Electrochemically Promoted Benzylation of [60]Fullerooxazolidinone

Benzylation of the electrochemically generated dianion from N-p-tolyl-[60]fullerooxazolidinone with benzyl bromide provides three products with different addition patterns. The product distribution can be dramatically altered by varying the reaction conditions. Based on spectral characterizations, these products have been assigned as mono-benzylated 1,4-adduct and bis-benzylated 1,2,3,16- and 1,4,9,25-adducts, respectively. The assigned 1,2,3,16-adduct has been further established by X-ray diffraction analysis. It is believed that the 1,4-adduct is obtained by decarboxylative benzylation of the dianionic species, while bis-benzylated 1,2,3,16- and 1,4,9,25-adducts are achieved via a rearrangement process. In addition, the electrochemical properties of these products have been studied.


Results and Discussion
Compound 1 was synthesized by the previously reported procedure [39]. As seen from the cyclic voltammogram (CV) of 1, the first redox was reversible, whereas the second redox was electrochemically irreversible (Figure 1). It was found that the CV of 1 was essentially the same at 25 • C and a slightly lower temperature such as 15 • C. This result indicated a cleavage of carbon-heteroatom bond of 1 after accepting two electrons. Previous work on fulleroimidazoline and fullerooxazoline derivatives showed that the C 60 -O and C 60 -N could be readily cleaved when they received two electrons [36,37], and we found that 1 (0.02 mmol) could be electrochemically converted at −1.09 V (the trough of the second wave) to dianion 1 2− , which was readily decomposed to C 60 during electrolysis at 25 • C. The electrolysis at lower temperature would slow down the decomposition of dianion 1 2− to C 60 , yet required a longer time to reach the theoretical number and would also cause partial decomposition of dianion 1 2− . On balance, we carried out our experiments on 1 (0.01 mmol) at a lower temperature of 15 • C. By controlled potential electrolysis (CPE) of 1 at −1.09 V in 1,2-C 6 H 4 Cl 2 solution containing 0.1 M tetra-n-butylammonium perchlorate (TBAP) at 15 • C under an atmosphere of argon, dianion 1 2− was generated after acceptance of two electrons. Similar to other dianionic C 60 -fused heterocycles, the ring-opened singly-bonded fullerenyl dianion was attained after addition of two electrons [26][27][28][29][30][31][32][33][34][35][36][37], as confirmed by the very different CV of dianion 1 2− ( Figure S21) compared to that of neutral 1 ( Figure 1). Then, 1 2− was treated with 20 equiv. of NaH and 50 equiv. of BnBr at 15 • C for 1 h (Scheme 1). Surprisingly, a ring-opened mono-benzylated 1,4-adduct 2 was isolated as the major product in 32% yield together with bis-benzylated 1,2,3,16-adduct 3 and 1,4,9,25adduct 4 in 21% and 4% yields, respectively. The formation of product 2 resulted from decarboxylative benzylation of 1 2− , which was in sharp contrast with the previously reported benzylation of dianionic C 60 -fused lactones [40]. The isolation of products 3 and 4 indicated that 1 2− could react with two molecules of BnBr. For the purpose of enhancing the possibility of adding the second BnBr, the amount of BnBr was increased to 100 equiv., and the yield of the mono-benzylated 1,4-adduct 2 was decreased to 23%, while the competing bis-benzylated 1,2,3,16-adduct 3 was obtained in 29% yield as the major product along with 1,4,9,25-adduct 4 in 3% yield as the minor product. In order to obtain more bis-benzylated 1,2,3,16-adduct 3, the reaction time was further increased to 10 h. Intriguingly, the bis-benzylated 1,2,3,16-adduct 3 could be obtained in 40% yield as the major product along with another bis-benzylated 1,4,9,25-adduct 4 in 14% yield and 1,4-adduct 2 in 4% yield as the minor products. Besides the above products, the reaction mixtures also contained decomposed C 60 , unreacted 1 and insoluble material (see details in Materials and Methods). It seemed that 1,4-adduct 2 was unstable under our experimental conditions, likely due to the attached arylamino moiety. In brief, when the dianion 1 2− was treated with 50 equiv. of BnBr for a short reaction time (1 h), mono-benzylated product 2 was the major product along with bis-benzylated products 3 and 4 as minor products.
When the amount of BnBr was increased to 100 equiv. for the purpose that the second BnBr could participate in the reaction system, and reaction time was further prolonged (10 h), products 3 and 4 were obtained exclusively accompanied with a small amount of 2. As seen from Scheme 1, the product distribution for the benzylation of 1 2− could be dramatically manipulated by varying the amount of BnBr and reaction time, either mono-benzylated 1,4-adduct 2 or bis-benzylated 1,2,3,16-adduct 3 could be obtained as the major product. Products 2-4 were characterized by various spectroscopic data, and 3 was further established by single-crystal X-ray crystallography. The MALDI-TOF mass spectra of 2-4 showed the expected molecular ion peaks. In its 1 H NMR spectrum of 2, two doublet peaks at 4.07 and 4.03 ppm with a coupling constant of 13.0 Hz for the methylene protons of the benzyl group attached to the fullerene skeleton and a singlet peak at 2.32 ppm for the methyl group of the p-toluidine moiety were observed. The 1 H NMR spectrum of 3 showed an AB quartet at 4.41 and 4.24 ppm with a coupling constant of 13.3 Hz for the methylene protons, while another AB quartet at 2.59 and 2.44 ppm with a coupling constant of 12.9 Hz, indicating that the latter methylene protons were located at the shielding region of a phenyl ring. Likewise, the 1 H NMR spectrum of 4 displayed the same phenomena for the chemical shifts and splitting patterns of the methylene protons attached to the fullerene skeleton. Herein, the two benzyl groups should be located at the different sides of the oxazolidinone moiety in compounds 3 and 4. The 13 C NMR spectrum of 2 showed 50 peaks for the 58 sp 2 -carbon atoms in the 156.15-137.93 ppm range and two sp 3 -carbon atom peaks of the fullerene cage at 68.28 and 60.01 ppm, and the 13 C NMR spectra of 3 and 4 displayed at least 52 peaks between 156.04-135.95 ppm for the 56 sp 2 -carbon atoms and four peaks between 90.31-56.52 ppm for the four sp 3 -carbon atoms of the fullerene skeleton, agreeing with their C 1 symmetry. The UV-vis spectrum of 2 showed a broad absorption band at 446 nm, which resembled those of other 1,4-adducts of C 60 [35,40,41]. The UV-vis spectrum of 3 exhibited two strong absorption bands at 254 and 324 nm, together with three weak absorption bands at 405, 431 and 690 nm, which were similar to those of 1,2,3,16-adducts in the literature [26,27,[30][31][32][33]35,37,38]. However, in the UV-vis spectrum of product 4, three strong absorption bands at 250, 268 and 330 nm, together with five weak absorption bands at 409, 450, 510, 591 and 672 nm were observed, and were very similar to those of 1,4,9,25-adducts in the literature [32,35].

