Aerobic oxidation of N-alkylamides catalyzed by N-hydroxyphthalimide under mild conditions. Polar and enthalpic effects

Article abstract of DOI:10.1021/jo016398e

The oxidation of N-alkylamides by O₂, catalyzed by N-hydroxyphthalimide (NHPI) and Co(II) salt, leads under mild conditions to carbonyl derivatives (aldehydes, ketones, carboxylic acids, imides) whose distribution depends on the nature of the alkyl group and on the reaction conditions. Primary N-benzylamides lead to imides and aromatic aldehydes at room temperature without any appreciable amount of carboxylic acids, while under the same conditions nonbenzylic derivatives give carboxylic acids and imides with no trace of aldehydes, even at very low conversion. These results are explained through hydrogen abstraction by the phthalimide-N-oxyl (PINO) radical, whose reactivity with benzyl derivatives is governed by polar effects, so that benzylamides are much more reactive than the corresponding aldehydes. The enthalpic effect is, however, dominant with nonbenzylic amides, making the corresponding aldehydes much more reactive than the starting amides. The importance of the bond dissociation energy (BDE) of the O-H bond in NHPI is emphasized.

Full text of DOI:10.1021/jo016398e

J . Org. Chem. 2002, 67, 2671-2676
2671
Aer obic Oxid a tion of N-Alk yla m id es Ca ta lyzed by
N-Hyd r oxyp h th a lim id e u n d er Mild Con d ition s. P ola r a n d
En th a lp ic Effects
Francesco Minisci,*,† Carlo Punta,† Francesco Recupero,† Francesca Fontana,‡ and
Gian Franco Pedulli§
Dipartimento di Chimica, Materiali e Ingegneria Chimica Giulio Natta, Politecnico di Milano,
via Mancinelli 7, 20131 Milano MI, Italy, Dipartimento di Ingegneria, Universita` di Bergamo,
viale Marconi 5, 24044 Dalmine BG, Italy, and Dipartimento di Chimica Organica “A.Mangini”,
Universita` di Bologna, via S. Donato 15, I-40127 Bologna BO, Italy
francesco.minisci@polimi.it.
Received December 21, 2001
The oxidation of N-alkylamides by O2, catalyzed by N-hydroxyphthalimide (NHPI) and Co(II) salt,
leads under mild conditions to carbonyl derivatives (aldehydes, ketones, carboxylic acids, imides)
whose distribution depends on the nature of the alkyl group and on the reaction conditions. Primary
N-benzylamides lead to imides and aromatic aldehydes at room temperature without any appreciable
amount of carboxylic acids, while under the same conditions nonbenzylic derivatives give carboxylic
acids and imides with no trace of aldehydes, even at very low conversion. These results are explained
through hydrogen abstraction by the phthalimide-N-oxyl (PINO) radical, whose reactivity with
benzyl derivatives is governed by polar effects, so that benzylamides are much more reactive than
the corresponding aldehydes. The enthalpic effect is, however, dominant with nonbenzylic amides,
making the corresponding aldehydes much more reactive than the starting amides. The importance
of the bond dissociation energy (BDE) of the O-H bond in NHPI is emphasized.
In tr od u ction
behavior of PINO and TEMPO (both N-oxyl radicals) to
the difference in bond dissociation energies (BDEs) of the
O-H bonds in the corresponding N-hydroxy derivatives.
The BDE of the O-H bond in N-hydroxytetramethyl-
piperidine is relatively low (70 kcal mol-1), while we have
shown3 that the BDE of the O-H bond in NHPI is at
least 16 kcal mol-1 stronger, as measured by EPR
spectroscopy of the equilibrium shown in eq 2, where Ar-
N-Hydroxyphthalimide (NHPI) combined with cobalt
salts has been recently shown, particularly by Ishii and
co-workers,1 to be an effective catalyst for the oxidation
of organic compounds by molecular oxygen under mild
conditions. All the evidence1 would indicate that hydro-
gen abstraction by the phthalimide-N-oxyl radical (PINO),
generated in situ, from C-H bonds (eq 1) plays a key
role in free-radical chains.
