A Dinitrodiphenyldiquinoline Host for Selective Inclusion of Polar Guests

Jun 7, 2006 - ... of Chemical and Engineering Sciences, 1 Pesek Road, Jurong Island, ... School of Chemistry, The UniVersity of New South Wales, UNSW ...
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A Dinitrodiphenyldiquinoline Host for Selective Inclusion of Polar Guests Alshahateet,*,§,†

Solhe F. Mouslim Messali§

Tien Teng

Ong,†

Roger

Bishop,‡

Fethi

Kooli,†

and

CRYSTAL GROWTH & DESIGN 2006 VOL. 6, NO. 7 1676-1683

Institute of Chemical and Engineering Sciences, 1 Pesek Road, Jurong Island, Singapore 627833, School of Chemistry, The UniVersity of New South Wales, UNSW Sydney, NSW 2052, Australia, and Department of Chemistry, Taibah UniVersity, P.O. Box 344, Almadinah Almunawarah, Saudi Arabia ReceiVed March 11, 2006; ReVised Manuscript ReceiVed April 29, 2006

ABSTRACT: The molecular framework of 1 has been used as the starting point for the design of new host molecules that use alternative sensor groups to the halogens employed previously. Addition of phenyl substituents increases the opportunities for π‚‚‚π interaction, and consequently, diquinoline 3 was, as expected, a nonhost. However, the further introduction of nitro sensor groups induced selectivity toward the inclusion of polar guest molecules for the first time. Hence the dinitrodiphenyldiquinoline 6 forms 1:1 inclusion compounds when crystallized from polar solvents such as methanol, N,N-dimethylformamide (DMF), and pyridine. The X-ray crystal structures of these compounds are reported and analyzed in crystal engineering terms. Introduction

Results and Discussion

Host-guest chemistry involving organic compounds involves a diverse variety of structural materials of considerable importance to chemists.1,2 The host molecules generally may be classified into those with (i) a permanent receptor structure and (ii) lattice inclusion hosts. Cyclodextrins, cavitands, and carcerands represent systems that possess a receptor structure that can form molecular complexes by accommodating convex guests within the concave cavity of the host. In contrast, lattice inclusion compounds result from multiple favorable interactions between the host and guest molecules comprising a crystal lattice. These pack together such that sites between the host molecules are occupied by guests. This outcome produces systems that are more flexible but often less selective. Due to this fundamental distinction, the design of new lattice inclusion hosts is more difficult and provides an interesting synthetic challenge.3-5 The design of selective lattice inclusion hosts is even more challenging. 6-8 In recent work, we have been investigating the inclusion phenomena of new diquinoline hosts.9-12 These molecules consist of a central alicyclic linker, aromatic wings, and sensor groups. The central alicyclic linker imposes actual or pseudoC2 symmetry on the molecule. This feature offers some conformational mobility, giving the molecule a flexible Vshaped structure and allowing it to rotate and twist. This flexibility allows the diquinoline to adjust itself to the accommodation of different guest molecules within its crystal lattice. The aromatic wings provide sites for aryl interactions,13,14 while the sensor groups help confer lattice inclusion properties on the resulting host molecules. Our approach to synthesis of these new families of lattice inclusion compounds is simple and is proving to be highly successful.15-18 Minor modifications in the molecular structure often lead to major changes in supramolecular behavior and the inclusion properties.

The basic molecular building block 1 has been synthesized in previous work, and as expected, it did not act as a host.11

* To whom correspondence should be addressed. E-mail: solhe_2005@ yahoo.com. Fax: Int + 966 4 8454770. Tel: Int + 966 5 68634121. § Taibah University. † Institute of Chemical and Engineering Sciences. ‡ University of New South Wales.

However, by adding bromine sensor groups to the central linker, the host molecule 211,19 was successfully obtained. Such substitution can inhibit efficient packing of the diquinoline and therefore is frequently an effective strategy in promoting guest inclusion. In the present work, we have added substituents on the aromatic wings instead. This alternative approach has also been successful in the past in yielding new inclusion hosts.12,16-18 However, the diphenyldiquinoline 3 was also expected to be a nonhost because its additional phenyl groups provide more opportunities for aryl interactions and hence greater packing efficiency, and this was confirmed by means of a series of crystallization experiments. Next, we proceeded to investigate the effect of change in electron density of the quinoline on guest inclusion. The nitro group was chosen for its strong electron-withdrawing properties to alter the π electron density within the diquinoline system. This functionality is a hydrogen bond acceptor and may compete for hydrogen bonding with the basic quinoline nitrogen. Hydrogen bonding has been employed frequently in selfassembling systems.20,21 By promoting intermolecular hydrogen bonding interactions, we aimed to induce selectivity of our new predicted dinitrodiphenyl host 6 toward polar guest molecules. This behavior would be entirely different from the properties shown by all our previous diquinoline hosts. Synthesis of the Diphenyldiquinoline Derivatives 3 and 6. Compound 3 was synthesized according to Scheme 1 by means of a Friedla¨nder condensation.22,23 Two equivalents of

