Synthesis, Structures, and Complexation with Phenolic Guests of Acridone‐Incorporated Arylene–Ethynylene Macrocyclic Compounds

Abstract

Acridone units were incorporated into the arylene–ethynylene structure as polar arene units. Cyclic trimers consisting of three acridone‐2,7‐diyl units and three 1,3‐phenylene units were synthesized by Sonogashira couplings via stepwise or direct route. X‐ray analysis revealed that the trimer had a nearly planar macrocyclic framework with a cavity surrounded by three carbonyl groups. In contrast, the corresponding tetramer had a nonplanar macrocyclic framework. ¹H NMR measurements showed that the trimer formed a 1 : 1 complex as a macrocyclic host with dihydric phenol guests, and the association constants were determined to be ca. 1.0×10³ L mol⁻¹ for hydroquinone or resorcinol guests in CDCl₃ at 298 K. The calculated structures of these complexes by the DFT method supported the presence of two sets of OH⋅⋅⋅O=C hydrogen bonds between the host and guest molecules. The spectroscopic data of the cyclic trimers and tetramers are compared with those of reference acridone compounds.

Acridone units were incorporated into π‐conjugated macrocyclic structures as polar aromatic units. Target compounds were synthesized by Sonogashira couplings. A macrocycle with three acridone units had a planar and rigid framework and formed complexes with dihydric phenol derivatives such as hydroquinone via hydrogen bonds. The host‐guest properties and the structures of the complexes were investigated by experimental and theoretical approaches.

Introduction

Macrocyclic compounds based on aromatic units and acetylene linkers are versatile motifs for constructing various organic frameworks. ^[1] The structures and properties of such compounds can be modified by changing the numbers and kinds of aromatic units. Cyclic oligomers consisting of six 1,3‐phenylene units and six acetylene linkers are typical examples of shape‐persistent hexagonal‐shaped compounds. ^[2] Some of their derivatives possess characteristic electronic properties due to extended π‐conjugation and self‐assembly behavior due to π⋅⋅⋅π interactions. ^[3] The size of the macrocyclic framework can be enlarged by incorporating large aromatic units that retain the geometrical requirement. ^[4] Kobayashi et al. reported such a compound having three 2,7‐anthrylene units at alternating positions, which underwent self‐assembly in a solution or in the solid state. ^[5] Recently, they synthesized an all 2,7‐anthrylene macrocycle, which included a [9]cycloparaphenylene molecule into the cavity. ^[6] These compounds inspired us to incorporate other aromatic units to create novel macrocycles having various properties. We then adopted 9(10H)‐acridinone (acridone) units instead of anthracene units without changing the unit size, because the acridone structure has been applied in functional materials such as dyes, luminescent sensors, and electronic devices (Figure 1). ^[7] It is remarkable that an acridone unit is highly polar with a large dipole moment (4.94 D) directing from the nitrogen side to the carbonyl side. ^[8] In addition, the electron rich carbonyl‐oxygen atom can serve as a hydrogen bond acceptor or a Lewis base. Acridone units have been intelligently applied for the design of functional molecular cages for various guest species by Clever and the coworkers. ^[9] Recently, we reported the synthesis of acyclic and cyclic acridone‐2,7‐diyl oligomers starting from 10‐mesitylacridone (1) by an iterative procedure. ^[10] We herein designed macrocycles C3, where three acridone units were incorporated into the 1,3‐phenylene–ethynylene cyclic hexamer structure at alternating positions. Because the three carbonyl groups direct toward the macrocyclic center, the cavity should be surrounded by an electron‐rich region and interacting sites. Compounds having this framework are expected to be macrocyclic hosts as well as new types of π‐conjugated diethynylacridones. We herein report the synthesis, structures, and properties of cyclic trimers C3 and tetramers C4, where we define oligomers as n‐mers depending on the number of acridone units. In particular, C3(Mes) having six mesityl (Mes) groups showed associative properties with phenolic guests such as hydroquinone via hydrogen bonds. The characteristic supramolecular behavior will be discussed on the basis of ¹H NMR measurements and DFT calculations.

Figure 1.

Structures of acridones and target macrocyclic compounds C3 and C4. Mes: 2,4,6‐trimethylphenyl (mesityl), Tip: 2,4,6‐triisopropylphenyl.

Results and Discussion

Synthesis and characterization

Preparation of building units. The target macrocycles were synthesized by the Sonogashira couplings from 2,7‐diethynylacridone derivatives and 1,3‐dihalobenzenes. Building units were prepared according to Scheme 1. We adopted 10‐mesitylacridone unit 1 to improve the solubility. The Sonogashira coupling of 2, prepared by the known method, ^[10] with (trimethylsilyl)ethyne afforded compound 3, which was then desilylated with tetrabutylammonium fluoride (TBAF) to give terminal alkyne 4. Reference compound 5 having two phenylethynyl groups was prepared by the Sonogashira coupling of 3 with bromobenzene. The singly silylated diethynylacridone unit was prepared by the Sonogashira coupling of 2 with (triisopropylsilyl)ethyne followed by desilylation of 6 with TBAF under a controlled condition, where the desired product 7 was separated from 4 and 6 by chromatography. Dibromobenzene derivatives 9(Mes) ^[11] and 9(Tip) were prepared by the Suzuki‐Miyaura coupling of 1,3,5‐tribromobenzene (8) and the corresponding boronic acids.

Scheme 1.

Preparation of 2,7‐diethynylacridone and 1,3‐phenylene units.

