The effect of metal salts on the oxidation reaction of (acetylphenyl)ferrocenes

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1 ORIGINAL ARTICLE Org. Commun. 6:3 (2013) The effect of metl slts on the oxidtion rection of (cetylphenyl)ferrocenes Yutk Okd * nd Miho Sski Deprtment of Applied Chemistry, Ritsumeikn University, Nojihigshi, Kustsu, Shig , Jpn. (Received December 25, 2012; Revised brury 4, 2013; Accepted August 23, 2013) Abstrct: The effect of metl slts on the oxidtion rection of (cetylphenyl)ferrocenes ws determined. For the p- nd m-isomers, the effect ws ccelerted, but for the o-isomer, the effect ws suppressed. This suppressing effect ws relted to the chelte ring contining the substrte nd the metl ion. Keywords: rrocene derivtives; oxidtion rection; metl slt; chelte effect. 1. Introduction The oxidtion rection of ferrocenes is one of the typicl rections of ferrocenes. rrocene is very stble in ir nd the oxidtion from (II) to (III) is not esy. However, under cidic conditions, it is esily oxidized by ir nd is converted to ferrocenium ion. The rection mechnism is shown in Figure 1. Bsed on this mechnism, ferrocene is converted to ferrocenonium ion by the coordintion of proton to the tom followed by bstrction of the hydrogen tom to form ferrocenium ion. 1-3 The oxidtion of ferrocenes to ferrocenium ion ws very importnt for the interprettion of its biologicl ctivity, 4 for exmple ntitumor ctivity, 5,6 nd synthesis of the bio-relted compounds For ferrocene derivtive, which hs substituent, the oxidtion rection rte is minly influenced by the electron densities of the intrmoleculr tom determined by the electronic effect of the substituents. As n exmple, for the oxidtion rection of (p-substituted phenyl)ferrocenes, liner reltionship ws recognized between the rte constnts nd the Hmmett s substituent constnts; the rection rte ws minly dominted by the electronic effect of the substituents. However, for the corresponding o-derivtives, the rte ws influenced not only by the electronic effect, but lso by steric effects. 12 The steric effects shown by these derivtives re s followings: 12 (i) The interction of the substituent with the intrmoleculr tom (the depression-effect for the oxidtion rection) For (o-methyl nd o-hydroxyphenyl)ferrocenes, the o-substituents tke n end conformtion due to the CH-d type interction or OH-d type hydrogen bond between the substituents nd intrmoleculr tom. The electron densities of tom re decresed by these interctions so tht the oxidtion rectivities re lower thn the corresponding p-isomers. * Corresponding uthor: Emil: ygvictor@sk.ritsumei.c.jp The rticle ws published by Acdemy of Chemistry of Globe Publictions Published 9/25/2013 EISSN:

2 121 Oxidtion rection of (cetylphenyl)ferrocenes + H + O 2 H + + HO 2 ferrocenonium ion ferrocenium ion Figure 1. Oxidtion mechnism of ferrocene (ii) The chelte effect (the oxidtion rection ccelerted effect) For (o-cetyl, o-methoxycrbonyl, nd o-methoxyphenyl)ferrocenes, coordintion of the ctlytic proton cn occur with the crbonyl or etherel oxygen. The proton is trnsferred to the tom by formtion of chelte ring s shown in Fig. 2. Due to this chelte effect, the oxidtion rections of these o-isomers re ccelerted when compred to the corresponding p-isomers. CH 3 H + C O Figure 2. Plusible conformtion of (o-cetylphenyl)ferrocene in cidic conditions Furthermore, for 1,1 - bis(o-cetyl- or (methoxycrbonyl)phenyl)ferrocenes, the ccelerting effect disppered. This ws ttributed to proton trnsfer between the two crbonyl oxygens. 13 In this wy, for (o-substituted phenyl)ferrocenes, the chrcteristic oxidtion rection occurs by these specific steric effects round the o-substituents. 2. Results nd discussion 2.1. The effect of metl slts on the oxidtion rection of (cetylphenyl) ferrocenes To discuss the influence of the metl slts on the oxidtion rection, the oxidtion rections of (cetyl phenyl)ferrocenes nd phenylferrocene were crried out. The rte constnts of these rections re summrized in Tble 1. Bsed on these results, for (p- nd m-cetylphenyl)ferrocenes nd phenylferrocene, the rectivities in the presence of the slts were higher thn those in the bsence of the slts. On the other hnd, for (o-cetylphenyl)ferrocene, the rectivities in the presence of the slts were lower thn those in the bsence of the slts; the slts lowered the rectivity of (ocetylphenyl)ferrocene. The influence by the number of chrges of the metl ions ws M 2+ > M 3+ regrdless of the position of the cetyl group.