10.1021/cg0601352 CCC: $33.50 © 2006 American Chemical Society Published on Web 06/07/2006

Dinitrodiphenyldiquinoline Host

Crystal Growth & Design, Vol. 6, No. 7, 2006 1677

Scheme 1

2-aminobenzophenone 4 (X ) H) and 1 equiv of bicyclo[3.3.1]nonane-3,7-dione 524 were dissolved in ethanol, along with a catalytic amount of concentrated HCl; the mixture was refluxed overnight and then filtered to yield 3 as a light brown powder in 75% yield. The dinitrodiphenyl analogue 6 was synthesized in an identical manner using 2 equiv of 2-amino-5-nitrobenzophenone 4 (X ) NO2) and 1 equiv of 5. Compound 6 was thereby obtained as a pale orange powder in 50% yield. Crystallization of 3 and 6. A series of crystallization experiments was performed and solvent-free crystals of diquinoline 3 of X-ray quality were obtained from methanol. As expected, the diquinoline 6 was insoluble in nonpolar hydro-

carbon solvents such as alkanes and benzene. Crystallization of 6 from a wide variety of polar solvents was performed. This compound demonstrated limited solubility in some of these such as diethyl ether, dichloromethane, chloroform, and trifluoromethylbenzene. Single crystals obtained from dimethylformamide (DMF) were not initially suitable for diffraction, but the addition of ibuprofen during crystallization in DMF produced single crystals of (6)‚(DMF) suitable for X-ray structure determination. Addition of ibuprofen was initially used to examine the competition between inclusion of ibuprofen (formation of cocrystal) and inclusion of the solvent (DMF). The mechanism for this phenomenon is still unclear. However, we think growth of the crystals was enhanced in the presence of ibuprofen (hetero-seeding). Currently we are investigating this phenomenon in more detail, and our findings will be presented somewhere else very soon. Crystals of suitable quality were also obtained from methanol and pyridine. These three polar guests have quite disparate functionality and hydrogen bonding properties. The crystal data and structural refinements for 3 and the three inclusion compounds of 6 are shown in Table 1, while the principal interactions present in each structure are summarized in Table 2. Crystal Structure of 3. Crystallization of 3 from methanol yielded crystals of the solvent-free compound in the monoclinic space group P21/c. This structure is relatively simple. Alternating enantiomers of the V-shaped molecule 3 simply stack on top of each other with their methylene bridges all pointing in the same direction. Adjacent stacks have the opposite alignment. The molecules of 3 within each stack are all linked in an identical manner by means of two different interaction motifs involving aliphatic hydrogen atoms of the central linker group. One of the methylene bridge hydrogen atoms of the first enantiomer forms a C-H‚‚‚N interaction (d ) 2.73 Å) with the nitrogen atom of the second enantiomer. Repetition leads to formation of a chain of these interactions joining the first set of wings of the 3 molecules. The second set of wings is linked

Table 1. Crystal Data and Structure Refinements compound empirical formula formula weight temp, K λ, Å crystal system space group a, Å b, Å c, Å R, deg β, deg γ, deg V, Å3 Z Dc, mg/m3 µ, mm-1 F(000) crystal size, mm3 θ range for collected data, deg index ranges min/max h,k,l reflns collected independent reflns completeness to θmax, % max and min transmission data/restraints/params goodness-of-fit on F2 final R indices [I > 2σ(I)] R indices (all data) largest diff. peak and hole, e Å-3

3

(6)‚(methanol)

(6)‚(DMF)

(6)‚(pyridine)

