Pyrrole- and Naphthobipyrrole-Strapped Calix[4]pyrroles as Azide

Article Cite This: J. Org. Chem. 2018, 83, 2686−2693

pubs.acs.org/joc

Pyrrole- and Naphthobipyrrole-Strapped Calix[4]pyrroles as Azide Anion Receptors Seung Hyeon Kim,† Juhoon Lee,‡ Gabriela I. Vargas-Zúñiga,‡ Vincent M. Lynch,‡ Benjamin P. Hay,§ Jonathan L. Sessler,*,‡ and Sung Kuk Kim*,† †

Department of Chemistry and Research Institute of Natural Science, Gyeongsang National University, Jinju 660-701, Korea Department of Chemistry, The University of Texas at Austin, 105 E. 24th, Street-Stop A5300, Austin, Texas 78712-1224, United States § Supramolecular Design Institute, 127 Chestnut Hill Road, Oak Ridge, Tennessee 37830-7185, United States ‡

S Supporting Information *

ABSTRACT: The binding interactions between the azide anion (N3−) and the strapped calix[4]pyrroles 2 and 3 bearing auxiliary hydrogen bonding donors on the bridging moieties, as well as of normal calix[4]pyrrole 1, were investigated via 1H NMR spectroscopic and isothermal titration calorimetry analyses. The resulting data revealed that receptors 2 and 3 have significantly higher affinities for the azide anion in organic media as compared with the unfunctionalized calix[4]pyrrole 1 and other azide receptors reported to date. Single crystal X-ray diffraction analyses and calculations using density functional theory revealed that receptor 2 binds CsN3 in two distinct structural forms. As judged from the metric parameters, in the resulting complexes one limiting azide anion resonance contributor is favored over the other, with the specifics depending on the binding mode. In contrast to what is seen for 2, receptor 3 forms a CsN3 complex in 20% CD3OD in CDCl3, wherein the azide anion is bound only vertically to the NH protons of the calix[4]pyrrole and the cesium cation is complexed within the cone shaped-calix[4]pyrrole bowl. The bound cesium cation is also in close proximity to a naphthobipyrrole subunit present in a different molecule, forming an apparent cation-π complex.

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INTRODUCTION The azide anion (N3−) has seen ever increasing use as the result of the currently popular click reaction. It is also pervasive as the propellant in automobile airbags, routinely used in shocksensitive detonators, and widespread in agriculture. 1−3 Unfortunately, the azide anion is toxic and, in analogy to the cyanide anion (CN−), known to cause dysfunction of cytochrome C oxidase.4 In addition, the azide anion forms explosive salts such as NaN3 and Pb(N3)2.2,3 The ubiquity of the azide anion and its Dr. Jekyl and Mr. Hyde character provides an incentive to develop anion receptors that are able to detect and capture the azide anion with high affinity and selectivity. Some effort has been made along these lines. For instance, a protonated azacryptand (as its hexa-perchlorate salt) was first found to bind the azide anion in aqueous media.5 On the other hand, most azide receptors reported to date contain Lewis acidic centers such as transition-metal cations or boron atoms within macrocyclic frameworks.6 A drawback of such receptors is that their binding ability can be highly dependent on the pH, either through deprotonation or ligand complexation, and therefore significantly weakened under basic conditions. Neutral anion receptors that rely on largely pH independent hydrogen and halogen bonding are generally free from such limitations. Although a large number of such © 2018 American Chemical Society

receptors are known, only a limited number have been found suitable for azide anion recognition.7 The azide anion is structurally linear and its negative charge is symmetrically distributed at its two terminal nitrogen atoms.8 Therefore, a macrocyclic receptor capable of forming noncovalent bonds with both negatively charged nitrogen atoms concurrently could prove particularly efficient in terms of binding the azide anion. Achieving such putative ditopic recognition within the context of a neutral, nonionizable receptor imposes significant geometric constraints in terms of receptor design. Basically, two recognition motifs have to be constrained at a distance appropriate to interact with the azide anion. We felt the calix[4]pyrrole core could be used to create such a receptor because its β-pyrrolic carbon or meso-carbon atoms can be easily functionalized.9 The so-called strappedcalix[4]pyrroles, where two diametrical meso-carbons are connected via various linkers, appeared particularly attractive. This is because relatively acidic hydrogens on the straps, provided by hydrogen bond donors such as amides, triazoles, pyrroles, and bipyrrole derivatives,10 could be used to complement the NH protons of the calix[4]pyrrole core for Received: December 12, 2017 Published: February 14, 2018 2686

