Precursor Control over the Self-Assembly of Organic Cages via Imine

Sep 20, 2018 - A series of tetrahedral cages and triangular prisms have been self-assembled by condensing ostensibly analogous trisformyl precursors w...
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Precursor Control over the Self-Assembly of Organic Cages via Imine Condensation Tianyu Jiao, Guangcheng Wu, Liang Chen, Cai-Yun Wang, and Hao Li* Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China

J. Org. Chem. 2018.83:12404-12410. Downloaded from pubs.acs.org by REGIS UNIV on 10/19/18. For personal use only.

S Supporting Information *

ABSTRACT: A series of tetrahedral cages and triangular prisms have been selfassembled by condensing ostensibly analogous trisformyl precursors with tris or bisamino linkers under the nominally reversible reaction conditions in the manner of either [4 + 4] or [2 + 3], respectively. We observed that the conformations of the trisformyl precursors have great impact on the self-assembly pathway and product yields. More specifically, a rigid and planar precursor favors the formation of prisms while a more twisted one favors tetrahedron. As a comparison, a more flexible precursor, which is able to adopt both relatively planar and twisted conformations, is capable of producing both prisms and tetrahedrons in relatively high yields. Both experimental and theoretical results indicate that the selfassembly preference is ascribed to subtle variations in the level of π−π and CH-π interactions that act as the driving forces for the formation of prisms and tetrahedrons, respectively.

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INTRODUCTION A hallmark of living systems is their ability to carry out chemical self-assembly, wherein complex structures are built up from simple building blocks. Typically, the underlying chemistry takes place without the need for protecting groups or purification. Nevertheless, a high degree of control is achieved such that different well-defined products are obtained from the same or similar basic precursors. Mimicking this fidelity in synthetic systems is a current challenge. Tremendous progress toward this goal has been made in the area of inorganic cage construction; wherein metal centers serve as “nodes” to link various metalcoordinating1−4 ligands. Here, operational correlations between geometry, size, number, and orientation of the ligating groups are emerging that allow predictions of specific products to be made on a rational basis. For example, Fujita et al. reported5 that by replacing a furan ring in a V-shaped ligand with a thiophene unit, which slightly increases the “bite angle” of the ligand, the resulting self-assembled coordinative spheres could be switched from M12L24 to M24L48. Dynamic covalent reactions, including imine6−19 or hydrazone20,21 condensations, as well as boronic ester formation,22 are also developed to produce threedimensional molecular entities. It has been demonstrated that when the organic building blocks become more preorganized, the self-assembly pathway becomes significantly more predictable, producing the target products in much improved yields. It is thus of importance to build a connection between the properties of the precursors and the self-assembly preference. Cooper et al. reported23 that the condensation between a trisaldehydes and a series of diamines containing polymethylene chains could occur in either [2 + 3] or [4 + 6] manner, depending on whether an odd or even number of methylene units were present in the bisamino precursors. Zhang19,24,25 © 2018 American Chemical Society

discovered that the angle and directionality of the reacting groups play important roles in determining the yields of selfassembled products. Mukherjee26 discovered that the geometry or rigidity of the precursors could affect the self-assembly of organic cages. Mastalerz10,27−30 demonstrated that, by employing intramolecular hydrogen bonding to control the orientation of imine bonds, a variety of cages could be self-assembled in high yields. More recently, the Mastalerz31 group and us32 independently reported that using steric hindrance to preorganize the conformation of the building blocks can help to increase the yields of self-assembled tetrahedral cages. In the current report, we further studied the impact of building block conformation on the self-assembly pathway by condensing three closely related trisformyl derivatives and tris(2-aminoethyl)amine (TREN, A1). In particular, we show that a trisformyl precursor with a twisted conformation favors the formation of a tetrahedral cage. As a comparison, a structurally similar, but more planar, trisformyl building block prefers to yield triangular prisms. In the case of a more flexible trisformyl precursor, because it can adopt both a planar and twisted conformation via C−C single bond rotation, both prisms and a tetrahedron can be self-assembled in relatively high yields. Both experimental and theoretical results demonstrate that these self-assembly preferences result from the self-assembled systems seeking to maximize intramolecular intercomponent forces, namely either π−π or CH-π interactions. Received: June 6, 2018 Published: September 20, 2018 12404

