Short communication Synthesis and Characterization of BINOL Based Axially Chiral Nitronyl Nitroxide Radicals Haibo Wang,1 Peng Gao,1 Linlin Jing,2 Xiaoli Sun1* and Ru Jiang1* 1 Department of Chemistry, School of Pharmacy, Fourth Military Medical University, Xi'an, China 2 Department of Pharmacy, Lanzhou General Hospital, Lanzhou Command, Lanzhou 730050, China * Corresponding author: E-mail: jiang_ru@yahoo.cn, xiaoli_sun@yahoo.cn Tel: +86-029-84776775; Fax: +86-029-84776945 Received: 11-05-2011 Abstract Four novel axially chiral nitronyl nitroxides derived from S- or _R-1,l'-bi-2-naphthol were synthesized and their crystal structures discussed. Circular dichroism spectra of these compounds showed significant Cotton effects between 200 and 400 nm, and also confirmed the optical activity of these enantiomers. The magnetic properties of the two pairs of nitronyl nitroxide radicals were characterized by magnetic susceptibility measurements. The results showed that in these four radicals exist antiferromagnetic interactions in all cases at low temperatures. Keywords: Nitronyl nitroxide radical; chirality; magnetic properties; organic ferromagnet 1. Introduction During the two last decades, magnetic materials based on purely organic molecules have attracted increasing interest, as their properties can be subtly modified by an adequate selection of substituents.1 Since Kinoshita's discovery of the first purely organic ferromagnet, different arrangements of spin carriers have been achieved by several strategies, among which the purely organic and the metal-organic approaches based on nitronyl nitroxide free radicals have proven particularly rewarding.2-5 In 1997 Rikken and Raupach discovered a small chiral paramagnetic material magnetochiral dichroism (MChD) in a chi-ral paramagnetic material. This combination of magnetic properties and optical activity has attracted increasing attention because the potential magneto-optical effects of the organic spin carriers, such as nitroxides, are well suited as potential precursors of such structures.6 Enantiopure nitroxides would afford materials crystallizing in chiral space groups and would give opportunities to characterize new exchange pathways. However, at there are few reports on pure chiral nitronyl nitroxides.7-14 Herein, we have designed and synthesized a series of enantiomerical-ly pure axially chiral nitronyl nitroxides (Figure 1). Their structure, magnetic properties, and optical characterization were investigated. Figure 1. Structures of synthesized chiral nitronyl nitroxides. 2. Experimental 2. 1. General Remarks All experiments sensitive to moisture or air were carried out in a nitrogen atmosphere. Commercial rea- gents were used as received without further purification unless otherwise noted. THF was distilled under N2 from Na/benzophenone, DMF was distilled from CaH2, and CH2Cl2 was redistilled before use. Compounds 5-7 were prepared according to reported procedures from commercially available (R)-BINOL or (S)-BINOL. The chiral nitronyl nitroxides (R)-1/(S)-1 and (R)-2/(S)-2 were prepared according to Ullman's method.15 Melting points were measured with an X-5 precision micro-melting point apparatus and were uncorrected. IR was collected on an FTIR-8400S spectrophotometer. 1H and 13C NMR were recorded on a Bruker AV-500 spectrometer in CDCl3 with TMS as an internal standard. Electrospray ionization (ESI) HRMS analyses were obtained using Bio TOF IIIQ mass-spectrograph or Varian 7.0T ESI-FTICR-MS. Elemental analyses were performed on a VarioEL III Elemental Analyzer. 2. 