DOI: 10.1021/acs.joc.7b03135 J. Org. Chem. 2018, 83, 2686−2693

Article

The Journal of Organic Chemistry

Figure 1. Partial 1H NMR spectra recorded during the titration of receptor 2 with TBAN3 in CDCl3. *Peak arising from the NMR solvent.

Figure 2. Partial 1H NMR spectra recorded during the titration of receptor 3 with TBAN3 in CDCl3. *Peak arising from the NMR solvent.

the purpose of azide anion binding. To date, a large number of modified calix[4]pyrrole derivatives have been synthesized, including many strapped systems, and their binding affinities and selectivities for specific anions studied in both organic and aqueous media.9−11 In spite of this, neither the parent calix[4]pyrrole (1) nor its derivatives has been studied in the context of azide anion recognition. Here, we report the interactions between the azide anion and calix[4]pyrrole 1, as well as with two derivatives the containing ancillary hydrogen bonding donors on the strap, i.e., the pyrrole- and naphthobipyrrole-strapped calix[4]pyrroles 2 and 3.12,13 1H NMR spectroscopic analyses and isothermal calorimetry (ITC) titrations provide evidence for the conclusion that receptors 2 and 3 are able to capture the azide anion with high affinity in organic media. Single crystal X-ray diffraction analyses provided

support for the proposed binding and revealed the details of the interactions between receptors 2 and 3 and the azide anion seen in the solid state. Further insights into the complexation energetics came from density functional theory (DFT) calculations.

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Figure 3. Partial 1H NMR spectra of (a) 2 only, and (b) 2 with 5.0 equiv of CsN3 in CD3OD/CDCl3 (1/4, v/v). *Peak arising from the NMR solvent.

Figure 4. Partial 1H NMR spectra of (a) 3 only and (b) 3 with 5.0 equiv of CsN3 in CD3OD/CDCl3 (1/4, v/v). *Peak arising from the NMR solvent.

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RESULTS AND DISCUSSION Compounds 2 and 3 were prepared using literature procedures (Schemes S1 and S2).12,13 Initial evidence that receptors 1−3 possess the ability to bind the azide anion came from 1H NMR spectroscopic analysis performed in CDCl3. For example, when calix[4]pyrrole 1 was subjected to 1H NMR spectral titration with the azide anion (as its tetrabutylammonium (TBA) salt (TBAN3)) in CDCl3, the pyrrole NH proton signal (Ha) appearing at δ ≈ 6.99 ppm gradually moved downfield as the relative concentration of the anion before saturation was reached at δ ≈ 7.72 ppm (Δδ ≈ 0.73 ppm) upon the addition of over 11 equiv of N3− (Figure S1). In contrast, the β-pyrrolic proton signal (Hb) underwent a slight upfield shift (Δδ ≈ 0.05 ppm), a result rationalized in terms of an increase in the electron density building up on the pyrroles. These findings mirror what has been seen in the case of other calix[4]pyrrole anion complexes and are consistent with hydrogen bonding interactions between the azide anion and the NH protons present in 1. Even more dramatic chemical shift changes were

