Formation of persistent organic diradicals from N,N′-diphenyl-3,7-diazacyclooctanes
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N,N′-Diphenyl-3,7-diazacyclooctane and structurally related N,N′-diphenylbispidine derivatives react with silver(I) ions in a high-yielding C–C coupling reaction to produce dication–diradical species, with the silver ions serving a double function both as template and as an oxidant. The resulting bis(benzidino)phane derivatives are persistent organic radicals, stable for several months in solution as well as in the solid state, at room temperature and above, as well as being exposed to the atmosphere. The molecular structure features a double-decker cyclophane motif, stabilized by intramolecular π-dimerization of two delocalized benzidinium radical segments. Intermolecular π-dimers are formed in the solid state.
KeywordsBiaryls Crystal structure Heterocycles Oxidative coupling
Persistent organic diradicals are of interest for a variety of applications as functional materials, such as molecular magnets and molecular electronics [1, 2, 3, 4, 5, 6]. In contrast to monoradicals, they offer the intriguing option of modulating their spin state. Diradicals with intramolecular π−π interactions are of particular interest, and only a few examples have been reported . Common structural motifs are based on the dimers of benzidine  (4,4′–diaminobiphenyl) or N,N,N′,N′-tetraaryl-(1,1′-biphenyl)-4,4′-diamines [8, 9, 10]. While these usually retain some structural flexibility regarding the π−π-interacting segments, attempts have been made to obtain “confronted arenes”  with closer interactions, such as found in cyclophane-like structures . We here report the serendipitous finding of a simple synthetic method to produce highly persistent organic diradicals with strong intramolecular π−π interactions.
Results and discussion
The structure of 5 was revealed by X-ray crystallography. In the crystals, two benzidine units are arranged into a cyclophane motif, and intercalated with counterions and solvent molecules. To balance the counterion charge (i.e., 2 × BF4−), a dicationic organic component is required. This would be possible if each benzidine unit carried one unpaired electron (Scheme 1).
Bond lengths in the benzidine segments of 5 deviate from those found in benzidine itself (Fig. S16, Supplementary), as would be expected for a quinoidal resonance structure, similar to recently reported benzidine cation radicals .
While the dication–diradical nature of 5–7 initially was inferred from the structure of 5 as revealed by X-ray crystallography (vide supra), several further observations support its electronic structure. First, the presence of unpaired electrons results in 1H NMR spectra of the isolated products 5–7 with very broad signals revealing their paramagnetic properties (Fig. S6, Supplementary). However, it was possible to obtain 19F NMR spectra with reasonably narrow signals for their BF4− counterions, due to some distance from the paramagnetic centers . Interestingly, diffusion coefficients determined by LED–PGSE NMR experiments on 19F corresponded well to the hydrodynamic radii of the proposed dimeric reaction products (Table S1, Supplementary) when relating these parameters via the Stokes–Einstein equation . This indicates the presence of tight ion pairs. Notably, for N,N′-diphenylpiperazine (4), which showed entirely different reactivity, the 19F detected BF4− diffusion coefficient remained essentially the same as that for an AgBF4 solution.
Second, the UV/Vis spectrum of dication–diradical 5 shows absorption maxima at 403 and 760 nm (Fig. S11, Supplementary), bands that have been assigned to cation radical dimers in other benzidines, whereas the bands at higher wavelengths (typically λ ≥ 800 nm), assigned to cation radical monomers [8, 14, 18], are completely absent. Interestingly, the dark green solid of 5, obtained by drying at atmospheric pressure, reversibly can be transformed into a black solid under vacuum, indicating a solvatochromic effect  due to removal of solvent molecules from the crystal lattice.
The charge passed at E A 0 (blue curve in Fig. 3) is comparable to the total charge passed at E B 0 and E C 0 (green curve in Fig. 3), and the two latter peaks are of the same size. This is consistent with a two-electron transfer in process A, and with processes B and C being two consecutive one-electron transfers.
Process A is thus the reduction of 5 to the neutral species 8, also obtained by chemical reduction, while processes B and C are oxidations to the tri- and tetracations, respectively. The benzidine units likely adopt a quinonoid structure upon oxidation, which would make the tetracation spinless.