Synthesis via stepwise routes. We first synthesized the target macrocycle in a stepwise manner following the reference approach (Scheme 2). ^[5] Compounds 11 a and 11 b having two terminal 3‐halophenyl moieties were prepared by the Sonogashira coupling of 4 and an excess amount of the corresponding 1,3‐dihalobenzenes. Another unit 13 having two terminal alkynes was prepared by the Sonogahira coupling of 7 and 1,3‐dibromobenzene [9(H)] in a 2 : 1 ratio followed by the desilylation of 12. Although the Sonogashira coupling of 11 a and 13 was conducted under a standard condition with Pd(PPh₃)₄ and CuI, we could not find the formation of the desired cyclized product. When iodide 11 b was used instead of bromide 11 a, we were able to isolate C3(H) from the reaction mixture after repeated chromatographic separations as a yellow solid in 12% yield. The macrocyclization was also performed under the copper‐free condition reported by Gelman and Buchwald, which tended to suppress the undesired homocoupling reaction. ^[12] The reaction of 11 a and 13 with PdCl₂(MeCN)₂, SPhos, and Cs₂CO₃ in DMF afforded C3(H) in 15% isolated yield, whereas the reaction of 11 b and 13 under the same conditions afforded a trace amount of the product.

Scheme 2.

Synthesis of macrocycle C3(H) via stepwise routes.

Direct synthesis from monomeric units. In order to shorten the overall steps, the six‐fold coupling directly from the monomeric units would be favorable over the stepwise route. Our early attempts to react 4 and 9(H) under the standard Sonogashira coupling conditions were unsuccessful. We then applied the above copper‐free condition to the cyclization of 4 and 9(H), which gave a trace amount of the desired product (Scheme 3). However, the reaction of 3 and 9(H) gave C3(H) in 15% isolated yield, where the desilylation and the coupling sequentially occurred under the reaction condition. ^[13] Eventually, this direct synthesis was much more efficient than the stepwise synthesis mentioned above.

Scheme 3.

Synthesis of macrocycles C3 and C4 from monomeric units.

Because of the low solubility of C3(H), we also synthesized derivatives with 5‐substituted 1,3‐phenylene units. The reaction of 3 and 9(Mes) having a Mes group was carried out under the same condition. From the reaction mixture, we were able to isolate C3(Mes) and C4(Mes) in 9.9% and 3.4% yields, respectively, after separation by recycle gel permeation chromatography (GPC). Similarly, the reaction of 3 and 9(Tip) afforded C3(Tip) and C4(Tip) in 5.6 and 2.2% yields, respectively.

Characterization. Macrocycle C3(H) was slightly soluble in CHCl₃ and CH₂Cl₂. Its structure was characterized by the spectroscopic data and the X‐ray analysis. This compound showed a molecular ion peak at m/z 1305.5 in the mass spectrum, being consistent with the expected molecular weight C₉₆H₆₃N₃O₃. The ¹H and ¹³C NMR spectra of C3(H) were simple, reflecting the formation of a cyclic structure of D _3h symmetry. In the ¹H NMR spectrum, the signals due to the acridone moieties were observed as one set of ABX system, where the signal due to the 1,8‐H atoms was shifted downfield (8.90 ppm) because of the anisotropic effect of the adjacent carbonyl group. In the ¹³C NMR spectrum, the carbonyl and alkyne signals were observed at 177 ppm (one peak) and 89 ppm (two peaks), respectively. The IR spectrum of C3(H) showed an intense absorption at 1646 cm⁻¹ due to the C=O stretching and a weak absorption at 2212 cm⁻¹ due to the C≡C stretching (Figure S8). ^[14] The other macrocycles were similarly characterized. For example, the mass spectra of C3(Mes) and C4(Mes) gave molecular ion peaks at m/z 1659.7 and 2213.0, respectively. As for the cyclic trimers, the solubility in ordinary organic solvents such as CHCl₃ increased in the order of C3(H), C3(Mes), and C3(Tip).

Molecular structures

We carried out X‐ray crystallographic analysis using a single crystal of C3(H) obtained from a 1,1,2,2‐tetrachloroethane/CH₃CN solution. The structures of a single molecule and a dimeric stacked pair are shown in Figure 2. The molecule had a hexagonal‐like framework of nearly D _3h symmetry consisting of three acridone units, three 1,3‐phenylene units, and six acetylene linkers. The macrocyclic framework is slightly deformed from the planar structure, where the dihedral angles between the acridone and phenylene units across the acetylene linkers are ca. ±12°. The Mes groups take a nearly bisecting conformation relative to the acridone planes. A molecule has a triangular cavity, where the distance between the carbonyl‐oxygen atom and the hydrogen atom at the opposite side is 12.89 Å, and the distance between the oxygen atoms is 9.48 Å. The inner diameter of the cavity is estimated to be 7.9 Å assuming the van der Waals radius of oxygen atoms (1.52 Å). This size was smaller than the cavity size of acridone‐2,7‐diyl cyclic hexamer (ca. 9.1 Å). ^[10]

Figure 2.

X‐ray structures of C3(H). Solvent molecules are omitted for clarity. (a) ORTEP drawings of a single molecule. (b) Structures of a dimeric pair. (c) Packing diagrams. In an expanded diagram on the right, assembled mesityl groups are represented as a space‐filling model to highlight CH⋅⋅⋅π contacts.

