Highly selective and efficient conversion of alkyl aryl and alkyl cyclopropyl ketones to aromatic and cyclopropane carboxylic acids by aerobic catalytic oxidation: A free-radical redox chain mechanism

Article abstract of DOI:10.1055/s-2002-22706

An efficient and convenient method has been developed for the oxidation of aryl alkyl and cyclopropyl alkyl ketones to aromatic and cyclopropane carboxylic acids by molecular oxygen at atmospheric pressure, catalysed by Mn(NQ₃)₂ in combination with Co(NO₃)₂ or Cu(NO₃)₂. This simple, cheap and highly selective process has a general character for the synthesis of carboxylic acids and it is particularly suitable for industrial applications.

Full text of DOI:10.1055/s-2002-22706

610
LETTER
Highly Selective and Efficient Conversion of Alkyl Aryl and Alkyl Cyclopropyl
Ketones to Aromatic and Cyclopropane Carboxylic Acids by Aerobic
Catalytic Oxidation: A Free-radical Redox Chain Mechanism.
Efficient
C
onv
r
ersion
o
a
f
A
lkyl
K
et
n
ones to Arom
c
atic and
C
e
yclopropan
s
e
Carboxy
c
lic
A
cids o Minisci,*a Francesco Recupero,a Francesca Fontana,b Hans-René Bjørsvik,c Lucia Liguoric
a
Dipartimento di Chimica, Materiali e Ingegneria Chimica “G.Natta”, Politecnico di Milano, via Mancinelli 7, 20131 Milano, Italy
Fax +39(2)23993080; E-mail: francesco.minisci@polimi.it
b
c
Dipartimento di Ingegneria, Università di Bergamo, viale Marconi 5, 24044 Milano, Italy
Department of Chemistry, University of Bergen, Allègaten 41, 5007 Bergen, Norway
Received 16 January 2002
sion to carboxylic acids particularly interesting either for
general synthetic purposes or for industrial applications.
A variety of other reagents [e.g. t-BuOOH and Re2O7,3 so-
dium nitrite–pyridinium poly(hydrogen fluoride),4 KOH,5
Abstract: An efficient and convenient method has been developed
for the oxidation of aryl alkyl and cyclopropyl alkyl ketones to aro-
matic and cyclopropane carboxylic acids by molecular oxygen at at-
mospheric pressure, catalysed by Mn(NO3)2 in combination with
Co(NO3)2 or Cu(NO3)2. This simple, cheap and highly selective sodium
bromite,6
C6F5I(OCOCF3)2,7
disodium
nitrosylpentacyanoferrate8] were also utilised.
process has a general character for the synthesis of carboxylic acids
and it is particularly suitable for industrial applications.
We now wish to report a general conversion of alkyl aryl
ketones to aromatic carboxylic acids, based on the catalyt-
ic oxidation by O2, much more selective, cheap and con-
venient compared to the above mentioned methods, and
suitable for industrial applications.9
Key words: carboxylic acids, kjetones, oxidation by molecular ox-
ygen, free-radical, redox catalysis
Recently, an efficient conversion of alkyl aryl ketones to
aromatic carboxylic acids by tetrabutyl ammonium perio-
date has been reported.1 The ready availability of alkyl
aryl ketones through electrophilic aromatic acylation with
a variety of acylating reagents (acyl chlorides, anhydrides,
carboxylic acids) and catalysts2 (AlCl3, FeCl3, protic acids
in homogeneous or heterogeneous phase, zeolites) or by
aerobic oxidation of alkyl aromatics makes their conver-
Our interest for the conversion of alkyl aryl ketones to ar-
omatic carboxylic acids arose during the investigation to
improve the Borregaard industrial process for the produc-
tion of vanillin by lignin oxidation.10 A by-product of this
oxidation is 4-acetovanillone, which was utilised through
NaOCl oxidation for the industrial production of veratric
acid.11 The reaction was not particularly selective and by-
products arising from ring chlorination were formed. We
Scheme 1
Synlett 2002, No. 4, 29 03 2002. Article Identifier:
1437-2096,E;2002,0,04,0610,0612,ftx,en;G00702ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

