13367-81-2

10,10'-Dimethyl-9,9',10,10'-tetrahydro-9,9'-biacridine acts as a unique two-electron donor in the electron-transfer oxidation with various organic oxidants.The rate-determining step is electron transfer from (AcrH)2 to oxidants, followed by facile cleavage of the C(9)-C bond of (AcrH)2.+ to yield the acridinyl radical (AcrH.) and 10-methylacridinium ion (AcrH+).The second electron transfer from AcrH. to oxidants is much faster than the initial electron transfer from (AcrH)2 to oxidants.On the other hand, the corresponding monomer, 10-methyl-9,10-dihydroacridine (AcrH2), acts as a normal hydride (two electrons and proton) donor in the reactions with oxidants.Rates of electron-transfer reactions from (AcrH)2 to various inorganic and organic one-electron oxidants depend solely on the one-electron-reduction potentials of the oxidants irrespective of the size of the oxidants, indicating that (AcrH)2 acts as a novel two-electron outer-sphere electron-transfer reagent.The one-electron-oxidation potential of (AcrH)2 (vs SCE) has been evaluated as 0.62 V, which is less positive than that of the corresponding monomer (0.80 V).

The cation radical of 9-tert-butyl-N-methylacridan, generated electrochemically or photochemically, offers, in the presence of strong bases, a remarkable example of a double fragmentation. Whereas in acidic or weakly basic media the tert-butyl radical is cleaved with concomitant formation of the methylacridinium cation, the presence of a strong base triggers the cleavage of both the methyl group borne by the nitrogen atom and the tert-butyl group on C-9 leading to acridine, formaldehyde and the tert-butyl anion, even though methylacridinium cation is stable under these conditions. The origin of this unprecedented behavior resides in the prior deprotonation of the methyl group borne by the nitrogen atom which outruns the usual deprotonation at the 9-carbon because this is slowed by the steric hindrance due to the presence of the tert-butyl group.

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The electronic substituent effects on the rates of acid catalysed reduction of aromatic aldehydes by an acid-stable NADH model compound (N-methylacridan) are shown to be very small, compatible with those observed for liver alcohol dehydrogenase catalysed reduction of aromatic aldehydes by NADH.

The C(9)-C bond of 9-(1-naphthylmethyl)-10-methyl-9,10-dihydroacridine (AcrHR) is readily cleaved by HClO4 in acetonitrile (MeCN) under irradiation of the absorption band of AcrHR to yield RH and AcrH+.The dependence of the fluorescence maximum on solvent dielectric constant indicates a highly polar singlet excited state with the dipole moment of ca. 15.6 D, while the fluorescence maximum of 9,10-dihydro-10-methylacridine (AcrH2) is insensitive to the solvent.The fluorescence of AcrHR is efficiently quenched by HClO4 with the rate constant of 8.6 * 109 M-1 s-1 in MeCN at 298 K.The same quenching rate constant has been obtained from the dependence of the quantum yields on for the photoinduced cleavage of the C-C bond of AcrHR by HClO4 in MeCN at 298 K.Thus, the photoinduced intramolecular charge transfer from the acridine moiety to the naphthalene moiety in AcrHR results in the generation of the highly polarized C-C bond which is susceptible to the cleavage by HClO4.The C(9)-C bond of AcrHR is also cleaved upon the intermolecular electron-transferoxidation of AcrHR by Fe(ClO4)3 and Fe(phen)3 and Fe(phen)33+ (phen = 1,10-phenanthroline) in MeCN to yield AcrH+, while the C(9)-H bond is cleaved in the case of AcrH2.

The kinetics of the hydride exchange reaction between NADH model compound 10-methyl-9,10-dihydroacridine (MAH) and 1-benzyl-3-cyanoquinolinium (BQCN+) ion in acetonitrile were studied at temperatures ranging from 291 to 325 K. The extent of reaction-time profiles during the first half-lives are compared with theoretical data for the simple single-step mechanism and a 2-step mechanism involving initial donor/acceptor complex formation followed by unimolecular hydride transfer. The profiles for the reactions of MAH deviate significantly from those expected for the simple single-step mechanism with the deviation increasing with increasing temperature. The deviation from simple mechanism behavior is much less pronounced for the reactions of 10-methyl-9,10-dihydro-acridine-10,10-d2 (MAD) which gives rise to extent of reaction dependent apparent kinetic isotope effects (KIEapp). Excellent fits of the experimental extent of reaction-time profiles with theoretical data for the 2-step mechanism, in the pre-steady-state time period, were observed in all cases. Resolution of the kinetics of the hydride exchange reaction into the microscopic rate constants over the entire temperature range resulted in real kinetic isotopes effects for the hydride transfer step ranging from 40 (291 K) to 8.2 (325 K). That the reaction involves significant hydride tunnelling was verified by the magnitudes of the Arrihenius parameters: EaD - EaH = 8.7 kcal mol-1 and AD/AH = 8 × 104. An electron donor acceptor complex (λmax = 526 nm) was observed to be a reaction intermediate. Theoretical extent of reaction-time profile data are discussed for the case where a reaction intermediate is formed in a non-productive side equilibrium as compared to the case where it is a real intermediate on the reaction coordinate between reactants and products. The common assumption that the two cases are kinetically indistinguishable is shown to be incorrect.