OH is a reference phenol (2,4,6-trimethylphenol, whose
BDE in benzene is 82.7 kcal mol-1
NHPI.
)
and >N-O-H is
3,5
The higher BDE for the O-H bond in NHPI would
explain the possibility of hydrogen abstraction following
eq 1. A similar reaction by TEMPO instead of PINO
would be too endothermic to occur, while on the other
hand, TEMPO is an inhibitor of free-radical chains, since
it rapidly traps intermediate free radicals (eq 3).
For example, primary alcohols are oxidized to carbox-
ylic acids2 or aldehydes3 at room temperature and
atmospheric pressure of oxygen. On the other hand, we
have recently reported4 that the aerobic oxidation of
primary alcohols, catalyzed by TEMPO (tetramethyl-
piperidine-N-oxyl) in combination with transition metal
salts, leads selectively to the corresponding aldehydes
under very mild conditions. We ascribed3 the different
* Corresponding author. Fax: +39-02-23993080.
† Politecnico di Milano.
The effectiveness of the catalytic activity of TEMPO
in selectively oxidizing alcohols to aldehydes by O2 is due
to the intermediate formation of the oxoammonium salt
(>N+dO), which is the actual oxidant, but also to the
‡ Universita` di Bergamo.
§ Universita` di Bologna.
(1) Recent review: Ishii, Y.; Sakaguchi, S.; Iwahama, T. Adv. Synth.
Catal. 2001, 343, 393.
(2) Iwahama, T.; Yoshino, Y.; Keitoku, T.; Sakaguchi, S.; Ishii, Y.
J . Org. Chem. 2000, 65, 6502.
(3) Minisci, F.; Punta, C.; Recupero, F.; Fontana, F.; Pedulli, G. F.
Chem. Commun. In press.
(4) Cecchetto, A.; Fontana, F.; Minisci, F.; Recupero, F. Tetrahedron
Lett. 2001, 42, 6651.
(5) Lucarini, M.; Pedulli, G. F.; Cipollone, M. J . Org. Chem. 1994,
59, 5063; Lucarini, M.; Pedrielli, P.; Pedulli, G. F.; Cabiddu, S.;
Fattuoni, C. J . Org. Chem. 1996, 61, 9259; Lucarini, M.; Pedulli, G.
F.; Valgimigli, L.; Amorati, R.; Minisci, F. J . Org. Chem. 2001, 66, 5456.
10.1021/jo016398e CCC: $22.00 © 2002 American Chemical Society
Published on Web 03/15/2002

2672 J . Org. Chem., Vol. 67, No. 8, 2002
Minisci et al.
Ta ble 1. Oxid a tion of La cta m s or Aceta m id es of Cyclic
Am in es by O2 in CH3CN
inhibition of the further free-radical oxidation of alde-
hydes by O2, which occurs in the absence of TEMPO.4
We have also observed3 that reaction 1 is strongly
affected by polar and enthalpic effects, so that, for
example, the oxidation of primary benzylic alcohols leads
selectively to aldehydes. This happens because benzylic
alcohols are much more reactive than the corresponding
aldehydes for polar reasons, the enthalpic effect being
substantially identical for alcohols and aldehydes. In
contrast, nonbenzylic alcohols selectively give carboxylic
acids, even at low conversion, because in this case
aldehydes are much more reactive than the correspond-
ing alcohols on enthalpic grounds.3
The amino group is a more effective electron-releasing
substituent than the hydroxy group (the values of the σp
Hammett constants are -0.57 and - 0.35 for -NH2 and
-OH groups, respectively) and therefore we would expect
a higher reactivity and a stronger polar effect in the
oxidation of alkylamines by O2 and NHPI catalysis
compared to the corresponding alcohols.
However, we observed that under conditions in which
the alcohols are easily oxidized, the corresponding amines
are substantially inert. We soon realized that this inert-
ness was due to the degradation of the catalyst (NHPI)
by the amine, according to eq 4.
a
0.25 mmol of m-chlorobenzoic acid was utilized for 5 mmol of
amide.
through the Beckmann rearrangement11,12 of the corre-
sponding oximes (eq 8).
