50387-36-5Relevant articles and documents
Mechanistic and synthetic aspects of amine oxidations promoted by 3-methyl-5-ethyllumiflavinium perchlorate
Hoegy, Susan E.,Mariano, Patrick S.
, p. 5027 - 5046 (2007/10/03)
Preparative and kinetic aspects of the chemistry of 3-methyl-5-ethyllumiflavinium perchlorate (1) with primary and secondary amines have been investigated. Reactions of! with primary and secondary amines leads to rapid production of modestly stable C4a-adducts. The rates of these processes, determined by stopped-flow kinetic methods, parallel amine nucleophilicities. The C4a-adducts undergo benzylamine promoted elimination reactions to produce N-benzylaldimine products with rates that parallel reactivity profiles expected for E2-elimination processes. Finally, flavinium salt 1 serves as a catalyst for oxidations of primary and secondary amines under aerobic conditions.
Flavin chemical models for monoamine oxidase inactivation by cyclopropylamines, α-silylamines, and hydrazines
Kim, Jong-Man,Hoegy, Susan E.,Mariano, Patrick S.
, p. 100 - 105 (2007/10/02)
Models for the inactivation of the monoamine oxidase A and B, two closely related flavoenzymes, by cyclopropylamines, α-silylamines, and hydrazines have been investigated in order to gain insight into the possible chemical mechanisms for these processes. The activated (i.e. high reduction potential and electrophilicity) flavin, 3-methyl-5-ethyllumiflavinium perchlorate (5), was employed in this effort along with trans-2-phenylcyclopropylamine (1), a host of monosubstituted hydrazines (13-16), and α-(trimethylsilyl)benzylamine (9). Admixture of 5 with 1 (25°C, MeCN) results in instantaneous formation of the stable and completely characterized flavin-amine adducts 6 (K(e) = 2 x 104) derived by addition of the amine function in 1 to the 4a-position of 5. Reaction of the 4a-adduct 6 with cyclopropylamine 1 (85°C, MeCN) cleanly (80%) produces the aldimine 7 formed by condensation of the initial product, trans-cinnamaldehyde and amine 5. These results demonstrate that 4a-adducts related to 6 are capable of undergoing cyclopropane ring opening reactions by polar pathways to produce electrophilic α,β-unsaturated carbonyl products. Consequently, ring opening reactions proposed for monoamne oxidase inactivation by primary and perhaps secondary cyclopropylamines can occur by polar routes and, thus, are not uniquely attributable to radical mechanistic pathways. In a similar manner, the flavinium salt 5 undergoes rapid reaction with the α-silylamine 9 to produce a stable 4a-adduct 10 (K(e) = 7 x 104). Reaction of this adduct with 9 (45°C, MeCN) leads to initial production of N-[(α-trimethylsilyl)benzyl]benzaldimine (12) which undergoes desilylation to produce N-benzylbenzaldimine (11) under these conditions. Also, 4a-adduct 10 is rapidly converted to aldilne 11 by reaction with TBAF at 25°C in MeCN. These results show that 4a-adducts, generated from activated flavins and α-silylamines, participate in fragmentation processes leading to silylation of nucleophiles and production of carbonyl products. This polar mechanistic pathway models the known inactivation reactions of the MAOs by α-silylamines previously attributed to SET (radical) routes. Reaction of flavinium salt 5 with phenyl- or benzylhydrazine results in formation of 4a-phenyl or -benzyl flavin adducts. For example, admixture of 5 and PhNHNH2 in CH3CN at 25°C provides the characterizable 4a-phenyl and 4a-cyanomethyl flavins, 21 (28%) and 22 (55%), and benzene. Benzylhydrazine reacts similarly with 5 to produce only the 4a-benzyl adduct 23 (89%). Information about the mechanism for adduct formation in these reactions has come from studies with the hydrazine analogs, NH2NHCO2CH2Ph (15) and NH2OCH2Ph (16). These substances react rapidly with 5 in MeCN at 25°C to cleanly produce stable 4a-hydrazine adducts, 17. The results suggest that 4a-alkylation or -arylation reactions of the activated flavin 5 with hydrazines probably occur via the intermediacy of 4a-hydrazine flavin adducts related to 17. Thus, a polar mechanistic model is also consistent with the known inactivation reactions of the MAOs with hydrazines which are also reported to generate 4a-flavin alkylated and arylated MAO derivatives.
Dioxygen Transfer from 4a-Hydroperoxyflavin Anion. 4. Dioxygen Transfer to Phenolate Anion as a Means of Aromatic Hydroxylation
Moto, Shigeaki,Bruice, Thomas C.
