Competitive Inclusion of Carboxylic Acids with a Metastable Crystal

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Competitive Inclusion of Carboxylic Acids with a Metastable Crystal Polymorph of p-tert-Butylthiacalix[4]arene Naoya Morohashi, Kohei Ebata, Hiroko Nakayama, Shintaro Noji, and Tetsutaro Hattori Cryst. Growth Des., Just Accepted Manuscript • DOI: 10.1021/acs.cgd.6b01765 • Publication Date (Web): 04 Jan 2017 Downloaded from http://pubs.acs.org on January 12, 2017

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Crystal Growth & Design

Competitive Inclusion of Carboxylic Acids with a Metastable Crystal Polymorph of p-tertButylthiacalix[4]arene Naoya Morohashi,* Kohei Ebata, Hiroko Nakayama, Shintaro Noji, and Tetsutaro Hattori*

Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, 6-6-11 Aramaki-Aoba, Aoba-ku, Sendai 980-8579, Japan

1 ACS Paragon Plus Environment


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ABSTRACT: Nanoporous molecular crystals (NMCs) are potential separation materials, but it is difficult to simultaneously achieve both high selectivity and wide applicability for adsorbates using NMCs, similar to other separation materials. Although the crystal of p-tertbutylthiacalix[4]arene (2α α) selectively includes organic molecules, its applicability is limited. To achieve higher applicability while maintaining the potential selectivity of 2α α, a metastable crystal polymorph (2β β ) was prepared and its inclusion capability for carboxylic acids was investigated. Crystal 2β β could be prepared based on the finding that inclusion crystal 2·MeOH, deposited during the crystallization of compound 2 from a mixture of MeOH/toluene, spontaneously desorbs the methanol upon leaving the crystal in the solvent. Crystal 2β β selectively included formic acid and acetic acid from 1:1 mixtures of HCO2H/MeCO2H and MeCO2H/EtCO2H, respectively. Further, 2β β included each acid with complete selectivity from a 1:1 mixture of HCO2H/EtCO2H by changing the temperature. This performance is superior to that of 2α α, which exhibited notable selectivity only for propionic acid over formic acid. The guest selectivity of 2β β can be rationalized based on (i) the inclusion rates of carboxylic acids, (ii) thermal stability of the resulting inclusion crystals, and (iii) aggregation states of carboxylic acids in acid mixtures.

INTRODUCTION Recently, much attention has been paid to the development of methods for the capture, separation, and/or storage of inorganic gases and organic compounds using nanoporous materials such as zeolites,1–3 metal–organic frameworks (MOFs),4–7 and covalent organic network polymers (COFs)8–10 from the perspectives of global environment protection, safety, and economy. Nanoporous molecular crystals (NMCs) consisting of discrete molecules with only


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weak noncovalent interactions have also been studied for these purposes.11–15 Among them, a considerable number of crystals show notable porosity, classified as “porosity without pores” by Barbour.16 Unlike other nanoporous materials, they do not have empty-channel structures; instead they have disconnected spatial voids to accommodate guest molecules.17–22 Bowl-shaped and cage compounds with intrinsic cavities tend to form such NMCs.23–25 One of the most representative classes of compounds are calixarenes (e.g., 1); their inclusion properties in crystals have been intensively investigated by Atwood’s,26–30 Ripmeester’s,31–35 Gorbatchuk’s,36– 40

Tsue and Tamura’s,41–45 and our groups.46–49 A pioneer study was carried out by Atwood et

al.27 They found that a single crystal of p-tert-butylcalix[4]arene (1β β ) included bromoethene accompanied by a single-crystal-to-single-crystal transition. The guest-free crystal 1β β has a bilayer structure with the conical cavities of the calixarene molecules appearing on both the surfaces (Figure 1b).27,50,51 Lamination of the bilayers forms slightly offset molecular capsules, i.e., discrete voids, between the adjacent bilayers. Amazingly, the inclusion of bromoethene into the cavities shifted the bilayers by ~6 Å while maintaining the integrity of the single crystal. Besides the abovementioned crystal, compound 1 affords a more stable crystal (1α α), in which a pair of calixarene molecules with a cone conformation include each other’s tert-butyl groups in their cavities to form a self-inclusion complex, thereby achieving tight packing with neither a channel nor a void structure to accommodate guest molecules (Figure 1a).52 However, this crystal can also include inorganic gases and small organic molecules in the cavity of compound 1, accompanied by a structural change of the host lattice.30,47,48 Although this observation can be regarded as a guest exchange from the tert-butyl group to an inorganic or organic molecule, there are many other examples of host crystals that absorb guest molecules despite the presence of neither a channel nor a void structure.53–58 Including these crystals, we are interested in using



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NMCs that show “porosity without pores” as separation materials because they have a potential to precisely discriminate molecules of similar sizes and structures by taking advantage of the differences in the activation energies (kinetic factor) for the formation of respective clathrates and in the lattice energies (thermodynamic factor) of the resulting crystals composed of discrete clathrates; in this respect, such NMCs are quite different from other porous materials that have permanent pores for capturing guest molecules by physisorption and/or chemisorption. In fact, we found that powdery crystals of p-tert-butylthiacalix[4]arene (2) with essentially the same crystal packing

as that of 1α α (2α α)59 selectively include ethanol from a 1:1 mixture of

MeOH/EtOH.48 Mechanistic studies showed that the inclusion of ethanol is both kinetically and thermodynamically advantageous compared to methanol. In competitive inclusion between dimethylamine and trimethylamine, 2α α included the individual amines with high selectivities (97–98%) under kinetic and thermodynamic controls, respectively.49 In a preliminary communication,46 we have also reported that this crystal included propionic acid with complete α exhibits high selectivity over formic acid from a 1:1 mixture of HCO2H/EtCO2H. Although 2α performance in discriminating the molecules of similar sizes and structures as shown in these examples, the crystal has a drawback: It can include only a limited number of compounds. These properties of 2α α are in contrast with those of 1α α, which includes diverse small molecules rather unselectively.48 We expected that the use of a metastable crystal polymorph of compound 2 would extend the applicability by decreasing the activation energy for the inclusion. The question is whether it can be done while maintaining the potential selectivity of 2α α. In this study, we have successfully prepared a metastable crystal polymorph of compound 2 (2β β) and examined its inclusion capability for carboxylic acids. Although a few studies have reported on the inclusion capability of metastable crystals,38,45 to the best of our knowledge, this is the first


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study that has attempted to achieve high levels of both selectivity and applicability using a metastable crystal.