DOI: 10.1021/acs.joc.8b01421 J. Org. Chem. 2018, 83, 12404−12410

Article

The Journal of Organic Chemistry

Scheme 1. Structural Formulae of the Prisms and Tetrahedron Self-Assembled by Condensing the Corresponding Trisformyl Precursors Including La, Lb, or Lc, and the Amino Linkers Including Tris(2-aminoethyl)amine (A1) or Bis(2-aminoethyl)amine (A2) in CDCl3

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RESULTS AND DISCUSSION Three relatively rigid trisformyl derivatives, namely La (1,3,5tri(4-formylphenyl)benzene),33 Lb (1,3,5-triethyl-2,4,6-tris(4formyl-phenyl)-benzene), 3 2 and Lc (1,3,5-tris(4formylphenyl)triazine),34 were prepared according to literature procedures. All three trisformyl derivatives (Scheme 1) have similar sizes and triangular geometries. However, they differ from one another in their conformations. Lc, which contains three phenyl rings grafted on a central triazine moiety, is expected to adopt a nearly planar conformation. In contrast, both La and Lb are subject to torsional twisting on account of the steric hindrance introduced by the protons or ethyl groups present on the 2, 4, and 6 positions of the central phenyl rings. In the case of Lb, the extent of torsional twisting between each adjacent two of the four phenyl units is expected to occur to a greater extent than that of La. This is because in Lb, the relatively more bulky ethyl groups introduce larger steric hindrance than the protons in La. In the case of La, the steric hindrance introduced by the relatively small-sized protons is relative weak. The adjacent phenyl moieties could undergo rotation along the C−C single bonds with relatively small energy barriers. The implication is that La represents a relatively flexible trisformyl precursor, which is able to adopt both twisted and relatively planar conformations. In one of our recent reports,32 we demonstrated that condensing La or Lb with A1 yielded two tetrahedral cages, namely, La4A14 and Lb4A14, whose NMR yields were determined to be 90% and 99%, respectively. As a comparison, combining TREN (A1) and Lc in a 1:1 ratio in CDCl3 only produced a mixture of uncharacterized oligomeric or polymeric products. The self-assembly pathway could be switched by raising the content of A1. For example, condensing a 2:1 mixture of A1 and Lc yielded Lc2A13 (Scheme 1) as the major product in 47% NMR yield, a triangular prism bearing three unreacted amino functional groups. Since La, Lb, or Lc have very similar shapes and sizes, we sought to understand the underneath mechanisms that lead to these differences in self-assembly pathway. In our previous report,32 we have demonstrated both experimentally and theoretically that the intramolecular CH−π interactions which occur between one phenyl proton and an adjacent π phenyl moiety, act as one of the major driving forces in the high-yielding syntheses of tetrahedral cages La4A14 and Lb4A14. The occurrence of these noncovalent interactions requires the

corresponding La and Lb residues within the tetrahedral cage frameworks to adopt twisted conformations. These conformations, fortunately, already occur in the corresponding free precursors, thanks to the preorganization provided by the protons or ethyl groups present on the central phenyl rings, respectively. In contrast, Lc adopts a more planar conformation that does not allow the occurrence of CH−π interactions. As a consequence, the hypothetical Lc4A14 did not form. In addition, within the cage frameworks of either La4A14 or Lb4A14, the A1 residues adopt a relatively preorganized conformation, i.e., its three CH2CH2NCH arms orientate in either a clockwise or counterclockwise manner. Each two of the three imine nitrogen atoms are separated by 4.3−4.7 Å.17,32,35−37 These distances are optimal allowing intramolecular CH−π interactions to occur between the three adjacent phenyl units in one of the four corners of tetrahedrons. When another amino linker A2, namely bis(2-aminoethyl)amine, was combined with any of the three trisformyl species, La, Lb, or Lc, in a 3:2 ratio in CDCl3, three structurally related prisms La2A23, Lb2A23, and Lc2A2 3 (Scheme 1) were obtained in yields of 90%, 36%, and 71% (Table 1), respectively, as inferred from the corresponding 1H Table 1. NMR Yields of the Cages Self-Assembled in the Chloroforma structure

La4A14

Lb4A14

Lc2A13

La2A23

Lb2A23

Lc2A23

NMR yield (%)

90

99

47

90

36

71

a

The concentrations of the corresponding trisformyl precursors are 1 mM.

