Re2O7-catalyzed carbon-carbon bond cleavage of ketones into carboxylic acids with aq. TBHP

Article abstract of DOI:10.1055/s-1999-2669

A mild and efficient catalytic method for the C-C bond cleavage of ketones to corresponding carboxylic acids in good yields is described using a catalytic amount of Re₂O₇ and 70% tert. butyl hydroperoxide (TBHP) as oxidant.

Full text of DOI:10.1055/s-1999-2669

LETTER
559
Re2O7-Catalyzed Carbon-Carbon Bond Cleavage of Ketones into Carboxylic
Acids with aq. TBHP
S. Gurunath, A. Sudalai*
Div. of Org. Chem. Technology, National Chemical Laboratory, Pune-411 008, India.
Fax +91-020-393614; E-mail: sudalai@dalton.ncl.res.in
Received 9 February 1999
quantities of Re-oxides. After some experimentation, we
Abstract : A mild and efficient catalytic method for the C-C bond
found that the combination of Re2O7 (6 mole%) and 70%
cleavage of ketones to corresponding carboxylic acids in good
yields is described using a catalytic amount of Re2O7 and 70% tert.
TBHP (8 equiv.) in acetic acid12 efficiently catalyzes the
desired oxidative cleavage of ketones to produce carbox-
ylic acid. As can be seen from the Table 1, a 55% conver-
sion of ketone to acid was realized in AcOH in 5h when
4-methoxyacetophenone was reacted with TBHP and cat-
alytic amount of Re2O7. Lowering the concentration of ei-
ther TBHP or Re2O7 lowers the yield of the product. The
activity of Re2O7 is found to be high in AcOH as solvent
compared to MeOH and t-BuOH. Other rhenium oxides
butyl hydroperoxide (TBHP) as oxidant
Key words: Re2O7, TBHP, C-C bond cleavage, ketones, carboxylic
acids
The direct oxidative C-C bond cleavage of aryl methyl ke-
tones to benzoic acids is of commercial importance in in-
dustry due to the easy accessibility of these ketones by
Friedel-Crafts’ acylation1. Also, a variety of substituted
benzoic acids are widely used in the pharmaceutical in-
dustry as drug intermediates for the synthesis of antirheu-
matics, antimalarials, tranquilizers etc., in agrochemicals
as herbicides and in polymer and dye-stuff industries as
modifiers for resins and dye sensitizer respectively2. Tra-
ditionally, the oxidative degradations of methyl ketones to
carboxylic acids are achieved by sodium hypohalites in
strongly basic conditions (haloform reaction)3. and by CrV
and MnVII reagents under stoichiometric conditions4. Al-
though these procedures are usually effective, problems
often crop up due to the lack of selectivity in oxidations
coupled with safety hazards associated with the use of
large quantities of toxic chromium and halo compounds.
8
such as ReO3OSiPh3 and CH3ReO3 show less activity and
selectivity. In fact, CH3ReO3 gave phenyl acetate, the
Baeyer-Villiger rearranged product in high yield9. Under
the conditions employed, carboxylic acid was not formed
in the absence of Re catalyst.
Heptavalent rhenium has received focal attention in recent
years in inorganic and organometallic chemistry5. More
recently, Re2O7 has proven to be an excellent catalyst for
epoxidation6 and dihydroxylation7 of alkenes when used
in combination with Me3SiOOSiMe3 and H2O2 as oxi-
dants respectively. Herein, we describe that Re2O7 effi-
ciently catalyzes the direct oxidative cleavage of methyl
ketones to carboxylic acids using 70% tert-butyl hydro-
peroxide (TBHP) as oxidant [Scheme 1].
The mild reaction conditions are compatible with sensi-
tive functional groups such as phenol, C-C double bond
etc. The reaction times are typically 5 h using Re2O7 (6
mole%) and 8 equivalents of TBHP. A remarkable feature
of the Re/TBHP catalytic system is its unusual regioselec-
tivity of oxidation exhibited towards methyl and ethyl ke-
tones. For example, 4-isobutylacetophenone and 4-
phenyl-3-buten-2-one underwent oxidation regioselec-
tively at the methyl group despite the significantly greater
Scheme 1
The new catalytic system consists simply of Re2O7, 70%
TBHP in an organic solvent and is totally free from any
organic or inorganic halides. We selected 4-methoxyace-
tophenone as the test substrate and subjected it to oxida-
tion with TBHP in various solvents with catalytic
Synlett 1999, No. 5, 559–560 ISSN 0936-5214 © Thieme Stuttgart · New York