Figure 1. Packing structures of 1α α52 (a) and 1β β 51 (b). Molecules are color-coded to clearly visualize the packing structure.



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RESULTS AND DISCUSSION Preparation of Metastable Crystal Polymorph of p-tert-Butylthiacalix[4]arene 2β β and Its Thermal Analysis. It has been reported that inclusion crystal 2·MeOH was obtained as a crystalline powder by adding methanol as an antisolvent to hot toluene saturated with compound 2, followed by cooling the resulting solution to room temperature.48 However, we have found that, when the crystals were left in the mixed solvent at room temperature for 48 h with stirring, the methanol absorbed in the crystals was spontaneously desorbed, affording guest-free crystals of compound 2 (2β β ). Powder X-ray diffraction (PXRD) analysis revealed that the crystal packing of 2β β is different from that of the stable crystal 2α α but similar to that of 2·MeOH (Figure 2a–c). In addition, the PXRD pattern of 2β β was nicely simulated from the single-crystal XRD data of 2·MeOH48 after removing the coordinates of the methanol molecule (Figure 2d); the positions of the simulated peaks slightly shifted to higher angles than the measured ones, which can be ascribed to the difference in the measurement temperature between the XRD (−50 °C) and PXRD analyses (rt). As reported previously,60,48 in the inclusion crystal 2·MeOH, an alcohol molecule is included in the cavity of compound 2 directing the methyl group inside the cavity (Figure 3a). The methyl group forms CH–π interactions with the four aromatic rings of the host molecule. The inclusion complex stacks in a head-to-tail manner by forming intermolecular hydrogen bonds between the hydroxy group of the alcohol molecule and the four hydroxy groups of an adjacent calixarene to construct an infinite columnar structure along the c-axis. When viewed along the direction perpendicular to the c-axis, the inclusion complexes stack by van der Waals interaction to construct a monolayer structure parallel to the a-b plane (Figure 3b); two complexes facing opposite directions along the c-axis are arranged alternately along the [1 1 0] direction, resulting in a dense packing (Figure 3c). The PXRD analysis shows that the peak at


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10.5° in the diffractogram of 2·MeOH (Figure 2b), which was assigned to the diffraction from the (0 0 1) plane, slightly shifted to a lower angle (10.38°) in the diffractogram of 2β β (Figure 2c). This indicates that the distance between the layers was slightly extended by the desorption of methanol, which connected two adjacent calixarene molecules, eventually, two adjacent layers through the CH–π interactions and intermolecular hydrogen bonds as mentioned above. The presence of a metastable crystal polymorph of compound 2 was suggested by Gorbatchuk and coworkers while studying the guest exchange of 2·2DCE (DCE = 1,2-dichloroethane) with vaporized organic compounds.39 In differential scanning calorimetric (DSC) analysis, inclusion crystal 2·0.83MeOH·0.02DCE, prepared by exposing 2·2DCE to methanol vapor, exhibited an exothermic peak with ∆H = −12 ± 2 kJ/mol at ~150 °C after desorbing most of the methanol. They attributed this exothermic peak to the phase transition from a metastable crystal phase of compound 2 to the self-inclusion crystal 2α α. We have succeeded for the first time in preparing a metastable crystal polymorph of compound 2 on a preparative scale.

Figure 2. PXRD patterns measured for 2α α (a), 2·MeOH (b), and 2β β (c) and simulated from the XRD data of 2·MeOH48 after removing the coordinates of MeOH (d).



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Figure 3. X-ray structure of 2·MeOH:48 The inclusion complex and its intermolecular interactions (a) and packing structures viewed along the direction of b-axis (b) and c-axis (c). Hydrogen atoms, disordered atoms, and guest molecules (except for a) are omitted for clarity. Molecules are color-coded to clearly visualize the packing structure. The red and blue dotted lines represent CH–π interactions and intermolecular hydrogen bonds, respectively. Selected distances: C8···ring A (3.842 Å), O2···O1′ (3.480 Å), S1···S1′ (8.236 Å).


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Figure 4 shows a comparison of the DSC thermograms between 2α α and 2β β. Metastable crystal 2β β exhibited an exothermic peak around 160 °C, whereas stable crystal 2α α exhibited no thermal change up to 200 °C. After this experiment, the former sample (2β β ) was subjected to PXRD analysis. The results showed that the crystal was transformed into 2α α (Figure S1). The enthalpy change for the phase transition from 2β β to 2α α was then calculated by integrating the DSC curve to be −12.8 kJ/mol, which is consistent with that reported by Gorbatchuk (vide supra). On the other hand, thermogravimetric analysis (TGA) showed that 2β β lost weight by 1% when the temperature was increased from room temperature to 150 °C (Figure 5). This is presumably due to the evolution of inorganic gases, which were included into the crystal from air. In fact, we found that 2β β was transformed to 2α α with the evolution of gases when immersed in hexane at room temperature (Figure S2).

Figure 4. DSC profiles of 2α α (blue line) and 2β β (red line). The data were corrected to pass through the point (200 °C, 0 mW) for easy comparison.



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Figure 5. TGA desorption curve of 2β β.

It might seem unusual that inclusion crystal 2·MeOH spontaneously desorbed methanol in a mixture of MeOH/toluene from which 2·MeOH was crystallized. The enthalpy change for the formation of 2β β from 2·MeOH in methanol was calculated using eq 4. We previously reported that it was difficult to calculate the enthalpy change for the thermal decomposition of 2·MeOH to 2α α (eq 1) by DSC analysis with good reproducibility, because 2·MeOH gradually released the methanol under air even at room temperature.48 However, when 2·MeOH with an almost constant composition (2:MeOH = 1: ~0.7) was subjected to DSC analysis soon after its preparation, the ∆H value was found to be within an acceptable error range (18.1 ± 0.8 kJ/mol) (Figure S3). The desired enthalpy change was calculated to be −6.5 kJ/mol (eq 4) using eq 1, along with the thermochemical equations for the phase transition from 2β β to 2α α (eq 2) and the vaporization of methanol (eq 3).61 As the entropy change for eq 4 is apparently positive, the negative sign of the enthalpy change confirms that the evolution of methanol from 2·MeOH proceeds spontaneously, which in turn indicates that 2·MeOH was crystallized favorably over 2α α and 2β β under kinetic control in a mixture of MeOH/toluene.