seen when the strapped calix[4]pyrroles 2 and 3 were treated with the azide anion. As shown in Figure 1, upon subjecting 2 to a 1H NMR spectral titration with N3−, both NH proton signals of the calix[4]pyrrole and the pyrrole on the strap underwent a remarkable downfield-shift (Δδ ≈ 3.35 and 1.98 ppm for Hd and Hf, respectively) before saturation was achieved after the addition of only 1.05 equiv of N3−. This observation leads us to suggest that the NH protons of the calix[4]pyrrole framework interact with the N3− anion in cooperation with those present within the pyrrole-containing strap and that this ditopic binding results in significantly enhanced binding relative to what is seen in the case of calix[4]pyrrole 1. In addition, the protons (He) of the methylene group directly linked to the meso-carbon of the calix[4]pyrrole core in 2 underwent a downfield shift (Δδ ≈ 0.69 ppm), a finding attributed to the interaction between these C−H protons and the bound N3− anion (Figure 1).12 In analogy to what was observed for receptor 2, the 1H NMR spectra recorded during the titration of receptor 3 with N3− in CDCl3 proved consistent with both the NH protons (Ha) of 2688


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horizontally to the mean plane defined by the four nitrogen atoms of the calix[4]pyrrole framework but vertically in the other binding mode (Figures 5 and 6). In the horizontal

the calix[4]pyrrole framework and those (Hb) of the naphthobipyrrole moiety participating in anion binding (Figure 2). For instance, chemical shift changes (Δδ) of the NH protons were found to be 1.87 and 3.23 ppm for Ha and Hb, respectively, with saturation attained upon treating 3 with 1.05 equiv of N3−. In addition, the aliphatic proton signal corresponding to He was seen to undergo a slight downfieldshift (Δδ ≈ 0.34 ppm), presumably as a result of CH−anion interactions (Figure 2). Noticeable 1H NMR spectral changes were also observed when receptors 1−3 were exposed to the cesium salt of the azide anion (CsN3) in 20% CD3OD in CDCl3 (Figures 3, 4, and S2). For instance, in analogy to what was seen for ion pair complexes of cesium halide salts with calix[4]pyrrole 1, the pyrrolic NHs and methyl and methylene CH proton signals on the meso-position were shifted to lower field, whereas the βpyrrolic CH protons underwent an upfield shift. These findings were interpreted in terms of the formation of an ion pair complex of CsN3, as shown in Figures 3, 4, and S2. In these proposed complexes, the N3− anionic guest is hydrogen-bonded to the calix[4]pyrrole frameworks as well as to ancillary NH donor sites present in the straps for receptors 2 and 3. As seen for other calix[4]pyrrole anion complexes, the Cs+ cation is held within the bowl-shaped calix[4]pyrrole cavity, presumably via π-metal cation interactions.14 The binding modes of receptors 2 and 3 with CsN3 as inferred from the 1H NMR spectroscopic analyses in solution were further supported by single crystal X-ray diffraction studies. Single crystals of the CsN3 complexes suitable for X-ray diffraction analysis were grown by evaporating mixtures of chloroform and methanol or ethanol containing receptors 2 or 3 and excess CsN3. In the case of receptor 2, two different kinds of crystals were grown in the same batch. The structure of the resulting CsN3 complex (2·CsN3) revealed that the calix[4]pyrrole core is fixed in the cone conformation and that the Cs+ cation is coordinated within the calix[4]pyrrole bowl (Figure 5). The distances between Cs+ and the centroids of the pyrrole rings were found to fall between 3.35 and 3.49 Å. These values are consistent with the range of π-cation interactions. By contrast, the N3− anion is found bound to receptor 2 in two different binding modes. In one mode, the N3− anion is bound

Figure 6. Top: Two different views of the single crystal X-ray diffraction structure of 2·CsN3 with the azide anion bound in the horizontal mode; see text for details. Bottom: Partial view of the extended structure seen in the crystal lattice.

