Halogen-Bonded Supramolecular Assemblies Based on

moieties have been synthesized and used for the formation of halogen bonding (XB)-based networks. X-ray crystal structure analyses indicate the domina...
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CRYSTAL GROWTH & DESIGN

Halogen-Bonded Supramolecular Assemblies Based on Phenylethynyl Pyridine Derivatives: Driving Crystal Packing through Systematic Chemical Modifications

2008 VOL. 8, NO. 8 3066–3072

Tanya Shirman,‡ Jean-Francois Lamere,‡ Linda J. W. Shimon,† Tarkeshwar Gupta,‡ Jan M. L. Martin,*,‡ and Milko E. van der Boom*,‡ Departments of Organic Chemistry and Chemical Research Support, The Weizmann Institute of Science, 76100 RehoVot, Israel ReceiVed February 24, 2008; ReVised Manuscript ReceiVed April 30, 2008

ABSTRACT: A series of phenylethynyl pyridine derivatives 1-4 possessing both perfluorocarbon (PFC) and hydrocarbon (HC) moieties have been synthesized and used for the formation of halogen bonding (XB)-based networks. X-ray crystal structure analyses indicate the dominance of XB synthons, which represent the one-dimensional (1D) structure directing interaction, leading to the formation of supramolecular chains. The influence of structural/electronic factors (e.g., electron donor/acceptor strength, sterically demanding substituents) on XB formation of compounds 1-4 have been compared with structurally related stilbazole systems (I, II). The XB-bonded networks are formed in collaboration with other noncovalent interactions such as π-π stacking, hydrogen bonding, C-H · · · F and F · · · F. Molecular electrostatic potentials and atomic polar tensor (APT) charges of the donor and acceptor sites have been determined by density functional theory (DFT) calculations. Introduction Crystal design and engineering has received much attention in recent years as its implications extend well beyond material science into areas such as solid-state synthesis and drug development.1–4 One of the most important issues in this field is the rational design and structural control of molecular packing, which affect and control the macroscopic properties of the material (e.g., electrical, optical, and electronic properties, supramolecular isomerism, and polymorphism). Hydrogen bonding, metal coordination, and aromatic noncovalent interactions have been widely exploited as directional motifs for the design and synthesis of supramolecular assemblies.5–10 Halogen bonding (XB) is another type of noncovalent interaction, which was shown to be an effective directional tool to assemble highly ordered supramolecular architectures.11,12 In XB, the carbonbound halogen atom (Cl, Br, I) acts as an acceptor for the lonepair electrons of a heteroatom (i.e., N, O, P, S). The more electron-withdrawing the atom or the moiety bound to the halogen, the stronger the halogen bond. Hence, the electron accepting ability in perfluorocarbon (PFC) halides is definitely higher than in corresponding hydrocarbon (HC) halides and is comparable in strength to hydrogen bonding (3-7 kcal mol-1).12,13 These Lewis acid-base interactions were shown to have great potential in fields as diverse as biopharmacology, material science, and crystal engineering.14–20 For example, a survey of protein and nucleic acid structures clearly demonstrates the potential of XB in ligand binding and recognition, as well as in molecular folding.16–18 XB-controlled solid-state reactivity and liquid crystal formation have been demonstrated recently.19,20 In addition, several theoretical investigations on XB have been conducted.21–23 Nevertheless, the XB concept is still largely unexplored and there are still many fundamental issues to be addressed. Halogen-bonded networks often consist of alternating separate donor and acceptor modules assembled into onedimensional (1D) infinite chains. Examples of heteroditopic self-

complementary XB-bonded modules combining both donor and acceptor in one molecular structure are relative rare.24–28 Recently we communicated the synthesis and characterization of new bifunctional stilbazole-based chromophores I and II capable of forming XB-based networks.29,30 Compound I combines pyridine-based electron donor and perfluorocarbon electron acceptor sites in one conjugated molecule.29 Its crystal structure consists of a network involving both interchain π-π stacking and N · · · Br interactions. Chromophore II consists of one hydrocarbon XB acceptor and two perfluorocarbon multifunctional XB donor/acceptor sites and exhibits a solid-state structure of infinite parallel helices, that are built-up of two kinds of halogen bonds, N · · · I and I · · · I, and which are interconnected by π-π stacking and C-H · · · F interactions.30 Compound II represents the first example of a unimolecular helical system based on XB.30–32 Apparently, the structural differences between I and II have a significant effect on the molecular packing.

