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2006 | 4 | 4 | 674-694
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RuO4-mediated oxidation of N-benzylated tertiary amines. 3. Behavior of 1,4-dibenzylpiperazine and its oxygenated derivatives

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1,4-Dibenzylpiperazine (1),-2-piperazinone (7),-2,6-piperazinedione (9), and 1-benzoyl-4-benzylpiperazine (30) were oxidized by RuO4 (generated in situ) by attack at their endocyclic and exocyclic (i.e., benzylic) aminic N-α-C-H bonds to afford various oxygenated derivatives, including acyclic diformamides, benzaldehyde, and benzoic acid. The reaction outcome was complicated by (i) the hydrolysis of diformamides, occurred during the work-up, and (ii) the reaction of benzaldehyde with the hydrolysis-derived amines giving imidazolidines and/or Schiff bases. Benzoic acid resulted from benzaldehyde only. Compounds 7, 30, and 1-benzylpiperazine, but not 9, were transiently formed during the oxidation of 1. In the same reaction conditions, 1,4-dibenzyl-2,3-(or 2,5)-piperazinedione, 1,4-dibenzyl-2,3,6-piperazinetrione, 4-benzyol-1-benzyl-2-piperazinone, and 1,4-dibenzoylpiperazine were inert. The proposed oxidation mechanism involves the formation of endocyclic and exocyclic iminium cations, as well as of cyclic enamines. The latter intermediates probably result by base-induced deprotonation of the iminium cations, provided an N +−β-proton is available. In the case of 1, the cations were trapped with NaCN as the corresponding α-aminonitriles. The statistically corrected regioselectivity (endocyclic/exocyclic) of the RuO4-induced oxidation reaction of 1, 7, and 30 was 1.2–1.3.
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  • “Costin D. Nenitzescu” Center of Organic Chemistry, 050461, Bucharest, P.O. 35, Box 108, Romania ,
  • “Costin D. Nenitzescu” Center of Organic Chemistry, 050461, Bucharest, P.O. 35, Box 108, Romania
  • “Costin D. Nenitzescu” Center of Organic Chemistry, 050461, Bucharest, P.O. 35, Box 108, Romania
  • “Costin D. Nenitzescu” Center of Organic Chemistry, 050461, Bucharest, P.O. 35, Box 108, Romania
  • [1] J.C. Sheehan and R.W. Tulis: “Oxidation of Cyclic Amines with Ruthenium Tetroxide”, J. Org. Chem., Vol. 39, (1974), pp. 2264–2267.[Crossref]
  • [2] R. Perrone, G. Bettoni and V. Tortorella: “Oxidation of Morpholine Derivatives with Ruthenium (VIII) Oxide”, Synthesis, (1976), pp. 598–600.
  • [3] G. Bettoni, C. Franchini, F. Morlacchi, N. Tangari and V. Tortorella: “Reactions of Nitrogen Compounds with Ruthenium Tetroxide. 2. Oxidation of Tertiary Amines as a Convenient Alternative to von Braun Degradation”, J. Org. Chem., Vol. 41, (1976), pp. 2780–2782.[Crossref]
  • [4] G. Bettoni, G. Carbonara, C. Franchini and V. Tortorella: “Oxidation of Tertiary Polycyclic Amines by RuO4”, Tetrohedron, Vol. 31, (1981), pp. 4159–4164.[Crossref]
  • [5] N. Tangari, M. Giovine, F. Morlacchi and C. Vetuschi: “Oxidation of Organic Nitrogen Compounds by Means of Ruthenium Tetroxide: Selective Preparation of N-substituted Lactams”, Gazz. Chim. Ital., Vol. 115, (1985), pp. 325–328.
  • [6] C. Vetuschi, N. Tangari, M. Giovine, C. Franchini and V. Tortorella: “Selective Oxidation of Piperazine Derivatives with Ruthenium Tetroxide”, Farmaco, Vol. 47, (1992), pp. 599–605.
  • [7] H. Petride, C. Drăghici, C. Florea and A. Petride: “RuO4-Mediated Oxidation of N-Benzylated Tertiary Amines. Are Amine N-Oxides and Iminium Cations Reaction Intermediates?”, Cent. Eur. J. Chem., Vol. 2, (2004), pp. 302–322.[Crossref]
  • [8] H. Petride, O. Costan, C. Drăghici, C. Florea and A. Petride: “RuO4-Mediated Oxidation of N-Benzylated Tertiary Amines. 2. Regioselectivity for N,N-Dimethyl-and N,N-Diethylbenzylamine as Substrates”, Arkivoc, Part X, (2005), pp. 18–32, [Crossref]
  • [9] H. Petride, O. Costan, C. Drăghici, C. Florea and A. Petride: “RuO4-Mediated Oxidation of N-Benzylated Tertiary Amines. 4. The Case of 1-Benzylpiperazine”, work in progress.