In the crystal, molecules form nearly fully stacked dimeric pairs at a separation of 2.96 Å (Figure 2b). The two molecules rotate by 36° each other along the axis passing through their centroids. This orientation should be preferable to maximize intermolecular π–π interactions and minimize the steric hindrance between the bulky Mes groups. In the crystal packing, dimeric pairs form a layer spreading along the a‐b plane in a hexagonal manner, and each layer stacks along the c axis in a sequence similar to the cubic closest packing structure (Figure 2c). Each cavity surrounded by host molecules is rather closed for C3(H). This type of packing was occasionally observed for disk‐type molecules, for example, a 1,3‐phenylene–ethynylene cyclic hexamer with phenolic hydroxyl groups, and a similar pyridine‐containing macrocycle.[ ^2b , ¹⁵ ] Interestingly, six peripheral mesityl groups each from different macrocyclic molecules form a cyclic network via CH⋅⋅⋅π interactions between the p‐Me groups and the benzene moieties (ca. 2.9 Å) as shown in Figure 2c. The X‐ray analysis revealed that C3(Tip) also formed dimeric pairs and a layer type packing in the crystal (Figure S9). In contrast to C3(H), each layer stacks in a sequence similar to the hexagonal closest packing structure to form one dimensional channels.

The molecular structure of C3(H) was optimized by the DFT method at B3LYP/6‐31G(d) level (Figure 3a). In contrast to the X‐ray structure, the macrocyclic framework was completely planar. This difference means that the out‐of‐plane deformation in the observed structure is attributed to the packing effect. The electrostatic potential (ESP) map was visualized for the calculated structure of C3(H) as shown in Figure 3b. ^[16] The electron‐rich red surface is located around the electronegative oxygen atoms and the acetylene moieties, resulting in a cavity surrounded by an electron‐rich wall. In contrast, the electron deficient blue surface spreads over the peripheral region involving the nitrogen atoms. The calculated dipole moment was nearly zero (μ 0.077 D) because of the formation of the symmetric cyclic structure.

Figure 3.

(a) Calculated structure of C3(H) at B3LYP/6‐31G(d) level and (b) its ESP map. Isodensity surface color: red (−0.03) to blue (+0.02).

We were able to obtain a single crystal of C4(Mes) from a THF solution as well. The X‐ray structures are shown in Figure 4. The macrocyclic framework takes a nonplanar conformation of nearly C _2h symmetry. Relative to the averaged macrocyclic plane, two acridone units at the opposite sides are nearly coplanar, and the other two units are nearly perpendicular toward the opposite directions. As a result, the dihedral angles between the acridone and phenylene units across four acetylene linkers are nearly 90°. This conformation is similar to a chair‐like conformation of 1,3‐phenylene–ethynylene cyclic octamer. ^[17] The distance between the carbonyl‐oxygen atoms in the coplanar acridone units is 17.34 Å, resulting in a large cavity of ca. 14 Å diameter along this direction. The bond angles at the acetylene carbons are in the range of 171.1–178.5°, indicating small bending deformations at some sp carbons. In the crystal, molecules form a columnar type stacking at a separation of 11.5 Å along the a axis to form cavity channels along the stacking direction (Figure 4b). The structural optimization of C4(H) at the B3LYP/6‐31G(d) level afforded two energy‐minimum structures, chair‐like conformation X and boat‐like conformation Y, where the former was less stable by 1.2 kJ mol⁻¹ than the latter (Figure 4c). The macrocyclic framework in the X‐ray structure of C4(Mes) is similar to the chair‐like conformation X of C4(H). The small energy difference suggests that the two conformers can exist in a comparable ratio in a solution. These conformers should readily exchange each other via rotation about the acetylene axes. ^[18]

Figure 4.

Molecular structures of C4. (a) X‐ray structures of a single molecule of C4(Mes). (b) Packing diagram of the X‐ray structure of C4(Mes). (c) Two energy‐minimum structures, X and Y, of C4(H) calculated at B3LYP/6‐31G(d) level.

UV‐vis and fluorescence spectra

UV‐vis absorption and fluorescence spectra of the macrocycles and the related compounds were measured in CHCl₃ (Table 1). The spectra of C3(Mes) and C4(Mes) are compared with those of 10‐mesitylacridone (1) and 2,7‐bis(phenylethynyl)acridone (5) as reference compounds in Figure 5. In the UV‐vis spectra, compound C3(Mes) showed intense peaks at 300–380 nm and weak structured bands at 380–430 nm. The latter bands are assigned to the HOMO–LUMO excitation accompanying intramolecular charge transfer from the electron rich phenylethynyl moieties to the electron deficient acridone moieties according to the time‐dependent (TD)‐DFT calculation of C3(H) (Figures S10 and S11), as observed for other 2,7‐bis(phenylethynyl)acridone derivatives. ^[19] The absorption maximum at the longest wavelength was observed at 422 nm, which was identical to that of 5 and red‐shifted by 20 nm relative to that of 1 (397 nm). The absorption bands of C4(Mes) slightly blue‐shifted relative to those of C3(Mes). These tendencies are consistent with the calculated HOMO–LUMO gap energies of 1, 5, C3(H), and C4(H), as shown in Table 1 and Figure 6.

Table 1.

UV‐vis and fluorescence spectral data of C3, C4, and related compounds measured in CHCl₃ at room temperature.

	UV‐vis[a]	FL[a]			Stokes shift	ΔE HOMO‐LUMO
	λ max [nm] (ϵ [L mol−1 cm−1])	λ em [nm]	Φ f [b]	τ f [ns][c]	[cm−1]	[eV][d]
C3(H)	421 (20600)	439	0.084	2.0	970	3.58
C4(H)	–	–	–	–	–	3.64
C3(Mes)	422 (16800)	439	0.091	2.1	920	3.58
C4(Mes)	418 (26500)	438	0.093	1.9 (0.74), 2.8 (0.26)	1100	–
C3(Tip)	422 (19300)	439	0.081	2.1	920	–
C4(Tip)	419 (26200)	438	0.092	2.1	1000	–
1	397 (10500)	405	0.39	5.7	380	4.08
5	422 (6190)	440	0.10	2.0	970	3.59

[a] Concentration at 1.0×10⁻⁵ mol L⁻¹. [b] Absolute fluorescence quantum yield. [c] Fluorescence lifetime. Values in parentheses are ratios of emission components. [d] Calculated at B3LYP/6‐31G(d) level.