Here we report how molecular changes of phenylethynyl pyridine derivatives 1-4 affect the structure of XB-based supramolecular networks. In particular, the influence of structural/ electronic factors on XB formation (e.g., CtC vs CdC, donor/ acceptor strength, sterically demanding substituents) has been addressed. For example, replacing the CdC bridge of I with a CtC moiety affords a highly symmetric molecule (1) that forms a noncentrosymmetric network with orientational disorder. Compound 3 having a strong electron donor site (N-oxide) forms a highly ordered structure and incorporation of a bulky tBuO group (4) disrupts the symmetry of the molecule while XB is conserved. Results and Discussion

* E-mail: [email protected];[email protected]. † Department of Organic Chemistry. ‡ Department of Chemical Research Support.

Synthesis. The phenylethynyl-pyridine derivatives 1 and 2 were obtained by a Sonogashira cross-coupling reaction between

10.1021/cg800208w CCC: $40.75  2008 American Chemical Society Published on Web 07/17/2008

Halogen-Bonded Supramolecular Assemblies

Crystal Growth & Design, Vol. 8, No. 8, 2008 3067 Table 1. APT Charges on Selected Atoms of Compounds 1-4 atom Br N O

ethynyl pyridine and a 2.5-fold excess of 1,4-dibromotetrafluorobenzene (1,4-C6F4Br2) using a catalytic amount (∼5%) of PdCl2(PPh3)2 and CuI in dry Et3N under N2 (Scheme 1). An excess of 1,4-C6F4Br2 suppressed the formation of doublecoupling products. Compounds 1 and 2 were isolated by column chromatography with 15 and 30% yields, respectively. Compound 1 was used for forming the N-oxide derivative 3. The N-oxide moiety is a stronger electron donor than the pyridine group of the parent compound (1) (vide infra). The reaction between compound 1 and m-chloroperbenzoic acid (mCPBA) in CHCl3 at room temperature afforded compound 3 in excellent yield (90%) after column chromatography (Scheme 1). Compound 4 was synthesized using a Horner-Wadsworth-Emmons (HWE)-type reaction.33 Condensation of compounds 5 and 6 in the presence of 2 equiv of tBuOK resulted in the formation of compound 4 with 40% yield (Scheme 2). The new compounds 1-4 have been characterized by combining 1H, 13C{1H}, 19F{1H} NMR, single-crystal X-ray diffraction analysis, mass spectrometry (MS), and elemental analysis. In addition, UV/vis and electrochemical data are provided in the Supporting Information. DFT Calculations. Electrostatic potentials have been found to be an effective tool for analyzing and predicting noncovalent interactions and for describing the ability of molecules to interact through the regions of positive and negative potential on its

1

2

3

4

-0.16 -0.45

-0.16 -0.41

-0.17 0.95 -1.14

-0.17 -0.47 -0.87

surface.34 In this regard, we have performed computational studies with the Gaussian 03 program package.35 Geometry optimization of compounds 1-4 was carried out at the density functional PBE0 computational level36 using the aug-cc-pVDZPP37 basis set for Br atom, aug-pc138 for other heteroatoms and pc139 for all remaining atoms. The optimized geometries are in good agreement with the X-ray structures (see Supporting Information). The torsion angle between the rings is 0° for compounds 1-3 and 8° for compound 4. The atomic polar tensor (APT) charges of the atoms in molecules 1-4 are presented in Table 1.40 As expected the largest negative value is observed for the oxygen atom in compound 3. The electron-donating character of the oxygen and nitrogen atoms can also be gauged from the relative energies of the highest occupied molecular orbitals (HOMOs). These are mostly localized on the oxygen atom in 3 and on the nitrogen atoms in 1, 2, and 4. In this case, the first highest occupied molecular orbital involving the oxygen atom in 3 is the HOMO with energy equal to -6.569 eV, and the nitrogen atom in 1, 2, and 4 is the HOMO-2 with energies equal to -7.907, -7.887, and -7.825 eV, respectively. These results suggest also that the oxygen atom in 3 is a stronger electron donor than the nitrogen atom in the others compounds. Figure 1 represents calculated electrostatic potentials mapped on the surface of the molecular electron density (0.002 e au-3), where red indicates negative and blue indicates a positive potential. Perfluorination of the aromatic ring inverts the electron distribution in comparison with the pyridine moiety. The region of positive electrostatic potential develops on the outermost portion of bromine atoms, around the intersection with the C-Br axis. This positive region has been referred to as a “σ-hole” and was found to be responsible