Reduction of compound 6 is quasireversible, while its oxidation is irreversible. Both reduction and oxidation of compound 7 are irreversible under the applied conditions. Even though the dications of 6 and 7 are extremely stable, and the oxidation of 5 is reversible; the tri- and tetracations of 6 and 7 are, hence, very unstable in solution. Electrochemical redox reactions of benzidine derivatives have previously been reported, with the redox potentials being very solvent-dependent [22, 23].
Final support for the presence of radical species is provided by the detection of EPR signals from 5 (Supplementary Fig. S15). Thus, for the solid material 5, an axial EPR signal with two g values (g| = 2.0040 and g⊥ = 2.0025, respectively) is observed. This signal is similar to the reported EPR signal of single-electron oxidized 3,3′-dimethyl-4,4′-diaminobiphenyl . In a frozen dimethylsulfoxide solution, the EPR signal is broad (g = 2.004) and does not show any hyperfine splittings, indicating spin-exchange interactions between the unpaired electrons of the two closely spaced benzidine units [24, 25]. Further indication of interaction between the two biphenyl units of 5 via π-pairing, i.e., intramolecular formation of π-dimers, is provided by the relative weakness of the EPR signals. The formation of intermolecular diamagnetic π-dimers has, otherwise, been reported for some cation radicals at low temperatures [26, 27]. This fits well with the molecular structure described above.
The temperature dependence of the magnetic susceptibility of 5 was studied over the temperature range 2–150 K at a magnetic field strength of 0.1 T (Supplementary Fig. S15c). The molar susceptibility increases continuously with decreasing temperature in the measured temperature range, indicating a paramagnetic spin-triplet ground state. This spin state is converted into a diamagnetic singlet state at ~ 160 K. Hence, the energy difference between these two spin states must be small, with a rather weak intramolecular spin-exchange interaction. The previously mentioned pairwise intermolecular π-stacking effect is featured in the Curie–Weiss plot (Supplementary Fig. S15d) exhibiting a positive Weiss temperature (\(\varTheta > 0)\), showing the presence of antiferromagnetic intermolecular interaction in the material.
This mechanism is in line with one discussed by Bondarchuk and Minaev for the oxidative coupling of anilines . More generally, it is related to the oxidative dimerization of arylamines to benzidines with Cu2+ or iron oxidants [22, 30, 31]. Furthermore, it also has some resemblance with the oxidative para-coupling of phenols, resulting in 4,4′-dihydroxybiphenyls, also involving radicals [32, 33]. However, the selective metal chelate-directed cyclization that we here propose to be the reason for the formation of the bisbenzidine motif, rather than polymers, in high yield has not been observed before.
Finally, the strikingly different reactivity of Ag+ with N,N′-diphenylpiperazine (4) calls for an explanation. This ligand enables the formation of a five-membered chelate ring, and with an ionic radius of 1.26 Å  Ag+ is expected to bind more strongly to the diazacyclohexane ligand 4 than to the diazacyclooctane ligands 1–3 and their subsequent reaction products, as shown in Scheme 3 [35, 36, 37, 38]. We, therefore, believe steric factors to be crucial, since the cyclization step (1d → 1e, Scheme 3), resulting eventually in the formation of stable diradicals with planar sp2 geometry at all four nitrogens (i.e., in 5, including resonance effects), is not possible for the piperazine backbone. Hence, persistent radical species are not formed from 4.
In conclusion, a selective oxidative cyclization between N,N′-diphenyl-3,7-diazacyclooctane or structurally related bispidines and Ag+ ions provides rapid access to cyclophanes incorporating two benzidine segments. These compounds are obtained as highly persistent dication–diradicals with both intramolecular spin interactions via π-pairing, as well as intermolecular π-pairing in the solid state.
