Preparation of some Quinoxaline Quinones, their Electrochemical Reduction, and EPR and Theoretical Studies on their Semiquinone Anions Sean L. W. McWhinnie,a Abid R. Ahmad,a Luis P. Candeias,b Lina K. Mehta,a John Parrick*a and Eric L. Shorta aDepartment of Chemistry, Brunel University, Uxbridge, Middlesex UB8 3PH, UK bGray Laboratory Cancer Research Trust, Mount Vernon Hospital, Northwood, Middlesex HA6 2JR, UK Novel 2,3-disubstituted quinoxaline quinones and a tricyclic quinone containing the quinoxaline nucleus are reported together with their one-electron reduction chemistry and the EPR spectra of the radical anions. The 2,3-substituents on quinoxaline quinones have an e€ect on the stability of the compounds.This is indicated by the observation that the parent quinone 1 is not stable and is best prepared immediately before use whereas the 2,3-bis(ethylsulfanyl)- and 2,3-dimethoxy-quinoxaline-5,8- quinones, 2 and 3, respectively are relatively stable in air and can be left in the solid state in the dark for a month or more without signi¢çcant decomposition.Our investigations were undertaken in order to gain more understanding of the e€ects produced by substituents at the 2- and 3-positions of the quinoxaline quinone nucleus on the ease of reduction of the quinone (Q) and the properties of the radical anion (Q ¢§ ) (Fig. 1). The present study was carried out using DMF as the solvent since semiquinones are more stable in aprotic solvents than in water.5 Good correlations exist between E(Q/Q ¢§ ) in water and in DMF.The tetrachloroquinoxaline quinone 5 was obtained from 5,8-dimethoxyquinoxaline 417 by oxidation with a mixture of concentrated nitric and hydrochloric acids, and the tetra- methoxyquinoxaline quinone 6 was formed by the action of sodium methoxide in methanol on 5 (Scheme 1). Reaction of 4 with 2 equiv. of disodium ethylene glycolate gave both 7 and 8, and 8 was also readily prepared from 7 by the action of sodium hydride in DMSO (Scheme 2).6 The tetra- methoxyquinoxaline 10 was available from 4.Oxidation of 5,8-dimethoxyquinoxalines 8, 9 and 10 to the corresponding quinones 11, 2 and 3 was achieved using ammonium cerium(IV) nitrate (CAN) (Scheme 2). The quinones showed a singlet between d 6.90 and 6.95 in their 1H NMR spectra due to the quinone ring hydrogens. This is at higher ¢çeld than for the quinoxaline-5,8-diones 1, 12 and 13 which have a singlet in their NMR spectra in the range d 7.24 to 7.29.The up¢çeld shift for 2, 3 and 11 is probably due to strong electron release from the 2- and 3-substituents. Treatment of the quinone 3 with 1-acetoxybutadiene gave 14 in a process involving both loss of acetic acid and dehydrogenation. The ¢çve compounds studied 2, 5, 6, 11 and 14, dis- played two reversible reduction processes corresponding to the reduction of Q to Q ¢§ and of Q ¢§ to Q2 ¢§ respectively, where Q2 ¢§ is the quinol dianion, with E(Q ¢§/Q2 ¢§ ) ¢§ E(Q/Q ¢§ ) values of between ¢§540 and ¢§700 mV (Table 1).Calculation of comproportion equilibrium constants (Kcom=exp{¢§(F/RT)[E(Q ¢§/Q2 ¢§ ) ¢§ E(Q/Q ¢§ )]}) from these data indicate that the semiquinones are stable with respect to disproportionation (Fig. 1). For comparison, the reduction potentials of 2,3-dichloro- 1,4-naphthquinone under identical