Scheme 1. Synthetic Scheme for Compounds 1-3 Possessing Both XB Donor and Acceptor Sites

Scheme 2. Synthetic Scheme for Bifunctional Compound 4 Possessing a Bulky tBuO Group

3068 Crystal Growth & Design, Vol. 8, No. 8, 2008

Shirman et al.

Figure 1. The computed molecular electrostatic potentials mapped on the surface of the electron density (0.002 e au-3) of compounds 1-4. Colors of atoms: carbon, gray; hydrogen, white; nitrogen, blue; fluorine, light blue; bromine, red; oxygen, light red.

Figure 2. ORTEP III views of the molecular structures of compounds 1, 3, and 4. Thermal ellipsoids are set at 50% probability. Colors of atoms: carbon, black; nitrogen, blue; fluorine, green; bromine, brown; oxygen, red. Hydrogen atoms are omitted for clarity. The crystal structure of 4 shows two symmetry-independent molecules, 4A and 4B. Table 2. Selected Parameters of the X-ray Analyses of Compounds 1-4, I and II compound crystal system

space group

1

monoclinic

Pc

3

monoclinic

P21/n

4A 4B Ib IIc

monoclinic monoclinic monoclinic orthorhombic

P21/c P21/c P212121

interactions d(Å) d/davdW C-Br · · · N C-Br · · · O C-H · · · O F· · ·F C-Br · · · N C-Br · · · N C-Br · · · N C-I · · · N

2.82 2.82 2.38 2.79 2.91 3.08 2.84 2.86

0.84 0.84 0.87 0.95 0.87 0.89 0.84 0.81

θ (°) 177.63 165.52 156.71 86.80 175.90 163.60 177.80 172.86

a Bondi, A. J. Phys. Chem. 1964, 68, 441-451. b Lucassen, A. C. B.; Vartanian, M.; Leitus, G.; van der Boom, M. E. Cryst. Growth Des. 2005, 5, 1671-1673. c Lucassen, A. C. B.; Zubkov, T.; Shimon, L. J. W.; van der Boom, M. E. CrystEngComm 2007, 9, 538.

for the occurrence of halogen bonding.41 A negative potential corresponds to an electron donor site, that is, nitrogen, and it is somewhat similar in compounds 1, 2, and 4. Single Crystal X-ray Studies. Compounds, 1, 3, and 4 have been characterized by single-crystal X-ray analysis and their molecular structures are shown in Figure 2. Selected geometrical parameters of intermolecular interactions in the crystal packing are listed in Table 2. For comparison, selected intermolecular geometries of the molecular packing of compounds I and II are also presented.29,30 Attempts to obtain crystals of compound 2 suitable for a detailed structural analysis did not succeed. A description of the preliminary structure is available in the Supporting Information.