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2·MeOH = 2α α + MeOH (g) – 18.1 kJ

(1)

2β β = 2α α + 12.8 kJ

(2)

MeOH (l) = MeOH (g) − 37.4 kJ

(3)

(1) – (2) – (3) 2·MeOH = 2β β + MeOH (l) + 6.5 kJ

(4)

Inclusion of Carboxylic Acids with Crystals 2α α and 2β β. Before describing the results of the inclusion experiments of carboxylic acids with 2β β, we would like to briefly summarize the α included previous results of the inclusion of carboxylic acids with 2α α.46 Powdery crystals of 2α acetic acid and propionic acid when suspended in the neat acids at room temperature for 24 h and afforded inclusion crystals 2·MeCO2H and 2·[EtCO2H]3, respectively. Formic acid was not included under the same conditions. Competitive experiments were carried out using equimolar mixtures of two acids at a low temperature (0 °C). Consistent with the single guest experiments, 2α α included propionic acid with complete selectivity from a HCO2H/EtCO2H mixture to afford 2·[EtCO2H]3. In contrast, the formation of 2·MeCO2H was inhibited by formic acid and propionic acid. As a result, no inclusion was observed in a HCO2H/MeCO2H mixture; however, inclusion crystals with the same crystal lattice as that of 2·[EtCO2H]3 incorporating acetic acid in an approximate molar ratio of 1:4 (MeCO2H/EtCO2H) were obtained in a MeCO2H/EtCO2H mixture. The inclusion capability of 2β β for the three acids was examined. Powdery crystals of 2β β were suspended in a neat acid, and the suspension was stirred at different temperatures for 24 h. The resulting crystals were filtered, washed with water, dried in vacuo (0.5–1.0 kPa), and analyzed by 1H NMR spectroscopy in CDCl3 to determine the average number of guest molecules per host molecule (݊ത) in the crystals. In the inclusion experiments of formic acid, the drying operation 11 ACS Paragon Plus Environment


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was omitted because formic acid is readily desorbed from inclusion crystals under reduced pressure. The results are listed in Table 1 and compared to those obtained for 2α α. Consistent with the previous result,46 crystal 2α α did not include formic acid in the temperature range from room temperature to 80 °C (entries 1–5). However, the inclusion occurred at a higher temperature (90 °C) (entry 6). In contrast, crystal 2β β included formic acid with moderate ݊ത values (~0.7) regardless of the temperature. This difference in the inclusion capabilities of 2α α and 2β β can be attributed to the difference in the activation energy for the inclusion, which should be higher for stable 2α α than for metastable 2β β. Acetic acid was included into both crystals 2α α and 2β β with high ݊ത values (~0.9) regardless of the temperature (entries 7–11). Propionic acid was also included into both the crystals with ݊ത values of ~2.7, but the inclusion had high temperature limits (40 °C for 2α α and 60 °C for 2β β ) (entries 12–17). When inclusion crystal 2·[EtCO2H]3 prepared separately by crystallization (vide infra) was heated in propionic acid at 70 °C for 24 h, the crystal decomposed, affording 2α α, as evidenced by PXRD analysis. Therefore, the high temperature limits for the inclusion of propionic acid can be attributed to the low thermal stability of 2·[EtCO2H]3 in the acid. PXRD analysis revealed that the inclusion crystals obtained by the inclusion with 2β β have the same crystal structures as those of the respective single crystals 2·HCO2H, 2·MeCO2H,46 and 2·[EtCO2H]346 (vide infra).


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Table 1. Inclusion of Carboxylic Acids with 2α α and 2β βa ݊തb entry

acid

temp (°C) 2α α

2β β

1

HCO2H

rt

–c

0.72

2

HCO2H

40

–c

0.65

3

HCO2H

50

–c

0.69

4

HCO2H

70

–c

0.67

5

HCO2H

80

–c

6

HCO2H

90

0.63

0.70

7

MeCO2H

rt

0.91

0.90

8

MeCO2H

40

0.93

0.92

9

MeCO2H

50

0.90

0.91

10

MeCO2H

70

0.92

0.92

11

MeCO2H

90

0.90

0.89

12

EtCO2H

rt

2.74

2.88

13

EtCO2H

40

2.76

2.89

14

EtCO2H

50

–c

2.90

15

EtCO2H

60

16

EtCO2H

70

–c

–d

17

EtCO2H

90

–c

–d

2.74

a

Conditions: host crystal (20 mg), acid (4 mL), indicated temperature, 24 h. bThe average number of guest molecules per host molecule in inclusion crystals determined by 1H NMR analysis as the average value of more than three runs. cInclusion was not observed.



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Competitive experiments were carried out following the same procedure as mentioned above by using equimolar mixtures of two acids (Table 2). The metastable crystal 2β β included both acids from a HCO2H/MeCO2H mixture regardless of the temperature (entries 1–6), as expected from the single guest experiments. Formic acid was included with a high selectivity (91%) at 0 °C, but the selectivity gradually decreased with increasing the temperature and reversed around 60 °C. Consistent with the previous result,46 2α α included neither acid from the HCO2H/MeCO2H mixture in the temperature range from room temperature to 50 °C (entries 1–4). However, the crystal included both the acids at higher temperatures with almost the same selectivities as those exhibited by 2β β at the respective temperatures (entries 5 and 6). This indicates that the inclusion inhibition of acetic acid with formic acid for 2α α was solved by increasing the temperature. Interestingly, 2β β included propionic acid at 0 °C (entry 7) and formic acid at higher temperatures α also (entries 8–12) from a HCO2H/EtCO2H mixture, both with complete selectivity. Although 2α included propionic acid at 0 °C with complete selectivity (entry 7), the crystal included neither acid at higher temperatures (entries 8–12). Similarly, the inclusion selectivity for a MeCO2H/EtCO2H mixture varied depending on the temperature, and the temperature dependence was different between 2α α and 2β β. Each crystal included both the acids with good selectivity for propionic acid (74–80%) at room temperature and lower temperatures (entries 13 and 14); the ݊ത value for 2α α varied with each run at room temperature as reported previously.46 In the temperature range 40–80 °C, 2β β exhibited complete selectivity for acetic acid, whereas 2α α included neither acid (entries 15–18). In summary, the metastable crystal polymorph 2β β included formic acid with a high selectivity (91%) from a HCO2H/MeCO2H mixture and acetic acid with complete selectivity from a MeCO2H/EtCO2H mixture. In addition, the crystal included each acid with complete selectivity 14 ACS Paragon Plus Environment

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α from a HCO2H/EtCO2H mixture by changing the temperature. In contrast, the stable crystal 2α exhibited notable selectivity only in the inclusion from a HCO2H/EtCO2H mixture for propionic acid. These results clearly indicate that 2β β has a higher inclusion capability than 2α α.