LETTER
Efficient Conversion of Alkyl Ketones to Aromatic and Cyclopropane Carboxylic Acids
611
have investigated a variety of transition metal salt cata- nificant synthetic and mechanistic aspect of the reaction
lysts for the aerobic oxidation of alkyl aryl ketones, thus concerns the fact that the oxidation of methyl-, ethyl- and
developing a particularly efficient and selective catalytic isopropyl-acetophenones involves oxidation of the acetyl
system, based on Mn(NO3)2 in combination with group by the couple Mn(II)–Co(II), while the oxidation of
Co(NO3)2 or Cu(NO3)2. The results are reported in the alkyl group takes place without appreciable oxidation
Table 1.
of the acetyl group when only a Co(II) salt is used as cat-
alyst. Moreover, phenyl methyl ketone, phenyl ethyl ke-
tone and phenyl isopropyl ketone are easily oxidised to
benzoic acid, while phenyl t-butyl ketone is completely
inert.
The mechanism of the oxidation is related to the fact that
a Mn(II) salt is necessary for the oxidation to occur; Co(II)
and Cu(II) salts alone are inactive, but they exalt the activ-
ity of the Mn(II) ion; among the different salts, the nitrates
proved to be particularly effective (Table 2). Another sig-
Table 1 Oxidation of Alkyl Aryl Ketones, Ar-CO-R, to Carboxylic Acids, ArCOOH.a
Ar-CO-R
Conversion (%)
ArCOOH, Selectivity (%)
Ph-COOH (95)
Ph-CO-Me
97
96
Ph-CO-Meb
Ph-COOH (96)
Ph-CO-Et
98
Ph-COOH (97)
Ph-CO-CH(Me)2
100
–
Ph-COOH (95)
Ph-CO-C(Me·)3
–
4-Me-C6H4-COMe
4-Et-C6H4-COMe
96
4-Me-C6H4-COOH (91)
4-Et-C6H4-COOH (89)
4-(Me)2CH-C6H4-COOH (85)
4-MeO-C6H4-COOH (94)
4-MeO-C6H4-COOH (95)
2-MeO-C6H4-COOH (91)
3,4-(MeO)2-C6H3-COOH (98)
4-Cl-C6H4-COOH (95)
1-Naphth-COOH (97)
1-Naphth-COOH (96)
1-Naphth-COOH (97)
4-OMe·-1-C10H6-COOH (94)
Naphth-1,5-di-COOH (90)
Naphth·-2-OMe-6-COCH(Me)2
4-COOH-C6H4-Ph (95)
4-COOH-C6H4-Ph (96)
4-CO-C6H4-C6H4-COOH-4 (90)
94
4-(Me)2CH-C6H4-COMe
4-MeO-C6H4-COMe
4-MeO-C6H4-COMeb
2-MeO-C6H4-COMe
3,4-(MeO)2-C6H3-COMe
4-Cl-C6H4-COMe
1-Naphth-COMe
95
100
96
100
100
93
100
100
100
100
92
1-Naphth-COC2H5
1-Naphth-COCH(Me)2
4-OMe-1-C10H6·COMe
C10H6-1,5-di-COCH(Me)2
C10H6·-2-OMe-6-COCH(Me)2
4-MeCO-C6H4-Ph
4-Me-CH2-CO-C6H4-Ph
4-MeCO-C6H4-C6H4-COMe-4
96
100
100
92
a Standard experimental procedure: A solution of ketone (10 mmol), Mn(NO3)2 (0.2 mmol), Co(NO3)2 (0.2 mmol) in 20 mL of acetic acid
was stirred for 6 h under oxygen atmosphere at 100 °C and ambient pressure. The solvent was evaporated and the residue was dissolved in
NaHCO3 aqueous solution, which was extracted with ethyl acetate. The aqueous solution was acidified with H2SO4 and the precipitated pure
aromatic acid was filtered, while the aqueous solution was extracted with ethyl acetate to recover the further amount of carboxylic acid de-
pending on its solubility in water.
b Cu(NO3)2 was utilised instead of Co(NO3)2.
Synlett 2002, No. 4, 610–612 ISSN 0936-5214 © Thieme Stuttgart · New York