4-(4-Bromo-2,3,5,6-tetrafluoro-phenylethynyl)-pyridine 1-oxide (3). Single crystals of compound 3 have been obtained from a saturated diisopropyl ether solution at room temperature and belong to the monoclinic space group P21/n. The use of the N-oxide moiety as a relatively strong electron donor resulted in the assembly of a solid-state XB-based framework (Figure 3).13,42 The two aromatic rings are twisted by 18.4°. The supramolecular organization of compound 3 consists of linear infinite 1D chains that are aligned in a head-to-tail fashion due to attractive XB forces. The Br · · · O distance of 2.82 Å is ∼16% shorter than the sum of van der Waals radii (Table 2) and is comparable to literature data.43 Two adjacent chains are oriented in opposite directions, forming layers with C-H · · · O hydrogen bonds (2.38 Å) and short F · · · F (2.79 Å) contacts (Figure 3A). In this system, hydrogen bonding and XB coexist and probably drive the selfassembly process.44,45 However, F · · · F segregation as a possible “player” in the structural assembly/organization of these molecules cannot be ruled out.46–49 The interlayer distance is ∼3.28 Å, which falls well within the range of π-π stacking interactions. The molecules belonging to different planes are not superimposed, perhaps as a result of C-H · · · O interactions. Consequently, the offset between two layers causes the distance between parallel ring centroids to be ∼4.83 Å. Apparently, π-π stacking interactions are relatively weak and parallel layers interact only by residual forces producing sheet-like structures. Adjacent sheets are orthogonal to each other and exhibit short C-H · · · F distances (Figure 3B). 4-(4-Bromo-2-tert-butoxy-3,5,6-trifluoro-phenylethynyl)pyridine (4). Colorless crystals of compound 4 were obtained from a saturated methanol solution at 4 °C. Compound 4 crystallizes in monoclinic space group P21/c. The steric hindrance between the tBuO groups may play an important role in controlling the molecular packing because it induces considerable changes in the geometry of compound 4. X-ray analysis reveals two symmetrically independent molecules, 4A and 4B, with different torsion angles, 32.4° and 13.4°, respectively (Figure 4). Recent theoretical and experimental studies showed that twisted π-electron molecular systems exhibit highly chargeseparated zwitterionic ground states and extremely large hyperpolarizabilities.50,51 The molecular packing of compound 4 exhibits a layered structure (Figure 4). In addition, the molecules are aligned in a head-to-tail fashion into 1D infinite chains due to attractive halogen bonds along the a axis. In each chain, 4A and 4B alternate, which causes two slightly different XB distances and contact angles (Table 2). Each chain interacts differently with two adjacent chains. For example, there are (i) weak C-H · · · F interactions between a methyl group of 4B and the fluorinated ring of 4B, (ii) π-π interactions between two molecules of 4A, and (iii) π-π interactions between two molecules of 4B. There is a zigzag structure propagating along the c axis. Similar to system I, adjacent pyridine and fluorinated rings are aligned face-to-face with separations of ∼4 Å between two ring centroids. Incorporating the bulky tBuO group into the structure of compound 1 significantly lowers the symmetry and gives rise to welldefined molecular packing through XB. The steric hindrance results in structural conformations that enable the molecules to achieve dense packing and to retain the XB network. In addition, π-π stacking interactions are involved in the 2D packing of compounds 4 and I (in contrast to compound 3). 4-(4-Bromo-2,3,5,6-tetrafluoro-phenylethynyl)-pyridine (1). Crystals of 1 were obtained as colorless needles from a saturated methanol solution at 4 °C and belong to the monoclinic

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Crystal Growth & Design, Vol. 8, No. 8, 2008 3069

Figure 3. (A) View of a 2D sheet for compound 3 by intermolecular interactions visualized by colored dashed lines: red, XB; blue, C-H · · · O; green, F · · · F. Colors of atoms: carbon, black; hydrogen, pink; nitrogen, blue; fluorine, green; bromine, brown; oxygen, red. (B) 3D supramolecular packing of compound 3. Hydrogen atoms are omitted for clarity.

Figure 4. (A) Crystal packing of compound 4 showing two types of XB in dashed lines. Colors of the atoms: carbon, black; nitrogen, blue; fluorine, green; bromine, brown; oxygen, red. (B) Crystal lattice colored according to the symmetrical equivalents.

noncentrosymmetric space group Pc. Compound 1 adopts two different orientations resulting in disorder of the bromine and ethynyl groups (Figure 5A). A similar orientational disorder was described for chloro- and bromo-substituted ethynylbenzenes and was attributed to the shape and interactional complementarities between the halogen and ethynyl groups.52–54 For 1, the

positions of these groups are superimposed along the b axis (Figure 5B, 1A and 1B). The positions of the carbon atoms at the ring in the two molecular orientations are similar. The ratio between 1A and 1B is approximately 2:1. The packing motif consists of 1D infinite chains in which the molecules are aligned in head-to-tail fashion and form layered domains in the ac plane

3070 Crystal Growth & Design, Vol. 8, No. 8, 2008

Figure 5. (A) Ball and stick representation of the disordered molecular orientations for compound 1. The colored and striped circles represent the different components of the disordered structure. (B) View of the different ordered domains for compound 1.

