Tris-Azo Triangular Paraphenylenes: Synthesis and Reversible Interconversion into Radial π-Conjugated Macrocycles

We report the synthesis of cycloparaphenylene derivatives featuring tris-azo groups. The smaller derivative, [3]cycloazobenzene, adopts a triangular all-cis form and exhibits thermally and photochemically stable characteristics due to significant ring strain as well as symmetric Kagome-patterned crystal packing. In contrast, the as-synthesized [3]cycloazobenzene with three biphenylene bridges adopts a triangular all-cis form, which undergoes photoinduced isomerization, leading to a photostationary state. Interestingly, the addition of an excess of acid selectively leads to the formation of an all-trans form. DFT calculations reveal that the interconversion from a triangular to a circular shape correlates with an increase in HOMO and a decrease in LUMO, characteristics intrinsic to radial π-conjugated systems.

π-Conjugated macrocycles have garnered significant attention due to their unique structures and properties. 1−3 These materials, known for their rigidity, are often referred to as shape-persistent macrocycles. 1 Several macrocycles have been synthesized containing ortho-or meta-phenylene units, forming planar structures and π-conjugated systems.Over the past decade, substantial research has focused on a new class of πconjugated macrocycles consisting of benzene linked at the para position, yielding a curved structure characteristic of a radial π-conjugated system.Typical examples of these are cycloparaphenylenes (CPPs) and related nanohoops. 2These molecules possess a radial π-conjugate system with a shallow highest occupied molecular orbital (HOMO) level and a deeper lowest unoccupied molecular orbital (LUMO) level compared with linear oligomers, resulting in a narrower HOMO−LUMO gap. 4 Azobenzene, a well-known stimuli-responsive molecule, undergoes trans-to-cis isomerization upon photoirradiation, a process reversible by subsequent photoirradiation, heat, or acid. 5While there are reports on macrocycles containing azobenzene units, π-conjugated macrocycles with three or more azobenzene units remain unexplored.The first macrocycle containing three trans azo groups linked with orthophenylene was synthesized by Dreiding et al. (Figure 1a). 6Wegner et al. attempted photoinduced isomerization, but the macrocycle did not adopt a cis form. 7Subsequently, they reported a macrocycle with three azobenzene units by metalinkage, which exhibits photoisomerization (Figure 1b). 8dditionally, Tamaoki et al. reported π-conjugated macrocycles containing two to four azobenzene units linked with orthophenylene that exhibit photoisomerization (Figure 1c). 9 Jasti et al. reported CPP incorporating a single azobenzene unit, cis-azo [9]CPP, which does not exhibit photoisomerization (Figure 1d). 10 They further described cis-azo[11]CPP, which is capable of photoisomerizable ring size alteration.CPPs with two or more azo groups would exhibit more pronounced shape changes in the macrocycle; however, exploration of such CPPs has been primarily theoretical, focusing on their potential host function. 11This study synthesizes CPP derivatives with three azo groups, one of which demonstrates reversible interconversion between triangular and radial π-conjugated macrocycle shapes via cistrans isomerization, triggered by photo-or acid-stimuli (Figure 1e).
Similar to our molecules, previously reported CPPs containing a single azo group were obtained solely as cis isomers from trans-4,4′-dibromoazobenzene. 10 Additionally, a macrocyclic stilbene tetramer was found to adopt a partial cis form, though it was synthesized from a trans-stilbene derivative. 13This cis formation resulted from ring strain in the intermediate macrocyclic Pt-complex.Strained phenylene bonds formation via the Au(III)-intermediate has been reported previously.12a In this work, the Au(III) azodiphenylene intermediates would exhibit high ring strain during the elimination of macrocyclic Au-complexes, causing the bending of trans azobenzene and thus leading to the formation of cis azobenzene.
