Crystal Engineering with Bis(thiourea) Derivatives - Crystal Growth

Crystal Engineering with Bis(thiourea) Derivatives† Gary L. Succaw, Timothy J. R. Weakley, Fusan Han, and Kenneth M. Doxsee* Department of Chemistry, University of Oregon, Eugene, Oregon 97403 Received April 18, 2005;

Revised Manuscript Received May 4, 2005

CRYSTAL GROWTH & DESIGN 2005 VOL. 5, NO. 6 2288-2298

ABSTRACT: Urea and thiourea functionalities, presenting opportunities for the formation of diverse hydrogenbonded networks, represent powerful crystal engineering building blocks. Herein we report the synthesis and structural analysis of a series of meta-substituted aromatic bis(thiourea) derivatives in which the steric bulk of the aromatic group and of the thiourea side chains is systematically varied. Two limiting structural types are observeds cyclic dimers and extended three-dimensional network structures, with considerable variability within each of these classes. Incomplete cyclic dimers observed in some cases appear to represent structures transitional between these two limiting classes. Thiourea conformations, hydrogen-bonding parameters, and solid-state packing issues, each playing a role in the determination of preferred solid-state structure, are discussed in detail. Introduction While the field of crystal engineering is maturing with respect to the establishment of an increasingly sophisticated level of understanding of the phenomena dictating the packing of organic molecules into the crystalline state, the great diversity of structures proffered by the organic chemical community continues to offer fresh opportunities for the observation and analysis of new packing motifs and structural complexity. We were struck by Tobe’s report1 of several meta-substituted aromatic bis(thiourea) derivatives exhibiting a unique head-to-tail hydrogen bonding of the NH groups on one molecule to the thiocarbonyl group on a second molecule to form a dimer with the aromatic rings lying along the same rotational axis but perpendicular to one another (Figure 1). While Tobe noted that a head-to-tail hydrogenbonding arrangement has been found in ureas,2-6 the orthogonal dimeric structure is unique to the bis(thiourea) derivatives. Our initial interest was in the use of the bis(thiourea) derivatives as test cases for the study of the dynamics of crystallization of self-assembling systems,7 an interest fueled by an intriguing set of papers by Nadarajah et al. regarding the aggregation state of the growth unit in the crystallization of lysozyme.8-10 However, in the course of these studies, our attention was drawn to the fascinating structural complexity presented by the seemingly simple dimerization of the Tobe bis(thiourea) derivatives,1 as suggested by Tobe’s crystallographic observation of an incomplete head-to-tail hydrogenbonding arrangement in the case of the bis(N-ethyl) analogue of the bis(thiourea) depicted in Figure 1. Tobe’s studies, varying the electron withdrawing groups on the aromatic ring (CF3, Br) and steric groups [cyclohexyl, benzyl, phenyl, tert-butyl, neopentyl, CH2C6H4OCH3(p), CH2C6H3F2(3,5), CH2C6F5, CH2C6H4CF3(p)] on the thiourea side chain, beautifully explored the impact of diverse structural changes on the solution dimerization constants for the bis(thiourea) derivatives. To complement these studies, permitting a comprehensive analy† This paper is dedicated to an inspirational scientist, J. Michael McBride, on the occasion of his 65th birthday. * E-mail: [email protected].

Figure 1. Molecular and crystal structure of a dimeric bis(thiourea): (a) molecular structure; (b) side view of the dimeric unit, indicating two representative hydrogen bonds (2.47, 2.55 Å) (disordered t-Bu groups are apparent); (c) top view, depicting the head-to-tail hydrogen-bonding arrangement of the thiourea groups.

sis of the influence of such substituents changes on the solid-state structures of the bis(thiourea) derivatives, we have prepared a number of new bis(thiourea) derivatives (Scheme 1), in which we systematically vary the substituent on the aromatic ring (R′ ) H, Me, Et, i-Pr, t-Bu) and the alkyl chain length (R ) Me, Et, n-Pr, n-Bu, n-pentyl, n-hexyl) to elucidate the factors that favor crystallization as dimers. In the course of these studies, we have begun to develop a more global recognition of

10.1021/cg050162c CCC: $30.25 © 2005 American Chemical Society Published on Web 10/07/2005

Crystal Engineering with Bis(thiourea) Derivatives Scheme 1.