3 Okd et l., Org. Commun. (2013) 6: Tble 1. The rte constnts of (substituted phenyl)ferrocenes in the presence of metl slts k 10 5 /s -1 Entry X CCl 2 SrCl 2 AlCl 3 Y Cl 3 1 H p-cetyl m-cetyl o-cetyl (substituted phenyl)ferrocenes : metl slt = 1: The oxidtion rectivity of (p- nd m-cetylphenyl) ferrocenes As mentioned in section 2.1, the oxidtion rectivities of (p- nd m-cetylphenyl)ferrocenes incresed by the ddition of the metl slts. To exmine the effect of the metl ions, the oxidtion rections with phenol or slicylic cid were crried out. As result, the oxidtion rectivity of (p-cetylphenyl) ferrocene incresed (Tble 2). The ccelerted effect by the metl slts would be due to either the metl ions or chloride ion. The result in which the oxidtion rectivity incresed by slicylic cid hving ction binding bility indicted tht metl ions hve suppressing effect, while chloride ion hs n ccelerting one. It is well known tht ferrocene is decomposed by nucleophilic regents to form the 3 + ion. 14,15 Therefore, chloride ion, which is wek nucleophile, would decompose the ferrocene nucleus. To confirm this supposition, the experiments to detect 2 + nd 3 + ions by 1,10- phennthroline nd potssium thiocynte, respectively, were done. As the results, 2 + nd 3 + ions were confirmed when the rection solution becme blue, tht is to sy, ferrocenium ion ws formed. These results indicte tht ferrocene is oxidized by the 3 + ion formed from the ferrocene nucleus. Tht is, the metl ion suppresses the oxidtion rection, but chloride ion ccelertes the rection. For (p- nd m-cetylphenyl)ferrocenes, the oxidtion rectivities would become higher by the metl slts s the finl result of these suppressing nd ccelerting effects. Tble 2. The rte constnts of (p-cetylphenyl)ferrocenes in the presence of some dditives Entry X metl slt dditive k 10 5 /s -1 1 p-cetyl 2 p-cetyl 3 p-cetyl 4 p-cetyl 6 o-cetyl 5 o-cetyl : (substituted phenyl)ferrocenes : metl slt : dduct = 1:1:1 phenol slicylic cid (o-cetylphenyl)ferrocene (p-cetylphenyl)ferrocene The oxidtion rectivity of (o-cetylphenyl)ferrocenes The oxidtion rection of (o-cetylphenyl)ferrocene ws suppressed by the metl slts s mentioned in section 2.1. The oxidtion rection of (p-cetylphenyl)ferrocene mentioned in section 2.2 ws crried out in the presence of (o-cetylphenyl)ferrocene insted of slicylic cid. As result, the rection of (pcetylphenyl)ferrocene ws ccelerted s well s with slicylic cid. Furthermore, the rectivity of (o-cetylphenyl)ferrocene ws similr to tht with no dditives. These results show tht (ocetylphenyl)ferrocene hs the ction binding bility with the sme degree s slicylic cid, therefore it forms chelte ring with the metl ions (Fig. 3). The metl ion would cuse the crowded conformtion round the intrmoleculr tom, which interferes with the pproch of ctlytic proton or 3 + ion. Moreover, the rection rte with M 3+ ws fster thn with M 2+. This would be due to the high chrge density on the ion surfce for esy formtion of the chelte ring.