Figure 5.

UV‐vis and fluorescence spectra of C3(Mes), C4(Mes), and related compounds measured in CHCl₃ at room temperature. Concentration 1.0×10⁻⁵ mol L⁻¹.

Figure 6.

Frontier Kohn‐Sham orbitals and orbital energy diagrams of 1, 5, C3(H), and C4(H) at the B3LYP/6‐31G(d) level.

In the fluorescence spectra, the emission bands of C3(Mes) and C4(Mes) were observed at ca. 440 nm, which was comparable to that of 5 and red‐shifted by 34 nm relative to that of 1. Compounds C3(Mes), C4(Mes), and 5 had similar values of the fluorescence quantum yields Φ _f (ca. 0.1), the fluorescence lifetimes τ _f (2.0 ns), and the Stokes shifts (ca. 1000 cm⁻¹). The relatively small Stokes shifts indicate small structural changes at the excited state. ^[20] The spectroscopic properties of other cyclic oligomers, C3(H), C3(Tip), and C4(Tip), are similar to those of C3(Mes) and C4(Mes). These data indicate that a 2,7‐bis(phenylethynyl)acridone substructure plays an important role in determining the photophysical properties of the macrocycles.

The UV‐vis and fluorescence spectra of soluble derivative C3(Tip) were measured in several organic solvents (Figures S5 and S6 and Table S1). The absorption band at the longest wavelength slightly red‐shifted with increasing the polarity from THF (392 nm) to CH₃OH (399 nm). The emission band also showed a red‐shift from THF (398 nm) to CH₃OH (415 nm). Even though the overall solvent effect was small, a significant red‐shift was observed in CH₃OH followed by CHCl₃ and DMSO. The solvent effect of CHCl₃ tends to be large compared with that expected from the solvent polarity as scaled by E _T(30). ^[21] This fact indicates that not only the solvent polarity but also the acceptor property, which can be scaled, for example, by acceptor number AN, ^[22] influences the overall solvent effect on the absorption and emission bands (Figure S7). It is understandable that solvents having large acceptor characters should interact with the carbonyl‐oxygen atoms regardless of their polarities.

DFT calculations

The molecular orbitals of C3(H) and C4(H) were calculated by the DFT method at the B3LYP/6‐31G(d) level. The energies of the HOMO and LUMO levels are shown in Figure 6. The HOMO‐LUMO gap of C3(H) (3.58 eV) is comparable to that of 5 (3.59 eV), and these values are smaller by ca. 0.5 eV than that of 1. For C3(H), the orbitals spread over two acridone units and attached phenylethynyl moieties at the HOMO level, whereas the orbitals are located on two acridone units at the LUMO level. The HOMO‐LUMO gap of C4(H) (3.64 eV) is larger than that of C3(H) due to the stabilization of the HOMO level. This finding is attributed to the nonplanar conformation of C4(H), which prevents the π‐conjugation across aromatic units. The small blue‐shift in the UV‐vis spectrum of C4(Mes) relative to C3(Mes) can be attributed to this difference.

Supramolecular chemistry

The ¹H NMR spectra of C3(Tip) were measured at variable concentrations in CDCl₃. The chemical shifts were almost unaffected by the concentration in the range of 1.0×10⁻⁴–2.0×10⁻² mol L⁻¹. This observation means that self‐association should be negligibly weak in the solution, in contrast to other disk‐type macrocycles.[ ² , ³ , ⁴ , ⁵ ]

We then investigated the association of C3(Mes) with external guest molecules. The cavity of C3(Mes) is surrounded by the electron‐rich oxygen atoms, which can interact with electron‐deficient moiety. In fact, acridone is known to be a good hydrogen bond acceptor according to the pK _HB parameter. ^[23] For these reasons, we selected phenol derivatives as guest candidates. ^[24] For the preliminary screening, we measured the ¹H NMR spectra of C3(Mes) in the presence of a large excess (10 eq.) of phenol derivatives in CDCl₃ (Figure S16). As a result, we observed small downfield shifts of the signals due to the aromatic protons directing inward (1,8‐H and 2’‐H) when resorcinol (RE), hydroquinone (HQ), and pyrogallol were added. On the other hand, changes were very small for phenol (PH), 1‐naphthol, catechol (CA), and other phenols. Therefore, we chose RE and HQ as promising guest candidates, and their behavior was compared with that of CA and PH.

We measured the ¹H NMR spectra of mixtures of C3(Mes) and HQ at various ratios in CDCl₃, where the sum of the host and guest concentrations was fixed at 1.0×10⁻³ mol L⁻¹ (Figure 7a). As the host/guest ratio increased, the signals of HQ significantly shifted downfield (Δδ 1.51 ppm for OH and Δδ 0.22 ppm for 2”‐H). The large shielding of the phenolic protons supports the formation of hydrogen bonds. Because the chemical shift of the OH signal would be sensitive to various factors, ^[25] that of the aromatic signal was used for the quantitative analysis (Figure 7bc). The Job's plot showing a maximum at 0.5 molar ratio suggests the formation of a 1 : 1 host‐guest complex. The least‐square fitting assuming the following equilibrium, H+G $\overrightarrow{\leftarrow }$ H ⋅ G, afforded the association constant K _a to be (1.00±0.09)×10³ L mol⁻¹, corresponding to 17.1 kJ mol⁻¹ in −ΔG ₂₉₈. This phenomenon was specific for C3(Mes), and no significant changes in the chemical shifts were observed for C4(Mes), 1, or 5 upon addition of HQ.

