Pyridazines in Crystal Engineering. A Systematic Evaluation of the

DOI: 10.1021/cg9015383

Pyridazines in Crystal Engineering. A Systematic Evaluation of the Role of Isomerism and Steric Factors in Determining Crystal Packing and Nano/Microcrystal Morphologies

2010, Vol. 10 2571–2580

Sunil Varughese# and Sylvia M. Draper* School of Chemistry, Trinity College Dublin, College Green, D2, Ireland. #Current Address: Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560 012, India. Received December 8, 2009; Revised Manuscript Received April 15, 2010

ABSTRACT: The present study focuses on understanding hydrogen bond patterns in a series of variably substituted pyridylpyridazines as a function of positional isomerism and steric factors. A relatively uncommon multiple hydrogen bond acceptor nature of pyridazine has been observed in the di- and tripyridazine compounds. With increasing aromatic substitution and thereby steric hindrance, a systematic transition has been observed from close-packed to porous solvated assemblies. Distinct morphologies of the organic nano/microparticles, obtained by the precipitation method, indicate that the molecules interact with the solvent system in different ways.

Introduction Pyridazines are a class of compounds known for their utility as efficient electron acceptors in conjugated D-A-D systems,1 as building units in several bioorganic compounds,2 and as ligands in the preparation of novel coordination complexes.3 In addition to the multiple N-atom sites for sustaining coordination to metal centers, this class of compounds can also interact with suitable coformers with acidic functionalities to generate novel supramolecular assemblies with exotic frameworks. However, unlike the N-atom donor ligands pyridines, pyrimidines, and pyrazines, the nitrogenrich, electron-deficient pyridazines are not well studied from a crystal engineering perspective. The pKa value of pyridazine is 2.1, making it a weaker base as compared to pyridine functionalities4 which is a well-studied moiety in noncovalent synthesis. This in turn makes pyridazine a weak lone-pair donor and a good candidate to investigate weak C-H 3 3 3 N hydrogen bonds in crystals. However, this class of compounds for crystal design has scarcely been explored, as evident from a CSD search.5 Further, it was noted that multiple hydrogen bond acceptor function is uncommon in pyridazines.6 Thus, substituted pyridazines make an interesting series to study weak interactions in organic molecules. Despite a surge in the utility of relatively stronger intermolecular interactions such as O-H 3 3 3 O, O-H 3 3 3 N, N-H 3 3 3 O, etc. in network designing and noncovalent synthesis, the seminal works of Dunitz, Gavezzotti, Bishop, Boese, Desiraju, Ohkita, and Nangia to name a few, have made a substantial contribution to the knowledge of weak interactions and their utility in crystal engineering.7-11 In contrast to the well studied C-H 3 3 3 O hydrogen bonds, the assemblies stabilized by C-H 3 3 3 N hydrogen bonds are less in number.12 In addition to weak interactions, steric factors, isomerism, and conformational preferences of molecules can bring about subtle variations in supramolecular synthons and crystal packing. Organic molecules with flexible torsions can in fact generate dissimilar conformations with different hydrogen

bond patterns and packing modes.13 Thus, a systematic evaluation of supramolecular synthons consisting of C-H 3 3 3 N hydrogen bonds in a series of conformationally flexible and sterically hindered pyridazines is interesting. In the present work, nine variably substituted pyridylpyridazines (Scheme 1) have been synthesized and analyzed for hydrogen bond patterns and three-dimensional supramolecular architecture. The effect of steric hindrance in the crystal packing was studied systematically using molecules with increasing substitution. It was assumed that the labyrinthine topology, steric hindrance, and pliability of the recognition patterns would bring about variations in the three-dimensional architecture. The aromatic heterocyclics included in the present studies make an interesting series, with conformational flexibility brought about by the C-C single bonds. The compounds have been synthesized by the inverse electron demand Diels-Alder reaction between the respective tetrazines and the corresponding alkynes, as represented in Scheme 1, and characterized using 1D 1H and 13C, 2D 1H-1H COSY, and 13C-1H COSY NMR techniques, thermogravimetry, and powder (PXRD) and single crystal X-ray diffraction (SXRD). Crystals suitable for X-ray diffraction studies were obtained by slow evaporation/vapor diffusion. Although we succeeded in obtaining single crystals of the 2-pyridyl and 4-pyridyl derivatives, 3-pyridyl compounds (2b and 3b) failed to form crystals suitable for the SXRD studies, even after several attempts. The structural details, along with the basic recognition patterns of all the assemblies, are enumerated followed by a collective analysis to understand the variations in and the similarity of the recognition patterns. It is interesting to note that in all the cases assemblies are stabilized by weak noncovalent interactions such as C-H 3 3 3 N, C-H 3 3 3 π, and π 3 3 3 π. The morphology of the nano/microcrystals, prepared by a precipitation method using a dimethylformamide (DMF)/water system, were studied using scanning electron microscopy (SEM). Results and Discussion

