Gradual Transition from NH···Pyridyl Hydrogen Bonding to the NH···O

Gradual Transition from NH · · · Pyridyl Hydrogen Bonding to the NH · · · O Tape Synthon in Pyridyl Ureas Peter Byrne, David R. Turner, Gareth O. Lloyd, Nigel Clarke, and Jonathan W. Steed* Department of Chemistry, Durham UniVersity, South Road, Durham, U.K., DH1 3LE

CRYSTAL GROWTH & DESIGN 2008 VOL. 8, NO. 9 3335–3344

ReceiVed March 4, 2008; ReVised Manuscript ReceiVed June 13, 2008

ABSTRACT: We report the synthesis and X-ray crystal structures of a series of pyridyl ureas of the type currently topical in anion binding and supramolecular gelation applications, along with their anion-binding ability in solution. The structures of the simple pyridyl ureas are dominated by urea · · · N(pyridyl) hydrogen bonding, because of steric congestion of the urea carbonyl by intramolecular CH · · · O interations. However, introducing a further competing synthon in the form of alkenic or π-stacking interactions causes a gradual changeover, through a number of interesting intermediate hydrogen bonding motifs, to the urea R-tape arrangement. Introduction The urea and thiourea functional groups are of central importance in supramolecular chemistry because of their strong hydrogen bond donor and acceptor ability which enables them to take part in self-association processes (e.g., formation of molecular capsules1-6 or bis(urea) gels7-14) or bind to guest anions.7,15-26 Pyridyl ureas such as N,N′-di-3-pyridyl urea27-29 have attracted a great deal of recent attention both in the anion binding and crystal engineering literature because of their selective anion binding,16,18,22,30-35 anion separation15,18,36,37 and supramolecular gelation properties.8,11,38,39 These kinds of aryl ureas also form fascinating solid state structures exhibiting a complex interplay between intramolecular hydrogen bonding interactions, NH · · · O urea tape hydrogen bonding and NH · · · Npyridyl interactions.29 Urea hydrogen bonding to anions adds a further dimension to this system of particular relevance to solid state anion separations.18 Original work by Etter on diaryl ureas bearing electron withdrawing groups (particularly bis(3-nitrophenyl)urea) showed that the compounds form cocrystals in which the urea NH protons interact with good hydrogen bond acceptors such as solvent molecules or cocrystallizing agents such as Ph3PdO, but the urea tape motif (synthon I in Figure 1) is very rarely observed.40-42 This work has recently been extended by Nangia who showed that in N,N′bis(3-pyridyl)urea and N,N′-phenyl-3-pyridylurea the aryl CH protons are sufficiently acidic to result in a planar conformation in which the urea tape motif (synthon I) is disfavored because the urea oxygen atom is engaged in intramolecular CH · · · O interactions (synthon III, Figure 1).29 As a result, the ureapyridyl interaction (synthon II, Figure 1) predominates despite the lower hydrogen bond basicity of pyridine compared with simple ureas such as tetramethyl urea (tetramethylurea has βH2 ) 0.743, pyridine has 0.62543-45). The pyridyl nitrogen atom thus plays a role analogous to that of the cocrystallizing agent in the nitrophenyl urea system. These CH · · · O interactions are favored by the increased hydrogen bond acidity of the CH protons arising from the electron withdrawing effect of the pyridyl or nitro groups. Thus N,N′-diphenylurea which has less acidic CH protons adopts a nonplanar conformation leaving the urea CdO free to form the R-tape synthon.29 The complex tradeoff between these various synthons in the solid state and their relevance to the ability of aryl ureas to form cocrystals, * To whom correspondence should be addressed. Tel: +44 (0)191 334 2085. Fax: +44 (0)191 384 4737. E-mail: [email protected].

gels or anion complexes has led us to explore a range of solidstate pyridyl ureas with a view to determining the factors leading to crossover between the synthons shown in Figure 1. In particular we now report an interesting series of compounds showing “intermediate” behavior between synthons I and II.

Results and Discussion The syntheses of the three isomeric ligands 1-3 were achieved in a straightforward manner by the reaction of p-tolylisocyanate with the appropriate aminopyridine isomer, as previously reported for 2 and 3.46,47 The thiourea analogue of 2, namely 4, was prepared via an analogous reaction using p-tolylisothiocyanate. Crystals suitable for single crystal X-ray diffraction were obtained for all of the monopyridylureas 1-4. The geometry of the ortho isomer 1 ligand differs from those of the other isomers in that the position of the urea substituents allows for the formation of an intramolecular six-membered hydrogen bonded ring incorporating the nitrogen atom of the pyridyl ring and the urea group, Figure 2. A conformation that allows this intramolecular interaction has previously been observed in solution for unsymmetrical N,N′-dipyridyl ureas with ortho-substitution.28 According to Etter’s rules,40 such an intramolecular interaction should occur favorably over intermolecular interactions. The furthest NH unit from the pyridyl ring is involved in an intramolecular interaction with the pyridyl nitrogen atom, causing the molecule to adopt a syn-anti conformation around the urea group. The NH group closest to the pyridyl ring is engaged in an intermolecular interaction with the carbonyl oxygen atom on a neighboring molecule, forming a dimer held together by an R22(8) motif (using graph set nomenclature48) analogous to that observed in carboxylic acid

10.1021/cg800247f CCC: $40.75  2008 American Chemical Society Published on Web 08/01/2008

3336 Crystal Growth & Design, Vol. 8, No. 9, 2008

Byrne et al.

Figure 1. Supramolecular synthons involving pyridyl ureas.

and amide dimers.49,50 The long-range structure is held together solely by means of edge-to-face π-stacking interactions between molecules. In contrast to the dimeric nature of 1, compounds 2 and 3 exist as infinite strands in the solid-state held together by a series of R12(6) NH · · · Npyridyl interactions between the urea groups and the pyridyl acceptor, Figure 3. The urea carbonyl groups are involved in intramolecular CH · · · O interactions in the same way as observed by Nangia for N,N′-bis(3-pyridyl)urea and N,N′phenyl-3-pyridylurea, consistent with the electron withdrawing nature of the pyridyl nitrogen atom. These interactions give a planar conformation in each case. The hydrogen bonded strands themselves are interacting together mostly via offset face-toface π-stacking with some edge-to-face interactions. In all three structures therefore, the pyridyl nitrogen atom acts as the strongest hydrogen bond acceptor because of steric hindernce around the urea carbonyl oxygen atom. In addition to the structure shown in Figure 3b, compound 2 also forms a hydrate cocrystal with the empirical formula 2 · 2H2O when crystallized from water. The enclathrated water in this structure is ordered within channels formed between molecules of the ligand, Figure 4a. One of the two included solvent molecules in the asymmetric unit is hydrogen bonded to the pyridyl nitrogen atom while the other is involved in interactions only with neighboring water molecules, Figure 4b.

Figure 2. Solid-state dimerization of 1.

Interestingly, the pyridyl urea itself is not planar, as in the previous structures, with both rings twisted by around 55° with respect to the urea group and hence there are no intramolecular hydrogen bonds of the type shown in synthon III, Figure 1. Instead, the pyridyl urea surprisingly forms a urea tape R-network (synthon I). Clearly, this motif occurs because the pyridyl nitrogen atom is engaged in interactions to water and hence is unavailable to form the pyridyl urea synthon II. Hence

Hydrogen Bonding in Pyridyl Ureas

Crystal Growth & Design, Vol. 8, No. 9, 2008 3337

Figure 3. Part of the infinite chains in the structures of (a) 3 and (b) 2 both involving synthons II and III.