2. Synthesis The synthetic route to chiral compounds is outlined in Scheme 1. Compounds 5-7 were prepared according to the reported literature.16 For the synthesis of new compounds, see Supporting Information. 2. 3. X-ray Crystallography Crystal structure determinations were carried out on a Bruker SMART 1000CCD system (Mo/Ka, X = 0.71073 nm, graphite monochromator). The data were processed by use of the SNINT3 data reduction software, and the structure was solved with the aid of the SHELXTL-97 software package. Anisotropic thermal factors were ap- plied for non-hydrogen atoms, and hydrogen atoms with isotropic thermal factors were refined with Full-matrix least-squares using the F2 refinement method. 2. 4. Physical Measurements Circular dichroism spectra were recorded with a JASCO-715 spectropolarimeter, and were processed by use of the associated software. ESR spectra were recorded in solution in DMF with an EMX-10/12 EPR spectrometer. Emission spectra were recorded on a Hitachi F-2500 fluorescence spectropho-tometer. The magnetic susceptibility of the chiral radicals was measured for randomly oriented polycrystalline samples on a Quantum Design SQUID magnetometer MPMS-XL with an applied magnetic field of 0.1 T in the temperature range of 1.9-300K. 3. Results and Discussion 3. 1. Synthesis of Compounds The synthetic route to chiral compounds is outlined in Scheme 1. The commercially available (R)-1,1'-bi-2,2'-naphthol (BINOL) was reacted with bromoethane to give (R)-5 in a high yield (98%). Selective bromination of (R)-5 also gave (R)-6 in good yield, which is purified by recrys-tallization. Lithiated (R)-6 was reacted with DMF to give (R)-7. Effects of the reaction temperature and water content were significant for the yield of (R)-7. Very little water can lead to a low yield of (R)-7. The title radical compound (R)-1 was obtained through condensation with 2,3-dihy- Scheme 1. Synthesis of chiral nitronyl nitroxides. droxylammonium-2,3-dimethylbutane, and the subsequent oxidation of the adducts with sodium periodate, following Ullman's classic procedure.15 (R)-2 can be obtained from (R)-6 using multistep synthesis. The enantiomers of these compounds were obtained in the same way. The nitronyl nitroxide (R)/(S)-1 and (R)/(S)-2 are both dark blue solids. Crystals suitable for X-ray diffraction in the form of small needles were obtained through slow evaporation from a dichloromethane/hexane solution. 3. 2. X-ray Structure Determination The molecular structures of (R)-1 were shown in Figure 2 and Table 1. The enantiopure radical (R)-1 crystallizes in the tetragonal P4(3)2(1)2 space group (Table 1), in which the imidazolidine heterocycle moiety was directly bound to a great conjugate n bond system. All atoms in the naphthyl ring are almost coplanar. Steric hindrance of two ethoxy groups and two O-N-C-N-O groups lead to a large dihedral angle between two naphthyl rings (86.09), and two planes of naphthyl moiety in same molecule are almost vertical to each other, producing axial chirality. Two vertical moieties are likely to weaken the intramolecular exchange interaction through the p-n conjugation in (R)-1. The dihedral angle between the N-C-N unit in the imidazolyl ring and the naphthyl ring is 38.434. The torsion angle of C(15)-N(2)-C(13)-N(1) and N(1)-C(14)-C(15)-N(2) are -5.4(2) and -20.65(18), respectively, which indicates that the imidazolyl ring is twisted. The distance between C(14)-C(15) is 1.554(3), which is slightly lager compared to 1.543 for the C-C bond length in the cy-clopentane. The N(1)-C(14) bond length and N(2)-C(15) bond length are 1.489(3) and 1.503(3), respectively. The distances between C(13) and its neighboring N atoms (N1 and N2) are 1.340(2) and 1.346(3), which are shorter than