612
LETTER
Table 2 Oxidation of Acetophenone under Different Catalytic
Conditions.a
Catalytic system
T
(°C)
Conv.
(%)
Select.
(%)
Mn(NO3)2
90
90
90
90
90
90
90
90
90
75
75
50
50
56
96
–
Co(NO3)2
–
Scheme 3
Cu(NO3)2
–
–
Mn(NO3)2; Co(NO3)2
Mn(NO3)2; Cu(NO3)2
Mn(OAc)2; Co(OAc)2
Mn(OAc)2; Cu(OAc)2
MnSO4
97
95
96
97
95
–
Actually, the oxidation of cyclopropyl methyl, cyclopro-
pyl ethyl and cyclopropyl isopropyl ketones under the
same conditions reported in Table 1 occurs with complete
conversion and formation of cyclopropane carboxylic
acid with 93%, 91% and 96% selectivities respectively.
95
30
32
–
References
MnCl2
–
–
(1) Lee, J. C.; Choi, J. H.; Lee, Y. C. Synlett 2001, 1563.
(2) Heaney, H.In Comprehensive Organic Synthesis, Vol. 2;
Trost, B. M.; Fleming, I., Eds.; Pergamon Press: New York,
1991, 733.
(3) Gurunath, S.; Sudalai, A. Synlett 1999, 559.
(4) Olah, G. A.; Ramos, M. T.; Wang, Q.; Surya Prakash, G. K.
Synlett 1991, 41.
Mn(NO3)2
40
95
98
97
–
Mn(NO3)2; Co(NO3)2
Mn(NO3)2; Co(NO3)2
Mn(OAc)2; Co(OAc)2
72
38
traces (< 2)
(5) abjek, A.; Petri , A. Tetrahedron Lett. 1999, 40, 6077.
(6) Kajigaeshi, S.; Nakagawa, T.; Nagasaki, N.; Fujisaki, S.
Synthesis 1985, 674.
a The standard procedure of Table 1 was utilised.
(7) Moriarty, R. M.; Prakash, I.; Penmasta, R. J. Chem. Soc.,
Chem.Commun. 1987, 202.
(8) Kathó, A.; Beck, M. T. Synlett 1992, 165.
(9) Minisci, F.; Fumagalli, C.; Pirola, R. It. Pat.
MI2000A000237, 2000.
(10) Bjørsvik, H.-R.; Minisci, F. Org. Process Res. Dev. 1999, 3,
330.
(11) Bjørsvik, H.-R.; Norman, K. Org. Process Res. Dev. 1999,
3, 341.
(12) (a) Citterio, A.; Gentile, A.; Minisci, F.; Serravalle, M. Gazz.
Chim. Ital. 1983, 113, 443; and references therein. (b)
More recent reviews: Melikian, G. G. Synthesis 1993, 833.
(c) Also see: Linker, T. J. Prakt. Chem. 1997, 339, 488.
(13) Walling, C. Active Oxygen in Chemistry; Foote, C. S.;
Valentine, J. S.; Greenberg, A.; Liebmann, J. L., Eds.;
Blackie Academic-Professional: New York, 1995, 42.
(14) A large scale procedure: 12 g of acetophenone, 2 mmol of
Mn(NO3)2, 2 mmol of Co(NO3)2 in 100 mL of acetic acid
were stirred under oxygen atmosphere at 100 °C and
ambient pressure for 6 h. The solution was analysed by GLC,
revealing the presence of 0.42 g of unreacted acetophenone.
The solution was evaporated and the residue was dissolved
in 100 mL of aqueous solution of NaHCO3; the aqueous
phase was extracted with ethyl acetate, then acidified with
H2SO4 and extracted again with ethyl acetate. By
evaporating the solvent 11.1 g of pure benzoic acid (> 99%
in GLC) were obtained. Conversion 96.5%, selectivity 93%.
All these results are well explained by a free radical redox
chain mechanism, according to Scheme 1.
The electron-transfer oxidation of ketones by Mn(III)
salts to form -ketoalkyl radicals (1) is well-known.12
Also the formation of alkoxyl radical from the hydroper-
oxide with Co(II) salt (4) is well documented.13 The Cu(I)
salt has a catalytic function similar to that of Co(II) salt in
Equations 4 and 6. The initiation step of the chain can be
due to traces of hydroperoxides formed by autoxidation or
due to the peroxyl radical Co(III)OO· formed from Co(II)
and O2. The overall stoichiometry is shown in Scheme 2.14
Scheme 2
The mechanism of Scheme 1 suggested that cyclopropyl
alkyl ketones should be oxidised by this catalytic system
to cyclopropane carboxylic acid because the bond dissoci-
ation energies (BDEs) of the C-H bonds in the cyclopro-
pane ring are higher than the BDEs of the C-H bonds in
the alkyl group. This should be reflected in the enolisation
and subsequent electron-transfer oxidation according to
Scheme 3, leading to cyclopropane carboxylic acid.
Synlett 2002, No. 4, 610–612 ISSN 0936-5214 © Thieme Stuttgart · New York