Cucurbit[n]urils (CB[n]s) are a series of macrocyclic molecules consisting of n glycoluril units bridged by 2n methylene groups . Because of their special rigid structures of one hydrophobic cavity lying between two polar carbonyl-lined portals, CB[n]s could include size-matched molecules, especially those cationic species, and have shown extensive uses in the field of supramolecular chemistry . Among these areas, using a CB[n] as a molecular container for catalytic synthesis  has been one of the key issues and many reports have thus emerged, for example, Mock and his co-workers have firstly reported applying CB for efficient triazole formation . Tao group reported CB-catalytic oxidation of aryl alcohols to aldehydes . Kim  reported a facile method using CB to induce stereoselective [2 + 2] photoreaction. Some other smart strategies such as photodimerization and chemoselective photoreaction , catalytic alcoholysis of epoxides , gas-phase reaction , acid catalysis , esterification  and oxidizing reaction  were also developed.
Diazonium salts are one sort of important intermediates for further preparation of phenols, aromatic halogens and other important organic compounds , in the way of decomposing into arene cations and then substituted by nucleophiles , or into arene radicals followed by hydrogen abstraction  or coupling . It has been found that diazonium salts could bind with CB[n]s to form host-guest complexes for their positive charged nature , however, there is no report about the decomposition of a diazonium-cucubituril complex according to our knowledge. Herein we report the encapsulation of 4-nitrobenzendiazonium borofluoride (4-NBD) by CB to form a 1:1 complex NBD@CB (Scheme 1). NBD@CB showed better thermo stability than 4-NBD, and its decomposition in the presence of CuCl in aqueous solution resulted in the formation of nitrobenzene (NB) and 4-nitrophenol (4-NP), in the yields of 61% and 33%, respectively, while in the absence of CuCl, it produced 4-NP in a yield of 27%. In comparison, the decomposition of free 4-NBD produced mainly 4-NP, whether CuCl existed or not, in the yields of 10% (with CuCl) and 60% (no CuCl).
To confirm that 4-NBD could combine with CB, the corresponding UV–vis job plots was carried out, as illustrated in Fig. S4 in Supporting information. The maximum value of the vertical axle corresponds to 0.5 at horizontal axle, indicating a 1:1 complexation. High resolution ESI-MS measurement also provides the evidence of the formation of NBD@CB, as can be seen in Fig. S2 in Supporting information, the peak at m/z 1312.3735 corresponds to the [M-BF4-]+ of NBD@CB (calcd. 1312.3739). Further 1H NMR experiments were carried out to investigate the complexation details. As can be seen in Fig. 1, the 1H NMR spectrum of 4-NBD in D2O shows two groups of proton resonances (δHa = 8.63 and δHb = 8.81) with 1:1 intensity. After the addition of CB to 4-NBD solution in a molar ratio of 1:1, Hb exhibits a distinct upfieldshifted signal (ΔδHb = -1.28) while Ha moves slightly downfield (ΔδHa = +0.12). In most cases, the protons within the cucurbituril cavity undergo shielding effects and those locate near the carbonyl portals are nearly unaffected . Therefore, the NMR results indicate that the benzene ring of 4-NBD is encapsulated by CB, leaving Ha sitting near the portal, as shown in Fig. 1B.
|Fig. 1. The 1H NMR spectra (400 MHz, D2O, 298 K) of free 4-NBD (A) and NBD@CB (B) (CNBD = 0.0106 mol/L, CCB = 0.0108 mol/L).|
ITC measurements were carried out in aqueous solution at 25 ℃ to evaluate the binding constant between 4-NBD and CB. The solutions of 0.156 mmol/L 4-NBD and 0.052 mmol/L CB were placed in the injection syringe and sample cell, respectively. The exothermic binding isotherm was recorded with the solution of 4-NBD being dropwise injected into the solution of CB. The obtained data were analyzed on the basis of binding model that are given in ITC tutorial guide. As shown in Fig. 2, the ITC results fit a 1:1 binding model, and the binding constant K is evaluated as (1.28 ± 0.207) × 105 L/mol.
|Fig. 2. ITC results for the complexation of 4-NBD with CB in aqueous solution at 25 ℃.|
It is well-known that diazonium salts should be stored at low temperature because of the poor thermostability [19, 20]. NBD@CB was expected to have better thermo stability because of the protection by CB, with the help of the electrostatic attractions between the diazonium cation and the CB portal carbonyls, which makes the diazonium group difficult to release a N2. The thermo-decomposition of 4-NBD and NBD@CB were monitored by UV–vis spectra. Both 4-NBD and NBD@CB aqueous solution showed a maximum absorption at around 260 nm. The two solutions were then heated at different temperatures for 1 h respectively and then the corresponding UV–vis spectra were recorded (Figs. S5 and S6 in Supporting information) and the absorption changes at 260 nm were illustrated in Fig. 3. It can be seen that the maximum absorption of 4-NBD appears accelerated decreases when the heating temperature is higher than 20 ℃. In comparison, the maximum absorption of NBD@CB keeps nearly unchanged even the temperature reaches to 50 ℃, and then begins to drop significantly when the heating temperature continues to increase (ΔA50→60 = -0.009; ΔA60→70 = -0.027). These results indicate that the thermo stability of 4-NBD is indeed considerably improved after being encapsulated by CB.
