Facile Synthesis of α-Ketocarbonyl Compounds from α-Hydroxycarbonyl Compounds

Article abstract of DOI:10.1081/SCC-120001505

Various α-ketocarbonyl compounds were obtained in excellent yields under mild condition from the reaction of the corresponding α-hydroxycarbonyl compounds with sodium hypobromite in the presence of HCl catalyst.

Full text of DOI:10.1081/SCC-120001505

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FACILE SYNTHESIS OF α-KETOCARBONYL COMPOUNDS
FROM α-HYDROXYCARBONYL COMPOUNDS
Hae Sung Chang , Jae Chun Woo a , Kyoung Mo Lee a , Young Kwan Ko a , Surk-Sik Moon b
& Dae-Whang Kim a
a Korea Research Institute of Chemical Technology , P.O. Box 107, Yusong, Daejeon,
305-606, Korea
b Department of Chemistry, Kongju National University , Kongju, 314-701, Korea
Published online: 21 Aug 2006.
To cite this article: Hae Sung Chang , Jae Chun Woo , Kyoung Mo Lee , Young Kwan Ko , Surk-Sik Moon & Dae-Whang
Kim (2002) FACILE SYNTHESIS OF α-KETOCARBONYL COMPOUNDS FROM α-HYDROXYCARBONYL COMPOUNDS , Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:1, 31-35, DOI:
10.1081/SCC-120001505
To link to this article: http://dx.doi.org/10.1081/SCC-120001505
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SYNTHETIC COMMUNICATIONS, 32(1), 31–35 (2002)
FACILE SYNTHESIS OF
a-KETOCARBONYL COMPOUNDS FROM
a-HYDROXYCARBONYL COMPOUNDS1
Hae Sung Chang,1, Jae Chun Woo,1
*
Kyoung Mo Lee,1 Young Kwan Ko,1
Surk-Sik Moon,2 and Dae-Whang Kim1
1Korea Research Institute of Chemical Technology,
P.O. Box 107, Yusong, Daejeon 305-606, Korea
2Department of Chemistry,
Kongju National University, Kongju 314-701, Korea
ABSTRACT
Various a-ketocarbonyl compounds were obtained in excel-
lent yields under mild condition from the reaction of the
corresponding a-hydroxycarbonyl compounds with sodium
hypobromite in the presence of HCl catalyst.
Since a-ketocarbonyl compounds have been used as important inter-
mediates in organic synthesis,2 there has been considerable interest in the
development of convenient methods for the synthesis of a-ketocarbonyl
compounds. Many researchers have published preparation methods for
a-ketocarbonyl compounds from various starting material.3 Among them,
oxidation of a-hydroxy carbonyl compounds constitutes one of the most
*Corresponding author.
31
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

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32
CHANG ET AL.
widely used procedures for a-ketocarbonyl compounds. A number of
methods are available for the synthesis of a-ketocarbonyl compounds by
oxidation of a-hydroxycarbonyl compounds with KMnO4,4 N-bromo-
succinimide,5 CrO3,6 lead tetraacetate,7 triphenylantimony dibromide,8
dimethyl selenide-N-bromosuccinimide complex,9 oxoaminium salts,10
perfluoro-cis-2-butyl-3-propyloxaziridine,11 and trichloro-oxyvanadium.12
In this paper, we report a new synthetic method for the synthesis of
a-ketocarbonyl compounds from a-hydroxycarbonyl compounds. In order
to establish the optimum condition for oxidation of the a-hydroxy-
carbonyl compounds, we have examined the reaction of n-butyl lactate 1 as
a model substrate with N-bromosuccinimide,5 or N-chlorosuccinimide, or
sodium hypochlorite as an oxidant in CCl4 or a mixed solvent (H2O/
CH2Cl2, v/v ¼ 1/1). But these reagents did not give satisfactory results
(Table 1). On the other hand, as shown in the run 5, the reaction of n-butyl
lactate 1 with sodium hypobromite in the presence of HCl catalyst afforded
the n-butyl pyruvate 2 in excellent yield.
To expand general utility of the NaOBr for the transformation of
a-hydroxycarbonyl compounds into the corresponding a-ketocarbonyl
Table 1. Optimization Study for Oxidation of n-Butyl Lactate
Oxidation
Condition
Reaction
Temp. (ꢀC)
Reaction
Time (h)
Yielda
(%)
Run
1
Solvent
CCl4
NBS/CaCO3
(1.3 eq/1.3 eq)
NCS/CaCO3
(1.3 eq/1.3 eq)
NaOCl/HCl
(1.3 eq/0.3 eq)
NaOCl/NaBr/HCl
(1.3 eq/1.3 eq/0.3 eq)
NaOBr/HCl
78
78
25
25
25
24
24
5
75b
10 <
23
2
3
4
5
CCl4
CH2Cl2/H2O
CH2Cl2/H2O
CH2Cl2/H2O
5
74
5
98
(1.3 eq/0.3 eq)
aYields were determined by GC.
bn-Butyl bromopyruvate was obtained in 10% yield as a side product.