A classical but new kinetic equation to estimate activation energies of various hydride transfer reactions was developed according to transition state theory using the Morse-type free energy curves of hydride donors to release a hydride anion and hydride acceptors to capture a hydride anion and by which the activation energies of 187 typical hydride self-exchange reactions and more than thirty thousand hydride cross transfer reactions in acetonitrile were safely estimated in this work. Since the development of the kinetic equation is only on the basis of the related chemical bond changes of the hydride transfer reactants, the kinetic equation should be also suitable for proton transfer reactions, hydrogen atom transfer reactions and all the other chemical reactions involved with breaking and formation of chemical bonds. One of the most important contributions of this work is to have achieved the perfect unity of the kinetic equation and thermodynamic equation for hydride transfer reactions. The Royal Society of Chemistry.

The rate constant (kH) of hydride transfer from an NADH analogue, 9,10-dihydro-10-methylacridine (AcrH2), to 1-(p-tolylsulfinyl)-2,5-benzoquinone (TolSQ) increases with increasing Sc 3+ concentration ([Sc3+]) to reach a constant value, when all TolSQ molecules form the TolSQ-Sc3+ complex. When AcrH 2 is replaced by the dideuterated compound (AcrD2), however, the rate constant (kD) increases linearly with an increase in [Sc3+] without exhibiting a saturation behavior. In such a case, the primary kinetic deuterium isotope effect (kH/kD) decreases with increasing [Sc3+]. On the other hand, the rate constant of Sc3+-promoted electron transfer from tris(2- phenylpyridine)iridium [Ir(ppy)3] to TolSQ also increases linearly with increasing [Sc3+] at high concentrations of Sc3+ due to formation of a 1:2 complex between TolSQ?- and Sc 3+, [TolSQ?- (Sc3+)2], which was detected by ESR. The significant difference with regard to dependence of the rate constant of hydride transfer on [Sc3+] between AcrH2 and AcrD2 in comparison with that of Sc3+-promoted electron transfer indicates that the reaction pathway is changed from one-step hydride transfer from AcrH2 to the TolSQ-Sc3+ complex to Sc3+-promoted electron transfer from AcrD2 to the TolSQ-Sc3+ complex, followed by proton and electron transfer. Such a change between two reaction pathways, which are employed simultaneously, is also observed by simple changes of temperature and concentration of Sc3+.

The products and kinetics for the reactions of ketone silyl acetals with a series of p-methoxy-substituted trityl cations have been examined, and they are compared with those of outer-sphere electron transfer reactions from 10,10′-dimethyl-9,9′, 10, 10′- tetrahydro-9,9′-biacridine [(AcrH)2] to the same series of trityl cations as well as other electron acceptors. The C-C bond formation in the reaction of β,β-dimethyl-substituted ketene silyl acetal (1: (Me2C=C(OMe)OSiMe3) with trityl cation salt (Ph3C+ClO4-) takes place between 1 and the carbon of para-positon of phenyl group of Ph3C+, whereas a much less sterically hindered ketene silyl acetal (3: H2C=C(OEt)OSiEt3) reacts with Ph3C+ at the central carbon of Ph3C+. The kinetic comparison indicates that the nucleophilic reactivities of ketene silyl acetals are well correlated with the electron transfer reactivities provided that the steric demand at the reaction center for the C-C bond formation remains constant.

The oxidation of a dimeric N-benzyldihydronicotinamide with various oxidants such as quinones, triphenyl carbenium ions and a triplet exited tris(bipyridine) ruthenium(II) complex occurs via initial outer-sphere electron transfer followed by fast C-C bond cleavage and second electron transfer. The kinetic studies allow the determination of the oxidation potential of this compound.