Shirman et al.

neighboring chains in 1 are negligibly stacked through π-π interactions, since the distance between the centroids of the rings is ∼4.9 Å, due to a quite large offset (5.183 Å) between two chains. In contrast, the crystal structure revealed the presence of a short distance (∼3.5 Å) between the carbon-carbon triple bond, with the pyridine ring on one side and the fluorinated ring on the other side.42,52–54 The assembly of compound I (having a bridging CdC moiety) does not exhibit the orientational disorder observed for compound 1. Both Ar · · · Ar and Ar · · · Arf π-π stacking interactions are present in the 2D structure of compound I, whereas the crystal structure of the alkyne analogue 1 indicates π(CtC) · · · π(Arf) interactions. In addition, the 3D overall packing of stibazole I is completed by short F · · · F interactions (2.832 Å) that are absent in the crystal packing of compound 1. The overall packing of 1 and I appear to be controlled by the type of bridging carbon-carbon bond between the XB donor and acceptor units. Summary and Conclusions The molecular packing of chromophores 1-4 and I indicates the presence of strong, attractive XB that causes the molecules to be aligned in 1D infinite head-to-tail chains. In contrast, the solid-state structure of compound II consists of infinite parallel helices.30 The intermolecular distances between XB donors and acceptors are 11-16% shorter than the sum of van der Waals radii, and the C-X · · · Y (Y ) N, O) angles are approximately linear (163°-178°), indicating the importance of the halogen bonding in driving the self-assembly. The carbon-carbon triple bond increases the symmetry of the molecule (i.e., 1 vs I) and apparently results in an orientational disorder in the molecular packing of compound 1. In contrast, the solid-state framework of compound 3 exhibits well-ordered supramolecular organization perhaps due to the incorporation of a stronger electron donor (N-oxide vs N) and the combination of XB and hydrogen bonding. The bulky tBuO group in compound 4 disrupts the molecular symmetry but not the XB network. This illustrates that variations of the molecular structures of stilbazole and phenylethynyl pyridines are clearly expressed in the supramolecular organization of halogen-bonded networks. Experimental Procedures

Figure 6. (A, B) Different views of crystal packing of 1. Red dashed lines indicate the XB. Colors of atoms: carbon, gray; nitrogen, blue; fluorine, green; bromine, brown. H atoms are omitted for clarity.

(Figure 6). Despite the disorder, the packing clearly shows the presence of Br · · · N halogen bonding with an intermolecular distance of 2.820 Å, which is ∼16% shorter than the sum of the van der Waals radii (Table 2). The similar Br · · · N distances for compounds 1 and I are in agreement with reported values (Table 2).55 The C-Br · · · N angle is nearly linear (177.63°), in agreement with the n f σ* character of XB interactions. Within each layer, the adjacent chains run parallel, with an interchain distance of 3.34 Å producing sheet-like structures in the ab plane. The neighboring sheets are almost orthogonal to each other (Figure 6B). In the molecular packing of I each chain is stacked on one side with an equivalent aromatic pyridine ring and on the other side with an unequivalent perfluorinated ring with a center-to-center distance of ∼3.8 Å. This packing motif is typical for areneperfluoroarene complexes, including rod-type compounds.49,56,57 In comparison with compound I, the aromatic rings of the

