Mendeleev Communications Electronic Version, Issue 5, 2001 1 Metal complex with the enaminoketone derivative of 2-imidazoline nitroxide Pavel A. Petrov,a Sergei V. Fokin,a Galina V. Romanenko,b Yuri G. Shvedenkov,a Vladimir A. Reznikova and Victor I. Ovcharenko*b a Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russian Federation b International Tomography Centre, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russian Federation.Fax: +7 3832 33 1399; e-mail: ovchar@tomo.nsc.ru 10.1070/MC2001v011n05ABEH001472 Functional derivatives of iminonitroxides were prepared by introducing a functional group into the side chain of 1-hydroxy-2- methyl-2-imidazoline; a K+ salt and a Cu2+ bischelate with the first enaminoketone derivative of 2-iminonitroxide were synthesised and structurally characterised. Heterospin systems based on metal complexes with 2-imidazoline nitroxides are widely used in molecular magnet design.1 However, the syntheses of nitronyl nitroxides 1 and iminonitroxides 2 containing functional groups R (Scheme 1), which are favourable for metal complex formation, were confined to only one synthetic procedure.This method, which was proposed by Ullman, involves the condensation of dihydroxyamine 3 with aldehydes or their synthetic equivalents and the subsequent oxidation of dihydroxyimidazolidines 4. Iminonitroxides 2 were generated by the reduction of 1.2 In this work, a donor group R (enaminoketone fragment) was introduced at the 2-position of a heterocyclic ring using another approach, the modification of 1-hydroxy-2- methyl-2-imidazoline (5, R = Me).First, we found an effective approach to the synthesis of 5. The process looks like the ‘thermal dehydration’ of 4 to 5 (Scheme 1). It proceeds with a high yield in boiling heptane (or toluene at 100 °C).† We found that the dehydration was not accelerated in the presence of para-toluenesulfonic acid.The conversion of 4 to 5 by thermal dehydration does not proceed in an inert atmosphere. The presence of atmospheric oxygen is indispensable. Thermal dehydration of 4 is a very effective onepot synthesis of 5. This easy route to 5 permits one to use 2,4,4,5,5-pentamethyl- 1-hydroxy-2-imidazoline (5, R = Me) as a starting compound for the syntheses of persistent enaminoketones of 2-imidazoline nitroxide.The reactions of 5 (R = Me) with esters in the presence of lithium diisopropylamide give enaminoketones 6 (Scheme 2). The introduction of the nitrile substituent into enaminoketones 6 (R1 = Ph, CF3) and further oxidation led to relatively persistent nitroxides 7 (MS, m/z: 276 [M+] R1 = CF3; m/z: 284 [M+] R1 = Ph). Nitroxide analogues of 7 with hydrogen substituted for the nitrile group are unstable and quickly decompose in solution.Nitroxide 7 (R1 = CF3) turned out to be the most long-living. However, we converted it every time to potassium salt 8 persistent under normal conditions. Single crystals of potassium salt 8‡ and Cu2+ complex 9§ with nitroxide 7 (R1 = CF3) were obtained, whose structures are shown in Figures 1 and 2, respectively.Synthesis¶ of 9 is actually a logical end of the chain of transformations presented in Scheme 2. NHOH NHOH RCHO N N OH R OH – H2O N N R OH 4 3 5 N N O R O 1 N N R O 2 Scheme 1 Scheme 2 Reagents and conditions: i, LDA, R1CO2Et, Et2O, 0 ºC; ii, NCS, CHCl3, room temperature; iii, NaCN, DMSO, room temperature; iv, PbO2, CHCl3. N N OH 5 N N OH 6 R1 O ii–iv i N N O 7 R1 O CN H H N N O 8 R1 = CF3, M = K R1 O CN 9 R1 = CF3, M = Cu/2 M R1 = CF3, Ph, CO2Et R1 = CF3, Ph † A typical procedure includes the boiling of a suspension of 1 g of 4 in 30–40 ml of heptane for 10–12 h.The precipitate of 1-hydroxy-2- imidazoline 5 was filtered off (85% yield for R = Me, 70% for R = Et and 50% for R = Ph) after recrystallization from hexane–ethyl acetate. 5 (R = Me): mp 104–106 °C. 1H NMR ([2H6]DMSO) d: 1.08 (s, 6H), 1.09 (s, 6H, 4,5-Me2), 1.93 (s, 3H, 2-Me), 8.08 (br. s, OH). 13C NMR ([2H6]DMSO) d: 13.5 (2-Me), 18.6, 23.4 (4,5-Me2), 65.1, 69.8 (C-4, C-5), 162.1 (C-2). IR (KBr, n/cm–1): 3160, 2900–2600, 1616. Found (%): C, 61.5; H, 10.5; N, 17.9. Calc. for C8H16N2O (%): C, 61.5; H, 10.3; N, 17.9. 5 (R = Et): mp 121–123 °C. 1HNMR (CD3OD) d: 1.15 (t, 3H, CH2Me), 1.21 (s, 6H), 1.24 (s, 6H, 4,5-Me2), 2.45 (q, 2H, CH2Me).IR (KBr, n/cm–1): 3110, 2900–2600, 1613. Found (%): C, 62.9; H, 11.1; N, 16.3. Calc. for C9H18N2O (%): C, 63.5; H, 10.7; N, 16.5. 5 (R = Ph): mp 190–191 °C. 1H NMR (CDCl3) d: 1.36 (s, 6H), 1.43 (s, 6H, 4,5-Me2), 7.25, 7.49 (2m, 5H, Ph), 8.33 (br. s, 1H, OH). IR (KBr, n/cm–1): 3110, 2900–2600, 1611, 1591, 1573.Found (%): C, 71.3; H, 8.2; N, 12.6. Calc. for C13H18N2O (%): C, 71.5; H, 8.3; N, 12.8. Hydroxylamine precursors of 7 (R1 = Ph): mp 213–214 °C. 1H NMR ([2H6]DMSO–CD3COCD3) d: 1.18 (s, 6H), 1.29 (s, 6H, 4,5-Me2), 7.39– 7.71 (m, 5H, Ph), 9.6 (br. s, 1H, NH), 10.1 (s, 1H, OH). 13C NMR (CD3OD) d: 18.5, 23.1 (4,5-Me2), 62.6 (C-4), 71.6 (C-5), 121.7 (CºN), 128.7, 128.9, 131.6, 141.5 (Ph), 166.3 (C-2), 194.0 (C=O).IR (KBr, n/cm–1): 3200–2800, 2209 (CºN), 1600, 1577, 1534. Found (%): C, 67.3; H, 6.8; N, 14.6. Calc. for C16H19N3O2 (%): C, 67.4; H, 6.7; N, 14.7. (R1 = CF3): mp 189–191 °C. 1HNMR ([2H6]DMSO) d: 1.11 (s, 6H), 1.21 (s, 6H, 4,5-Me2), 9.30 (s, NH), 10.4 (s, OH). 13C NMR ([2H6]DMSO) d: 18.3, 22.2 (4,5-Me2), 61.9 (C-4), 63.6 (=C–CN), 70.3 (C-5), 115.8 (CºN), 117.2 (q, CF3, JC–F 291 Hz), 162.8 (C-2), 173.8 (q, C=O, JC–F 32 Hz).IR (KBr, n/cm–1): 3400–3200, 2218 (CºN), 1620, 1547. Found (%): C, 47.7; H, 4.5; N, 14.8. Calc. for C11H14N3O2F3 (%): C 47.7; H, 5.1; N, 15.2.Mendeleev Communications Electronic Version, Issue 5, 2001 2 The structure of 8 is ionic. The distances between the paramagnetic centres in 8 are at least 6.71 A, leading to constant meff (1.68 B.M.) in the temperature range from 300 to 10 K.In complex 9, the distorted octahedral environment of the central atom is formed by the O and N atoms of the two deprotonated enaminoketone ligands and by the N atoms of acetonitrile, and the nitrile group of the neighbouring bis-chelate molecule, leading to formation of polymer chains.The temperature dependence of the magnetic susceptibility of 9 is presented in Figure 3. It is adequately approximated by a cluster model with the parameters g = 2.0, J = 90 cm.1 and nJ' = .0.3 cm.1. The J value is the highest positive value of the intramolecular exchange interaction energy among the known copper bis-chelates with stable nitroxides. This value points to the presence of highly effective exchange clusters inside the bis-chelate