NMR spectra containing an internal standard (Figures S29− S31). Single crystals of the triangular prism cages La2A23 and Lc2A23 were also obtained (Figure 2C,D) by slowly evaporating the solvent. As expected, the Lc residues in Lc2A23 adopt an almost planar conformation, while the dihedral angles between each two adjacent phenyl rings in La2A23 are around 30°. In both La2A23 and Lc2A23, the distances between the two central aromatic rings in the “top” and “bottom” platforms of the prisms are around 3.5 Å. While not a proof, such distances indicate the presence of stabilizing π−π interactions. These π−π interactions are expected to favor formation of prisms, including La2A23, Lb2A23, and Lc2A23. The π−π interactions in La2A23 are expected to be more favorable than those in Lc2A23 because the La residues have a more flexible conformation than that in Lc, 12405

DOI: 10.1021/acs.joc.8b01421 J. Org. Chem. 2018, 83, 12404−12410

Article

The Journal of Organic Chemistry

confirmed by theoretical calculation, which reveals an average distance of 5.04 Å between the two Lb residues in Lb2A23 (Figure 3). The suppressed intramolecular interactions thus well explain the low yield of Lb2A23 (36%).

Figure 3. Calculated structures of (a) Lb2A23 and (b) Lc2A13, optimized by DFT methods (M06-2X/6-31G(d), SMD(chloroform)). Both Lb2A23 and Lc2A13 are shown in tubular models. Carbon, gray; nitrogen, light blue.

Since the precursor conformation leads to different selfassembly preference, we investigated the possibility of selfsorting of these conformationally different precursors. When Lb, Lc, and A1 were mixed in a 2:1:4 molar ratio in CDCl3, Lb4A14 and Lc2A13 were formed almost exclusively (cf. Figure 1D). This self-sorting behavior can be explained by the fact that when the trisformyl species Lb undergoes self-assembly to form the tetrahedral cage Lb4A14, the precursor with twisted conformation induces favorable CH−π interactions as the driving forces. In the case of the relatively planar counterpart, namely Lc, adopting such a twisted conformation is relatively energy demanding. As a result, the tetrahedron formation could distinguish “self” (Lb) from “nonself” (Lc). Mixing La, A1, and A2 in a 2:2:3 ratio produced both the tetrahedral organic cage La4A14 and the prismatic cage La2A23 in a roughly 10:9 ratio (Figure S45), indicating that self-sorting occurs to a less extent. This is ascribed to the fact that precursor La, representing a relatively flexible trisformyl compound, could adopt both more twisted and relatively planar conformations. As a consequence, it favors the formation of both tetrahedral and prismatic cages, by supporting CH−π and π−π interactions as the corresponding driving forces, respectively. In contrast, a 2:2:3 mixture of Lb, A1, and A2 gives rise to the tetrahedral cage Lb4A14 to almost near exclusion over other possible products (Figure S46), including the putative prisms Lb2A13 and Lb2A23; such a finding is consistent with the proposition that Lb, possessing a twisted conformation, cannot support the π−π interactions between the top and bottom of the prisms. The absence of driving forces therefore results in the failure of the formation of those two prismatic structures. This strong preference for Lb to react with A1 over A2 for tetrahedron formation was employed to accomplish a prism-to-tetrahedron transformation. Specifically, when Lb2A23 was combined with A1 in CDCl3 in a 1:2 ratio, prism Lb2A23 was gradually transformed into the tetrahedral cage Lb4A14 as the major product (Figure 4), releasing the corresponding diamine A2. In sum, we have demonstrated that a series of triangular prisms and tetrahedral cages could be self-assembled via imine condensation, using a series of trisaldehyde precursors and trisor bis-amino linkers as the precursors. The self-assembly pathway, as well as the yields of the target products, are determined at least partially by the conformation of the trisaldehyde precursors. We demonstrated that self-assembly system favors the products that are able to maximize the intramolecular π−π and CH-π interactions, which require the building blocks to adopt planar and twisted conformation,

Figure 1. Partial 1H NMR spectrum of (A) La4A14, (B) a 2:1:4 mixture of La, Lc, and A1, (C) Lc2A13, (D) a 2:1:4 mixture of Lb, Lc, and A1, and (E) Lb4A14.

