Crystallographic Studies of Supramolecular Synthons in Amine

CRYSTAL GROWTH & DESIGN

Crystallographic Studies of Supramolecular Synthons in Amine Solvates of trans-1,5-Dichloro-9,10-diethynyl-9,10dihydroanthracene-9,10-diol

2006 VOL. 6, NO. 11 2507-2516

Raju Mondal,† Judith A. K. Howard,*,† Rahul Banerjee,‡ and Gautam R. Desiraju*,‡ Department of Chemistry, UniVersity of Durham, South Road, Durham DH1 3LE, United Kingdom, and School of Chemistry, UniVersity of Hyderabad, Hyderabad 500 046, India ReceiVed May 2, 2006; ReVised Manuscript ReceiVed August 22, 2006

ABSTRACT: Solvent inclusion in organic crystals is quite uncommon, as it is observed in only 15% of cases. Solvation could be imagined to result from the interruption of the “normal” crystallization process because of the preferential formation of directional hydrogen bonds between the included solvent and the organic component. However, it is surprising to note that only a limited number of studies have been performed using amine based solvents, yet amines, next to hydroxyl groups, are the most extensively studied functional group in the field of crystal engineering. In this work, we attempt to determine a correlation between molecular functionality and crystal structures among the 15 different pseudopolymorphs of 1,5-dichloro-trans-9,10-diethynyl-9,10-dihydroanthracene-9,10-diol (DDDA). This work aims to gain an insight into the interaction hierarchy between four molecular functionalities of a solvent molecule, namely, a hydroxy group (benzylic), an ethynyl group, an aromatic chlorine atom, and an amino group and the DDDA molecule. Introduction The field of inclusion complexes,1 clathrates,2 pseudopolymorphs,3 and host-guest systems4 has grown dramatically in recent years because of the great potential of these materials for a variety of fundamental and practical applications. Molecular recognition lies at the heart of inclusion compound chemistry; indeed, during the past decade or so, the major part of crystal engineering studies associated with topics such as pseudopolymorphism involve designing host molecules with different shapes, steric bulk, and functionalities.5 Weber suggested that a successful host molecule would be bulky, rigid, and preferably contain host-guest interaction-specific functional groups.6 Undisputedly, most host molecules were discovered accidentally rather than by a premeditated design.7 Solvent inclusion in organic crystals is quite uncommon, as it is observed in only 15% of cases. A detailed examination of the Cambridge Structural Database (CSD) reveals that only 20 commons solvents are incorporated in more than 50 cases of solvation. The reluctance/tendency of solvent molecules to be included in a crystal was rationalized by a multipoint recognition model put forward by Nangia and Desiraju.8 On the basis of this model, solvation occurs only when the enthalpic gain from the solute-solvent multipoint interaction outweighs the combined effects of the entropy gain by solvent extrusion during the nucleation process and the enthalpic gain from the formation of robust supramolecular synthons by the solute molecules. In other words, solvation could be imagined as a resulting from the interruption of the “normal” crystallization process9 by the preferential formation of directional hydrogen bonds. Theoretically, this means that compounds that pack in the crystalline state without forming the optimum number of hydrogen bonds are more likely to form solvates. The overwhelming majority of O-containing solvents further shows the significance of the multipoint recognition model. However, it is surprising to note that not a single amine solvent * Corresponding author. E-mail: [email protected]. (J.A.K.H.); [email protected] (G.R.D.). † University of Durham. ‡ University of Hyderabad.

secures a place in the list of solvents included in crystal structures, although amines, next to hydroxyl groups, are the most extensively studied functional group in the field of crystal engineering. The volatile nature of the amines solvents and the subsequent unstable nature of the solvates could be attributed as a major reason for this. The determination of a direct correlation between the molecular functionality of a given compound and its crystal structure is a major challenge in crystal engineering. It becomes even more challenging for solvates, wherein the all-important location and orientation of functionalities belonging to the incorporated guest molecule (solvent) are not precise but unpredictable. In this work we attempt to draw a correlation between molecular functionality and the crystal structures of the 15 different pseudopolymorphs of 1,5-dichloro-trans-9,10diethynyl-9,10-dihydroanthracene-9,10-diol (DDDA) (Scheme 1). From the work presented herein, we aim to gain an insight into the interaction hierarchy between four molecular functionalities on the solvent molecule, namely, a hydroxy group (benzylic), an ethynyl group, an aromatic chlorine atom, an amino group, and the DDDA solute, by systematically investigating the structural interference and the steric variance of the incorporated solvent molecules. Experimental Section General. Solvents were purified by standard methods and dried if necessary. Reagents used were of commercial quality. DDDA was characterized by NMR and IR spectroscopic techniques. The 1H NMR spectra were recorded at 200 MHz on a Bruker ACF instrument. IR spectra were recorded on a Jasco 5300 spectrometer. All melting points were measured in a Fischer-Jones melting point instrument. Synthesis. DDDA was synthesized from 1,5-dichloro-9,10-anthraquinone, using a two-step procedure. All operations were carried out in a dry nitrogen atmosphere using a standard syringe-septum technique. (i) A solution of trimethylsilylacetylene (4.4 mmol) in THF (15 mL) was mixed with n-butyllithium (4.2 mmol) at 195 K. After stirring for 15 min, we added a solution of 1,5-dichloro-9,10anthraquinone dropwise and continued stirring for 30 min at 195 K and then for a further 1 h at room temperature. Brine was added to the reaction mixture, and the products were extracted with diethyl ether. The organic phase was dried over magnesium sulfate and filtered, and

10.1021/cg060258m CCC: $33.50 © 2006 American Chemical Society Published on Web 10/18/2006