Figure 4. The structure of 2 · 2H2O (a) showing the urea R-tape motif and (b) hydrogen bonding to the pyridyl rings (some hydrogen atoms omitted for clarity).

the structure is entirely consistent with Etter’s rules since water, as the strongest donor interacts with the pyridyl unit as the strongest acceptor. This interaction, interestingly however, acts synergically to break the intramolecular CH · · · O interactions allowing the formation of the urea tape synthon I. The thiourea analogue 4 was also characterized by X-ray crystallography. The longer CdS bond compared to CdO makes the thiourea sulfur atom far less sterically hindered and therefore a stronger hydrogen bond base. The structure of 4 is remarkably different from that of the oxygen-containing analogue 2. The urea group adopts an anti-anti conformation rather than the syn-syn geometry seen for 2 and 3, Figure 5. The result is a thiourea ribbon synthon IV in which the sulfur atom is nowhere near the aryl CH protons and engages in a series of linked R22(8) motifs. The structure is disordered and the pyridyl and tolyl rings share occupancy of the same position in the crystal structure, leaving a disordered half-molecule in the asymmetric unit. The pyridyl nitrogen atom, as the weaker hydrogen bond acceptor, is not involved in any significant intermolecular interactions.51,52 Hydrogen bond parameters for compounds 1-4 are summarized in Table 1. The structure of 2 · 2H2O suggests that synthons I and II exist in a fine balance. Previously we have shown that replacing the p-tolyl group in compounds of type 2 with a sterically bulky

Figure 5. The crystal structure of the thiourea compound 4 showing the thiourea ribbon synthon IV.

aliphatic substituent can result in strong directional constraints, and can give rise to polar crystals with Z′ >153 and distorted R-tape type packing of the urea substituents.54 As part of our work on metallogels and anion binding coordination polymers11,24 we have prepared the homologous series of bis(pyridylurea)al-

3338 Crystal Growth & Design, Vol. 8, No. 9, 2008

Byrne et al.

Table 1. Hydrogen Bond Data for Structures of 1-4a d (D-H)/Å

d (D · · · A)/Å

∠ DH · · · A/°

1.96 1.96

2.688(15) 2.837(15)

139 176

2.21 2.22 2.22 2.31

3.049(3) 3.057(3) 2.860(4) 2.911(4)

160 159 124 121

2.63 2.17 2.26 2.25

3.313(4) 2.976(3) 2.857(4) 2.870(4)

136 151 120 122

2.13 1.98 1.96(3) 1.98(10) 2.07(4)

2.911(11) 2.801(11) 2.854(10) 2.813(12) 2.918(12)

148 154 172(11) 152(20) 158(8)

2.48

3.3054(19)

156.3

d (H · · · A)/Å 1

N(3)-H(3N) · · · N(1) N(2)-H(2N) · · · O(1)#1

0.88 0.88 2

N(2)-H(2N) · · · N(1)#2 N(3)-H(3N) · · · N(1)#2 C(5)-H(5) · · · O(1) C(8)-H(8) · · · O(1)

0.88 0.88 0.95 0.95

N(2)-H(2N) · · · N(1)#3 N(3)-H(3N) · · · N(1)#3 C(4)-H(4) · · · O(1) C(8)-H(8) · · · O(1)

0.88 0.88 0.95 0.95

N(2)-H(2N) · · · O(1)#4 N(3)-H(3N) · · · O(1)#4 O(2)-H(1O) · · · N(1) O(2)-H(2O) · · · O(3)#5 O(3)-H(3O) · · · O(2)

0.88 0.88 0.90(2) 0.90(2) 0.89(2)

N(1)-H(1N) · · · S(1)#6

0.88

3

2 · 2H2O

Figure 6. Crystal structure of the bis(3-pyridylurea) compound 5a showing the “intermediate bifurcated” hydrogen bonded synthon (V). Hydrogen bond distances N2 · · · N1 2.9896(14), N3 · · · N1 3.3025(15), N3 · · · O1 2.9498(13) Å.

4 a

Where no esd is reported CH and NH lengths are normalized to standard X-ray distances.64 Symmetry equivalents used: #1, -x + 1, -y + 1, -z; #2, -x + 1/2, y - 1/2, z + 1/2; #3, -x - 1/2, y + 1/2, -z + 1/2; #4, x + 1/2, -y + 3/2, -z; #5, -x + 1/2, y - 1/2, z; #6 -x, -y + 1, -z + 1.

kanes 5a-c and the related aryl analogues 6 and 7. Compounds 5 in particular retain the electron-withdrawing pyridyl substituent on one side of the urea CdO group and hence should engage in the CH · · · O synthon III but are sterically unencumbered on the other side of the urea carbonyl, meaning that the carbonyl oxygen atom should be relatively available to take part in hydrogen bonding. Moreover the availability of compounds of varying chain length allows the possibility of increasing the influence of another synthon, namely interactions between adjacent oligomethylene chains, which increase by ca. 5 kJ mol-1 per sCH2s unit.55 Compounds 5a-c are readily prepared by reaction of 3-isocyanato-pyridine, formed in situ by a Curtius rearrangement of nicotinoyl azide, with the appropriate R,ω-diamino alkane. Crystals of all three compounds were grown from a mixture of tetrahydrofuran and water (3:2) and characterized by X-ray crystallography. The X-ray crystal structure of 5a is shown in Figure 6. The structure retains one strong urea NH · · · Npyridyl hydrogen bond from one of the two NH groups of the single crystallographically unique urea functionality (Z′ ) 0.5); however the other urea NH donor forms a remarkable bifurcated interaction to both the pyridyl nitrogen atom and a urea carbonyl acceptor. The conformation of the molecule is “kinked” involving two gauche N-C-C-N torsion angles at the ethylene bridge a seen for analogous phenylethyl bis(urea) gelators56 and this hydrogen bonding arrangement which is somewhat “intermediate” between synthons I and II allows an approximately orthogonal arrangement of successive layers of molecules. We term this pattern the “intermediate bifurcated” synthon (V). The pyridyl CH · · · O interaction, synthon III is also present on one side of the urea carbonyl group and hence the angle of approach of the NH vector is rather out of the sterically congested urea plane. The analogous propylene-bridged compound 5b moves further along the path linking synthon II to tape synthon I. The asymmetric unit comprises one whole molecule and hence there

Figure 7. Crystal structure of the bis(3-pyridylurea) compound 5b showing the orthogonal “intermediate non-bifurcated” hydrogen bonding synthon VI. Hydrogen bond distances N2 · · · N6 2.892(2), N3 · · · O2 2.799(2), N4 · · · O1 2.900(2), N5 · · · O1 2.918(2) Å.

are two unique urea moieties. The propylene bridge comprises one gauche and one anti N-C-C-C torsion angle and the urea carbonyl groups are crowded by the intramolecular CH · · · O bonded synthon III in both cases. Nevertheless, one urea group, adjacent to the anti substituent chain, forms a full R-tape synthon I motif, while the other urea group adjacent to the gauche torsion exhibits another new hydrogen bonding mode in which one NH group interacts with an orthogonal pyridyl nitrogen atom on an adjacent molecule, while the other forms a nonbifurcated, short hydrogen bond with a urea carbonyl from a third molecule. We term this pattern the “intermediate nonbifurcated” synthon (VI). The tape motif (I) and intermediate nonbifurcated motif (VI) alternate along stacks of urea groups, thus there is a continuous hydrogen-bonded urea chain but orthogonal to the classical infinite R-tape and with one NH in every four interacting with an pyridyl N atom instead of a urea carbonyl (Figure 7). This arrangement appears to allow the methylene groups of the propylene bridge to maximize van der Waals stacking and indeed the stacking of polymethylene chains is a well-known supramolecular synthon in its own right.55 If methylene stacking is important in these systems then it should begin to dominate over the intermediate synthons as we move to longer chain length. This trend is borne out in moving

