Synthon Robustness and Solid-State Architecture in Substituted gem

Synthon Robustness and Solid-State Architecture in Substituted gem-Alkynols Rahul

Banerjee,†

Raju

Mondal,‡

Judith A. K.

Howard,‡

and Gautam R.

Desiraju*,†

School of Chemistry, UniVersity of Hyderabad, Hyderabad 500 046, India, and Department of Chemistry, UniVersity of Durham, South Road, Durham DH1 3LE, England

CRYSTAL GROWTH & DESIGN 2006 VOL. 6, NO. 4 999-1009

ReceiVed NoVember 10, 2005; ReVised Manuscript ReceiVed January 23, 2006

ABSTRACT: Analysis of crystal packing of related compounds is a necessary ingredient of crystal engineering. We report here the crystal structures of 14 cyclic and fused ring gem-alkynols, compounds that are known for their supramolecular inconsistency because of the juxtaposition of two hydrogen-bond donors (O-H, CtC-H) and two hydrogen-bond acceptors (O-H, CtC-H) in the molecules. Because of the competition between these hydrogen-bond donors, or hydrogen-bond acceptors, the packing pattern in any particular crystal structure is highly sensitive to substitution by functional groups. The compounds studied here are methyl and chloro derivatives of the parent compounds 1a (benzo series, 1b-1f), 2a (naphtha series, 2b-2f), 3a and 4a (anthra series, 3b, 4b-4d). Structures 2a and 4a are prototypes because the O-H‚‚‚O, C-H‚‚‚O, O-H‚‚‚π, and C-H‚‚‚π hydrogen bonds form sheets in these cases with the interdigitating hydrocarbon residues perpendicular to the sheets. The hydrogen bonds are arranged to give centrosymmetric synthons I and II, which are noteworthy for their robustness. Orthogonality of the hydrogen-bonded and hydrocarbon regions in these crystals leads to structural insulation so that the addition of an extra fused ring in going from, say, 2a to 4a, leaves the structure unaltered. Many types of methyl substitution on these rings also preserve the packing so that it may be inferred that methyl substitution is supramolecularly akin to benzo annelation in these compounds. A new synthon [(I)0.5(II)0.5], which is a hybrid of synthons I and II, is also observed. This hybrid, H, is thermodynamically comparable to synthons I and II because it contains the same cooperative network of strong and weak hydrogen bonds, O-H‚‚‚O-H‚‚‚CtC-H‚‚‚CtC-H‚‚‚OH‚‚‚, which is the key structural element in this family. Chloro substitution is in general more aggressive than methyl substitution, and Cl/Me exchange does not operate in the benzene series. In contrast, Cl/Me exchange perturbs only some elements of the crystal packing in the naphthalene series. Also observed is a homology between crystal structures related by a naphtha/anthra exchange. Identifying robust supramolecular synthons and proving their repetition is a challenging task in a system as fragile as the gemalkynols, and we note that prior to this work there was no repetition of a major hydrogen-bonded supramolecular synthon in the 144 gem-alkynols with published crystal structures. Also noteworthy is that synthons I, II, and H are fairly largesthe real challenge in crystal engineering is to find a big enough synthon that occurs often enough. Large synthons that occur frequently constitute the most useful structural domains in crystal families, and we believe that we have identified such a domain in the gem-alkynol group of compounds. Introduction Crystal engineering is the rational design of functional molecular solids with tailored intermolecular interactions.1 This endeavor includes three distinct activities, which form a continuous sequence: (i) studying intermolecular interactions;2 (ii) establishing relationships between molecular functionality and crystal packing;3 and (iii) optimizing crystal properties.4 Colloquially speaking, these three stages represent the “what”, “how”, and “why” of crystal engineering. This paper is concerned with the second of these aims, which attempts to develop strategies of crystal design. In this context, the key link between molecular and crystal structure is the supramolecular synthonsa specific pattern of intermolecular interactions is associated with a specific type of molecular array in the solid state.5 Accordingly, one attempts to identify and then reproduce reliable supramolecular synthons so as to lead to desired crystal structures. Reliability, or robustness, means that a synthon repeats in a number of crystal structures.6 In contrast, the crystal structure of a new molecule in a series of known compounds can also be unpredictable: this is the most vexatious problem confronting those wishing to design specific crystalline arrays.7 Such unpredictability arises because the manifestation of †

University of Hyderabad. University of Durham. * To whom correspondence [email protected]. ‡

should

be

addressed.