conditions were ¢§0.472 and ¢§1.480 V respectively and fall within the range of the values obtained for the quinoxaline quinones so indicating that the nitrogen atoms have little e€ect upon the reduction potentials.Plots of return current against the square root of the scan rate for the ¢çrst reduction processes gave straight lines even when the second reduction was cycled and thus also con¢çrm the reversibility of the couples. The EPR spectra of the radical anions revealed g values of 12.005, typical of organic radicals, and small hyper¢çne J. Chem. Research (S), 1998, 224¡¾225 J.Chem. Research (M), 1998, 1043¡¾1055 Fig. 1 Stepwise one-electron reduction of a para-quinone and the equilibrium between quinone, radical anion and dianion Scheme 1 Reagents and conditions: i, concentrated HCl, concentrated HNO3, r.t., 1.5 h; ii, MeOH, NaOMe, r.t., 1 h Scheme 2 Reagents and conditions: i, HOCH2CH2OH, Na, THF, reflux, 4 h; ii, DMSO, NaH, r.t., 4 h; iii, EtSNa, EtOH, reflux, 2 h; iv, MeOH, NaOMe, r.t., 1 h; v, CAN, MeOH, H2O, ice-bath, 0.5 h *To receive any correspondence. 224 J.CHEM. RESEARCH (S), 1998Table 1 Electrochemical data for compounds 2, 5, 6, 11 and 14a E(Q/Q ¢§ ) E(Q ¢§/Q2 ¢§) E(Q/Q ¢§ ) ¢§ Comproportion equilibrium Compound E1/2/V DEp/mV E1/2/V DEp/mV E(Q ¢§/Q2 ¢§)/V constants 2 ¢§0.91 145 ¢§1.58 675 ¢§0.67 1.91011 5 ¢§0.49 85 ¢§1.19 85 ¢§0.70 6.01011 6 ¢§1.07 110 ¢§1.61 335 ¢§0.54 1.2109 9 ¢§0.96 75 ¢§1.55 195 ¢§0.59 8.4109 14 ¢§1.19 115 ¢§1.77 465 ¢§0.58 5.8109 aConditions are given in the Experimental section (full text).splittings (<1 mT), showing that the hyper¢çne coupling constants of the active nuclei are small. Initial attempts to record the spectrum of compound 5 led to the observation of a weak spectrum without the application of a current due to chemical reduction by the mercury working electrode. Semiempirical INDO calculations were carried out on the radical anions of the quinones as an aid to the assignment of the hyper¢çne coupling constants and in order to obtain their signs.We thank the Government of Pakistan for ¢çnancial support (A.R.A.), Mrs S. Sadiq for the preparation of 14 and Professor P. Wardman for helpful discussions. L.P.C. thanks the Cancer Research Campaign for support. Techniques used: IR, 1H NMR, EPR, mass spectrometry, cyclic voltammetry, INDO calculations References: 17 Schemes: 3 Fig. 2: Some resonance e€ects in 2,3-dimethoxyquinoxaline 5,8- quinone Fig. 3: Cyclic voltammogram of compound 5 at scan rate 200 mV s¢§1 Fig. 4: Cyclic voltammogram of compound 14 at scan rate 200 mV s¢§1 Fig. 5: g Values and hyper¢çne coupling constants of the radical anions of compounds 2, 5, 6, 11 and 14. Calculated hyper¢çne coupling constants are given in parentheses Fig. 6: Experimental and simulated EPR spectra of the radical anion of compound 2, (a) whole spectrum, (b) expansion Fig. 7: Experimental and simulated EPR spectra of the radical anion of compound 14 Received, 29th August 1997; Accepted, 7th January 1998 Paper E/7/06324E References cited in this synopsis 5 A. R. Ahmad, L. K. Mehta and J. Parrick, J. Chem. Soc., Perkin Trans. 1, 1996, 2443. 6 W. F. Gum, Jr. and M. M. JoullieA , J. Org. Chem., 1967, 32, 53. 17 S. Oguchi, Bull. Chem. Soc. Jpn, 1968, 41, 980. J. CHEM. RESEARCH (S), 1998 225