Hydrogen Bonding in Pyridyl Ureas

Figure 8. (a, b) Two views of the crystal structure of the bis(3pyridylurea) compound 5c showing the parallel “intermediate nonbifurcated” hydrogen bonding synthon VI. Hydrogen bond distances N2 · · · O2 2.880(4), N3 · · · O2 2.920(4), N4 · · · O1 2.925(4), N5 · · · N6 3.024(4) Å.

to the X-ray crystal structure of the butylene-bridged compound 5c. In this case now all of the N-C-C-C and C-C-C-C torsion angles at the butylene bridges are anti giving a more colinear arrangement of the molecules. The structure is similar to 5b in that alternating urea tape and intermediate nonbifurcated synthons of type VI are observed along the antiparallel urea end-to-end chains; however, the geometry of the intermediate synthon in this case has the molecules bearing the pyridyl and carbonyl acceptors much more colinear with the donor molecule rather than orthogonal to it. This arrangement allows efficient stacking of the methylene groups (Figure 8), as observed in related systems.56 Extending the concept of competing synthons still further, other synthons capable of stacking, such as π-stacking interactions, should also bring about a change from pyridyl-urea (synthon II) to urea tape (type I) interactions. We therefore examined the structures of the p-phenylene-bridged bis(3pyridylurea) ligand 6 and the napthalenyl analog 7 which should result in replacing methylene stacking with π-π stacking interactions and hence bring about behavior similar to compounds 5b or 5c. Compound 6 was crystallized from 10% aqueous THF solvent and its X-ray crystal structure determined. The structure proves to be very similar to that of 5c (indeed they are isomorphous) with essentially a double urea tape motif that is broken only by the fact that one of the total of four unique urea NH groups forms a shorter interaction to a twisted pyridyl nitrogen atom rather than the nearby carbonyl oxygen atom. The compound thus contains a bifurcated donor interaction but is distinct from synthon V because it is the carbonyl oxygen atom that accepts two hydrogen bonds, not the pyridyl nitrogen atom. We refer to this new synthon as the intermediate O2Nbifurcated synthon (VII). This synthon again alternates with the urea tape synthon (I) as in 5c. The p-phenylene spacers form an offset π-stack arrangement very much analogous to the stacking of the all anti butylene chains in 5c (Figure 9). Finally in the case of 7 π-π stacking interactions should be even more dominant than in 6 and indeed this proves to be the case with 7 entirely relinquishing the pyridyl CH · · · O synthon III to give a structure that comprises solely the urea R-tape motif I in conjunction with offset face-to-face π-π stacking of the napthalenyl residues. The pyridyl and napthalenyl residues are twisted out of the plane of the urea functionality allowing ready access to the carbonyl oxygen atom, Figure 10. The insignificance of interactions to the pyridyl nitrogen atom (which are of the CH · · · N type) is exemplified by a 2-fold disorder of the

Crystal Growth & Design, Vol. 8, No. 9, 2008 3339

Figure 9. Crystal structure of 6 showing the almost-complete urea tape and the “intermediate bifurcated O2N” synthon VII. Hydrogen bond distances: N2 · · · O2 2.851(4), N3 · · · O2 2.925(4), N4 · · · O1 2.853(4), N5 · · · N6 3.082(4), N5 · · · O1 3.219(4) Å.

Figure 10. Crystal structure of 7 showing the full urea R-tape motif accompanied by offset face-to-face π-π stacking of the napthalenyl residues. Note the absence of intramolecular CH · · · O interactions (synthon III). Hydrogen bond distances: N2 · · · O1 2.788(2), N3 · · · O1 2.891(2) Å.

pyridyl residue that swaps the positions of the pyridyl nitrogen atom and one CH group. Clearly these structures indicate a considerable degree of competition between urea carbonyl and pyridyl acceptors in which the balance may be tipped by the demands of additional factors such as oligomethylene chain, and π-π stacking interactions. We have shown that metal complexes of pyridyl urea ligands in which the coordinated pyridyl nitrogen atom cannot accept hydrogen bonds form a mixture of urea tape and urea · · · anion interactions depending on the number of anions present (if there are too few anions available in comparison to urea groups then the urea tape is formed).24,46 A simpler expedient to examination of the interplay between urea · · · urea and urea · · · anion interactions is to protonate the pyridyl nitrogen atom. We were fortunate to obtain crystals of the protonated form of 2 as its H2SiF6 salt serendipitously from the reaction of Fe(BF4)2 with the ligand in a glass vessel. It is believed that HF was generated in situ from action of HF generated from the BF4- anion which in turn reacted with the glass to produce the hexafluorosilicate anion, as has been observed in other systems.57 The salt has the formula [(2)H]2(SiF6). The structure of

3340 Crystal Growth & Design, Vol. 8, No. 9, 2008

Byrne et al.

Table 2. Hydrogen Bonds within the Structure of [(2)H]2(SiF6)a d d d (D-H)/Å (H · · · A)/Å (D · · · A)/Å N(1)-H(1N) · · · F(4)#1 N(1)-H(1N) · · · F(5) N(2)-H(2N) · · · F(1) N(2)-H(2N) · · · F(2) N(2)-H(2N) · · · F(3) N(3)-H(3N) · · · F(3) N(4)-H(4N) · · · F(1)#1 N(4)-H(4N) · · · F(2)#2 N(5)-H(5N) · · · F(4) N(5)-H(5N) · · · F(5) N(6)-H(6N) · · · F(6) a

0.90(2) 0.90(2) 0.88 0.88 0.88 0.88 0.92(2) 0.92(2) 0.88 0.88 0.88

1.86(2) 2.37(2) 2.37 2.55 2.37 2.02 2.00(2) 2.07(2) 2.13 2.42 1.96

2.7327(17) 2.9739(17) 3.1795(18) 3.2248(16) 3.1347(17) 2.8168(17) 2.8023(18) 2.8277(16) 2.9680(17) 3.0550(15) 2.8291(16)

∠ DH · · · A/° 161.9(19) 124.6(16) 153.7 134.4 145.0 150.5 145.9(18) 138.7(17) 158.8 129.0 169.1

Urea hydrogen atoms are in fixed positions.

this unexpected product is interesting as it shows that the urea group does indeed form hydrogen bonds even with relatively weak hydrogen bond acceptor anions, Table 2. The structure consists of two crystallographically unique dimeric [(2)H]2(SiF6) units (Z′ ) 2), with the anion bridging between the two urea groups in each case. The difference between these crystallographically independent dimers arises from the orientation of the urea · · · anion interactions, Figure 11. One of the dimers acts in the more expected manner, with the two NH donors interacting with the anion forming separate NH · · · F bonds in an R22(8) ring. The other dimer, however, contains a more unusual situation, in which one of the NH groups, N2, is a trifurcated donor. This is akin to the arrangement observed between protonated DABCO and hexachloropalladate(IV),58 although the interaction to SiF62- is uncommon as fluorosilicates are not as good hydrogen bond acceptors as metal-coordinated chloride, for example.59 The relatively large SiF62- anions each also accept hydrogen bonds from the protonated pyridinium NH groups, while the urea carbonyl is not involved in hydrogen bonding interactions to NH. Anion Association Behavior of Simple Pyridyl Ureas. The pyridyl-urea compounds reported herein are potentially useful in anion binding when appended in charged systems with either an organic or inorganic core. However, the ligands themselves also show significant anion association, despite being uncharged.60,61 Such associations demonstrate the intrinsic strength of binding offered by the two acidic NH sites of urea that are able to act in a cooperative manner to associate with both simple spherical and more complex anions, as shown by the urea-anion synthons in Figure 1. Simple, disubstituted ureas have previously been observed to associate with carboxylates in such a manner, for example.62 The ability of 2 and 3 to associate with some simple anions was explored, to assess the viability of this family of ligands for inclusion within host systems. Binding constants were obtained by carrying out 1H NMR spectroscopic titrations using various anions and processing the data using the program HypNMR.63 The anions were added as tetrabutylammonium (TBA) salts in all cases, as the TBA cation is less competitive than cations in other commercially available salts, such as metals, for association with the anions and the salts are also highly soluble. The values obtained for the 1:1 association (log K11) are shown in Table 3. Compound 1 was not tested, as the urea on the pyridyl ring is in an unfavorable position relative to the pyridyl nitrogen atom for forming intermolecular interactions. Previous work has also shown that ortho-substituted pyridyl ligands are quite unreactive and therefore hard to attach to central cores to form receptor species.64 The titrations of 2 and 3 show that the urea-based ligands possess an intrinsic affinity for anion species. In some cases