Figure 2. Single crystal structure of (a) La4A14, (b) Lb4A14, (c) La2A23, and (d) Lc2A23. Solvent molecules are omitted for the sake of clarity. Carbon, gray; nitrogen, light blue; hydrogen, white. The close H-centroid contacts are shown by using red arrows. The values of dihedral angles and distances are averaged ones obtained from the corresponding crystal structures.

helping to maximize the π−π interactions. In addition, π−π interactions between the two phenyl units in La might be more favored than that between the two electron-deficient triazine units in Lc, another possible explanation that might account for the lower yield of Lc2A23 (71%) compared to that of La2A23 (90%). In the case of Lb2A23, the two Lb residues adopt a more twisted conformation. This twisted conformation increases the interplanar distance between the two Lb platforms and therefore suppresses the π−π interactions. This assumption was 12406

DOI: 10.1021/acs.joc.8b01421 J. Org. Chem. 2018, 83, 12404−12410

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The Journal of Organic Chemistry

matched the previously reported32 spectrum (see the Supporting Information). 13C NMR (125 MHz, CDCl3, ppm): δC = 161.7, 143.9, 143.4, 135.6, 128.5, 128.1, 126.5, 59.7, 55.0. HRMS: m/z [M+2H]2+ calcd for C132H122N162+: 966.0029, found: 966.0007; [M+3H]3+ calcd for C132H123N163+: 644.3377, found: 644.3386; [M+4H]4+ calcd for C132H124N164+: 483.5051, found: 483.5039. Cage Lb4A14. Method 1. Chloroform (40 mL) was added to Lb (250 mg, 0.527 mmol) in a glass vial at room temperature. A solution of TREN (A1; 80.9 mg, 0.553 mmol) in chloroform (5 mL) was added. The transparent reaction solution was sealed and heated at 40 °C without stirring for 12 to 48 h. The reaction progress was monitored by 1 H NMR spectroscopy. After the aldehyde-to-imine conversion was completed, the reaction solution was washed with saturated aqueous K2CO3 twice. The chloroform layer was separated and dried over anhydrous Na2SO4. Cage product was obtained as a light yellow shining powder after removing the solvent under vacuum (295 mg, 99%). Method 2. A solution of TREN (A1; 80.9 mmol, 0.553 mmol) in dichloromethane (5 mL) was added into a glass vial containing Lb (250 mg, 0.527 mmol) and dichloromethane (40 mL). The transparent reaction solution was sealed and kept at room temperature for 3−5 days without stirring. The product Lb4A14 gradually crystallized from solution after 2 days. The crystals were connected by filtration and washed with methanol. After drying in atmosphere, the cage product containing solvent was obtained as a white shining powder. Desolvation was accomplished under vacuum, yielding the cage product as a light yellow shining powder (124 mg, 42%). 