The UV−vis absorption spectrum of all-cis [3]CAB-0 in 1,2dichloroethane shows a peak at 429 nm, attributed to the azo group.Photoirradiation of the [3]CAB-0 solution did not induce significant changes in the absorption band (Figure S24).Consequently, our investigation shifted to larger [3]CAB-1.Its UV−vis spectrum, recorded immediately after dissolution in 1,2-dichloroethane, exhibits an absorption band at 446 nm (Figure 3a).Irradiation of the solution at 254 nm demonstrated the significant change, showing an increase in absorption at 383 nm and a decrease at 329 nm within 15 min, indicative of cis-to-trans photoisomerization.Irradiation at 365 or 445 nm, as well as exposure to ambient light, resulted in different levels of photostationary states (Figures S25−S30).These spectral changes could be repeated (Figure S31).
Given that cis-azobenzene is known to rapidly isomerize to its trans form upon acid addition, 5a−d we explored the acid response of tris-azo macrocycles (Figures S40−S53 the protonated state of azobenzene.Conversely, a CDCl 3 solution of [3]CAB-0 exhibited a minor color change after adding 1.2 M CF 3 COOH, with the 1 H NMR spectrum confirming only the presence of the cis form (Figure S51).
UV−vis spectra were recorded for [3]CAB-1 in 1,2dichloroethane at the photostationary state under ambient light at 25 °C, with varying concentrations of CF 3 COOH (Figure 3b).Increasing the CF 3 COOH concentration caused the absorption shoulder around 400 nm to shift to longer wavelengths, and a new absorption peak emerged at 519 nm.Excess acid is necessary due to the weak basicity of azobenzene (Figure S64).In comparison, the addition of CF 3 COOH to a 1,2-dichloroethane solution of [3]CAB-0 did not significantly alter the absorption wavelength to around 430 nm (Figure S40).Interestingly, when the acidic solution of [3]CAB-1 was irradiated at 520 nm, the solution color promptly changed from purple to blue at the line irradiated by the 520 nm laser, accompanied by a shift in absorption maxima from 519 to 565 nm (Figure 3b, its inset photo, and Figure S44).The color and spectrum rapidly reverted to their original state once the light source was removed (Figure S45).Irradiation at 365 and 405 nm also induced a bathochromic shift of about 20 nm (Figure S44).However, irradiation at 254 nm resulted in the disappearance of the absorption band at 519 nm, suggesting compound decomposition (Figure S46).
The reversibility of [3]CAB-1 was investigated by introducing triethylamine to a 1,2-dichloroethane solution containing 15000 equiv of CF 3 COOH.Upon adding only 6000 equiv of triethylamine, less than half of the CF 3 COOH amount, the spectrum largely recovered (Figure S48).Subsequent readdition of CF 3 COOH caused the absorption at 450 nm to reappear.Methanol also facilitated deprotonation, reverting the spectrum to the all-cis [3]CAB-1 upon adding 30700 equiv (Figure S49).
Thermal isomerization of [3]CAB-1 was also studied (Figures S32−S39).Heating to 60 °C led to a decrease in the absorption band around 400 nm, indicating an increase in the all-cis form (Figure S37).In contrast, [3]CAB-0 exhibited no significant change from its as-synthesized cis form (Figure S24), thus confirming its stability as a photo-, acid-, and thermally stable cis-azobenzene.Similar examples of stable cisazobenzene include azo[9]CPP 10 and methylene-bridged azobenzene macrocyclic dimers. 14he difficulty in inducing the stimuli-responsive isomerization of [3]CAB-0 is largely attributed to its ring strain.This was quantified using DFT calculations based on the reaction enthalpy of the homodesmotic reaction (Table S4).The calculations (ωB97M-V 15 /def2-QZVP 16 //r 2 SCAN-3c, 17 using ORCA 18 ) revealed the ring strain energies for all-cis, cis-cistrans, cis-trans-trans, and all-trans [3]CAB-0 to be 34.4,52.2, 62.6, and 76.3 kcal mol −1 , respectively (Figure S54).In comparison, [3]CAB-1 showed lower strain energies of 34.7, 40.6, 40.7, and 42.0 kcal mol −1 , respectively (Figure 4a and Figure S55).Notably, the ring strain in [3]CAB-0 increased by 17.8 kcal mol −1 with the inclusion of one trans azo group.However, the difference in ring strain in [3]CAB-1 was reduced to 5.9−7.3kcal mol −1 when transitioning from one to all-trans form due to its larger macrocyclic size.The relative Gibbs energy is also within a range of 5.5−7.1 kcal mol −1 , indicating that the slight energy differences in [3]CAB-1 facilitate isomerization under external stimuli such as photoirradiation and acids (Figure 4a).Additionally, relative Gibbs energies for the double-protonated states of [3]CAB-1 were  estimated, with the double-protonated all-trans state being the most stable (Figure 4b and Figure S64).
