Photosensitized regeneration of carbonyl compounds from oximes

Article abstract of DOI:10.1021/ol025978a

(Matrix Presented) Deprotection of oximes to their corresponding carbonyl compounds through the use of photosensitized electron-transfer reactions proceeds in reasonable to good yields. Better yields are obtained in nonpolar solvents and when triplet sensitizers are used. Preliminary mechanistic studies suggest the involvement of an iminoxyl radical.

Full text of DOI:10.1021/ol025978a

ORGANIC
LETTERS
2002
Vol. 4, No. 14
2325-2328
Photosensitized Regeneration of
Carbonyl Compounds from Oximes
H. J. Peter de Lijser,* Fadia H. Fardoun, Jody R. Sawyer, and Michelle Quant
Department of Chemistry and Biochemistry, California State UniVersity Fullerton,
Fullerton, California 92834-6866
pdelijser@fullerton.edu
Received April 5, 2002
ABSTRACT
Deprotection of oximes to their corresponding carbonyl compounds through the use of photosensitized electron-transfer reactions proceeds
in reasonable to good yields. Better yields are obtained in nonpolar solvents and when triplet sensitizers are used. Preliminary mechanistic
studies suggest the involvement of an iminoxyl radical.
There has been a growing interest in the development of
methods for the generation of carbonyl compounds from
oximes.1 In addition to the numerous classical methods such
as hydrolytic, reductive, and oxidative cleavage reactions,
the photochemistry of oximes and its use as a method for
the regeneration of carbonyl compounds has also been
explored.2-6 Of particular interest is the work by Haley and
Yates, who investigated the photochemical deprotection of
oximes to aldehydes and ketones.6 Both aromatic aldoximes
and ketoximes were found to undergo photohydrolysis via
their lowest excited singlet state; however, the quantum
yields for these processes were generally low (Φ ) 0.01-
0.15), and certain substituents (e.g., nitro) prevented the
photohydrolysis reactions from taking place. Evidence was
presented for the formation of an oxaziridine intermediate
in these and other photolysis reactions.
of photosensitized electron transfer (PET) as a method for
the deprotection of oximes. The main focus of this paper is
on the photochemical reactions of a series of aldoximes and
aliphatic, cyclic, and aromatic ketoximes in the presence of
chloranil (CA). The oximes considered for this research are
shown in Figure 1.7 The general reaction that takes place
under these conditions is shown in Scheme 1, and the results
Scheme 1
Because of the low quantum yields and the poor reactivity
of some of the substrates under normal photochemical
conditions, we have focused our research efforts on the use
of these experiments are listed in Table 1.
It can be seen that in general the deprotection of oximes
to their carbonyl compounds proceeds in reasonable yield,
although the material balance sometimes is poor. In several
cases, less than 8 h is required to achieve complete
(1) Sandler, S. R.; Karo, W. Organic Functional Group Preparation;
Academic Press: San Diego, 1989; pp 430-481.
(2) Amin, J. H.; de Mayo, P. Tetrahedron Lett. 1963, 1585.
(3) (a) Just, G.; Pace-Asciak, C. Tetrahedron 1966, 22, 1069. (b) Taylor,
R. T.; Douek, M.; Just, G. Tetrahedron Lett. 1966, 4143. (c) Just, G.; Ng,
L. S. Can. J. Chem. 1968, 46, 3381. (d) Cunningham, M.; Ng Lim, L. S.;
Just, G. Can. J. Chem. 1971, 49, 2891. (e) Just, G.; Cunningham, M.
Tetrahedron Lett. 1972, 1151.
(7) In a typical experiment, a solution (5 mL) of the oxime (25 mM)
and chloranil (CA; 50 mM) in acetonitrile was photolyzed at 350 nm through
Pyrex using a Rayonet reactor (16 lamps) for a maximum of 8 h. The
progress of the reaction was followed by capillary column gas chromatog-
raphy with flame ionization detector (GC/FID) or with mass selective
detector (GC/MS). The products were identified by means of their mass
spectra and by comparison of the retention times with authentic standards
on two different columns. The yields were determined by calibrated GC/
FID.
(4) Suginome, H.; Furukawa, K.; Orito, K. J. Chem. Soc., Perkin Trans.
1 1991, 917.
(5) (a) Ogata, Y.; Takagi, K.; Mizuno, K. J. Org. Chem. 1982, 47, 3684.
(b) Oine, T.; Mukai, T. Tetrahedron Lett. 1969, 157.
(6) Haley, M. F.; Yates, K. J. Org. Chem. 1987, 52, 1817.
10.1021/ol025978a CCC: $22.00 © 2002 American Chemical Society
Published on Web 06/13/2002