1H NMR (400 MHz, CDCl3, ppm): δH = 8.09−8.12 (dd, J1 = 8.1 Hz, J2 = 1.4 Hz,12H), 7.65 (s, 12H), 7.47−7.50 (dd, J1 = 8.1 Hz, J2 = 1.2 Hz, 12H), 7.04−7.07 (dd, J1 = 7.7 Hz, J2 = 1.2 Hz, 12H), 5.91−5.94 (dd, J1 = 7.8 Hz, J2 = 1.4 Hz, 12H), 3.46 (t, J = 11.6 Hz, 12H), 3.81−3.85 (dd, J1 = 10.8 Hz, J2 = 3.1 Hz, 12H), 3.32 (t, J = 11.0 Hz, 12H), 3.00 (t, J = 11.8 Hz, 12H), 2.50−2.54 (dd, J1 = 13.2 Hz, J2 = 4.3 Hz, 12H), 2.15−2.32 (m, two almost resolved signals (1:1 ratio), each has six signal peaks, 24H), 0.65 (t, J = 7.4 Hz, 36H). The 1H NMR spectrum of the pure product matched the previously reported32 spectrum (see the Supporting Information).13C NMR (100 MHz, CDCl3, ppm): δC = 162.4, 143.8, 140.4, 138.5, 134.7, 132.5, 130.9, 129.8, 124.6, 59.8, 55.9, 24.8, 15.6. HRMS: m/z [M +2H]2+ calcd for C156H170N162+: 1134.1908, found: 1134.1868; [M +3H]3+ calcd for C156H171N163+: 756.4629, found: 756.4615; [M +4H]4+ calcd for C156H172N164+: 567.5990, found: 567.5975. Prism La2A23. Chloroform (40 mL) was added to La (200 mg, 0.512 mmol) in a glass vial at room temperature. A solution of bis(2aminoethyl)amine (A2; 81.6 mg, 0.791 mmol) in chloroform (5 mL) was added. The transparent reaction solution was sealed and heated at 40 °C for 12 to 48 h without stirring. The reaction progress was monitored by 1H NMR spectroscopy. After the aldehyde-to-imine conversion was completed, the reaction solution was washed with saturated aqueous K2CO3 twice. The chloroform layer was separated and dried over anhydrous Na2SO4. Cage product was obtained as a light yellow shining powder after removing the solvent under vacuum (228 mg, 91%). 1H NMR (400 MHz, CDCl3, ppm): δH = 8.23 (s, 6H), 7.49 (s, 6H), 7.45 (d, J = 8.2 Hz,12H), 7.31 (d, J = 8.2 Hz,12H), 3.82 (t, J = 4.4 Hz, 12H), 3.03 (t, J = 4.8 Hz, 12H). 13C NMR (100 MHz, CDCl3, ppm): δC = 162.5, 142.6, 141.2, 134.7, 128.3, 127.0, 124.7, 60.7, 47.9. HRMS: m/z [M + Na]+ calcd for C66H63N9Na+: 1004.5104, found: 1004.5061; [M+2H]2+ calcd for C66H65N92+: 491.7676, found: 491.7640; [M+H+Na]2+ calcd for C66H64N9Na2+: 502.7586, found: 502.7565; [M+2Na]2+ calcd for C66H63N9Na22+: 513.7495, found: 513.7479. Prism Lb2A23. CDCl3 (1 mL) was added into a glass vial at room temperature to dissolve Lb (4.5 mg, 9.5 × 10−3 mmol). A solution of A2, namely, bis(2-aminoethyl)amine (75.6 μL, 1.9 × 10−1 M) in CDCl3 was then added. The transparent reaction solution was sealed and heated at 40 °C for 12 to 48 h without stirring. The reaction progress was monitored by 1H NMR spectroscopy, which indicates that, after aldehyde-to-imine was completed, a prism Lb2A23 was obtained as the major product. Even although Lb2A23 was not isolated as a pure compound, its formation is confirmed by both NMR spectroscopy and mass spectrometry. The peak assignment in 1H NMR and 13C NMR spectra was done by using the corresponding 2-D NMR spectra. 1H

Figure 4. Partial 1H NMR spectrum of Lb2A23 (A) before and (B) after 2 equiv A1 was added inot the solution. The spectrum in B was recorded after heating the reactions mixtures in CDCl3 for 5 days in order to let the system reach equilibrium.

respectively. These underneath rules would improve our fundamental understanding of how to employ the subtle changes on precursors to control the self-assembly pathway via imine condensation.