2508 Crystal Growth & Design, Vol. 6, No. 11, 2006 Scheme 1.

Mondal et al. Amine Pseudopolymorphs of DDDA

the ether was then removed. (ii) The solid product from step (i) was dissolved in methanol; 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 ethyl acetate. The product was dried over magnesium sulfate and the solvent was removed. Crystals were obtained by purification of the crude material (column chromatography 30% ethyl acetate and hexane) followed by recrystallization. Data for 1,5-Dichloro-trans-9,10-diethynyl-9,10-dihydroanthracene9,10-diol (DDDA). Yield: 60%. 1H NMR (200 MHz CDCl3): δ 8.10 (dd, J 8, 3 Hz, peri 2H), 7.51 (m, 4H), 4.46 (s, 2H) 2.70 (s, 2H); IR (cm-1): 3312, 3288, 3177, 3001, 2881, 2116, 1973, 1811, 1595, 1562, 1456, 1300, 1205, 1039, 679, 515. Mp: 553 °C (dec). Crystallization. All crystallization experiments were carried out under almost identical conditions. The crude material was dissolved in the respective solvent system, followed by the slow evaporation of the solvent at room temperature. However, most of the amines used in these studies are either volatile or have low boiling points, and the corresponding solvates are mostly unstable. Some precautions were undertaken while mounting these crystals. When removed from the mother liquor, some of the crystals rapidly lost solvent, resulting in polycrystalline or opaque material. To overcome this problem, once the crystals were taken out of the sample vial in which they were grown, they were placed immediately into inert oil with a high surface tension. The crystals, covered in this oil, were subsequently mounted on a diffractometer goniometer and flash-cooled to 120 K by being placed directly under a cold N2 gas stream. X-ray Crystallography. X-ray diffraction intensities for DDDA and its pseudopolymorphs were collected at 120 K (Oxford Cryosystems N2 cooling system) on a Bruker SMART CCD diffractometer (Bruker Systems Inc., 1999a) using Mo KR X-radiation. Data were processed using the Bruker SAINT software package (Bruker Systems Inc., 1999b) and the structure solution and refinement procedure were performed using SHELX97 (Sheldrick, 1997).10 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 the difference Fourier maps for all 15 structures and refined freely (including Uiso). Crystal and structure refinement data 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.

Deposition numbers are given in the 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 The crystal structure of DDDA is quite unusual, as it is part of only 1% of molecules in the CSD that contain an inversion center (i) as the only molecular symmetry element, but does not occupy this special position in the crystal.9a The less-thanoptimal formation of hydrogen bonds in the packing was compensated by a tetrachloro supramolecular synthon lying on the inversion center, which enables the largest number of atoms to aggregate with the shortest possible separations. The reason for this apparently incomprehensible crystal structure was attributed to the steric hindrance resulting from the close juxtaposition of the two chlorine atoms and the gem-alkynol groups, and the subsequent formation of intramolecular O-H‚ ‚‚Cl-C hydrogen bridges.11 In effect, DDDA, having failed to satisfy the hydrogen bond potential (i.e., not all the potential hydrogen bond donor/acceptor sites are utilized), emerged as a possible host molecule for solvate formation. Five solvates of DDDA have already been reported elsewhere,9a wherein the DDDA molecules occupy an i site in the crystal structures and form strong linear O-H‚‚‚O hydrogen bonds with the solvent molecules that are present. For this work, instead of choosing any common solvents, we specifically selected amines for two reasons. First, even though 15% of organic crystals in the CSD are pseudopolymorphs,12 only a very few of them contain amine as solvent. Organic bases are well-known to promote solvation, and amines should do the same. However, even a cursory inspection of the CSD shows that the occurrences of amine solvates are random and that they are either disordered or unstable, and most importantly, only a few of them

Supramolecular Synthons in Amine Solvates of DDDA

Crystal Growth & Design, Vol. 6, No. 11, 2006 2509

Table 1. Crystallographic Data and Structure Refinement Parameters for the 1° Amine Solvates (1-7)a empirical formula fw cryst syst space group a (Å) b (Å) c (Å) R (deg) β (deg) γ (deg) Z′ V (Å3) Dcalcd (g cm-3) µ (mm-1) 2θ (deg) range h range k range l no. of reflns collected no. of unique reflns no. of obsd reflns R1 [I > 2σ(I)] wR2 (all) GOF cryst size (mm3) largest diff. peak and hole (e Å-3) CCDC no. a

1

2

3

6

7

C14H16ClNO 249.73 monoclinic P21/c 10.8061(3) 11.4830(3) 10.0223(2) 90 93.518(1) 90 0.5 1241.29(5) 1.336 0.290 5.18 to 55 -14 to14 -14 to 14 -13 to 13 12 440 2843 2436 0.0316 0.0839 1.042 0.42 × 0.16 × 0.08 0.423 and 0.251 605423

C30H36Cl2N2O2 527.51 monoclinic P21/n 9.6765(19) 11.311(2) 26.025(5) 90 92.57(3) 90 1.0 2845.6(10) 1.231 0.257 3.92 to 55 -12 to 12 -14 to 14 -32 to 33 22 256 6545 5000 0.0386 0.0988 1.025 0.42 × 0.42 × 0.28 0.362 and 0.251 605421

C16H20ClNO 277.78 monoclinic P21/c 13.8867(3) 11.3975(3) 9.4693(2) 90 101.280(1) 90 0.5 1469.79(6) 1.255 0.252 3.0 to 55 -18 to 18 -14 to 14 -12 to 12 20 502 3385 2767 0.0444 0.1224 1.037 0.4 × 0.04 × 0.02 0.408 and -0.426 605420

C17H24ClNO 293.82 monoclinic P21/c 14.877(3) 8.7544(18) 13.476(3) 90 113.52(3) 90 0.5 1609.2(6) 1.213 0.234 5.52 to 55 -19 to 19 -11 to 11 -17 to 17 24 128 3692 2798 0.0596 0.1506 1.121 0.22 × 0.18 × 0.02 0.512 and 0.438 605431

C33H29Cl3N2O3 607.93 triclinic P1h 9.787(2) 11.727(2) 13.902(3) 79.01(3) 82.36(3) 67.48(3) 1.5 1443.6(5) 1.399 0.356 3.8 to 55 -12 to 12 -15 to 15 -18 to 18 17 143 6632 5677 0.0375 0.1015 1.047 0.26 × 0.20 × 0.12 0.532 and-0.276 605422

For details of compounds 4 and 5, see ref 3a.

Scheme 2.

Supramolecular Synthons Observed in Selected DDDA:Amine Pseudopolymorphs

incorporate the free amine. To the best of our knowledge, we are the first to report a complete series of amine solvates. Second, as a part of our ongoing interest in crystal engineering, we have considered the hydrogen bond patterns formed by three different functional groups, namely, hydroxyl, amine, and alkyne groups, in two different sets of crystals and molecular complexes that contain two of these different functional groups: aminehydroxyl (supraminol)13 and ethynyl-hydroxyl (gem-alkynol).14 Notwithstanding, the structural interplay among these three functional groups has not been studied so far.