the values obtained are quite remarkable (albeit in a relatively noncompetitive solvent), especially considering that the interactions are not charge assisted. Accurate binding constants could not be obtained with chloride and acetate as the magnitude of K11 is too large to be obtained via NMR spectroscopic methods (with an upper limit of around 104 M-1). The curves obtained following the urea proton closest to the pyridyl ring for the 2 titrations are shown in Figure 12. The largest chemical shift changes observed those with acetate, which is a more basic anion than the others. The binding constants obtained for nitrate show that the 3 ligand has slightly more affinity for this anion than the 2 ligand does. This difference is attributed to an electronic effect arising from the difference in the substitution position of the urea group on the pyridyl ring. Conclusions In this paper we have extended the work of Etter and Nangia to shown that steric crowding around a urea carbonyl acceptor arising from synthon III and leading to the urea-pyridyl motif (synthon II) can be overcome by the introduction of further competing supramolecular synthons, namely polymethylene stacking and π-π stacking. The interplay between these competing factors leads to a progression of structure from synthon II through three intermediate synthons (V to VII) to a pure urea R-tape motif in 7 with increasing dominance of interactions to the urea carbonyl oxygen acceptor rather than the pyridyl nitrogen atom, accompanied with an increasing occurrence of the urea R-tape synthon (I), as oligomethylene chain length or π-stacking surface area increases. In acetone solution selfassociation of these simple urea ligands by NH · · · pyridyl and NH · · · OdC hydrogen bonding as observed in the solid state does not compete with hydrogen bonding to anions which are much stronger hydrogen bond bases. The anion binding by 2 and 3 contrasts to work on bis(ureas) related to compounds of type 5 where there is significant competition between selfassociation and anion complexation.56 Given the considerable interest in this class of compound in supramolecular gelation and in anion binding, the present insights into their mutual interactions are potentially of broad interest. Experimental Procedures Instrumental. NMR Spectra. 1H and 13C{1H} NMR spectra were measured with a Bruker Avance NMR spectrometer, operating at proton frequencies of 400 or 360 MHz, or a 200 MHz Varian Mercury instrument. Chemical shifts are reported in ppm relative to tetramethylsilane. Fast Atom Bombardment (low resolution) mass spectra were obtained with a Kratos MS 890 Mass Spectometer or using a Micromass LCT or a Thermo LTQ FT spectrometer in ES+ mode. High resolution mass spectra were obtained with a Bruker Apex III Mass Spectrometer by Electrospray Ionization. IR spectra were measured on a PerkinElmer 100 FT-IR spectrometer, using a golden gate apparatus. Elemental Analysis for carbon, hydrogen and nitrogen was carried out by the Elemental Analysis Service at Durham and at the London Metropolitan University. X-ray Crystallography. All crystallographic measurements were carried out either with a Nonius KappaCCD or Bruker SMART 1000 diffractometer equipped with graphite monochromated Mo KR radiation. Data collection temperature was 120 K, maintained by using an Oxford Cryosystem low temperature device. Integration was carried out by the Denzo-SMN package.65 Data sets were corrected for Lorentz and polarization effects and for the effects of absorption (Scalepack65) and crystal decay where appropriate. Structures were solved using the direct methods option of SHELXS-9766 and developed using conventional alternating cycles of least-squares refinement (SHELXL-97)67 and difference Fourier synthesis with the aid of the program XSeed.68 In all cases non-hydrogen atoms were refined anisotropically except for some disordered, while C-H hydrogen atoms were fixed in idealized

Hydrogen Bonding in Pyridyl Ureas

Crystal Growth & Design, Vol. 8, No. 9, 2008 3341

Figure 11. The two crystallographically unique [(2)H]2SiF6 dimers within the X-ray structure of this salt. Table 3. A Comparison of the Binding Constants (log K11) of 2 and 3 in Acetone at Room Temperature pyridyl urea

2

3

ClNO3CH3CO2ReO4-

>4 2.98 >4 4 3.54 >4 2σ(I) (refinement on F2), 156 parameters, 30 restraints. Lp and absorption corrections applied, µ ) 0.084 mm-1. ISOR restraints were applied to atoms N(3), C(2), C(5), C(9) and C(10).

Figure 12. A comparison of the chemical shift changes observed for the urea proton closest to the pyridyl ring during titrations of 2 with various anions.

Crystal Data for 2 (Nonhydrated). C13H13N3O, M ) 227.26, colorless needle, 0.18 × 0.12 × 0.10 mm3, monoclinic, space group Pn (No. 7), a ) 6.3926(4), b ) 8.4521(5), c ) 10.6951(7) Å, β ) 91.899(3)°, V ) 577.55(6) Å3, Z ) 2, Dc ) 1.307 g/cm3, F000 ) 240, Bruker SMART 1K, Mo KR radiation, λ ) 0.71073 Å, T ) 120(2) K, 2θmax ) 54.2°, 3748 reflections collected, 1957 unique (Rint ) 0.0518). Final GooF ) 0.965, R1 ) 0.0351, wR2 ) 0.0731, R indices based on 1614 reflections with I > 2σ(I) (refinement on F2), 194 parameters, 2 restraints. Lp and absorption corrections applied, µ ) 0.086 mm-1. Absolute structure parameter ) 0.4(15).69 Crystal Data for 2 · 2H2O. C13H17N3O3, M ) 263.30, colorless plate, 0.25 × 0.20 × 0.08 mm3, orthorhombic, space group Pbcn (No. 60), a ) 9.1628(9), b ) 9.7560(10), c ) 30.271(3) Å, V ) 2706.0(5) Å3, Z ) 8, Dc ) 1.293 g/cm3, F000 ) 1120, Bruker SMART 1K CCD, Mo KR radiation, λ ) 0.71073 Å, T ) 120(2)K, 2θmax ) 49.5°, 9132 reflections collected, 2068 unique (Rint ) 0.0707). Final GooF ) 1.419, R1 ) 0.1855, wR2 ) 0.3396, R indices based on 1696 reflections with I > 2σ(I) (refinement on F2), 190 parameters, 131 restraints. Lp and absorption corrections applied, µ ) 0.094 mm-1. Crystal Data for 3. C13H13N3O, M ) 227.26, colorless needle, 0.1 × 0.1 × 0.3 mm3, monoclinic, space group P21/n (No. 14), a ) 6.9698(14), b ) 12.734(3), c ) 12.676(3) Å, β ) 95.85(3)°, V ) 1119.2(4) Å3, Z ) 4, Dc ) 1.349 g/cm3, F000 ) 480, Nonius KappaCCD, Mo KR radiation, λ ) 0.71073 Å, T ) 120(2) K, 2θmax ) 54.8°, 1858 reflections collected, 1291 unique (Rint ) 0.0818). Final GooF ) 0.987, R1 ) 0.0491, wR2 ) 0.0992, R indices based on 825 reflections with I > 2σ(I) (refinement on F2), 156 parameters, 0 restraints. Lp and absorption corrections applied, µ ) 0.089 mm-1. Crystal Data for 4. C13H13N3S, M ) 243.32, colorless block, 0.20 × 0.10 × 0.10 mm3, orthorhombic, space group Pbcn (No. 60), a ) 11.3094(4), b ) 14.0244(4), c ) 8.3930(3) Å, V ) 1331.19(8) Å3, Z ) 4, Dc ) 1.214 g/cm3, F000 ) 512, Bruker SMART 1K CCD, Mo KR radiation, λ ) 0.71073 Å, T ) 120(2) K, 2θmax ) 52.0°, 2390 reflections collected, 1297 unique (Rint ) 0.0291). Final GooF ) 1.141, R1 ) 0.0533, wR2 ) 0.1431, R indices based on 1111 reflections with I > 2σ(I) (refinement on F2), 97 parameters, 1 restraint. Lp and absorption corrections applied, µ ) 0.225 mm-1. Crystal Data for [(2)H]2(SiF6). C26H28F6N6O2Si, M ) 598.63, colorless block, 0.15 × 0.15 × 0.10 mm3, triclinic, space group P1j (No. 2), a ) 7.3551(15), b ) 13.731(3), c ) 13.869(3) Å, R ) 70.07(3), β ) 83.74(3), γ ) 86.46(3)°, V ) 1308.5(5) Å3, Z ) 2, Dc ) 1.519 g/cm3, F000 ) 620, Bruker SMART 1K CCD, Mo KR radiation, λ ) 0.71073 Å, T ) 120(2) K, 2θmax ) 55.0°, 9013 reflections collected, 5866 unique (Rint ) 0.0289). Final GooF ) 1.029, R1 ) 0.0359, wR2 ) 0.0914, R indices based on 5093 reflections with I > 2σ(I) (refinement on F2), 384 parameters, 0 restraints. Lp and absorption corrections applied, µ ) 0.171 mm-1. Crystal Data for 5a. C16H20N6O2, M ) 328.38, colorless plate, 0.34 × 0.23 × 0.10 mm3, triclinic, space group P1j (No. 2), a ) 6.244(4), b ) 7.169(4), c ) 17.566(11) Å, R ) 79.026(11), β ) 87.000(11), γ ) 88.644(10)°, V ) 770.7(8) Å3, Z ) 2, Dc ) 1.415 g/cm3, F000 ) 348, Smart 6K, Mo KR radiation, λ ) 0.71073 Å, T ) 393(2) K, 2θmax ) 50.0°, 5407 reflections collected, 2690 unique (Rint ) 0.0325). Final GooF ) 1.257, R1 ) 0.0762, wR2 ) 0.1865, R indices based on 2347