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EXPERIMENTAL SECTION

General Considerations. All reagents were purchased from commercial suppliers and used without further purification unless stated otherwise. The precursors 1,3,5-tri(4-benzaldehyde)benzene (La),33 1,3,5-triethyl-2,4,6-tris(4-formylphenyl)benzene (Lb),32 and 1,3,5-tris(4-formyl-phenyl)triazine (Lc)34 were synthesized as reported previously. Nuclear magnetic resonance (NMR) spectra were recorded at ambient temperature using Bruker AVANCE III 400/500 spectrometers, with working frequencies of 400/500 and 100/125 MHz for 1H and 13C, respectively. Chemical shifts are reported in ppm relative to the signals corresponding to the residual nondeuterated solvents (CDCl3, δH 7.26 ppm and δC 77.16 ppm). High-resolution mass spectra were measured using Shimadzu liquid chromatograph mass spectrometry ion trap time-of-flight (LCMS-IT-TOF) instrument. Cage La4A14. Method 1. Chloroform (40 mL) was added to La (200 mg, 0.512 mmol) in a glass vial at room temperature. A solution of TREN (A1; 78.6 mg, 0.537 mmol) in chloroform (5 mL) was added. The transparent reaction solution was sealed and heated at 40 °C without stirring for 12 to 48 h. The reaction progress was monitored by 1 H NMR spectroscopy. After the aldehyde-to-imine conversion was completed, the reaction solution was washed with saturated aqueous K2CO3 twice. The chloroform layer was separated and dried over anhydrous Na2SO4. Cage product was obtained as a light yellow shining powder after removing the solvent under vacuum (227 mg, 92%). Method 2. A solution of TREN (A1; 78.6 mmol, 0.537 mmol) in dichloromethane (5 mL) was added into a glass vial containing La (200 mg, 0.512 mmol) dissolved in dichloromethane (40 mL). The transparent reaction solution was sealed and kept at room temperature for 3−5 days without stirring. The product La4A14 gradually crystallized from solution after 2 days. The crystals were connected by filtration and washed with methanol. After drying in atmosphere, the cage product containing solvent was obtained as a white shining powder. Desolvation was accomplished under vacuum, yielding the cage product as a light yellow shining powder (116 mg, 47%). 1H NMR (500 MHz, CDCl3, ppm): δH = 7.84 (s, 12H), 7.42 (s, 12H), 7.23 (d, J = 8.1 Hz, 24H), 7.15 (d, J = 8.1 Hz, 24H), 3.85 (d, J = 11.1 Hz, 12H), 3.46 (t, J = 11.6 Hz, 12H), 3.14 (t, J = 12.1 Hz, 12H), 2.45−2.48 (dd, J1 = 12.9 Hz, J2 = 3.1 Hz, 12H). The 1H NMR spectrum of the pure product 12407

