it is not necessary to incorporate molecules of solvent to stabilize these solids. Conversely, the values for Ck* for thioureas are low, ranging between 0.65 and 0.69. These low values indicate cyclic thioureas do not pack as efficiently as cyclic ureas.28 Two of the cyclic thioureas (2-SH2-β and 1-SBr2) crystallize as solvates, whereas none of the solids of cyclic ureas were found to include solvent. Values for β for the solvents used to crystallize both cyclic thioureas and cyclic ureas are listed in Table 3.17 All three cyclic ureas form tapes comprised of N-H- - -O hydrogen bonds, despite being crystallized from solvents with competitive acceptors. This result suggests that the acceptor strength of the CdO moiety
Crystalline Solids of Cyclic Thioureas
Crystal Growth & Design, Vol. 1, No. 1, 2001 43
Table 2. Inter- and Intratape Distances for the Cyclic Thioureas 1-SMe2-β
2-SH2-β
1-SBr2
D-H- - -A (Å)
N-H- - -S: 3.303(0.005)
N-H- - -S: 3.345(0.002)
D-H- - -A (deg)
N-H- - -S: 165.08(4.54)
N-H- - -S: 161.80(4.00)
shortest dist between two tapes within same sheet (Å) shortest dist between two tapes in adjacent sheets (Å) dist between two tapes within same sheet (Å) dist between two tapes within adjacent sheets (Å)
14.073 (S1-N1) 3.347 (N1-N1) 16.53 3.56
17.499 (S1-N1) 3.334 (N1-N1) 19.7 3.52
C-H- - -Br: 3.835(0.008) C-H- - -Br: 3.803(0.009) C-H- - -Br: 156.7(0.11) C-H- - -Br: 170.2(0.17) 7.631 (S1-Br1) 3.054 (Br1-H7) 9.83 3.18
Table 3. Patterns of Packing in Solids of Cyclic Thioureas and Cyclic Ureas, Crystallization Solvents, and Solvent Parameters thiourea
tapes (D-H- - -Y)
packing of tapes
solvate
Ck*a
crystallizn solvent
β
1-SMe2-β 1-Me2 1-SH2-β 2-H2 1-SBr2 1-Br2
yes (N-H- - -S) yes (N-H- - -O) yes (N-H- - -S) yes (N-H- - -O) yes (C-H- - -Br) yes (N-H- - -O)
| | | X, 85° Z, 145.4° |
no no yes no yes no
0.67 0.71 0.69, 0.59 0.72 0.66, 0.46 0.72
ethyl acetate DMF acetone MeOH DMSO, H2O MeOH
0.46 0.76 0.48 0.62 0.76, 0.18 0.62
a
Values calculated for Ck* with and without solvent present, respectively.
Figure 6. (a) Molecules on both sides of a planar tape residing in the same plane. Planar tapes pack into planar sheets that stack efficiently. (b) Molecules on one side of a stepped tape occupying a different plane than molecules on the other side of a stepped tape. These two planes are parallel relative to each other and are separated by ∼1 Å (i.e., gray squares reside in a plane below the black squares). Stepped tapes pack into stepped sheets that stack efficiently. (c) Puckered tapes consisting of molecules that lie at an angle (>0°,