Figure 7.

(a) ¹H NMR spectra of mixtures of C3(Mes) (host: H) and hydroquinone HQ (guest: G) at various ratios in CDCl₃ at 298 K. [H]+[G]=1.0×10³ mol L⁻¹. (b) Job's plot. (c) Plot of chemical shift changes Δδ of HQ vs [G]/[H] ratio. The aromatic signal of HQ (2”‐H) was analyzed for (b) and (c).

We performed similar measurements with C3(Mes) and RE (Figure S17). The observed data supported the formation of a 1 : 1 complex, and the association constant K _a was (0.99±0.14)×10³ L mol⁻¹ by monitoring the chemical shift of the 4’’,6’’‐H aromatic signal of RE. ^[26] The analyses of other aromatic signals (2’’‐H or 5’’‐H) gave comparable association constants, confirming that all the probes give information of the identical process. Although the screening experiment had been almost negative, the measurements with CA showed small chemical shift changes by monitoring the chemical shift of the 3’’,6’’‐H aromatic signal of CA (Figure S18). The association constant K _a was estimated to be (2.3±0.3)×10² L mol⁻¹ according to the data measured at the total host and guest concentration of 2.0×10⁻³ mol L⁻¹. No changes were observed during the measurements upon addition of PH (Figure S19).

The above data mean that macrocycle C3(Mes) associates with HQ and RE with a comparable strength, weakly with CA, and negligibly weakly with PH. This tendency means that multipoint interactions between the two OH groups in the guest and the carbonyl‐oxygen atoms in the macrocyclic host are important in the association behavior. In addition, the association energies depend on the position, namely distance and direction, of the two OH groups in the guest molecules.

In order to obtain further information on the host‐guest interactions, we calculated the structures and energies of the complexes of C3(H) by the DFT method. We preliminary searched possible structures of 1 : 1 complexes by CONFLEX program (Figure S12). ^[27] The major structures were further optimized at the B3LYP/6‐31G(d) level in the gas phase. Selected structures are shown in Figure 8. Table 2 lists complexation energies (−ΔE, −ΔH ₂₉₈, and −ΔG ₂₉₈) obtained from the thermodynamic parameters calculated for the complex and the free host and guest molecules. To estimate the energy of a single hydrogen bond, we also calculated complex C3(H) ⋅ PH, where the stabilization energy was −ΔE 48.1 kJ mol⁻¹ (Figure 8a). Because this energy is almost the same as that of 10‐mesitylacridone(1) ⋅ PH complex (48.6 kJ mol⁻¹), a carbonyl group in C3(H) behaves independently toward a PH molecule as a hydrogen bond acceptor. These values are in the range of moderate hydrogen bonds (17–63 kJ mol⁻¹) classified by Emsley ^[28] as exemplified by the calculated hydrogen bond energy of N‐methylacetamide ⋅ PH complex (49.7 kJ mol⁻¹). ^[29]

Figure 8.

Optimized structures of (a) C3(H) ⋅ PH, (b) C3(H) ⋅ HQ, (c) C3(H) ⋅ RE, and (d) C3(H) ⋅ CA 1 : 1 complexes calculated at B3LYP/6‐31G(d) level. Red values in the structures are the OH⋅⋅⋅O=C distances in Å. As for the HQ, RE, and CA complexes, only the most stable complexes are shown. Other structures are provided in Figure S13.

Table 2.

Calculated thermodynamic parameters for complexation of C3(H) with phenolic guests, phenol (PH), hydroquinone (HQ), resorcinol (RE), and catechol (CA), at the B3LYP/6‐31G(d) level.^[a]

	−ΔE [kJ mol−1]	−ΔH 298 [kJ mol−1]	−ΔG 298 [kJ mol−1]	−ΔE H [kJ mol−1][b]	−ΔE G [kJ mol−1][c]
PH	48.1	40.9	−13.2	−1.9	−0.9
PH [d]	48.6	41.5	1.9	–	–
HQ A	73.8	63.1	15.9	−3.1	−2.4
HQ B	67.0	57.3	7.4	–	–
HQ C	63.6	53.6	9.5	–	–
RE A	80.0	71.6	15.9	−3.4	−2.2
RE B	66.7	59.0	7.8	–	–
RE C	64.8	57.2	11.5	–	–
CA A	45.8	39.2	−10.6	−3.1	−33.0
CA B	35.7	29.8	−7.8	–	–

[a] Structures are shown in Figures 8 and S13. Full thermodynamic data are provided in Table S4. [b] Energies required for the structural change of the host moiety upon complexation. [c] Energies required for the structural change of the guest moiety upon complexation. [d] Complex with 10‐mesitylacridone (1).

