Selective functionalisation of hydrocarbons by nitric acid and aerobic oxidation catalysed by N-hydroxyphthalimide and iodine under mild conditions

Article abstract of DOI:10.1016/S0040-4039(03)01687-3

Alkylbenzenes are selectively functionalised to the corresponding acetates by nitric aerobic oxidation catalysed by N-hydroxyphthalimide and iodine. With cyclohexane the oxidation leads to a mixture of cyclohexyl acetate and trans-2-iodocyclohexyl acetate. The mechanism is discussed.

Full text of DOI:10.1016/S0040-4039(03)01687-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6919–6922
Selective functionalisation of hydrocarbons by nitric acid and
aerobic oxidation catalysed by N-hydroxyphthalimide and iodine
under mild conditions
Francesco Minisci,* Francesco Recupero, Cristian Gambarotti, Carlo Punta and Roberto Paganelli
Dipartimento di Chimica, Materiali e Ingegneria Chimica ‘Giulio Natta’, Politecnico di Milano, via Mancinelli 7,
I-20131 Milano MI, Italy
Received 8 June 2003; revised 4 July 2003; accepted 4 July 2003
Abstract—Alkylbenzenes are selectively functionalised to the corresponding acetates by nitric aerobic oxidation catalysed by
N-hydroxyphthalimide and iodine. With cyclohexane the oxidation leads to a mixture of cyclohexyl acetate and trans-2-iodocyclo-
hexyl acetate. The mechanism is discussed.
©
2003 Elsevier Ltd. All rights reserved.
The selective functionalisation of hydrocarbons is a
challenging process of the organic chemistry. It is a
primary essential tool in organic synthesis and indus-
trial chemistry.
allows us to obtain benzyl alcohols from alkylbenzenes
through the corresponding acetates by nitric aerobic
oxidation of alkylbenzenes, catalysed by NHPI an I
(Eq. (1)) in acetic acid solution.
2
(1)
1
,2
Recently, we
have determinated the absolute rate
The results are reported in Table 1.
constants in the hydrogen abstraction by the phthal-
imido-N-oxyl (PINO) radical from a variety of hydro-
In a typical example, a solution of 4 mmol of Ph-CH2-
CH , 0.2 mmol of NHPI, 0.01 mmol of Co(OAc) , 2
−
1
−1
carbons (0.047, 0.38, 2.24, 3.25, 28.3 M
s
at 25°C
3
2
for cyclohexane, toluene, ethylbenzene, cumene and
benzyl alcohol, respectively). Since benzyl alcohols are
much more reactive than toluene and ethylbenzene
towards the hydrogen abstraction by the PINO radical,
which is considered the rate-determining step in the
aerobic oxidation of these substrates catalysed by N-
mmol of I
2
and 0.4 mmol of HNO
3
68% w/w in 10 mL
of AcOH was stirred for 6 h at 80°C under an atmo-
sphere of air. The analysis by GC, by using benzyl
acetate as internal standard, indicates a complete con-
version of Ph-CH
-CH and a quantitative yield of
2
3
Ph-CH(OAc)-CH . the AcOH solution was concen-
3
1
,2
trated to 2 mL and a solution of NaHCO was added
hydroxyphthalimide (NHPI), the oxidation of toluene
and alkyl benzenes can not lead selectively to the benzyl
alcohols, not even at low conversion. The higher reac-
3
to the residue. The extraction by CH Cl provides 0.623
2
2
g of pure Ph-CH(OAc)-CH (95%).
3
2–4
tivity of benzyl alcohol was mainly ascribed to polar
and enthalpic effects in the hydrogen abstraction by the
PINO radical.
We explain the formation of benzyl acetates by a
catalytic cycle initiated by the oxidation of NHPI by
HNO (Eq. (2)) with formation of the PINO radical,
3
which abstract hydrogen from benzylic CꢀH bonds (Eq.
In this communication we report a new process, which
(
3)) with the rate constants above reported.
(
(
2)
3)
Keywords: acetoxylation; N-hydroxyphthalimide; oxygen; functionali-
sation; alkylaromatics; iodine; cyclohexane.
*
Corresponding author. Tel.: +39-02-2399-3030, fax: +39-02-2399-
080; e-mail: francesco.minisci@polimi.it
3
0
040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01687-3