It was observed during earlier supraminol studies that the utilization of all possible sites for hydrogen bond formation and the resulting characteristic β-As sheet packing seldom occurs when the C-N and C-O vectors are not parallel. Instead, crystal structures with different supramolecular synthons such as the square synthon or an infinite chain pattern appear (Scheme 2). Wherein one of the two donor amine hydrogen atoms either remain inactive or form relatively weak N-H‚‚‚π interactions; hence, in this study, we used amines that differ in the number of donor protons available for forming intermolecular interac-

2510 Crystal Growth & Design, Vol. 6, No. 11, 2006

Figure 1. Crystal packing of 1, showing synthon I composed with cooperative (a) N‚‚‚H-O, (b) O‚‚‚H-N, (c) N‚‚‚H-O, and (d) N-H‚‚‚π interactions.

tions. From this study, we intend to gain a deeper understanding of the importance of the number of donor amine hydrogen atom(s) toward synthon selection and the overall packing. In this paper, we have subdivided the solvates into three groups, namely, primary, secondary, and tertiary amines. Primary Amines. Three different types of primary amines were used in this study, cyclic, acyclic, and cyclic diamines. The steric bulk of the cyclic amines was gradually increased by using cyclopentylamine (1), cyclohexylamine (2), cycloheptylamine (3), and cyclooctylamine (4, 5). Octylamine (6) was used as an acyclic amine and 1,2-Cyclohexyl diamine (7). These different types of amine were used to study the effect of interaction interferences on the crystal packing. (Cyclopentylamine)2. DDDA (1). The asymmetric unit of 1 contains a half molecule of DDDA, which lies on an inversion center, and one full molecule of cyclopentylamine. The solvate crystallizes in the centrosymmetric space group P21/c. Like in other dipolar aprotic solvates, the solute DDDA forms strong directional hydrogen bonds. More interestingly, characteristics of both the supraminol and gem-alkynol structures are prominent in the 1:2 solute-solvent modules of 1. An infinite cooperative array of O-H‚‚‚N (1.87 Å, 177.9°) and N-H‚‚‚O (2.38 Å, 146.3°) hydrogen bonds dominates the interaction pattern. The other amine hydrogen atom is directed toward the ethynyl groups of the DDDA molecules and forms an N-H‚‚‚π (2.84 Å, 168.9°) interaction, creating the supramolecular synthon I (Figure 1), whereas the ethynyl hydrogen atom forms a C-H‚‚‚Cl-C (3.11 Å, 169.5°) interaction.15 Such an infinite cooperative array accompanied by a N-H‚‚‚π interaction is one of three of the most frequently observed structural motifs, in addition to the β-As sheet and the centrosymmetric square motif, for supraminols.13a The packing is reminiscent of other gemalkynol molecules, except that the amine group replaces the hydroxyl group; because of the unavailability of an additional ethynyl group, a C-H‚‚‚Cl-C bond rather than a C-H ‚‚‚π or C-H‚‚‚O bond is formed, decreasing the probability that supramolecular synthon V and VI, which are usually observed in the gem-alkynol family, will be seen in the crystal structure of 1. (Cyclohexylamine)2. DDDA (2). The crystal packing of 2 is almost analogous to that of 1. Compound 2 crystallizes in the monoclinic space group P21/n. Again, a 1:2 solute-solvent module is obtained that displays an infinite cooperative arrangement similar to that of synthon I. Although the topology is the same as synthon I, the larger steric requirement of the six-membered ring does influence the crystal packing. The almost perpendicular alignment of the cyclohexyl ring with

Mondal et al.

Figure 2. Crystal packing of 2 showing synthon I. Notice how the orientation of the cyclohexyl rings prevents the ethynyl hydrogen atoms from taking part in hydrogen bond formation.

Figure 3. Crystal packing of 3 showing synthon I. Note that ring hydrogen atoms of the cycloheptylamine molecules are not shown for clarity.

respect to DDDA makes the ethynyl hydrogen atom too far away from any acceptor atom to form a hydrogen bond, and it remains free. As if to compensate for this, both O-H‚‚‚N (1.81 Å, 177.2°) and N-H‚‚‚O (2.21 Å, 163.5°) bonds are shorter in 2 than in 1, whereas the N-H‚‚‚π (2.83 Å, 168.8°) distance is comparable (Figure 2). (Cycloheptylamine)2. DDDA (3). Even with the larger ring group like cycloheptyl, the crystal packing of 3 closely resembles that of 1 and 2, with the DDDA molecule sitting on an inversion center in the monoclinic space group P21/c. An infinite cooperative arrangement akin to synthon I (O-H‚‚‚N, 1.83 Å, 172°; N-H‚‚‚O, 2.25 Å, 175°, N-H‚‚‚π 3.05 Å, 169.2°) is apparent in the 1:2 solute-solvent module. There are hardly any noticeable differences in the crystal packing for compounds 3 and 2. Again, the almost perpendicular orientation of the cycloheptyl ring ruled out any possibility of a hydrogen bond being formed with the ethynyl hydrogen atom (Figure 3). (Cyclooctylamine)2. DDDA (4); (Cyclooctylamine). DDDA (5). The Crystal structures of 4 and 5 represent an unusual occurrence of conformational pseudopolymorphism.3 In an unprecedented occurrence of two different conformations of the cyclooctylamine, these pseudopolymorphs form two distinct 1:2 (4) and 1:1 (5) solvates, respectively (Figure 4). The crystal structure of 4 is directly analogous to those of the other cyclic amines discussed above and crystallizes in the monoclinic space group P21/c. There is one-half of a DDDA molecule and



Figure 4. Two different conformations of the cyclooctylamines in 4 (light brown) and 5 (light gray). Hydrogen atoms have been removed for clarity.

Figure 6. Crystal packing of 5 showing synthon IV. Notice the orientation of the two ethynyl groups (separated by 4.59 Å) that show close similarity to synthon V.

Figure 5. Crystal packing of 4 showing synthon I.

one cycloctylamine molecule in the asymmetric unit. As expected, synthon I (O-H‚‚‚N, 1.85 Å, 171°; N-H‚‚‚O, 2.38 Å, 173°, N-H‚‚‚π, 2.85 Å, 171.8°) appears to be the major interaction pattern (Figure 5) in 4. It is imperative to note here that the occurrence of two energetically different conformations of a conformationally flexible solvent molecule being trapped in the crystal lattice of the same solute molecule is extremely rare. The crystal structure of 5 shows an unusual packing behavior with respect to the other solvates. The asymmetric unit of 5 (triclinic, P1h) comprises two-half molecules of DDDA sitting on distinct inversion centers and one cyclooctylamine molecule. As a result, the interaction hierarchies for the two DDDA molecules are noticeably different. Interestingly, whereas one of the gem-alkynol functionalities forms a supramolecular synthon IV (O-H‚‚‚O, 1.92 Å, 175°; C-H‚‚‚O, 2.28 Å, 161°) that is the hallmark of gem-alkynol family,14 the hydroxy group of the second forms a strong O-H‚‚‚N (1.92 Å, 175°) bond with the amine and restricts the two ethynyl groups from forming the supramolecular synthon V. However, the orientation of the ethynyl groups is closely reminiscent to the cooperative synthons IV and V, but in 5, a strong O-H‚‚‚N bond with the solvent molecules outweighs the weakest C-H‚‚‚π bond observed in the supramolecular synthon V, and the supramolecular arrangement is more akin to synthon IV. The sudden appearance of the supramolecular synthon IV in 5 once again proves the difficulty in performing a systematic study of these groups that are subject to solvent-interaction interference. The steric demand of the cyclic octyl rings in the two different conformations turns out to be the major reason for these packing

