New selective metal-free oxidations of primary alcohols by HNO3 or HNO3 and O2, catalyzed by Br2

Article abstract of DOI:10.1055/s-2004-832808

Primary benzylic alcohols are selectively oxidized to the corresponding aromatic aldehydes by molecular oxygen at atmospheric pressure, under Br ₂-HNO₃ catalysis in a biphasic medium (1,2-dichloroethane- water, 5:1) at 60 °C. Under paragonable experimental conditions the aliphatic alcohols are oxidized to esters.

Full text of DOI:10.1055/s-2004-832808

LETTER
2203
New Selective Metal-Free Oxidations of Primary Alcohols by HNO3 or HNO3
and O2, Catalyzed by Br2
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sco Minisci,* Ombretta Porta, Francesco Recupero, Carlo Punta, Cristian Gambarotti, Monica Pierini,
Laura Galimberti
Dipartimento di Chimica, Materiali e Ingegneria Chimica G. Natta, Politecnico di Milano, via Mancinelli, 7, 20133 Milano, Italy
Fax +39(02)23993080; E-mail: francesco.minisci@polimi.it
Received 10 May 2004
Abstract: Primary benzylic alcohols are selectively oxidized to the
corresponding aromatic aldehydes by molecular oxygen at atmo-
spheric pressure, under Br2–HNO3 catalysis in a biphasic medium
(1,2-dichloroethane–water, 5:1) at 60 °C. Under paragonable exper-
imental conditions the aliphatic alcohols are oxidized to esters.
Equation 1
Equation 2
Key words: alcohols, aldehydes, bromine, nitric acid, aerobic oxi-
dation
The oxidation of primary alcohols to the corresponding
aldehydes or carboxylic acids is a transformation of great
interest for both general synthetic purposes and industrial
applications. A variety of oxidants have been successfully
employed, including metal salts (i.e. Cr, Mn, Ru), Swern
and Dess–Martin oxidations.1,2 However, most of these
oxidations are not convenient from economical and envi-
ronmental point of view.
The results are summarized in Table 1. Also in this case,
as in the above mentioned H2O2-oxidation,3 Br2 is the ac-
tual oxidant and the function of HNO3 is to continuously
regenerate, at least in part, Br2 by oxidation of HBr,
according to Equation 3.
Nowadays, all the ecological standards require the devel-
opment of new catalytic processes characterized not only
by oxidant-economy but, above all, involving ecofriendly
clean oxidants such as hydrogen peroxide3,4 or molecular
oxygen. Obviously, molecular oxygen is both a conve-
nient and a good oxidant but, due to its triplet ground state
structure, its direct utilization is restricted by the spin
conservation; thus catalysis is necessary for the aerobic
oxidation of alcohols under mild conditions.
Equation 3
In the presence of oxygen, the fast oxidation of NO regen-
erates HNO3 in the aqueous phase, making the whole
process catalytic in HNO3.
The oxidation is well explained by the free radical chain
mechanism of the following Equations.
A large variety of metal salt complexes, with few
excepitions4–6 expensive, have been successfully utilized
as catalysts or co-catalysts for the aerobic oxidation of al-
cohols under homogeneous7 or heterogeneous8 catalysis.
Few years ago we have reported3 the H2O2-oxidation of
alcohols catalyzed by Br2, in which the function of H2O2
is to continuously regenerate Br2 from HBr.
Equation 4
Equation 5
Equation 6
Equation 7
Equation 8
We now wish to report new simple procedures of primary
alcohol oxidation by HNO3 or HNO3 and O2 catalyzed by
Br2 in a two phase system (H2O:ClCH2CH2Cl) in the
absence of metal salts.9
While primary benzyl alcohols afford selectively the
corresponding aldehydes (Equation 1) primary aliphatic
alcohols give the esters even at low conversion
(Equation 2).
SYNLETT 2004, No. 12, pp 2203–2205
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Advanced online publication: 03.09.2004
DOI: 10.1055/s-2004-832808; Art ID: G15104ST
© Georg Thieme Verlag Stuttgart · New York