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a-KETOCARBONYL COMPOUNDS
33
Table 2. Oxidation of a-hydroxycarbonyl Compounds by NaOBr/HCl System in a
Mixed Solvent (CH2Cl2/H2O, v/v ¼ 1/1)a,b
Run
R1
R2
Yieldc (%)
1
2
3
4
5
6
7
8
9
CH3
CH3
CH3
CH3
CH3
CH3
-OCH3
90
92
96
92
92d
93e
93
90
93
94
90
93
-OCH2CH3
-OCH2CH2CH2CH3
-OCH(CH3)2
-OCH2CH(CH3)2
-OCH2CH2CH(CH3)2
-OCH2CH2
-OH
-OCH2CH2
-OCH2CH2
Ph
CH3CH2CH2CH2
Ph
Ph
PhCH2CH2
Ph
2-Pyridine
10
11
12
2-Pyridine
aMolar ratio; substrate: NaOBr : HCl ¼ 1 : 1.3 : 0.3.
bThe reaction time was 5 h.
cIsolated yields.
dCH3 COCO2 CH2CH(CH3)2 : CH3COCO2CH2CBr(CH3)2 ¼ 80 : 20, the ratio was
1
determined by H NMR.
eCH3COCO2CH2CH2CH(CH3)2 : CH3COCO2CH2CH2CBr(CH3)2 ¼ 75 : 25, theratio
1
was determined by H NMR.
compounds, we performed the oxidation reaction using a-hydroxycarbonyl
compounds 3 such as a-hydroxy esters, a-hydroxyacid, and a-hydroxy-
ketones. The results were summarized in Table 2.
As shown in Table 2, most of the oxidation with sodium hypobromite
in the presence of HCl catalyst proceeded smoothly at room temperature.
On the other hand, in case of iso-butyl lactate, isoamyl lactate (Run 5, 6), a
mixture of the corresponding a-ketoester and bromo-substituted a-ketoester
was obtained.
a-Hydroxylketones as well as a-hydroxyesters could be easily
transformed into the corresponding a-diketones under mild condition
(Run 11, 12). When the same reaction condition was applied to the oxida-
tion of pantolactone 5, ketopantolactone 6 could be obtained in high yield.

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CHANG ET AL.
In conclusion, various a-ketocarbonyl compounds could be easily
prepared from the a-hydroxycarbonyl compounds by using NaOBr/HCl
system under facile and mild conditions in high yields.
EXPERIMENTAL
Synthesis of Pyruvic Acid Butyl Ester: Typical Procedure
700 mL of water and 104 g (2.6 mol) of sodium hydroxide were placed
into a 2 L three-necked flask equipped with a cooler, a mechanical stirrer,
and a thermometer. The mixture was cooled to ꢁ5ꢀC. 67 mL (1.3 mol) of
bromine was dropwise added for 2 h, keeping the internal temperature at
ꢁ5ꢀC to generate sodium hypobromite (NaOBr). 700 mL of cold dichloro-
methane and 148.12 mL (1 mol) of a-hydroxypropionic acid butyl ester were
added slowly to the aqueous sodium hypobromite solution so that the
temperature does not exceed 0ꢀC. 26.1 mL (0.3 mol) of concentrated hydro-
chloric acid was dropwised for 15 min, keeping the temperature of the
reaction mixture at 0ꢀC. After removing the cooler, the reaction mixture
was stirred for 5 h at room temperature. After addition of sodium thiosul-
fonate (100 mL of water and 124 g of Na2S2O35H2O), the reaction mixture
was stirred for 15 min. The organic layer was separated, and the aqueous
layer was extracted twice with dichloromethane. The combined organic
layer was dried over magnesium sulfate and filtered. The filtrate was eva-
porated and distilled under reduced pressure (20 mmHg, b.p. 83–86ꢀC) to
give 138.2 g of n-butyl pyruvate (96% yield).
1H NMR (CDCl3): d 4.25 (t, 2H), 2.46 (s, 3H), 1.72 (m, 2H), 1.43
(m, 2H), 0.95 (t, 3H)
REFERENCES
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Press: Oxford, 1991, Vol. 8, pp 144–155.

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a-KETOCARBONYL COMPOUNDS
35
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Received in Japan November 9, 2000

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