differences. For 4, the reduced steric hindrance surrounding the solvent, with respect to 5, makes it possible for the two hydrogen atoms of the amines to take part in hydrogen bonding, resulting in synthon I. In 5, because of greater steric demand of the octyl ring conformation, the amine hydrogen atoms could only form a very weak N-H‚‚‚π bond, and the structure is further stabilized by the formation of the robust supramolecular synthon IV (Figure 6). Again, two relatively weak diminishing N-H‚‚‚π (2.96 and 3.15 Å) interactions could be rationalized as being one step closer to the crystallization point for unsolvated DDDA, in which solvent extrusion from the bulk has occurred. (1,1,3,3-Tetramethyl-butylamine)2. DDDA (6). Having noticed that steric hindrance could force the DDDA molecules to adopt a normal gem-alkynol-like crystal packing, the question then arose of whether the crystal packing with synthon IV or V could be reproduced by increasing the steric bulk of the amine. Compound 6 crystallized in the monoclinic space group P21/c,with one-half molecule of DDDA and one amine molecule in the asymmetric unit. The crystal packing of 6 is different from the other cyclic amines we have reported so far, although the 1:2 solute-solvent ratio persists. The steric bulk of the solvent in 6, as in 5, stops the amine hydrogen atoms from taking part in an infinite O-H‚‚‚N and N-H‚‚‚O network (Figure 7). Instead, the more prominent steric bulk of the amine causes synthon III (O-H‚‚‚N, 1.832 Å, 175.8°; Scheme 2) to form in preference to synthon I. 1,2-Cyclohexyl Diamine. (DDDA)1.5 (7). In all the amine solvents used so far, the nonpolar parts of the solvent molecules are flexible. To identify the effect of strain on the structure of the solvent molecules, we focused our attention on a more rigid primary amine system. To study the structural as well as interaction interference, we crystallized DDDA with 1,2cyclohexyl diamine. The resulting crystal structure is unique with an asymmetric unit composed of three symmetryindependent half molecules of DDDA and one full amine molecule (1:1.5) in the triclinic space group P1h. The interaction hierarchies for the two amine groups of the cyclohexyl diamine molecule are distinctly different. To our surprise, a supramolecular square synthon II (O-H‚‚‚N, 1.92 Å, 172°; N-H‚‚‚O, 2.67 Å, 154°) dominates the packing. Conversely, the second amine group is involved in an interaction pattern O-H‚‚‚O-H‚‚‚N-H‚‚‚π that is closely related to


Figure 7. Crystal packing of 6 showing synthon III with a weak C-H‚ ‚‚π (benzene) interaction shown as light dashed lines.

Figure 8. Crystal packing of 7 showing square synthon II sandwiched between two interaction patterns that are similar to synthon I.

synthon I, except that an O-H‚‚‚O (1.90 Å, 176°) terminates the alternative N(H)O bonding, whereas both of the amine hydrogen atoms are involved in N-H‚‚‚π interactions (2.65 Å, 151.5° and 2.83 Å, 157.5°) (Figure 8). It is quite unusual to see two amine groups in the same molecule showing such different kinds of interaction behavior. Whereas the amine group that forms synthon I behaves more like a primary amine, the second amine group with one inactive hydrogen atom behaves more like a secondary amine (see below). Discussion of Primary Amine Solvates. The crystal structures of 1-7 show an interesting and unusual property in that they display crystal packing patterns that are composites of patterns typically observed in gem-alkynol and supraminol compounds. Such composite packing highlights the importance of all the functional groups in dictating the packing arrangement, and as such, the crystal packing for 1-7 can be understood by considering the crystal packing patterns seen in both the supraminol and gem-alkynol classes of compounds.

Mondal et al.

From a supraminol perspective, the amine and hydroxyl groups compliment each other perfectly. Our recent studies on supraminol13a,b,h show that the mutually parallel orientation of the C-O and C-N vector (as in the archetypal 4-aminophenol)13b is a prerequisite if all the sites available for hydrogen bond formation are to be used and for the expected β-As sheet to be formed. The absence of such linearity of the C-O and C-N vectors results in supramolecular synthons such as the infinite chain and square motifs being generated. For the present work, a closer inspection of the space group could help us to understand the absence of the β-As network. Crystal structures containing the β-As network usually lack a 21 screw axis, whereas for structures containing an infinite chain, the 21 screw axis is quite important. The reason appears to be that a 21 screw axis permits greater flexibility, which is required for the creation of an infinite chain pattern. In agreement with this hypothesis, in the series of compounds presented herein, all those structures that adopt an infinite chain pattern crystallize in space group P21/c, and those adopting other kinds of packing crystallize in space group P1h. The absence of the β-As network can be rationalized because in the P21/c space group, the DDDA molecule lies on an inversion center, whereas the corresponding amine molecule sit on a general position. This makes C-O and C-N vectors almost perpendicular to each other, an arrangement with the lowest probability of forming a β-As network. Instead, an infinite N(H)O chain with N-H‚‚‚π contacts dominates the crystal packing. Interestingly, these infinite chain patterns closely resemble those of supraminols, where (instead of an ethynyl group) a benzene ring takes part in the N-H‚‚‚π interaction. The greater strain in the two amine groups in 7 causes an interaction interference and the infinite chain was terminated by a shorter O-H‚‚‚O bond on either side of a square synthon. From the gem-alkynol point of view, the whole series (1-7) could be better understood by considering the theory of pseudopolymorphism and a multipoint recognition model. Solvation is considered to be an interruption of the normal crystallization process, where strong bonds between the solute and solvent molecules intervene in the formation of the robust supramolecular synthon. A good hydrogen bond acceptor like a primary amine participates in an infinite N(H)O chain with the solute, which stops the formation of other supramolecular synthons. In this process, the compound crystallizes with the solvent molecule trapped within the lattice. Secondary Amines. We noticed recurring crystal packing patterns reminiscent of the supraminol family for the primary amine solvates, where the second amine hydrogen atom forms a N-H‚‚‚π interaction. The appearance of the square synthon in 7 involving only one active hydrogen atom prompted us to study the packing patterns for solvates formed with secondary amines. Secondary amines should be prone to form strong N-H‚ ‚‚O interactions rather than weak N-H‚‚‚π bonds, which should prevent the crystal packing from displaying synthon I. It is noteworthy that an infinite chain of only N(H)O bonds without any N-H‚‚‚π interactions is seldom observed for supraminols. Formation of infinite chains needs flexibility in the amine orientation, but strained systems such as secondary amines should change the type of networks observed in the crystal structures of the DDDA solvates. Accordingly, five different secondary amines, with increasing steric bulk, were investigated. (Et2NH)2.(DDDA) (8). As we observed earlier, the emergence of synthon I appears to be directly related to the space group; the structure of 8 with one-half a molecule of DDDA and one Et2NH molecule in the asymmetric unit (space group P1h) reinforces these findings. The DDDA molecule resides on an



Figure 9. Crystal packing of 8 showing the square motifs as bold dashed bonds, whereas the DDDA molecules interlink with C-H‚‚‚ Cl-C bonds, shown as light dashed bonds.