3342 Crystal Growth & Design, Vol. 8, No. 9, 2008 reflections with I > 2σ(I) (refinement on F2), 217 parameters, 0 restraints. Lp and absorption corrections applied, µ ) 0.098 mm-1. Crystal Data for 5b. C14H16N6O2, M ) 300.33, colorless prism, 0.29 × 0.27 × 0.25 mm3, monoclinic, space group P21/c (No. 14), a ) 8.4334(6), b ) 8.8676(6), c ) 9.8416(7) Å, β ) 112.234(2)°, V ) 681.27(8) Å3, Z ) 2, Dc ) 1.464 g/cm3, F000 ) 316, Smart-6K, Mo KR radiation, λ ) 0.71073 Å, T ) 120(2) K, 2θmax ) 70.0°, 7672 reflections collected, 2814 unique (Rint ) 0.0358). Final GooF ) 1.014, R1 ) 0.0555, wR2 ) 0.1460, R indices based on 1914 reflections with I > 2σ(I) (refinement on F2), 100 parameters, 0 restraints. Lp and absorption corrections applied, µ ) 0.104 mm-1. Crystal Data for 5c. C15H18N6O2, M ) 314.35, colorless plate, 0.45 × 0.38 × 0.12 mm3, monoclinic, space group P21/c (No. 14), a ) 16.447(3), b ) 5.2902(11), c ) 18.364(4) Å, β ) 105.112(7)°, V ) 1542.6(5) Å3, Z ) 4, Dc ) 1.354 g/cm3, F000 ) 664, Smart 6K, Mo KR radiation, λ ) 0. refinement on F2), 208 parameters, 0 restraints. Lp and absorption corrections applied, µ ) 0.095 mm-1 Mo KR radiation, λ ) 71073 Å, T ) 120(2) K, 2θmax ) 52.0°, 9467 reflections collected, 3032 unique (Rint ) 0.0843). Final GooF ) 0.864, R1 ) 0.0416, wR2 ) 0.0759, R indices based on 1741 reflections with I > 2σ(I). Crystal Data for 6. C18H16N6O2, M ) 348.37, colorless plates, 0.21 × 0.13 × 0.06 mm3, triclinic, space group P1j (No. 2), a ) 6.276(3), b ) 7.316(4), c ) 17.205(8) Å, R ) 80.168(14), β ) 83.754(15), γ ) 85.013(13)°, V ) 771.8(6) Å3, Z ) 2, Dc ) 1.499 g/cm3, F000 ) 364, Smart-1K, Mo KR radiation, λ ) 0.71073 Å, T ) 120(2) K, 2θmax ) 52.0°, 4903 reflections collected, 3017 unique (Rint ) 0.0445). Final GooF ) 0.983, R1 ) 0.0661, wR2 ) 0.1496, R indices based on 1766 reflections with I > 2σ(I) (refinement on F2), 235 parameters, 0 restraints. Lp and absorption corrections applied, µ ) 0.104 mm-1. Crystal Data for 7. C22H18N6O2, M ) 398.42, colorless plate, 0.40 × 0.20 × 0.10 mm3, monoclinic, space group P21/c (No. 14), a ) 18.2108(17), b ) 4.5671(4), c ) 11.3315(10) Å, β ) 106.092(3)°, V ) 905.52(14) Å3, Z ) 2, Dc ) 1.461 g/cm3, F000 ) 416, SMART 6k, Mo KR radiation, λ ) 0.71073 Å, T ) 120(2) K, 2θmax ) 58.3°, 14787 reflections collected, 2442 unique (Rint ) 0.0528). Final GooF ) 1.057, R1 ) 0.0566, wR2 ) 0.1397, R indices based on 1662 reflections with I > 2σ(I) (refinement on F2), 146 parameters, 0 restraints. Lp and absorption corrections applied, µ ) 0.099 mm-1. NMR Spectroscopic Titrations. 1H NMR titration experiments were carried out at room temperature using either a Bruker AV-500 spectrometer operating at 500 MHz or a Varian Mercury 400-BB operating at 400 MHz. All chemical shifts are reported in ppm relative to TMS as an internal reference. A solution of the host species of known concentration, typically 0.02 M, was made up in an NMR tube using the appropriate deuterated solvent (0.5 mL) with TMS added. Solutions of the anions, as tetrabutylammonium salts, were made up in volumetric flasks (2 mL) with a concentration five times greater than that of the host. The guest solution was typically added in 10 µL aliquots, representing 0.1 equiv of the guest with respect to the host. Larger aliquots were used in some cases where no inflection of the trace was evident. Spectra were recorded after each addition and the trace was followed simultaneously. Results were analyzed using the curve-fitting program HypNMR,63,70 simultaneously fitting as many peaks as could be accurately followed throughout the experiment. Syntheses. Materials were obtained from standard commercial sources. The preparation of 2 and 3 has been reported previously.46 1-Pyridin-2-yl-3-p-tolyl-urea (1). 2-Aminopyridine (0.40 g, 4.35 mmol) and p-tolylisocyanate (0.58 g, 4.35 mmol) were dissolved in dichloromethane (50 mL). The solution was placed under reflux for 24 h while stirring. After this time the solution was concentrated under reduced pressure, resulting in the precipitation of a white solid. The pure product was isolated by filtration. Further concentration of the filtrate gave a second batch of the product. Combined yield 0.63 g, 2.78 mmol, 64%. 1H NMR (DMSO-d6, 400 MHz, δ/ppm, J/Hz): 10.51 (1H, s, NH); 9.46 (1H, s, NH); 8.33 (1H, m, ArH); 7.80 (1H, m, ArH); 7.53 (1H, d, J ) 8.4, ArH); 7.47 and 7.17 (4H, AA’BB′, J ) 8.6, ArH); 7.06 (1H, m, ArH); 2.32 (3H, s, CH3). 13C{1H} NMR (DMSOd6, 100 MHz, δ/ppm): 152.9, 152.1, 146.8, 138.4, 136.4, 131.3, 129.2, 118.9, 117.3, 111.8, 20.3. EI-MS: m/z ) 227 [M]+. Anal: Calc. for C13H13N3O: C, 68.71; H, 5.77; N, 18.49% Found: C, 68.63; H, 5.73; N, 18.54%. IR (ν/cm-1): 1693 (s), 3119 (s), 3203 (s). 1-Pyridin-3-yl-3-p-tolyl-thiourea (4). 3-Aminopyridine (0.96 g, 4.35 mmol) and p-tolylisothiocyanate (0.96 g, 6.4 mmol) were dissolved in dichloromethane (50 mL). The solution was placed under reflux for