DOI: 10.1021/acs.joc.8b01421 J. Org. Chem. 2018, 83, 12404−12410

Article

The Journal of Organic Chemistry NMR (400 MHz, CDCl3, ppm): δH = 8.45 (s, 6H), 8.15−8.18 (dd, J1 = 7.7 Hz, J2 = 0.8 Hz, 6H), 7.50−7.53 (dd, J1 = 7.7 Hz, J2 = 1.5 Hz, 6H), 7.39 (d, J = 3.9 Hz, 6H), 7.27 (d, partially overlapped with the residual solvent peak of CHCl3), 3.85 (t, J = 4.1 Hz, 12H), 3.02 (t, J = 4.7 Hz, 12H), 2.0−2.2 (m, 12H), 0.60 (t, J = 7.4 Hz, 18H). 13C NMR (125 MHz, CDCl3, ppm): δC = 161.6, 143.7, 139.7, 138.7, 135.1, 131.4, 130.0, 129.9,125.7, 59.6, 50.6, 24.6, 15.4. HRMS: m/z [M+2H]2+ calcd for C78H89N92+: 575.8615, found: 575.8584; [M+H+Na]2+ calcd for C78H88N9Na2+: 586.8525, found: 586.8505; [M+2Na]2+ calcd for C78H87N9Na22+: 597.8434, found: 587.8397. Prism Lc2A23. CDCl3 (1 mL) was added into a glass vial at room temperature to dissolve Lc (1.3 mg, 3.3 × 10−3 mmol). A solution of A2, namely, bis(2-aminoethyl)amine (26.3 μL, 1.9 × 10−1 M) in CDCl3 was then added. The colorless transparent reaction solution was sealed and kept at room temperature for 12−48 h without stirring. The reaction progress was monitored by 1H NMR spectroscopy, which indicates that, after aldehyde-to-imine was completed, a prism Lc2A23 was obtained as the major product. Even although Lc2A23 was not isolated as a pure compound, its formation is confirmed by both NMR spectroscopy and mass spectrometry. The peak assignment in 1H NMR and 13C NMR spectra was done by using the corresponding 2-D NMR spectrum (see the Supporting Information). 1H NMR (400 MHz, CDCl3, ppm): δH = 8.38 (d, J = 8.1 Hz, 12H), 8.31(s, 6H), 7.54 (d, J = 8.1 Hz, 12H), 3.88(s, 12H), 3.13(s, 12H).13C NMR (125 MHz, CDCl3, ppm): δC = 170.7, 162.5, 138.9, 137.6, 129.0, 127.9, 60.8, 47.4. HRMS: m/z [M+2H]2+ calcd for C60H59N152+: 494.7533, found: 494.7514; [M +H+Na]2+ calcd for C60H58N15Na2+: 505.7443, found: 505.7422; [M +2Na]2+ calcd for C60H57N15Na22+: 516.7353, found: 516.7327. Prism Lc2A13. CDCl3 (1 mL) was added into a glass vial at room temperature to dissolve Lc (1.3 mg, 3.3 × 10−3 mmol). A solution of A1, namely, bis(2-aminoethyl)amine (48.3 μL, 1.4 × 10−1 M) in CDCl3 was then added. The colorless transparent reaction solution was sealed and kept at room temperature for 12 to 48 h without stirring. The reaction progress was monitored by 1H NMR spectroscopy, which indicates that, after aldehyde-to-imine was completed, a prism Lc2A13 was obtained as the major product. Even although Lc2A23 was not isolated as a pure compound, its formation is confirmed by both NMR spectroscopy and mass spectrometry. The peak assignment in 1H NMR and 13C NMR spectra could be done by using the corresponding 2-D NMR spectra (see the Supporting Information). 1H NMR (400 MHz, CDCl3, ppm): δH = 8.34 (d, J = 6.5 Hz, 12H), 8.31(s, 6H), 7.49 (d, J = 6.6 Hz, 12H), 3.78 (s, 12H), 2.98 (t, J = 4.2 Hz, 6H), 2.90 (s, 12H), 2.67 (t, J = 4.1 Hz, 6H). 13C NMR (125 MHz, CDCl3, ppm): δC = 170.5, 162.4, 139.5, 137.2, 129.0, 127.8, 59.0, 55.2, 52.8, 39.5. HRMS: m/z [M +2H]2+ calcd for C66H74N182+: 559.3166, found: 559.3147; [M+H +Na]2+ calcd for C66H73N18Na2+: 570.3076, found: 570.3050; [M +2Na]2+ calcd for C66H72N18Na22+: 581.2986, found: 581.2952. NMR Yield Measurement. The formation yields of cages La4A14, Lb4A14, as well as the prisms La2A23, Lb2A23, Lc2A23, and Lc2A13 were calculated by adding ethyl acetate at a constant concentration, (i.e., 2.1 mg in 6 mL of CDCl3 for La2A23, Lb2A23, and Lc2A23, and 0.4 mg in 3 mL of CDCl3 for Lc2A13) as an internal reference into the corresponding 1H NMR samples of both the self-assembled products and their corresponding trisaldehyde precursors. The concentrations of these trisaldehyde precursors are as follows: La2A23: 4.5 mg of La in 1.4 mL of CDCl3; Lb2A23: 5.2 mg of Lb in 1.4 mL of CDCl3; Lc2A23: 1.7 mg of Lc in 1.4 mL of CDCl3; Lc2A13: 1.6 mg of Lc in 1.4 mL of CDCl3. The concentrations of the products and their precursors could be determined by measuring the integrations of the resonances of both the products and reactants relative to the internal reference. The NMR yields of these products are equal to the product-to-reactant concentration ratios. Using this method, the yields of La4A14, Lb4A14, La2A23, Lb2A23, Lc2A23, and Lc2A13 were calculated to be approximately 90%, 99%, 90%, 36%, 71%, and 47%, respectively. X-ray Crystallography. For the methods and crystal parameters of La4A14 and Lb4A14, please see the previously reported literature.32 (a) Method. The self-assembly solution of La2A23 or Lc2A23 in CDCl3 were used directly for the crystallization, 0.3 mL of the solution was passed through a 0.22 μm filter into one 1 mL clean glass tube. The tube was placed in a 20 mL vial containing 0.3 mL of acetonitrile, and the vial