Table 2. Competitive Inclusion from 1:1 Mixtures of Carboxylic Acids with 2α α and 2β βa ݊തb entry

temp (°C) 2α α

2β β

HCO2H

MeCO2H

HCO2H

MeCO2H

1

0

–c

–c

0.60

0.06

2

rt

–c

–c

0.42

0.26

3

40

–c

–c

0.37

0.24

4

50

–c

–c

0.43

0.35

5

70

0.34

0.48

0.32

0.47

6

90

0.33

0.46

0.33

0.43

HCO2H

EtCO2H

HCO2H

EtCO2H

7

0

–c

2.48

–c

2.87

8

rt

–c

–c

0.64

–c

9

40

–c

–c

0.69

–c

10

50

–c

–c

0.65

–c

11

70

–c

–c

0.67

–c

12

90

–c

–c

0.65

–c

13

0

MeCO2H EtCO2H

MeCO2H EtCO2H

0.51

0.51

1.94

1.98

(To be continued to the next page.)



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14

rt

0–0.60

0–1.91

0.74

2.11

15

40

–c

–c

0.85

–c

16

50

–c

–c

0.84

–c

17

70

–c

–c

0.83

–c

18

80

0.83

–c

19

90

–c

–c

–c

–c

a

Conditions: host crystal (20 mg), acid mixture (1:1 mol/mol, 4 mL), indicated temperature, 24 h. bThe average number of guest molecules per host molecule in inclusion crystals determined by 1H NMR analysis as the average value of more than three runs. cInclusion was not observed. α was inhibited not In a previous paper,46 we reported that the inclusion of acetic acid with 2α only with formic acid and propionic acid, but also with water. We then investigated the inclusion of carboxylic acids from water/acid mixtures with varying compositions to understand how the difference in the stability of host crystals affects the inhibition (Figure 6). The inclusion of acetic acid with 2α α was quite sensitive to water; no inclusion was observed from H2O/MeCO2H mixtures when the mole fraction of water (x) was 0.1 and higher (Figure 6a). On the other hand, in the inclusion with 2β β, the ݊ത value gradually decreased with increasing the amount of water. In the inclusion of propionic acid with each crystal (Figure 6b), the ݊ത value drastically decreased within a narrow x range, but the threshold x value for the inclusion was higher for 2β β (>0.9) than for 2α α (~0.55). The metastability of 2β β lowers the activation energies for the inclusion of these acids; this is probably responsible for the low susceptibility to the inhibition with water and the high inclusion capability from solutions of low acid concentrations for 2β β compared to 2α α.


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Figure 6. Dependence of the inclusion ratios (݊ത) of carboxylic acids on the mole fraction of water (x) in water/carboxylic acid mixtures for the inclusion with 2α α (●) and 2β β (▲) at rt.



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Single-crystal XRD Analysis of the Inclusion Crystals of Carboxylic Acids. In our previous paper,46 we reported the crystal structures of 2·MeCO2H and 2·[EtCO2H]3. The XRD data were reanalyzed, and the resulting X-ray structures are shown in the Supporting Information. Inclusion crystal 2·MeCO2H (Figure S4) has a similar structure to both 2·MeOH (Figure 3) and 2·HCO2H (Figure 7); crystallographic data for these crystals are shown in Table S1. In contrast, 2·[EtCO2H]3 has a different crystal structure from the others (Figure S5 and Table S2). In 2·[EtCO2H]3, two host molecules stack to form a capsule, in which a propionic acid dimer is included. An aggregate of four propionic acid molecules is interposed between the ends of two capsules and connects them via intermolecular hydrogen bonds. Single crystals of 2·HCO2H were grown at a liquid–liquid interface between formic acid and a solution of compound 2 in toluene and subjected to XRD analysis (Figure 7). The crystal belongs to the tetragonal system with the P4/nmm space group. Compound 2 adopts a cone conformation with C4 symmetry; a formic acid molecule is included in its cavity directing the hydroxy group inside the cavity. The acid molecule is disordered over two positions, and the disordered structures share the carbonyl carbon, which is located on the C4 symmetry axis along with either the hydroxy (Figure 7a) or carbonyl oxygen (Figure 7b). The hydroxy group of each formic acid forms OH–π interactions with the aromatic rings of the host molecule, while the carbonyl oxygen forms intermolecular hydrogen bonds with the hydroxy groups of an adjacent host molecule; the numbers of OH–π interactions and C=O···HO bonds are different between the disordered structures, depending on the spatial arrangement of the acid molecule. Through these interactions, the acid molecule connects two neighboring host molecules in a head-to-tail manner, thus constructing an infinite columnar structure along the c-axis. Similar to the crystal structure of 2·MeOH (Figure 3), the inclusion complexes construct a layer structure parallel to


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the a-b plane in such a way that two complexes facing opposite directions along the c-axis are arranged alternately along the [1 1 0] direction.

Figure 7. Two disordered structures of the inclusion complex in 2·HCO2H. All the hydrogen atoms and part of the carbon atoms of disordered tert-butyl groups are omitted for clarity. Red and blue dotted lines represent CH–π interactions and intermolecular hydrogen bonds, respectively. Selected distances: O2A···ring A (3.573 Å), O3A···O1′ (3.039 Å), O3A···O1′′ (3.469 Å), O3A···O1′′′ (3.469 Å), O2B···ring A (3.686 Å), O2B···ring B (2.964 Å), O2B···ring C (3.686 Å), O3B···O1′ (3.254 Å), S1···S1′ (8.263 Å).



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TGA of the Inclusion Crystals of Carboxylic Acids. Inclusion crystals of the three acids, 2·HCO2H (݊ത = 0.42), 2·MeCO2H (݊ത = 0.90), and 2·[EtCO2H]3 (݊ത = 2.88), were prepared from 2β β following the same procedure as for the inclusion experiments (entries 1, 7, and 12 in Table 1) and subjected to TGA in a temperature range of 25–250 °C (Figure 8). The crystals lost weight by 3.3% (HCO2H), 7.4% (MeCO2H), and 22.3% (EtCO2H), consistent with the theoretical weight losses of 2.6% (HCO2H), 7.0% (MeCO2H), and 22.8% (EtCO2H) calculated from the chemical formulas and ݊ത values of the samples. Inclusion crystal 2·HCO2H desorbed formic acid even at room temperature, and the desorption was completed at 160 °C. Inclusion crystal 2·MeCO2H began to desorb acetic acid at ~70 °C. The desorption became rapid at ~150 °C and was completed at 180 °C. Inclusion crystal 2·[EtCO2H]3 drastically desorbed propionic acid at a narrow temperature range of 65–90 °C. These observations indicate that the thermodynamic stabilities of the inclusion crystals decrease in the order 2·MeCO2H > 2·[EtCO2H]3 > 2·HCO2H.