Bis(thiourea) Derivatives

the diversity of solid-state structures displayed by the bis(thiourea) derivatives in particular and the thiourea functionality in general.11 Experimental Section Full experimental details and characterizations for new compounds are provided as Supporting Information. Representative procedures and partial characterizations are presented here. Preparation of 1,3-Bis[(N′-methylthioureido)methyl]benzene (1a). Methyl isothiocyanate (2.9 g, 0.040 mol) was added to a solution of 2.0 mL (0.0154 mol) of 1,3-bis(aminomethyl)benzene (9a) in 60 mL of THF in a nitrogen purged flask. After concentration on the rotary evaporator, the crude oily residue was triturated with diethyl ether to obtain a powdery solid. The crude product was recrystallized from ethanol/DMSO (3:1 mixture), then from absolute ethanol (ca. 50 mL). The final yield was 2.26 g (52%), mp 179.8-180.3 °C. 1 H NMR (300 MHz, DMSO-d6, δ): 2.848 (br s, 6H, CH3), 4.643 (br s, 4H, CH2), 7.181 (t, 3H, Ar-H), 7.277 (t, 1H, ArH), 7.485 (br s, 2H, NH), 7.896 (br s, 2H, NH). Anal. Calcd for C12H18N4S2: C, 51.03; H, 6.42; N, 19.84; S, 22.71. Found: C, 50.89; H, 6.42; N, 19.7; S, 22.4. Preparation of 1,3-Bis[(N′-pentylthioureido)methyl]5-methylbenzene (2e). n-Pentyl isothiocyanate (2.9 mL, 0.021 mol) was added to a solution of 1.488 g (0.0099 mol) of crude 1,3-bis(aminomethyl)-5-methylbenzene (9b) in 60 mL of THF in a nitrogen purged flask. Concentration on the rotary evaporator and recrystallization from absolute ethanol afforded a yield of 1.197 g (30%) in the form of two very large crystals, mp 102.8-105.0 °C. 1H NMR (300 MHz, CDCl3, δ): 0.840 (t, 6H, CH3), 1.120 (m, 12H, CH2), 2.348 (s, 3H, ArCH3), 2.788 (br s, 4H, CH2), 4.957 (br s, 4H, ArCH2), 6.917 (s, 1H, ArH), 6.950 (s, 2H, ArH), 7.437 (br s, 2H, NH), 7.671 (br s, 2H, NH). Anal. Calcd for C21H36N4S2: C, 61.72; H, 8.88; N, 13.71; S, 15.69. Found: C, 61.77; H, 8.89; N, 13.66; S, 15.47. Preparation of 5-Ethyl-1,3-bis[(N′-ethylthioureido)methyl]benzene (3b). Ethyl isothiocyanate (0.350 mL, 0.00400 mol) was added to a solution of 0.282 g (0.00171 mol) of crude 1,3-bis(aminomethyl)-5-ethylbenzene (9c) in 20 mL of THF in a nitrogen purged flask. After 2 h of refluxing, the reaction mixture was allowed to cool to room temperature, and the solvent was removed on a rotary evaporator. The crude product was triturated in a minimal amount of 9:1 CH2Cl2/ethyl acetate, then recrystallized from DMF/water, affording crystalline product suitable for X-ray crystallographic analysis (0.3143 g, 54% yield), mp 167.0-169.0 °C. 1H NMR (300 MHz, DMSOd6, δ): 1.074 (t, 6H, CH3), 1.165 (t, 3H, CH3), 2.530 (q, 2H, CH2), 3.384 (br s, 4H, CH2), 4.599 (br s, 4H, ArCH2), 7.013 (s, 3H, ArH), 7.445 (br s, 2H, NH), 7.735 (br s, 2H, NH). Anal. Calcd for C16H26N4S2: C, 56.77; H, 7.74; N, 16.55. Found: C, 56.90; H, 8.10; N, 16.38. Preparation of 5-Isopropyl-1,3-bis[(N′-pentylthioureido)methyl]benzene (4e). Pentyl isothiocyanate (0.500 mL, 0.00360 mol) was added to a solution of 0.209 g (0.00117 mol) of crude 1,3-bis(aminomethyl)-5-isopropylbenzene (9d) in 3 mL of THF in a nitrogen purged flask. After 2 h of refluxing, the reaction mixture was cooled to room temperature, and the solvent was removed on a rotary evaporator. The crude product was recrystallized from absolute ethanol (0.0816 g, 16% yield), mp 133.0-135.5 °C. 1H NMR (300 MHz, CDCl3, δ): 0.809 (t, 6H, CH3), 1.113 (br multiplet, 12H, CH2), 1.233 (d, 6H, CH3),

Crystal Growth & Design, Vol. 5, No. 6, 2005 2289 2.777 (br s, 4H, CH2), 2.889 (sextet, 1H, CH), 4.849 (br s, 4H, ArCH2), 6.921 (s, 1H, ArH), 6.971 (s, 2H, ArH), 7.509 (br s, 2H, NH), 7.721 (br s, 2H, NH). Anal. Calcd for C23H40N4S2: C, 63.25; H, 9.23; N, 12.83. Found: C, 62.98; H, 9.68; N, 12.83. Preparation of 5-tert-Butyl-1,3-bis[(N′-propylthioureido)methyl]benzene (5c). Propyl isothiocyanate (4.6 mL, 0.044 mol) was added to a solution of 4.028 g (0.02094 mol) of 1,3-bis(aminomethyl)-5-tert-butylbenzene (9e) in 120 mL of THF in a nitrogen purged flask. The mixture was heated at reflux for 1-2 h, cooled, and concentrated on a rotary evaporator. The crude solid was recrystallized from absolute ethanol to yield a white powdery solid. Recrystallization from toluene afforded larger and better defined crystals, 2.825 g (34.2%), mp 121.0-124.5 °C. 1H NMR (300 MHz, CDCl3, δ): 0.655 (t, 6H, CH3), 1.125 (sextet, 4H, CH2), 1.230 (s, 9H, CH3), 2.700 (br s, 4H, CH2), 4.953 (br s, 4H, ArCH2), 6.909 (s, 1H, ArH), 7.103 (s, 2H, ArH), 7.439 (br s, 2H, NH), 7.754 (br s, 2H, NH). Anal. Calcd for C20H34N4S2: C, 60.87; H, 8.68; N, 14.20; S, 16.25. Found: C, 60.78; H, 8.59; N, 14.24; S, 16.12. X-ray Crystallography. Data acquisition was carried out on either an Enraf-Nonius CAD-4 diffractometer at 22-23 °C or a Bruker Smart Apex diffractometer at 0 °C with graphitemonochromated Mo KR radiation (λ ) 0.71073 Å). The structures were solved by either the SIR9212 direct method using the TEXSAN13 program suite or SHELXTL-97 and SADABS.14 Table 1 provides a summary of selected crystallographic data. Full information regarding the structures and refinement are provided as Supporting Information.

Results and Discussion Synthesis. Bis(thiourea) derivatives 1a-f were prepared from commercially available 1,3-bis(aminomethyl)benzene. Preparation of the tert-butyl derivatives (5a-f) was effected using a modification of Tobe’s reported approach (Scheme 2). Bromination of tertbutyl-m-xylene (6e) with N-bromosuccinimide in tetrachloroethene reduced the reaction time to 4 h from the 10 h reported1 when using carbon tetrachloride. Treatment of dibromide 7e with potassium phthalimide in DMF for 48 h at room temperature afforded the bis(phthalimide), 8e, as an easily isolable, solid product in 87% yield (lit. 70%). Hydrazinolysis of the phthalimide to the corresponding diamine (9e) proceeded as described1 with enhanced yields made possible by initial concentration of the ethanol/water mixture obtained in the workup prior to extraction (see Supporting Information). Given its apparent air sensitivity, the diamine was not purified but was converted directly to the bis(thiourea) derivatives 5a-f by treatment with the appropriate alkyl isothiocyanate, following Tobe’s protocol.1 Preparation of the 5-methyl derivatives, 2a-f, necessitated preparation of 1,3-bis(bromomethyl)-5-methylbenzene (7b) (Scheme 2). Bromination of mesitylene (6b) affords 1,2,3-tris(bromomethyl)benzene, as well as 7b. The crude bromination mixture, which was powerfully lachrymatory, was used without purification in the next step, with the desired phthalimide derivative (8b) easily separated from the triphthalimide by column chromatography. Hydrazinolysis to the corresponding diamine (9b) and conversion to the bis(thiourea) derivatives 2a-f proceeded analogously to the tert-butyl derivatives. While many of the bis(thiourea) derivatives crystallize nicely from ethanol, the lower alkyl derivatives (1a-c, 2a-c) are less soluble, and colored impurities coprecipitate from ethanol solutions. Dropwise addition of DMSO to a refluxing suspension of the bis(thiourea) in