Byrne et al. 24 h while stirring. After this time the solution was concentrated under reduced pressure, resulting in the precipitation of a white solid. The pure product was isolated by filtration. Yield 0.98 g, 4.0 mmol, 62%. 1 H NMR (DMSO-d6, 360 MHz, δ/ppm, J/Hz): 9.93 (1H, s, NH); 9.76 (1H, s, NH); 8.60 (1H, d, J ) 2.4, pyH); 8.31 (1H, dd, J ) 4.6 and 1.2, pyH); 7.94 (1H, dd, J ) 8.2 and 1.7, pyH); 7.36 (1H, m, pyH); 7.34 and 7.16 (4H, AA’BB′, J ) 8.1, ArH); 2.29 (3H, s, CH3). 13 C {1H}-NMR (DMSO-d6, 90 MHz, δ/ppm): 180.6, 145.8, 145.5, 136.8, 134.4, 131.7, 129.4, 124.4, 124.2, 123.4, 20.9. EI-MS: m/z ) 243 [M]+. Anal: Calc. for C13H13N3S: C, 64.17; H, 5.39; N, 17.27% Found: C, 64.14; H, 5.53; N, 17.59%. IR (ν/cm-1): 1582 (s), 3175 (s), 3217 (s). Nicotinoyl Azide. Nicotinic acid (1.02 g, 8.29 mmol) was suspended in dry DMF (6 mL) and was dissolved upon addition of triethylamine (0.89 g, 8.76 mmol). Diphenylphosphoryl azide (2.40 g, 8.70 mmol) was added and the solution warmed slightly. After stirring at room temperature for 1.5 h, the solution had become slightly yellow and was poured into water (30 mL) precipitating a colorless solid that was extracted with diethyl ether (3 × 15 mL). The organic layers were combined and washed with water (3 × 15 mL), dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure to yield the product as a colorless solid. Yield 0.79 g, 5.33 mmol, 65%). Mp 45-46 °C.1H NMR (CDCl3, 200 MHz, δ/ppm, J/Hz): 9.21 (1H, d, J ) 1.8, ArH), 8.83 (1H, dt, J ) 1.8, 4.8, ArH), 8.29 (1H, dt, J ) 1.8, 8.0, ArH), 7.42 (1H, dd, J ) 4.8, 8.0, ArH). 13C{1H}-NMR (CDCl3, 100 MHz, δ/ppm): 170.9 (CdO), 154.3 (CH), 150.3 (CH), 136.4 (CH), 126.2 (C), 123.3 (CH). EI-MS: m/z ) 349 [M+H]+. Anal: Calc. for C6H4N4O: C, 48.65; H, 2.72; N, 37.82% Found: C, 48.17; H, 2.78; N, 35.72%. IR (ν/cm-1): 2134 (s, -N3). N,N′′-Ethane-1,2-diylbis(3-pyridin-3-ylurea) (5a). Nicotinoyl azide (1.00 g, 6.75 mmol) was dissolved in dry toluene (50 mL) and stirred at reflux for 2 h when no more N2 was evolved. The solution was cooled to room temperature and 1,2-diaminoethane (0.49 g, 3.40 mmol) was added, precipitating a colorless solid. The suspension was stirred for 15 min, filtered under suction and washed with diethyl ether (2 × 15 mL) to yield the product as a white solid. Yield 0.42 g, 1.40 mmol, 21% Mp ) 210 - 211 °C. 1H NMR (DMSO-d6, 400 MHz, δ/ppm, J/Hz): 8.76 (2H, s, NH), 8.53 (2H, d, J ) 2.5, PyH), 8.10 (2H, dd, J ) 1.4, 4.7, PyH), 7.88 (2H, dq, J ) 1.4, 2.5, 8.3, PyH), 7.24 (2H, dd, J ) 4.7, 8.3, PyH), 6.37 (2H, t, J ) 5.4, NH), 3.21 (4H, m, J ) 2.5, 5.4, CH2). 13C{1H}-NMR (DMSO-d6, 100 MHz, δ/ppm): 155.3 (C), 142.1 (CH), 139.6 (CH), 137.1 (C), 124.5 (CH), 123.4 (CH), 39.6 (CH2). EI-MS: m/z ) 121 [PyNHCO]+, 151, 301 [M+H]+, 323 [M+Na]+, 623 [2M+Na]+. Anal. Calc. for C14H16N6O2: C, 55.99; H, 5.37; N, 27.98% Found: C, 55.70; H, 5.31; N, 27.80%. IR (ν/cm-1): 3301 (m, (N-H)str), 1640 (strong, sharp, (CdO)str) 1549 (strong, sharp, (N-H)def). N,N′′-Propane-1,3-diylbis(3-pyridin-3-ylurea) (5b). Prepared as 5a, using 1,3-diaminopropane. Yield 0.19 g, 0.60 mmol, 86%. Mp ) 195 °C; 1H NMR (DMSO-d6, 400 MHz, δ/ppm, J/Hz): 8.71 (2H, s, NH), 8.53 (2H, d, J ) 2.6, PyH), 8.10 (2H, dd, J ) 1.4, 4.6, PyH), 7.88 (2H, dq, J ) 1.4, 2.6, 8.3, PyH), 7.24 (2H, dd, J ) 4.6, 8.3, PyH), 6.34 (2H, t, J ) 5.7, NH), 3.14 (4H, q, J ) 6.6, CH2), 1.59 (2H, m, J ) 6.6, CH2). 13C{1H}-NMR (DMSO-d6, 100 MHz, δ/ppm): 155.3 (C), 142.0 (CH), 139.5 (CH), 137.2 (C), 124.4 (CH), 123.4 (CH), 36.6 (CH2), 30.5 (CH2). EI-MS: m/z ) 121 [PyNHCO+], 221, 315 [M+H]+, 337 [M+Na]+, 651 [2M+Na]+. Anal: Calc. for C15H18N6O2: C, 57.31; H, 5.77; N, 26.74% Found: C, 56.94; H, 5.79; N, 26.13%. IR (ν/cm-1): 3319 (m, (N-H)str), 1656 (strong, sharp, (CdO)str) 1544 (strong, sharp, (N-H)def). N,N′′-Butane-1,4-diylbis(3-pyridin-3-ylurea) (5c). Prepared as 5a, using 1,4-diaminobutane. Yield 4.16 g, (89%). Mp ) 209-210 °C. 1 H NMR (DMSO-d6, 400 MHz, δ/ppm, J/Hz): 8.60 (2H, s, NH), 8.52 (2H, s, ArH), 8.10 (2H, d, J ) 4.6, ArH), 7.87 (2H, d, J ) 8.1, ArH), 7.23 (2H, dd, J ) 4.6, 8.1, ArH), 6.30 (2H, t, J ) 5.2, NH), 3.11 (4H, d, J ) 5.2, CH2), 1.46 (4H, s, CH2). 13C{1H}-NMR (DMSO-d6, 100 MHz, δ/ppm): 155.6 (C), 142.5 (CH), 139.8 (CH), 137.7 (C), 124.9 (CH), 123.9 (CH), 39.4 (CH2), 27.7 (CH2). EI-MS: m/z ) 165 [M+2H]2+, 329 [M+H]+, 351 [M+Na]+, 657 [2M+H]+, 679 [2M+Na]+. Anal: Calc. for C16H20N6O2: C, 58.52; H, 6.14; N, 25.59% Found: C, 58.31; H, 6.10; N, 25.49%. IR (ν/cm-1): 3323 (m, (N-H)str), 1643 (strong, sharp, (CdO)str) 1552 (strong, sharp, (N-H)def). N,N′′-1,4-Phenylenebis(3-pyridin-3-ylurea) (6). Prepared as 5a, using 1,4-diaminobenzene. Yield 0.51 g, 1.46 mmol, 43%. Mp ) Decomposes above 280 °C. 1H NMR (DMSO-d6, 400 MHz, δ/ppm, J/Hz): 8.79 (2H, s, NH), 8.69 (2H, s, NH), 8.59 (2H, s, PyH), 8.17