Figure 11. Crystal packing of 10 showing the square synthon II with interlinking C-H‚‚‚Cl-C bonds. Notice that the DDDA molecules and the butyl chains are tilted.

Figure 10. Crystal structure of 9 showing synthon II as bold dashed bonds, and C-H‚‚‚Cl-C interactions as light dashed bonds. Notice the tilted orientation with respect to the planar square synthon II of DDDA molecules compared to those of 8.

Figure 12. Crystal packing of 11 showing the square motifs (synthon II). Note that the orientations of cyclohexyl rings restricts the formation of C-H‚‚‚Cl-C bonds.

inversion center, and a closed loop of hydrogen bonds forms a square synthon II consisting of a N-H‚‚‚O (2.23 Å, 169.2°) and an O-H‚‚‚N (1.95 Å, 166.0°) hydrogen bond (Scheme 2) that dominates the packing (Figure 9). The topology of the packing with square synthon in 8 is almost analogous to those of supraminols such as 4-(4-aminobenzyl)phenol.13b However, this is in sharp contrast with 7, where synthon II is sandwiched between two synthons that are closely related to synthon I (primarily due to steric hindrance caused by the in-plane orientation of 1,2-cyclohexyl diamine). (Pr2NH)2. DDDA (9). The crystal packing of 9 is almost identical to that of 8, with the supramolecular square synthon II also being the major interaction pattern and C-H‚‚‚Cl-C interactions interlinking the DDDA molecules (Figure 10). (Bu2NH)2. DDDA (10). The crystal packing of 10 is almost a replica of 9. It crystallizes in the triclinic space group P1h with one-half a molecule of DDDA and one complete amine molecule in the asymmetric unit. The structure of 10 again shows the centrosymmetric supramolecular square synthon II (O-H‚‚‚N, 1.89 Å, 165°; N-H‚‚‚O, 2.49 Å, 158°) playing the central role in the packing arrangement with C-H‚‚‚Cl-C bonds interlinking the DDDA molecules. As seen in 9, to accommodate the larger butyl groups, the DDDA as well as butyl molecules adopt a tilted orientation with respect to the planar square synthon II (Figure 11), resulting in a slight lengthening of the intermolecular bonds in synthon II.

(Dicyclohexylamine)2. DDDA (11). DDDA was recrystallized from an acetone and dicyclohexylamine mixture in order to compare the resulting solvate with the acyclic secondary amine solvates. The amine solvent molecules adopt a chairchair conformation, which in effect orientates the ring carbon atoms, which can be thought of as being like two parallel propyl chains, away from the hydroxyl groups of the DDDA molecules. In other words, the dicyclohexyl ring does not increase the effective steric interference any more than observed for the propylamines. Therefore the crystal packing does not experience, as one might expect, any extra influence from the presence of the rigid rings in the solvent molecules. This is manifest in the fact that synthon II (O-H‚‚‚N, 1.99 Å, 162.5°; N-H‚‚‚O, 2.38 Å, 169.0°) is the principle supramolecular synthon in 11 (Figure 12). (iPr2NH)2. DDDA (12). The crystal structure of 12 has a 1:2 solute-solvent module and crystallizes in the triclinic space group P1h with one-half a molecule of DDDA and one amine molecule in the asymmetric unit. To our surprise, di-isopropylamine adopts a packing unlike the secondary amines reported above but quite similar to those of primary amine solvates that display synthon III (O-H‚‚‚N, 2.05 Å, 174.7°). The donor hydrogen atom of the amine forms a relatively weak N-H‚‚‚π (2.90 Å, 176.8°) bond rather than an N-H‚‚‚O bond, whereas the ethynyl hydrogen atom of DDDA forms the usual C-H‚‚ ‚Cl-C (3.16 Å, 125.7°) bond (Figure 13). For both structures 6 and 12, the bulky nonpolar chains on the amine solvent


Mondal et al.

Figure 14. Crystal packing of 13 (N,N-dimethyl ethylamine), showing synthon III with interlinking C-H‚‚‚Cl-C interactions.

Figure 13. Crystal packing of 12 showing synthon I-like interaction patterns. Note the absence of the N-H‚‚‚O bond.

molecules restrict the other polar functional groups from becoming close enough to form the square synthon (II). Discussion of Secondary Amine Solvates. The crystal structures of solvates 8-12 (see Table 2) are apparently simple but are also intriguing and deserve further attention. The adoption of the same supramolecular synthon by solvates 8-12 as that seen in the packing of 5 suggests that steric hindrance plays a vital role in directing the packing arrangement within the crystal structures of the secondary amine solvates. We found that for secondary amines, most adopt a staggered conformation and are symmetrically extended on either side of the nitrogen atom in a zigzag fashion. Yet, the bulky di-isopropylamine, in a manner similar to that of octylamine, shows puckered geometry rather than planar, resulting in a different synthon from I and II. This indicates a correlation between steric interference and a preference for certain synthons. Primary amines, being more flexible than secondary amines, preferentially opt for infinite chain patterns rather than the square synthon. Tertiary Amines. Structural analyses of the crystal structures of the primary amine solvates 1-7 and secondary amine solvates 7-12 show a clear correspondence between the crystal structure adopted and the number of amine hydrogen atoms. This inevitably focused our attention toward the behavior of tertiary amines, which, being devoid of any donor hydrogen atoms, should not form either infinite chains or square motifs, and in effect will help us validate the importance of amine hydrogen atom(s) toward directing the crystal packing in DDDA-amine solvates. Following the method established for investigating the solvates formed by primary and secondary amines, we used tertiary amines with increasing steric bulk to complete this study. (EtMe2N)2. DDDA (13). N,N,N-Dimethyl ethylamine forms solvate crystals with DDDA (13) with a structure that is directly analogous to that of 6. Despite the fact that there is no donor amine hydrogen atom, in many respects, the crystal packing closely follows those of the primary amines rather than secondary amines, with a 1:2 solute-solvent motif reappearing that displays with a strong O-H‚‚‚N (1.83 Å, 166.8°) interactions. The orientations of the amine molecules with respect to DDDA closely resemble those of a primary amine, although the lack of any donor amine hydrogen atom rules out any infinite cooperative arrangement. Notwithstanding, one methylene

