Iron(III)-ethylenediaminetetraacetic acid mediated aerobic oxidation of α-hydroxyketones: a simple and convenient synthesis of α-diketones

Article abstract of DOI:10.1081/SCC-120006026

Iron(III)-ethylenediaminetetraacetic acid in aqueous methanol offers a simple, environmentally acceptable synthetic tool to oxidize α-hydroxyketones α-diketones with molecular oxygen, in excellent yields and under mild conditions and without any side reactions.

Full text of DOI:10.1081/SCC-120006026

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
IRON(III)-ETHYLENEDIAMINETETRA-ACETIC
ACID MEDIATED AEROBIC OXIDATION OF α-
HYDROXYKETONES: A SIMPLE AND CONVENIENT
SYNTHESIS OF α-DIKETONES
T. Venkateshwar Rao , Rajendra S. Dongre , Suman L. Jain & Bir Sain
To cite this article: T. Venkateshwar Rao , Rajendra S. Dongre , Suman L. Jain & Bir Sain
(2002) IRON(III)-ETHYLENEDIAMINETETRA-ACETIC ACID MEDIATED AEROBIC OXIDATION OF
α-HYDROXYKETONES: A SIMPLE AND CONVENIENT SYNTHESIS OF α-DIKETONES, Synthetic
Communications, 32:17, 2637-2641, DOI: 10.1081/SCC-120006026
To link to this article: http://dx.doi.org/10.1081/SCC-120006026
Published online: 20 Aug 2006.
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 17, pp. 2637–2641, 2002
IRON(III)-ETHYLENEDIAMINETETRA-
ACETIC ACID MEDIATED AEROBIC
OXIDATION OF a-HYDROXYKETONES: A
SIMPLE AND CONVENIENT SYNTHESIS
OF a-DIKETONES
T. Venkateshwar Rao, Rajendra S. Dongre,
*
Suman L. Jain, and Bir Sain
Chemical and Biosciences Division, Indian Institute of
Petroleum, Dehradun-248 005, India
ABSTRACT
Iron(III)-ethylenediaminetetraacetic acid in aqueous metha-
nol offers a simple, environmentallyacceptable snythetic
tool to oxidize a-hydroxyketones a-diketones with molecular
oxygen, in excellent yields and under mild conditions and
without anyside reactions.
Key Words: a-Hydroxyketone; a-Diketone; Molecular oxy-
gen; Iron(III)-ethylenediaminetetraacetic acid
a-Diketones are synthetically important building blocks[1] and have
been used for benzylic acid rearrangement[2] and synthesis of heterocyclic
compounds.[3–7] The oxidation of a-hydroxyketones is a simple and direct
route for the synthesis of a-diketones and manystoichiometric reagents such
*Corresponding author. E-mail: birsain@iip.res.in
2637
DOI: 10.1081/SCC-120006026
Copyright & 2002 byMarcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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2638
RAO ET AL.
as cupric salts,[8,9] ammonium nitrate,[10] bismuth oxide,[11] thallium
nitrate,[12] have been reported to be effective oxidants for this transforma-
tion. The increasing environmental concerns surrounding the use of toxic
and dangerous oxidants have impelled organic chemists to develop catalytic
oxidation methodologies using molecular oxygen as primary oxidant.[13–16]
[17]
In this context Nobile et al.
reported the oxidation of a-hydroxy-
ketones to a-diketones with molecular oxygen using Co(II) and Fe(II) com-
plexes as catalysts and excess of aldehyde or aldoacetal as sacrificial agent.
This method suffers from the drawback that 3.6 mmol of isobutyraldehyde
or 6.0 mmol of propionaldehyde dimethyl acetal per mmol of a-hydroxy-
ketone are required as sacrificial agent. Recently, Kirihara et al. [18] reported
the aerobic oxidation of a varietyof a-hydroxyketones to a-diketones using
VOCl3 as catalyst without the use of sacrificial aldehyde or aldoacetal.
However, VOCl3 is moisture sensitive, hazardous material and is not easy
to use in practice.[19] Among the transition metals iron has been singled out
as nontoxic and in the recent years, increasing emphasis, is being given on
the development of iron-based oxidants.[20–22]
Earlier we reported iron(III)-ethylenediaminetetraacetic acid catalyzed
aerobic oxidation of 2,6 di-tert-butylphenol, substituted hydroquinones and
thiols.[23,24] Herein, we report for the first time Iron(III)-ethylenediaminete-
traacetic acid [Fe(III)-EDTA][25–27] mediated oxidation of a-hydroxy-
ketones (1) to a-diketones (2) using molecular oxygen as the sole oxidant
(Scheme 1).
Oxidation of a varietyof a-hydroxyketones with molecular oxygen in
presence of catalytic amount of Fe(III)-EDTA yielded a-diketones in
excellent yields, without anyevidence for the formation of anybyproduct
which could arise due to cleavage of carbon–carbon bond of a-diket-
ones[28,29] (Table 1). Benzoins containing electron withdrawing groups
were found to be more reactive and required lesser reaction time for
their oxidation.
To determine the effect of pH, we studied the Fe(III)-EDTA catalyzed
oxidation of benzoin at different pH. The reaction was found to be highly
dependent upon pH of the system. While oxidation of benzoin to benzil at
Scheme 1.