fragments.Thus, a convenient route to a series of 4,4,5,5-tetramethyl-1- hydroxy-2R-2-imidazolines (5, R = Me, Et, Ph) has been found. Derivative 5 (R = Me) may be used as a substrate for syntheses of persistent spin-labeled enaminoketones (7, R1 = CF3, Ph). The first metal complex with the enaminoketone derivative of 2-iminonitroxide 9 has been isolated.A transition from metal complexes with spin-labeled 3-imidazoline enaminoketones, characterised by intramolecular exchange interaction energies of about 5.15 cm.1, to the complex with 2-imidazoline analogue allowed us to achieve noticeably higher intramolecular exchange interaction energies between the unpaired electrons of paramagnetic centres (90 cm.1).Studies are currently under way to synthesise other metal complexes with the enaminoketone derivatives of 2-imidazoline nitroxide and to investigate their structure and magnetic properties. This work was supported by CRDF (grant REC-008), Russian Foundation for Basic Research (grant nos. 00-03-32987 and 00-03-04006) and the ¡®Integration¡� Foundation. ¢Ô Crystal data for 8: C11H12F3KN3O2, M = 314.34, monoclinic, a = = 11.068(2) A, b = 9.203(2) A, c = 14.177(3) A, b = 92.19(3)¡Æ, V = = 1443.0(5) A3, T = 293 K, space group P21/c (no. 14), Z = 4, dcalc = = 1.447 g cm.3, m(MoK¥á) = 0.405 mm.1. 2194 Ihk(2012 unique Ihkl, Rint = 0.1104) were measured on a Bruker AXS P4 four-circle automatic diffractometer (lMoK¥á, graphite monochromator, q/2q-scan, 2.64 < q < < 24.98¡Æ).The structure was solved using the SIR97 program and refined by the full-matrix least-squares technique in an anisotropic approximation for all non-hydrogen atoms. All hydrogen atoms were located in a difference Fourier map and then refined in an isotropic approximation. The final R indexes are: R1 = 0.0542, wR2 = 0.1006 for 2012 unique Ihkl > 2s(I), GOOF = 0.664.¡× Crystal data for 9: C24H27CuF6N7O4, M = 655.07, orthorhombic, a = = 14.045(2) A, b = 12.342(2) A, c = 17.259(3) A, V = 2991.7(8) A3, T = = 293 K, space group Pca21 (no. 29), Z = 4, dcalc = 1.454 g cm.3, m(MoK¥á) = 0.809 mm.1. 2723 Ihkl (2723 unique Ihkl) were measured on a Bruker AXS P4 four-circle automated diffractometer (lMoK¥á, graphite monochromator, q/2q-scan, 2.36 < q < 24.99¡Æ, empirical absorption correction). The structure was solved by the SIR97 program and refined by the full-matrix least-square technique in an anisotropic approximation for all non-hydrogen atoms.Positions of all hydrogen atoms were located in a difference Fourier map and than refined in an isotropic approximation. The final R indexes for 406 refined parameters are: R1 = 0.0576, wR2 = = 0.1427 for Ihkl > 2s(I), GOOF = 1.024.All calculations were carried out using the SHELX97 program. Atomic coordinates, bond lengths, bond angles and thermal parameters have been deposited at the Cambridge Crystallographic Data Centre (CCDC). For details, see ¡®Notice to Authors¡�, Mendeleev Commun., Issue 1, 2001. Any request to the CCDC for data should quote the full literature citation and the reference number 1135/98.