Photolysis of aldoximes 1-3 in the presence of CA results
in the formation of aldehydes (1a, 2a, 3a) and nitriles (1b,
2b, 3b), except for oxime 1, which also reacts to give an
amide (1c). For both 2 and 3, the nitrile was the major
product. This is in stark contrast with the results from the
photohydrolysis reactions of aldoximes, where the major
pathway was cis-trans isomerization, and only a small
amount of the aldehyde was observed.6 The presence of 1c
in the product mixture is interesting because, to the best of
our knowledge, it represents the first example of a PET-
induced Beckmann rearrangement of aldoximes. The pho-
tochemical Beckmann rearrangement has been proposed to
proceed via an oxaziridine intermediate,2-6 and more re-
cently, Shine and co-workers9,10 also proposed an oxaziridine
radical cation intermediate to explain the formation of
oxadiazoles and isoxazoles in the reactions of several
aldoximes with thianthrene perchlorate radical cation salt.
However, it must be noted that the reduction potential of
the thianthrene radical cation is +1.1 V,11 indicating that
the one-electron oxidation of the aldoximes is highly
endothermic (∆V ≈ +1 V) and, therefore, unlikely to occur
under these conditions. The formation of oxadiazoles in the
reactions of aldoximes is most likely due to acid-base
reactions of the oxime resulting in the formation of nitrile
oxides, which can react with nitriles (such as acetonitrile)
to form oxadiazoles.12
Figure 1. Oximes used in the photoinduced electron-transfer
reactions.
CA-sensitized photolysis of a series of cyclic ketones (4-
7) results in the formations of the corresponding ketones 4a-
7a in low yields (Table 1). Both the yield and the mass
balance decrease with increasing ring size. The photolysis
of a series of cyclic (C4-C8) ketoximes in the absence of a
photosensitizer results in the formation of amides, lactams,
and ketones.3d In those studies, a higher conversion and an
increased ketone yield were obtained with an increase in ring
size, the opposite of our results. These photochemical
reactions proceed via oxaziridine intermediates, which react
further (photochemically or thermally) to give lactams and
amides. Under our conditions, no lactams or amides were
conversion of the starting material; however, even during
this relatively short period of time, a significant amount of
polymerization can occur as noted by the dark color of the
solutions after photolysis was completed. The free energy
for electron transfer (∆GET) was calculated using the Weller
equation.8 From Table 1, it can be seen that the oxidation
potentials of the aldoximes are higher than those of the other
substrates; however, ∆GET is exothermic for all oximes and
∼0 kcal/mol for 1. On the basis of these results, we expect
ET to be the dominant pathway for all oximes under these
conditions.
Table 1. Summary of Results for the Photolyses of Oximes in Acetonitrile in the Presence of Chloranil
yield (product)e
nitrile
b
oxime
Eox a (V)
∆GE (kcal/mol)
timec (h)
conversiond (%)
carbonyl
amide
T
benzaldehyde (1)
cinnamaldehyde (2)
phenylglyoxal (3)
cyclopentanone (4)
cyclohexanone (5)
cycloheptanone (6)
cyclooctanone (7)
2-heptanone (8)
2.15
1.92
2.04
1.53
1.47
1.56
1.33
1.68
1.65
1.65
1.79
0
6
4
8
8
8
8
8
8
8
8
1
99
98
71
99
90
87
78
99
84
99
94
43 (1a )
28 (2a )
<5 (3a )
40 (4a )
43 (5a )
33 (6a )
27 (7a )
44 (8a )
38 (9a )
61 (10a )
66 (11a )
31 (1b)
65 (2b)
59 (3b)
<5 (1c)
-5.3
-2.5
-14.3
-15.7
-13.6
-18.9
-10.8
-11.5
-11.5
-8.3
4-heptanone (9)
acetophenone (10)
9-fluorenone (11)
<10 (10c)
a Oxidation potentials measured by cyclic voltammetry (0.1 M tetraethylammonium perchlorate in CH3CN, Ag/AgCl electrode). b Calculated using the
Weller equation (ref 8): ∆GET ) 23.06[Eox - Ered- ET] kcal/mol; ET is the triplet energy of CA (2.13 eV) and Ered is the reduction potential of CA (0.02V).
c Irradiation time. d Conversion was calculated on the basis of the GC-FID peak area of the oxime before and after photolysis. e Absolute yields determined
by calibrated GC/FID.
2326
Org. Lett., Vol. 4, No. 14, 2002