*To whom correspondence should be addressed. Phone: þ353-1-8962026. E-mail: [email protected].

Monopyridazine Compounds (1a -1c). The 2-pyridyl moieties in phenyl-3,6-di(2-pyridyl)pyridazine, 1a, are in a trans,

r 2010 American Chemical Society

Published on Web 05/04/2010

pubs.acs.org/crystal

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Crystal Growth & Design, Vol. 10, No. 6, 2010

Varughese and Draper

Scheme 1. The Synthetic Reagents (x and y axes) and Reaction Conditions (y axis) Used to Produce the Pyridazine Products 1a-1c, 2a-2c, and 3a-3c

Figure 1. The three-dimensional packing and interactions in 1a.

trans-arrangement with respect to the pyridazine heteroatoms and play no role in the hydrogen bond formation.14 This can be attributed to the orientation of the pyridyl rings toward an unfavorable sterically demanding environment resulting from the phenyl moiety. The molecules of 1a make zigzag tapes, and adjacent tapes are stabilized by weak C-H(pyridine) 3 3 3 π interactions (Figure 1). Phenyl-3,6-di(3-pyridyl)pyridazine, 1b, has different conformational preferences and orientation of the heteroatoms which in turn results in a different architecture. The phenyl

and the two pyridyl rings deviate from the mean plane of the pyridazine by 53.3°, 49.7°, and 1.6° respectively and the pyridyl heteroatoms are arranged gauche, syn to the pyridazine aza-atoms. In the three-dimensional arrangement, molecules make a corrugated sheet structure (Figure 2a) wherein individual sheets are made of molecules, stabilized by bifurcated C34-H34 3 3 3 N21/C15-H15...N21 (H 3 3 3 N 2.62 and 2.81 A˚) hydrogen bonds (Figure 2b(A)). Adjacent tapes interact through single point C43-H43 3 3 3 N31 (H 3 3 3 N, 2.67 A˚) hydrogen bonds, as shown in Figure 2b(B). The 4-pyridyl derivative, 1c, exhibits considerable variation in the torsion angle with respect to its isomers, 1a and 1b. While the phenyl ring is more aligned with the mean plane of the pyridazine ring (40.3°), both the 4-pyridyl moieties show an increase in the torsion angle (27.2° and 43.3°) and make an entirely different recognition pattern. Two molecules of 1c interact to form a centrosymmetric dimer, through C46-H46 3 3 3 N21 (H 3 3 3 N, 2.80 A˚) hydrogen bonds, utilizing one of the pyridyl ring (Figure 3b(A)). Adjacent dimers make C44-H44 3 3 3 N11 (H 3 3 3 N 2.62 A˚) hydrogen bonds, forming a ladder-like assembly in 2D arrangement. Thus, the three isomers of the monopyridazines (1a-1c) yielded close-packed structures, although with distinct threedimensional architectures. To evaluate the influence of the degree of substitution and steric hindrance in crystal packing, 1,4-di- and 1,3,5-tripyridazine compounds were considered. While all the compounds were synthesized as per the reaction conditions represented in Scheme 1, the 3-pyridyl derivatives failed to yield crystals suitable for SXRD analysis. Dipyridazine Compounds (2a-2c). 1,4-Phenyl-bis[3,6-di(2-pyridyl)pyridazine], 2a, crystallizes in R3 space group,

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Figure 2. Crystal structure of 1b. (a) The undulated sheet structure. (b) The intermolecular interactions existing in an individual sheet. (The linear arrangement of molecules is represented as thin red lines.)