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Table 1. Crystal Data crystal data formula formula weight crystal system space group a, b, c (Å) R, β, γ (deg) V (Å3) Z dcalcd (g‚cm-3) T (°C) µ (cm-1) F000 rel trans coefft no. obsd rflns total indep rflns R(F), wR(F) [I g σ(I)] R(F2), wR(F2) (all data) S [I g σ(I)], S (all data) no. indep rflns scanned no. params function minimized or refinement on weighting factor w max ∆/σ, last cycle max, min in final diff map (e Å-3) crystal data formula formula weight crystal system space group a, b, c (Å) R, β, γ (deg) V (Å3) Z dcalcd (g‚cm-3) T (°C) µ (cm-1) F000 rel trans coefft no. obsd rflns

1a

1c

1d

2b

2e

3a

3e

5a

C12H18N4S2 282.42

C16H26N4S2 338.53

C18H30N4S2 366.6

C13H20N4S2 324.5

C21H36N4S2 408.7

C14H22N4S2 310.48

C22H38N4S2 422.69

C16H26N4S2 338.5

orthorhombic

monoclinic

monoclinic

monoclinic

tetragonal

monoclinic

tetragonal

monoclinic

Pbca

P21/a

C2/c

C2/c

I41/a

P21/c

I41/a

C2/c

14.7407(21), 9.1370(15), 20.5421(22) 90, 90, 90 2767(1) 8 1.356

8.834(4), 12.4201(18), 17.0105(17) 90, 96.51(2), 90 1854(1) 4 1.212

39.055(9), 12.437(3), 8.824(2) 90, 101.08(2), 90 4206(2) 8 1.158

23.056(3), 8.6042(9), 9.4497(14) 90, 107.380(11), 90 1789.0(4) 4 1.205

16.975(2), 16.975(2), 17.007(2) 90, 90, 90 4900.4(8) 8 1.108

17.470(3), 9.6949(15), 9.5174(14) 90, 90.275(3), 90 1612.0(4) 4 1.279

16.755(2), 16.755(2), 18.559(3) 90, 90, 90 5210(1) 8 1.078

43.780(5), 9.814(5), 18.682(3) 90, 108.49(1), 90 7612(3) 16 1.181

23 3.7 1200 0.965-1.000 (ψ) 1575 [I g σ(I)] 2420

23 0.289 728

23 2.60 1584

23 2.97 696

0 0.327 664

1636 2728

1241 [I g σ(I)] 2920

1190 [I g σ(I)] 1567

23 2.30 1776 0.965-1.000 (ψ) 1095 [I g σ(I)] 2179

2323

23 2.18 1840 0.97-1.00 (ψ) 1131 [I g σ(I)] 2302

22 2.82 2912 0.95-1.00 (ψ) 2306 [I g σ(I)] 4633

0.044, 0.042

0.078, 0.074

0.121, 0.110

0.062, 0.088

0.078, 0.072

0.381, 0.1095

0.069, 0.079

0.070, 0.055

0.072, 0.093

0.138, 0.156

0.252, 0.228

0.089, 0.178

0.107, 0.149

0.0496, 0.1273

0.074, 0.143

0.137, 0.122

1.14, 1.08 2774 (incl 353 syst absent) 235 ∑w(|Fo| |Fc|)2

1.93, 1.58 2921

2.13, 1.49 3093

3.52, 3.24 1567

2.44, 1.84 2179

0.900, 0.900 9691

2.66, 1.75 2387

197 |F|2

161 |F2

97 ∑w(|Fo| |Fc|)2

124 ∑w(|Fo| |Fc|)2

182 F

133 |F|2


1/σ2(F)

1/σ2(F)

1/σ2(F)

1/σ2(F)

1/σ2(F)

1/σ2(F)

1/σ2(F)

0.01

0.042

0.01

0.01

0.01

1/[σ2(Fo2) + (0.1000P)2] 0.042

0.02

0.01

0.51, -0.59

0.70, -0.62

1.00, -1.16

0.42, -0.36

0.53, -0.56

0.638, -0.286

0.33, -0.28

0.59, -0.73

5a‚0.5toluene

1904

4a

4d

5a

C15H24N4S2 324.50

C21H36N4S2 408.66

C16H26N4S2 338.5

C19.5H30N4S2 384.60

C20H34N4S2 394.6

5c

C22H38N4S2 422.7

5d

C24H42N4S2 450.74

5e

monoclinic

tetragonal

monoclinic

monoclinic

triclinic

tetragonal

tetragonal

P21/c

I41/a

C2/c

P21/a

P1 h

I41/a

I41/a

17.571(6), 10.062(4), 9.506(3) 90, 91.699(6), 90 1680.1(10) 4 1.283

16.854(3), 16.854(3), 18.943(4) 90, 90, 90 5381.1(16) 8 1.078

43.780(5), 9.814(5), 18.682(3) 90, 108.49(1), 90 7612(3) 16 1.181

18.535(3), 9.878(1), 25.659(4) 90, 110.15(1), 90 4410.5(11) 8 1.158

13.151(2), 15.054(1), 25.211(3) 86.30(1), 80.03(1), 8.09(1) 4560.7(9) 8 1.149

16.696(5), 16.696(5), 18.989(4) 90, 90, 90 5293(3) 8 1.061

16.705(4), 16.705(4), 19.205(7) 90, 90, 90 5359(3) 8 1.117

0 0.317 696

0 0.213 1904

22 0.251 1656

23 2.44 1712

947

3467

7493 [I g σ(I)]

23 2.14 1840 0.777-1.000 (ψ) 867 [I g σ(I)]

0 0.216 1968

2002

22 2.82 2912 0.95-1.00 (ψ) 2306 [I g σ(I)]

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Crystal Growth & Design, Vol. 5, No. 6, 2005 2291

Table 1 (Continued) crystal data total indep rflns R(F), wR(F) [I g σ(I)] R(F2), wR(F2) (all data) S [I g σ(I)], S (all data) no. indep rflns scanned no. params function minimized or refinement on weighting factor w max ∆/σ, last cycle max, min in final diff map (e Å-3)