To avoid the deactivation of the catalyst (eq 4), we
considered the possibility of protecting the amino group
by acylation. Obviously, the acetamido group has a lower
electron-releasing character than the amino group, but
the enthalpic and polar effects should be still marked
enough for the selective oxidation of N-alkylamides to
occur by O2 with NHPI catalysis. Actually, the oxidation
of N-alkylamides by O2, catalyzed by NHPI and Co salts,
occurs under mild conditions, leading to carbonyl prod-
ucts (imides, carboxylic acids, ketones, aldehydes). The
exact product distribution depends on the structure of
the alkyl group and the reaction conditions.
In this paper we report, as mentioned above, a new
simple oxidation by O2, catalyzed by NHPI, which allows
the reverse transformation of alkylamines to carbonyl
compounds through the intermediate amides (eq 9).
Classical organic chemical reactions allow the trans-
formation of carbonyl derivatives into amines; the car-
boxylic acids can be converted to amines through well-
known reactions, such as the Hofmann6,7 (eq 5) and
Curtius8,9 (eq 6) rearrangements.
Resu lts a n d Discu ssion
Moreover, carbonyl derivatives can be transformed into
amino derivatives by reductive ammonolysis10 (eq 7) or
Cyclic Am id es. The oxidation of lactams or aceta-
mides of cyclic amines does not lead to the cleavage of
the ring but to the formation of cyclic imides (eq 10) or
N-acetyl lactams (eq 11) (Table 1).
(6) Malpass, J . R. In Comprehensive Organic Chemistry; Sutherland,
I. O., Ed.; Pergamon Press: Oxford, 1979; Vol.2, p 17.
(7) Banthorpe, D. V. The chemistry of the amino group; Patai, S.,
Ed.; Wiley: New York, 1968; p 630.
(11) Challis, B. C.; Challis, J . A. In Comprehensive Organic Chem-
(8) Reference 6, p 18.
(9) Reference 7, p 623.
istry, Sutherland, I. O., Ed.; Pergamon Press: Oxford, 1979; Vol.2, p
966.
(10) Reference 6, p 10.
(12) Reference 7, p 624.

Aerobic Oxidation of N-Alkylamides
J . Org. Chem., Vol. 67, No. 8, 2002 2673
is, why does the peroxyl radical abstract a hydrogen atom
from NHPI generating the PINO radical (eq 18) and not
directly from the amide (eq 19), while the PINO radical
abstracts a hydrogen atom from the amide (eq 16) and
not from the hydroperoxide under mild conditions (room
temperature)?
The hydrolysis of the cyclic imides leads to dicarboxylic
acids; for example, caprolactam gives the cyclic imide in
high yields and, by hydrolysis, it turns into adipic acid
(eq 12).
The question arises from the fact that both nitroxyl
and peroxyl radicals have a clear-cut electrophilic char-
acter, so both reactions 16 and 19 should be favored by
polar effects, while reaction 18 should be negatively
affected by the polar effect and substantially governed
by the enthalpic effect.
We know the BDE for the O-H bond in the hydro-
peroxide (88 kcal mol-1) but only the lower limit for the
BDE of the O-H bond in NHPI (>86 kcal mol-1),3 and
we can reasonably assume that reaction 18 is either
almost thermoneutral or slightly endothermic, so the
general eq 20 can be considered an equilibrium process.
The hydrolysis of N-acetyllactams leads to lactams (eq
13).
Equation 13 represents a simple procedure for the
transformation of cyclic amines to lactams by acetylation,
O2 oxidation, and hydrolysis. The mechanism of the
transformation of the methylene into the carbonyl group
must explain the combined catalytic activity of NHPI and
Co(II) salts (both are necessary for the oxidation under
mild conditions). Co(II) salts appear to have a 2-fold
function: they can initiate (eqs 14, 15) chain processes,
as suggested by Ishii.1
Moreover, we know the absolute rate constants for
hydrogen abstraction from C-H bonds by peroxyl radi-
cals (eq 19) (∼10-2-10-1 M-1 s-1at room temperature),
but we have not yet determined13 the order of magnitude
for hydrogen abstraction by PINO radical.