Figure 3. (a) The layered architecture in 1c. (b) The intermolecular interactions and the ladder assembly. Table 1. Crystallographic Information of 1b, 1c, 2a, 2c, and 3c 1b

1c

2a

2c

3c

CCDC No. formula

CCDC 727300 C20H14N4

CCDC 727301 C20H14N4

CCDC 727302 C34H22N8, 2(CH3OH)

CCDC 727303 C34H22N8, 2(CH3OH)

formula wt crystal system space group a (A˚) b (A˚) c (A˚) R (o) β (o) γ (o) V (A˚3) Z D(calc) g/cm3 T (K) λMo μ (mm-1) 2θ (o) total reflns R(int) unique reflns reflns used no. of parameters GOF on F2 final R1; wR2

310.35 monoclinic P21/n 14.359(4) 7.104(2) 15.820(5) 90 105.420(6) 90 1555.6(8) 4 1.325 123(2) 0.71073 0.082 50.10 15249 0.0365 2743 1854 217 1.020 0.0428; 0.1041

310.35 orthorhombic Pbca 7.466(7) 10.534(1) 38.576(4) 90 90 90 3034(3) 8 1.359 123(2) 0.71073 0.084 50.18 15932 0.0456 2693 2126 217 1.042 0.0382; 0.0864

606.68 trigonal R3 35.650(5) 35.650(5) 6.306(2) 90 90 120 6941(3) 9 1.306 123(2) 0.71073 0.085 56.74 28713 0.0488 3840 3139 210 1.134 0.0705; 0.1896

606.68 monoclinic P21/c 11.776(1) 17.635(1) 7.598(2) 90 106.240(1) 90 1514.9(4) 2 1.330 123(2) 0.71073 0.086 50.04 15874 0.0215 2663 2492 211 1.036 0.0362; 0.0978

CCDC 727304 2(C48H30N12), 2(C2H6NCHO), H2O 1697.76 triclinic P1 9.977(7) 13.808(1) 16.792(1) 92.350(3) 100.730(2) 110.860(1) 2109.3(15) 1 1.337 123(2) 0.71073 0.086 50.38 11449 0.0766 7196 3692 595 0.989 0.0887; 0.2144

with a half molecule and a methanol in the asymmetric unit (Table 1). The central phenyl ring is 56.8° out of the mean plane of the pyridazine ring, while the pyridyl rings are closer to the plane of the central pyridazine ring (26.5° and 3.6°). Although the 2-pyridyl rings make a trans,trans conformation with the heteroatoms of the pyridazine ring, unlike in 1a, the heterocycle plays an important role in stabilizing the assembly through C-H 3 3 3 N hydrogen bonds . Interlocking

of three H-shaped molecules of 2a generates a triangular unit, with a side length of 21.92 A˚, as represented in Figure 4b. The inward looking heteroatoms of the 2-pyridyl moieties together with the pyridazine functionality stabilize the triangular unit, through a two-tier hydrogen bond network. While the C35-H35 3 3 3 N31 (H 3 3 3 N 2.87 A˚) hydrogen bonds involving three internally oriented 2-pyridyl units make the inner core, the peripheral area is bound by bifurcated

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Figure 4. Crystal structure of 2a. (a) The porous assembly with hexagonal channels. (b) The triangular units and the schematic representation of the helical assembly. (c) The methanol clusters (inset shows a different orientation of the methanol cluster).