4a

5a‚0.5toluene

5c

5d

5e

1936

4633

5678

12633

2493

1938

0.1243, 0.3291

0.0850, 0.2348

0.070, 0.055

0.098, 0.097

0.093, 0.107

0.116, 0.071

0.1102, 0.2229

0.1387, 0.3391

0.1410, 0.2567

0.137, 0.122

0.154, 0.188

0.157, 0.215

0.184, 0.152

0.1536, 0.2406

1.914, 1.914 9892

1.283, 1.283 16462

3.00, 2.36 6361

3.35, 2.66 12694

1.82, 1.19 2493

1.243, 1.243 16174

191 F

124 F


397 |F|2

827 |F|2

142 |F|2

152 F

1/[σ2(Fo2) + (0.1000P)2] 0.098

1/[σ2(Fo2) + (0.1000P)2] 0.317

1/σ2(F)

1/σ2(F)

1/σ2(F)

1/σ2(F)

0.01

0.02

0.03

0.03

1/[σ2(Fo2) + (0.1000P)2] 0.201

1.709, -0.604

0.521, -0.167

0.59, -0.73

0.77, -0.59

1.13, 0.93

0.56, -0.57

0.606, -0.353

Synthesis of Bis(thiourea) Derivatives 2a-f and 5a-fa

(i) 2 equiv N-bromosuccinimide/C2Cl4; (ii) 2 equiv potassium phthalimide/DMF, 25 °C, 48 hr; (iii) N2H4/EtOH; (iv) 2 equiv RsNdCdS.

Scheme 3.

a

5a

2433

Scheme 2.

a

4d

Synthesis of 1,3-Bis(thiourea) Derivatives 3a-f and 4a-fa

(i) I2, CaCO3/PhMe/H2O; (ii) isoamyl nitrite/DMF; (iii) Zn(CN)2/DMF; (iv) H2/catalyst/EtOH; (v) 2 equiv RsNdCdS.

ethanol, followed by cooling, precipitates the bis(thiourea), leaving the colored impurities behind. A second recrystallization from a larger amount of ethanol yields white, crystalline, and analytically pure bis(thiourea). Single crystals of suitable size and form for X-ray crystallography were obtained by recrystallization from DMF/water for 1d, 2b, 3a, and 4a and by vapor diffusion of heptane into toluene solutions of bis(thioureas) 3f and 5d or diethyl ether into solutions of 5a in CHCl3. Although the bis(thioureas) 2a-f may be accessed through initial stoichiometric control of the bromination of mesitylene, analogous bromination en route to the corresponding ethyl and isopropyl derivatives (3a-f, 4a-f) would favor bromination at the ethyl and isopropyl groups in which the benzylic positions are also reactive 2° and 3° positions. Thus, we developed an

alternative synthetic scheme, depicted in Scheme 3, that does not require a benzylic bromination step. (This route is similar to an alternate synthetic scheme in ref 1 but was designed to exploit more benign reagents.) Selective iodination of the aromatic ring, affording modestly light-sensitive 11c,d, is effected with molecular iodine in toluene/water in the presence of CaCO3 to neutralize HI.15 Reductive deamination with isoamyl nitrite16 provides a convenient preparation of the diiodoarenes (12c,d), replacing the more standard twostep diazotization/reduction procedure. Catalytic cyanation to afford 13c,d using zinc cyanide17 suffers from inferior yields if 12c,d are not first purified by column chromatography (silica gel, hexanes). This unusual reaction is critically dependent on the use of zinc cyanide as the source of cyanide. (Zinc cyanide is more “covalent” in nature than sodium or potassium cyanide,

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Table 2. Crystal Morphology, Structure Type, and Space Group for Bis(thiourea) Derivatives 1-5 dithiourea

morphology

dimer?

1a 1b 1c

needles needles needles

no no no

1d 1e 1f 2a 2b 2c 2d 2e 2f 3a 3b 3c 3d 3e 3f 4a 4b 4c 4d 4e 4f 5a 5b 5c 5d 5e 5f

needles needles needles needles needles needles needles pseudooctahedra needles needles needles needles needles pseudooctahedra pseudooctahedra needles needles needles needles pseudooctahedra pseudooctahedra pseudooctahedra pseudooctahedra pseudooctahedra pseudooctahedra pseudooctahedra pseudooctahedra

no no no no no no no yes no no no no no yes yes no no no no yes yes yes yesb yesb yes yes yes

space group Pbca Pbcaa Pbcaa P21/c (tw) C2/c Pbcaa P21/c Pbcaa C2/c Pbcaa P21/c I41/a P21/ca P21/c P21/ca P21/ca P21/ca I41/a I41/a P21/c Pbcaa P21/ca Pbcaa I41/a I41/a C2/c P1 h P1 h I41/a I41/a I41/a

a Probable space group based on comparison of powder X-ray diffraction patterns with powder X-ray diffraction patterns of samples analyzed by single-crystal X-ray diffraction. b Incomplete dimers-see discussion in text.

providing a smaller amount of “free” cyanide.17 An excessive amount of “free” cyanide poisons the catalyst, preventing the oxidative addition of the aromatic iodide.) Catalytic hydrogenation of dinitriles18 13c,d affords the corresponding diamines (9c,d). Interestingly, in our hands, the reduction of 13c is effected by palladium on activated carbon but not by platinum(I) oxide, while 13d is effectively reduced using platinum(I) oxide but not palladium on activated carbon. As for the other derivatives (9a,b,e), each of these diamines may be converted to the corresponding bis(thioureas) by treatment with alkyl isothiocyanates (Scheme 3). The ethyl and isopropyl derivatives 3a-d and 4a-d may be recrystallized from DMF/water after either column chromatography or simple trituration with methylene chloride/ethyl acetate. Ethyl and isopropyl derivatives 3e,f and 4e,f may be recrystallized from ethanol. Structural Analysis. All the bis(thiourea) derivatives examined are highly crystalline. Table 2 summarizes the morphology and crystallographic space groups for the bis(thiourea) derivatives. Interestingly, some derivatives crystallize only as clusters of very fine needles, apparently regardless of the choice of crystallization solvent, while others crystallize as well-shaped, isolated pseudooctahedral crystals. For each compound that forms discrete dimers in the solid state, the wellshaped pseudooctahedral crystals are obtained, while compounds that do not form discrete dimers in the solidstate crystallize as needles. The tert-butyl dibutyl derivative (5d) is typical of the bis(thiourea) derivatives that form well-defined single