was capped and placed in a 4 °C fridge. Slow solvent evaporation of the mixture solution of La2A23 or Lc2A23 in the presence of acetonitrile solution over the course of 1 week yielded either colorless single crystals of La2A23 or yellow single crystals Lc2A23. (b) Crystal Parameters. La2A23: [C66H63N9]2·(CHCl3)2·(CCl3)2; colorless block, 0.49 × 0.30 × 0.23 mm; orthorhombic, Pbca; a = 26.1980(11), b = 15.1390(5), and c = 31.8305(11) Å; α = 90.00, β = 90.00, and γ = 90.00°; V = 12624.3(8) Å3; Z = 4; T = 170 K; ρcalc = 1.284 g cm−3; R(reflections) = 0.0956(7570), wR2(reflections) = 0.3132(11489); CCDC no.: 1506717. Lc2A23: [C60H57N15]·(CHCl3)2; yellow block, 0.48 × 0.43 × 0.38 mm; monoclinic, P21/c; a = 15.5704(8), b = 25.7255(10), and c = 16.0579(9) Å; α = 90.00, β = 110.885(6), and γ = 90.00°; V = 6009.49 Å3; Z = 4; T = 170 K; ρcalc = 1.356 g cm−3; R(reflections) = 0.0620(6831), wR2(reflections) = 0.1762(10975); CCDC no.: 1506258. The determination of the unit cell parameters and data collection were performed on an Oxford Xcalibur Gemini Ultra diffractometer with an Atlas detector. The data were collected using graphite monochromatic enhanced ultra Mo Kα radiation (λ = 0.71073 Å). Data collection, unit cell refinement, and data reduction were performed using Agilent Technologies CrysAlisPro V 1.171.35.31.38 The structures of were solved by direct methods, and refined by fullmatrix least-square methods with the SHELX 97 program package.39 Computational Methods. All calculations were performed using Gaussian 09 software package.40 Geometry optimization of Lb2A23 and Lc2A13 was carried out at the M06-2X level of theory41,42 with the 631G(d) basis set43 and in the self-consistent reaction field (SCRF) using the SMD implicit solvent model44 to evaluate the solvent effects in chloroform. Geometry optimization of La, Lb, and Lc was carried out at the B3LYP level of theory45,46 with the 3-21G* basis set.47 The vibrational frequencies of the optimized stationary points are calculated under the same level of theory, to obtain the zero-point vibrational energy (ZPVE) and thermal corrections at 298 K as well as verifying whether each of optimized stationary points is an energy minimum. The rotational energy barriers for La, Lb, and Lc were approximated from scans of the potential-energy surface, which was computed at the B3LYP/3-21G* level. The 3D diagrams of optimized structures were generated using CYLView.48

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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.8b01421. X-ray crystallographic data of La2A23 (CIF) X-ray crystallographic data of Lc2A23 (CIF) NMR spectra and HRMS spectra of La4A14, Lb4A14, La2A23, Lb2A23, Lc2A23, as well as Lc2A13; NMR spectra used for yields calculations; summary data of TREN (A1) conformation in imine cages; effect of precursor stoichiometry on self-assembly outcome; self-sorting studies; computational analysis of precursors’ rotational energy barriers; computed energies; and Cartesian coordinates for the optimized structures (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Hao Li: 0000-0002-6959-3233 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the Chinese “Thousand YouthTalents Plan”, the National Natural Science Foundation of China (No. 21772173), and the Natural Science Foundation 12408

DOI: 10.1021/acs.joc.8b01421 J. Org. Chem. 2018, 83, 12404−12410

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The Journal of Organic Chemistry

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of Zhejiang Province (No. LR18B020001). We thank Prof. Xin Hong (Department of Chemistry, Zhejiang University) for his help in providing computational resources used in this study. T.J. acknowledges a grant from Zhejiang University for Academic Award for Outstanding Doctoral Candidates.

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