E-mail:

intermolecular interactions from functional groups is not modular.8 Unexpected interactions or synthons can ensue, leading to a phenomenon that we term interaction interference,9 so that it is difficult to anticipate when a particular chemical modification will conserve a synthon, and when not. The family of geminal alkynols or gem-alkynols, molecules that contain equal stoichiometries of hydroxyl and ethynyl groups attached to the same carbon atom, offers an assorted structural behavior that is suited to the effective exploration of the relationships between molecular functionality and crystal packing.10 The lack of structural repetition among the 144 published crystal structures in this family is an additional challenge.11 Failure to find repeating structural relationships in this family arises from the close juxtaposition of two hydrogenbond donors (O-H, C-H) and two acceptors (O-H, CtCH). In this sterically hindered situation, the four interactions that are possible, namely, O-H‚‚‚O, C-H‚‚‚O, O-H‚‚‚π, and C-H‚‚‚π, become competitive. This leads to high levels of interference among these four interaction types (Scheme 1). Accordingly, one finds 95 O-H‚‚‚O, 78 C-H‚‚‚O, 18 O-H‚‚‚π, and 88 C-H‚‚‚π hydrogen bonds in these 144 crystal structures. In other words, the packing pattern in any particular crystal structure in this family is highly sensitive with respect to changes in the substitution pattern of the molecular skeleton. As a result, attempts to establish a molecule-supermolecule correspondence via the supramolecular synthon approach are extremely difficult. Previously, we have studied trans-1,4-

10.1021/cg050598s CCC: $33.50 © 2006 American Chemical Society Published on Web 02/15/2006

1000 Crystal Growth & Design, Vol. 6, No. 4, 2006

Banerjee et al.

Scheme 1. Supramolecular Synthons Observed Previously in the gem-Alkynol Family

Scheme 2. gem-Alkynols in This Study

diethynyl-1,4-dihydroxy-2,5-cyclohexadiene (1a), trans-1,4diethynyl-1,4-dihydronaphthalene-1,4-diol (2a), and trans-9,10diethynyl-9,10-dihydroanthracene-9,10-diol (4a), which are prototype gem-alkynols.9g To further explore and assess the structural fidelity in this family, this paper presents an analysis of the crystal structures of 14 related compounds (Scheme 2), which are classified according to the quinones from which they were synthesized. Alkynols 1a-1f are based on benzoquinone (BQ), 2a-2f are based on naphthoquinone (NQ), 3a and 3b are based on 1,4-anthraquinone, and 4a-4d are based on 9,10anthraquinone (AQ). The compounds in the present study are chloro and methyl derivatives in the BQ, NQ, and AQ series. Chemical substituents exert both steric and electronic effects on crystal structures. These effects result in what may be termed the “geometrical” and “chemical” components of molecular recognition.12 It is convenient to distinguish these components on the basis of distance dependence of the corresponding interactions. The short range, isotropic interactions give rise to geometrical attributes (shape, size), while the longer range, anisotropic interactions (hydrogen bonding, polarization) give rise to specific orientations of molecules. Both geometrical and chemical factors are important. The former constitute a sort of isotropic background upon which are superimposed the chemical factors. The default packing for organic molecular solids is the Kitaigorodskii close packed model, which is based on geometrical recognition. Deviations, small and large, from this model are explained on the basis of chemical factors, that is anisotropic interactions. To probe these factors, the chemist studies compounds wherein the substitutional changes preserves one effect while varying the other. Substituents such as Cl and Me have nearly the same size but different chemical properties.

Accordingly, if replacement of a Cl group by a Me group (or say, a -CHdCH- group by an -S- group) leaves a crystal structure unaltered, it is concluded that geometrical factors are important.13 If the structure is altered, chemical factors are invoked. In this paper, we describe the formation, modulation, and robustness of weak supramolecular synthons with respect to the substitutional changes in these BQ, NQ, and AQ molecular cores. In many cases, the reader will note that the observed crystal structures result from a balance of several factors; interaction interference can at least be understood. We are not claiming structural control. Experimental Section General. Solvents were purified by standard methods and dried if necessary. Reagents used were of commercial quality. All the compounds were characterized with IR and NMR spectra. IR spectra were recorded on a Jasco 5300 spectrometer. The 1H NMR spectra were recorded at 200 MHz on a Bruker ACF instrument. All melting points were measured using a Fischer-Johns melting point instrument. Synthesis. All gem-alkynols were synthesized from the respective quinones using a two-step procedure. The operations were carried out in a dry N2 atmosphere using standard syringe-septum techniques. (i) A solution of Me3SiCtCH (4.4 mmol) in THF (15 mL) was mixed with nBuLi (4.2 mmol) at 195 K. After the sample was stirred for 15 min, a solution of the respective quinone (1 mmol) in THF was added dropwise and stirring was continued for 30 min at 195 K and for a further 1 h at room temperature. The product was obtained after standard workup. (ii) The solid product from step (i) was dissolved in MeOH and methanolic KOH was added slowly, and the mixture was stirred for 1 h at room temperature. Water was added to the reaction mixture, and the product was extracted with EtOAc. The product was dried over

Synthon Robustness in Substituted gem-Alkynols

Crystal Growth & Design, Vol. 6, No. 4, 2006 1001

Table 1. Crystallographic Data and Structure Refinement Parameters of Different gem-Alkynols Studied in This Papera alkynol