Succaw et al.

crystals. This compound crystallizes as discrete dimers, illustrated in Figure 1, as reported by Tobe.1 Each of the four thiourea groups displays an anti/anti geometry with each SdC-N-H dihedral angle close to 180° (Table 3). (We here define the anti conformation as that with a SdC-N-H dihedral close to 180° and the syn conformation as that with a SdC-N-H dihedral close to 0°. Figure 2a presents a schematic representation of the hydrogen bonding in 5d in a form that facilitates its comparison to the hydrogen bonding in the other bis(thiourea) derivatives (vide infra). This hydrogen-bonding arrangement is very similar to that seen in other anti/anti thioureas, which, however, adopt infinite chain arrangements rather than the cyclic dimers seen for these bis(thiourea) derivatives.19 The tight, symmetrical dimer structure is maintained in the tert-butyl derivatives with longer N-alkyl chains, 5e and 5f (also crystallizing in the I41/a space group), as highlighted by the metrics presented in Table 3. However, bis(thiourea) derivative 5a adopts a considerably less symmetrical dimeric structure, illustrated in Figure 3. In 5a, the planes of the phenyl rings are oriented roughly perpendicular to each other, as in symmetrical dimer 5d, but the C2 axis in the dimer of 5d, passing through both the tert-butyl groups, is no longer present in 5a. The dimer of 5a appears “bent” relative to the dimer of 5d, revealed by generally longer and more variable hydrogen-bonding distances (see Table 3). Crystallization from toluene affords a toluene solvate of 5a. Interestingly, the solvate molecule is accommodated with minimal changes in molecular dimensions or contacts, leading to only negligible structural differences between the dimeric bis(thiourea) units in 5a and 5a‚toluene (Table 3). In 5b-c, the planes of the phenyl rings are roughly perpendicular, as in symmetrical dimer 5d, yet the intradimer hydrogen-bonding network is incompletely developed. Interestingly, in 5b, one of the four thiocarbonyl groups adopts a syn/anti conformation, with one SdC-N-H dihedral angle near 0° (Table 3), in marked contrast to the anti/anti conformation found for each thiourea moiety in 5d. These conformational differences are depicted schematically in Figure 2b. This altered conformation prohibits completion of the full intradimer hydrogen-bonding network. The thiocarbonyl group, which loses one of its two intradimer hydrogen bonds due to this syn/anti conformation, gains a second hydrogen bond from a neighboring dimer. The conformational change required to accommodate this interdimer hydrogen bond, however, results in movement of the thiourea group out of hydrogen-bonding range for the neighboring intradimer thiourea. The thiocarbonyl group of the latter “dangling” thiourea group participates in interdimer hydrogen bonding with the thiourea of an adjacent dimer, and the “dangling” thiourea of this second dimer symmetrically participates in hydrogen bonding back to the first dimer, effectively forming a “dimer of dimers” (Figure 4). This intermolecular interaction appears frequently for thioureas adopting the syn/anti conformation, both in the case of pyridylsubstituted thioureas20 designed to favor the syn/anti conformation and for simpler thioureas for which rea-



Table 3. Selected Torsional Angles, Hydrogen-Bond Lengths, and Hydrogen-Bond Angles for Bis(thiourea) Derivativesa 5cb

5cb

1a

1c

1d

2b

3a

4a

171.5 172.6 173.6 175.0

HintsNsCdS (deg) 171.3 175.0 173.6 171.8 173.2 174.1 175.7 173.7 172.4 176.8 176.0 178.2

174.7 179.9 178.4 13.9

174.7 177.9

172.1 10.1

175.5 9.8

174.6

176.2 173.8

170.8 176.4

179.8

176.7 176.9 177.9 178.3

HextsNsCdS (deg) 174.6 173.6 174.1 176.4 5.5 4.6 177.6 174.5 178.0 178.7 175.4 173.5

174.0 0.2 173.5 178.0

0.8 6.4

2.9 173.7

1.7 173.6

0.6

173.1 6.8

173.8 9.4

2.6

2.5 2.5 2.6 2.7

2.5 2.5 2.6 2.7

S-Hint (Å) 2.6* 2.5* 2.8 2.5 2.7 2.6 2.5 2.6

2.7

2.5 2.5

2.5 2.5

2.6

2.7 2.7

2.6 2.7

S-Hext (Å) 2.7* 3.0* 2.6 2.6 2.6 2.7 2.530* 2.6

2.6 2.6

2.5

2.6

2.5

2.5 2.6

2.6 2.7

155.2

152.3 154.9

153.6 156.5

136.1

150.2 150.8

154.8 155.2

149.3 160.9

158.4

159.3

170.9

155.2 160.3

149.3 160.3

107.4

103.0 105.8

101.3 107.5

100.9

102.6 122.6

105.4 124.2

94.0 96.7

105.2

104.8

115.8

101.2 107.6

99.4 104.2

2e

3e

5e

3f

5d

4d

5a

171.4

171.2

173.3

170.5

169.2

171.7

177.5

179.5

179.5

172.7

177.5

2.5

2.5

2.6

2.5

2.5

5a‚tol

5b

2.5

2.6

2.6

2.7

2.6

2.7

2.5 2.5 2.5 2.8

2.4 2.5 2.5 2.7

158.5

160.1

160.9

164.2

160.5

161.0

155.1 155.9 158.6 167.2

SsHintsN (deg) 153.8 150.9* 157.0* 155.3 151.6 157.7 160.2 157.9 160.1 164.2 163.0 160.8

159.6

159.4

159.8

152.3

159.4

160.0

153.7 158.8 160.1 163.0

SsHextsN (deg) 157.4 156.6* 149.1* 159.8 164.7 159.1 161.7 162.1 158.2 159.9

80.9

82.2

82.2

86.2

82.4

81.7

76.7 85.5 88.5 94.2

75.8 85.8 86.8 97.4

95.9 98.7 103.9 107.1

CdSsHext (deg) 93.7 103.2* 98.5* 97.8 103.5 105.3 104.3 117.9* 106.2 111.8 109.6

98.1

97.8

95.9

105.4

98.2

96.2

CdSsHint (deg) 123.1* 116.5* 75.6 78.7 124.8 124.5 88.9 86.6

2.6 2.5 2.6 3.1* 2.5 2.6

155.2 161.7 157.9 152.4* 163.9 157.5

76.5 86.3 95.6 120.4* 103.3 111.5

a H b int refers to the NH group bearing the benzyl group; Hext refers to the NH group bearing the N-alkyl substituent. Data for two inequivalent dimers in the asymmetric unit. The / represents an interdimer contact.

