Photoinduced Electron Transfer Reactions of Oximes.
Our initial efforts in this area were directed towards developing a strategy
for using photoinduced electron transfer (PET) as a method for the deprotection
of oximes. A variety of oximes (aromatic, aliphatic, cyclic, acyclic, etc.)
were irradiated in the presence of chloranil (CA) in acetonitrile. In general,
the oximes can be converted into their corresponding carbonyl compounds in
moderate to good yields. Solvent studies have shown that the reactions are
faster (and give higher yields) in non-polar solvents such as benzene and
dichloromethane. These results support our hypothesis that the initial steps
in the PET reactions of oximes involve electron transfer from the oxime to
the sensitizer followed by loss of a proton (with the sensitizer acting as
the base) to form an iminoxyl radical. In non-polar solvents the oxime and
sensitizer will be held together more tightly which will result in a faster
reaction. Preliminary studies on the effect of the photosensitizer also support
these findings. Triplet sensitizers give better results than singlet sensitizers,
which is thought to be a result of the fact that return electron transfer
is more favorable in the case of singlet sensitizers. Also, the singlet sensitizers
used in this study are poor bases and will not assist in the deprotonation
of the oxime radical cation (ref. i). However, it cannot be ruled out that
the reaction proceeds by a hydrogen atom transfer mechanism rather than an
electron transfer-proton transfer sequence. Our current focus is on nanosecond
laser flash photolysis studies of oximes to unravel these intricate mechansims.
A recent study on the influence of substituents on the PET reactions of acetophenone
oximes also supports the involvement of iminoxyl radicals as the intermediates
in these reactions and is most consistent with the electron transfer-proton
transfer sequence. Photolysis of the oximes in the presence of chloranil
results in the formation of the chloranil radical anion, which reacts rapidly
with the oxime radical cation to form the semiquinone radical and an iminoxyl
radical. Evidence for the formation of the chloranil radical anion
and the semiquinone radical was obtained from LFP studies. The measured quenching
rates from the LFP studies correlate very well with the calculated oxidation
potentials (ΔΔHf) and therefore represent the rates of electron transfer
from the oximes to triplet chloranil. This data was correlated to various
radical and polar substituent constants. The Hammett studies suggest
that steric, polar, and radical effects are important for ortho-substituted
acetophenone oximes, polar effects are important for para-substituted oximes,
and radical stabilization is more important than polar effects for the meta-substituted
substrates. The calculated ionization potentials of the oximes show
an excellent correlation with the measured quenching rates supporting the
electron transfer pathway. All of the available data suggests that the conversion
of the oximes is controlled by two energetically opposing reactions, namely
oxidation of the neutral oxime, which is favorable for oximes with electron-donating
substituents, and deprotonation of the oxime radical cation, which is favorable
for oximes with electron-withdrawing substituents. The overall result
is a reaction with little selectivity as far as substituent effects are concerned.
More evidence for the electron transfer-proton transfer sequence comes from
the observation that the quenching rates for the reaction of triplet CA with
the substituted acetophenone oximes depends on the substituent. However,
according to a study by Bordwell and co-workers the O-H bond strength in
substituted acetophenone oximes shows very little variation. If the reaction
were to proceed via a hydrogen atom transfer mechanism, we would expect the
quenching rates to be very similar, which is not the case (ref. ii). Similar
studies are underway for aldoximes as well as for a series of adamantyl oximes.
In order to further investigate the important deprotonation step in the proposed
mechanism, we have shifted our focus to a series of oxime ethers. In these
substrates the (acidic) proton is replaced by an alkyl group and as a result,
a different reactivity was expected. Our initial studies on the PET reactions
of acetophenone oxime ethers have shown that the reactivity of these substrates
is solvent-dependent. In order for the oxime ether radical cation to react
more readily, α-protons must be available on the alkyl group. The O-methyl,
O-ethyl, and O-benzyl acetophenone oximes all reacted readily to give acetophenone
oxime as the major product (as well as an aldehyde derived from the O-alkyl
group), whereas O-t-butyl acetophenone oxime did not. The product formation
can be explained by a mechanism that involves electron transfer followed
by proton transfer (α to the oxygen) and subsequent β-cleavage. When using
O-benzyl acetophenone oxime in MeOH, a change in the product formation is
observed; the most important difference being the presence of benzyl alcohol
rather than benzaldehyde as the major product. Based on the data from LFP
and steady-state experiments, the competing mechanism seems most consistent
with a sequence involving electron transfer, followed by a nucleophilic attack
on the nitrogen, a MeOH-assisted [1,3]-proton transfer, and subsequent loss
of benzyl alcohol (ref iii). We are currently investigating similar reactions
of aldoxime ethers.