Figure 8. TGA desorption curves for the inclusion crystals of HCO2H (blue, ݊ത = 0.42), MeCO2H (red, ݊ത = 0.90), and EtCO2H (green, ݊ത = 2.88).


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Kinetic Experiments for the Inclusion of Carboxylic Acids with Crystal 2β β. To understand the inclusion behavior of 2β β , the time course of the change in inclusion ratios was analyzed at 0 °C and 50 °C for noncompetitive inclusion from neat acids and competitive inclusion from equimolar mixtures of two acids; the noncompetitive inclusion from formic acid and acetic acid was carried out at room temperature instead of 0 °C to avoid the freezing of these acids. In the noncompetitive experiments, formic acid was included faster than acetic acid (Figure S6a and b). The inclusion reached equilibrium after 3 h and 12 h for formic acid and acetic acid, respectively, at room temperature. Increasing the temperature to 50 °C shortened the time to reach equilibrium for both the acids. The inclusion of propionic acid was much faster than that of the other acids, reaching equilibrium within 1 min regardless of the temperature (Figure S6c). On the basis of these observations, it is concluded that the inclusion rate decreases in the order EtCO2H >> HCO2H > MeCO2H. In the competitive inclusion from a HCO2H/MeCO2H mixture at 0 °C (Figure 9a), first a rapid inclusion of formic acid occurred, which was followed by a slow inclusion of acetic acid after an induction period. The ݊ത value of formic acid reached the maximum (~0.6) ~1 d after starting the experiment and then gradually decreased, whereas that of acetic acid continued to increase. This gradually led the system toward a steady state; the molar ratio of the acids included in the crystals after 7 d was ~11:9 (HCO2H/CH3CO2H). The ݊ത against t plots at 50 °C (Figure 9b) exhibited a similar profile, where the maximum ݊ത value of formic acid was ~0.6. The inclusion reached a steady state after 5 d in a molar ratio of ~2:3 (HCO2H/MeCO2H). In the competitive inclusion from a HCO2H/EtCO2H mixture at 0 °C (Figure 9c), first the inclusion of formic acid started, which was followed by the inclusion of propionic acid after an induction period. The



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formic acid in the crystals was smoothly replaced with propionic acid, affording crystals including only propionic acid with an ݊ത value of ~2.7 after 1 h. On the other hand, at 50 °C (Figure 9d), formic acid was included with complete selectivity, and the inclusion reached equilibrium after 3 h with an ݊ത value of ~0.7. Guest exchange was not observed at this temperature. In the competitive inclusion from a MeCO2H/EtCO2H mixture at 0 °C (Figure 9e), both the acids were simultaneously included, and the inclusion reached equilibrium after 20 min; the ݊ത values of acetic acid and propionic acid were 0.6 and 2.0, respectively. At 50 °C (Figure 9f), acetic acid was included with complete selectivity, and the inclusion reached equilibrium after 10 min with an ݊ത value of 0.8.


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Figure 9. Time course of the change in the inclusion ratios (݊ത) of HCO2H (●), MeCO2H (▲), and EtCO2H (■) in the inclusion from acid mixtures (1:1) with 2β β . Dotted lines with open symbols represent the time course of the change in the inclusion from the neat acids marked with closed symbols of the same type (Figure S6).



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Mechanistic Considerations for the Guest Selectivity in the Inclusion from Acid Mixtures with Crystal 2β β. As mentioned above, the inclusion rates of carboxylic acids with 2β β decreased in the order EtCO2H >> HCO2H > MeCO2H (Figure S6), while the thermal stability of inclusion crystals decreased in the order 2·MeCO2H > 2·[EtCO2H]3 > 2·HCO2H (Figure 8). On the basis of these observations and the time course of the change in ݊ത values in the competitive inclusion (Figure 9), the guest selectivity of 2β β observed in the competitive experiments carried out at different temperatures for a fixed time (24 h) (Table 2) can be rationalized as follows: In the inclusion from the HCO2H/MeCO2H mixture, 2β β selectively included formic acid at 0 °C, but the selectivity was changed in favor of acetic acid with increasing the temperature (entries 1–6 in Table 2). Considering the orders of the inclusion rate (HCO2H > MeCO2H) and crystal stability (2·MeCO2H > 2·HCO2H), the ݊ത against t plots (Figure 9a and b) can be interpreted as that formic acid was first included under kinetic control, and the resulting 2·HCO2H was then converted to the thermodynamically more stable 2·MeCO2H. Therefore, the high guest selectivity for formic acid at 0 °C (entry 1 in Table 2) can be attributed to the difference in the inclusion rates of the two acids. The change in selectivity at higher temperatures can be explained by guest exchange, leading to the thermodynamic equilibrium between the inclusion crystals. Crystal 2β β included propionic acid from the HCO2H/EtCO2H mixture at 0 °C and formic acid at higher temperatures, both with complete selectivity (entries 7–12 in Table 2). As in the case of competitive inclusion between formic acid and acetic acid, the ݊ത against t plots at 0 °C (Figure 9c) suggest that formic acid was included under kinetic control, and the resulting inclusion crystal 2·HCO2H was converted to more stable 2·[EtCO2H]3. However, the former suggestion is inconsistent with the order of the abovementioned inclusion rate (EtCO2H >> HCO2H). In Figure


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9c, the ݊ത change in the inclusion from neat propionic acid is transcribed from Figure S6 as a dotted line. As shown in this figure, propionic acid was included from the HCO2H/EtCO2H mixture much slower than from neat propionic acid. The proton-donating ability of carboxylic acids decreases in the order HCO2H > MeCO2H > EtCO2H, according to their acidity. Therefore, in the HCO2H/EtCO2H mixture, hydrogen bonds among propionic acid molecules are disturbed by formic acid. This should negatively affect the inclusion of propionic acid, as propionic acid is included as an aggregate. As a result, formic acid seems to be preferentially included from the HCO2H/EtCO2H mixture at 0 °C. The resulting inclusion crystal 2·HCO2H is easily converted to more stable 2·[EtCO2H]3 by guest exchange, as evidenced by the ݊ത against t plots (Figure 9c). Therefore, we can conclude that the complete guest selectivity for propionic acid at 0 °C (entry 7 in Table 2) was achieved under thermodynamic control. The ݊ത against t plots at 50 °C (Figure 9d) show that formic acid was first included under kinetic control as at 0 °C, but it was not followed by guest exchange. We considered that the higher the temperature, the easier the interruption of the hydrogen bonds among propionic acid molecules by formic acid, which is necessary for the guest exchange. Therefore, the complete guest selectivity for formic acid at room temperature and higher temperatures (entries 8–12 in Table 2) can be attributed to the complete inclusion inhibition of propionic acid with formic acid. From the MeCO2H/EtCO2H mixture, 2β β preferentially included propionic acid at room temperature and a lower temperature, and acetic acid with complete selectivity at higher temperatures (entries 13–19 in Table 2). At the low temperatures, the inclusion did not yield 2·MeCO2H and 2·[EtCO2H]3 separately. Instead, it afforded a crystal with the same crystal lattice as that of 2·[EtCO2H]3, in which some propionic acid molecules were replaced with acetic acid molecules; in a previous paper,46 we suggested that one-third of the propionic acid



