Cristina Florea

Stereoelectronic Inhibition of Deprotonation in the Radical Cation of N-Benzylpiperidine: a Contribution to the Debate on the Mechanism of N-Dealkylation of Tertiary Amines

capable to aid in solving this mechanistic conundrum, atleast for biomimetic processes, since a significant differencein the composition of the products mixture results underHAT or ET reaction conditions.Products analysis of the oxidation reactions of the vari-ous substrates investigated here were performed by GC andGC/MS methods, and the results are reported in Table 1,together with some representative blank experiments.

RuO4-mediated oxidation ofN-benzylated tertiary amines. Are amineN-oxides and iminium cations reaction intermediates?

N-Benzylmorpholine,-piperidine, and-pyrrolidine (1A-C, resp.) are oxidised by RuO4 (generatedin situ) at both endocyclic and exocyclic (benzylic)N—α-methylene positions to afford lactams (and dioxo-derivatives) and benzaldehyde (and benzoyl derivatives), respectively. TheN-oxides of1A-C, formed by a minor side reaction, are not involved as intermediates. Control experiments showed the transient formation of endo- and exocyclic iminium cations trapped with NaCN as the corresponding nitriles. The proposed course of the RuO4-mediated oxidation of1A-C involves the consecutive steps1⇒iminium cations+cyclic enamine⇒oxidation products. The endocyclic/exocyclic regioselectivity of the oxidation reaction lies between 0.8 (for1A) and 2.1 (for1B). The amine cation radical and theN-α-C· carbon-centered radical seem not to be involved.

Oxidation ofN-Benzyl Aziridine by Molecular Iodine: Competition of Electron Transfer and Heterolytic Pathways

Excess N-benzyl aziridine (1) reacts with I2 to afford dimer 2, tetramer 3, benzaldehyde (4), and iodoamine 5. The reaction is interpreted as occurring by both electron transfer (ET) and heterolytic mechanisms. An ET mechanism is substantiated for the oxidation by I2 of dimer 2 and tetramer 3, both being substrates easier to oxidise by electron abstraction than 1. Several auxiliary reactions were performed on 1 in order to firmly establish the boundaries to the competition between the ET and heterolytic mechanisms. For the reaction of 1 with 5 a reaction scheme is proposed; in a particular case, a pseudo-first order kinetic law is followed.

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

Abstract1,4-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.

RuO4-Mediated oxidation of secondary amines. 1. Are hydroxylamines main intermediates?

The RuO 4 -catalyzed oxidation of secondary amines Bn-NH-CH 2 R ( 1a - b ; R=H, Me) gave mainly amides, but minute amounts of nitrones PhCH=N(O)-CH 2 R ( 9a - b ) and traces of Bn-N(OH)-CH 2 R (R=H, 4a ) were also detected. In the presence of cyanide, up to 22 reaction products were identified, but mainly α-aminonitriles. Comparison of the oxidation products of 1a - b with those of 4a - b , 9a - b , and Bn-N(O)=CHR ( 10a - b ) showed that 4a - b cannot be main reaction intermediates formed from 1a - b .

RuO4-Mediated oxidation of secondary amines 2. Imines as main reaction intermediates

Oxidation by RuO 4 (generated in situ from RuO 2 and NaIO 4 ) of secondary amines like Bn-NH-CH 2 R ( 1 ; R=H, Me) gave complex reaction mixtures, but mainly amides. In the presence of cyanide, the leading products were α-aminonitriles. Comparison of the oxidation products of 1 with those from the corresponding imines PhCH=N-CH 2 R and Bn-N=CH-R showed that formation of the indicated imines is the first main step in the oxidation of 1 . A detailed mechanism is proposed.