1b

1c

1d

1e

2b

2c

2d

structural formula formula weight crystal system space group T (K) a (Å) b (Å) c (Å) R (°) β (°) γ (°) V (Å3) Z Fcalc (g/cm3) µ (mm-1) R1 [I > 2σ(I)] wR2 goodness-of-fit reflns collected unique reflns obsd reflns crystal size

C12H12O2 188.23 triclinic P1h 120(2) 6.6905(4) 8.6781(6) 10.1446(7) 70.615(3) 75.058(3) 88.865(3) 535.43(6) 2 1.167 0.079 0.0426 0.1160 1.086 6335 2445 2141 0.42 × 0.36 × 0.20 288932

C12H12O2 188.23 monoclinic P21/c 120(2) 10.8340(3) 10.2757(2) 9.7859(2) 90 107.015(1) 90 1041.75(4) 4 1.200 0.081 0.0373 0.1051 1.067 10448 2396 2013 0.40 × 0.24 × 0.20 288933

C14H16O2 216.28 orthorhombic Fdd2 120(2) 32.5783(12) 18.3051(6) 25.6653(10) 90 90 90 15305.5(10) 24 1.126 0.074 0.0427 0.1067 1.055 42794 8760 8176 0.46 × 0.38 × 0.18 288934

C10H6Cl2O2 229.26 monoclinic P21/c 120(2) 7.1489(14) 13.333(3) 10.614(2) 90 104.00(3) 90 981.7(3) 4 1.550 0.627 0.0269 0.0665 1.026 10763 2251 2011 0.46 × 0.40 × 0.22 288935

C16H14O2 238.29 triclinic P1h 120(2) 8.4194(3) 8.7817(3) 10.3302(4) 114.080(1) 102.774(2) 99.085(2) 653.12(4) 2 1.212 0.079 0.0605 0.1441 1.083 8092 3418 2664 0.43 × 0.39 × 0.10 288936



alkynol

2e

2f

3a

3b

4b

4c

4d

structural formula formula weight crystal system space group T (K) a (Å) b (Å) c (Å) R (°) β (°) γ (°) V (Å3) Z Fcalc (g/cm3) µ (mm-1) R1 [I > 2σ(I)] wR2 goodness-of-fit reflns collected unique reflns observed reflns crystal size


C16H12Br2O2 396.08 orthorhombic P212121 120(2) 9.5729(2) 10.3511(2) 15.1691(3) 90 90 90 1503.11(5) 4 1.750 5.391 0.0148 0.0363 1.047 17002 3441 3328 0.48 × 0.24 × 0.16 288940


C18H10Cl2O2 329.19 orthorhombic P212121 120(2) 6.7139(1) 7.4777(1) 29.8603(4) 90 90 90 1499.12(4) 4 1.458 0.436 0.0279 0.0706 1.120 17835 3407 3366 0.46 × 0.24 × 0.22 288942




CCDC No.

CCDC No. a

For details of compounds 1a, 1f, 2a, and 4a see ref 9g.

MgSO4, and the solvent was removed. Crystals for X-ray work were obtained by purification of the crude material (column chromatography) followed by recrystallization from 1:1 CHCl3-benzene. All IR, NMR, and melting point information is given in Supporting Information. X-ray Crystallography. X-ray diffraction intensities for all gemalkynols reported in this paper were collected at 120 K (Oxford Cryosystems cooler) on a Bruker SMART CCD diffractometer (Bruker Systems Inc., 1999a)14 using Mo KR X-radiation. Data were processed using the Bruker SAINT package (Bruker Systems Inc., 1999b)15 with structure solution and refinement using SHELX97 (Sheldrick, 1997).16 The structures of all the compounds were solved by direct methods and refined by full-matrix least-squares on F2. H-atoms were located in all 14 structures and refined freely with isotropic displacement parameters. Crystal data and details of data collections, structure solutions, and refinements are summarized in Table 1. Crystallographic data (excluding structure factors) for the structures reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as deposition No. CCDC 288932-288945 (see also Table 1). Copies of the data can be obtained, free of charge, on application to the CCDC, 12 Union Road, Cambridge CB2 lEZ UK (fax: + 44 (1223) 336 033; e-mail: [email protected]).