C35H26N2 474.58 223(2) 0.71073 monoclinic P21/c 20.5368(16) 10.8023(9) 11.0168(8) 90 97.276(2) 90 2424.3(3) 4 1.300 0.076 1000 0.30 × 0.09 × 0.09 2.00 to 25.00 -23/24, -12/12, -13/13 13598 4267 [R(int) ) 0.0851] 100.0% 0.9932 and 0.9777 4267/0/334 1.143 R1 ) 0.0970, wR2 ) 0.1652 R1 ) 0.1524, wR2 ) 0.1840 0.309 and -0.238

C36H28N4O5 596.62 223(2) 0.71073 monoclinic P21/c 10.5589(6) 18.0631(12) 15.6600(9) 90 95.732(2) 90 2971.8(3) 4 1.333 0.090 1248 0.30 × 0.20 × 0.10 1.73 to 25.00 -12/12, -20/21, -18/18 20223 5232 [R(int) ) 0.0756] 100.0 0.9910 and 0.9734 5232/0/411 1.146 R1 ) 0.0945, wR2 ) 0.1615 R1 ) 0.1521, wR2 ) 0.1810 0.221 and -0.162

C38H31N5O5 637.68 223(2) 0.71073 triclinic P1h 8.1942(4) 10.8035(6) 17.8465(9) 94.0800(10) 92.7610(10) 93.742(2) 1570.30(14) 2 1.349 0.091 668 0.18 × 0.18 × 0.09 1.15 to 25.00 -9/9, -12/12, -21/21 17244 5533 [R(int) ) 0.0515] 100.0 0.9918 and 0.9838 5533/0/435 1.192 R1 ) 0.0839, wR2 ) 0.1624 R1 ) 0.1167, wR2 ) 0.1757 0.365 and -0.210

C40H29N5O4 643.68 223(2) 0.71073 monoclinic P21/c a ) 11.0319(6) b ) 16.4711(9) c ) 17.5415(9) 90 94.9240(10) 90 3175.7(3) 4 1.346 0.089 1344 0.50 × 0.26 × 0.18 1.70 to 27.50 -14/9, -21/21, -21/22 22280 7300 [R(int) ) 0.0263] 100.0 0.9842 and 0.9569 7300/0/442 1.044 R1 ) 0.0601, wR2 ) 0.1350 R1 ) 0.0789, wR2 ) 0.1454 0.349 and -0.230

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Table 2. Interactions Present in the Crystal Structures compound 3

(6)‚(methanol)

(6)‚(DMF)

(6)‚(pyridine)

interactionsa

dimer type

py N‚‚‚link H‚‚‚quin C quin C‚‚link H‚‚quin C py N‚‚‚link H quin C‚‚link H py N‚‚‚quin H Link H‚‚‚OH‚‚‚py N phenyl H‚‚‚NO‚‚‚phenyl H NO‚‚‚link H NO‚‚‚link H NO‚‚‚phenyl H NO‚‚‚ py N CH‚‚‚ON quin H‚‚‚CO‚‚‚quin H link H‚‚‚CO‚‚‚phenyl H CHO‚‚‚py N‚‚‚HC py C‚‚‚NO‚‚‚py C phenyl H‚‚‚NO‚‚‚phenyl H link H‚‚‚NO‚‚‚link H CH‚‚‚py N N‚‚‚link H CH‚‚‚NO‚‚‚HC NO‚‚‚link H link H‚‚‚NO‚‚‚link H phenyl H‚‚‚NO‚‚‚phenyl H py C‚‚‚NO‚‚‚py C NO‚‚‚phenyl H‚‚‚ON

bifurcated bifurcated single single single bifurcated bifurcated cycle single cycle cycle single bifurcated bifurcated bifurcated bifurcated bifurcated bifurcated single single bifurcated single bifurcated bifurcated bifurcated bifurcated

ring size (no. atoms)

assembly typeb

distance, Åc

angle, deg

host fold angle, degd

3 3

h-h h-h h-h h-h h-h h-g-h h-h dimer h-h dimer h-h h-h dimer h-h dimer g-h h-g-h h-g-h g-h-g h-h dimer h-h dimer h-h dimer g-h g-h g-h-g h-h h-h dimer h-h dimer h-h dimer h-h dimer

2.68, 2.78 2.70, 2.76 2.73 2.82 2.64 2.98, 2.89 2.54, 2.94 2.73 2.86 2.82 3.15 2.59, 2.67 2.68, 2.94 2.71, 2.65 2.73, 2.78 3.16, 3.14 2.64, 2.83 2.74, 2.79 2.70 2.68 2.91, 2.95 2.97 2.63, 2.77 2.60, 2.94 3.13, 3.10 2.97, 2.95