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OXIDATION OF a-HYDROXYKETONES TO a-DIKETONES
2639
Table 1. Iron(III)-ethylenediaminetetraacetic Acid Catalyzed Oxidation of
a-Hydroxyketones (1) to a-Diketones (2) with Molecular Oxygen
Reaction
Time (h)
a-Diketone
1
EntryR
R2
pH
Yield (%)a
1
2
C6H5
C6H5
C6H5
C6H5
9.50
8.00
3.50
12.0
98
96
3
4
9.60
9.59
7.0
5.0
90
89
5
6
7
8
9
4-ClC6H4
4-CH3C6H4
4-CH3OC6H4
C6H5
C6H5
4-ClC6H4
4-CH3C6H4
4-ClC6H4
4-CH3C6H4
9.58
9.60
9.61
9.60
9.61
9.60
9.60
4.5
15.5
22.5
14.0
12.0
10.5
20.0
96
93
94
92
91
94
95
4-CH3OC6H4
4-CH3OC6H4
4-(CH3)2NC6H4
4-(CH3)2NC6H4
4-CH3OC6H4
10
11
aIsolated yield.
pH 9.5 could be completed in 3.5 h (Entry1), at pH 8.0 the observed reac-
tion time remained 12 h (Entry2) (Table 1).
To evaluate the catalytic effect of Fe(III)-EDTA, blank, experiment
was carried out with benzoin, under similar conditions but without catalyst
and it was observed that even after 48 h the reaction did not complete.
Although mechanism of this reaction is not clear at this stage, probably
the reaction proceeds through removal of proton from carbon attached to
hydroxyl group of a-hydroxyketone by hydroxide ion leading to the forma-
tion of carbanion and subsequent transfer of one electron of Fe(III)-EDTA.
The radical thus generated is oxidized to a-diketones and Fe(II)-EDTA
formed is reoxidized to Fe(III)-EDTA bymolecular oxygen (Scheme 2).
This type of mechanism has been conceived by Smith et al.,[30] for oxidation
of substituted benzyl alcohols with ferrate (VI) ion. Our observations that the
reaction rate is increased with the increase in pH and that the presence of
electron donating substituents in the benzene ring of a-hydroxyketones
decreases the rate of reaction, support this mechanism of reaction. Further
studies concerning the mechanistic aspects of this reaction are currently
underway.
In conclusion, simplicity of the system, excellent yields, wide applic-
abilityand reasonable reaction time make Fe(III)-EDTA catalyzed oxida-
tion with molecular oxygen, an attractive and environmentally acceptable
synthetic tool for the oxidation of a-hydroxyketones to a-diketones.

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2640
RAO ET AL.
Scheme 2.
EXPERIMENTAL
Fe(III)-EDTA (0.1 M) solution was prepared byadding ethylenedi-
aminetetraacetic acid (EDTA) disodium salt solution to the ammonium
ferric sulphate solution and raising the pH of the mixture to 8.00 by
adding aqueous sodium carbonate solution. A typical experimental pro-
cedure is as follows: a-hydroxyketone (1 mmol), Fe(III)-EDTA (0.1 mmol,
1 mL of 0.1 M solution) and methanol (10 mL) were taken in 50 mL double
necked round bottomed flask fitted with gas inlet tube and reflux condenser.
The solution was brought to the desired pH (9.5–9.6) byadding 5% aqueous
sodium carbonate solution. The mixture was then stirred and refluxed with
oxygen gas bubbled into at slow rate. The reaction progress was monitored
byTLC (SiO gel) and after completion methanol was removed under
2
reduced pressure. The residual mixture was then taken in toluene (20 mL)
and toluene layer was washed three times with distilled water (3 Â 20 mL)
followed by drying (anhydrous Na2SO4) and passing through a small
column of silica gel. Evaporation of toluene yielded pure a-diketone.
ACKNOWLEDGMENTS
We are thankful to the Director IIP, for his kind permission to publish
these results. Suman L. Jain is thankful to CSIR, New Delhi for the award
of a research fellowship.
REFERENCES
1. Vollhardt, K.P.C.; Schore, N.E. Organic Chemistry, 2nd Edn.; Freeman:
New York, 1994; 924–929.
2. Gill, G.B. In Comprehensive Organic Synthesis; Pattenden, G., Ed.;
Pergamon Press: New York, 1991; Vol. 3, 821–838.