C26-H26 3 3 3 N12/C26-H26 3 3 3 N11 (H 3 3 3 N 2.50 and 2.59 A˚) hydrogen bonds, formed by the pyridazine moiety. These interactions extend along the c-axis to form a helical assembly, as represented in Figure 4b. The edge-sharing arrangement of the triangular helical entities generates hexagonal frameworks with channels (12.45 12.45 A˚2) down the c-axis. The channels are occupied by clusters of methanol molecules. Each cluster is made of six molecules exhibiting a cyclohexane-type chair conformation and stabilized by O-H(methanol) 3 3 3 O(methanol) hydrogen bonds (H 3 3 3 O, 1.90 A˚) (Figure 4c). A similar unusual and interesting methanol hexamer with a S6 symmetry was reported previously by Wieghardt et al.15 The guest methanol molecules make C-H(methanol) 3 3 3 π(pyridine) interactions with the framework. An isostructural hydrate form of the compound was obtained from a CH2Cl2-hexane solution with disordered oder and cowater molecules occupying the channel.14 Schr€ workers reported two solid-state forms of compound 2a - a chloroform solvate and a solvent-free form.16 In the chloroform solvate, pyridazines are arranged as columns, stabilized by weak π 3 3 3 π interactions and separated from the adjacent columns by CHCl3 molecules. In the case of the nonsolvated pure form, the molecules form a close-packed structure generated by the interlocking of the H-type molecules and stabilized by several centrosymmetric and noncentrosymmetric C-H 3 3 3 N hydrogen bonds (see Supporting Information). Thus, unlike the close-packed structure observed in the case of compound 1a, the 1,4-derivative form both porous and nonporous assemblies. As the 2-pyridyl moieties exhibited a trans,trans conformation in all the aforementioned cases, the observed disparity in the recognition pattern and supramolecular architecture may be brought about by the torsional flexibility possible in the molecules (see Supporting Information). Thus, it

can be inferred that in addition to the position of the hydrogen bond forming functionalities, the conformational preferences of the molecules also play an important role in determining the three-dimensional architecture. Compared to 2a, in the 4-pyridyl compound (2c) all the aromatic rings tend to deviate away from the mean plane of the pyridazine ring (phenyl (62.2°); 4-pyridyl (13.4° and 33.0°)). Of the four pyridyl rings, two are bound to methanol molecules; the other two pyridyl units make hydrogen bonds with adjacent units. Each molecule interacts with adjacent units through cyclic C35-H35 3 3 3 N11/C36-H36 3 3 3 N12, (H 3 3 3 N, 2.69 and 2.70 A˚) hydrogen bonds, forming a layered assembly (Figure 5a). Further, these layers make a herringbone type arrangement. The arrangement of the molecules generates porous networks with channels down the z-axis. These channels are occupied by linear chains of methanol molecules, stabilized by C90-H90C 3 3 3 O90 (H 3 3 3 O, 2.88 A˚) hydrogen bonds. The guest molecules are held to the host framework through O90-H90 3 3 3 N21 (H 3 3 3 N, 2.02 A˚) hydrogen bonds (Figure 5). Tripyridazine Compounds (3a-3c). Compared to the mono- and dipyridazine compounds the 1,3,5-tripyridazine molecule, 3a, is sterically hindered and make a paddle-wheel topology.14 The molecules self-assemble to form a doublewalled porous assembly, stabilized by C-H 3 3 3 N hydrogen bonds involving both pyridyl and pyridazine moieties (Table 2). The void space is occupied by diethyl ether molecules, held to the host framework through C-H(ether) 3 3 3 π(pyridine) interactions, involving the ethyl group and the aromatic rings. Thus, by employing an increasing number of aromatic rings, molecules with labyrinthine topology can be obtained that make it difficult to form solvent-free crystal structures.17

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Crystals of the 4-pyridyl isomer, 3c, were grown by vapor diffusion of diethyl ether into a DMF solution and the compound crystallizes in P1, with a tripyridazine, a dimethylformamide and water in the asymmetric unit. In the crystal, four pyridazine molecules interact to form cavities, as shown in Figure 6b, and are stabilized by several weak C-H 3 3 3 N and C-H 3 3 3 π interactions. In a typical assembly, the pyridazine units are involved in the formation of cyclic C322-H322 3 3 3 N312/C323-H323 3 3 3 N311 (H 3 3 3 N, 2.77 and 2.84 A˚) dimers while the pyridine units form centrosymmetric C-H(pyridine) 3 3 3 N(pyridine) hydrogen bonds. Of the six 4-pyridyl units available per molecule, five are involved in the cyclic C-H 3 3 3 N hydrogen bonds with the adjacent units, while the remaining one interacts with disordered water molecules forming O300-H(water) 3 3 3 N321 (O 3 3 3 N, 2.85 A˚) hydrogen bonds. The guest DMF molecules make multiple C-H 3 3 3 O hydrogen bonds with pyridazine molecules. The

Figure 5. (a) The zigzag layer formed in 2c (The guest methanol molecules are represented in the space-fill mode) and the intermolecular interactions existing in a layer. (b) The cavity formed in 2c. The linear chain of methanol molecules in the channel is shown in the inset.