binding mode, one terminal nitrogen atom of the N3− forms three hydrogen bonds with two pyrrolic NHs of the calix[4]pyrrole and the pyrrolic NH proton of the strap. The resulting N−N3− interaction distances range between 2.85 and 3.33 Å. The other azide anion terminal nitrogen atom is hydrogen-bonded to the other two NH protons of the calix[4]pyrrole framework. The distances associated with this latter N−N3− interactions are identical at 3.35 Å. It is noteworthy that N−N bond distances between the central and terminal nitrogen atoms within the horizontally bound N3− anion are significantly different. Specifically, the central-toterminal N−N bond distance for the azide nitrogen atom interacting with the strap pyrrole is much shorter than the terminal N3− anion (1.126 vs 1.206 Å; Figure 5). This finding leads us to propose that in this binding mode a limiting resonance structures with N−N−N single-triple bond character is favored over one with two identical N−N double−double bonds. Such a deviation from symmetry is also seen for free CsN3, where evidence of a nonsymmetrical azide anion structure with disparate N−N distances (1.168 vs 1.201 Å) was inferred from theoretical calculations (vide infra); presumably, this reflects the cesium cation making direct contact with only one terminal nitrogen atom (Figure S3). In the vertical binding mode, one terminal nitrogen atom of N3− is hydrogen-bonded to the four NHs of the calix[4]pyrrole moiety with the N−N3− distances ranging from 2.99 to 3.05 Å. The other terminal azide nitrogen atom forms a hydrogen bond to the pyrrolic NH on the strap for which an N−N3− distance of 3.08 Å is found. In this case, the bound N3− is relatively symmetric, as inferred from central-to-terminal N−N bond lengths of 1.166 and 1.189 Å; Figure 7. Thus, in this case, the dominant resonance structure is that in which both N−N bonds with the bound N3− anion have double bond character. For complex 2·CsN3 in the vertical azide binding mode, the cesium cation bound within the calix[4]pyrrole cavity is also coordinated to a carbonyl oxygen atom of another molecule of 2 in the solid state (Figure 5). The net result is an extended

Figure 5. Top: Two different views of the single crystal X-ray diffraction structure of 2·CsN3 with the azide anion bound in the vertical mode; see text for details. Bottom: Partial view of the extended structure seen in the crystal lattice. 2689


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intercomplex effects that are seen in the solid state (Figures 8 and 9). In both calculated structures, the bound azide ions were found to have different N−N bond lengths. In both cases, these lengths differ from the purely symmetric structure expected for a free azide ion (calculated to be 1.173 Å). Among the two binding modes, the horizontal azide is predicted to more symmetrical with calculated bond lengths of 1.178 and 1.189 Å. This modest difference in N−N bond lengths differs from the substantial difference (1.126 vs 1.206 Å) seen in the solid state (cf Figure 5). Presumably, this disparity reflects the fact that more complex interactions, including intermolecular effects, are present in the experimental structure. In further contrast to the solid state structural findings, the calculated structure for the vertical complex was found to be much less symmetrical (N−N distances of 1.162 and 1.209 Å; cf. Figure 8) than revealed by X-ray diffraction analysis (N−N distances of 1.166 and 1.189 Å; Figure 7). As noted above, an unsymmetrical structure was also calculated for free CsN3 for which N−N distances of 1.201 and 1.168 Å were obtained. Taken in concert, this combination of structural and theoretical analyses provides support for the notion that it is relatively easy to induce a breaking in the symmetry of the azide anion such that unequal N−N bond lengths are observed in the case of the N3− anion, whether it is found in a salt (e.g., free CsN3) or bound in a complex (e.g., 2· CsN3). Single crystal X-ray diffraction analyses also revealed the ability of receptor 3 to stabilize a CsN3 complex in the solid state. Diffraction grade single crystals of the 3·CsN3 were obtained by subjecting a methanol/chloroform solution of receptor 3 to undergo slow evaporation in the presence of excess CsN3. Only a vertical azide anion binding mode was observed in the resulting X-ray crystal structure (Figure 10). One terminal nitrogen atom of the azide anion is hydrogenbonded to the 4 NH protons of the calix[4]pyrrole with N− H−N3− distances of 2.11−2.20 Å. In addition, one terminal azide nitrogen atom interacts with the axial methyl groups on the meso-carbons of the calix[4]pyrrole via presumed CH− anion hydrogen bonds characterized by C−H−N3− distances of 2.66 to 2.99 Å. The other terminal azide nitrogen atom is hydrogen-bonded to the 2 NHs of the naphthobipyrrole with N−N3− distances of 2.86 and 2.87 Å. The cesium cation is bound within the bowl-shaped calix[4]pyrrole cavity in analogy to what was seen from receptor 2. The distances between the bound Cs+ cation and the centroids of the pyrrole rings range from 3.44 to 3.56 Å (Figure 10). Based on the metric parameters, the complexed cesium cation is thought to form a π-metal complex with the aromatic ring of the naphthobipyrrole subunit present in another molecule of 3 with a separation distance of 3.29 Å (Cs+−centroid of the benzene ring). This interaction is believed to provide a driving force for the formation of a zigzag-type coordination polymer in the in the solid state. This polymeric form is different from either structure seen in the case of 2·N3 (Figure 10). In an effort to quantify the binding affinities of receptors 1−3 for the azide anion, we carried out ITC experiments in acetonitrile. The interactions of receptor 1 and 2 with the azide anion (as its TBA+ salt) are driven entirely by enthalpy with an unfavorable entropic contribution to the binding being seen (ΔH = −8.02 kcal/mol and TΔS = −2.69 kcal/mol for receptor 1; ΔH = −10.0 kcal/mol and TΔS = −1.91 kcal/mol for receptor 2) (Figures S4 and S5). In contrast, the interactions between receptor 3 and the azide anion are characterized by