  • [10] H. Petride, O. Costan, C. Florea and S. Udrea: “Competitive Hydrolysis of Mono-and Diformylated Ethylenediamine Derivatives”, Rev. Roum. Chim., Vol. 51, (2006), pp. 245–253.
  • [11] H. Petride, C. Drăghici, C. Florea, M. Maganu and S. Udrea: “E/Z Isomerism of Some Diformamides”, Rev. Roum. Chim., Vol. 51, (2006), in press.
  • [12] H. Petride, A. Corbu, O. Costan, C. Florea, V. Marin, A. Petride and E. Şerban: “N-Oxides of Some N-Benzyl Azacycloalkanes. Preferred Conformation by NMR Spectroscopy”, Rev. Roum. Chim., Vol. 50, (2005), pp. 633–640.
  • [13] C. Chapius, A. Gauvreau, A. Klaebe, A. Lattes and J. J. Perie: “Condensation de Diamines-1,2 sur les Composés Carbonylés. Synthèses d’imidazolidines: Mécanisme de la Réaction”, Bull. Soc. Chim. France, (1973), pp. 977–985.
  • [14] Compound 20 might be present as at least two E/Z stereoisomers. The corresponding 1H-NMR spectrum could contain (the values belonging to the major isomer are underlined): 4.17+4.23+4.47+4.54 (s+s+s+s, 4H, N2-CH2+N2-Bn), 4.80+5.01 (s+s, 2H, N1-Bn), 8.26+8.35 (s+s, 1H, N2-CHO), 9.07+9.16 (s+s, 1H, N1-CHO). Some of these signals were observed also in the 1-oxidation mixtures (work-up A), but a reliable quantification was not possible because of extensive signal superposition (4–5 and 8.1–8.4 ppm) and gross errors caused by its relatively small amount (9.0–9.2 ppm).
  • [15] H. Tanaka: “Oxidation Reaction of Steroid Alcohols by Ruthenium Tetroxide”, Tetrahedron, Vol. 19, (1969), pp. 1959–1963.
  • [16] P.E. Morris, Jr. and D.I. Kielly: “Ruthenium Tetraoxide Phase-Transfer-Promoted Oxidation of Secondary Alcohols to Ketones”, J. Org. Chem., Vol. 52, (1987), pp. 1149–1152.[Crossref]
  • [17] S. Giddins and A. Mills: “Optimization of a Simple System for the Oxidation of Octan-2-ol With Sodium Bromate, Mediated by Ruthenium Tetraoxide Generated in situ”, J. Org. Chem., Vol. 53, (1988), pp. 1103–1107.[Crossref]
  • [18] A. Mills and C. Holland: “Effect of Ultrasound on the Kinetics of Oxidation of Octan-2-ol and Other Secondary Alcohols with Sodium Bromate, Mediated by Ruthenium Tetraoxide in a Biphasic System,” Ultrason. Sonochem., Vol. 2, (1995), pp. 533–538.
  • [19] S. Rajendran and D. C. Trivedi: “Ruthenium Tetroxide as a Phase Transfer Catalyst in Biphasic System and Its in situ Electrochemical Regeneration: Oxidation of Aromatic Primary Alcohols and Aldehydes”, Synthesis, (1995), pp. 153–154.
  • [20] S. Torii, T. Inokuchi and K. Kondo: “A Facile Procedure for Oxidative Cleavage of Enolic Olefins to the Carbonyl Compounds with Ruthenium Tetraoxide (RuO4)”, J. Org. Chem., Vol. 50, (1985), pp. 4980–4982.[Crossref]
  • [21] A. Dornow and H. Thies: “Über die Umsetzung von Nitroessigsäureäthylester mit Mannich-Basen”, Liebigs Ann. Chem., Vol. 581, (1953), pp. 219–224.
  • [22] Compounds similar to 20 (i.e., 2, 5, 31, 34) were stable during their (attempted) RuO4-oxidation reactions.
  • [23] Cation 25 is less stable than 26 owing to electron withdrawal of the carbonyl bond. Thus, both AM1 and PM5 semiempirical MO methods (J. J. P. Stewart: MOPAC 2002 2.3, Fujitsu Ltd., Tokyo, 2002) indicated 25 as being less stable than 26 by 17.6 and 14.3 kJ/mol, respectively. As expected, the inverse situation held for the respective anions: that corresponding to 25 is more stable than the anion corresponding to 26, by 75 kJ/mol (AM1).