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methyl group of the solvent makes C-H 3 3 3 N hydrogen bonds with the pyridazine molecules and holds adjacent molecules together. Both the 1,3,5-tripyridazine compounds, 3a and 3c, yielded porous solvated assemblies. Although in the tripyridazine compounds the positions of the pyridine functionalities are in two distinct environments, the basic recognition patterns (the cyclic C-H 3 3 3 N) are common to both their crystal structures. Also, the pyridazine moieties exhibit similar recognition patterns in both assemblies.

Figure 6. (a) The double-walled porous network formed in 3a and the intermolecular interactions stabilizing the assembly. (b) The network formed in 3c, viewed along the y-axis. The solvent DMF molecules are represented in space-fill mode.

Table 2. Characteristic Data of Hydrogen Bonds [Bond Lengths in A˚, Angles in o]a C-H...N

1a

1b

1c

2a

2c

3a

3c

2.81 3.66 149

2.61 3.52 160 2.62 3.53 161 2.67 3.35 129 2.81 3.74 168 2.89 3.48 121

2.56 3.47 160 2.62 3.54 162 2.65 3.46 144 2.69 3.57 155 2.80 3.55 136

2.50 3.24 135 2.59 3.38 142 2.59 3.45 150 2.87 3.77 159

2.65 3.49 148 2.69 3.48 141 2.70 3.45 137 2.74 3.50 137

2.53 3.48 178 2.60 3.37 138 2.70 3.47 138 2.73 3.53 142 2.73 3.51 140 2.86 3.61 137

2.59 3.48 157 2.63 3.36 134 2.67 3.30 124 2.75 3.44 130 2.77 3.51 135 2.82 3.49 129 2.83 3.44 123 2.84 3.53 130 2.84 3.51 128

C-H...O

O-H...O O-H...N a

2.37 3.32 172 2.66 3.50 148 2.88 3.43 119 2.90 3.56 163 1.90 2.70 159

The three columns correspond to H 3 3 3 A, D 3 3 3 A (A˚) distances and D-H 3 3 3 A (o) angle.

2.02 2.85 169

2.30 3.24 171 2.41 3.32 159 2.65 3.60 171 2.80 3.59 141 2.91 3.50 122

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Figure 7. The overlap diagram of (a) mono-, (b) di-, and (c) tripyridydazine compounds. (Color code: green (2-pyridyl), yellow (3-pyridyl), and red (4-pyridyl)). (d) The histogram representation of torsion angles (along the y-axis) exhibited by pyridazines a1-3 and c1-3 with respect to the phenyl ring.

Analysis of Torsion Angles. A comparative analysis of the torsion angles (calculated as the angles between the mean planes of the rings) of the 2-pyridyl and 4-pyridyl pyridazine compounds was carried out. From the overlap diagrams of the mono-, di-, and tripyridazine, it was observed that further to the orientation of the heteroatoms, the molecules exhibit diverse conformational preferences. This also might have contributed to the variation in the supramolecular architecture (Figure 7). In the case of monopyridazines (1a-1c), diverse three-dimensional architecture are observed, although all are close-packed structures. In the dipyridazine compounds (2a and 2c), the isomers exhibit considerable conformational variation and are clearly visible in the crystal packing. For the tripyridazine compounds 3a and 3c, although large torsional shifts exist, the global packing arrangement is not very perturbed, with the formation of porous solvated assemblies, perhaps due to the operation of the same principles governing the space filling in accordance with crystallographic symmetry rules. The variations in the torsion angles of the pyridazine moiety with respect to the phenyl rings are compiled to form a chart (Figure 7d). The mono- and dipyridazine compounds 1a and 2a showed similar torsion angles as against 1c and 2c, where a substantial variation exists (∼22°). While all the three pyridylpyridazine substituents of 3a exhibit diverse torsion angles with respect to the central phenyl ring, only marginal shifts exist in 3c. Thus, along with the position of the hydrogen bond forming functionalities, torsional variation brought about by the steric strain, lattice constraints,