Figure 7. Top: Two observed binding modes for the horizontal and vertical CsN3 complexes of receptor 2 (see text for details) and the azide anion N−N bond distances as inferred from single crystal X-ray diffraction structures. Bottom: The two limiting azide anion resonance forms seen upon complexation with receptor 2.

complex array. In contrast, in the horizontal azide binding mode, the cesium cation found in 2·CsN3 forms a contact ion pair with an azide anion bound by a neighboring molecule (Figure 6). This results in a very different coordination polymer in the solid state. To compare the stabilities of the two distinct azide binding modes seen in 2·CsN3, the relative energies of the N3− complexes were calculated using DFT at the B3LYP level of theory.15 Two optimized structures of the CsN3 complex of 2 were obtained starting with the X-ray structure coordinates (Figure 8). The optimized structure with a bound vertical azide

Figure 8. Optimized structures for the cesium azide complex of receptor 2 (left) in two limiting binding modes referred to as vertical (top) and horizontal (bottom) and calculated N−N distances for the bound azide anions (right). Two putative dominant resonance forms of the azide anions are also shown.

anion was calculated to be 2.07 kcal/mol more stable than the one with the azide anion bound in a horizontal manner. Interestingly, the structure calculated for the vertical azide complex was found to correspond well with that obtained by Xray diffraction analysis. In contrast, in the horizontal azide complex, the pyrrole on the strap adopts more perpendicular position in the calculated structure (Figure 9). Presumably, this is so the pyrrole NH proton can better engage the azide anion via N−H hydrogen bonding interactions in the absence of the 2690


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Figure 9. Overlay of crystal (silver) and calculated (gold) structures of 2·CsN3 in binding mode 1 (left) and binding mode 2 (right).

studies revealed that receptors 2 and 3 containing ancillary hydrogen bonding donors on their respective straps are able to bind the azide anion with markedly high affinity as compared with the unfunctionalized calix[4]pyrrole 1. Single crystal X-ray diffraction analyses and DFT calculations revealed that CsN3 is bound to receptor 2 in two distinct binding modes, vertical or horizontal, that give rise to different N−N bond lengths within the bound azide anion. Two different coordination polymers were also observed in the solid state depending on the underlying azide binding modes. In contrast, receptor 3 was found to bind CsN3 in a single binding mode, wherein the azide anion is vertically bound to the NH protons of the calix[4]pyrrole core. In this complex, the cesium cation is encapsulated by the cone shaped-calix[4]pyrrole bowl but also interacts with π-face of the naphthobipyrrole subunit of a neighboring molecule. This results in the formation of a zigzagtype coordination polymer that is distinct from what is seen in the case of 2·CsN3. The present results thus highlight the utility of modified calix[4]pyrroles as receptors for the potentially hazardous N3− anion, as well as the diversity of structural types that can be supported using ostensibly similar anion recognition motifs. They also provide an approach to breaking the symmetry of the azide anion and the stabilization of resonance structures characterized by unequal N−N bond lengths.