Materials and Methods. All reactions were performed under argon or nitrogen unless otherwise stated. Chemicals were obtained from Aldrich and used as received. Reaction flasks were washed with deionized (DI) water, followed by acetone, and then dried in an oven at 130 °C overnight prior to use. The 1H, 13C{1H} NMR spectra were recorded at 400.19 and 100.6 MHz, respectively, on a Bruker AMX 400 NMR spectrometer, at 500.13 and 125.77 MHz on a Bruker AMX 500 NMR spectrometer, and at 250.17 and 62.9 MHz, respectively, on a Bruker DPX 250 NMR spectrometer. The19F{1H} NMR spectra were recorded at 356.1 MHz on a Bruker AMX 400 NMR spectrometer and at 235.0 MHz on a Bruker DPX 250 NMR spectrometer. All chemical shifts (δ) are reported in ppm and coupling constants (J) are in Hz. The 1H and 13C{1H} NMR chemical shifts are relative to tetramethylsilane; the resonance of the residual protons of the solvent were used as an internal standard for 1H (δ 7.15 benzene; 7.09 toluene; 2.06 acetone) and all-d solvent peaks for 13C (δ 128.0 benzene; 20.4 toluene; 206.0 acetone). 19F{1H} NMR chemical shifts are relative to hexafluorobenzene in CDCl3 at δ ) -163.0 ppm (external reference). Assignments in the 1H and 13C{1H} NMR were aided by 1H{31P} NMR and 13C-DEPT-135 NMR measurements. All measurements were carried out at 298 K. Mass spectrometry was carried out using a Micromass Platform LCZ 4000 instrument. Elemental analyses were performed by H. Kolbe, Mikroanalytisches laboratorium, Mu¨lheim an der Ruhr, Germany.