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molecules in 2·[EtCO2H]3 can be replaced with acetic acid molecules without decomposing the crystal lattice. As acetic acid has a stronger proton-donating ability than propionic acid, acetic acid thrusts into the aggregates of propionic acid in the MeCO2H/EtCO2H mixture. The ݊ത against t plots at 0 °C (Figure 9e) suggest that the resulting hetero-aggregates with a constant composition of acetic acid and propionic acid were included into the host crystals. With increasing the temperature, the acid molecules come to aggregate at random; thus, propionic acid-enriched aggregates necessary to construct the crystal structure of 2·[EtCO2H]3 are not formed. As a result, 2·MeCO2H seems to be formed exclusively (Figure 9f). Therefore, we may conclude that the guest selectivity for acetic acid at 40 °C and higher temperatures (entries 15–18 in Table 2) is ascribed to the inclusion inhibition of propionic acid with acetic acid. In Figure 9d and f, the ݊ത changes in the inclusion from neat acids are transcribed from Figure S6 as dotted lines for the acids selectively included from the respective acid mixtures. As shown in these figures, propionic acid promoted the inclusion of acetic acid from the MeCO2H/EtCO2H mixture at 50 °C (Figure 9f), whereas it had little effect on the inclusion of formic acid from the HCO2H/EtCO2H mixture at the same temperature (Figure 9d). The proton-donating ability of propionic acid is not much weaker than that of acetic acid, judging from the small difference in the acidities of the two acids. Therefore, propionic acid will assist acetic acid to dissociate from its aggregate. This promotes the inclusion of acetic acid, as acetic acid is included as a monomer. On the other hand, propionic acid is not likely to significantly affect the aggregation state of formic acid because the proton-donating ability of propionic acid is much weaker than that of formic acid. As a result, propionic acid seems to be ineffective for the inclusion rate of formic acid. This consideration is supported by the following observations. As butyric acid was not included in 2β β, its effect on the inclusion of acetic acid was compared to that of propionic acid.


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Acetic acid was included from a MeCO2H/PrCO2H mixture faster than from the neat acid at 50 °C but the promotion effect of butyric acid was inferior to that of propionic acid (Figure S7). In addition, butyric acid did not affect the inclusion rate of formic acid (Figure S8). Therefore, we may conclude that a weak acid accelerates the formation of a 1:1 inclusion crystal of a strong acid with 2β β by assisting the dissociation of the strong acid from its aggregate only when the acidities of the two acids are not so significantly different from each other.

CONCLUSIONS In conclusion, we developed a method to prepare metastable crystal 2β β . In addition to acetic acid and propionic acid, 2β β included formic acid under the conditions where stable crystal 2α α did not. In competitive inclusion, 2β β achieved high selectivities for all the pairs of these acids under kinetic or thermodynamic control, and in one case, the selectivity could be switched by changing the temperature. These achievements were enabled by the instability of 2β β and the interaction between carboxylic acids in the mixture, except for the selectivity for propionic acid over formic acid, which had already been achieved by 2α α. The instability of 2β β lowered the activation energy for the inclusion (formic acid) and made the inclusion insusceptible to the inhibition with a coexistent acid (the formation of 2·MeCO2H in the presence of formic acid or propionic acid). The interaction between carboxylic acids inhibited (the inclusion of propionic acid in the presence of formic acid or acetic acid at high temperatures) or promoted the inclusion of the counterpart (the inclusion of acetic acid in the presence of propionic acid at high temperatures). The results reported in this paper indicate that the use of a metastable crystal polymorph provides a promising method to increase the usefulness of NMC with “porosity without pores” as a separation material.



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EXPERIMENTAL SECTION General. 1H NMR spectra were measured on a Bruker Avance-400 MHz spectrometer using CDCl3 and tetramethylsilane as a solvent and internal standard, respectively. Stable crystal 2α α was prepared by crystallizing compound 2 from xylene/acetone, followed by heating the resulting crystals at 140 °C under reduced pressure (0.5–1.0 kPa) for 4 h.49,60 Carboxylic acids were used as purchased. Preparation of metastable crystal 2β β. To a stirred solution of 2α α (100 mg) in toluene (10 mL) was added methanol (50 mL) at 60 °C, and the resulting suspension was allowed to cool to room temperature. After stirring for 48 h at room temperature, the suspension was filtered, and the filter cake was washed with methanol and dried in vacuo (0.5–1.0 kPa) at room temperature for 8 h to give 2β β (73.4 mg) as a colorless powder. 1H NMR analysis of the crystal showed that it contained no methanol (Figure S9). General procedure for the inclusion of carboxylic acids with 2α α and 2β β (Tables 1 and 2). Powdery crystals of 2α α or 2β β (20.0 mg, 27.7 µmol) were placed in a screw cap vial equipped with a stir bar and suspended by the addition of a carboxylic acid (4.0 mL) or an equimolar mixture of two kinds of carboxylic acids (4.0 mL). The suspension was stirred at a fixed temperature for 24 h, and the resulting crystals were collected by filtration, washed with water (5 mL × 3), and dried in vacuo (0.5–1.0 kPa) at room temperature for 2 h. The crystals were dissolved in CDCl3 and analyzed by 1H NMR spectroscopy to determine the ݊ത value. This experiment was repeated more than three times and the obtained ݊ത values were averaged. When formic acid was used as an inclusion target, the drying operation was omitted because it is easily desorbed from inclusion crystals under reduced pressure.