560
S. Gurunath, A. Sudalai
LETTER
oxidizability of the benzylic C-H and C = C bonds respec-
tively (entries 7 and 13).
Scheme 2: Re-catalytic cycle
References and Notes
(1) Heany, H. in Comprehensive Organic Synthesis, Ed. Trost B.
M. and Fleming I., Pergamon Press, New York, Vol. 2, 1991
p. 733,.
(2) Maki T., Suzuki Y. in Ullmann,s Encyclopedia of Industrial
Chemistry, Executive Ed. Wolftgang Gerhartz, 5th Edition
VCH, vol. A3, 1985 p. 555.
(3) (a) Kajigaeshi S., Nakagawa T., Nagasaki N., Fujisaki S.,
Synthesis, 1985, 674, (b) Fusion R.C, Bull B. A., Chem. Rev.
1934, 15, 275.
(4) Moriarty R.M., Prakash I., Penmasta R., J. Chem. Soc. Chem.
Commun.,1987, 202.
(5) a. Romao C.C., Kuehn F. E, Herrmann W. A., Chem. Rev.
1997, 97, 3197.
b. Rudolph J., Reddy K. L., Chiang J.P., Sharpless K.B., J.
Am. Chem. Soc. 1997, 119, 6189.
(6) Rudolph J., Reddy K. L., Chiang J.P., Sharpless K.B., J. Am.
Chem. Soc. 1997, 119, 6189.
(7) Warwel S., gen. Klass M. R., Sojka M., J. Chem. Soc. Chem.
Commun. 1991, 1578.
(8) Schoop T., Roesky H. W, Noltemeyer M., Schmidt H. G.;
Organometallics 1993, 12, 571.
(9) Herrmann W. A., Fischer R. W., Correia J. D. G., J. Mol. Cat.
1994, 94, 213.
(10) Herrmann W. A., Correia J. D. G., Kuehn F. E., Artus G.R.J.,
Romao C.C., Chem. Eur. J. 1996, 2, 168.
(11) Van Heldon R. V., Kooyman E. C., Rec. Trav. Chim. Pays-
Bas, 1961, 80, 57.
Even the heteroaromatic substrate, 2-acetylpyrrole under-
went oxidative cleavage to afford pyrrole-2-carboxylic
acid in 60% yield. However, cyclohexanone failed to un-
dergo oxidation under the reaction conditions. Also the re-
covered catalyst from the reaction mixture was found to
be inactive when it was recycled.
Scheme 2 presents a possible mechanistic pathway for the
above reaction. The first step involves the reaction of
Re2O7 with TBHP to produce catalytically active highly
oxygenated peroxo species 110. This active peroxide spe-
cies 1, oxidises the enol form of the ketone11 at the α-po-
sition to give keto alcohol, 2, which then subsequently
undergoes oxidation to produce the less stable keto acid,
3. Oxidative elimination of CO2 (confirmed by GLC anal-
ysis) afforded benzoic acids.
(12) Typical procedure:
The commercially available Re2O7 and 70% TBHP were
procured from Aldrich, USA. In a typical procedure, a mixture
of (4-isobutylphenyl) methyl ketone (500 mg, 2.8 mmol),
TBHP (22.3 mmol) and Re2O7 (81.31mg, 6 mole%) in AcOH
(5 ml), was stirred magnetically at 100°C for 5 h. The progress
of the reaction was monitored by TLC. After 5 h, the products
were analysed by GLC. The reaction mixture was quenched
with water (8 ml) and carboxylic acid was isolated by its
extraction with ether (4×10 ml). Removal of solvent furnished
4-isobutylbenzoic acid (364 mg, 72%). 1H NMR (200 MHz,
CDCl3, 25 °C), d0.8 (d, J = 7 Hz, 6H, 2 × -CH3), 1.85 (m, 1 H,
-CH), 2.55 (d, J = 6 Hz, 2H, -CH2), 7.25 (d, J = 8 Hz, 2H, Ar-
H), 8.1 (d, J = 8 Hz, 2 H, Ar-H). MS: m/z (rel. intensity) 178
(M+, 47), 161 (16), 149 (30), 136 (100), 91 (70), 77 (30), 65
(22).
In summary, we have developed an elegant method for the
direct synthesis of carboxylic acids from ketones using
commercially available Re2O7 as catalyst and 70% TBHP
as oxidant. This process displays good functional group
tolerance and high regioselectivity.
Article Identifier:
1437-2096,E;1999,0,05,0559,0560,ftx,en;L00199ST.pdf
Synlett 1999, No. 5, 559–560 ISSN 0936-5214 © Thieme Stuttgart · New York