Figure 15. Crystal packing of 14 showing synthon III as bold lines and the C-H‚‚‚Cl-C interactions as light lines. Note the C-H‚‚‚O interactions involving the solvent methyl group.

hydrogen atom of the solvent is directed toward the ethylene group of the DDDA to form a C-H‚‚‚π (3.01 Å, 162.3°) bond, resulting in the generation of synthon III (Scheme 2). Interestingly, these discrete hydrogen bonded units are linked by the familiar C-H‚‚‚Cl-C (3.02 Å, 155.6°) bonds (Figure 14). (Et3N)2. DDDA (14). The crystal structure of 14 is similar to that of 13, with one-half a molecule of DDDA and a half molecule of amine in the asymmetric unit, and it crystallizes in the triclinic space group P1h. Synthon III (O-H‚‚‚N, 1.91 Å, 172°) again plays a dominant role in the packing, and as seen in the structure of 13, discrete hydrogen bonded units are connected by familiar C-H‚‚‚Cl-C bonds (2.95 Å, 142°; Figure



Table 2. Crystallographic Data and Structure Refinement Parameters for 2° and 3° Amine Solvates (8-15) 8 empirical formula fw cryst syst space group a (Å) b (Å) c (Å) R (deg) β (deg) γ (deg) Z′ V (Å3) Dcalcd (g cm-3) µ (mm-1) 2θ (deg) range h range k range l no. of reflns collected no. of unique reflns no. of obsd reflns R1 [I > 2σ(I)] wR2 (all) GOF cryst size (mm3) largest diff. peak and hole (e Å-3) CCDC no.

9

10

11

12

13

14

15

C13H16ClNO 237.72 triclinic P1h 8.8625(4) 8.8881(5) 9.5190(5) 109.609(2) 116.003(2) 90.739(2) 0.5 623.39(6) 1.266 0.285 4.96 to 55 -11 to 11 -10 to 11 -12 to 12 7477

C30H38Cl2N2O2 531.54 monoclinic P21/c 9.1961(2) 8.8730(2) 36.8668(9) 90 91.621(1) 90 1.0 3007.02(12) 1.174 0.243 4.43 to 55 -11 to 11 -11 to 11 -47 to 47 34604




C26H32Cl2N2O2 475.44 triclinic P1h 9.9854(3) 10.2540(3) 12.7257(4) 88.250(1) 72.431(1) 87.261(1) 1.0 1240.61(7) 1.273 0.287 4.57 to 55 -12 to 12 -12 to 12 -15 to 15 15089

C15H20ClON 265.77 triclinic P1h 7.8896(3) 9.0728(3) 11.4777(4) 79.135(1) 70.273(1) 71.331(1) 0.5 729.69(4) 1.210 0.251 3.78 to 55 -10 to 10 -11 to 11 -14 to 14 8469

C17H22ClNO 291.81 monoclinic P21/n 7.9119(2) 17.7382(5) 11.1360(3) 90 102.270(1) 90 0.5 1527.16(7) 1.269 0.246 4.39 to 55 -10 to 10 -23 to 23 -14 to 14 20484

2862 2634 0.0387 0.1052 1.055 0.28 × 0.08 × 0.04 0.327, -0.629

6903 4084 0.0689 0.1908 1.278 0.32 × 0.10 × 0.08 0.944, -0.585

3776 2885 0.0625 0.1308 1.086 0.2 × 0.12 × 0.04 0.521, -0.276

4239 3503 0.0359 0.0991 1.032 0.42 × 0.15 × 0.14 0.347, -0.234

3247 2920 0.0323 0.0897 1.065 0.38 × 0.20 × 0.17 0.309, -0.268

4873 4331 0.0488 0.1265 1.119 0.30 × 0.18 × 0.08 0.781, -0.343

3326 2793 0.0661 0.1692 1.038 0.36 × 0.16 × 0.12 0.495, -0.469

3519 3144 0.0303 0.0825 1.042 0.28 × 0.22 × 0.16 0.412, -0.199

605426

605429

605424

605425

605427

605428

605432

605430

15). It is interesting to note that in all occurrences of synthon III, the donor hydrogen atom is a methylene hydrogen atom (from the R-carbon atom) and not a methyl hydrogen atom. The only difference in the packing of 13 and 14 is that in 14 there is a strong C-H‚‚‚O (2.49 Å, 141°) bond between one of the methyl hydrogen atoms of the amine and DDDA. N,N-Dimethylcyclohexylamine. DDDA (15). In 14, as in 13, the donor hydrogen atom that forms a C-H‚‚‚π bond is attached to the R-carbon atom. By examining these two structures, the question arose as to whether this particular structural type could be reproduced with more complex tertiary amines. To answer this question, we crystallized DDDA with N,N-dimethylcyclohexylamine, which has two free methyl groups and as such would be more likely to form C-H‚‚‚π interactions than a rigid cyclohexyl ring. It was astonishing to see that synthon III (OH‚‚‚N, 1.89 Å, 170.5°) is the major interaction pattern in 15, with a C-H‚‚‚π (2.92 Å, 155.8°) interaction (Figure 16) formed by a methylene hydrogen atom of the cyclohexyl ring and not with a methyl group hydrogen atom.

Discussion of Tertiary Amine Solvates. The crystal structures of 13-15 represent an interesting series, with all the molecules adopting a supramolecular synthon III pattern with supporting C-H‚‚‚Cl-C interactions. All these solvates show that even a single strong solute-solvent O-H‚‚‚N interaction is enough to stabilize a solvate. The crystal packing of 6, 7, and 14 is important is this respect. For the crystal structure of 14, steric hindrance was the driving force for the secondary amine solvate to adopt a crystal structure, more like a primary amine solvate. In the case of the crystal structure of 7, the rigidity of the cyclohexyl ring prevents the second amine hydrogen atom from forming hydrogen bonds, effectively causing a primary amine solvate to adopt a secondary amine solvate-like structure. On the other hand, in 6, the steric hindrance of the octyl group was enough to prevent both of the amine hydrogen atoms from forming hydrogen bonds, and in effect, 6 has a structure that is equivalent to that of tertiary amine in that it exhibits the supramolecular synthon III. Thus, steric hindrance does indirectly control synthon formation by controlling the number of amine hydrogen atoms participating in strong hydrogen bond formation with DDDA. Conclusion

Figure 16. Crystal packing of 15 showing synthon III with the C-H‚ ‚‚Cl-C bond shown as light dashed bonds.