Halogen-Bonded Supramolecular Assemblies Synthesis of 4-(4-Bromo-2,3,5,6-tetrafluoro-phenylethynyl)-pyridine (1). A mixture of 4-ethynylpyridine (0.36 g, 3.5 mmol), dibromotetrafluorobenzene (1.85 g, 7.0 mmol), PdCl2(PPh3)2 (70 mg, 0.10 mmol), CuI (20 mg, 0.10 mmol), and dry Et3N (30 mL) in dry THF (5 mL) was heated at 105 °C for 3 days. The volatiles were removed under vacuum and the residue was dissolved in CH2Cl2 and filtered. Evaporation yielded a crude yellow-brown powder product that was chromatographed on a basic alumina column using hexane/ether (9:1) as eluent to yield compound 1 as an off-white powder (0.2 g, 15%). 1H NMR (400.19 MHz, CDCl3) δ (ppm): 8.6 (d, 2H, JHH ) 6.0 Hz), 7.5 (d, 2H, JHH ) 6.0 Hz). 19F{1H} NMR (356.1 MHz, CDCl3) δ (ppm): -132.3 (m, 2F), -134.3 (m, 2F). 13C{1H} NMR (100.6 MHz, CDCl3) δ (ppm): 149.3 (s, CPyr), 148.2 (m, CF), 146.2 (m, CF), 145.7, (m, CF), 143.7 (m, CF), 130.2 (s, pyridine-C-CtC-), 125.7 (s, CPyrCtC), 102.2 (CtC-CC5F4Br), 98.6 (t, -CtC-), 78.7 (t, -CtC-). EIMS: (M+) 330.0. Elemental analysis calcd (%) for C13H4BrF4N: C 47.30, H 1.22, N 4.24 found: C 47.62, H 1.57, N 4.01. Synthesis of 5-(4-Bromo-2,3,5,6-tetrafluoro-phenylethynyl)-pyridine (2). A glass pressure tube was charged with 3-ethynylpyridine (0.50 g, 4.9 mmol), dibromotetrafluorobenzene (2.80 g, 9.7 mmol), PdCl2(PPh3)2 (70 mg, 0.10 mmol), CuI (20 mg, 0.10 mmol), and 40 mL of dry Et3N. The reaction mixture was heated at 105 °C for 2 days, after which the solvent was removed under vacuum. Subsequently, the residue was dissolved in CH2Cl2 and filtered. Evaporation of the obtained solution yielded a crude brown powder product. Column chromatography on basic alumina (hexane/ether 9:1) yielded compound 2 as a white powder (0.5 g, 30%). 1H NMR (250.17 MHz, CDCl3) δ (ppm): 8.8 (s, 1H), 8.6 (d, 1H), 7.9 (d, 1H), 7.3 (t, 1H). 19F{1H} NMR (356.1 MHz, CDCl3) δ (ppm): -132.8 (dd, 2F), -134.9 (dd, 2F). 13 C{1H} NMR (100.6 MHz, CDCl3) δ (ppm): 151.8 (s), 149.3 (s), 148.1 (m), 146.2 (m), 145.6 (m), 143.6 (m), 139.3 (s),123.4 (s), 119.0 (s), 103.7 (m), 101.5 (m), 98.3 (s), 77.5 (m). Elemental analysis calcd (%) for C13H4BrF4N: C 47.30, H 1.22, N 4.24 found: C 47.36, H 1.24, N 4.12. Synthesis of 4-(4-Bromo-2,3,5,6-tetrafluoro-phenylethynyl)-pyridine-1-oxide (3). A solution of compound 1 (0.20 g, 0.60 mmol) in CHCl3 (20 mL) was cooled to 0 °C and m-chloroperbenzoic acid (mCPBA) (0.11 g, 0.60 mmol), dissolved in CHCl3 (5 mL), was added dropwise. The resulting mixture was warmed to room temperature and stirred for 20 h. Purification by column chromatography (basic alumina, CHCl3) yielded compound 3 as a yellowish powder (0.12 g, 90%). 1H NMR (250.17 MHz, CDCl3) δ (ppm): 8.2 (d, 2H), 7.4 (d, 2H). 19F{1H} NMR (356.1 MHz, CDCl3) δ (ppm): -132.3 (m, 2F), -134.5 (m, 2F). 13 C{1H} NMR (100.6 MHz, CDCl3) δ (ppm): 148.1 (m), 146.2 (m), 145.4 (m), 143.6 (m), 139.4 (s), 128.8 (s), 121,34 (s), 102,5 (s), 97.2 (s), 80.9 (s). EI-MS: (M+) 344.9. Elemental analysis calcd (%) for C13H4BrF4NO: C 45.12, H 1.16, N 4.05 found: C 45.36, H 1.21, N 3.90. Synthesis of 4-(4-Bromo-2-tert-butoxy-3,5,6-trifluoro-phenylethynyl)-pyridine (4). Precursors 5 and 6 were prepared according to published procedures.23 In a dry 100 mL three-necked flask equipped with stirring bar and drying tube, 6 (1.1 g, 4.3 mmol) and 5 (1.5 g, 4.1 mmol) were dissolved in THF (50 mL). After the sample was stirred for a ∼5 min, tBuOK (1.25 g, 12.0 mmol) was added and the reaction mixture was stirred under argon for 3 h at room temperature. The solvent was evaporated and the residue was extracted with CH2Cl2/ H2O, dried over Na2SO4, and filtered. Next, the solvent was removed and the crude product was purified by column chromatography (silica gel, hexane/diethyl ether 9:1) to yield compound 4 as an off-white solid (0.17 g, 40%). 1H NMR (250.17 MHz, CDCl3) δ (ppm): 8.6 (d, 2H), 7.4 (d, 2H), 1.4 (s, 9H). 19F{1H} NMR (356.1 MHz, CDCl3) δ (ppm): -119.0 (d, 1F, JFF ) 11.0 Hz), -132.9 (d, 1F, 3JFF ) 22.8 Hz), -134.8 (q, 1F, 3JFF ) 23.0 Hz, 4JFF ) 10.6 Hz). 13C{1H} NMR (100.6 MHz, CDCl3) δ (ppm): 152.1 (t), 150.2 (t), 149.9 (s, CPyr), 148.2 (dd), 146.3 (dd), 145.6 (dd), 143.7 (dd), 141.5 (m), 130.3 (s, CPyr-CtC-), 125.3 (s, CPyr), 110.6 (m, CtC-C6F3-pBr), 101.5 (m, C-Br), 97.0 (s, -Ct C-), 85.9 (s, -CtC-), 83.2 (s, O-C(CH3)3), 29.0 (s, O-C(CH3)3). Elemental analysis calcd (%) for C17H13BrF3NO: C 53.15, H 3.41, N 3.65; found: C 53.34, H 3.48, N 3.61. DFT Calculations. The optimized geometries of the compounds 1-4 were calculated using density functional theory (DFT) with a locally modified version of the Gaussian 03 electronic structure program.35 Crystal structural data was used for the optimizations. The PBE0 functional36 was used for the investigation with the aug-cc-pVDZ-PP37 basis set for Br atom, aug-pc138 for other heteroatoms and pc139 for