those of N(1)-C(14) and N(2)-C(15). The molecules are linked into a two-dimensional network by the intermolecular van der Waals. The data of lengths, angles and dihedral angles in (S)-1 are consistent with the data of (R)-1. Table 1. X-ray crystallographic data of chiral nitronyl nitroxides. Compound (R)-1 (R)-2 Formula C38H44N4O6 C31H33N2O4 M 652.77 497.59 Crystal system Tetragonal Orthorhombic Space group P4(3)2(1)2 P2(1)2(1)2(1) a [Ä] 14.0950(14) 9.2308 (7) b [Ä] 14.0950(14) 12.1004 (10) c [Ä] 17.883(3) 24.048 (2) a=ß=Y 90 deg 90 deg V [Ä3] 3552.8(7) 2686.0(4) Z 4 4 Calculate density 1.220 1.230 R(I) 0.0374 0.0764 Rw(I) 0.1051 0.1860 The molecular structure of (R)-2 is shown in Figure 2 and Table 1. The enantiopure radical (R)-2 crystallizes in the orthorhombic P2(1)2(1)2(1) space group (Table 1). In (R)-2 is only one imidazolidine heterocycle moiety bound to a naphthyl ring. As shown in Figure 2, the torsion angle between the naphthyl ring and the O-N-C-N-O group is 20.9 in (R)-2, relatively smaller than that of (R)-1. The dihedral angle between the two naphthyl rings is 79.70, and is also smaller than that of (R)-1, which can lead to a stronger intramolecular exchange interaction through the n-conjugation. The results show that the number of nitronyl nitroxide moiety not only affects the torsion angles between the naphthyl ring and the O-N-C-N-O group, but also affects the dihedral angles between the two naphthyl rings in a 1,1'-binaphthalene moiety. 3. 3. CD Spectrum The CD spectrum of (S)-1 exhibits a negative Cotton effect at Amax = 230, 295 and 330 nm, and a positive dichroic signal centered at Amax = 265 nm, while (R)-1 Figure 2. ORTEP views of (R)-1 and (R)-2 at the 50% probability level. The hydrogen atoms are omitted. Figure 3. CD spectra of two pairs of chiral nitronyl nitroxides in CH2Cl2. shows Cotton effects of the opposite sign at the same wavelengths (Figure 3). The solution state CD spectra of the two enantiomers reveals a broad Cotton effect of moderate intensity centered at 330 nm, followed by an intense exciton coupled effect at approximately 265 nm, which coincides with the absorption maximum for the n-n* transition. There are no detectable Cotton effects in the region corresponding to the n-n* transition at 640 nm. It should be pointed out that the magnitudes of the Cotton effects are much greater than those observed for the chiral radicals prepared to date in which the stereogenic center is located on the phenyl substituent at the 2-position of the im-idazolyl ring. 3. 4. Magnetic Susceptibility Data Compounds (R)-1 and (S)-1 show the same magnetic behaviors because they are a pair of enantiomers. The temperature dependence of xMT values of (R)-1 and (S)-1 is displayed in Figure 4 in the range 3-300 K at 2,000 Oe. The xmT value for the (R)-1 radical at room temperature is 0.740 cm3 mol-1 K, which is close to the expected value for an uncorrelated S = 1/2 spin (0.75 cm3 mol-1 K), as shown in Figure 4. As the temperature decreases, xMT gradually decreases, which indicates the presence of intramolecular antiferromagnetic interactions in crystals. When the temperature is below 20 K, the xMT value decreases dramatically. Upon further cooling, the xMT value abruptly decreases to a minimum value of 0.12 cm3 mol-1 K at 1.9 K. This is confirmed with the fitting results according to the Curie-Weiss law, xm = C/T - 6. The Curie constant is C = 0.345 cm3 mol1 K, and the Weiss constant is 6 = -0.46 K. The negative Weiss constant may be ascribed to the intermolecular antiferromagnetic interaction. The data were therefore simulated applying the Heisenberg-Dirac-Van Vleck hamiltonian H = -2JSR1SR2, with