Results and Discussion Prototype Structures. Figure 1 shows the crystal structures of the prototype alkynols 1a, 2a, and 4a previously published by us.9g The unsubstituted BQ compound 1a has a unique structure with an infinite cooperative O-H‚‚‚O-H‚‚‚O-H chain, and additional C-H‚‚‚O and C-H‚‚‚π bridges in a perpendicular plane so that all the interactions form a 3-D network. Effectively, the various functional groups in 1a (hydroxy, ethynyl, alkene) are intimately involved with each another in the packing. Accordingly, any substitutional perturbation of this molecule is expected to alter the packing completely. In contrast, the NQ prototype, 2a, and the 9,10-AQ prototype, 4a, have more generic packings because the O-H‚‚‚O, C-H‚‚‚O, and C-H‚‚‚π hydrogen bonds form a 2-D network with the hydrocarbon residues perpendicular to this plane (Scheme 3). Note that the O-H‚‚‚O, C-H‚‚‚O, and C-H‚‚‚π bridges (Table 2) form the clearly defined centrosymmetric synthons I and II (Scheme 4) in 2a and 4a and that the manner


Banerjee et al. Scheme 3. Interdigitation of Aromatic Residues in the NQ and AQ Prototypes 2a and 4aa

a Note that the hydrogen-bonded layers and the aromatic residues are perpendicular.

Scheme 4. Supramolecular Synthons Discussed in This Study

Figure 1. Crystal structures of the prototype compounds 1a, 2a, and 4a. In 1a, the figure shows the C-H‚‚‚O and C-H‚‚‚π interactions between gray-colored molecules and O-H‚‚‚O interactions between gray and green molecules. The orthogonality of these sets of hydrogen bonds renders this crystal structure incapable of further modulation. In 2a and 4a, however, all the hydrogen bonds are in the same layer making structural modulation possible. Note that structures 2a and 4a are nearly the same with synthons I and II, and the manner in which they are attached, are identical.

in which these synthons are fused together to generate a planar hydrogen-bonded sheet is identical in both structures. Scheme 3 shows that the aromatic residues interdigitate to form a bilayer structure in NQ and a continuous structure in 9,10-AQ. This orthogonality of the hydrogen-bonded and hydrocarbon regions

leads to structural insulation so that it is not difficult to understand that the addition of an extra fused ring in going from 2a to 4a leaves the structure unaltered. In principle, substitution on these rings might also preserve this structure with orthogonal hydrogen bonding and aromatic interdigitation. Last, we note that two molecules of the symmetrical 4a lie on distinct crystal inversion centers such that Z′ ) (0.5 + 0.5), whereas for the unsymmetrical 2a, Z′ ) (1 + 1) to maintain the same packing. Benzoquinone (BQ)-Based Structures. To understand the modulation of the packing in terms of geometrical and chemical effects, we systematically replaced the alkenic protons in 1a with Cl and Me groups to obtain 1b-1f. 2,5-Dimethyl-trans-1,4-diethynyl-1,4-dihydroxy-2,5-cyclohexadiene (1b) adopts space group P1h with Z′ ) (0.5 + 0.5). The packing of this symmetrical molecule is exactly the same as in 4a (also P1h), and indeed one can visualize the two Me groups as vestigial benzo rings; the cell edges in 1b (6.6905, 8.6781, 10.1446 Å) and 4a (8.7684, 8.9558, 10.315 Å) show a close correspondence with the a-axis being the direction of the Me groups in 1b and of the benzo rings in 4a. Synthons I and II occur as previously noted in 2a and 4a (Figure 2). As before, these synthons involve both symmetry independent molecules (A and B). Synthon I is constituted with O-H‚‚‚O and C-H‚‚‚O hydrogen bonds, while II contains C-H‚‚‚O and C-H‚‚‚π bonds. It is noteworthy that the fusion of synthons I



Table 2. Hydrogen Bridges in Crystal Structures of the gem-Alkynols in This Studya alkynol 1a 1b

1c

1d

1e 2a

2b

2c 2d

2e 2f

3a

3b 4a

4b

4c 4d

hydrogen bridge

d/Å (H‚‚‚A)

D/Å (X‚‚‚A)

θ/deg ∠X-H‚‚‚A

O-H‚‚‚O C-H‚‚‚O C-H‚‚‚π O-H‚‚‚O C-H‚‚‚O O-H‚‚‚π C-H‚‚‚π O-H‚‚‚O C-H‚‚‚O O-H‚‚‚π C-H‚‚‚π O-H‚‚‚O O-H‚‚‚O C-H‚‚‚O O-H‚‚‚π C-H‚‚‚π O-H‚‚‚O C-H‚‚‚O O-H‚‚‚O C-H‚‚‚O O-H‚‚‚π C-H‚‚‚π O-H‚‚‚O C-H‚‚‚O O-H‚‚‚π C-H‚‚‚π O-H‚‚‚O C-H‚‚‚O O-H‚‚‚π O-H‚‚‚O C-H‚‚‚O O-H‚‚‚π C-H‚‚‚π O-H‚‚‚O O-H‚‚‚Cl O-H‚‚‚O C-H‚‚‚O O-H‚‚‚π C-H‚‚‚π O-H‚‚‚O O-H‚‚‚O C-H‚‚‚O O-H‚‚‚π C-H‚‚‚π O-H‚‚‚O C-H‚‚‚O O-H‚‚‚O C-H‚‚‚O O-H‚‚‚π C-H‚‚‚π O-H‚‚‚O O-H‚‚‚O C-H‚‚‚O C-H‚‚‚O O-H‚‚‚π C-H‚‚‚π O-H‚‚‚O O-H‚‚‚π C-H‚‚‚π O-H‚‚‚O C-H‚‚‚O