Crystal Growth & Design, Vol. 8, No. 8, 2008 3071 all remaining atoms. The atomic polar tensors (APT) charges are based on the derivatives of dipole moment.40 X-ray Crystallography. X-ray diffraction data were measured on a Nonius KappaCCD diffractometer, Mo KR (λ ) 0.71073 Å), graphite monochromator at T ) 120(2) K. The data were processed with DenzoScalepack. Structures were solved with SHELXS-97 and refined as fullmatrix least-squares based on F2 with SHELXL-97. 1 C13H4BrF4N, M ) 330.08, colorless, plate, 0.20 × 0.20 × 0.1 mm3, monoclinic, space group Pc, a ) 9.9477(2), b ) 5.18527(1), c ) 11.5038(3) Å, β ) 109.055(2)°, V ) 560.59(2) Å3, Z ) 2, Dc ) 1.955 mg cm-3, F000 ) 1536, µ ) 3.702 mm-1, -15 e h e 14, 0 e k e 8, 0 e l e 17, frame scan width ) 1.0°, scan speed 1.0° per 30 s, typical peak mosaicity 0.61°, 11 648 reflections collected, 2454 independent reflections (Rint ) 0.043), 255 parameters with 452 restraints, final R1 ) 0.0447 (based on F2) for data with I > 2σ(I) and R1 ) 0.0475 on 2242 reflections, goodness-of-fit on F2 ) 1.242, largest electron density peak ) 0.875 e Å-3. The crystal has been solved with the packing disorder modeled. 3 C13H4BrF4NO, M ) 346.08, orange, plate, 0.30 × 0.10 × 0.05 mm3, monoclinic, space group P21/n, a ) 12.0974(1), b ) 4.8330(4), c ) 20.3142(8) Å, β ) 98.324(2)°, V ) 1175.1(1) Å3, Z ) 4, Dc ) 1.956 mg cm-3, µ ) 3.543 mm-1, -15 e h e 15, 0 e k e 6, 0 e l e 26, frame scan width ) 1.0°, scan speed 1.0° per 120 s, typical peak mosaicity 0.45°, 22 306 reflections collected, 5292 independent reflections (Rint ) 0.071), 197 parameters with 0 restraints, final R1 ) 0.0302 (based on F2) for data with I > 2σ(I) and R1 ) 0.0468 on 2662 reflections, wR2 ) 0.0627 (all data), goodness-of-fit on F2 ) 1.006, largest electron density peak ) 0.345 e Å-3. 4 C17H13NOF3Br, M ) 384.19, colorless, plate, 0.20 × 0.20 × 0.05 mm3, monoclinic, space group P21/c, a ) 24.111(5), b ) 12.836(3), c ) 10.303(2) Å, β ) 100.87(3)°, V ) 3131.5(11) Å3, Z ) 8, Dc ) 1.630 mg cm-3, µ ) 2.660 mm-1, -31 e h e 30, 0 e k e 16, 0 e l e 13, frame scan width ) 1.0°, scan speed 1.0° per 60 s, typical peak mosaicity 0.57°, 20 778 reflections collected, 7401 independent reflections (Rint ) 0.053), 421 parameters with 0 restraints, final R1 ) 0.0403 (based on F2) for data with I > 2σ(I) and, R1 ) 0.0703 on 7068 reflections, goodness-of-fit on F2 ) 0.983, largest electron density peak ) 0.597 e Å-3.

Acknowledgment. This research was supported by Minerva, BSF, and BMBF. M.E.vdB. is the incumbent of the Dewey David Stone and Harry Levine Career Development Chair and Head of the Minerva Junior Research Group on Molecular Materials and Interface Design. J.M.L.M. is the Baroness Thatcher Professor of Chemistry. T.G. wishes to thank the sixth Framework Program (FP6) of the EU for an incoming Marie Curie fellowship. Supporting Information Available: Crystallographic information files, UV/vis spectra, electrochemical characterization, and optimized geometries of compounds are available free of charge via the Internet at http://pubs.acs.org.

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