The impetus for the work presented herein was the quest to increase the hydrogen bonding in DDDA by solvation using good hydrogen-bond-accepting solvents.9 We have vindicated our strategy of using amines, not simply as solvents, but as an essential component molecule for the study of the competitive nature of amine, hydroxyl, and ethynyl groups in the formation of secondary interactions. In the present study, the introduction of any new functional group to the already crowded gem-alkynol moiety would create enough interaction interference for a molecule to crystallize in a predictable manner. In this respect, DDDA with fewer hydrogen bonds provides us with a unique opportunity to overcome this problem by introducing amines in the form of a


solvent into the crystal structures, in the same way that diphenols cocrystallize with dianilines, to give rise to molecular complexes. We have been able to identify three major synthons that would be helpful in the prediction of structural motifs for these kinds of systems and were successful in quantifying the importance of the amine hydrogen atoms. There is a clear correlation between the number of amine hydrogen atoms present, or type of amine used, and the supramolecular synthon that is present in the resultant solvate. Accordingly, we can describe synthon I, II, and III as primary, secondary, and tertiary synthons, respectively. Interestingly, the exceptions to these trends do show the importance of steric hindrance and structural interferences. For instance, the ring strain and consequent structural interferences shown by the amine solvent molecules in 4 and 5 did change the crystal packing from a typical supraminol packing to one that is characteristic of the gem-alkynol family. These results further help us to understand which structure would be obtained when the β-As sheet is disrupted by a bulky group on the amine molecule. Acknowledgment. J.A.K.H. thanks the EPSRC for a Senior Research Fellowship during the course of this work, R.M. acknowledges the receipt of an Overseas Research Scholarship and thanks Olga Chetina for useful suggestions regarding crystallization techniques. Continuing support over the years from the DST and the CSIR to G.R.D.’s research programs is gratefully acknowledged. R.B. thanks the UGC for the award of a Senior Research Fellowship. References (1) Some recent references on inclusion complexes: (a) Caira, M. R.; Chang, Y. P.; Nassimbeni, L. R.; Su, H. Org. Biomol. Chem. 2004, 2, 655. (b) Atwood, J. L.; Barbour, L. J.; Heaven, M. W.; Raston, C. L. Angew. Chem., Int. Ed. 2003, 42, 3254. (c) Steed, J. W.; Atwood, J. L. Supramolecular Chemistry; Wiley: Chichester, U.K., 2000. (c) Caira, M. R.; Nassimbeni, L. R.; Vujovic, D.; Toda, F. J. Phys. Org. Chem. 2000, 13, 75. (d) Nassimbeni, L. R. Crystal Engineering. From Molecules and Crystals to Materials; Braga, D., Grepioni, F., Orpen, A. G., Eds.; Kluwer Academic Publishers: Dordrecht, The Netherlands, 1999; pp 163-179. (e) Vo¨gtle, F. Supramolecular Chemistry; Wiley: Chichester, U.K., 1991. (2) Some references on clatharates: (a) Natural Gas Hydrates: Properties, Occurrence and RecoVery; Cox, J. L., Ed.; Butterworth Publishers: Boston, 1983. (b) Sloan, E. D., Jr. Clathrate Hydrates of Natural Gases, 2nd ed.; Marcel Dekker: New York, 1998. (c) Makogan, Y. F. Hydrates of Hydrocarbons; Penn Well Publishing Co.: Tulsa, OK, 1997. (d) Davidson, D. W. Clathrate Hydrates. In Water: A ComprehensiVe Treatise; Frank, F., Ed.; Plenum: New York, 1973; Vol. 2, 115-234. (e) Ripmeester, J. A.; Ratcliffe, C. I. Solid State NMR Studies of Inclusion Compounds. In Inclusion Compounds; Atwood, J. L., Davies, J. E. D., Macnicol, D. D., Eds.; Oxford University Press: Oxford, U.K., 1991; Vol. 5, pp 37-89. (f) Mao, W. L.; Mao, H.-K.; Goncharov, A. F.; Struzhkin, V. V.; Guo, Q.; Hu, J.; Shu, J.; Hemley, R. J.; Somayazulu, M.; Zhao, Y. Science 2002, 297, 2247. (3) Some recent references on pseudopolymorphs: (a) Mondal, R.; Howard, J. A. K. CrystEngComm 2005, 7, 462. (b) Mondal, R.; Howard, J. A. K.; Banerjee, R.; Desiraju, G. R. Chem. Commun. 2004, 644. (c) Plass, K. E.; Kim, K.; Matzger, A. J. J. Am. Chem. Soc. 2004, 126, 9042. (d) Izotova, L. Y.; Ibragimov, B. T.; Weber, E.; Ashurov, D. M.; Talipov, S. A.; Perrin, M. J. Inclusion Phenom. 2004, 48, 69. (e) Pedireddi, V. R.; Reddy, P. J. Tetrahedron Lett. 2003, 44, 6679. (f) Jetti, R. K. R.; Boese, R.; Thallapally, P. K.; Desiraju, G. R. Cryst. Growth Des. 2003, 3, 1033. (g) Kobayashi, K.; Sato, A.; Sakamoto, S.; Yamaguchi, K. J. Am. Chem. Soc. 2003, 125, 3035. (h) Raj, S. B.; Muthiah, P. T.; Rychlewska, U.; Warzajtis, B. CrystEngComm 2003, 5, 48. (i) Alshahateet, S. F.; Bishop, R.; Craig, D. C.; Scudder, M. L.; Ung, A. T. Struct. Chem. 2001, 12, 251. (j) Ahn, S.; Kariuki, B. M.; Harris, K. D. M. Cryst. Growth Des. 2001, 1, 107. (k) Tanifuji, N.; Kobayashi, K. CrystEngComm 2001, 3, 15. (4) Some recent references on host-guest materials: (a) Toda, F.; Miyamoto, H.; Inoue, M.; Yasaka, S.; Matijasic, I. J. Org. Chem. 2000, 65, 2728. (b) Weber, E.; Hens, T.; Brehmer, T.; Cso¨regh, I. J.