Figure 10. Top: Two different views of the single crystal X-ray diffraction structure of 3·CsN3. Bottom: Partial view of the extended structure seen in the crystal lattice.

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both favorable enthalpic and entropic terms (ΔH = −6.04 kcal/ mol and TΔS = 1.88 kcal/mol) (Figure S6). The overall energies (ΔG) for the binding of the azide anion to this series of receptors are −5.33 kcal/mol for 1, −8.13 kcal/mol for 2, and −7.91 kcal/mol for 3, respectively. The corresponding binding constants are estimated to be 8.01 × 103, 9.14 × 105, and 6.35 × 105 M−1 for receptors 1, 2, and 3, respectively (Figures S4−S6). The considerably higher azide anion affinities displayed by receptors 2 and 3 as compared to receptor 1 or other reported azide receptors6,7 are attributable to the pyrrole or naphthobipyrrole subunits on the straps of these two calix[4]pyrrole derivatives, which are believed to provide ancillary hydrogen bonding donors and better preorganized three-dimensional structures.

EXPERIMENTAL SECTION

All solvents and chemicals used were purchased from Aldrich, TCI, and Acros and used without further purification. Compounds 2−9 were prepared as previously reported.12,13 NMR spectra were recorded on a Varian Mercury 400 instrument. The NMR spectra were referenced to solvent, and the spectroscopic solvents were purchased from Cambridge Isotope Laboratories and Aldrich. Chemical ionization (CI) and electrospray ionization (ESI) mass spectra were recorded on a VG ZAB-2E instrument and a VG AutoSpec apparatus, respectively. TLC analyses were carried out by using Sorbent Technologies silica gel (200 mm) sheets. Column chromatography was performed on Sorbent silica gel 60 (40−63 mm). X-ray crystallographic analyses were carried out on either a Rigaku AFC12 diffractometer equipped with a Saturn 724+ CCD or an Agilent Technologies SuperNova Dual Source diffractometer. Further details of the structures and their refinement are given in the Supporting Information. Synthesis of Compound 7. 2,5-Pyrrole dicarboxylic acid 4 (1.12 g, 7.23 mmol) was heated at reflux in thionyl chloride (40 mL) for 23 h. The excess thionyl chloride was removed by simple distillation, and the resulting residue was dried under high vacuum for 1 h. After dissolving the resulting acid chloride 5 in CH2Cl2 (50 mL), pyridine

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CONCLUSION In conclusion, the interactions between three congeneric calix[4]pyrroles, i.e., 1−3, and the azide anions (N3−) in the form of its TBA+ and Cs+ salts were studied in solution as well as in the solid state. 1H NMR spectroscopic analyses and ITC 2691


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ArH (naphthobipyrrole)), 7.44 (br s, 4H, pyrrole-NH), 6.05 (t, 4H, ArH (pyrrole), J = 3.20), 5.93 (t, 8H, ArH (pyrrole), J = 3.20), 4.15 (br t, 4H, OCH2CH2, J = 6.40), 3.66 (q, 4H, ArCH2CH3, J = 7.61), 2.20 (t, 4H, CH2CH2CH2, J = 6.80), 1.83 (s, 6H, CH3), 1.65 (m, 4H, CH2CH2CH2), 1.50−1.45 (m, 4H, ArCH2CH3; 12H, CH3). 13C NMR (100 MHz, CDCl3): δ 162.6, 139.4, 136.9, 132.7, 127.3, 124.4, 124.1, 123.5, 120.3, 120.1, 104.0, 103.3, 62.9, 38.8, 36.6, 35.5, 30.6, 28.5, 27.6, 25.2, 19.5, 14.3. HRMS (ESI) m/z 853.44120 [M + Na]+ calcd for C52H58N6O4Na, found 853.44050.