solvent incorporation, etc. also might have contributed to the final supramolecular architecture. Variation in the Hydrogen Bond Patterns. The multiple hydrogen bond acceptor properties of pyridazines are relatively uncommon.6 In the present study, pyridazine moiety exhibits three different supramolecular synthons as a function of degree of substitution and availability of hydrogen bond forming functionalities in its vicinity. While monopyridazines (1a and 1c) exhibited regular single point C-H 3 3 3 N interactions, the pyridazine moiety acts as a multiple hydrogen bond acceptor in di- and triderivatives, making bifurcated and noncentrosymmetric C-H 3 3 3 N hydrogen bonds (Figure 8a). Thus, the availability of more hydrogen bond donors, although weak, brought about by the increase in substitution has resulted in distinct recognition patterns in contrast to that of molecules with minimal substitution. The H 3 3 3 N distance of the C-H 3 3 3 N hydrogen bonds observed in the assemblies are plotted in a chart for an easy comparison (Figure 8b). The number of hydrogen bonds in 1a is substantially lower than in its 3- and 4-pyridyl counterparts, 1b and 1c. But, in 3a and 3c, the C-H 3 3 3 N hydrogen bonds are similar in number and H 3 3 3 N bond distance. This indeed is brought about by the enhanced availability of hydrogen bond forming functionalities with the increase in substitution, making the orientation of the heteroatoms relatively insignificant. Thermal Analysis and PXRD Studies. The stability and phase purity of the assemblies were analyzed using

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thermogravimetry (TG) and powder X-ray diffraction (PRXD). While the TG plots of 1a-1c, 2a, and 2c do not show any solvent loss, 18% mass loss up to 400 °C was observed in the case of 3a and can be attributed to the initial loss of diethyl ether followed by breakdown of the assembly. The crystals of 2a and 2c lose their crystalline luster once exposed to air. The prior and rapid loss of solvent probably

Figure 8. (a) The variation in the hydrogen bond patterns observed in pyridazines as a function of substitution. (b) A plot of hydrogen bond distances in seven pyridazine compounds.


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accounts for the absence of weight loss, corresponding to solvent, in the thermogravimetric plots. A molecule of lattice water and two DMF units (12%) were lost in the case of 3c by 200 °C, with further decomposition occurring with an onset temperature of 425 °C (see Supporting Information). Although there exist the effect of morphology and crystallite size on some of the features of patterns, the peak positions of the experimental diffraction patterns of compounds, 1a-1c are consistent with that of the simulated. The powder patterns for 2c, 3a and 3c show considerable variation with respect to the simulated pattern along with a decrease in the crystalline nature. This may be due to the collapse of the molecular framework initiated by the solvent loss. However in 2a the framework is maintained even after the removal of solvent molecules, as evidenced from the similar experimental and simulated diffraction patterns (see Supporting Information). Nano/Microcrystal Analysis. The morphology variations of nanocrystals as a function of steric interactions, π-π stacking, and hydrogen bonding motifs is known in the literature, although the manipulation of nanoparticle morphology by altering the molecular geometry of the compound has been met with limited success.16 Thus, a rational and simple approach to synthesize organic nanocrystalline materials is highly desirable for understanding the various factors that influence the morphology variations and stability. In conjunction with the structural analysis, the organic nano/microparticles were prepared by the precipitation method (by rapid injection of the respective compounds in DMF into water). It was noticed that all nine compounds

Figure 9. The SEM images of the nano/microparticles of 1a, 1b, and 1c. The observed transistion from spherical metastable particles to microcrystals in the case of 1b is represented by the arrow.

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Figure 10. The SEM images of the nano/microcrystals of 2a-2c and 3a-3c. The magnified image of the particles, in the case of 2c is given in inset.

yielded particles with distinct morphology, although they lack monodispersity. To evaluate the stability of the nano/ microparticles formed, SEM studies were carried out three times over a period of one week, one month and two months, after the initial sample preparation. Except for 1b, all the nano/microparticles were observed to be stable. Also the experiments were carried out in similar conditions to establish the reproducibility, and the results were found to be consistent. The isomer effect of the compounds was analyzed by comparing the morphology of the nano/microparticles obtained in the case of 1a, 1b, and 1c (Figure 9). While compounds 1a and 1c formed crystals with distinct faces and edges, the 3-pyridyl compound, 1b, formed spherical particles. Compound 1a formed bundles of long needles with an average dimension of 50 3 μm; 1b yielded zero-dimensional spherical particles with an average dimension of 1 μm.