Hydrogen Bonding in Pyridyl Ureas (2H, d, J ) 4.7, PyH), 7.93 (2H, d, J ) 8.4, PyH), 7.38 (4H, s, ArH), 7.30 (2H, dd, J ) 4.7, 8.4, PyH). 13C{1H}-NMR (DMSO-d6, 100 MHz, δ/ppm): 152.5 (C), 142.7 (CH), 139.8 (CH), 136.4 (C), 133.8 (C), 125.3 (CH), 123.6 (CH), 119.3 (CH). EI-MS: m/z ) 175 [M+2H]2+, 349 [M+H]+, 670 [2M+H]+. Anal: Calc. for C18H16N6O2: C, 62.06; H, 4.63; N, 24.12% Found: C, 61.79; H, 4.65; N, 24.01%. IR (ν/cm-1): 3279 (m, (N-H)str), 1645 (strong, sharp, (CdO)str) 1594 (strong, sharp, (N-H)def). N,N′′-Naphthalene-1,5-diylbis(3-pyridin-3-ylurea) (7). Prepared as 5a, using 1,5-diaminonapthalene to give a pale brown solid. The solid was dissolved in DMSO and the product precipitated as a white powder upon addition of water. The product was isolated by filtration and washed with acetone. Yield 0.05 g, 0.13 mmol, 4%. Mp ) Decomposes above 280 °C. 1H NMR (DMSO-d6, 400 MHz, δ/ppm, J/Hz): 9.23 (2H, s, NH), 8.90 (2H, s, NH), 8.65 (2H, s, PyH), 8.21 (2H, dt, J ) 1.5, 4.7, PyH), 8.03 (2H, d, J ) 7.6, ArH), 7.99 (2H, m, PyH), 7.88 (2H, d, J ) 8.6, ArH), 7.58 (2H, t, J ) 8.1, ArH), 7.34 (2H, dd, J ) 4.7, 8.3, PyH). 13C{1H}-NMR (DMSO-d6, 100 MHz, δ/ppm): 153.0 (C), 142.9 (CH), 140.0 (CH), 136.5 (C), 134.5 (C), 126.9 (C), 125.6 (CH), 125.1 (CH), 123.6 (CH), 118.1 (CH), 116.8 (CH). EI-MS: m/z ) 399 [M+H]+, 421 [M+Na]+, 797 [2M+H]+. Anal. Calc. for C22H18N6O2: C, 66.32; H, 4.55; N, 21.09% Found: C, 66.45; H, 4.78; N, 20.37%. IR (ν/cm-1): 3275 (m, (N-H)str), 1635 (strong, sharp, (CdO)str) 1542 (strong, sharp, (N-H)def).

Acknowledgment. We are grateful to the EPSRC and the Commonwealth Scholarships Commission for financial support of this work. We thank Prof. Mike H. Abraham (University College London) for valuable discussions. Supporting Information Available: Crystallographic information files for the X-ray crystal structures are available (in.cif format). This material is available free of charge via the Internet at http://pubs.acs.org.

References (1) Rebek, J., Jr.; Rudkevich, D. M.; Cho, Y. L. J. Am. Chem. Soc. 2000, 122, 9868–9869. (2) Rebek, J., Jr.; Castellano, R. K. J. Am. Chem. Soc. 1998, 120, 3657– 3663. (3) Alajarı´n, M.; Lo´pez-La´zaro, A.; Pastor, A.; Prince, P. D.; Steed, J. W.; Arakawa, R. Chem. Commun. 2001, 169–170. (4) Alajarı´n, M.; Pastor, A.; Orenes, R. A.; Steed, J. W. J. Org. Chem. 2002, 67, 7091–7095. (5) Turner, D. R.; Pastor, A.; Alajarı´n, M.; Steed, J. W. Struct. Bonding (Berlin) 2004, 108, 97–168. (6) Alajarı´n, M.; Pastor, A.; Orenes, R. A.; Steed, J. W.; Arakawa, R. Chem.-Eur. J. 2004, 10, 1383–1397. (7) Stanley, C. E.; Clarke, N.; Anderson, K. M.; Lenthall, J. P.; Steed, J. W. Chem. Commun. 2006, 3199–3201. (8) Arai, S.; Imazu, K.; Kusuda, S.; Yoshihama, I.; Tonegawa, M.; Nishimura, Y.; Kitahara, K.; Oishi, S.; Takemura, T. Chem. Lett. 2006, 35, 634–635. (9) Jeong, Y.; Hanabusa, K.; Masunaga, H.; Akiba, I.; Miyoshi, K.; Sakurai, S.; Sakurai, K. Langmuir 2005, 21, 586–594. (10) Fages, F.; Vo¨gtle, F.; Z˘inic, M. Top. Curr. Chem. 2005, 256, 77–131. (11) Applegarth, L.; Clark, N.; Richardson, A. C.; Parker, A. D. M.; Radosavljevic-Evans, I.; Goeta, A. E.; Howard, J. A. K.; Steed, J. W. Chem. Commun. 2005, 5423–5425. (12) Schoonbeek, F. S.; van Esch, J. H.; Hulst, R.; Kellogg, R. M.; Feringa, B. L. Chem.-Eur. J. 2000, 6, 2633–2643. (13) de Loos, M.; Ligtenbarg, A. G. J.; van Esch, J.; Kooijman, H.; Spek, A. L.; Hage, R.; Kellogg, R. M.; Feringa, B. L. Eur. J. Org. Chem. 2000, 3675–3678. (14) vanEsch, J.; Kellogg, R. M.; Feringa, B. L. Tetrahedron Lett. 1997, 38, 281–284. (15) Custelcean, R.; Remy, P.; Bonnesen, P. V.; Jiang, D.-e.; Moyer, B. A. Angew. Chem., Int. Ed. 2008, . in press. (16) Wu, B.; Huang, X.; Xia, Y.; Yang, X.-J.; Janiak, C. CrystEngComm 2007, 9, 676–685. (17) Schazmann, B.; Diamond, D. New J. Chem. 2007, 31, 587–592. (18) Custelcean, R.; Moyer, B. A. Eur. J. Inorg. Chem. 2007, 1321–1340. (19) Gunnlaugsson, T.; Glynn, M.; Tocci, G. M.; Kruger, P. E.; Pfeffer, F. M. Coord. Chem. ReV. 2006, 250, 3094–3117. (20) Evans, L. S.; Gale, P. A.; Light, M. E.; Quesada, R. New J. Chem. 2006, 30, 1019–1025.