The intriguing aspects of eqs 16 and 18 could be
explained by a more marked polar effect for hydrogen
abstraction by PINO than by the peroxyl radical, which
would make eq 16 faster than eq 19 and thus shift the
equilibrium of eq 20 to the right. This polar effect should
be due to the carbonyl groups bonded to nitrogen (eq 21).
PINO then initiates a free-radical chain, leading to the
hydroperoxide under mild conditions (eqs 16-18).
The effect is, in our opinion, similar to that observed
for acylperoxyl radicals, R-C(dO)OO•, compared to alkyl-
peroxyl radicals, R-OO•; the former is more electrophilic
than the latter.14 The phenomenon would be more
marked with PINO than with acylperoxyl radicals,
because nitrogen can settle a positive charge, as in eq
21, better than oxygen.
For the same reason we believe the BDE for the O-H
bond to be higher in NHPI than in alkyl-N-hydroxy
derivatives: for NHPI, a conjugation similar to eq 21
increases the polarization of the O-H bond and therefore
the electrostatic attraction between H and O and hence
the BDE of the O-H bond.
Again the situation is similar to that of peracids and
hydroperoxides (the BDE values for the O-H bonds in
ROO-H and R-C(dO)OO-H are respectively 88 and 93
The C-H bonds adjacent to either NH or CO groups
are both activated from an enthalpic standpoint, but
reaction 16, involving the electrophilic PINO radical,
occurs selectively to the CH2 next to the NH for polar
reasons.
The free-radical chain of eqs 16-18, suggested by Ishii
in general for the oxidations by O2 catalyzed by NHPI,
would appear, however, quite intriguing. The question
(13) The determination by ESR spectroscopy of the absolute rate
constants for hydrogen abstraction from NHPI by alkoxyl and peroxyl
radicals and from C-H bonds by PINO is in progress (G. F. Pedulli,
et al.)
(14) Bravo, A.; Bjørsvik, H.-R.; Fontana, F.; Minisci, F.; Serri, A. J .
Org. Chem. 1996, 61, 9409.

2674 J . Org. Chem., Vol. 67, No. 8, 2002
Minisci et al.
kcal mol-1) and it is reflected also in alcohols and
carboxylic acids (the BDE values for the O-H bonds in
RO-H and R-C(dO)O-H are respectively 103 and 110
kcal mol-1).
However, a more plausible explanation, in our opinion,
can be due to a more complex mechanism, characterized
by a superimposition of a redox chain (which represents
the other function of the Co salt beside eqs 14 and 15) to
the free-radical chain of eqs 16-18.
Ta ble 2. Oxid a tion of N-Ben zyla ceta m id es,
ARCH2NHCOCH3, by O2 in CH3CN or AcOH
T
t
conv
products
selectivity (%)
run
1
Ar
solvent (°C) (h) (%)
Pha
Ph
CH3CN
CH3CN
AcOH
20
4
89 ArCHO (21)
ArCONHCOCH3 (77)
43 ArCOOH (42)
ArCONHCOCH3 (56)
100 2.5 75 ArCOOH (96)
ArCONHCOCH3 (3)
92 ArCHO (24)
ArCONHCOCH3 (73)
65 ArCOOH (38)
ArCONHCOCH3 (60)
91 ArCOOH (93)
ArCONHCOCH3 (4)
88 ArCHO (22)
ArCONHCOCH3 (76)
71 ArCOOH (35)
ArCONHCOCH3 (62)
93 ArCOOH (89)
ArCONHCOCH3 (8)
97 ArCHO (16)
ArCONHCOCH3 (82)
96 ArCHO (11)
2
3
4
5
6
7
8
9
60
5
Ph
a
p-CH3C6H4
p-CH3C6H4
p-CH3C6H4
CH3CN
CH3CN
AcOH
20
80
4
5
3
4
5
3
2
2
The imide can be, in fact, obtained from the hydro-
peroxide by loss of water,15 but more probably by a redox
chain according to eqs 22-24.