We found three energy‐minimum structures of C3(H) ⋅ HQ with two OH⋅⋅⋅O=C hydrogen bonds, and their bond distances (1.85–1.89 Å) were in the range of moderate hydrogen bonds (1.5–2.2 Å). ^[28] In the global‐minimum structure A (Figure 8b), the two OH groups, which are coplanar with the benzene plane and anti with each other, bond to different C=O groups from the opposite sides of the macrocyclic plane. As a result, the benzene ring of the HQ guest is nearly standing relative to the macrocyclic plane. Upon complexation, the destabilizations by structural changes of the host (−ΔE _H 3.1 kJ mol⁻¹) and guest (−ΔE _G 2.4 kJ mol⁻¹) moieties are rather insignificant as shown in Table 2. The association energy of C3(H) ⋅ HQ, 73.8 kJ mol⁻¹, is smaller than twice that of C3(H) ⋅ PH. This finding means that each hydrogen bond cannot be maximized for the structural constraint in the cyclic host‐guest system. The significantly small −ΔG value (15.9 kJ mol⁻¹) relative to the −ΔE value is attributed to a large contribution of the entropic term resulting from the formation of one complex from two independent molecules. The presence of hydrogen bonds in this complex was visualized by the noncovalent interaction (NCI) plot (Figure 9a).[ ^24e , ³⁰ ] The blue isosurfaces between the interacting O and H atoms indicate strong attractive interactions due to the hydrogen bonds in these regions. The other two structures, B and C, which have different orientations between the host and guest molecules, are less stable than the global minimum A.

Figure 9.

Noncovalent interaction (NCI) plots for partial structures around guest molecules of (a) C3(H) ⋅ HQ A and (b) C3(H) ⋅ RE A 1 : 1 complexes calculated at B3LYP/6‐31G(d) level (isosurface value 0.6). The colors of the isosurface are blue (attractive interactions), green (weak vdW interactions), and red (repulsive interactions). Blue arrows indicate isosurfaces for hydrogen bonds. NCI plots of other complexes are provided in Figure S14. The two dimensional reduced density gradient (RDG) vs. sign(λ ₂)ρ plots are shown in Figure S15.

The complexes with RE and CA were similarly calculated. The most stable structures are shown in Figure 8. For C3(H) ⋅ RE, we obtained three energy‐minimum structures, where the two OH groups interact with different C=O moieties in various modes. The association energy of the most stable C3(H) ⋅ RE complex A (80.0 kJ mol⁻¹) is slightly larger than that of C3(H) ⋅ HQ (73.8 kJ mol⁻¹), but the free energies of association are identical for the two complexes. The presence of hydrogen bonds is supported by the NCI plot of C3(H) ⋅ RE as shown in Figure 9b. For C3(H) ⋅ CA, the two OH groups almost equally interact with one C=O moiety (1.87 Å), because the distance between them is too short to bridge two C=O moieties in the macrocyclic host. The association energy of the most stable C3(H) ⋅ CA complex A (45.8 kJ mol⁻¹) is much smaller than those of the other complexes. This small association energy is attributed to not only the contribution of only one C=O moiety but also the destabilization of the guest molecule (33 kJ mol⁻¹). The latter factor involves the dissociation of an intramolecular hydrogen bond in CA, which requires at least 15–20 kJ mol⁻¹ as suggested by the DFT calculation. ^[31] These calculated data are consistent with the tendency in the observed association constants, HQ≈RE>CA.

Conclusion

We synthesized new acridone incorporated arylene–ethynylene cyclic oligomers by Sonogashira coupling. Cyclic trimers had a planar and rigid macrocyclic framework, where the cavity was surrounded by three carbonyl groups. In contrast, cyclic tetramers had a nonplanar and nonrigid macrocyclic framework. Cyclic trimer C3(Mes) associates with phenolic guest molecules, HQ and RE, in 1 : 1 ratio in solutions. Their association constants were ca. 1.0×10³ L mol⁻¹, as determined by the ¹H NMR measurements. The DFT calculations revealed that the complexes were stabilized by two OH⋅⋅⋅O=C hydrogen bonds between the host and guest molecules. Because the guest molecules examined in this study are smaller than the cavity size, the cavity space (size‐fitting) as well as the noninteracting carbonyl group (multipoint recognition) is not fully utilized well for the molecular recognition. We are seeking for such guest molecules that can bind to the macrocyclic hosts tightly or selectively. We will be able to transform carbonyl moieties in acridone units into other groups to tune the size and the electronic demand of the cavity. Further studies of the synthesis of other acridone cyclic oligomers and their supramolecular properties by applying the polar and donor characters are in progress.

Experimental Section

The synthetic procedures of selected key macrocyclization steps and the physical and spectroscopic data of the final products are described here. Other materials are provided in Supporting Information.

Macrocyclization of 11 b and 13. In a 100 mL round‐bottom flask, a mixture of 11 b (23.8 mg, 31.1 μmol), 13 (24.4 mg, 30.6 μmol), Pd(PPh₃)₄ (7.3 mg, 6.3 μmol), and CuI (1.1 mg, 5.8 μmol) in a degassed mixture of Et₃N (15 mL) and THF (15 mL) was heated at 60 °C for 22 h under N₂ atmosphere. After cooling to room temperature, the mixture was treated with water (100 mL) and the organic materials were extracted with CHCl₃ (30 mL×3). The combined organic layer was dried over Na₂SO₄ and evaporated. The crude product was purified by chromatography on silica gel with CHCl₃/EtOAc 1 : 1 eluent and recycle gel permeation chromatography (GPC) with CHCl₃ eluent to give 4.9 mg (12%) of C3(H) as a yellow solid. C3(H): mp 285–286 °C; R _f 0.40 (CH₂Cl₂); ¹H NMR (500 MHz, CDCl₃): δ=8.90 (d, J=2.0 Hz, 6H), 7.88 (s, 3H), 7.64 (dd, J=9.0, 2.0 Hz, 6H), 7.48 (dd, J=8.0, 2.0 Hz, 6H), 7.33 (t, J=8.0 Hz, 3H), 7.19 (s, 6H), 6.70 (d, J=9.0 Hz, 6H), 2.48 (s, 9H), 1.88 (s, 18H); ¹³C NMR (125 MHz, CDCl₃): δ=176.83, 145.95, 141.26, 140.00, 137.15, 136.46, 133.03, 132.19, 130.88, 130.67, 128.50, 123.89, 122.36, 117.06, 116.03, 89.59, 89.13, 21.42, 17.38; UV‐vis (CHCl₃, 1.0×10⁻⁵ mol L⁻¹): λ _max (ϵ) 421 (20600), 400 (23800), 360 (178000), 349 (162000), 326 nm (205000 L mol⁻¹ cm⁻¹); FL (CHCl₃, 1.0×10⁻⁵ mol L⁻¹): λ _em 439 nm, λ _ex 422 nm (Φ _f 0.084); IR (KBr): $\tilde{v}$ =1646 (C=O), 2212 cm⁻¹ (C≡C); HRMS (FAB): m/z calcd for C₉₆H₆₃N₃O₃: 1305.4869 [M]⁺; found 1305.4867.