2.12 2.39 2.98 1.88 2.08 2.58 2.92 1.84 2.09 2.38 3.06 1.84 1.92 2.08 2.62 3.00 1.89 2.44 1.89 2.06 2.68 2.90 1.92 2.12 2.59 3.05 1.82 2.22 2.73 1.83 2.12 2.37 3.20 1.92 2.62 1.83 2.22 2.69 3.07 1.86 1.91 2.04 2.50 2.86 1.81 2.43 1.90 2.06 2.42 2.97 1.69 1.71 2.02 2.03 2.79 3.26 1.89 2.29 2.80 1.83 2.16

3.075(1) 3.305(1) 3.654 2.851(1) 3.153(1) 3.395 3.791 2.811(1) 3.173(1) 3.271 3.893 2.781(1) 2.882(1) 3.160(2) 3.442 3.886 2.809(2) 3.414(2) 2.836(2) 3.140(2) 3.486 3.805 2.860(2) 3.181(3) 3.391 3.948 2.788(1) 3.274(1) 3.508 2.797(1) 3.191(1) 3.255 4.044 2.864(2) 3.382(1) 2.801(2) 3.197(2) 3.469 3.976 2.813(2) 2.826(2) 3.085(2) 3.311 3.745 2.787(2) 3.446(1) 2.845(2) 3.120(3) 3.372 3.863 2.665(4) 2.659(4) 3.013(6) 3.095(6) 3.613 4.092 2.849(1) 3.170 3.681 2.738(2) 3.217(2)

162.1 141.2 127.6 166.4 168.2 158.2 155.1 169.5 171.2 171.9 150.4 159.5 162.5 178.9 159.1 154.5 155.7 147.3 162.7 169.2 149.5 156.5 159.8 167.5 162.1 156.5 166.3 164.4 172.3 169.6 170.4 170.8 152.3 160.9 133.9 169.8 148.8 169.4 146.9 161.4 152.3 160.8 169.7 159.8 170.2 156.1 158.8 162.5 162.3 157.7 169.8 161.6 172.9 165.6 161.8 149.2 163.4 170.6 160.8 151.9 165.2

Figure 2. Crystal structure of 1b. Note the cooperative network of strong and weak interactions in synthons I and II. A and B represent the two distinct molecules in the asymmetric unit.

Figure 3. Supramolecular synthon [(I)0.5(II)0.5] in 1c. Note the unsymmetrical nature of this synthon, denoted H in the figure.

Scheme 5. Representation of Hybrid [(I)0.5(II)0.5] as a Heterosynthon

a The prototype alkynols 1a, 2a, and 4a are also included here. These crystal structures were originally reported in ref 9g.

and II is accompanied by a characteristic cooperative chain of hydrogen bridges, O-H‚‚‚O-H‚‚‚CtC-H‚‚‚CtC-H‚‚‚OH‚‚‚, which form an infinite pattern. In principle, the packing of 2,3-dimethyl- trans-1,4-diethynyl1,4-dihydroxy-2,5-cyclohexadiene (1c) could follow that of 1b except that the molecule is unsymmetrical like 2a. Indeed, the packing in space group P21/c is generally similar (Figure 3), but there is a very interesting variation in the synthon structure.

A new synthon [(I)0.5(II)0.5], H, is observed, which is obtained by bisecting synthons I and II and joining the different halves (Scheme 5). Accordingly, we find that this hybrid is constituted


Banerjee et al.

Figure 4. Transformation of homosynthons I and II to the hybrid [(I)0.5(II)0.5]. Minimal molecular movement is required for this supramolecular transformation.

with one O-H‚‚‚O, two C-H‚‚‚O, and one C-H‚‚‚π interactions. Synthon [(I)0.5(II)0.5] is comparable thermodynamically with synthons I and II, containing as it does the same elaborate cooperative network of strong and weak hydrogen bonds, O-H‚‚‚O-H‚‚‚CtC-H‚‚‚CtC-H‚‚‚O-H‚‚‚ and the supramolecular transformation involved in going from I and II to [(I)0.5(II)0.5] is given in Figure 4. Suggestively, the symmetrical 1b gives the centrosymmetric synthons I and II, while the unsymmetrical 1c leads to the unsymmetrical hybrid. The hybrid [(I)0.5(II)0.5] has a close parallel in the heterosynthons that were first identified by Zaworotko in his studies of hydrogen-bonded molecular complexes.17 Scheme 5 shows that if synthons I and II are taken as homosynthons, then [(I)0.5(II)0.5] becomes the corresponding heterosynthon. 2,3,5,6-Tetramethyl-trans-1,4-diethynyl-1,4-dihydroxy-2,5cyclohexadiene (1d) is a symmetrical molecule and is an extension of 1b or 1c in which all the H-atoms in the cyclohexadiene ring are replaced by Me groups (Figure 5). The packing is similar to that of 1b with synthons I and II observed instead of hybrid [(I)0.5(II)0.5]. Curiously, for a symmetrical molecule that adopts a crystal structure with symmetrical synthons, the space group is noncentrosymmetric (Fdd2, Z′ ) 0.5 + 0.5 + 1 +1).