¢Ò For the synthesis of 8, a solution of KOH (4.0 mmol) in MeOH (5 ml) was added to the solution of 7 (R1 = CF3) (1 g, 3.6 mmol) in ethyl acetate (100 ml) with stirring. Salt 8 was precipitated from the reaction mixture by adding toluene (50% yield). Single crystals were grown by slow diffusion of benzene into an ethyl acetate solution of 8.To prepare 9, a mixture of Cu(NO3)2(H2O)3 (39 mg, 0.16 mmol) and 8 (100 mg, 0.32 mmol) was dissolved in 10 ml of dry acetonitrile, and the solution was allowed to stand at .10 ¡ÆC. After 2 days, the KNO3 precipitate was filtered off; after one more day, dark red crystals of the complex were isolated (yield 45%). 8: mp 257.262 ¡ÆC (decomp.).IR (KBr, n/cm.1): 2190 (C��N), 1603, 1553. Found (%): C, 41.8; H, 3.9; N, 13.1. Calc. for C11H12N3O2F3K (%): C, 42.0; C, 3.9; N, 13.4. 9: mp 176.179 ¡ÆC (decomp.). IR (KBr, n/cm.1): 2220 (C��N), 1588, 1523. Found (%): C, 43.6; C, 4.0; N, 14.8. Calc. for C24H27N7O4F6Cu (%): C, 44.0; H, 4.2; N, 15.0. Figure 1 Molecular structure of 8 with displacement ellipsoids drawn at a 35% probability level (hydrogen atoms omitted for clarity).Selected distances (A) and angles (¡Æ): K.O(11a) 2.688(4), K.O(1) 2.719(4), K.N(2a) 2.821(7), K.N(1) 2.854(5), O(1).C(1) 1.255(7), C(1).C(2) 1.343(7), C(2). C(21) 1.407(9), C(2).C(3) 1.422(7), C(21).N(2) 1.172(8), O(11).N(11) 1.281(5), C(3).N(1) 1.287(6); O(1).K.N(1) 62.78(13), C(1).O(1).K 120.9(4), O(1).C(1).C(2) 126.9(6), C(1).C(2).C(3) 121.6(6), N(2).C(21).C(2) 177.5(8), O(11).N(11).C(3) 126.4(5), O(11).N(11).C(4) 123.4(4), C(3).N(11).C(4) 109.8(5), N(1).C(3).C(2) 127.6(5), C(3).N(1).K 124.9(4). O(11a) C(52) C(51) C(41) C(42) C(4) N(11) N(1) K N(2a) C(3) O(11) C(2) O(1) C(1) C(11) F(3) F(1) F(2) Figure 2 Molecular structure of 9 with displacement ellipsoids drawn at a 35% probability level (hydrogen atoms omitted for clarity). Selected distances (A) and angles (¡Æ): Cu.O(2) 1.953(7), Cu.O(1) 1.963(6), Cu.N(1) 2.024(6), Cu.N(2) 2.033(6), Cu.N(11a) 2.299(9), Cu.N(1a) 2.774(14), O(1).C(1) 1.290(10), C(1).C(2) 1.368(11), C(2).C(3) 1.437(11), C(2).C(21) 1.441(12), C(21).N(111) 1.142(11), C(3).N(1) 1.266(10), N(11). O(11) 1.264(10), O(2).C(6) 1.263(11), C(6).C(7) 1.386(14), C(7).C(8) 1.409(14), C(7).C(71) 1.435(15), C(71).N(211) 1.148(16), C(8).N(2) 1.296(10), N(21).O(21) 1.269(10), N(1a).C(1a) 1.071(17), C(1a).C(2a) 1.43(2); O(1).Cu.N(1) 87.9(3), O(2).Cu.N(2) 88.5(3), N(11a).Cu.N(1a) 178.0(4), C(1a).N(1a).Cu 139.8(13).F(6) F(5) F(4) C(06) C(6) O(2) C(1a) C(2a) N(2) C(10) C(102) C(101) C(9) C(92) C(91) N(21) O(21) C(8) C(7) C(71) N(211) N(1a) Cu N(11a) C(5) C(51) C(52) C(4) C(42) C(41) O(11) N(11) C(3) N(1) C(2) N(111) C(21) C(1) O(1) F(1) F(2) F(3) C(01) 3.8 3.6 3.4 3.2 3.0 0 50 100 150 200 250 T/K 300 meff (B.M.) Figure 3 The temperature dependence of meff for 9.Mendeleev Communications Electronic Version, Issue 5, 2001 3 References 1 (a) A. Caneschi, D. Gatteschi, R. Sessoli and P. Rey, Acc. Chem. Res., 1989, 22, 392; (b) O. Kahn, Molecular Magnetism, VCH, New York, 1993; (c) V. I. Ovcharenko and R. Z. Sagdeev, Usp. Khim., 1999, 68, 381 (Russ. Chem. Rev., 1999, 68, 345). 2 (a) E. F. Ullman, L. Call and J. H. Osiecki, J. Org. Chem., 1970, 35, 3623; (b) J. H. Osiecki and E. F. Ullman, J. Am. Chem. Soc., 1968, 90, 1078; (c) D. G. B. Boocock, R. Darcy and E. F. Ullman, J. Am. Chem. Soc., 1968, 90, 5945; (d) E. F. Ullman, J. H. Osiecki, D. G. B. Boocock and R. Darcy, J. Am. Chem. Soc., 1972, 94, 7049. Received: 7th May 2001; Co