UV–Vis measurements were carried out on a Varian Cary 3 Bio spectrophotometer using 10 or 5 mm quartz cuvettes at r.t. with acetone as solvent. Purification by preparative HPLC was performed on a Gilson 231 system connected to an ACE AQ C18 (10 µm, 100 × 21 mm) column using a gradient of MeCN/H2O with 0.1% TFA, flow rate 10 cm3 min−1, and detection at 254 nm or 760 nm. NMR investigations were carried out on a Varian Unity Inova (1H at 499.94 MHz, 19F at 470.34 MHz, 13C at 125.7 MHz) spectrometer. Chemical shifts are reported in ppm referenced to tetramethylsilane via the residual solvent signal (CDCl3, 1H at 7.26 and 13C at 77 ppm; acetone-d6, 1H at 2.05 and 13C at 39.5 ppm). 19F chemical shifts were referenced to external CF2Br2 (7.0 ppm). Signal assignments were derived from P.E.COSY , gHSQC , gHMBC , gNOESY , ROESY , and TOCSY  spectra. D (diffusion coefficients) were determined from LED–PGSE experiments [45, 46], using z-gradients, acquiring a series of 10–20 spectra for an array of gradient pulse strengths (0–20 gauss/cm). Typically, a relaxation delay of 1 s, 9 ms gradient pulse duration, 100 ms diffusion delay, and 5 ms storage delay were used. The LED–PGSE spectra were evaluated by plotting the square of the gradient strength against the natural logarithm of the signal amplitude, resulting in a straight line with a slope proportional to − D. The actual value for D was obtained by relating this slope to that of a compound with known D, measured under the same conditions. In the present investigation, we have used KF in H2O (D = 1.14 × 10−9 m2 s−1) . Melting points were determined using a Stuart Scientific melting point apparatus SMP10. Commercially available compounds were used without purification. HRMS was acquired using a Thermo Scientific LTQ Orbitrap Velos apparatus in infusion mode. An Autolab PGSTAT302 N potentiostat (Ecochemie, The Netherlands) was used for electrochemical measurements. The analytes were dissolved to 0.50 mM in dry acetonitrile (MeCN) with 0.1 M tetrabutylammonium hexafluorophosphate (TBAHFP) supporting electrolyte. A polished glassy carbon (GC) disk electrode (3.0 mm diameter) was used as working electrode, a Pt wire as counter electrode, and the reference electrode consisted of a Ag0/Ag+ electrode (10 mM AgNO3, 0.1 M TBAHFP, − 0.096 V vs. Fc0/Fc+) that was kept in a separate compartment. The electrolyte was thoroughly degassed with solvent-saturated N2 (g) and kept under N2 (g) atmosphere throughout the measurements. Formal potentials were determined as the average of cyclic voltammetry (CV) oxidation and reduction peak potentials.
The EPR spectra of 5 were recorded on a Bruker EMXmicro spectrometer using an ER 4119HS resonator (solid sample) and a Bruker E500-ELEXSYS spectrometer using an ER 4122SHQE resonator equipped with ESR900 cryostat and an Oxford ITC503 temperature controller (frozen solution sample).
Magnetic susceptibility data of 5 in a powder sample were measured on a SQUID magnetometer (Quantum Design MPMSXL-5) as a function of temperature between 2 and 160 K at the magnetic field of 0.1 T. Diamagnetic corrections were determined from Pascal’s constants and background subtrated in RSO-operating mode.
Synthesis of N,N′-diphenyl-1,5-diazacyclooctane (1) was carried out according to the literature procedures with some modifications  (see the Supplementary data for details). N,N′-diphenyl-3,7-diazabicyclo[3.3.1]nonane (2) , N,N′-diphenyl-1,5-dicarbomethoxybispidinone (3) , and N,N′-diphenylpiperazine (4)  were prepared according to the literature procedures.
1,8-Diaza-4,11-diazaniumyl-2,3,9,10(1,4)-tetrabenzenatricyclo[18.104.22.168,8]eicosaphane bis(tetrafluoroborate) (5, C36H40N4)
N,N′-Diphenyl-1,5-diazacyclooctane (1, 195 mg, 0.73 mmol) in 4 cm3 acetone was added to a solution of 0.44 g AgBF4 (1.15 mmol, 3.1 eq.) in 4 cm3 acetone. Directly upon mixing the combined solutions turned to an intense dark green colour and a silver mirror started to form on the inside of the vial within seconds. After standing for 48 h (r.t., dark), purification of the reaction mixture was possible by preparative HPLC achieving excellent separation and allowing isolation of the product (Fig. S7). Evaporation of solvents yielded compound 5 as a dark green solid (224 mg, 0.31 mmol, 87%). It should be noted that 5 was stable at r.t. both as a solid as well as in solution for several months. M.p.: 208–210 °C; 1H NMR (500 MHz, acetone-d6, 25 °C): δ = 6.26 (broad, w = 367.3 Hz) ppm; 19F NMR (470.34 MHz, acetone-d6, 25 °C): δ = − 147.0 ppm; UV/Vis (acetone, r.t.): λ = 325, 403, 760 nm; HRMS: [M]2+ calcd. for C36H40N4 m/z = 264.1621, found 264.1593.