Crystal Growth & Design, Vol. 8, No. 9, 2008 3343 (21) Amendola, V.; Esteban-Gomez, D.; Fabbrizzi, L.; Licchelli, M. Acc. Chem. Res. 2006, 39, 343–353. (22) Turner, D. R.; Smith, B.; Spencer, E. C.; Goeta, A. E.; Evans, I. R.; Tocher, D. A.; Howard, J. A. K.; Steed, J. W. New J. Chem. 2005, 29, 90–98. (23) Gomez, D. E.; Fabbrizzi, L.; Licchelli, M.; Monzani, E. Org. Biomol. Chem. 2005, 3, 1495–1500. (24) Applegarth, L.; Goeta, A. E.; Steed, J. W. Chem. Commun. 2005, 2405–2406. (25) Gale, P. Amide and Urea-Based Anion Receptors, In Encyclopedia of Supramolecular Chemistry; Steed, J. W.; Atwood, J. L., Eds.; Marcel Dekker: New York, 2004; Vol. 1, pp 31-41. (26) Bondy, C. R.; Gale, P. A.; Loeb, S. J. J. Am. Chem. Soc. 2004, 126, 5030–5031. (27) Chen, J.; Ling, G.; Lu, S. Tetrahedron 2003, 59, 8251–8256. (28) Singha, N. C.; Sathyanarayana, D. N. J. Chem. Soc., Perkin Trans. 2 1997, 157–162. (29) Reddy, L. S.; Basavoju, S.; Vangala, V. R.; Nangia, A. Cryst. Growth Des. 2006, 6, 161–173. (30) Turner, D. R.; Spencer, E. C.; Howard, J. A. K.; Tocher, D. A.; Steed, J. W. Chem. Commun. 2004, 1352–1353. (31) Martinez-Manez, R.; Sancenon, F. Chem. ReV. 2003, 103, 4419–4476. (32) Blondeau, P.; van der Lee, A.; Barboiu, M. Inorg. Chem. 2005, 44, 5649–5653. (33) Wu, B.; Liang, J. J.; Yang, J.; Jia, C. D.; Yang, X. J.; Zhang, H. R.; Tang, N.; Janiak, C. Chem. Commun. 2008, 1762–1764. (34) Wu, B.; Huang, X. J.; Liang, J. J.; Liu, Y. Y.; Yang, X. J.; Hu, H. M. Inorg. Chem. Commun. 2007, 10, 563–566. (35) Huang, X. J.; Xia, Y.; Zhang, H. R.; Yan, Z. Z.; Tang, Y.; Yang, X. J.; Wu, B. Inorg. Chem. Commun. 2008, 11, 450–453. (36) Custelcean, R.; Moyer, B. A.; Bryantsev, V. S.; Hay, B. P. Cryst. Growth. Des. 2006, 6, 555–563. (37) Custelcean, R. Chem. Commun. 2007, . asap. (38) Baddeley, C.; Yan, Z.; King, G.; Woodward, P. M.; Badjic´, J. D. J. Org. Chem. 2007, 72, 7270–7278. (39) Kumar, D. K.; Jose, D. A.; Das, A.; Dastidar, P. Chem. Commun. 2005, 4059–4061. (40) Etter, M. C.; Urbanczyk-Lipkowska, Z.; Zia-Ebrahimi, M.; Panunto, T. W. J. Am. Chem. Soc. 1990, 112, 8415–8426. (41) Etter, M. C.; Panunto, T. W. J. Am. Chem. Soc. 1988, 110, 5896– 5897. (42) Huang, K. S.; Britton, D.; Etter, M. C.; Byrn, S. R. J. Mater. Chem. 1995, 5, 379–383. (43) Abraham, M. H.; Grellier, P. L.; Prior, D. V.; Morris, J. J.; Taylor, P. J. J. Chem. Soc., Perkin Trans 2 1990, 521–529. (44) Laurence, C.; Berthelot, M. Persp. Drug Disc. Des. 2000, 18, 39–60. (45) Abraham, M. H. Chem. Soc. ReV. 1993, 22, 73–83. (46) Turner, D. R.; Smith, B.; Goeta, A. E.; Evans, I. R.; Tocher, D. A.; Howard, J. A. K.; Steed, J. W. CrystEngComm 2004, 6, 633–641. (47) Vishnyakova, T. P.; Golubeva, I. A.; Glebova, E. V. Russ. Chem. ReV. 1985, 54, 249–261. (48) Bernstein, J.; Davis, R. E.; Shimoni, L.; Chang, N.-L. Angew. Chem., Int. Ed. Engl. 1995, 34, 1555–1573. (49) Allen, F. H.; Motherwell, W. D. S.; Raithby, P. R.; Shields, G. P.; Taylor, R. New. J. Chem. 1999, 23, 25–34. (50) Anderson, K. M.; Afarinkia, K.; Yu, H.-W.; Goeta, A. E.; Steed, J. W. Cryst. Growth Des. 2006, 6, 2109–2113. (51) Wierzejewska, M.; Sadyka, M. Chem. Phys. Lett. 2004, 391, 143– 147. (52) Venkatachalam, T. K.; Sudbeck, E.; Uckun, F. M. J. Mol. Struct. 2004, 687, 45–56. (53) Steed, J. W. CrystEngComm 2003, 5, 169–179. (54) Todd, A. M.; Anderson, K. M.; Byrne, P.; Goeta, A. E.; Steed, J. W. Cryst. Growth Des. 2006, 6, 1750–1752. (55) Desiraju, G. R. Angew. Chem.-Int. Ed. Engl. 1995, 34, 2311–2327. (56) Piepenbrock, M.-O. M.; Lloyd, G. O.; Clarke, N.; Steed, J. W. Chem. Commun. 2008, 2644–2646. (57) Anderson, K. M.; Goeta, A. E.; Hancock, K. S. B.; Steed, J. W. Chem. Commun. 2006, 2138–2140. (58) Rivas, J. C. M.; Brammer, L. Inorg. Chem. 1998, 37, 4756–4757. (59) Brammer, L.; Bruton, E. A.; Sherwood, P. Cryst. Growth. Des. 2001, 1, 277–290. (60) Kaufmann, D. E.; Otten, A. Angew. Chem., Int. Ed. Engl. 1994, 33, 1832–1834. (61) Antonisse, M. M. G.; Reinhoudt, D. N. Chem. Commun. 1998, 443– 448. (62) Hamann, B. C.; Branda, N. R.; Rebek, J., Jr. Tetrahedron Lett. 1993, 34, 6837–6840. (63) Gans, P. HypNMR 2006; University of Leeds: Leeds, 2006.

3344 Crystal Growth & Design, Vol. 8, No. 9, 2008 (64) Wallace, K. J.; Belcher, W. J.; Turner, D. R.; Syed, K. F.; Steed, J. W. J. Am. Chem. Soc. 2003, 125, 9699–9715. (65) Otwinowski, Z.; Minor, W. In Methods in Enzymology; Carter, C. W.; Sweet, R. M., Eds.; Academic Press: London, 1997; p 307. (66) Sheldrick, G. M. SHELXS-97; University of Go¨ttingen: Germany, 1997. (67) Sheldrick, G. M. SHELXL-97; University of Go¨ttingen: Germany, 1997.

Byrne et al. (68) Barbour, L. J. J. Supramol. Chem. 2001, 1, 189–191. (69) Flack, H. D. Acta Crystallogr., Sect. A 1983, 39, 876–881. (70) Frassineti, C.; Ghelli, S.; Gans, P.; Sabatini, A.; Moruzzi, M. S.; Vacca, A. Anal. Biochem. 1995, 231, 374–382.

CG800247F