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OXIDATION OF a-HYDROXYKETONES TO a-DIKETONES
2641
3. Mukaiyama, T.; Nambu, H.; Kumamoto, T. J. Org. Chem. 1964, 29,
2243.
4. Flament, I.; Stoll, M. Helv. Chim-Acta 1967, 50, 1754.
5. Rothkopf, H.W.; Wohrle, D.; Muller, R.; Kossmehl, G. Chem. Ber.
1975, 108, 875.
6. Wynberg, H.; Kooreman, H.J. J. Am. Chem. Soc. 1965, 87, 1739.
7. Paudler, W.W.; Barton, J.M. J. Org. Chem. 1966, 31, 1720.
8. Hartman, W.W.; Dickey, J.B. J. Am. Chem. Soc. 1933, 55, 1228.
9. Ruggli, P.; Zeller, P. Helv. Chim. Acta 1945, 28, 741.
10. Weiss, M.; Appel, M. J. Am. Chem. Soc. 1948, 70, 3666.
11. Righy, W. J. Chem. Soc. 1951, 793.
12. McKillop, A.; Sivann, B.P.; Ford, M.E.; Tylor, E.I. J. Am. Chem. Soc.
1973, 95, 3641.
13. Mukaiyama, T.; Yamada, T. Bull. Chem. Soc. Jpn. 1995, 68, 17.
14. Barton, D.H.R., Sawyer, D.T., Eds. The Activation of Dioxygen and
Homogeneous Catalytic Oxidation; Plenum Press: New York, 1993.
15. Cusumano, J.A. Chemtech. 1992, 2, 482.
16. Sheldon, R.A. Chem. Ind. 1997, 12.
17. Dell’ Anna, M.M.; Mastrorilli, P.; Nobile, C.F.; Lopez, L. J. Mol. Cat.
A. 1996, 111, 33.
18. Kirihara, M.; Ochiai, Y.; Takizawa, S.; Takahata, H.; Nemoto, H.
Chem. Commun. 1999, 1387.
19. Hwang, Der-Ren; Chen, Pyeng-Chen; Uang, Biing-Juin. Chem.
Commun. 1999, 1207.
20. Knepper, W.A. In Kirk-Othmer Encyclopedia of Chemical Technology,
3rd Ed.; Wiley: New York, 1981; Vol. 13, 735–753.
21. Delaude, L.; Laszlo, P. J. Org. Chem. 1996, 61, 6360.
22. Lee, D.G.; Gai, H. Can. J. Chem. 1993, 7, 1394.
23. Sain, B.; Murthy, P.S.; Venkateshwar Rao, T.; Prasada Rao, T.S.R.;
Joshi, G.C. Tetrahedron Lett. 1994, 35, 5083.
24. Rao, T.V.; Sain, B.; Murthy, P.S.; Prasada Rao, T.S.R.; Jain, A.K.;
Joshi, G.C. J. Chem. Res. (s) 1997, 300.
25. Hart, J.R. Chemtech. 1987, 17, 313.
26. Wubs,H.J.;Beenaekers,A.A.C.M.Am.Inst.Chem.Eng.J.1994,40,433.
27. Conway, M.; Holman, S.; Jones, L.; Leenhouts, R.; Willamson, G.
Chem. Eng. 1999, 106(3), 86.
28. Ho, T.-L. Synthesis 1972, 560.
29. Takezawa, E.; Sakaguchi, S.; Ishii, Y. Org. Lett. 1999, 1, 715.
30. Audette, R.J.; Quail, J.W.; Smith, P.J. J. Chem. Soc., Chem. Commun.
1972, 38.
Received in the Netherlands September 2, 2001

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