formed, and with the observation that the reactivity is
reversed, we believe that the oxaziridine is not an important
intermediate in the electron-transfer reactions of cyclic
ketoximes.
Photolysis of 2-heptanone oxime (8) and 4-heptanone
oxime (9) under the typical conditions results in the formation
of the corresponding ketones (8a and 9a) in 44% and 38%
yield, respectively. Comparing the reactivity of the acyclic
oximes (8, 9) to that of a similar cyclic oxime (6), it can be
seen that both have a similar reactivity, suggesting that steric
factors may not be very important in the PET reactions of
oximes; however, more detailed studies are necessary to
confirm this observation.
approximately the same when using benzene, DCM, or
MeCN as the solvents. These results can be explained on
the basis of the proposed deprotonation step. Under the
conditions of these reactions, the radical anion, a strong base,
reacts with the oxime radical cation to yield the iminoxyl
radical (Scheme 2). This reaction will be favored in nonpolar
Scheme 2
Photolysis of a solution of acetophenone oxime (10) and
chloranil in acetonitrile results in the formation of acetophe-
none (10a) and acetamide (10c). The presence of 10c in the
product mixture is once again an example of a PET-induced
Beckmann rearrangement. Other aromatic oximes did not
yield amides upon photolysis in the presence of chloranil.
The only product observed for 11 is fluorenone (11a), and
the reaction was completed within 1 h.
The exact mechanism of the photosensitized regeneration
of carbonyl compounds from oximes is unclear. Previous
work by Rhodes on benzophenone oxime using ESR has
shown that the oxime radical cation undergoes rapid depro-
tonation to form an iminoxyl radical.13a This is consistent
with other reports on oximes and iminoxyl radicals.13 We
currently favor this mechanistic pathway rather than the
formation of an oxaziridine radical cation. Support for the
deprotonation mechanism comes from solvent-dependence
studies. The PET reactions of 10 with CA in both polar and
nonpolar solvents (Table 2) show that there is a significant
solvent effect.
solvents where the radical ion pair is close together and the
deprotonation can take place rapidly. In contrast, in a more
polar solvent the radical ions can diffuse apart and result in
lower yields. Furthermore, polar protic solvents such as
MeOH and TFE could potentially associate with the oxime
or the sensitizer radical anion (e.g., hydrogen bonding) and
thus prevent the deprotonation from taking place, which
would also result in lower yields.14
At this point, the exact mechanism for the formation of
the parent ketones remains uncertain. Two potential pathways
Scheme 3
Table 2. Solvent Effects on the Photolysis of CA and
Acetophenone Oxime (10)a
solventb
conversionc (%)
yieldc (%)
benzene
DCM
MeOH
MeCN
TFE
75
79
13
71
37
45
49
4
45
5
starting from the iminoxyl radical are shown in Scheme 3.15
The first pathway involves oxidation of the iminoxyl radical
followed by hydrolysis. Although the oxidation potential of
this radical is unknown, it has been shown that certain
radicals with heteroatoms in the â-position can have very
low oxidation potentials, and as a result, oxidation of this
radical could occur via reaction with CA* or possibly even
a [CA] ) 0.025 M; [10] ) 0.025 M; all solutions were irradiated for 2
h. b Dichloromethane (DCM), methanol (MeOH), acetonitrile (MeCN),
2,2,2-trifluoroethanol (TFE). c Product yields and conversions calculated
using calibrated GC/FID.
The conversions and the yields are much lower when using
the polar protic solvents (MeOH and TFE), but they are
(13) The formation of iminoxyl radicals from oxime radical cations
generated by chemical and other methods is well documented: (a) Rhodes,
C. J. J. Chem. Soc., Faraday Trans. 1990, 86, 3303. (b) Bird, J. W.; Diaper,
D. G. M. Can. J. Chem. 1969, 47, 145. (c) Brokenshire, J. L.; Roberts, J.
R.; Ingold, K. U. J. Am. Chem. Soc. 1972, 94, 7040. (d) Eisenhauer, B. M.;
Wang, M.; Brown, R. E.; Labaziewics, H.; Ngo, M.; Kettinger, K. W.;
Mendenhall, G. D. J. Phys. Org. Chem. 1997, 10, 737. (e) Eisenhauer, B.
M.; Wang, M.; Labaziewics, H.; Ngo, M.; Mendenhall, G. D. J. Org. Chem.
1997, 62, 2050. (f) Everett, S. A.; Naylor, M. A.; Stratford, M. R. L.; Patel,
K. B.; Ford, E.; Mortenson, A.; Ferguson, C.; Vojnovic, B.; Wardman, P.
J. Chem. Soc., Perkin Trans. 2 2001, 1989. (g) Benchariff, L.; Tallec, A.;
Tardivel, R. Electrochim. Acta 1997, 42, 3509.
(8) Rehm, D.; Weller, A. Isr. J. Chem. 1970, 8, 59.
(9) Shine, H. J.; Chiou, S.; Hoque, A. K. M. M. J. Org. Chem. 1990,
55, 3227.
(10) Hoque, A. K. M. M.; Lee, W. K.; Shine, H. J. J. Org. Chem. 1991,
56, 1332.
(11) Houmam, A.; Shukla, D.; Kraatz, H. B.; Wayner, D. D. M. J. Org.
Chem. 1999, 64, 3342.
(12) Grundman, Ch. In The Chemistry of the Cyano Group; Rappoport,
Z., Ed.; John Wiley & Sons: New York, 1970; Chapter 14.
Org. Lett., Vol. 4, No. 14, 2002
2327