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F. Minisci et al. / Tetrahedron Letters 44 (2003) 6919–6922
a
2
Table 1. Oxidation of hydrocarbons by O and or HNO , catalysed by NHPI and I
2
3
Entry
Hydrocarbon
4 mmol)
NHPI
(mmol)
Co(OAc)2
(mmol)
I2
HNO3
(mmol)
O , N
(1 atm) (°C)
T
Conversion Selectivity
2
2
(
(mmol)
(%)
(%)
1
2
3
4
PhCH Me
0.2
0.2
0.2
0.2
0.01
0.01
–
2
2
2
0.8
0.4
0.4
0.4
0.4
Air
O2
O2
O2
80
80
80
80
100
100
100
88
PhCH(OAc)Me (100)
PhCH(OAc)Me (99.8)
PhCH(OAc)Me (100)
PhCH(OAc)Me (91)
PhCOMe (8)
2
PhCH Me
2
PhCH Me
2
PhCH Me
0.01
2
5
PhCH Me
0.2
0.01
0.4
0.4
O2
80
78
PhCH(OAc)Me (78)
PhCOMe (23)
2
6
7
8
PhCH2 CHMe2
PhCH2 CHMe2
Ph-Me
0.2
0.2
0.4
0.2
0.01
0.01
–
2
2
2
0.8
0.4
0.4
4
Air
O2
N2
Air
80
80
100
80
100
100
30
PhCH(OAc)CHMe2 (95)
PhCH(OAc)CHMe2 (97)
PhCH OAc (98)
2
b
9
Ph-Me
0.02
0.4
64
PhCH OAc (89)
2
PhCHO (11)
1
0b
1
Ph-Me
0.4
0.4
0.02
0.02
0.4
2
0.4
4
O2
N2
100
100
75
78
PhCH OAc (84)
2
PhCHO (16)
1
p-Cl-C H -Me
p-Cl-C H -CH OAc (72)
6
4
6
4
2
p-Cl-C H -CH(OAc) (10)
6
4
2
p-Cl-C H -CHO (18)
6
4
1
1
2
3
p-NO -C H -Me 0.2
–
–
0.8
4
0.4
4
Air
O2
100
100
20
58
p-NO -C H -CH I (94)
p-CN-C H -CH I (86)
6 4 2
2
6
4
2 6 4 2
p-CN-C H -Me 0.4
6
4
p-CN-C H -CH OAc (14)
6
4
2
1
1
4
5
Tetralin
Cyclohexane
10 mmol)
0.4
0.2
–
0.01
2
2
0.4
2
O2
Air
80
80
100
100
Naphthalene (100)
trans-2-Iodocyclohexyl
acetate (68)
c
(
Cyclohexyl acetate (32)
a
The reagents in the amounts reported in Table 1 in 10 ml of AcOH are stirred for 6 h at 80 or 100°C under an atmosphere of O , air or N .
2
2
The reaction product were analysed by GC with internal standard (m-methylbenzyl acetate) utilising the response factors obtained from
authentic samples.
The reaction was carried out for 24 h.
An excess of cyclohexane (10 mmol) was utilised; conversion is based on HNO3.
b
c
The benzyl radical can be trapped by three very fast
reactions (Eq. (4)), all characterised by almost diffusion
derivatives, with the exception for the presence of
strongly electron-withdrawing groups (NO , CN) in
the phenyl ring, plainly supporting the reaction mecha-
nism.
2
9
10
−1 −1
controlled rates (10 –10
M
s ).
HI is quickly oxidised by HNO , NO or O to I ,
3
2
2
2
which is not consumed, acting as a catalyst. No benzyl
acetate is formed under the same conditions in the
absence of I2.
(
4)
When the oxidation is carried out with catalytic
amount of HNO in presence of O the overall catalysis
3
2
also involves the formation of the PINO radical by
hydrogen abstraction from NHPI by NO (Eq. (6)),
2
generated in Eq. (2) and regenerated by the aerobic
oxidation of NO, arising from the decomposition of
HNO and making catalytic the process in HNO .
Recently, the nitration of hydrocarbons by NO and
2
5,6
NHPI catalysis has been reported. However benzyl
iodides are selectively formed if the concentration of I2
is much higher than that of NO and O . Under the
2
3
2
2
reaction conditions the solvolysis of benzyl iodides
leads to benzyl acetates (Eq. (5)).
(6)
(
5)
Thus, the stoichiometry of the reaction with stoichio-
metric amount of HNO under a nitrogen atmosphere
3
is given by Eq. (7), while with catalytic amount of
HNO in the presence of O the stoichiometry is given
Blank experiments have shown that under the reaction
conditions benzyl iodides undergo solvolysis to acetoxy
3
2
by Eq. (8).

F. Minisci et al. / Tetrahedron Letters 44 (2003) 6919–6922
6921
(7)
ination with formation of cyclohexene (Eq. (9a)) and to
a minor extent nucleophilic substitution (Eq. (9b)).
(
8)
In both cases (Eqs. (7) and (8)) the reactions are
catalytic in I , which is continuously regenerated, but
2
(9)
they require a relatively high concentration of I in
2
order that Eq. (4c) can prevail over Eqs. (4a) and (4b).
No oxidation occurs in the absence of NHPI, cleary
showing the fundamental role of Eq. (3).
HI is fast oxidised to I and the electrophilic addition to
2
The reaction is particularly selective for the oxidation
cyclohexene leads to the trans-2-iodocyclohexyl acetate
(Eq. (10)).
of the benzylic CH group; the secondary benzyl acetate
2
appears to be much less reactive than the starting
alkylbenzenes and the further oxidation does not occur
also with complete conversion of the alkylbenzenes
(10)
(
entries 1–3, 6–7). We ascribe this behaviour to the
2–4
sensitivity to the polar effect of acetoxy group in the
hydrogen abstraction by the PINO radical.
7
Very recently an analogous process has reported by
oxidation of cycloalkanes by diacetoxyiodobenzene and
Minor but significant amounts of acetophenone are
t-BuOH (Eq. (11)), in which the hydrogen abstraction
8
formed when the concentration of I is lower (entries 4
from the alkane occurs by the t-butoxyl radical, but
2
and 5), due to the competition of Eq. (4b).
the suggested mechanism is somewhat different.
(11)
With toluene a high selectivity (entry 8) in benzyl
acetate was observed by using stoichiometric amount of
Moderate yields of benzylic acyloxylation of alkyl aro-
matic were previously obtained by a variety of much
more complex and expensive processes, such as the use
HNO under a nitrogen atmosphere; however, in the
3
9–12
13,14
18
15,16
presence of oxygen significant amounts of benzaldehyde
are formed, due to the competition of Eq. (4b) (entries
of Pb(OAc)4,
Pd(OAc)2,
peroxyesters,
17
hydroperoxydes, peroxy acids; most of these pro-
cesses are characterised by free-radical mechanisms.
9
and 10).
With isopropyl aromatics, as cumene, the reaction gives
poor results, due to the formation of small amount of
phenol by acid decomposition of hydroperoxide formed
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