Encouraged by the fact that the synthon structure and packing arrangement are preserved in the BQ series so far, we considered next the dichloro and tetrachloro derivatives, 1e and 1f. The latter structure (I41/a) has been published by us previously and an O-H‚‚‚O hydrogen-bonded tetramer ring was noted.9f The importance of O-H‚‚‚O hydrogen bonding is rationalized by the fact that the O-H group is activated as a donor by the Cl atoms. 2,3,-Dichloro-trans-1,4-diethynyl-1,4-dihydroxy-2,5-cyclohexadiene (1e) (P21/c, Z′ ) 1) shares features of both the tetrachloro 1f and the methyl derivatives 1b-1d (Figure 6). It is like 1f in that the dominant interaction pattern is again the O-H‚‚‚O tetramer. It resembles the methyl derivatives in that (a distorted) synthon I is present. Therefore, the Cl/Me exchange rule does not operate in the BQ series. This suggests a chemical role for these substituents in the crystal packing; this is hardly surprising when interactions involving these groups are so intimately involved in the structural organization. Naphthoquinone (NQ)-Based Structures. We now move to the NQ-based compounds. In the prototype, 2a, the disposition of the fused benzo rings is such that the rings are situated on the same side of the hydrogen-bonded sheets (Scheme 3). These rings interdigitate with aromatic edge-to-face interactions to give a bilayer of molecules that closely pack. Once again, we decided


Figure 5. Crystal structure of 1d. Note the presence of synthons I and II as in 1b.


Figure 7. Crystal structure of 2b to show synthons I and II.

Figure 8. Crystal structure of 2c. Note how synthon I has changed its shape and is engaged in a ladder network with synthon III. Note the additional Cl‚‚‚Cl interaction.

Figure 6. Perspective views of 1e displaying (a) O-H‚‚‚O tetrameric synthon and (b) distorted synthon I.

to explore the packing behavior of methyl- and halogensubstituted derivatives. Compounds 2b-2f constitute the NQ group, and their crystal structures show the limits to which the prototype structures 2a and 4a may be conserved, and when and why this structural domain is exceeded. The packing of 2,3-dimethyl-trans-1,4-diethynyl-1,4-dihydronaphthalene-1,4-diol (2b) (P1h, Z′ ) 0.5 + 0.5) contains synthons I and II as seen previously in 2a and 4a (Figure 7). Because of a disorder between the methyl groups and the benzo ring, the structure is almost identical to that of the AQ derivative

4a, and the cell edges (8.4194, 8.7817, 10.3302 Å) are nearly the same. Alkynol 2b is closer to 4a than is 1b (which has a similar mimicry but is not disordered). The interdigitation of rings is similar to 4a. A comparison of 2b with alkynol 2c, 2,3-dichloro-trans-1,4diethynyl-1,4-dihydronaphthalene-1,4-diol, (P21/c, Z′ ) 1) is more interesting (Figure 8). While synthon I (with its O-H‚‚‚O bonds) is preserved, II has disappeared and is replaced by a new C-H‚‚‚O dimer synthon III (Scheme 3) and an additional O-H‚‚‚π and type-II Cl‚‚‚Cl contact.18 In contrast to the BQ series wherein replacement of Me groups by Cl groups changed the structure completely (1c f 1e, 1d f 1f), Cl/Me exchange in the NQ series (2b f 2c) perturbs only some elements of the crystal packing. Still, chloro substitution enhances the significance of O-H‚‚‚O hydrogen bonding as in the BQ series. 6,7-Dimethyl-trans-1,4-diethynyl-1,4-dihydronaphthalene-1,4diol (2d) (P21/c, Z′ ) 1) may be compared with the unsubstituted NQ compound 2a and the dimethyl BQ derivative 1c, both of which are unsymmetrical. The packing is similar to 1c in that the hybrid synthon [(I)0.5(II)0.5] is present (Figure 9). In alkynol 2e, 2,3-dichloro-6,7-dimethyl- trans-1,4-diethynyl1,4-dihydronaphthalene-1,4-diol (P21/c, Z′ ) 1), the effect of two Cl groups is sufficient to ensure total disruption of the NQ prototype structure. The structure (Figure 10) is completely different with a new tetramer loop synthon consisting of


Banerjee et al.