Photoreduction of dialkyl sulfoxides by an acid-stable NADH analogue, 9,10-dihydro-10-methylacridine (AcrH2), proceeds in the presence of perchloric acid in acetonitrile via photoinduced electron transfer from the singlet excited state of AcrH2 to protonated sulfoxides to yield the corresponding dialkyl sulfides.

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When an oxygen-saturated acetonitrile (MeCN) solution containing the NADH model compound, 9,10-dihydro-10-methylacridine (AcrH2), is irradiated with u.v. light firstly in the presence and secondly in the absence of perchloric acid (HClO4), AcrH2 is oxidized by oxygen to yield the 10-methylacridinium ion (AcrH+) and 10-methyl-9-acridone (Acr=O) respectively, and reduction of oxygen yields hydrogen peroxide.The u.v. irradiation of a neutral aqueous solution containing 1-benzyl-1,4-dihydronicotinamide (BNAH) also results in the oxidation of BNAH by oxygen to yield BNA+ and H2O2.Kinetic studies and detection of radical intermediates by e.s.r. spectroscopy have revealed that the photo-oxidation of NADH model compounds by oxygen proceeds via radical-chain reactions, which are initiated by electron transfer from the singlet excited state of NADH model compounds to oxygen.The chain carrier for the photo-oxidation of AcrH2 in the presence of HClO4 in MeCN as well as for the photo-oxidation of BNAH in a neutral aqueous solution is hydroperoxy radical (HO2.), while acridinylperoxy radical (AcrO2.) acts as a chain carrier for the photo-oxidation of AcrH2 in the absence of HClO4 in MeCN.Although no photo-oxidation of AcrH2 by oxygen occurs under visible-light irradiation, AcrH2 is efficiently oxidized to AcrH+ in the presence of a flavin analoque used as a sensitizer, in MeCN under otherwise identical conditions.The flavin-sensitized photo-oxidation of AcrH2 by oxygen proceeds via one-electron reduction of a flavin analoque by AcrH2 followed by the efficient oxidation of the reduced flavin by oxygen without the appreciable contribution of radical-chain processes.

A series of aromatic aldehydes have successfully been reduced by N-metylacridan (AcH2) in the presence of perchloric acid (HClO4) in a mixture of acetonitrile and acetic acid (MeCN/MeCOOH, 4:1 v/v) at 323 K.The effects of HClO4 as well as Mg(ClO4)2 on hydride-transfer reactions from AcH2 to a series of p-benzoquinone derivatives (Q) in MeCN have also been examined.Perchloric acid shows both accelerating and retarding effects on the hydride-transfer reactions depending on the p-benzoquinone derivative.It is shown that AcH2 forms a 1 : 1 complex with HClO4 and the protonated species AcH3+ is inactive for the reduction of p-benzoquinon derivatives.Thus, for p-benzoquinone drivatives being weak oxidants such as p-benzoquinone which have the redox potentials E0(Q/Q-.) 0(Q/Q-.) > 0, HClO4 shows an overall retarding effect on the reduction where HClO4 has hardly catalysed the reaction of free AcH2 with Q.A proposed reaction mechanism involving electron transfer from AcH2 to Q followed by proton transfer from AcH2+ to Q-. in the rate-determining step of the hydride-transfer reactions provides a quantitative evaluation of the single and unified correlation of the logarithm of the rate constant for the hydride-transfer reactions from free AcH2 to Q with the redox potential of Q in the absence and presence of Mg(ClO4)2 or HClO4.The electronic substituent effects on the rate of acid-catalysed reduction of aromatic aldehydes by AcH2 are shown to be very small, as being compatible with those observed for liver alcohol dehydrogenase (LADH)-catalysed reduction of the corresponding aldehydes by NADH.Moreover, the absolute value of the rate constant for the hydride-transfer step from free AcH2 to the protonated benzaldehyde in our model system is also shown to be compatible with that in the LADH-enzyme system.

Equilibrium constants, K, have been determined for the reduction of 10-methylacridinium ion by 15 N-heterocyclic hydride donors: acridine, quinoline, pyridine, and phenanthridine derivatives.The solvent was a mixture of 2-propanol and water in the ratio 4 : 1 by volume.Reduction potentials have been estimated for the corresponding cations in aqueous solution by assuming that the K's would be the same and accepting -361 mV as the reduction potential of the 3-(aminocarbonyl)-1-benzylpyridinium ion.These reduction potentials span 430 mV.Values of pKR have also been determined for six of the cations in the same solvent.For derivatives of the same ring system, -ΔlogK is approximately equal to ΔpKR, but a 4 log unit discrepancy appears when phenanthridine derivatives are compared with the 9-methylacridinium ion.