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PXRD analysis. Data were collected on a Rigaku RINT-2200VHF powder X-ray diffractometer using CuKα radiation at increments of 0.02° and an exposure time of 1.2 s/step in the angular range 3–30° (2θ) at room temperature. DSC analysis. A Seiko Instrument DSC6100 calorimeter was used for DSC analysis. A sample was placed on an aluminum pan and heated at a rate of 1–4 °C min−1 under nitrogen atmosphere with an empty aluminum pan used as a reference. TGA. A Seiko DTA-TGA6200 was used for TGA. A sample (10–12 mg) was placed on a platinum pan and heated at a rate of 4 °C/min under nitrogen. Sapphire (10 mg) on a platinum pan was used as a reference. Preparation of 2·HCO2H and its single-crystal XRD analysis. Compound 2 was dissolved in toluene by heating and the solution was floated on formic acid. The two phases were left at room temperature to give single crystals at the liquid-liquid interface. One of the crystals was picked up and subjected to XRD analysis. The X-ray diffraction data was collected on a Bruker APEX-II with a CCD diffractometer equipped with a multi-layered confocal mirror and a finefocus rotating anode, using Mo-Kα radiation (λ = 0.71073 Å). The structure was solved by the direct method and refined by the least-squares method on F2 using SHELXL-97.62 Yadokari-XG 2009 was used as a GUI for SHELXL-97.63,64 The crystallographic data and ORTEP drawing are shown in Table S1 and Figure S10, respectively.



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ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publication website at DOI: PXRD chart of 2β β after heating, Photo of 2β β upon immersion in hexane, DSC chart of 2·MeOH, Crystal structures of 2·MeCO2H and 2·[EtCO2H]3, Time course of the change in the inclusion ratios of carboxylic acids in the inclusion from neat acids and acid mixtures (additional figures), 1

H NMR chart of 2β β, Crystallographic data for 2·HCO2H, 2·MeCO2H, 2·MeOH, and

2·[EtCO2H]3, and ORTEP drawing of 2·HCO2H. Accession Codes CCDC 1517156–1517158 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif or by emailing [email protected] or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

AUTHOR INFORMATION Corresponding Authors *[email protected] *[email protected] Notes The authors declare no competing financial interest.


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ACKNOWLEDGMENT The authors wish to thank Prof. T. Yoshioka and Prof. K. Asai (Tohoku University) for courteous permission to use instruments. This work was supported in part by JSPS KAKENHI Grant Number 25410032.

REFERENCES (1) Caro, J.; Noack, M. Micropor. Mesopor. Mater. 2008, 115, 215. (2) Tao, Y.; Kanoh, H.; Abrams, L.; Kaneko, K. Chem. Rev. 2006, 106, 896. (3) Cheetham, A. K.; Férey, G.; Loiseau, T. Angew. Chem. Int. Ed. 1999, 38, 3268. (4) Murray, L. J.; Dincă, M.; Long, J. R. Chem. Soc. Rev. 2009, 38, 1294. (5) Férey, G. Chem. Soc. Rev. 2008, 37, 191. (6) Kitagawa, S.; Kitaura, R.; Noro, S. Angew. Chem. Int. Ed. 2004, 43, 2334. (7) Yaghi, O. M.; O’Keeffe, M.; Ockwig, N. W.; Chae, H. K.; Eddaoudi, M.; Kim, J. Nature 2003, 423, 705. (8) Waller, P. J.; Gándara, F.; Yaghi, O. M. Acc. Chem. Res. 2015, 48, 3053. (9) Ding, S.-Y.; Wang, W. Chem. Soc. Rev. 2013, 42, 548. (10) Feng, X.; Ding, X.; Jiang, D. Chem. Soc. Rev. 2012, 41, 6010.



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(11) Hashim, M. I.; Hsu, C.-W.; Le, Ha T. M.; Miljanić, O. Š. Synlett 2016, 27, 1907. (12) Mastalerz, M. Chem. Eur. J. 2012, 18, 10082. (13) Tian, J.; Thallapally, P. K.; McGrail, B. P. CrystEngComm 2012, 14, 1909. (14) Mckeown, N. B. J. Mater. Chem. 2010, 20, 10588. (15) Holst, J. R.; Trewin, A.; Cooper, A. I. Nat. Chem. 2010, 2, 915. (16) Barbour, L. J. Chem. Commun. 2006, 1163. (17) Dianin, J. J. Russ. Phys. Chem. Soc. 1914, 46, 1310. (18) Barrer, R. M.; Shanson, V. H. J. Chem. Soc., Chem. Commun. 1976, 333. (19) Miyahara, Y.; Abe, K.; Inazu, T. Angew. Chem. Int. Ed. 2002, 41, 3020. (20) Dobrzańska, L.; Lloyd, G. O.; Raubenheimer, H. G.; Barbour, L. J. J. Am. Chem. Soc. 2006, 128, 698. (21) Takamizawa, S.; Kohbara, M. Dalton Trans. 2007, 3640. (22) Hashimoto, D.; Uchida, S. Chem. Lett. 2015, 44, 1179. (23) Henkelis, J. J.; Carruthers, C. J.; Chambers, S. E.; Clowes, R.; Cooper, A. I.; Fisher, J.; Hardie, M. J. J. Am. Chem. Soc. 2014, 136, 14393. (24) Kane, C. M.; Ugono, O.; Barbour, L. J.; Holman, K. T. Chem. Mater. 2015, 27, 7337. (25) Kane, C. M.; Banisafar, A.; Dougherty, T. P.; Barbour, L. J.; Holman, K. T. J. Am. Chem. Soc. 2016, 138, 4377.


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(26) Dalgarno, S. J.; Thallapally, P. K.; Barbour, L. J.; Atwood, J. L. Chem. Soc. Rev. 2007, 36, 236. (27) Atwood, J. L.; Barbour, L. J.; Jerga, A.; Schottel, B. L. Science 2002, 298, 1000. (28) Thallapally, P. K.; Wirsig, T. B.; Barbour, L. J.; Atwood, J. L. Chem. Commun. 2005, 4420. (29) Thallapally, P. K.; Dalgarno, S. J.; Atwood, J. L. J. Am. Chem. Soc. 2006, 128, 15060. (30) Thallapally, P. K.; McGrail, B. P.; Dalgarno, S. J.; Schaef, H. T.; Tian, J.; Atwood, J. L. Nat. Mater. 2008, 7, 146. (31) Ripmeester, J. A.; Enright, G. D.; Ratcliffe, C. I.; Udachin, K. A.; Moudrakovski, I. L. Chem. Commun. 2006, 4986. (32) Brouwer, D. H.; Moudrakovski, I. L.; Udachin, K. A.; Enright, G. D.; Ripmeester, J. A. Cryst. Growth Des. 2008, 8, 1878. (33) Udachin, K. A.; Moudrakovski, I. L.; Enright, G. D.; Ratcliffe, C. I.; Ripmeester, J. A. Phys. Chem. Chem. Phys. 2008, 10, 4636. (34) Ananchenko, G. S.; Moudrakovski, I. L.; Coleman, A. W.; Ripmeester, J. A.; Angew. Chem. Int. Ed. 2008, 47, 5616. (35) Alavi, S.; Woo, T. K.; Sirjoosingh, A.; Lang, S.; Moudrakovski, I.; Ripmeester, J. A. Chem. Eur. J. 2010, 16, 11689. (36) Gorbatchuk, V. V.; Tsifarkin, A. G.; Antipin, I. S.; Solomonov, B. N.; Konovalov, A. I.; Seidel, J.; Baitalov, F. J. Chem. Soc., Perkin Trans. 2 2000, 2287. 33 ACS Paragon Plus Environment