Under acidic conditions, the tris-azo macrocycles exhibit absorption bands at significantly longer wavelengths in the UV−vis spectra compared to those of cycloparaphenylenes, 4 neutral azobenzene, and its cation.5d TD(TDA)-DFT calculations (SOS-ωPBEPP86 19 /cc-pVDZ 20 //r 2 SCAN-3c) were conducted for the tris-azo macrocycles to predict their UV− vis absorption properties (Figures S56−S62 and Tables S6−  S29).The results suggest that the protonated species of [3]CAB-1 exhibit absorption at longer wavelengths.Thus, the observed UV−vis spectra comprise contributions from both neutral and protonated states.The calculated absorption spectra for both all-cis and all-trans forms demonstrate a shift toward shorter wavelengths with an increase in the number of protons, with the all-trans form displaying absorption at longer wavelengths and higher intensity compared to the all-cis form.The reversible photochromism of [3]CAB-1 is attributed to both deprotonation in excited states and isomerization from the remaining cis form to the trans form.As photochromism is not observed in [3]CAB-0 upon photoirradiation (Figure S42), isomerization is considered the main driver of the photochromic process.
Furthermore, the electronic structure of [3]CAB-1, determined by DFT (CAM-B3LYP 21 /def2-TZVP 16 // r 2 SCAN-3c) calculations, reveals that in the all-trans form, both HOMO and LUMO are degenerate, while in the all-cis form, they are nondegenerate (Figure 5 and Figure S63).Similar to previously reported CPPs, which demonstrated an increase in HOMO and decrease in LUMO due to radial πconjugation, 4 we observed a comparable trend in orbital energies for [3]CAB-1 transitioning from triangular to radial πconjugation.Accompanying the structural change from all-cis to all-trans, the HOMO increased by +0.17 eV, and the LUMO decreased by −0.44 eV, narrowing the HOMO−LUMO gap by 0.60 eV from 5.79 to 5.19 eV.The orbital shapes reveal that the all-cis form prominently includes a lone pair from the azo group in both HOMO and LUMO, while the all-trans form predominantly involves the π orbital, distributed on the exterior of the azo groups with the lone pair orbital located on the interior of the macrocycle.
In conclusion, we have successfully synthesized tris-azo macrocycles featuring three symmetrically placed azo groups within CPP skeletons.The smaller macrocycle maintains a persistent all-cis structure, whereas the larger macrocycle exhibits reversible cis-trans isomerization upon photoirradiation or acid/base addition.Rapid and reversible photochromism is also observed in an acidic solution of the larger macrocycle.This represents a first example of reversible interconversion between triangular and radial π-systems, distinct from reported irreversible conversions of acetyleneincorporated CPPs with azides. 22We anticipate that these switchable macrocycles could serve in photo-or chemically stimulated molecular machines and host−guest chemistry, leveraging their significant shape and electronic state changes.
Additional experimental details, materials and methods, 1 H and 13 C NMR, MS, and UV−vis spectra, crystallographic data, and computational details (PDF)