100
20
a
m-CH3C6H4
m-CH3C6H4
m-CH3C6H4
CH3CN
CH3CN
80
ACOH 100
a
10 p-CH3OC6H4 CH3CN
20
80
11 p-CH3OC6H4 CH3CN
ArCOOH (35)
ArCONHCOCH3 (49)
12 p-CH3OC6H4 AcOH
100
1
97 ArCHO (13)
ArCOOH (82)
ArCONHCOCH3 (3)
a
13 p-ClC6H4
14 p-ClC6H4
15 p-ClC6H4
CH3CN
CH3CN
AcOH
20
80
4
5
2
87 ArCHO (19)
ArCONHCOCH3 (78)
86 ArCOOH (30)
ArCONHCOCH3 (64)
92 ArCOOH (66)
ArCONHCOCH3 (32)
Co(III), formed in eqs 22 and 24, can be reduced to
Co(II) either by NHPI (eq 25) or by the hydroperoxide
(eq 26) formed in eqs 18 and 24, generating a redox chain.
Reaction 22 shifts the equilibrium of eq 20 to the right
by decomposing the hydroperoxide; the alkoxyl radical
reacts with NHPI (eq 23) much faster than the peroxyl
radical (eq 18) for enthalpic reasons (eq 23 is more
exothermic than eq 18 by about 15 kcal mol-1), generat-
ing an effective chain process by the combination of eqs
16-18 and 22-26.
100
a
0.25 mmol of m-chlorobenzoic acid was utilized for 5 mmol of
N-benzyl derivative. The oxidation of PhCH(CH3)NHCOCH3 under
all the conditions reported in this table always gives PhCOCH3
with selectivity >90%.
acids and variable amounts of imides, depending on the
reaction solvent, at higher temperature (60-100 °C)
(Table 2).
The oxidation, catalyzed by NHPI and Co(OAc)2, takes
place at room temperature in CH3CN only in the presence
of a catalytic amount of m-chlorobenzoic acid, which
avoids the precipitation of the cobalt salt, necessary for
the oxidation to occur, as already observed for the
oxidation of alcohols.2,3 Moreover, Co benzoates appear
to be more efficient in the redox decomposition of the
hydroperoxides.1 The formation of imides can be ex-
plained by the same mechanism above-discussed for
cyclic amides; the formation of the aldehyde is clearly
due to the hydrolysis of the hydroxyamide (eq 28), formed
in eq 23, in competition with its further oxidation
according to eq 24.
In any case, for this mechanism to be effective,
hydrogen abstraction from C-H bonds always has to be
faster by PINO than by the peroxyl radical, as above-
discussed, and hydrogen abstraction by the alkoxyl
radical must be much faster from NHPI than from C-H
bonds.13 The only byproduct, formed in small amounts
in the oxidation of N-acetyltetrahydroisoquinoline, is the
dihydroisoquinoline, very likely arising from the competi-
tive â-scission of the benzylic radical (eq 27) at low oxygen
concentration.
Acetamide is, in fact, a byproduct of the oxidation; its
formation together with that of the aldehyde supports
the oxidation mechanism leading to imides (eqs 16-18
and 22-26). No appreciable amount of carboxylic acid is
formed under these conditions, meaning that the N-
benzylamide is more reactive than the corresponding
aromatic aldehyde. We16 have recently observed a similar
behavior in the oxidation of N-benzylamides by H2O2
catalyzed by Br2; the aldehyde is the main reaction
product because the strong acidic medium, due to the
N-Ben zyla cet a m id es. The oxidation of N-benzyl-
acetamides leads either to imides and minor amounts of
aromatic aldehydes at room temperature or to carboxylic
(15) Bravo, A.; Bjørsvik, H.-R.; Fontana, F.; Liguori, L.; Minisci, F.
J . Org. Chem. 1997, 62, 3849.
(16) Bjørsvik, H.-R.; Fontana, F.; Liguori, L.; Minisci, F. Chem.