28.90 29.98

89.78

50.87 48.77

97.96

5 5 20 30 26 5 8 6 4 5 6 5 6 5 4 4

94.74 47.76 55.80 46.90 42.76 49.90 54.75 96.04 46.29 56.71 49.04 43.23 42.71

a py ) pyridine ring within the quinoline wing; quin ) benzene ring within the quinoline wing; link ) central linker. b h ) host; g ) guest. c All hydrogen positions are calculated values. d Host fold angle is the angle present between the aromatic wings of the diquinoline structure and the central linker carbon, that is, the angle of O2N-C‚‚‚bridge CH2‚‚‚C-NO2, see structure 6.

by pairs of C-H‚‚‚N (d ) 2.68 Å) and C-H‚‚‚π (d ) 2.70 Å) interactions, again operating between opposite enantiomers of 3. These attractions involve the second hydrogen atom of the methylene bridge and a bridgehead methine hydrogen. These arrangements are illustrated in Figure 1. The quinoline nitrogen atom involved in the C-H‚‚‚N interaction (d ) 2.73 Å) with its opposite enantiomer in the same stack (see above) also participates in another C-H‚‚‚N interaction (d ) 2.64 Å) with another molecule of the same handedness in a neighboring stack. This results in the tetrameric centrosymmetric arrangement illustrated in Figure 2. This means of interstack packing enables the molecules of 3 to achieve a close-packed solvent-free crystal structure. Crystal Structure of (6)‚(Methanol). Crystallization of 6 from methanol yielded crystals of the lattice inclusion compound (6)‚(CH3OH) in the monoclinic space group P21/c. The asymmetric unit contains one host and one methanol molecule. Opposite enantiomers of 6 are arranged in layers of parallel zigzag rows, in which the host molecules interact by means of aromatic offset face-face (OFF) interactions (Figure 3, top). The methanol guest molecule is positioned between two host molecules of opposite chirality that belong to two adjacent zigzag rows. It is hydrogen bonded, -O-H‚‚‚N (d ) 2.89 Å), to one of the host quinoline nitrogen atoms; the second nitrogen does not associate with guests. The methanol also associates with the same host molecule by means of an O‚‚‚H-C (d ) 2.98 Å) weak hydrogen bond25 and by a further O‚‚‚H-C (d ) 2.84 Å) to the second host (of opposite handedness). Both these aliphatic hydrogen atoms belong to host central linker groups (Figure 3, bottom). The nitro groups of 6 were introduced as sensor groups that would act in a different manner from the halogens used in our previous work. In particular, they were expected to promote intermolecular hydrogen bonding, and this proved to be the case. In (6)‚(CH3OH), the nitro groups play a major role in linking

the host molecules, and they achieve this by means of two different types of supramolecular interactions. The first type is the N-O‚‚‚H-C motif. One nitro group of a 6 molecule forms a bifurcated Ar-H‚‚‚O‚‚‚H-Ar interaction (d ) 2.54 and 2.94 Å) with one wing of another host molecule of opposite chirality. The second nitro group of the first molecule also participates in an N-O‚‚‚H-C interaction (d ) 2.73 Å) but with an aliphatic central linker hydrogen belonging to a second host of opposite handedness. As can be seen in Figure 4, the repetition of these motifs generates centrosymmetric packing relationships and layers of 6 molecules. The second type of interhost supramolecular interaction is the N-O‚‚‚π attraction. These occur between both homochiral and heterochiral pairs of 6 molecules (Figure 5). Hence, a combination of aromatic OFF, N-O‚‚‚H-C, and N-O‚‚‚π interactions are employed collectively to generate the host lattice in crystals of (6)‚(CH3OH). The nitro sensor groups help direct this packing but are not directly involved in inclusion of the methanol guests. These interact directly with molecules of 6 by means of O-H‚‚‚N and O‚‚‚H-C hydrogen bonds. Crystal Structure of (6)‚(DMF). Crystallization of 6 from dimethylformamide (DMF) produced crystals of the lattice inclusion compound (6)‚(DMF) in the triclinic space group P1h. The asymmetric unit contained one host and one DMF guest. Opposite enantiomers of the host 6 are arranged as zigzag rows by means of aromatic OFF and N-O‚‚‚π interactions as shown in Figure 6. In the previous inclusion compound (6)‚(methanol), the guest was located near the apex of one host molecule and the concavity of a second. The location of the guest in (6)‚(DMF) is rather similar, and the dimethylformamide associates with molecules of the host in several different ways as shown in Figure 7. The formyl hydrogen interacts with one molecule of 6 by means of a C-H‚‚‚N interaction (d ) 2.73 Å), and its carbonyl oxygen associates with two hydrogens of a second host molecule by means of a bifurcated aryl-H‚‚‚O‚‚‚H-aliphatic