1,4,8,11-Tetraaza-2,3,9,10(1,4)-tetrabenzenatricyclo[22.214.171.124,8]eicosaphane (8, C36H40N4)
Dication–diradical 5 (2 mg, 0.0029 mmol) was dissolved in 0.5 cm3 acetone and 0.5 cm3 of a saturated solution of Na2SO3 in H2O was added dropwise during stirring until the dark green solution turned pale brown. Extraction with CHCl3 and evaporation of solvents afforded the bis(benzidino)phane 8 as an oily beige solid (2 mg, quant). 1H NMR (500 MHz, CDCl3/D2O/acetone-d6 1:1:1, 25 °C): δ = 6.62 (d, J = 8.6 Hz, 8H, Ar), 6.05 (d, J = 8.6 Hz, 8H, Ar), 3.78 (dm, J = 15.2 Hz, 8H, CH2), 3.13–2.84 (m, 16 H, CH2) ppm; UV/Vis (acetone, r.t.): λ = 325 nm; HRMS: [M+H]+ calcd. for C36H40N4 m/z = 529.3315, found 529.3321.
1,8-Diaza-4,11-diazaniumyl-2,3,9,10(1,4)-tetrabenzenatricyclo[126.96.36.199,8.16,19.113,16]docosaphane bis(tetrafluoroborate) (6, C38H40BF4N4)
3,7-Diphenyl-3,7-diazabicyclo[3.3.1]nonane 2 (50 mg, 0.18 mmol) in 1 cm3 acetone was added to a solution of 105 mg AgBF4 (0.54 mmol, 3.1 eq.) in 1 cm3 acetone. Directly upon mixing the combined solutions turned into an intense dark green colour and a silver mirror started to form on the inside of the vial within minutes. After standing for 48 h (r.t., dark), purification of the reaction mixture with preparative HPLC afforded the isolation of the product 6 that, after evaporation of solvents, was obtained as a dark green solid (48 mg, 0.07 mmol, 73%). M.p.: 120 °C (dec.); 1H NMR (500 MHz, acetone-d6, 25 °C): δ = 3.11 (broad, w = 182.1 Hz) ppm; 19F NMR (470.34 MHz, acetone-d6, 25 °C): δ = − 147.1 ppm; UV/Vis (acetone, r.t.): λ = 223, 323, 394, 751 nm; HRMS: [M+BF4]+ calcd. for C38H40BF4N4 m/z = 639.3271, found 639.3264.
6,13,16,19-Tetracarbomethoxy-1,8-diaza-4,11-diazaniumyl-2,3,9,10(1,4)-tetrabenzenatricyclo[188.8.131.52,8.16,19.113,16]docosaphane-21,22-dione bis(tetrafluoroborate) (7, C46H47N4O10)
3,7-Diphenyl-1,5-dicarbomethoxybispidinone 3 (50 mg, 0.12 mmol) in 1 cm3 acetone was added to a solution of 71.5 mg AgBF4 (0.37 mmol, 3.1 eq.) in 1 cm3 acetone. Directly upon mixing the combined solutions turned to a dark brown that within hours shifted into deep green. After standing (r.t., dark) for 48 h, a silver flake had formed on the inside of the vial. The flake could be removed from the flask as a single piece of Ag(s) (see Supplementary for image, Fig. S8). HPLC analysis of the reaction mixture proved a complex mixture and the product 7 could not be fully isolated. 1H NMR (500 MHz, acetone-d6, 25 °C, crude mixture): δ = 4.70 (broad, w = 115.5 Hz) ppm; HRMS: [M +3H]+ calcd. for C46H47N4O10 m/z = 815.3292, found 815.3279; analysis (calcd., found for Ag flake): Ag (100.0, 100.0); UV/Vis (acetone, r.t., crude): λ = 332, 389, 746 nm.
X-ray crystallography data
CCDC 1850267 and CCDC 1850282 contain the crystallographic data for compound 5. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
This work was supported by grants from The Swedish Research Council (Vetenskapsrådet). We are grateful to Bo Ek for recording the HRMS spectra.
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