Figure 9. Crystal structure of 2d. Note the recurrence of hybrid synthon [(I)0.5(II)0.5]. Figure 11. Crystal structure of the dibromo NQ derivative 2f. Br atoms (pink) here play a space-filling role, and the crystal structure is same as the nonbrominated 2d.

Figure 10. Tetramer loop synthon in 2e consisting of O-H‚‚‚O, C-H‚ ‚‚O, and C-H‚‚‚π interactions. Note that the structure is completely different from 2a through 2d.

O-H‚‚‚O, C-H‚‚‚O, and C-H‚‚‚π bridges. The interdigitation of aromatic residues has also vanished. We note that dichloro substitution in going from 2a to 2c is insufficient to perturb synthon I; only the more feeble synthon II is affected. However, a similar dichloro substitution on 2d to give 2e has exceeded the structural limits of the NQ family. Curiously, the corresponding dibromo substitution to give alkynol 2f, 2,3-dibromo-6,7-dimethyl- trans-1,4-diethynyl-1,4dihydronaphthalene-1,4-diol, (P212121, Z′ ) 1) conserves the layer interdigitated structure of 2d along with the hybrid [(I)0.5(II)0.5]. We conclude that the nature of the halogen atom (Br, Cl) affects the donor and acceptor properties of the hydrogenbonding functionalities in these molecules in very subtle ways. Because the systems are structurally very fragile, the slightly different effects of Br and Cl are amplified in the final outcome. Put another way, the Br groups are chemically not as aggressive as Cl and are unable to change the 2d packing; they revert to a space filling role (Figure 11). Anthraquinone (AQ)-Based Structures. Two sets of compounds were studied, based on 1,4-anthraquinone (3a and 3b) and on 9,10-anthraquinone (4a, 4b, 4c, 4d). Alkynol 3a, trans1,4-diethynyl-1,4-dihydroanthracene-1,4-diol, is the benzo extension of the NQ prototype 2a, and it is pleasing to note that it has the same packing (P21/c, Z′ ) 1 + 1) with a corresponding increase in one of the axial lengths (3a, 10.8363, 27.5202, 10.3894; 2a, 10.8247, 22.6384, 10.4783). Indeed, this naphtha/ anthra homology has been noted since the earliest days of crystallography.19 In 3a, the alternating centrosymmetric synthons I and II characterize the packing along with aromatic edge-to-face interdigitation (Scheme 3, Figure 12). Similarly,

Figure 12. Crystal structure of alkynol 3a. Note synthons I and II.

2,3-dichloro-trans-1,4-diethynyl-1,4-dihydroanthracene-1,4-diol (3b) (P212121 , Z′ ) 1) is the benzo extension of 2c, and its crystal structure is also similar to that of 2c (P21/c) with the expected axial length relationships (3b, 6.7139, 7.4777, 29.8603; 2c, 7.4303, 23.2596, 7.5476). Such homology, across different sets of structures, is impressive and shows that modularity can be found even in the alkynol family, which is well-known for interaction interference and the resulting synthon fragility (Figure 13). The modularity shown in most of the NQ and 1,4-AQ derivatives begins to break down in the 9,10-AQ derivatives. The unsubstituted 4a has been discussed previously, and it is related to the NQ derivatives. Monomethyl substitution gives 4b, 2-methyl-trans-9,10-diethynyl-9,10-dihydroanthracene-9,10diol, which has a related structure (P21/c, Z′ ) 1) with synthons I and II (Figure 14). However, while synthon I is undistorted, the C-H‚‚‚π bridges in II are distorted (d ) 3.26), and this is a prelude to the process of synthon disruption, which is complete in 4c and 4d (Figure 15), although some vestiges of a cooperative network of hydrogen bonds is seen in the form of a finite O-H‚‚‚O-H‚‚‚CtC-H‚‚‚CtC-H‚‚‚π chain.



Figure 13. Crystal structure of alkynol 3b. Note the similarity to 2c.

Figure 15. Packing diagram of 4c (left) and 4d (right). Synthons I and II are absent.

Figure 14. Crystal structure of 4b. Distortion of synthon II is because of the Me group.