Figure 2. Schematic of the hydrogen-bonding pattern in symmetric and “peeled back” bis(thiourea) dimers: (a) all anti/anti thioureas; (b) a single syn/anti thiourea; (c) two syn/anti thioureas. Only intradimer hydrogen-bonding interactions are depicted. In panel a, the right-hand thiocarbonyl is hydrogen bonded to the two left-hand N-H groups; in panels b and c, these groups are not involved in intradimer hydrogen bonding.

sons for the adoption of this conformation are less apparent.21,22 Bis(thiourea) 5c, with two dimers in the asymmetric unit, proffers still greater structural complexity. One of the two dimers displays a structure virtually identical to that of 5b, with the presence of a single syn/anti thiourea group leading to a partial breakdown of the dimer structure and the formation of a “dimer of dimers” (Figures 2b and 4). The second dimeric unit, in contrast, has two syn/anti thioureas, leading to further erosion

of the discrete dimeric structure and an increasing number of interdimer hydrogen-bonding contacts (Figure 2c). Surprisingly, one of syn thioureas is on the internal (benzylic) side, the other on the external (Nalkyl) side. Each of the other crystallographically characterized bis(thiourea) derivatives bearing longer N-alkyl chains (2e, 3e,f, 4e,f) also forms the tight, symmetrical dimer structure displayed by 5d (Table 3). (Each of these derivatives crystallizes in the I41/a space group.) In

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Figure 3. Crystal structure of the incomplete dimer of bis(thiourea) 5a, including intradimer hydrogen-bonding contacts.

Figure 4. Interdimer hydrogen-bonding interactions in bis(thiourea) 5b and 5c. Black spheres indicate carbon atoms, dark gray spheres sulfur, lighter gray nitrogen, and lightest gray hydrogen; dashed lines indicate hydrogen bonds. Intradimer hydrogen bonds are also indicated.

marked contrast, bis(thiourea) 2f, rather curiously, crystallizes in the needlelike morphology that appears to correlate to nondimeric structures, serving to illustrate rather graphically that, while we are often able to draw useful general conclusions from comparative structural analyses, Nature is always willing to provide exceptions to the rule. As the size of the N-alkyl substitutent and/or the aromatic side chain is reduced (compounds 1a-f, 2ad, 3a-d, 4a-d), the breakdown of the dimeric structure heralded by compounds 5b and 5c is further enhanced. Indeed, each crystallographically characterized bis(thiourea) in this set of compounds (1a,c,d, 1f (not refined), 2b, 2d (not refined), 3a, 4a) adopts an extended hydrogen-bonded network structure rather than the discrete dimer structures discussed above. Unfortunately, only about one-half of these bis(thiourea) derivatives, all of which crystallize with the needle morphology of 1a, afforded crystals suitable for X-ray crystallographic analysis. However, comparison of the powder X-ray diffraction patterns of those derivatives not amenable to single-crystal X-ray analysis with the powder patterns of those derivatives that were successfully analyzed by single-crystal methods is strongly suggestive of nondimeric, extended network structures being favored by each of these derivatives as well. The extended hydrogen-bonded network structures of bis(thiourea) derivatives 1a,c,d, 2b, 3a, and 4a appear superficially similar. Closer analysis, however, reveals a number of intriguing features. Most notably, without

Succaw et al.

the constraint of a tight dimer, the thiourea groups have greater conformational freedom. Derivatives 3a and 4a each have one anti/anti and one syn/anti thiourea (Figure 5a), while in 1a and 2b, both thioureas adopt the syn/anti conformation (Figure 5b,c). Compounds 1c and 1d similarly have two syn/anti thioureas, but in contrast to 1a and 2b, one of the syn thioureas is on the internal (benzylic) side (Figure 5d), as seen in 5c. These conformational differences, as well as the intermolecular hydrogen-bonding interactions, are depicted schematically in Figure 5. Figures 6-9 show the monomeric units and crystal packing for 1a, 1d, and 3a, representing the three limiting cases depicted in Figure 5. In Figures 7-9, selected molecules are highlighted to more clearly illustrate that the hydrogen bonding is not confined to a dimer but is extended throughout the crystal. The largest S‚‚‚H-N hydrogen-bonding distance observed in these structures (3a, 2.69 Å) is comparable to those seen in the dimeric structures (Table 3). Derivatives 3a and 4a each display a symmetrical cyclic intermolecular hydrogen-bonding interaction analogous to the interaction forming the “dimers of dimers” (Figure 4) in 5b and 5c. Both thioureas in compound 2b are involved in such intermolecular contacts, while the conformationally closely related derivative 1a, surprisingly, adopts a less efficient and less symmetrical hydrogen-bonding pattern (Figure 5b). Derivatives 1c and 1d display maximal hydrogen-bonding interactions but do not form the simple symmetrical cyclic intermolecular hydrogen bonds seen in 3a, 4a, or 2b. The incomplete, “peeled back” dimer structure of bis(thiourea) derivatives 5b,c (Figures 2 and 3) appears transitional between the full dimer structures and the nondimeric hydrogen-bonded network structures. In this structure, the head-to-tail hydrogen bonding of the NH groups to thiocarbonyl is not as complete as that in 5d. Only two thiocarbonyls are hydrogen bonded to two NH groups each, while one is hydrogen bonded to only one NH group, and the fourth thiocarbonyl is not hydrogen bonded within the dimer. Interdimer contacts bearing similarity to those in the extended structures complete the hydrogen-bonding scheme in these derivatives. While Tobe attributed these less symmetrical structures to crystal packing forces,1 we feel they are perhaps representative of a nearly-balanced competition between the tight dimeric structure and the extended hydrogenbonded network structure. Solution 1H NMR spectra for each of the bis(thiourea) derivatives show the same broadening of the R-protons of the alkyl chains as that for compound 5d, implying that similar dimerization is occurring in solution for each bis(thiourea) derivative. The nature of the solid-state structurestight dimer, “peeled back” dimer, or extended structuresthen, is dependent on the dynamic process of crystallization. The tight dimer places geometric constraints on the N-H‚‚‚S hydrogen bonding, potentially preventing optimal orientations of the interacting groups. Thus, while the number of hydrogen bonds per monomer is equivalent in the tight dimer and the extended structures, the extended structure would appear to be more enthalpically favorable. However, entropically the extended structure should be disfavored due to its higher order. To test this hypothesis, we determined the energetics



Figure 5. Schematic of the hydrogen-bonding pattern in extended bis(thiourea) structures: (a) 3a, 4a; (b) 1a; (c) 2b; (d) 1c, 1d. Superscript letters indicate intermolecular contacts to symmetry-related bis(thiourea) molecules. For example, in panel a, the left-hand thiocarbonyl (S1) participates in hydrogen bonds with H1 and H2 of a second bis(thiourea) molecule, symmetry-related as (x, 1.5 - y, 0.5 + z).