(2.5 mL, 30.7 mmol) was added followed by a solution of 5-(3hydroxypropyl)-5-methyl dipyrromethane 6 (6.02 g, 27.6 mmol in CH2Cl2 100 mL) at 0 °C. The resulting mixture was stirred for 48 h. Then, water (200 mL) was added. The mixture was extracted with CH2Cl2 (50 mL × 4). The combined organic layers were dried over Na2SO4, and after filtration, the solvent was removed. The residue mixture was purified by column chromatography over silica gel (CH2Cl2/EtOAc = 19/1, eluent), yielding compound 7 (4.02 g, 7.23 mmol, 99%). 1H NMR (400 MHz, CDCl3) δ 9.74 (br s, 1H, NH), 7.76 (br s, 4H, NH), 6.82 (d, 2H, J = 6.82 Hz, pyrrolic β-H), 6.61− 6.59 (m, 4H, pyrrolic α-H), 6.13−6.10 (m, 4H, pyrrolic β-H), 6.09− 6.07 (m, 4H, pyrrolic β-H), 4.20 (t, 4H, J = 6.61 Hz, OCH2), 2.07− 2.03 (m, 4H, CH2), 1.67−1.61 (m, 4H, CH2), 1.59 (s, 6H, CH3). 13C NMR (100 MHz, CDCl3) δ 160.4, 137.4, 126.2, 117.2, 115.4, 107.8, 104.7, 65.2, 38.8, 37.2, 26.2, 24.1. HRMS (CI) m/z 556.2924 [M + H]+ calcd for C32H38N5O4, found 556.2925. Synthesis of Compound 2. To a solution of compound 7 (1.07 g, 1.93 mmol) in acetone (500 mL) was added BF3·OEt2 (0.070 mL, 0.55 mmol). The resulting reaction mixture was stirred for 1 h at room temperature, and then TEA (3.0 mL) was added, and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (CH2Cl2/EtOAc = 49/1, eluent), yielding 0.180 g (0.30 mmol, 15%) of 2. 1H NMR (400 MHz, CDCl3) δ 9.48 (br s, 1H, NH), 7.17 (br s, 4H, NH), 7.03 (d, 2H, J = 2.56 Hz, pyrrolic β-H), 5.98−5.96 (m, 4H, pyrrolic-H), 5.95−5.93 (m, 4H, pyrrolic-H), 4.27 (t, 4H, J = 6.35 Hz, OCH2), 2.03−1.98 (m, 4H, CH2), 1.79−1.72 (m, 4H, CH2), 1.55 (s, 6H, CH3), 1.51 (s, 6H, CH3), 1.47 (s, 6H, CH3). 13C NMR (100 MHz, CDCl3) δ 159.3, 138.1, 136.7, 125.8, 117.1, 104.0, 103.6, 65.1, 38.6, 37.6, 35.5, 30.6, 28.0, 27.2, 25.3. HRMS (CI) calcd for m/z C38H46N5O4 636.3550 [M + H]+, found 636.3547. Synthesis of Compound 9. A mixture of naphthobipyyrole dicarboxylic acid 8 (2.00 g, 5.71 mmol), 5-(3-hydroxypropyl)-5-methyl dipyrromethane 6 (2.86 g, 13.1 mmol), EDCI (1-ethyl-3-(3(dimethylamino)propyl)-carbodiimide, 3.28 g, 17.1 mmol), and DMAP (4-dimethylaminopyridine, 1.39 g, 11.4 mmol) in dry dichloromethane (100 mL) was stirred overnight at room temperature and concentrated under reduced pressure to give a yellowish oil. To this crude product, dichloromethane (200 mL) and water (200 mL) were added. The organic phase was separated off and washed twice with water (200 mL). The resulting organic layer was dried over anhydrous MgSO4, and the volatiles were evaporated off in vacuo to give a yellowish solid. Recrystallization from dichloromethane/hexanes (1/9), followed by column chromatography over silica gel (ethyl acetate/hexane = 1/3, eluent), gave 8 (2.24 g, 52% yield) as a yellowish solid. 1H NMR (400 MHz, CDCl3): δ 11.32 (br s, 2H, naphthobipyrrole-NH), 8.44−8.41 (dd, 2H, ArH (naphthobipyrrole)), 8.29 (br s, 4H, pyrrole-NH), 7.48−7.46 (dd, 2H, ArH (naphthobipyrrole)), 6.60−6.58 (m, 4H, ArH (pyrrole)), 6.07−6.06 (m, 8H, ArH (pyrrole)), 4.31 (t, 4H, OCH2CH2, J = 6.40), 3.33 (q, 4H, ArCH2CH3, J = 7.61), 2.23−2.19 (p, 4H, CH2CH2CH2), 2.01 (s, 6H, CH3), 1.73− 1.66 (m, 4H, CH2CH2CH2), 1.38 (t, 4H, ArCH2CH3, J = 7.61). 13C NMR (100 MHz, DMSO-d6): δ 162.0, 138.7, 129.9, 127.6, 124.1, 120.9, 119.1, 117.3, 107.3, 104.5, 65.2, 39.0, 37.6, 25.8, 25.0, 15.4. HRMS (ESI) m/z 751.39663 [M + H]+ calcd for C46H51N6O4, found 751.39649. Synthesis of Compound 3. To compound 9 (2.10 g, 2.80 mmol) in acetone (500 mL) was added BF3·OEt2 (0.34 mL, 2.80 mmol) in one portion. The resulting solution was stirred for 2 h at room temperature and then quenched with triethylamine (3 mL). Evaporation of the volatile components in vacuo afforded a reddish solid. To this crude product, dichloromethane (150 mL), water (100 mL), and aqueous NaOH solution (sat., 10 mL) were added, and the organic phase was separated off and washed three times with water (100 mL). The organic layer was dried over anhydrous MgSO4, and the volatiles were evaporated off in vacuo to give a reddish solid. Recrystallization from a mixture of dichloromethane and methanol (9/ 1), followed by column chromatography over silica gel (eluent:dichloromethane), gave 0.40 g (17% yield) of 3 as a white solid. 1H NMR (400 MHz, CDCl3): δ 10.10 (br s, 2H, naphthobipyrrole-NH), 8.56−8.53 (dd, 2H, ArH (naphthobipyrrole)), 7.59−7.56 (dd, 2H,