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(37) Gorbatchuk, V. V.; Tsifarkin, A. G.; Antipin, I. S.; Solomonov, B. N.; Konovalov, A. I.; Lhoták, P.; Stibor, I. J. Phys. Chem. B 2002, 106, 5845. (38) Yakimov, A. V.; Ziganshin, M. A.; Gubaidullin, A. T.; Gorbatchuk, V. V. Org. Biomol. Chem. 2008, 6, 982. (39) Galyaltdinov, S. F.; Ziganshin, M. A.; Drapailo, A. B.; Gorbatchuk, V. V. J. Phys. Chem. B 2012, 116, 11379. (40) Galyaltdinov, S. F.; Ziganshin, M. A.; Gubaidullin, A. T.; Vyshnevsky, S. G.; Kalchenko, O. I.; Gorbatchuk, V. V. CrystEngComm 2014, 16, 3781. (41) Tsue, H.; Ishibashi, K.; Tokita, S.; Takahashi, H.; Matsui, K.; Tamura, R. Chem. Eur. J. 2008, 14, 6125. (42) Tsue, H.; Matsui, K.; Ishibashi, K.; Takahashi, H.; Tokita, S.; Ono, K.; Tamura, R. J. Org. Chem. 2008, 73, 7748. (43) Tsue, H.; Ono, K.; Tokita, S.; Ishibashi, K.; Matsui, K.; Takahashi, H.; Miyata, K.; Takahashi, D.; Tamura, R. Org. Lett. 2011, 13, 490. (44) Tsue, H.; Takahashi, H.; Ishibashi, K.; Inoue, R.; Shimizu, S.; Takahashi, D.; Tamura, R. CrystEngComm 2012, 14, 1021. (45) Tsue, H.; Ono, K.; Tokita, S.; Takahashi, H.; Tamura, R. CrystEngComm 2013, 15, 1536. (46) Morohashi, N.; Noji, S.; Nakayama, H.; Kudo, Y.; Tanaka, S.; Kabuto ,C.; Hattori, T. Org. Lett. 2011, 13, 3292. (47) Morohashi, N.; Shibata, O.; Hattori, T. Chem. Lett. 2012, 41, 1412. 34 ACS Paragon Plus Environment

Page 35 of 37

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(48) Morohashi, N.; Nanbu, K.; Tonosaki, A.; Noji, S.; Hattori, T. CrystEngComm 2015, 17, 4799. (49) Morohashi, N.; Shibata, O.; Miyoshi, I.; Kitamoto, Y.; Ebata, K.; Nakayama, H.; Hattori, T. Cryst. Growth Des. 2016, 16, 4671. (50) Atwood, J. L.; Barbour, L. J.; Jerga, A. Chem. Commun. 2002, 2952. (51) Atwood, J. L.; Barbour, L. J.; Lloyd, G. O.; Thallapally, P. K. Chem. Commun. 2004, 922. (52) Brouwer, E. B.; Udachin, K. A.; Enright, G. D.; Ripmeester, J. A.; Ooms, K. J.; Halchuk, P. A. Chem. Commun. 2001, 565. (53) Albrecht, M.; Lutz, M.; Spek, A. L.; Koten, G. Nature 2000, 406, 970. (54) Dalrymple, S. A.; Shimizu, G. K. H. Chem. Commun. 2006, 956. (55) Espallargas, G. M.; Hippler, M.; Florence, A. J.; Fernades, P.; van de Streek, J.; Brunelli, M.; David, W. I. F.; Shankland, K.; Brammer, L. J. Am. Chem. Soc. 2007, 129, 15606. (56) Tian, J.; Thallapally, P. K.; Dalgamo. S. J.; Atwood, J. L. J. Am. Chem. Soc. 2009, 131, 13216. (57) Metrangolo, P.; Carcenac, Y.; Lahtinen, M.; Pilati, T.; Rissanen, K.; Vij, A.; Resnati, G. Science 2009, 323, 1461. (58) Naka, K.; Kato, T.; Watase, S.; Matsukawa, K. Inorg. Chem. 2012, 51, 4420. (59) Bilyk, A.; Hall, A. K.; Harrowfield, J. M.; Hosseini, M. W.; Skeltone, B. W.; White, A. H. Inorg. Chem. 2001, 40, 672.



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Page 36 of 37

(60) Akdas, H.; Bringel, L.; Graf, E.; Hosseini, M. W.; Mislin, G.; Pansanel, J.; Cian, A. D.; Fisher, J. Tetrahedron Lett. 1998, 39, 2311. (61) Polak, J.; Benson, G. C. J. Chem. Thermodyn. 1971, 3, 235. (62) Sheldrick, G. M. SHELEX-97, Programs for the Refinement of Crystal Structures, University of Göttingen, Göttingen, Germany, 1997. (63) Wakita, K. Yadokari-XG, Software for Crystal Structure Analyses, 2001. (64) Kabuto, C.; Akine, S.; Nemoto, T.; Kwon, E. J. Cryst. Soc. Jpn. 2009, 51, 218.


Page 37 of 37

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For Table of Contents Use Only

Competitive Inclusion of Carboxylic Acids with a Metastable Crystal Polymorph of p-tertButylthiacalix[4]arene Naoya Morohashi, Kohei Ebata, Hiroko Nakayama, Shintaro Noji, and Tetsutaro Hattori

Table of Contents Graphic

Synopsis: The crystal of p-tert-butylcalix[4]arene (2α α) selectively includes organic molecules but its guest applicability is limited. The use of a metastable crystal polymorph (2β β ) has extended the applicability toward carboxylic acids, while maintaining the potential selectivity of 2α α.


Competitive Inclusion of Carboxylic Acids with a Metastable Crystal

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