Commun. 2001, 523.

Aerobic Oxidation of N-Alkylamides
J . Org. Chem., Vol. 67, No. 8, 2002 2675
Ta ble 3. Oxid a tion of N-Alk yla ceta m id es, RNHCOCH3,
formation of HBr, catalyzes the hydrolysis according to
eq 28. Bromine atom is the hydrogen-abstracting species
that determines the selectivity of the oxidation, suggest-
ing that also in this case the N-benzylamide is more
reactive than the corresponding aromatic aldehyde.
The enthalpic effect is quite similar for hydrogen
abstraction from N-benzylamide and aromatic aldehyde
(BDE is about 87 kcal mol-1 for both ArCH(NH-
COCH3)-H and ArCO-H) and the polar effect, due to
the electrophilic character of the bromine atom and the
PINO radical (eq 16), determines the selectivity by
making the benzylamide more reactive than the alde-
hyde.
The oxidation takes place at higher temperatures (60-
100 °C) also in the absence of m-chlorobenzoic acid in
CH3CN or in AcOH solution. Under these more drastic
conditions, aldehydes are oxidized to carboxylic acids and
the reaction products are mixtures of carboxylic acids and
imides; the former prevail in AcOH solution at 100 °C,
the latter in CH3CN solution at 60-80 °C. The higher
temperature and the acidic medium favor the hydrolysis
according to eq 28, thus increasing the amount of
carboxylic acid. Since the imide can be easily converted
into the carboxylic acid by hydrolysis catalyzed by a
strong acid (eq 29), high yields in carboxylic acids can
be obtained from benzylamines by this oxidation method.
by O2 in CH3CN
T
t
conv
products
run
1
R
(°C) (h) (%)
selectivity (%)
n-hexyla
20
80
20
80
5
4
5
6
4
70
98
74
97
60
n-C4H9COOH (4)
n-C5H11COOH (15)
n-C5H11CONHCOCH3 (67)
n-C4H9COOH (14)
n-C5H11COOH (13)
n-C5H11CONHCOCH3 (68)
n-C10H21COOH (2)
n-C11H23COOH (8)
n-C11H23CONHCOCH3 (81)
n-C10H21COOH (6)
n-C11H23COOH (11)
n-C11H23CONHCOCH3 (81)
cyclohexanone (98)
2
3
4
n-hexyl
n-dodecyla
n-dodecyl
5
cyclohexyl 80
a
0.25 mmol of m-chlorobenzoic acid was utilized for 5 mmol of
amide.
The same behavior was observed in the oxidation of
primary alcohols by O2 with NHPI catalysis; the benzyl
alcohol selectively gives the aldehyde while nonbenzylic
alcohols give carboxylic acids. The oxidation selectivity
of the former is governed by the polar effect, while the
enthalpic effect is dominant for the latter.3
This behavior appears to be general when hydrogen
abstraction by an electrophilic radical is involved in the
oxidation. The same selectivity was, in fact, observed in
the oxidation of alcohols, ethers, and amides by H2O2 with
Br2 catalysis, where the bromine atom is the hydrogen-
abstracting species: benzyl derivatives selectively give
aldehydes, while carboxylic acids and esters are formed
with nonbenzylic derivatives.16-18
Secondary N-benzylamides give selectively the corre-
sponding ketones and acetamide (eq 30).
When a secondary alkyl group is involved in the
oxidation of alkylamides, the corresponding ketones are
obtained according to eq 30 for both benzylic and non-
benzylic amides.
(b) At higher temperatures (80-100 °C) in CH3CN or
AcOH, the oxidation always leads to a mixture of imides
and carboxylic acids, as in point (a), but the amount of
carboxylic acids significantly increases and above all, in
addition to carboxylic acids corresponding to the alkyl
groups (RCH2CH2- f RCH2COOH), also the carboxylic
acid showing loss of a carbon atom is formed (RCH2CH2-
f RCOOH). The plausible explanation for the formation
of the latter is related, in our opinion, to the â-scission
of the alkoxy radical (eq 31) formed in eq 22 in competi-
tion with hydrogen abstraction from NHPI (eq 23).