, p. 2284 - 2290 (2007/10/02)
Potassium 2,6-di-tert-butylphenolate (1-) in the presence of N5-ethyl-4a-hydroperoxy-3-methyllumiflavin anion (4a-FlEtOO-) yields (30 deg C, absolute t-BuOH; anaerobic) 2,6-di-tert-butylbenzoquinone (2), 4,4'-dihydroxy-3,3',5,5'-tetra-tert-butylbiphenyl (4), and 3,3',5,5'-tetra-tert-butyl-4,4'-diphenoquinone (5).The 4a-FlEtOO- is converted in turn to N5-ethyl-3-methyllumiflavin radical (FlEt.) and 1,5-dihydro-N5-ethyl-3-methyllumiflavin anion (FlEt-).Kinetic and product studies establish the sequence of eq A to be competent.The product 4 is proposed to arise by rearrangement of 3,3',5,5'-tetra-tert-butyl--4,4'-dione (3), which is known to be a product of dimerization of 1.In separate experiments, the rearrangement 3 -> 4 has been shown to occur (absolute t-BuOH) spontaneously (k = 1.3 * 10-4 s-1) and to be catalyzed by t-BuO-K+ (k = 3.5 * 103 M-1 s-1).The transfer of the peroxy substituent from 4a-FlEtOO- to 1-, yielding the quinone 2 and FlEt-, undoubtedly occurs via the cyclohexadienone peroxide anion (as shown).This is supported by the finding that the rate constant for conversion of 4a-FlEtOO- to reactive intermediate (X) is the same (0.37 s-1) as found previously for peroxidation of other ambident nucleophiles by 4a-FlEtOO- (i.e., 0.375 +/- 0.016 s-1).Of possible relevance to the mechanism of dioxygen transfer are the findings that 1- undergoes 1e- oxidation by FlEt. (k = 2.45 * 104 M-1 s-1) (products FlEt- + 1/2 4), a feature shown by other ambident nucleophilic substrates, and that the second-order rate constant for reaction of 1- with 3O2 (k ca. 0.9 M-1 s-1) is too small for this to be of importance in the formation of 2.It is pointed out that, since dioxygen transfer from 4a-FlEtOO- to 1- yields reduced flavin (FlEt-) and a quinone (2) and since FlEt- reduces quinones to hydroquinones, the oxygen-transfer mechanism could serve as a means of hydroxylation of phenols.
Dioxygen Transfer from 4a-Hydroperoxyflavin Anion. 3. Oxygen Transfer to the 3-Position of Substituted Indoles
Muto, Shigeaki,Bruice, Thomas C.
, p. 7559 - 7564 (2007/10/02)
The 4a-hydroperoxyflavin anion (4a-FlEtO2(-)) spontaneously decays with a rate constant of 4.2E-2 s-1 (tert-butyl alcohol, 30 deg C).In the presence of the anions of 2,3-dimethylindole (1a-) and 5-methoxy-3-methyl-2-phenylindole (2a-) the pseudo-first-order rate constant (Kobsd) for disappearance of 4a-FlEtO2(-) increase.Plots of 1/kobsd vs. 1/-> and 1/-> are linear, and the limiting rate constants for 4a-FlEtO2(-) disappearance at high values of -> and -> were calculated, from the intercepts, to be 0.33 and 0.37 s-1, respectively.In a previous study the limiting rate constants were 0.36 and 0.37 s-1 when the anions of 2,6-di-tert-butyl-4-methylphenol and 3,5-di-tert-butylcatechol were employed.This limiting rate constant of 0.36 s-1 is assigned as the forward rate for the conversion of 4a-FlEtO2(-) (in an endothermic equilibrium) to a species (X) which, on being trapped by substrate anion, transfers a peroxy moiety to the trapping agent.The yields of the dioxygen-transfer products formed from 1a- and 2a- are 24percent and 41percent, respectively.The singlet oxygen-trapping agents, 2,5-dimethylfuran and tetramethylethylene, do not increase the rate of disappearance of 4a-FlEtO2(-) and, therefore, do not trap X.Species X cannot be solvent separated 1O2 and FlEt(-).Moreover, the rate constants for reaction of triplet oxygen with 1a- and 2a- are 1E3 - 1E4 too small for X to be solvent separated 3O2 and FlEt(-).The possibility of X being solvent separated FlEt* and O2(-*) is considered.Possible identities for X include a complex of an oxygen and a flavin species and a 4a,10a-dioxetane of reduced flavin.