Macrocyclization of 11 a and 13 (copper‐free condition). In a 50 mL round‐bottom flask, a mixture of 11 a (20.2 mg, 30.1 μmol), 13 (24.0 mg, 30.1 μmol), PdCl₂(MeCN)₂ (1.1 mg, 4.1 μmol), SPhos (2.7 mg, 6.7 μmol), and Cs₂CO₃ (43.5 mg, 134 μmol) in degassed DMF (10 mL) was heated at 90 °C for 22 h under N₂ atmosphere. After cooling to room temperature, the mixture was treated with water (100 mL). The organic materials were extracted with CHCl₃ (30 mL×3). The combined organic layer was dried over Na₂SO₄ and evaporated. The crude product was purified by chromatography on silica gel with CH₂Cl₂/EtOAc 1 : 1 eluent and recycle GPC with CHCl₃ eluent to give 5.8 mg (15%) of C3(H) as a yellow solid.

Macrocyclization of 3 and 9(H) (typical procedure). In a 100 mL round‐bottom flask, a mixture of 3 (100 mg, 199 μmol), 1,3‐dibromobenzene (9(H), 24.1 μL, 200 μmol), PdCl₂(MeCN)₂ (5.2 mg, 20 μmol), SPhos (16.5 mg, 40.2 μmol), and Cs₂CO₃ (259 mg, 796 μmol) in degassed DMF (67 mL) was heated at 90 °C for 23 h under N₂ atmosphere. After cooling to room temperature, the mixture was treated with water (50 mL). The organic materials were extracted with CH₂Cl₂ (30 mL×3). The combined organic layer was dried over Na₂SO₄ and evaporated. The crude product was purified by chromatography on silica gel with CH₂Cl₂/EtOAc 30 : 1 eluent and recycle GPC with CHCl₃ eluent (Figure S1) to give 13.3 mg (15%) of C3(H) as a yellow solid.

Macrocyclization of 3 and 9(Mes). This reaction was carried out according to the typical procedure from 3 (60.7 mg, 120 μmol) and 9(Mes) (35.5 mg, 100 μmol). The crude products were separated by chromatography on silica gel with CH₂Cl₂ eluent and recycle GPC with CHCl₃ eluent (Figure S2) to give C3(Mes) and C4(Mes) as yellow solids. C3(Mes): Yield 5.5 mg (9.9%); mp 301–304 °C (dec.); R _f 0.65 (CH₂Cl₂); ¹H NMR (500 MHz, CDCl₃): δ=8.93 (d, J=2.0 Hz, 6H), 7.87 (s, 3H), 7.60 (dd, J=9.0, 2.0 Hz, 6H), 7.28 (d, J=2.0 Hz, 6H), 7.17 (s, 6H), 6.94 (s, 6H), 6.69 (d, J=9.0 Hz, 6H), 2.46 (s, 9H), 2.33 (s, 9H), 2.05 (s, 18H), 1.87 (s, 18H); ¹³C NMR (125 MHz, CDCl₃): δ=176.85, 141.72, 141.25, 139.99, 137.55, 137.10, 136.45, 136.05, 133.86, 132.99, 132.20, 131.83, 130.66, 128.21, 124.07, 122.35, 117.02, 116.05, 89.67, 89.27, 21.40, 21.20, 20.92, 17.37 (one aromatic peak was overlapped); UV‐vis (CHCl₃, 1.0×10⁻⁵ mol L⁻¹): λ _max (ϵ) 422 (16800), 400 (20800), 362 (179000), 351 (161000), 327 nm (188000 L mol⁻¹ cm⁻¹); FL (CHCl₃, 1.0×10⁻⁵ mol L⁻¹): λ _em 439 nm, λ _ex 423 nm (Φ _f 0.091); IR (KBr): $\tilde{v}$ =1650 (C=O), 2211 cm⁻¹ (C≡C); HRMS (FAB): m/z calcd for C₁₂₃H₉₃N₃O₃: 1659.7217 [M]⁺; found 1659.7217. C4(Mes): Yield 1.9 mg (3.4%); mp 288–290 °C (dec.); R _f 0.90 (CH₂Cl₂); ¹H NMR (500 MHz, CDCl₃): δ=8.81 (d, J=2.0 Hz, 8H), 7.74 (t, J=2.0 Hz, 4H), 7.62 (dd, J=9.0, 2.0 Hz, 8H), 7.28 (d, J=2.0 Hz, 8H), 7.17 (s, 8H), 6.94 (s, 8H), 6.69 (d, J=9.0 Hz, 8H), 2.45 (s, 12H), 2.32 (s, 12H), 2.05 (s, 24H), 1.85 (s, 24H); ¹³C NMR (125 MHz, CDCl₃): δ=176.86, 141.74, 141.26, 140.02, 137.47, 137.14, 137.08, 136.91, 136.05, 133.24, 132.99, 132.43, 131.53, 130.68, 128.25, 123.98, 122.25, 117.04, 116.11, 89.45, 89.11, 21.40, 21.19, 20.93, 17.35; UV‐vis (CHCl₃, 1.0×10⁻⁵ mol L⁻¹): λ _max (ϵ) 418 (26500), 398 (30500), 355 (189000), 343 (170000), 323 nm (202000 L mol⁻¹ cm⁻¹); FL (CHCl₃, 1.0×10⁻⁵ mol L⁻¹): λ _em 438 nm, λ _ex 419 nm (Φ _f 0.093); IR (KBr):$\tilde{v}$ =1650 (C=O), 2207 cm⁻¹ (C≡C); HRMS (FAB): m/z calcd for C₁₆₄H₁₂₄N₄O₄: 2212.9623 [M]⁺; found 2212.9624.