Dinitrodiphenyldiquinoline Host

Figure 1. The top panel shows part of a stack of molecules in the crystal structure of 3, showing how the two sets of wings of the molecules are linked. The opposite enantiomers of 3 are colored light or dark green. Atom code: C, green; N, dark blue; H, light blue. Numerical values of the shortest interatomic distances in the vicinity of the two interaction types are indicated in Å. The bottom panel shows the crystal packing of two stacks of molecules of 3 in the solid state, viewed down the b direction and showing their relative orientation and the arrangement of the two enantiomers.

Figure 2. The centrosymmetric C-H‚‚‚N packing unit that provides a means of efficient association between neighboring stacks of molecules in the crystal structure of 3.

motif (d ) 2.65 and 2.71 Å, respectively). In addition, hydrogen atoms of the DMF methyl groups form C-H‚‚‚O interactions (d ) 2.59, 2.67, and 2.69 Å) with host nitro groups. Crystal Structure of (6)‚(Pyridine). Crystallization of 6 from pyridine afforded crystals of the lattice inclusion compound (6)‚(pyridine) in the monoclinic space group P21/c. The asymmetric unit contained one host with one pyridine guest. The spatial arrangement of the host and guest molecules is rather

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Figure 3. The top panel shows the association of host 6 molecules and methanol guest in solid (6)‚(CH3OH). Host molecules 6 of opposite chirality (dark or light green) are arranged as zigzag rows and are associated by means of aromatic offset face-face (OFF) interactions. O‚‚‚H interactions under 3 Å are shown as red dotted lines. The bottom panel shows the three hydrogen bonds (dashed lines) present between the methanol guest and opposite enantiomers of 6. Color code: host C, green; O, orange; N, dark blue; H, light blue; guest C, purple.

similar to the previous two examples. Once again the host molecules form zigzag chains of alternating enantiomers (Figure 8, upper), and the host molecules are linked through nitro group N-O‚‚‚H associations (Figure 8, lower). The aromatic pyridine guest was found to have an interesting supramolecular association with two molecules of host 6 with the same handedness. Its nitrogen atom accepts a N‚‚‚H-C (d ) 2.68 Å) weak hydrogen bond, as might be expected, from one host molecule. More surprisingly, one of the hydrogens adjacent to the pyridine nitrogen is donated to form a C-H‚‚‚N hydrogen bond (d ) 2.70 Å) with a quinoline nitrogen belonging to a second molecule of 6. This combination provides the efficient host-guest fit illustrated in Figure 9. TGA and DSC Studies. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) were performed to examine the thermal stability and decomposition profile of these inclusion crystals. TGA results are summarized in Table 3. The methanol and DMF inclusion compounds decomposed in a single step, while the pyridine inclusion compound decomposed in two steps. The measured mass loss from the three inclusion compounds agreed with the calculated values within the limits of experimental error. Each decomposition step

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Figure 4. The two interhost N-O‚‚‚H-C attraction motifs present between opposite host enantiomers in solid (6)‚(CH3OH).

Figure 5. The interhost OFF interactions are reinforced by N-O‚‚‚π attractions between molecules of 6.

Figure 6. The molecular packing in crystalline (6)‚(DMF) viewed down the crystallographic b axis. Aromatic OFF interactions between opposite enantiomers of 6 are reinforced by nitro‚‚‚aromatic N-O‚‚‚π contacts. The opposite enantiomers of 6 are colored light or dark green. Color code: host C, green; O, orange; N, dark blue; H, light blue; guest C, purple.