General Information
All electrochemical measurements and reactions were performed under an atmosphere of argon atmosphere using a Shanghai Chenhua CHI620E workstation. The electrolyte TBAP was recrystallized from absolute ethanol and then dried in a vacuum at 40 • C prior to use. Other chemicals were obtained commercially and used without further purification. CV measurements were performed in a conventional three-electrode cell. A 2 mm diameter platinum disc electrode and a platinum wire auxiliary electrode were used as working and counter electrodes, respectively, and the reference electrode was saturated calomel electrode (SCE). CPE was carried out on a potentiostat/galvanostat using an "H" type cell. Two platinum gauze (15 mm × 30 mm) electrodes served as working and counter electrodes, respectively, and were separated by a sintered glass frit. The SCE was separated from the bulk of the solution by a fritted-glass bridge of low porosity which contained the solvent/supporting electrolyte mixture.

Single-Crystal Growth and Characterization of 3
Black block crystals of 3 were obtained by slow evaporation of the CS 2 solution of 3 at room temperature. Single-crystal X-ray diffraction data were collected on a diffractometer (SuperNova, Rigaku, Rigaku Polska Sp. Z oo UI, Wroclaw, Poland) equipped with a CCD area detector using graphite-monochromated Cu Kα radiation (λ = 1.54184 Å) in the scan range 8.174 • < 2θ < 150.64 • . Using Olex2, the structure was solved with the ShelXT structure solution program using Intrinsic Phasing and refined with the ShelXL refinement package using Least Squares minimization. Crystallographic data have been deposited in the Cambridge Crystallographic Data Centre as deposition number CCDC 2163434.

Conclusions
In conclusion, benzylation of the electrochemically generated dianionic N-p-tolylfullerooxazolidinone with benzyl bromide affords a ring-opened mono-benzylated 1,4adduct 2, bis-benzylated 1,2,3,16-adduct 3 and 1,4,9,25-adduct 4. The product distribution can be manipulated by altering the reaction conditions. The structural assignments for products 2-4 are established by spectroscopic data and single-crystal X-ray crystallography. A possible reaction mechanism for the formation of the three types of adducts is proposed. The present work provides a new avenue for the electrochemical functionalization of C 60 -fused heterocycles.

Data Availability Statement:
The data presented in this study are available in the article and Supplementary Materials.

Conflicts of Interest:
The authors declare no conflict of interest.