Discussion Robustness or lack of structural interference is a sought after goal in synthon-based crystal design. In the gem-alkynol family, there are several structural options based on different types of hydrogen bonds. Identifying a robust supramolecular synthon and proving its repetition is in itself a challenging task in a system as fragile as this: it will be noted that there is no repetition of a major hydrogen-bonded supramolecular synthon in the 144 gem-alkynols, the structures of which have been published prior to our work. In this context, the crystal structures of alkynols 1a-1f, 2a-2f, 3a, 3b, 4a, and 4b prove the robustness and repetitive character of synthons I, II, and their near equivalent [(I)0.5(II)0.5]. The following observations are noteworthy in this series: (i) The main structure type is obtained in which the hydrogen bonds occur in a planar arrangement, and the aromatic residues are perpendicular to this plane. (ii) This hydrogen-bond arrangement manifests itself as a combination of synthons I and II, or alternatively their hybrid [(I)0.5(II)0.5]. (iii) In both these cases, an infinite chain O-H‚‚‚O-H‚‚‚CtC-H‚‚‚CtC-H‚‚‚OH‚‚‚ is the basis of the structure and is probably the kinetically relevant synthon. (iv) The aromatic residues emerge from one or both sides of the hydrogen-bonded layer and interdigitate with similar residues from adjacent layers. (v) Addition of a

fused benzo residue, say, 2a f 3a or 2c f 3b, does not perturb the structure because it is a manifestation of naphtha/anthra homology. (vi) The addition of one or two Me groups is akin to benzo annelation and explains the similarities between pairs of structures such as 1b and 4a, 1d and 4a, or 2b and 4a. (vii) Cl substitution results in more deep-seated chemical changes, and pairs of compounds such as 1c and 1e, 1d and 1f, or 2b and 2c are not isostructural. (viii) A rare case of Br/H mimicry is seen in the pair of compounds 2d and 2f. Bromine is able to fulfill a space-filling role that chlorine cannot. (ix) At a subtle level, the preference for the formation of synthons I and II versus the hybrid [(I)0.5(II)0.5] does not seem to be directly related to molecular symmetry. However, we note that no centrosymmetric molecule takes the hybrid synthon. Each intermolecular force will have some influence on the result of the crystallization process, but it is evident that some intermolecular interactions will be more significant than the others in the final crystal. The probability that a certain synthon will emerge in the end could be taken as a measure of the yield of a supramolecular reaction.20 That synthon I, II, or synthon [(I)0.5(II)0.5] emerges as a robust supramolecular synthon in the gem-alkynol crystal structures is in itself a significant result because such robustness has not been previously observed in this family. However, the question still remains as to why synthon I, II, or synthon [(I)0.5(II)0.5] are formed, and not something else. Synthons I, II, and [(I)0.5(II)0.5] appear to be very similar or indeed almost identical when they are considered in terms of the individual interactions. The major structural element in both cases is the infinite cooperative network of strong and weak hydrogen bonds O-H‚‚‚O-H‚‚‚CtCH‚‚‚CtC-H‚‚‚O-H‚‚‚ running in two directions. This infinite chain is the key to the structural similarity in this family. Finally, we need to comment about polymorphism or the lack of it in this family. Polymorphism is a rare phenomenon in the gem-alkynols, and we have searched the crystallization batches adequately to be able to make this assertion. Why this is the case, and whether polymorphism may eventually be found in this family of structures, we cannot say. In principle, 1b and 1c should be good candidates for polymorphic behavior, as they are kinetically and thermodynamically very similar (hydrogenbond energy and packing coefficient for 1b is -3.65 kcal/mol and 0.68 and for 1c it is -3.59 kcal/mol and 0.66). But no


Banerjee et al.

polymorphs were found for these compounds. It is possible that the infinite chain referred to above is both kinetically and thermodynamically preferred, leading thereby to a single stable crystal form. This behavior is reminiscent of the aminophenols wherein a similar role has been ascribed to an infinite (O-H‚‚‚N-H‚‚‚)n chain.3g Conclusion The value of a supramolecular synthon as an indicator of crystal packing arises from its frequency of occurrence. However, another indicator that should be used while assessing the utility of a synthon is its size. A synthon symbolizes a carryover of structural information from a molecule to a crystal and between crystal structures: as its size increases, so does its information content. So larger synthons are potentially more informative than smaller ones (I, II, and [(I)0.5(II)0.5] as opposed to, say, the O-H‚‚‚O tetramer). But as synthon size increases its occurrence becomes less frequent. The real challenge in crystal engineering is to find a big enough synthon that occurs often enough. There must lie an optimal region between the extremes of small size and numerous occurrences, and large size and infrequent occurrences. It is in this domain that the synthons are the most useful, and where the visualization of crystal structures in terms of supramolecular synthons and the comparison of crystal structures is most effectively accomplished. We believe that we have identified such a domain in this family of gem-alkynols, a group of compounds well-known for their structural inconsistency.

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Acknowledgment. Continuing support over the years from the DST and the CSIR to G.R.D.’s research programs is acknowledged. R.B. thanks the UGC for the award of a Senior Research Fellowship. J.A.K.H. thanks the EPSRC for a Senior Research Fellowship, R.M. acknowledges the receipt of an Overseas Research Scholarship. Supporting Information Available: ORTEP diagrams (50% probabilitiy), IR, NMR, and melting point data for the gem-alkynols in this study. This material is available free of charge via the Internet at http:// pubs.acs.org.

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CG050598S

Synthon Robustness and Solid-State Architecture in Substituted gem

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