Dinitrodiphenyldiquinoline Host

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Figure 7. Two views of the various host-guest associations in the compound (6)‚(DMF). The centrosymmetric nature of these arrangements is highlighted.

corresponded to an endotherm in the DSC, but the decompositions were complex and did not allow us to compare onset temperatures with the boiling points of the guests directly. The experimental values should be lower compared to the calculated values; we believe that some initial decomposition of the host started to occur in the temperature range used to calculate the weight loss. Conclusions The strategy of introducing polar substituents on the aromatic wings of the molecular framework 1 was successful in conferring lattice inclusion properties on the new diquinoline derivative 6. Nitro sensor groups were effective in providing multiple hydrogen bonding interactions between the host molecules. These were robust and directional supramolecular attractions that provided closely related host packing arrangements for all three inclusion compounds of 6. The guest molecules differed in their functionality, hydrogen bonding strength, and physical size. However, regardless of the example, these guests were all located near one of the host quinoline nitrogen atoms and interacted with it by means of O-H‚‚‚N or C-H‚‚‚N hydrogen bonds. The nitro groups were not directly involved in hostguest interaction. Rather the role of the nitro groups was to assemble the host lattice and thereby providing a guest cavity in each case. In conclusion, the supramolecular behavior of host 6 is unique compared to the other diquinolines that we have reported recently. It interacted selectively with polar guest molecules for the first time. Therefore, it is a potential candidate for the separation and purification of polar compounds from a mixture. Zaworotko et al.26,27 have reported the formation of pharmaceutical binary solids between cocrystal-forming pyridines [4,4′bipyridine and trans-1,2-bis(4-pyridyl)ethylene] and active pharmaceutical ingredients such as rac-ibuprofen. By analogy, the supramolecular heterocyclic system 6 could be exploited as a similar reagent for the formulation of pharmaceutical cocrystals. However, the toxicity of these new diquinoline

Figure 8. The top panel shows the crystal packing of the host and guest molecules in the compound (6)‚(pyridine) as viewed down the crystallographic a axis, showing the zigzag chains of host molecules and the inclusion of guest pyridine molecules. The bottom panel shows association of the host molecules by means of N-O‚‚‚H-C (d ) 3.10 and 3.13 Å) and N-O‚‚‚π (d ) 2.60 and 2.63 Å) interactions.

Figure 9. The host-guest C-H‚‚‚N interactions present in solid (6)‚(pyridine).

derivatives should be considered very carefully in case of testing the new cocrystal as new drugs. The use of the supramolecular heterocyclic system as cocrystal former can be a useful approach

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Table 3. Thermal Analysis Data compound H/G ratio TG results DSC results

calcd % mass loss exptl % mass loss peak A T, °C (endo) peak B T, °C (endo)