|Fig. 3. The maximum absorptions of 4-NBD (4.22 ×10-5 mol/L) and NBD@CB (C4-NBD = 4.22 ×10-5 mol/L, CCB = 1.12 ×10-3 mol/L) aqueous solutions after being heated at different temperatures for 1 h, respectively.|
The decomposition of an aromatic diazonium salt would result in the releasing of N2 molecule, and at the same time the formation of an arene cation, which would readily combine with nucleophile species such as OH— in aqueous solution, forming a phenol . In comparison, the addition of Cu+ to an aromatic diazonium salt generally favors the single electron transfer (SET) process from Cu+ to the diazonium group when it decomposes, and as a result generates an arene radical . The formed radical could have a further reaction such as hydrogen abstraction and the diazonium group is finally replaced by H atom to form an arene.
The decomposition of 4-NBD and NBD@CB at 0 ~ 5 ℃ in the presence of CuCl was firstly monitored by UV–vis absorption. The samples of the two solutions (C0 = 0.014 mol/L) at different reaction time were diluted from 20 μL to 10 mL and detected by UV-vis, the curves are shown in Fig. 4. It can be seen that the maximum absorption band of the 4-NBD aqueous solution at 261 nm keeps nearly unchanged in the presence of 2.0 equiv. CuCl even after standing at 0 ~ 5 ℃ for 44 h (Fig. 4A). In comparison, the addition of 2.0 equiv. of CuCl to the NBD@CB solution results in a distinct decomposition of 4-NBD guest at this temperature (Fig. 4B), and the absorption band at 261 nm vanishes quickly within 30 min.
|Fig. 4. UV-vis spectra of 4-NBD (A) and NBD@CB (B) aqueous solutions after the addition of 2.0 equiv. of CuCl at 5 ℃, both diluted from 20 μL of the reacted aqueous solutions (C0 = 0.014 mol/L) to 10 mL.|
The substitution products during the decomposition were then investigated. A solution of 4-NBD or NBD@CB in the presence of different amounts of CuCl was decomposed at a certain temperature. The precipitate was obtained by filtration (P1) and the filtrate was extracted by CH2Cl2. The CH2Cl2 exact was dried and solvent was evaporated at 30 ℃ on a rotary evaporator (P2). The 1H NMR of P1 and P2 in CDCl3 were recorded (Figs. S8-S15 in Supporting information). Nitrobenzene (NB) and 4-NP were found being the main products and the yields of NB and 4-NP were determined during the 1H NMR measurements using DMSO as the internal standard and the results are illustrated in Table 1.
It can be seen that CuCl enables the decomposition of NBD@CB at around 0 ℃, while at this temperature has no effect on free 4-NBD (4-NBD keeps stable). This is most likely caused by the complexation of the CB carbonyl rims of NBD@CB with Cu+ ion , which favors the SET process. The reductive NB is the main products (yield 61%) and 4-NP is the minor one (yield 33%) during the CuCl-catalyzed substitution of NBD@CB, and the total yield is satisfactory. In comparison, the decomposition of 4-NBD in the presence of either CB or CuCl, or both absence, 4-NP is the main product, and the total yields are relatively low, especially in the presence of CuCl (3% NB + 10% 4-NP) or CB (4% NB + 27% 4-NP) alone. It should be noted that there was scarcely detectable byproducts, besides NB and 4-NP, could be found during CuCl-catalyzed substitution of NBD@CB while a large amount of unknown byproducts were obtained during the latter three substitutions (Figs. S10, S12 and S14 in Supporting information). Thus the CuCl-catalyzed substitution of 4-NBD/CB complex to NB/4-NP is an more effective and economic way than common substitutions, and 4-NP can be easily separated from NB by being simply basified to phenol salt.
In summary, 4-NBD and CB could form a complex NBD@CB in a molar ratio of 1:1 in aqueous solution and the binding constant is about 1.28 × 105 L/mol. NBD@CB shows a better thermostability than 4-NBD in aqueous solution, and its decomposition in the presence of CuCl results in a high total yield of NB/4-NP mixture (NB 61%, 4-NP 33%). In comparison, the decomposition of 4-NBD in the presence of either CB or CuCl, or both absence, brings about significant amounts of unknown byproducts. This work might provide an economic and effective way to obtain arenes or phenols through the substitution of diazonium salts.Acknowledgments
This work was financially supported by the National Natural Science Foundation of China (Nos. 21572063 and 21372076), the Science Fund for Creative Research Groups (No. 21421004), the Program of Introducing Talents of Discipline to Universities (No. B16017), and the Fundamental Research Funds for the Central Universities (No. 222201717003).
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