  • [24] A black amorphous solid is often formed during the RuO4-catalyzed oxidations performed in CCl4/water mixtures. See for instance, P.H.J. Carlsen, T. Katsuki, V.S. Martin and K.B. Sharpless: “A Greatly Improved Procedure for Ruthenium Tetraoxide Catalyzed Oxidations of Organic Compounds”, J. Org. Chem., Vol. 46, (1981), pp. 3936–3938.[Crossref]
  • [25] N.J. Leonard and F.P. Hauck, Jr.: “Unsaturated Amines. X. The Mercuric Acetate Route to Substituted Piperidines, Δ2-Tetrahydropyridines and Δ2-Tetrahydroanabasines”, J. Am. Chem. Soc., Vol. 79, (1957), pp. 5279–5292.[Crossref]
  • [26] D.S. Gierson, M. Harris and H.P. Husson: “Synthesis and Chemistry of 5,6-Dihydropyridinium Salt Adducts. Synthons for General Electrophilic and Nucleophilic Substitution of the Piperidine Ring System”, J. Am. Chem. Soc., Vol. 102, (1980), pp. 1064–1082.[Crossref]
  • [27] B. Ho and N. Castagnoli, Jr.: “Trapping of metabolically generated electrophilic species with cyanide ion: metabolism of 1-benzylpyrrolidine”, J. Med. Chem., Vol. 23, (1980), pp. 133–139.[Crossref]
  • [28] A. Koshinen and M. Lounasmaa: “Regiospecific Functionalisation of Carbon Atoms α to Heterocyclic Nitrogen”, Tetrahedron, Vol. 39, (1983), pp. 1627–1633.[Crossref]
  • [29] L.M. Sayre, D.A. Engelhart, B. Venkataraman, M.K.M. Babu and G.D. McCoy: “Generation and Fate of Enamines in the Microsomal Metabolism of Cyclic Tertiary Amines”, Biochem. Biophys. Res. Commun., Vol. 179, (1991), pp. 1368–1376.[Crossref]
  • [30] M. Căproiu, C. Florea, C. Galli, A. Petride and H. Petride: “Oxidation of N-Benzyl Aziridine by Molecular Iodine: Competition of Electron Transfer and Heterolytic Pathways”, Eur. J. Org. Chem., (2000), pp. 1037–1043. [Crossref]
  • [31] H. Petride, A. Corbu, C. Florea, A. Petride and S. Udrea: “N-α-Cyano Derivatives of Some N-Benzyl Azacycloalkanes”, Rev. Roum. Chim., Vol. 51, (2006), in press.
  • [32] D.W. Henry: “A Facile Synthesis of Piperazines from Primary Amines”, J. Heterocyclic Chem., Vol. 3, (1966), pp. 503–511.[Crossref]
  • [33] Yu.S. Tsizin, N.L. Sergovskaya and S.A. Tcherniak: “Synthesis of 1-Alkyl (aralkyl)-4-acyl-2-piperazinones”, Khim. Geterotsikl., (1986), pp. 514–517.
  • [34] J.C. Craig: “Preparation of 1-Benzylpiperazine”, J. Chem. Soc., (1959), pp. 3634–3635.
  • [35] J. Cymerman-Craig, W.P. Rogers and M.E. Tate: “Chemical Constitution and Anthelmintic Activity. III. Preparation of Substituted Phenothiazines and Some Mono-and Dicyclic Analogues”, Aust. J. Chem., Vol. 9, (1956), pp. 397–405.[Crossref]
  • [36] S. Groszkowski, A. Serper, M. Ionesco, A. Soresco, A. Hacic and D. Panaitesco: “Piperazine Derivatives and their Anthelmintic Effectiveness in Vitro”, Ann. Pharm. Franc., Vol. 16, (1958), pp. 517–525; Chem. Abstr., Vol. 53, (1959), p. 8151e.
  • [37] J. Speziale and E.G. Jaworski: “N-Substituted Glycinate and Alalinate Esters”, J. Org. Chem., Vol. 25, (1960), pp. 728–732.[Crossref]
  • [38] T. Yamazaki and M. Nagata: “Electrolytic Reduction of 2,5-dioxopiperazine Derivatives by Tafel’s Method”, Yakugaku Zasshi, Vol. 79, (1959), pp. 1222–1224.; Chem. Abstr., Vol. 54, (1960), p. 4596f.
  • [39] C. J. Pouchert and J. Behnke: The Aldrich Library of 13C and 1H FT NMR Spectra, Vol. 2: [39a] n. 932B; [39b] n. 1063B, Aldrich Chemical Company, Inc., 1993.
  • [40] H.E. Gottlieb, V. Kotlyar and A. Nudelman: “NMR Chemical Shifts of Common Laboratory Solvents as Trace Impurities”, J. Org. Chem., Vol. 62, (1997), pp. 7512–7515.[Crossref]
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