O-H ··· N Heterosynthon: A Robust Supramolecular Unit For Crystal Engineering Mujeeb Khan, Volker Enkelmann, and Gunther Brunklaus* Max-Planck-Institut fu ¨r Polymerforschung, Postfach 3148, D-55021 Mainz, Germany ReceiVed NoVember 11, 2008; ReVised Manuscript ReceiVed February 19, 2009 ABSTRACT: To explore the robust nature of template resorcinols in organic solid-state reactions, a series of mono- and dipyridines were cocrystallized with different substituted resorcinols. The organizational consequences of hydrogen-bonds in the hydroxyl ··· pyridine heterosynthon in the presence of competitive hydrogen-bonding functional groups are elucidated. C-O bond flexibility, steric hindrance, and formation of undesired intramolecular hydrogen bonds have strongly affected the ability of the template for a parallel alignment of olefins. Finally, structural changes that occurred at a molecular level during [2 + 2] photodimerization of the complex of 1,4- bis[(E)-2-(4-pyridyl)ethenyl]-2-fluorobenzene (bpef) with 2,4-dihydroxy-benzaldehyde were studied in detail by performing a rather rare single-crystal-to-single-crystal photoirradiation. 1. Introduction Crystal engineering comprises an understanding of intermo- lecular interactions that govern crystal packing, thus allowing the design of solids with tailored physical and chemical properties. 1-5 Indeed, an organic crystal can be regarded as an ultimate supermolecule (that is not only assembled via molecular recognition but also stabilized by rather weak, noncovalent interactions). 6,7 In recent work, great efforts have been put onto selective control or modification of reactant compounds yielding rationally designed crystal lattices. 8-10 A prominent example is given by the [2 + 2] photodimerization that has provided a large variety of compounds. 11-15 To steer olefins to react, researchers employed attractive intermolecular forces such as halogen-halogen 16,17 interactions as well as others, yielding molecules that may be difficult to achieve in solutions, such as donor-acceptor interactions 18 and hydrogen bonds. 19 Recently, both the strength and directionality of hydrogen bonds of resorcinol have been exploited to enforce topochemical alignment of olefins in the solid state to allow for a selective [2 + 2] photoreaction. 20 A thorough understanding of supramo- lecular synthons (resorcinol-pyridine, O-H ··· N) such as their preferred geometries, competitive hydrogen bonds, strength, and recognition pattern is a prerequisite for rational design and supramolecular synthesis of novel cocrystals. 21-23 Two distinct categories of synthons are known: so-called supramolecular homosynthons, composed of self-complementary functional groups, e.g., carboxylic acid dimer, 24 and supramolecular heterosynthons, 23c,24 which are composed of different but complementary functional groups. The latter category includes hydroxyl ··· pyridine, 20a hydroxyl ··· amine, 25 acid ··· pyridine, 26 and acid ··· amide 27 supramolecular synthons. Studies suggest that some supramolecular heterosynthons are strongly favored over related supramolecular homosynthons. 23-27 It has already been established that resorcinol, when cocrystallized with pyridine, largely forms hydroxyl ··· pyridine supramolecular heterosynthons. 20a In some cases, however, the respective heterosynthons do not have the favorable orientation (ring formation, with parallel arrangement of double bonds separated at 4 Å) that is required for topochemical reactions. 28 In this contribution, we discuss organizational consequences of hydrogen bonds within hydroxyl ··· pyridine heterosynthons in the presence of competitive hydrogen-bonding functional groups. To explore the robustness of such hydroxyl-pyridyl heterosynthons, we cocrystallized differently substituted resor- cinols with mono- and dipyridines and determined their crystal structures. One of the supramolecular heterosynthon sustained in a favorable orientation, as shown in Scheme 1, was picked for single-crystal-to-single-crystal photodimerization, thus yield- ing detailed insights into intermediate states of the reaction at an atomic level. Different complementary techniques such as atomic force microscopy (AFM), 29 vibrational spectroscopy, 30 X-ray diffraction 31 and solid-state NMR 32 have been success- fully applied to reveal the respective reaction mechanism, but each method has certain limitations. Because AFM is primarily sensitive to surfaces, no direct structural information can be obtained; although vibrational spectroscopy (infrared and Ra- man) can be indeed applied to monitor the topochemical nature of organic solid-state reactions, no conformational details of intermediate states can be obtained. In principle, X-ray crystallography is the method of choice to study photodimerization reactions within single crystals. Upon broadband irradiation, however, crystals tend to disintegrate into microcrystalline particles as the dimerization proceeds, rendering X-ray analysis of resulting products rather difficult. This can be overcome 31a,33 when photoactive crystals are irradiated by light for which they have low absorptivity so that the intensity * Corresponding author. E-mail: brunklaus@mpip-mainz.mpg.de. Scheme 1. Reaction Scheme for the Single-Crystal-to-Single-Crystal (SCSC) [2 + 2] Photo-Dimerization of 2,4-Dihydroxy-benzaldehyde and 1,4-Bis[(E)-2-(4-pyridyl)-ethenyl]-2-fluorobenzene (bpef) CRYSTAL GROWTH & DESIGN 2009 VOL. 9, NO. 5 2354–2362 10.1021/cg801249b CCC: $40.75  2009 American Chemical Society Published on Web 03/23/2009 Downloaded by MPI MASTER on July 8, 2009 Published on March 23, 2009 on http://pubs.acs.org | doi: 10.1021/cg801249b