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Chem. Soc., Perkin Trans. 2 2000, 235. (c) Jetti, R. K. R.; Xue, F.; Mak, T. C. W. Nangia, A. J. Chem. Soc., Perkin Trans. 2 2000, 1223. (d) Kobayashi, K.; Shirasaka, T.; Sato, A.; Horn, E.; Furukawa, N. Angew. Chem., Int. Ed. 1999, 38, 3483. (e) MacGillivray, L. R.; Atwood, J. L. Angew. Chem., Int. Ed. 1999, 38, 1018. (f) Chui, S. S.-Y.; Lo, S. M.-F.; Charmant, J. P. H.; Orpen, A. G.; Williams, I. D. Science 1999, 283, 1148. (g) Caira, M. R.; Nassimbeni, L. R.; Toda, F.; Vujovic, D. J. Chem. Soc., Perkin Trans. 2 1999, 2681. (h) Yaghi, O. M.; Li, H.; Davis, C.; Richardson, D.; Groy, T. L. Acc. Chem. Res. 1998, 31, 474. (i) Swift, J. A.; Pivovar, A. M.; Reynolds, A. M.; Ward, M. D. J. Am. Chem. Soc. 1998, 120, 5887. (j) Endo, K.; Ezuhara, T.; Koyanagi, M.; Masuda, H.; Aoyama, Y. J. Am. Chem. Soc. 1997, 119, 499. (k) Hertzsch, T.; Budde, F.; Weber, E.; Hulliger, J. Angew. Chem., Int. Ed. 2002, 41, 2282. (l) Ma, B.Q.; Coppens, P. Chem. Commun. 2003, 2290. (m) Fournier, J. H.; Maris, T.; Wuest, J. D.; Gao, W. Z.; Galoppini, E. J. Am. Chem. Soc. 2003, 125, 1002. (n) Fournier, J. H.; Maris, T.; Wuest, J. D. J. Org. Chem. 2004, 69, 1762. (a) Bernstein, J. Polymorphism in Molecular Crystals; Clarendon: Oxford, U.K., 2002. (b) Thaimattam, R.; Xue, F.; Sarma, J. A. R. P.; Mak, T. C. W.; Desiraju, G. R. J. Am. Chem. Soc. 2001, 123, 4432. (c) McCrone, W. C. Physics and Chemistry of the Organic Solid State; Fox, D., Labes, M. M., Weissberger, A., Eds.; WileyInterscience: New York, 1965; Vol. 2. (d) Nassimbeni, L. R. Acc. Chem. Res. 2003, 36, 631. (e) Sarma, J. A. R. P.; Desiraju, G. R. Polymorphism and Pseudopolymorphism in Organic Crystals: A Cambridge Structural Database Study. In Crystal Engineering; Seddon, K. R., Zaworotko, M., Eds.; Kluwer: Norwell, MA, 1999. (a) Weber, E. In Inclusion Compounds; Atwood, J. L., Davis, J. E. D., Macnicol, D. D., Eds.; Oxford University Press: Oxford, U.K., 1991; Vol. 4. (b) Weber, E. In Kirk-Othmer Encyclopedia of Chemical Technology, 4th ed.; Kroschwitz, J., Ed.; Wiley: New York, 1995; Vol. 14. (a) Bishop, R. Synlett. 1999, 9, 1351. (b) Kumar, V. S. S.; Kuduva, S. S.; Desiraju, G. R.; J. Chem. Soc., Perkin Trans. 2 1999, 1069. (a) Nangia, A.; Desiraju, G. R. Chem. Commun. 1999, 605, (b) Gorrbitz, H.; Hersleth, P. Acta Crystallogr., Sect. B 2000, 56, 526. (a) Banerjee, R.; Desiraju, G. R.; Mondal, R.; Batsanov, A. S.; Broder, C. K.; Howard, J. A. K. HelV. Chim. Acta 2003, 86, 1339. (b) Anthony, A.; Desiraju, G. R. Supramol. Chem. 2001, 13, 11. Sheldrick, G. M. SHELX97; University of Go¨ttingen: Go¨ttingen, Germany, 1997. Banerjee, R.; Desiraju, G. R.; Mondal, R.; Howard, J. A. K. Chem.s Eur. J. 2004, 10, 3373. (a) Allen, F. H.; Kennard, O. Chem. Des. Autom. News 1993, 8, 3037, (b) Allen, F. H. Acta Crystallogr., Sect. B 2002, 58, 380-388. Selected references on supraminol: (a) Allen, F. H.; Hoy, V. J.; Howard, J. A. K.; Thalladi, V. R.; Desiraju, G. R.; Wilson, C. C.; McIntyre, G. J. J. Am. Chem. Soc. 1997, 119, 3477. (b) Vangala, V. R.; Bhogala, B. R.; Dey, A.; Desiraju, G. R.; Broder, C. K.; Smith, P. S.; Mondal, R.; Howard, J. A. K.; Wilson, C. C. J. Am. Chem. Soc. 2003, 125, 14495. (c) Ermer, O.; Eling, A. J. Chem. Soc., Perkin Trans. 2 1994, 925. (d) Hanessian, S.; Gomtsyan, A.; Simard, M.; Roelens, S. J. Am. Chem. Soc. 1994, 116, 4495, (g) Hanessian, S.; Saladino, R. In Crystal Design, Structure and Function, PerspectiVe in Supramolecular Chemistry; Desiraju, G. R., Ed.; Wiley: New York, 2003; pp 7, 77. (h) Dey, A.; Desiraju, G. R.; Mondal, R.; Howard, J. A. K. Chem. Commun. 2004, 2528. Selected references on gem-alkynol: (a) Madhavi, N. N. L.; Bilton, C.; Howard, J. A. K.; Allen, F. H.; Nangia, A.; Desiraju, G. R. New J. Chem. 2000, 24, 1. (b) Madhavi, N. N. L.; Desiraju, G. R.; Bilton, C.; Howard, J. A. K.; Allen, F. H. Acta Crystallogr., Sect. B 2000, 56, 1063-1070. (c) Bilton, C.; Howard, J. A. K.; Madhavi, N. N. L.; Allen, F. H.; Wilson, C. C. Chem. Commun. 1999, 1675. (d) Banerjee, R.; Mondal, R.; Howard, J. A. K.; Desiraju, G. R. Cryst. Growth Des. 2006, 6, 999. C-H‚‚‚halogen interactions have been the topic of recent papers: (a) Thallapally, P. K.; Nangia, A. CrystEngComm 2001, 27, 1. (b) Brammer, L.; Bruton, E. A.; Sherwood, P. Cryst. Growth Des. 2001, 1, 277. (c) Neve, F.; Crispini, A. Cryst. Growth Des. 2001, 1, 387. (d) James, S. L.; Verspui, G.; Spek A. L.; van Koten, G. Chem. Commun. 1996, 1309. (e) Aakero¨y, C. B.; Evans, T. A.; Seddon, K. R.; Pa´linko´, I. New J. Chem. 1999, 23, 145. (a) Desiraju, G. R. CrystEngComm 2003, 5, 466. (b) Seddon, K. R. Cryst. Growth Des. 2004, 4, 1087. (c) Desiraju, G. R. Cryst. Growth Des. 2004, 4, 1089. Threlfall, T. L. Analyst 1995, 120, 2435.

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Crystallographic Studies of Supramolecular Synthons in Amine

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