the expression for the magnetic susceptibility,17 Z s i = f 2 Ng2ß2 kB (T-0)[ 3 + exp(-2 J / knT)} (1) with N, g, P, kB, f and J having their usual meanings in equations: g is Lande constants, kB is Boltzmann constant, P is Bohr magneton, N is Avogadro's constant, f is modifying factor, and J is coupling constant. A least-square fit to the magnetic susceptibility data gives the values J/kB= -0.65 K, g = 1.90, 6 = -1.53 K, and f = 0.95. The temperature dependence of xMT and xM-1 for (R)-2 in the range 3-300 K at 2,000 Oe is shown in Figure 5. The xMT value for the (R)-2 radical at room temperature is 0.730 cm3 mol-1 K, which is slightly less than that of S = 1/2 spins system (0.75 cm3 mol-1 K). When the temperature is at 2 K, the xMT value decreases dramatically to a minimum value of 0.50 cm3 mol-1 K. This is confirmed with the fitting results by the Curie-Weiss law. The Curie constant is C = 0.381 cm3 mol1 K, and the Weiss constant is 6 = -0.53 K. According to the equation (1) the best fit- Figure 4. Temperature dependence of xMT and xM 1 for (R)-1 and their corresponding theoretical curves (solid lines). T/K Figure 5. Temperature dependence of xMT and xM-1 f°r (R)-2 and their corresponding theoretical curves (solid lines). ting for the data gives J/kB= -0.59 K, g = 2, f = 0.95, and 0 = -1.28 K. 4. Conclusions In summary, four enantiomorphous chiral nitronyl nitroxide radicals were synthesized and the molecular structures of (R)-/(S)-1 and (R)-/(S)-2 were discussed. The circular dichroism (CD) spectra confirms the optical activity and enantiomeric nature of these chiral radicals. They also showed antiferromagnetic interactions at low temperatures. Further investigation of the magnetic properties of metal complexes of these chiral nitronyl nitroxide radicals is underway. 5. Acknowledgments This work was financially supported by the NSFC (81001398, 20972189, 30901883). 6. Appendix A. Supplementary data CCDC 807907, 807908, 807909, 807910 contain the supplementary crystallographic data for (R)-1, (S)-1, (R)-2, and (S)-2. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223336-033; or e-mail: deposit@ccdc.cam.ac.uk. 7. References 1.0. Kahn, Molecular Magnetism, VCH Publishers Inc, New-York, Weinheim Cambridge, 1993. 2. M. Tamura, Y. Nakazawa, D. Shioni, K. Nazawa, Y. Hoso-koshi, M. Ishikawa, M. Takahashi, M. Kinoshita, Chem. Phys. Lett., 1991, 186, 401-405. 3. V. I. Ovcharenko, R. Z. Sagdeev, Russ. Chem. Rev., 1999, 68, 345-363. 4. A. Caneschi, D. Gatteschi, R. Sessoli, P. Rey, Acc. Chem. Res, 1989, 22, 392-398. 5. A. Caneschi, D. Gatteschi, P. Rey, Progr. Inorg. Chem., 1991, 39, 331-429. 6. G. L. J. A. Rikken, E. Raupach, Nature, 1997, 390, 493-494. 7. S. Shimono, R. Tamura, N. Ikuma, T. Takimoto, N. Kawame, O. Tamada, N. Sakai, H. Matsuura, J. Yamauchi, J. Org. Chem., 2004, 69, 475-481. 8. H. Matsuura, R. Tamura, J. Yamauchi, Synthetic Metals, 2003, 133-134, 605-607. 9. M. Minguet, D. B. Amabilino, J. Cirujeda, K. Wurst, I. Mata, E. Molins, J. J. Novoa, J. Veciana, Chem. Eur. J, 2002, 6, 2350-2361. 10. M. Minguet, D. Luneau, E. L'Hotel, V. Villar, C. Paulsen, D. B. Amabilino, J. Veciana, Angew. Chem. Int. Ed., 2002, 41, 586-589. 11. J. V. Gancedo, M. Minguet, D. Luneau, D. B. Amabilino, J. Veciana, J. Phys. Chem. Solids., 2004, 65, 723-726. 12. M. Minguet , D. Luneau , C. Paulsen, E. Lhotel, A. Gorski, J. Waluk, D. B. Amabilino, J. Veciana, Polyhedron, 2003, 22, 349-2354. 13. C. Hirel, J. Pecaut, S. Choua, P. Turek, D. B. Amabilino, J. Veciana, P. Rey, Eur. J. Org. Chem, 2005, 2, 348-359. 14. X. Y. Qin, G. Xiong, Y. G. Sun, M. Y. Guo, Y. Ma, Q. F. Wang, P. Liu, P. Gao, X. L. Sun, J. Mol. Struct, 2011, 989, 10-19. 