2204
F. Minisci et al.
LETTER
HBr formed in Equation 4, Equation 5, Equation 6 and
Equation 8 is oxidized to Br2 by HNO3 making the pro-
cess catalytic in Br2. Ketyl (Equation 5) and acyl
(Equation 7) radicals react very fast with Br2 (close to the
diffusion rate) and it would seem that the reactions of the
same radicals with O2, NO and NO2, though fast, do not
significantly compete, owing to the higher Br2 stationary
concentration.
Equation 9
a) R = aryl, both Equation 4 and Equation 6 are almost
thermoneutral (BDE value of H-Br bond is 87 kcal/mol),
but a greater polar effect (see Equation 9) makes the alco-
hol much more reactive than the corresponding aromatic
aldehyde, which is then selectively formed in the oxida-
tion process.
In any case, no oxidation occurs in the absence of Br2,
under paragonable experimental conditions, even by
using an excess of HNO3.
The different behaviour of benzylic (Equation 1) and
aliphatic primary alcohols (Equation 2) is related to the
different bond dissociation enthalpies (BDE) of the H-
CH(OH)R bond (87 kcal/mol for R = aryl10 and ca. 96
kcal/mol for R = alkyl).11
The importance of the polar effect is well showed by the
lower conversions of nitro- and cyano- benzyl alcohols
compared with benzyl alcohol under the same conditions.
b) R = alkyl, Equation 6 is still thermoneutral, but
Equation 4 is endothermic (DH ~ 8–10 kcal/mol). The
dominant enthalpic effect makes the aldehyde much more
reactive than the corresponding aliphatic alcohol and the
ester is selectively obtained even at low conversion, ac-
cording to Equation 2 (and Equation 6, Equation 7 and
Equation 8).
Table 1 Aerobic Oxidation of Primary Alcohols, Catalyzed by
Br2–HNO3 at 60 °C under O2 at Atmospheric Pressure.9
Alcohol
Ar-CH2OH
Br2
(%)
HNO3
(%)
Conversion ArCHO,
Selectivity (%)
(%)
87
100
76
98
45
93
85
80
31
55
68
48
53
47
78
84
93
41
C6H5-a,b
5
20
10
20
20
20
20
20
10
20
20
20
20
20
40
20
20
20
50
32
50
110
32
65
32
65
50
32
65
32
32
65
65
32
110
32
98
96
97
94
96
99
98
99
98
99
98
97
94
96
99
97d
92d
94d
C6H5-
The reaction rates increase by increasing the amount of
Br2 and HNO3, which however, are not consumed operat-
ing in the presence of O2 and can be recycled by separat-
ing the aqueous from the organic phase. The lower
conversions observed under N2 atmosphere clearly indi-
cate the contribution of O2 in a catalytic cycle involving
the oxidation of nitrogen oxides.
C6H5-a
C6H5-c
C6H5-c
p-Cl-C6H4-
p-Cl-C6H4-
o-Cl-C6H4-
m-CN-C6H4-
m-CN-C6H4-
m-CN-C6H4-
p-CN-C6H4-
p-NO2-C6H4-
p-NO2-C6H4-a
m-NO2-C6H4-
n-C9H19-
With secondary alcohols this new oxidation method is
poorly effective, because the acidic medium catalyzes the
enolization of the ketones initially formed and Br2 is
consumed in the formation of a-bromoketones with con-
sequent catalysis inhibition.
References
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(9) Standard Experimental Procedure: A mixture of benzyl
alcohol (10 mmol), Br2 (2 mmol), HNO3 (3 mmol) in 20 mL
of 1,2 dichloroethane and 4 mL of H2O (biphasic system)
was stirred for 24 h under oxygen atmosphere at 60 °C.
n-C9H19-c
n-C9H19-c
a Reactions are carried out under air atmosphere.
b Reaction time 48 h, in all the other examples 24 h.
c Reactions are carried out under N2 atmosphere.
d Decyldecanoate is formed with the aliphatic 1-decanol.
Since the BDE values of the aldehydic C-H bond are
substantially the same (ca. 87 kcal/mol)12 for both ali-
phatic and aromatic aldehydes the resulting selectivity is
as follows:
Synlett 2004, No. 12, 2203–2205 © Thieme Stuttgart · New York

LETTER
New Selective Metal-Free Oxidations of Primary Alcohols
2205
The organic phase was separated from the aqueous solution
(11) Deminov, E. T.; Denosava, T. G. Handbook of Antioxidants;
CRC Press: New York, 2000.
and analyzed by GC with p-chlorobenzaldehyde as internal
standard. Conversion of benzyl alcohol was quantitative and
benzaldehyde was formed in 96% yield.
(12) (a) Atkinsen, R.; Baulsh, D. L.; Cox, R. A.; Hampson, R. F.;
Kerr, J. A.; Rossi, M. J.; Tral, J. J. Phys. Chem. Ref. Data
1999, 111, 4923. (b) Luo, Y. R. Handbook of Bond
Dissociation Energies in Organic Compounds; CRC Press:
New York, 2003, 62.
(10) Flash chromatography on silica gel lead to the separation of
8.9 mmol of pure benzaldehyde (91% yield of isolated
product). All the reactions of Table 1 were carried out
according to this procedure with exception of the examples
(a) under air and (b) under N2 atmosphere.
Synlett 2004, No. 12, 2203–2205 © Thieme Stuttgart · New York