4 123 Oxidtion rection of (cetylphenyl)ferrocenes CH 3 M n+ C O Figure 3. Plusible conformtion of (o-cetylphenyl)ferrocene in the presence of metl ion For (o-cetylphenyl)ferrocene, the ccelerting effect by chloride ion should exist. However, the remrkble suppressing effect by formtion of the chelte ring suppresses the ccelerting effect: Overll, the oxidtion rection of (o-cetylphenyl)ferrocene ws suppressed. 3. Experimentl 3.1. Syntheses (Substituted phenyl)ferrocenes were synthesized from ferrocene bsed on previously reported procedure Mesurements of oxidtion rectivity The oxidtion rections were crried out using trichlorocetic cid s the ctlyst t 40. The mixed solvent ws ethnol: dioxne (9:1). The metl slts included, CCl 2, SrCl 2, AlCl 3, nd YCl 3. The conversion ws mesured by nlyzing the mounts of unrected ferrocenes by HPLC. The rte constnts were clculted s pseudo-first order rection regrding the ferrocene derivtive. H + References [1] Bromly, A. M. R.; Updhyy, J.; Wssermn, A.; Woollims, P. R. Prmgnetic ferrocene cid dducts. Kinetics of electron trnsfer to proton cids. Chem. Commun. 1965, [2] Bitterwolf, T. E.; Ling, A. C. Metllocene bsicity. II. Rection of the ferrocenonium ction with moleculr oxygen nd sulfur dioxide. J. Orgnomet. Chem. 1972, 40, C29-C32. [3] Bitterwolf, T. E.; Ling, A. C. Metllocene bsicity. I. Ring tilt nd restricted rottion in protonted lkylferrocenes. J. Orgnomet. Chem. 1972, 40, [4] Koepf-Mier, P.; Koepf, H.; Neuse, E. W. rrocenium slts- The first ntineoplstic iron compounds. Angew.Chem. Int. Ed. Engl. 1984, 23, [5] Georgopoulou, A. S.; Mingos, D. M. P.; White, A. J. P.; Willims, D. J.; Horrocks, B. R.; Houlton, A. Bifunctionl ferrocene derivtives for moleculr recognition of DNA duplexes. J. Chem. Soc. Dlton Trns. 2000, [6] Osell, D.; rrli, M.; Znello, P.; Lschi, F.; Fontni, M.; Nervi, C.; Cvigiolio, G. On the mechnism of the ntitumor ctivity of ferrocenium. Inorg. Chim. Act. 2000, 306, [7] Zor, M.; Guengoer, E. U. Rection of ferrocenylcrbene complexes of Cr, Mo nd W with lkynes: synthesis of ferrocenylcyclobutes, ferrocenylfurns nd ferrocenylketoesters. Tetrhedron Lett. 2001, 42, [8] Zor, M.; Yucel, B.; Peynircioglu, N. B. Coupling of ferrocenyl chromium crbene complex with cyclobutenediones. J. Orgnomet. Chem. 2002, 656,

5 Okd et l., Org. Commun. (2013) 6: [9] Zor, M.; Yucel, B.; Aciklin, S. Synthesis of ferrocenyl quis. Tetrhedron Lett. 2003, 44, [10] Zor, M.; Kokturk, M.; Erlp, T. Synthesis of 2-ferrocenylidene-4-cyclopentene-1,3-diones. Tetrhedron 2006, 62, [11] Zor, M.; Tumy, T. A.; Bueyuekguengoer B. Coupling of cyclopropylcrbene chromium complex with ferrocenyl lkynes: synthesis of 5-ferrocenyl-5-hydroxy-2-cyclopentes nd 4-ferrocenyl-4- cyclopentene-1,3-diones. Tetrhedron 2007, 63, [12] Okd, Y.; Ymmoto, N.; Hyshi, T. Studies on ferrocene derivtives. V. Oxidtion rection of (osubstituted phenyl)ferrocenes. Bull. Chem. Soc. Jpn. 1989, 62, [13] Okd, Y.; Kitguchi, H.; Yoshimur, K. Oxidtion rection of 1,1 -bis(o-substituted phenyl)ferrocenes. Org. Commun. 2010, 3, [14] Iscs, N. S. Rective Intermedite in Orgnic Chemistry, John Wiley & Sons, New York, [15] Hyshi, T.; Okd, Y.; Ymshit, T. Studies on ferrocene derivtives. VII. Solvent effect on the oxidtion rection of tert-butylferrocenes. Bull. Chem. Soc. Jpn. 1991, 64, [16] Hyshi, T.; Okd, Y. Studies on ferrocene derivtives. I. A conformtionl study of (substituted phenyl)ferrocenes by the method of proton NMR. Nippon Kgku Kishi. 1987, Reproduction is free for scientific studies