15. E. F. Ullman, J. H. Osiecki, G. B.Boocock, R. Darcy, J. Am. Chem. Soc., 1972, 94, 7049-7059. 16. C. Dong, J. L. Zhang, W. Z. Zheng, L. F. Zhang, Z. L. Yu, M. C. K. Choi, A. S. C. Chan, Tetrahedron Asymm, 2000, 11, 2449-2454. 17. M. H. Wang, PhD dissertationh, Graduate University of Chinese Academy of Sciences, Beijing, 2005. Povzetek V prispevku je predstavljena sinteza štirih novih aksialno kiralnih nitronil nitroksidov, pripravljenih iz S- oziroma ^-1,1'-bi-2-naftola, in analiza njihovih kristalnih struktur. CD spektri teh spojin kažejo precejšen Cottonov efekt med 200 in 400 nm in potrjujejo optično aktivnost vseh enantiomer. Magnetne lastnosti obeh parov nitronil nitroksidnih radikalov so bile ugotovljene s pomočjo meritev magnetne susceptibilnosti. Rezultati kažejo, ta v vseh štirih spojinah obstajajo antiferomagnetne interakcije pri nizkih temepaturah. Electronic Supporting Information 1. General remarks All experiments sensitive to moisture or air were carried out in a nitrogen atmosphere. Commercial reagents were used as received without further purification unless otherwise noted. THF was distilled under N2 from Na/benzophenone, DMF was distilled from CaH2, and CH2Cl2 was redistilled before use. Compounds 5-7 were prepared according to reported procedures from commercially available (R)-BINOL or (S)-BINOL.1 The chiral ni-tronyl nitroxides (R)-1/(S)-1 and (R)-2/(S)-2 were prepared according to Ullman's method.2 Melting points were measured with an X-5 precision micro-melting point apparatus and were uncorrected. IR was collected on an FTIR-8400S spectrophotometer. 1H and 13C NMR were recorded on a Bruker AV-500 spectrometer in CDCl3 with TMS as an internal standard. Elec-trospray ionization (ESI) HRMS analyses were obtained using Bio TOF IIIQ mass-spectrograph or Varian 7.0T ESI-FTICR-MS. Elemental analyses were performed on a VarioEL III Elemental Analyzer. ESR spectra were recorded in solution of the compound in DMF with a EMX-10/12 EPR spectrometer. Emission spectra were recorded on a Hitachi F-2500 fluorescence spectrophotometer. Crystal structure determinations were carried out with the aid of a Bruker SMART 1000CCD system (Mo/Ka, X = 0.71073 nm, graphite monochromator). The data were processed by use of the SNINTP3P data reduction software, the structure was solved with the aid of the SHELXTL-97P4P software package. Anisotropic thermal factors are applied for non-hydrogen atoms. Hydrogen atoms with isotropic thermal factors are refined with Full-matrix least-squares on FP2P refinement method. The magnetic susceptibility of the chiral radicals we obtained is measured for randomly oriented polycrystalli-ne samples on a Quantum Design SQUID magnetometer MPMS-XL with an applied magnetic field of 0.1 T in the temperature range of 1.9 -300 K. Cirular dichroism spectra were recorded with a JAS-CO-715 spectropolarimeter, and were processed by use of the associated software. 2. Synthesis of Chiral Nitronyl Nitroxides 2. 1. Synthesis of Compound or (S)-8 To a stirred sotution of (R)-6 or (S)-6 (2.0 g, 4.0 mmol) in 30mL dry THF under NB2B atmosphere was added n-BuLi (2.75 mL, 4.4 mmol, 1.6 M in hexane) over 30 min at -78 °C. The mixture was stirred for 2 h at the same temperature. Then saturated aqueous NHB4BCl was added to quench the reaction. The reaction mixture was extracted with CHB2BClB2B several times. The combined organic layer was washed subsequently with water and brine and then dried over MgSOB4B. Evaporation of solvent gave the crude product, which was further purified by flash >OH Mal OH CH3CH2Br (R) - BINOL 'OCsH5 Br, iOC2H5 CH2CI (.R)-2 Schema: Synthesis of Chiral Nitronyl Nitroxides