to isolate and purify the active pharmaceutical ingredient (API) from a mixture of reaction products. Experimental Section NMR data were recorded using a Bruker 400 MHz standard bore instrument, and carbon substitution information was determined using the DEPT procedure. Electrospray HRMS data were recorded using a Finnigan/MAT 95XL-T mass spectrometer, melting points were determined using a Bu¨chi B-540 melting point instrument, and infrared data were obtained using an Excalibur Series, Biorad FTS3000MX. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were performed on a TA instrument SDT 2960 with simultaneous DSC-TGA. Crystals were dried in air and placed in alumina sample pans. Sample masses in each case were 10-15 mg, and these were purged using a stream of nitrogen flowing at 200 mL min-1. All experiments were carried out with a temperature program starting from room temperature, isothermal for 10 min, followed by 10 °C min-1 ramp up to 750 °C. 8,16-Diphenyl-6,7,14,15-tetrahydro-7,15-methanocycloocta[1,2b:5,6-b′]diquinoline (3). 2-Aminobenzophenone (4, X ) H) (2.60 g, 13.2 mmol) and bicyclo[3.3.1]nonane-3,7-dione (5) (1.00 g, 6.6 mmol) were dissolved in ethanol, and concentrated HCl (5 mL) was added with stirring. The mixture was then refluxed overnight. The precipitated product was filtered and washed with ethanol and then diethyl ether to yield the diquinoline (3) (2.34 g, 75%) as a light brown powder; mp > 385 °C; IR (KBr) 3046, 2949, 1959, 1636, 1583, 1519, 1482, 1456, 1439, 1382, 1344, 1245, 1150, 1030, 1007, 760, and 705 cm-1; 1H NMR (MeOD) δ 2.51 (s, 2H), 3.46 and 3.50 (d, JAB ) 18.8 Hz, 2H), 3.60 and 3.64 (dd, JAB ) 18.8 Hz, JBX ) 6.4 Hz, 2H), 4.00 (s, 2H), 7.55-7.66 (m, 6H), 7.74-7.87 (m, 8H), 8.04-8.07 (m, 2H), and 8.13 and 8.15 (d, J ) 8.8 Hz, 2H); 13C NMR (MeOD) δ 27.63 (CH2), 29.07 (CH), 37.74 (CH2), 120.99 (CH), 128.68 (CH), 129.38 (CH), 130.32 (CH), 130.40 (CH), 130.50 (CH), 130.89 (CH), 131.13 (CH), 133.71 (C), 134.82 (C), 135.64 (CH), 139.21 (C), 155.74 (C), 159.55 (C), and one quaternary C not obsd; anal. HRMS m/z calcd for MH+ (C35H27N2)+ 475.2169, found 475.2180. 2,10-Dinitro-8,16-diphenyl-6,7,14,15-tetrahydro-7,15-methanocycloocta[1,2-b:5,6-b′]diquinoline (6). 2-Amino-5-nitrobenzophenone (4, X ) NO2) (3.20 g, 13.2 mmol) and bicyclo[3.3.1]nonane-3,7-dione (5) (1.00 g, 6.6 mmol) were dissolved in ethanol, and concentrated HCl (5 mL) was added with stirring. The mixture was then refluxed overnight. The precipitated product was filtered and washed with ethanol and then diethyl ether to yield the dinitrodiquinoline (6) (1.85 g, 50%) as a pale orange powder; mp > 300 °C; IR (KBr) 3099, 3055, 2939, 2873, 2825, 1641, 1593, 1539, 1480, 1381, 1344, 821, and 704 cm-1; 1 H NMR (DMSO) δ 2.35 (s, 2H), 3.23 and 3.28 (d, JAB ) 18.4 Hz, 2H), 3.40-3.46 (m, 2H), 3.74 and 3.75 (d, J ) 2.8 Hz, 2H), 7.527.54 (m, 2H), 7.57 and 7.59 (d, J ) 7.6 Hz, 2H), 7.72-7.74 (m, 4H), 7.71-7.82 (m, 2H), 8.05 and 8.05 (d, J ) 2.8 Hz, 2H), 8.22 and 8.24 (d, JAB ) 9.2 Hz, 2H), and 8.43 and 8.45 (dd, J ) 9.2 Hz, J ) 2.4 Hz, 2H); 13C NMR (DMSO) δ 26.80 (CH2), 28.55 (CH), 40.02 (CH2), 122.50 (CH), 123.78 (CH), 125.90 (C), 127.49 (CH), 128.68 (CH), 129.03 (CH), 129.34 (CH), 129.38 (CH), 129.53 (CH), 133.62 (C), 133.79 (C), 144.98 (C), 151.58 (C), 160.04 (C), and one quaternary C not obsd; anal. HRMS m/z calcd for MH+ (C35H25N4O4)+ 565.1876, found 565.1871. Solution and Refinement of the Crystal Structures. The singlecrystal X-ray diffraction experiments were carried out on a Bruker SMART APEX diffractometer equipped with a CCD detector and Mo KR sealed tube at 223(2) K. SMART28 was used for collecting frames data, indexing reflection, and determining lattice parameters. SAINT28 was used for integrating intensity of reflections and scaling. SADABS29 was used for absorption correction and SHELXTL30 for space group and structure determination and least-squares refinements on F2. All C-H hydrogen atoms were placed in calculated positions for the

(6)‚(methanol)

(6)‚(DMF)

(6)‚(pyridine)

1:1 5.37 4.53 191.63

1:1 11.46 12.86 205.76

1:1 12.29 13.51 131.09 201.72

purpose of structure factor calculation. Crystallographic data (cif) have been deposited with the Cambridge Structural Data Centre, CCDC reference numbers 280483-280486. See http://www.rsc.org/suppdata/ for crystallographic data in cif format. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax +44(0)-1223-336033 or e-mail [email protected]].