Clusters of microparticles with the appearance of rice grains with dimensions in the range of 700 nm to 2 μm were obtained for 1c. The three isomers exhibited different hydrogen bond forming abilities in the supramolecular assemblies and this in turn is reflected in the nano/microparticle morphologies. This change in morphology can therefore be attributed to the different interactions at a supramolecular level brought about by variation in the position of the pyridine heteroatoms and the influence of their interactions with the solvent system. However, we are unaware of the possibility of the solvent trapped in these particles. A similar report of distinct nanostructures from isomeric molecules was presented by Yao et al. using bis(iminopyrrole)benzenes as representative examples.18 In a recent paper, Lee and coworkers proposed that the variation in the morphology can also be brought about by the dipole moments, with zerodimensional spherical nanoparticles formed by the molecules

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with a lower dipole moment.19 In the case of 1b, the particles exhibited a spherical morphology, and over a period of two months they transformed to microcrystalline particles. A similar observation was reported for a series of intramolecular charge transfer (ICT) compounds.19 It was reported that over a period of time the metastable aggregates dissolved and transformed to grow into crystallites along the direction of the directional interactions. Although we have not carried out an in situ experiment to analyze this phase transition, it is possible to postulate that recrystallization might have been involved in this process, as the amount of these spherical particles were found to vary over a different time period and also in repeated experiments. Such transitions were not observed in the case of other pyridazines, as all the other compounds yielded crystalline particles. The particles obtained in the case of dipyridyl pyridazine compounds, 2a, 2b, and 2c, also exhibited interesting morphologies (Figure 10). While 2a formed circular flakes, the 4-pyridyl analogue, 2c, formed blunt rectangular particles. In the case of 2b, twisted crystals were obtained. Although infinite helical tapes are known in gels and were reported earlier, their crystalline counterparts for small molecules are relatively uncommon.20 The 1,3,5-tripyridazine compounds (3a, 3b, and 3c) formed thin platelets with distinct features. In the case of 3a, thin flakes of several micrometers were observed. Compounds 3b and 3c formed platelets with a dimension of ∼2 μm. The distinct morphologies of the nanoparticles of tripyridazine compounds may be due to the decrease in the molecular planarity brought about by the increase in substitution, thus making the rearrangement and stacking between molecules more difficult. Similar observations of steric effects hindering the formation of one-dimensional nanostructures and the formation of thin platelets and nanoparticles instead can be found in the literature.21 The results show that the morphology of the nanostructures of small molecular organic materials can be readily tuned by varying the isomer or the steric hindrance. Attempts were made to prepare nanocrystals of the compounds from DMF/toluene to study the solvent effects, but the systems failed to form any assembly, possibly because of the solubility of the compounds in the binary solvent system. Conclusion A series of mono-, 1,4-di-, and 1,3,5-tripyridylpyridazines have been synthesized and analyzed. The hydrogen bond properties and crystal packing were found to depend on the positional isomerism and steric effects. Although the extent of influence of steric hindrance and isomerism in crystal packing cannot be reached a posteriori, it is known in the literature that efficiency of close packing decreases with an increase in steric hindrance and uneven topology of the molecules. While close-packed assemblies were observed in monopyridazines, both porous and close-packed systems are formed in dipyridazine derivatives. The trisubstituted compounds with labyrinthine topology consistently yielded porous solvated assemblies. In all the cases, the steric strain of the molecules were analyzed by calculating the angles between the best leastsquares planes of the rings and were found to be a function of the extent of substitution. In all the cases, the assemblies are stabilized by weak noncovalent interactions such as C-H 3 3 3 N, C-H 3 3 3 π, and π 3 3 3 π. In the present series of compounds, due to the steric strain, the interactions extend well beyond the sum of the van der Waals radii, thus making it weaker in nature. The relatively uncommon multiple hydrogen

