A new, highly selective synthesis of aromatic aldehydes by aerobic
free-radical oxidation of benzylic alcohols, catalysed by
n-hydroxyphthalimide under mild conditions. Polar and enthalpic effects
Francesco Minisci,* Carlo Punta, Francesco Recupero, Francesca Fontana and Gian Franco Pedulli
Dipartimento di Chimica del Politecnico, via Mancinelli 7, I-20131, Milano MI, Italy.
E-mail: francesco.minisci@polimi.it
Università di Bergamo, Dipartimento di Ingegneria, viale Marconi 5, I-24044, Dalmine BG, Italy
Università di Bologna, Dipartimento di Chimica Organica ‘A.Mangini’, via S.Donato 15, I-40127, Bologna
BO, Italy
Received (in Corvallis, OR) 14th November 2001, Accepted 6th February 2002
First published as an Advance Article on the web 4th March 2002
A new selective synthesis of aromatic aldehydes is described,
based on catalytic oxidation of benzyl alcohols with molec-
ular oxygen at rt and atmospheric pressure.
in the H2O2 oxidation is determined by hydrogen abstraction by
the electrophilic bromine atom,9 these results suggest that
hydrogen abstraction by the electrophilic PINO radical could
also show a similar selectivity.
Recently a variety of interesting aerobic oxidations of organic
compounds, including alkanes, under mild conditions was
achieved by using N-hydroxyphthalimide (NHPI) combined
with Co salt catalysis, particularly by the Ishii group.1 It was, in
particular, reported2 that primary alcohols are easily oxidised to
carboxylic acids at rt and atmospheric pressure, but no example
of benzylic alcohols was given; a few years ago the aerobic
oxidation of benzyl alcohol catalysed by NHPI at 100 °C was
reported, by the same research group, to give a mixture of
benzoic acid and benzaldehyde.3 In all these oxidations the
phthalimide-N-oxyl (PINO) radical, generated in situ, plays a
key role in the catalytic process, acting as the hydrogen
abstracting species.
Actually the aerobic oxidation of primary benzylic alcohol,
catalysed by NHPI and Co salts under mild conditions in MeCN
solution leads to aromatic aldehydes with high selectivities,
without appreciable formation of carboxylic acids (Table 1)
(eqn. (2))
(2)
Under the same conditions non-benzylic alcohols lead to
carboxylic acids, even at low conversions. A variety of metal
salt complexes (Ru,10 Cu,11 Mn,4 Co,4 Pd12) in combina-
tion4,10,11 or not12,13 with TEMPO was utilised for the aerobic
oxidation of primary alcohols to aldehydes. To the best of our
knowledge, the catalysts Mn(II) and Co(II) or Cu(II) nitrates in
combination with TEMPO4 or Co(OAc)2 in combination with
NHPI, described in this Communication, appear to be the
cheapest and the most effective (the oxidation takes place in
both cases with air at atmospheric pressure and rt with high
selectivity), and suitable for industrial applications. The
advantage in using TEMPO is related to the general character of
the oxidation of benzylic and non-benzylic alcohols, while the
use of NHPI is limited to benzylic alcohols for the below
discussed mechanistic aspects, but NHPI (obtained from
phthalic anhydride and NH2OH) is cheaper than TEMPO and
moreover it can be more easily recovered and recycled, due to
its low solubility in several solvents.
Very recently we4 have reported a general, particularly
convenient process for the aerobic oxidation of primary
alcohols (both benzylic and non-benzylic) to aldehydes,
catalysed by TEMPO (tetramethylpiperidine-N-oxyl) radical
combined with transition metal salts. A main function of
TEMPO, which makes the oxidation particularly selective, is to
inhibit the further free radical oxidation of aldehydes by O2.
We have supposed that the different catalytic behaviour of
PINO and TEMPO (both N-oxyl radicals) is due to the different
bond dissociation energy (BDE) of the O–H bond of the
corresponding N-hydroxy derivatives. The BDE for the piper-
idine N-hydroxy derivative is known and it is relatively low (70
kcal mol21); thus we have tried to determine the BDE of the O–
H bond for acyl N-hydroxy compounds by a method previously
described,5–7 based on the size of the equilibrium constants for
the hydrogen transfer between a reference phenol and the N-
hydroxy derivative and the corresponding radicals (eqn. (1)) by
means of EPR spectroscopy.
Table 1 Oxidation of benzylic alcohols, X-C6H4-CH2OH, to aromatic
aldehydes by oxygena
Selectivity
X
Time/h
Conversion (%)
(%)
(1)
H
2
4
3
1
2
3
3
4
4
3
3
2
4
100
85
86
75
100
85
100
Traces
88
100
92
92
94
91
94
—
99
98
—
91
95
97
95
98
Hb
Hc
We succeeded in determining the BDE of the O–H bond for
benzoylphenylhydroxylamine (PhCON(OH)Ph) (80 kcal
mol21) but for NHPI, until now, only a lower limit (BDE for the
O–H bond > 86 kcal mol21) was established. These results,
even if not yet complete,8 clearly show that the substitution of
an alkyl by an acyl group strongly increases the BDE of the O–
H bond in N-hydroxy derivatives and explains well the opposite
behaviour of PINO and TEMPO: the former plays a key role in
determining free-radical chains, the latter inhibits free-radical
processes.
p-OMe
p-OMed
m-OMe
p-NO2
p-NO2
m-NO2
p-Cl
m-Cl
p-Me
m-CN
b
100
100
a Standard procedure: 3 mmol of benzylic alcohol, 0.3 mmol of NHPI, 0.015
mmol of Co(OAc)2, 0.15 mmol of m-chlorobenzoic acid in 15 mL of
acetonitrile with O2 at atmospheric pressure and rt. b As in (a) without m-
chlorobenzoic acid. c As in (a) with air instead of O2. d 98% of p-
methoxybenzoic acid was obtained.
On the other hand, recently, we9 have reported the oxidation
of alcohols, ethers and amides by H2O2, catalysed by bromine;
in particular primary benzylic alcohols give selectively the
aromatic aldehydes, while non-benzylic alcohols give the
carboxylic acids, even at low conversions. Since the selectivity
688
CHEM. COMMUN., 2002, 688–689
This journal is © The Royal Society of Chemistry 2002