This result is good evidence supporting the mechanism
for the imide formation (eqs 16-18 and 22-26).
N-Alk yla ceta m id es. Two aspects of the oxidation of
N-alkylacetamides are different from that of N-benzyl-
acetamides (Table 3): (a) No traces of aldehyde are
formed in CH3CN at room temperature, even at low
conversion, but the imide and the carboxylic acid are the
reaction products when a primary alkyl group is involved.
Also in this case, the hydrolysis of the imide according
to eq 29 gives high yields in carboxylic acid, and the
overall process represents a simple and cheap way to
transform an alkylamine into a carboxylic acid.
This â-scission is more favored by an increase in
temperature and by a protic solvent19 than hydrogen
abstraction, and the result represents a further signifi-
cant support for the oxidation mechanism (eqs 16-18 and
22-26).
The absence of the aldehyde, even at low conversion,
suggests that the aldehyde is much more reactive than
the starting amide. This is due to the fact that the
selectivity in hydrogen abstraction by PINO (eq 16),
contrary to the behavior of the benzyl derivatives, is
governed in this case by the enthalpic effect (BDE for
the CONHC-H bond is 6-8 kcal mol-1 higher than for
RCO-H), which makes the aldehyde much more reactive
than the amide.
Exp er im en ta l Section
All the starting materials and the catalysts (N-hydroxy-
phthalimide and Co(OAc)2) were obtained from commercial
sources and used as such.
(17) Amati, A.; Dosualdo, G.; Fontana, F.; Minisci, F.; Bjørsvik, H.-
R. Org. Proc. Res. Devel. 1998, 2, 261.
(18) Minisci, F.; Fontana, F. Chim. Ind. (Milan) 1998, 80, 1309.
(19) Avila, D. V.; Brown, C. E.; Ingold, K. U.; Lusztyk, J . J . Am.
Chem. Soc. 1993, 115, 466.

2676 J . Org. Chem., Vol. 67, No. 8, 2002
Minisci et al.
Gen er a l P r oced u r es. Meth od A. A solution of the amide
(5 mmol), N-hydroxyphthalimide (0.5 mmol), and Co(OAc)2
(0.025 mmol) in 10 mL of the solvent (CH3CN or AcOH) was
placed in a three-necked flask under an atmosphere of O2. The
solution was stirred at the temperatures and for the times
reported in Tables 1-3. The catalyst was removed through
silica gel and the solution was analyzed by gas chromatogra-
phy by using the internal standard technique. All the reaction
products were known and were identified by GC-MS spectra
and comparison with authentic samples. The results are
reported in Tables 1-3.
Meth od B. The procedure is identical to method A with the
difference that 0.25 mmol of m-chlorobenzoic acid was also
added and the temperature was kept in all cases at 20 °C for
the reaction times reported in Tables 1-3.
Most of the reaction products (aromatic aldehydes, aromatic
and aliphatic carboxylic acids, cyclohexanone, succinimide) are
well-known, common commercial products. The acetylbenzoyl-
amines (MeCONH-CO-Ar, Table 2) were prepared according
to the procedure reported by Tanaka et al.20 The aliphatic
imides (RCONH-COMe) were prepared according to a known
procedure.21 Cyclic imides obtained in runs 1, 3, and 5 of Table
1 were prepared respectively according to the known pro-
cedures.22-24
J O016398E
(20) Tanaka, K. I.; Yoshifuji, S.; Nitta, Y. Chem. Pharm. Bull. 1987,
35, 364.
(21) Petterson, R. C.; Wambsgans, A. J . Am. Chem. Soc. 1964, 86,
1648.
(22) Rieche, A.; Schoen, W. Chem. Ber. 1966, 99, 3238.
(23) Venkov, A. P.; Statkova-Abeghe, S. M. Tetrahedron 1996, 52,
1451.
(24) Hall, H. K., J r.; Brandt, M. K.; Mason, R. M. J . Am. Chem.
Soc. 1958, 80, 6420.