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bond acceptor nature of pyridazine is observed in the di- and trisubstituted compounds. The powder X-ray analysis clearly indicates that in most of the solvated assemblies the molecular frameworks collapse with the loss of solvents. The nano/microparticles of the pyridazines exhibit distinct morphologies and indicate that the resulting disparity can be brought about by the difference in the intermolecular interactions existing between the molecules and also with the solvent system. Thus, the present study contributes toward an understanding of hydrogen bond patterns and crystal packing in a series of pyridazines as a function of isomerism and steric effects and its consequence on the morphology of nano/microcrystals. Experimental Details The chemicals were purchased from Aldrich and used without further purification. Reagent grade toluene was used for the reaction. The 1,4-phenylene-diacetylene and 1,3,5-phenylene-triacetylene were prepared by Sonogashira coupling following the literature methods.22 The tetrazines were prepared from the corresponding cyanopyridines as per the procedures available in the literature.23 General Procedure for 1a, 1b, and 1c. Phenyl acetylene (0.102 g; 1 mmol) and 3,6-di(2-pyridyl)tetrazine (0.236 g; 1 mmol) were refluxed in 5 mL of toluene in a pressure tube (15 mL) at 140 °C for 48 h. By the end of the reaction, the purple color disappears to form a pale yellow precipitate. The solvent was removed under a vacuum and the compound was run through a column on silica using ethylacetate-methanol (9:1) as eluent. General Procedure for 2a, 2b, and 2c. 1,4-Phenylene-diacetylene (0.126 g; 1 mmol) and 3,6-di(2-pyridyl)tetrazine (0.472 g; 2 mmol) was refluxed in 7 mL of toluene in a pressure tube (15 mL) at 160 °C for 48 h. By the end of the reaction, the purple color disappears and a pale yellow precipitate is formed. The compound was purified using column chromatography on silica using dichloromethane-acetone (7:3) as the eluent. General Procedure for 3a, 3b, and 3c. 1,3,5-Phenylene-triacetylene (0.150 g; 1 mmol) and 3,6-di(2-pyridyl)tetrazine (0.708 g; 3 mmol) was refluxed in 10 mL of toluene in a pressure tube (25 mL) at 180 °C for 48 h. By the end of the reaction, the purple color disappears and a pale yellow precipitate is formed. The compound was purified using column chromatography on silica using ethylacetate-methanol (9:1) as eluent. (In the case of the preparation of 3c, the acetylene/ tetrazine ratio should exceed 1:5.) X-ray Analysis. Single crystals of 1a-3c were carefully chosen after they were viewed through a microscope supported by a rotatable polarizing stage. The crystals were glued to a thin glass fiber using NVH immersion oil and mounted on a diffractometer equipped with an APEX CCD area detector. All the data were collected at 123 K. The intensity data were processed using Bruker’s suite of data processing programs (SAINT), and absorption corrections were applied using SADABS.24 The structure solution of all the complexes was carried out by direct methods, and refinements were performed by full-matrix least-squares on F2 using the SHELXTL-PLUS suite of programs.24 All the non-hydrogen atoms were refined anisotropically, and the hydrogen atoms were fixed on the calculated positions using appropriate AFIX commands and were refined isotropically. Intermolecular interactions were computed using the PLATON program.25 Nanoparticle Preparation and Analysis. The nanoparticles were prepared by the rapid injection of 50 μL of 10-3 M compound in DMF (filtered through a nanoporous alumina membrane (Whatman, Anodisc 13)) to 20 mL of Millipore water under ultrasonication. The turbid solution was kept at isothermal conditions (40 °C) for 48 h and was filtered through anodisc (20 nm). The morphology of the nanoparticles was analyzed using a TESCAN scanning electron microscope using a beam voltage of 5 kV. Thermal Analysis. Thermogravimetric analyses were carried out using a Perkin-Elmer Pyris 1 TG analyzer, and the experiments were carried out in inert atmosphere with a heating rate of 10 °C/min.

Acknowledgment. This material is based upon works supported by Science Foundation Ireland [05PICAI819]. S.V.

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thank Prof. T. N. Guru Row and Dr. S. Philip Anthony for fruitful discussions. Supporting Information Available: Additional crystallographic and spectroscopic information, figures, tables, TG plots, PXRD patterns, and SEM images. This information is available free of charge via the Internet at http://pubs.acs.org/.

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Pyridazines in Crystal Engineering. A Systematic Evaluation of the

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