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b03135. Crystallographic information for 2·CsN3 (CIF) Crystallographic information for 2·CsN 3 ·CH 3 Cl· 1.5CH3CH2OH (CIF) Crystallographic information for 3·CsN3 (CIF) NMR spectroscopic binding data; ITC data; and X-ray structural data for 2·CsN3 (CCDC 1586343), 2·CsN3· CH3Cl·1.5CH3CH2OH (CCDC 1586342), and 3·CsN3 (CCDC 1586344) (PDF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Jonathan L. Sessler: 0000-0002-9576-1325 Sung Kuk Kim: 0000-0001-6995-1144 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the Basic Science Research Program (Grants 2015R1C1A1A02037578 and 2017R1A4A1014595 to S.K.K.) funded by the National Research Foundation (NRF) under the Ministry of Science, ICT & Future Planning of Korea. The work in Austin was supported by the U.S. National Institutes of Health (Grant GM103790A to J.L.S.) and the Robert A. Welch Foundation (Grant F-1018 to J.L.S.). This work used resources of the National Energy Research Scientific Computing Center, a DOE Office of Science User Facility supported by the Office of Science of the U.S. Department of Energy (Grant DE-AC0205CH11231 to B.P.H). The authors express their appreciation to Sinisa Vukovic for his assistance in performing the DFT calculations.

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Pyrrole- and Naphthobipyrrole-Strapped Calix[4]pyrroles as Azide

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