ground-state CA.16 Clearly, this pathway would show a
dependence on the presence of water in the solution.
Although it is hard to completely remove water from
acetonitrile, reactions with anhydrous acetonitrile gave
similar results as those with regular acetonitrile. Due to the
long reaction times, it is possible that some water ac-
cumulates in the reaction mixture during the photolysis and
only small amounts of water would be necessary for this
reaction to go to completion. A second pathway is the
reaction with oxygen followed by a second iminoxyl radical
to form a peroxide. Thermal or photochemical cleavage of
the O-O bond and release of NO would result in the
formation of the carbonyl compound. This mechanism
somewhat resembles that of the iron porphyrin catalyzed
oxidation of oximes, which proceeds via a five-coordinate,
high-spin oximatoiron(III) porphyrin species.17 We have
found that in the absence of oxygen, the reactions proceed
somewhat slower; however, the product distribution did not
seem to be affected.18 At this point, it is not possible to favor
either of these mechanisms, nor is it possible to rule out any
alternative pathways. Clearly, more experiments are needed
to determine the exact nature of the intermediates and the
reaction pathways that are being followed.
In conclusion, we have shown that photoinduced electron
transfer can be used for the deprotection of oximes to their
corresponding carbonyl compounds. Although the reactions
have not yet been optimized, this method may offer some
potential as a synthetic method for certain types of oximes
because of their simplicity. However, in order for this method
to become attractive as an alternative for the regeneration
of carbonyl compounds from oximes, a number of aspects
need to be clarified. The mechanistic details remain obscure;
however, the first step in these reactions seems to involve
deprotonation of the oxime radical cation to form an iminoxyl
radical rather than rearrangement to an oxaziridine. This is
supported by both solvent and sensitizer studies. Further
studies on the scope and mechanism of these reactions and
the reactive intermediates involved are currently underway.
(14) The proposed first step also implies an important role for the
sensitizer as it acts as the base to generate the iminoxyl radical. Preliminary
studies on the effect of the photosensitizer on the PET reactions of oximes
indicate that photolysis of a solution containing 10 and 1,2,4,5-tetra-
cyanobenzene (TCB) using biphenyl as the co-donor resulted in a low
conversion and yield, despite the favorable energetics. This is attributed to
the fact that TCB is expected to react via its singlet state and as a result
back-electron transfer will be faster than for triplet sensitizers and will lower
the yield of the reaction. Furthermore, in the absence of a good base (such
as a quinone radical anion), the deprotonation step is slow leading to lower
yields.
(15) Several mechanisms can be proposed; however, on the basis of these
and other experiments, we believe that the two mechanisms discussed here
are among the more viable.
(16) Wayner, D. D. M.; McPhee, D. J.; Griller, D. J. Am. Chem. Soc.
1988, 110, 132.
Acknowledgment. This work was supported by Research
Corporation, the Petroleum Research Fund, administered by
the American Chemical Society, and California State Uni-
versity, Fullerton.
(17) Wang, C.-Y.; Ho, D. M.; Groves, J. T. J. Am. Chem. Soc. 1999,
121, 12094.
(18) Further studies on different oximes indicate that there is a more
important role for oxygen than is obvious from these earlier experiments.
We will report on these and other mechanistic studies in a future publication.
OL025978A
2328
Org. Lett., Vol. 4, No. 14, 2002