Many of our past and present studies are geared towards understanding the
relationship between structure and reactivity. Of specific interest to us
is to determine whether steric inhibition of resonance is of importance in
ortho-substituted acetophenone and benzaldehyde oximes. We are in the process
of preparing a variety of ortho-substituted substrates, whose structure and
reactivity will be studied in the gas-phase (theoretical methods), in solution
(NMR), and in the solid state (X-ray crystallography).
In another project we have prepared sterically hindered oximes derived from
cyclohexanones and are currently studying their reactivity. The synthesis
of one of these compounds (2,6-diphenyl¬cyclo¬hexanone oxime) was
problematic and yielded an unusual product, as revealed by X-ray analysis
(ref. iv). Further analysis of the structure by means of spectroscopic (NMR,
IR) techniques and computational methods (semi-empirical, Hartree-Fock, Density
Functional Theory) showed that in solution two low-energy conformers rapidly
interconvert, whereas in the solid state crystal packing does not allow for
this movement. We are now looking a a number of other cyclohexanone oxime
derivatives. In addition we are looking at Steric Inhibition of Resonance
(SIR) effects in orth-substituted acetophenone and benzaldehyde oximes.
Photoinduced Acid-Catalyzed Reactions.
In the course of our studies on oxime ethers we discovered that photolysis
of benzaldehyde in methanol in the presence of chloranil resulted in the
quantitative formation of the dimethyl acetal. Further studies have shown
that the reaction proceeds rapidly for most aldehydes and also for certain
ketones. These results are similar to those of simple acid catalyzed acetalization
of carbonyl compounds, suggesting the involvement of a photochemically generated
acid. On the basis of steady-state and laser flash photolysis data the reaction
is proposed to involve the in-situ generation of a photocatalyst (2,3,5,6-tetrachloro-1,4-hydroquinone,
TCHQ) via reaction of CA with the solvent. The acetalization process is initiated
by ionization of TCHQ, followed by loss of a proton to the solvent or the
carbonyl, which starts a catalytic reaction. The photocatalyst is regenerated
via a disproportionation reaction (ref. v). We are currently investigating
other possible applications of these interesting reactions.
Recent Publications.
i. “Photosensitized Regeneration of Carbonyl Compounds
From Oximes”, H.J.P. de Lijser, F.H. Fardoun, J.R. Sawyer, and M. Quant,
Org. Lett., 2002, 4, 2325-2328 (2002).
ii. “Substituent Effects in Oxime Radical Cations. 1. Photosensitized
Reactions of Acetophenone Oximes”, H.J.P. de Lijser, J.S. Kim, S.M. McGrorty,
and E.M. Ulloa, Can. J. Chem., 2003, 81, 575-585.
iii. “Photosensitized Reactions of Oxime Ethers. A Steady-State
and Laser Flash Photolysis Study”, H.J.P. de Lijser and C.K. Tsai, J. Org.
Chem., 2004, 69, 3057-3067.
iv. “Preparation and Structure of an Unexpected Dehydrogenation
Product from 2,6-Diphenylcyclohexanone Oxime”, H.J.P. de Lijser, C.E. Dedeian,
J.R. Sawyer, S.R. Herron, and K.A. Kantardjieff, J. Chem. Cryst., 2004, 34,
103-110.
v. “Photochemical Acetalization of Carbonyl Compounds in
Protic Media Using an in Situ Generated Photocatalyst”, H.J.P. de Lijser
and N.A. Rangel, J. Org. Chem., 2004, 69, 8315-8322.
vi. “Substituent Effects in Oxime Radical Cations. 2. Steady-State
Photolysis of Acetophenone Oximes”, H.J.P. de Lijser, J.S. Kim, and A. Park,
manuscript in preparation.