Macrocyclization of 3 and 9(Tip). This reaction was carried out according to the typical procedure from 3 (101 mg, 200 μmol), 9(Tip) (87.7 mg, 200 μmol). The crude products were separated by chromatography on silica gel with CH₂Cl₂ eluent and recycle GPC with CHCl₃ eluent (Figure S3) to give C3(Tip) and C4(Tip) as yellow solids. C3(Tip): Yield 7.2 mg (5.6%); mp 318–320 °C (dec.); R _f 0.83 (CH₂Cl₂); ¹H NMR (500 MHz, CDCl₃): δ=8.94 (d, J=2.0 Hz, 6H), 7.88 (t, J=2.0 Hz, 3H), 7.60 (dd, J=9.0, 2.0 Hz, 6H), 7.32 (d, J=2.0 Hz, 6H), 7.17 (s, 6H), 7.06 (s, 6H), 6.69 (d, J=9.0 Hz, 6H), 2.94 (sept, J=7.0 Hz, 3H), 2.66 (sept, J=7.0 Hz, 6H), 2.45 (s, 9H), 1.86 (s, 18H), 1.30 (d, J=7.0 Hz, 18H), 1.12 (d, J=7.0 Hz, 36H); ¹³C NMR (125 MHz, CDCl₃): δ=176.86, 148.48, 146.66, 141.42, 141.25, 139.99, 137.09, 136.50, 135.62, 133.79, 133.01, 132.22, 130.66, 123.61, 122.37, 120.71, 117.05, 116.04, 89.60, 89.41, 34.48, 30.43, 24.40, 24.25, 21.40, 17.35 (one aromatic peak was overlapped); UV‐vis (CHCl₃, 1.0×10⁻⁵ mol L⁻¹): λ _max (ϵ) 422 (19300), 400 (24300), 363 (206000), 352 (183000), 328 nm (210000 L mol⁻¹ cm⁻¹); FL (CHCl₃, 1.0×10⁻⁵ mol L⁻¹): λ _em 439 nm, λ _ex 423 nm (Φ _f 0.081); HRMS (FAB): m/z calcd for C₁₄₁H₁₂₉N₃O₃: 1912.0034 [M]⁺; found 1912.0078. C4(Tip): Yield 2.8 mg (2.2%); mp 307–310 °C (dec.); R _f 0.95 (CH₂Cl₂); ¹H NMR (500 MHz, CDCl₃): δ=8.81 (d, J=2.0 Hz, 8H), 7.75 (t, J=2.0 Hz, 4H), 7.62 (dd, J=9.0, 2.0 Hz, 8H), 7.32 (d, J=2.0 Hz, 8H), 7.16 (s, 8H), 7.06 (s, 8H), 6.69 (d, J=9.1 Hz, 8H), 2.93 (sept, J=7.0 Hz, 4H), 2.66 (sept, J=7.0 Hz, 8H), 2.45 (s, 12H), 1.85 (s, 24H), 1.30 (d, J=7.0 Hz, 24H), 1.12 (d, J=7.0 Hz, 48H); ¹³C NMR (125 MHz, CDCl₃): δ=176.87, 148.49, 146.66, 141.44, 141.25, 140.02, 137.06, 136.91, 135.52, 133.20, 132.97, 132.75, 131.56, 130.67, 123.50, 122.24, 120.75, 117.05, 116.09, 89.37, 89.21, 34.46, 30.43, 24.41, 24.23, 21.40, 17.34; UV‐vis (CHCl₃, 1.0×10⁻⁵ mol L⁻¹): λ _max (ϵ) 419 (26200), 398 (30400), 355 (203000), 323 nm (213000 L mol⁻¹ cm⁻¹); FL (CHCl₃, 1.0×10⁻⁵ mol L⁻¹): λ _em 438 nm, λ _ex 420 nm (Φ _f 0.092); HRMS (FAB): m/z calcd for C₁₈₈H₁₇₂N₄O₄: 2549.3379 [M]⁺; found 2549.3330.

X‐ray crystallography. Deposition numbers 2171120 for C3(H), 2171123 for C4(Mes), and 2171121 for C3(Tip) contain the supplementary crystallographic data for this paper. These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum Karlsruhe Access Structures service.

Computational methods. The conformational search of host‐gest complexes was carried out by using CONFLEX program. ^[27] The selected stable structures were further optimized by DFT method at B3LYP/6‐31G(d) level with Gaussian 16 program (Figure 8). ^[32] The frequency analysis was carried out for each optimized structure, giving no imaginary wavenumber for energy minimum structures.

Conflict of interest

The authors declare no conflict of interest.

Supporting information

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Supporting Information

Komori T., Tsurumaki E., Toyota S., Chem. Asian J. 2023, 18, e202201003.

Data Availability Statement

The data that support the findings of this study are available in the supplementary material of this article.