Acknowledgment. We would like to thank the Agency for Science, Technology and Research (A*STAR) for the financial support and Prof. Koh Lip Lin and Ms. Tan Geok Kheng from the National University of Singapore for their technical support and assistance. Special thanks are due to Ms. Emily Lau for her great contribution to this work. References (1) Seddon, K. R.; Zaworotko, M. J. Crystal Engineering: The Design and Application of Functional Solids; Kluwer Academic: Boston, MA, 1999. (2) Moulton, B.; Zaworotko, M. J. Chem. ReV. 2001, 101, 1629-1658. (3) Goldberg, I. In Inclusion Compounds; Atwood, J. L., Davies, J. E. D., MacNicol, D. D., Eds.; Oxford University Press: Oxford, U.K., 1991; Vol. 4, Chapter 10, pp 406-447. (4) Bishop, R. Chem. Soc. ReV. 1996, 25, 311-319. (5) Bishop, R. Synlett 1999, 1351-1358. (6) Marjo, C. E.; Bishop, R.; Craig, D. C.; O’Brien, A.; Scudder, M. L. Chem. Commun. 1994, 2513-2514. (7) Marjo, C. E.; Bishop, R.; Craig, D. C.; Scudder, M. L. Eur. J. Org. Chem. 2001, 863-873. (8) Rahman, A. N. M. M.; Bishop, R.; Craig, D. C.; Scudder, M. L. Org. Biomol. Chem. 2003, 1, 1435-1441. (9) Bishop, R. Crystal Engineering of Halogenated Heteroaromatic Clathrate Systems. In Frontiers in Crystal Engineering; Tiekink, E., Vittal, J. J., Eds.; Wiley: Chichester, U.K., 2006; Chapter 5, pp 91116. (10) Alshahateet, S. F.; Bishop, R.; Scudder, M. L.; Hu, C. Y.; Lau, E. H. E.; Kooli, F.; Judeh, Z. M. A.; Chow, P. S.; Tan, R. B. H. CrystEngComm 2005, 7 (21), 139-142. (11) Alshahateet, S. F.; Bishop, R.; Craig, D. C.; Scudder, M. L. Cryst. Growth Des. 2004, 4 (4), 837-844. (12) Rahman, A. N. M. M.; Bishop, R.; Craig, D. C.; Scudder, M. L. Org. Biomol. Chem. 2004, 2, 175-182. (13) Desiraju, G. R.; Gavezzotti, A. Acta Crystallogr., Sect. B 1989, 45, 473-482. (14) Hunter, C. A.; Lawson, K. R.; Urch, C. J. J. Chem. Soc., Perkin Trans. 2 2001, 651-669. (15) Alshahateet, S. F.; Bishop, R.; Craig, D. C.; Scudder, M. L. CrystEngComm 2001, 3 (55), 264-269. (16) Rahman, A. N. M. M.; Bishop, R.; Craig, D. C.; Marjo, C. E.; Scudder, M. L. Cryst. Growth Des. 2002, 2, 421-426. (17) Rahman, A. N. M. M.; Bishop, R.; Craig, D. C.; Scudder, M. L. Eur. J. Org. Chem. 2003, 72-81. (18) Ashmore, J.; Bishop, R.; Craig, D. C.; Scudder, M. L. CrystEngComm 2004, 6 (100), 618-622. (19) Alshahateet, S. F.; Bishop, R.; Craig, D. C.; Scudder, M. L. CrystEngComm 2001, 3 (48), 225-229. (20) Ng, M. T.; Deivaraj, T. C.; Klooster, W. T.; McIntyre, G. J.; Vittal, J. J. Chem.sEur. J. 2004, 10, 5853-5859. (21) Sreenivasulu, B.; Vittal, J. J. Angew. Chem., Int. Ed. 2004, 43, 57695772. (22) Cheng, C.-C.; Yan, S.-J. Org. React. 1982, 28, 37-201. (23) Thummel, R. P. Synlett 1992, 1-12. (24) Bertz, S. H. J. Org. Chem. 1985, 50, 3585-3592. (25) Desiraju, G. R.; Steiner, T. The Weak Hydrogen Bond in Structural Chemistry and Biology; Oxford University Press: Oxford, U.K., 1999.

Dinitrodiphenyldiquinoline Host (26) Baily Walsh, R. D.; Bradner, M. W.; Fleichman, S.; Morales, L. A.; Moulton, B.; Rodriguez-Hornedo N.; Zaworotko, M. J. Chem. Commun. 2003, 186-187. (27) Almarsson, O.; Zaworotko, M. J. Chem. Commun. 2004, 1889-1897. (28) SMART and SAINT Software Reference Manuals, version 4.0; Siemens Energy and Automation, Inc., Analytical Instrumentation: Madison, WI, 1996.

Crystal Growth & Design, Vol. 6, No. 7, 2006 1683 (29) Sheldrick, M. SADABS, software for empirical absorption correction; University of Go¨ttingen: Go¨ttingen, Germany, 1996. (30) SHELXTL Reference Manuals, version 5.03; Siemens Energy and Automation, Inc., Analytical Instrumentation: Madison, WI, 1996.

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