Figure 6. Monomeric structures for 1a, 3a, and 1d, illustrating differences in conformations leading to the varied H-bonding depicted in Figure 5.

of crystallization of 1d and 5d. The concentrations of saturated solutions of 1d and 5d in ethanol at several temperatures were determined (Table 4). As per eq 1,10,23 a plot of the logarithm of the solubility (S, in g/L) versus 1/T has a slope of ∆H/R.

ln S ) ∆H/(RT) + constant The heats of recrystallization (∆H) of 1d and 5d in ethanol are -81.4 kJ/mol and -46.9 kJ/mol (Figure 10),

respectively, consistent with our expectation of an enthalpic preference for the extended structure. If the intercept of eq 1 is interpreted as ∆S/R,23 then the entropies of recrystallization of 1d and 5d are 286 J/(mol‚K) and 783 J/(mol‚K), respectively, again in accord with expectationsthe highly ordered extended structure has an appreciably lower ∆Scryst than the tight dimer structure. Crystallization of orthogonal dimers or extended structures appears to be governed by a balance between

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Succaw et al.

Figure 7. Crystal structure of 1a highlighting the extended hydrogen bonding. Note the “tape” motif when viewed from this axis and the appearance of stacking of the phenyl rings.

Figure 8. Crystal structure of 1d highlighting the extended hydrogen bonding. Note stacking of the phenyl rings, similar to 1a.

Figure 9. Crystal structure of 3a highlighting the extended hydrogen bonding and illustrating stacking of phenyl rings.

maximizing the extent of hydrogen bonding and minimizing steric repulsion between the alkyl groups on the aromatic rings and between the thiourea side chains. For example, 1a and 5a lie on opposite extremes of steric repulsions1a has a hydrogen atom on the aromatic ring

and 5a the tert-butyl group. Bis(thiourea) 1a adopts the extended structure, while 5a adopts a dimeric structure. Figure 11 illustrates that the tert-butyl bis(thiourea) derivatives (5a-f) cannot adopt an extended structure because the tert-butyl groups would be in repulsive


Crystal Growth & Design, Vol. 5, No. 6, 2005 2297 Table 5. Melting Ranges for 5a-f

Figure 10. Heat of crystallization determination for 1d and 5d in absolute ethanol.

Figure 11. Partial view of crystal structure of 1a. Circles indicate positions that would be occupied by tert-butyl groups if 5a packed in this structure. Table 4. Solubility Data for 1d and 5d temp (°C) 60 55 53 50 47 45 43 40 35

S (g/L) 1d (EtOH)

S (g/L) 5d (EtOH) 269 212

56.1 45.1 35.9 27.4 22.3

146 114 91.5 68.3

contact. Interestingly, although 5a does not crystallize in the I41/a space group typical for the cyclic dimers (C2/c instead), 5a still exhibits a tight dimer structure in the solid state instead of the more typical extended structure exhibited by other bis(thiourea) derivatives crystallizing in the C2/c space group (1d and 2b).

compound

mp (°C)

5a 5b 5c 5d 5e 5f

113.9-115.9 151.0-152.5 121.0-124.5 153.0-154.2 138.5-140.5 165.0-165.5

While consideration of the steric influence of the aromatic ring substituent is sufficient to explain the structural preference of the tert-butyl bis(thiourea) derivatives (5a-f), consideration of the effects of the N-alkyl substituents appears necessary to understand the behavior of the other bis(thiourea) derivatives (14). For 5a-f, the only effect observed for the side chains is that the melting points follow an odd-even pattern with the melting points of the even-chain compounds (5b,d,f) higher than those of the odd-chain compounds (5a,c,e) (Table 5). While this odd-even melting point behavior has been long recognized for the n-alkanes,24 only recently was its origin firmly established as due to differences in crystal packing density.25 While evennumbered alkanes are able to pack efficiently, oddnumbered alkanes pack more loosely with longer intermolecular distances at one end. While the molecular packing in crystalline 5a-f is appreciably more complex, the primary intermolecular forces (i.e., between dimeric units) are van der Waals forces, and the odd-even melting point behavior is maintained throughout this series. In the methyl series (2a-f), the extended structure is adopted by 2a-d, and 2f, but 2e adopts the dimeric structure. Bis(thiourea) derivatives 2a-d may adopt the extended structure because the alkyl thiourea side chains are not long enough to overcome the hydrogen-bonding stability afforded by the extended structure. This is no longer the case with 2e, which favors the dimeric structure. Curiously, adding one more carbon to the side chain (2f) favors the extended structure again, suggesting that the energetic balance between dimeric and extended structures can be very subtle. The ethyl (3a-f) and isopropyl (4a-f) bis(thiourea) derivatives favor the dimeric structure for the dipentyl and dihexyl derivatives (3e,f and 4e,f). While the ethyl and isopropyl groups are sterically bulkier than the methyl group, this destabilization of the extended structure is not sufficient to force a dimeric structure until the alkyl side chains are long enough. Consideration of the Kitaigorodski packing indices,26 calculated using the PLATON program,27 for the tight dimeric vs the extended structures is also suggestive of steric determinants, although disorder in many of the structures limits the utility of this analysis. The dimer structures appear to display significantly lower packing indices (ca. 55-60% spatial occupancy) than the extended structures (ca. 70% spatial occupancy). Conclusions The thiourea functionality is clearly a versatile contributor to the field of crystal engineering. With multiple syn/anti conformational possibilities and the availability of multiple hydrogen bond donor and acceptor sites in the bis(thiourea) derivatives forming the basis of this study, the range of potential solid-state structures is vast. Two limiting structural classes are clearly pre-

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ferred, one comprising the cyclic dimers and the other extended three-dimensional network structures. Within each of these classes, considerable variability is evinced. The cyclic dimers are complete and highly symmetrical in some cases, less symmetrical in others, and incomplete in still others, with the beginnings of more complex network structures foreshadowed by the interdimer hydrogen-bonding contacts in the latter. Within the extended network structures, also, varying degrees of hydrogen bonding and a set of distinct thiourea conformations lead to a range of solid-state structures. Steric interactions in the alternate packing arrangements, efficiency of hydrogen bonding, and packing density all appear to play a role in the determination of the favored solid-state structures. Acknowledgment. We express our most sincere gratitude to Professor Tobe for discussions of and insights regarding the bis(thiourea) derivatives. The partial support of the U.S. Department of Education (GAANN grant to G.L.S.) and the National Science Foundation (Division of Materials Research) is gratefully acknowledged. Supporting Information Available: Full experimental details and compound characterizations (mp or bp, 1H, 13C NMR, IR, MS, elemental analysis) for all bis(thiourea) derivatives and their synthetic precursors and full information regarding the X-ray crystallographic structure solutions and refinements in the form of a cif file. This material is available free of charge via the Internet at http://pubs.acs.org.

References (1) Tobe, Y.; Sasaki, S.; Mizuno, M.; Hirose, K.; Naemura, K. J. Org. Chem. 1998, 63, 7481-7489. (2) Zhao, X.; Chang, Y.; Fowler, F. W.; Lauher, J. W. J. Am. Chem. Soc. 1990, 112, 6627-6634. (3) Etter, M. C.; Urban˜czyk-Lipkowska, Z.; Zia-Ebrahimi, M.; Panunto, T. W. J. Am. Chem. Soc. 1990, 112, 8415-8426. (4) Hamann, B. C.; Shimizu, K. D.; Rebek, J., Jr. Angew. Chem., Int. Ed. Engl. 1996, 35, 1326-1329. (5) Mogck, O.; Bo¨hmer, V.; Vogt, W. Tetrahedron 1996, 52, 8489-8496. (6) Shimizu, K. D.; Rebek, J., Jr. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 12403-12407. (7) Succaw, G. L. Ph.D. Dissertation, University of Oregon, Eugene, OR, 2004. (8) Nadarajah, A.; Li, M.; Pusey, M. L. Acta Crystallogr. 1997, D53, 524-534. (9) Nadarajah, A.; Forsythe, E. L.; Pusey, M. L. J. Cryst. Growth 1995, 151, 163-172.

Succaw et al. (10) Li, M.; Nadarajah, A.; Pusey, M. L. J. Cryst. Growth 1995, 156, 121-132. (11) Thioamides and thioureas, while perhaps not as intensely studied as the corresponding amides and ureas, are receiving increasing attention in the realm of molecular recognition and crystal engineering. For recent discussions, see: Nesterov, V. N.; Nesterov, V. V. Acta Crystallogr., Sect. C 2004, 60 (11), o781-785. Ruangpornvisuti, V. THEOCHEM 2004, 686, 47-55. Simonov, Y. A.; Fonari, M. S.; Zaworotko, M. J.; Abourahma, H.; Lipkowski, J.; Ganin, E. V.; Yavolovskii, A. A. Org. Biomol. Chem. 2003, 1 (16), 2922-2929. (12) Altomare, A.; Cascarano, G.; Giacovazzo, C.; Guagliardi, A.; Burla, M. C.; Polidori, G.; Camalli, N. J. Appl. Crystallogr. 1994, 27, 435. (13) TeXsan Software for Single-Crystal Structure Analysis, version 1.7; X-ray crystallographic analysis software; Molecular Structures Corporation: The Woodlands, TX, 1997. (14) Sheldrick, G. M. SHELXL-97 Program for Crystal Structure Refinement; Institu¨t fu¨r Anorganische Chemie der Universita¨t: Go¨ttingen, Germany, 1997. Sheldrick, G. M. SADABS, version 2, Multiscan Absorption Correction Program; Institu¨t fu¨r Anorganische Chemie der Universita¨t: Go¨ttingen, Germany, 1997. (15) Wheeler, H. L.; Liddle, L. M. Am. Chem. J. 1909, 42, 441461. (16) Doyle, M. P.; Dellaria, J. F., Jr.; Siegfried, B.; Bishop, S. W. J. Org. Chem. 1977, 42, 7481-7489. (17) Tschaen, D. M.; Desmond, R.; King, A. O.; Fortin, M. C.; Pipik, B.; King, S.; Verhoeven, T. R. Synth. Commun. 1994, 24, 887-890. (18) Hartung, W. H. J. Am. Chem. Soc. 1928, 50, 3370-3374. (19) As but one example, 1-cyclohexyl-3-(2-tolyl)thiourea displays infinite chains of hydrogen-bonded thiourea units. Akilan, R.; Sivakumar, K.; Subramanian, K.; Janarthanan, N.; Ramadas, K.; Fun, H.-K. Acta Crystallogr., Sect. C 1995, 51, 1627. (20) See, for example: Kaminsky, W.; Kelman, D. R.; Giesen, J. M.; Goldberg, K. I.; Claborn, K. A.; Szczepura, L. F.; West, D. X. J. Mol. Struct. 2002, 616, 79 and references therein. (21) Soriano-Garcia, M.; Chavez, G. T.; Cedillo, F. D.; Perez, A. E. D.; Hernandez, G. A. Anal. Sci. 2003, 19, 1087. (22) Wozniak, K.; Wawer, I.; Stroehl, D. J. Phys. Chem. 1995, 99, 8888-8895. Janssen, M. J. Rev. Trav. Chim. 1962, 81, 650-660. (23) See, for example: Price, F. P. Polym. Eng. Sci. 2004, 4, 151156. Vekilov, P. G.; Feeling-Taylor, A. R.; Yau, S.-T.; Petsev, D. Acta Crystallogr. 2002, D58, 1611-1616. (24) Baeyer, A. Ber. Chem. Ges. 1877, 10, 1286. (25) Boese, R.; Bla¨ser, D.; Weiss, H. C. Angew. Chem., Int. Ed. 1999, 38, 988-992. (26) Kitaigorodski, A. I. Molecular Crystals and Molecules; Academic Press: New York, 1973. (27) Spek, A. L. Acta Crystallogr. 1990, A46, C34.

CG050162C

Crystal Engineering with Bis(thiourea) Derivatives - Crystal Growth

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