DMSO/N2H4·H2O/I2/H 2O/CH3CN: A new system for selective oxidation of alcohols in hydrated media

Article abstract of DOI:10.1021/jo0494984

A new alternative system for the oxidation of secondary alcohols to ketones with DMSO/N₂H₄·H₂O/I₂/H ₂O/CH₃CN in hydrated media has been developed. The system also selectively oxidizes the secondary alcoholic groups to the corresponding ketones in the presence of primary alcoholic groups present within the same molecule in moderate to very good yields at reflux temperature.

Full text of DOI:10.1021/jo0494984

DMSO/N
2
H
4
‚H
2
O/I
2
/H
2
O/CH
3
CN: A New
SCHEME 1
System for Selective Oxid a tion of Alcoh ols
in Hyd r a ted Med ia
Pranjal Gogoi, Gautam Kumar Sarmah, and
Dilip Konwar*
Organic Chemistry Division, Regional Research Laboratory,
J orhat 785006, Assam, India
are generally less reactive and secondary alcohols were
oxidized at faster rates than primary.6 However, the
methods of oxidation by DMSO have disadvantages
because of their involvement under anhydrous and low-
3
dkonwar @yahoo.co.uk
Received March 27, 2004
6
3c-f,5,6
temperature conditions, use of moisture-sensitive
3e
5,6
and toxic reagents and bases, and in some cases,
3
a
occurrence of Pummerer rearrangements (up to 50%).
Therefore, development of a better selective reagent is
desirable.
Abstr a ct: A new alternative system for the oxidation of
secondary alcohols to ketones with DMSO/N2H4‚H2O/I2/H2O/
CH3CN in hydrated media has been developed. The system
also selectively oxidizes the secondary alcoholic groups to
the corresponding ketones in the presence of primary
alcoholic groups present within the same molecule in moder-
ate to very good yields at reflux temperature.
In our previous communications, we reported deoxy-
genation of nitrones and azoxy compounds to the corre-
7
sponding imines and azo compounds catalyzed by HI
(generated from AlCl
3
2 2 3
‚6H O/NaI/H O/CH CN). The same
system was used in the dehydration of oximes and amides
to nitriles and the Beckmann rearrangements and the
8
Oxidation of alcohols to carbonyl compounds is one of
the most important transformations in organic synthe-
ses. The selective oxidation of alcohols is still a chal-
Bischler-Napieralski reactions in hydrated media. We
now report here the selective oxidation of secondary
1
alcohols to ketones using DMSO catalyzed by HI (gener-
9
lenging task to organic chemists particularly when both
secondary and primary groups within the same molecule
are present. Many selective reagents for the oxidation of
secondary alcohols to ketones have been reported, includ-
ing halogen-based oxidants,2 e.g., N-chloroacetamide,
ated insitu from N
at reflux temperature (Scheme 1).
A 1 M quantity of N ‚H O and a 2 M quantity of I
2
H
4
‚H
2
O and I
2
) in hydrated media
2
H
4
2
2
were stirred in aqueous acetonitrile (5:1) for a period of
15 min at room temperature under a nitrogen atmo-
sphere followed by addition of secondary alcohols, and
the reaction mixture was stirred for 5 min. To this
mixture, was added a 5 M quantity of DMSO and the
mixture refluxed at 80 °C, which produced the corre-
sponding ketones in 46-95% yields (Table 1).
a
N-chloro/bromosuccinaamide, Cl
NaHCO , (Bu Sn) O/Br , NaOCl/CH
NaHSO , and CeSO /NaBrO . Other important selective
2
/pyridine, Br
2
/HMPT/
3
3
2
2
3
COOH, NaBrO /
3
3
4
3
oxidizing agents viz. Mo/Zr/W/Ru compounds, peroxides,
dioxiranes, and enzymatic methods are also efficient
reagents for the selective oxidation of secondary alcohols.
Oxidation by DMSO and related methods is widely used
in organic syntheses, although few examples of primary-
secondary selectivity have been reported.4 Aliphatic
primary and secondary alcohols were oxidized in the
2
b
The aliphatic secondary alcohols (Table 1, entries 1a -
1c) reacted faster than the phenyl-substituted aromatic
secondary alcohols (Table 1, entries 1d -1f). The rate as
well as the yield of the reactions is dependent on the
substituents present in the substrates. Electron-donating
groups such as (CH ) CHCH or OH (Table 1, entries 1e-
3
presence of allylic or benzylic alcohols using the DMSO/
3
2
2
5
(
CF
3
CO)
2
/Et
3
N
system. The competitive oxidation of
SO/(COCl) /Et N at -60 °C has dem-
onstrated that alcohols bearing electron-deficient groups
1g) on the aromatic ring accelerated the rate of the
reaction. But aromatic primary alcohols (Table 2, entries
1j and 1k ) formed the corresponding aldehydes (only 3.7
and 7%, respectively) after heating for 30 h at 80 °C. The
reagent selectively oxidized only the secondary alcohol
groups to the corresponding ketones when both the
primary and the secondary groups were present within
the same molecules (Table 2, entries 1l-1o). The reagent
did not reduce alcohols to the corresponding saturated
compounds10 or form any Pummerer rearrangement
type of products. Moreover, oxidations of the secondary
alcohols 1a -i with DMSO catalyzed by HI (57 wt %)
under the same reaction conditions produced 30-45%
yields of ketones. Acetonitrile was the best solvent for
alcohols with Me
2
2
3
(
1) (a) Larock, R. C. Comprehensive Organic Transformation, A
guide to functional group preparation; VCH Publications, Inc.: New
York, 1989; pp 604-614. (b) Ley, S. V.; Norman, J .; Griffith, W. P.;
Marsden, S. P. Synthesis 1994, 7, 639-666 (c) Kim, S. S.; J ung, H. C.
Synthesis 2003, 2135-2137.
(
2) (a) Stevens, R. V.; Chapman, K. T.; Stubbs, C. A.; Tam, W. W.;
Albizati, K. F. Tetrahedron Lett. 1982, 23, 4647-4650 (b) Arterburn,
3a
J . B. Tetrahedron 2001, 57, 9765-9787 and references therein.
(
3) (a) Omura, K.; Swern, D. Tetrahedron 1978, 34, 1651-1660. (b)
Tidwell, T. T. Synthesis 1990, 857-870. (c) Epstein, W. W.; Sweat, F.
W. Chem. Rev. 1967, 67, 7-260. (d) Albright, J . D. J . Org. Chem. 1974,
3
1
9, 1977-1979. (e) Albright, J . D.; Goldman, L. J . Am. Chem. Soc.
965, 87, 4214-4216. (f) Fenselau, A. H.; Moffatt, J . G. J . Am. Chem.
Soc. 1966, 88, 1762-1765.
(
4) (a) Godfrey, J . D., J r.; Gordon, E. M.; Langen, D. J . V. Tetrahe-
dron Lett. 1987, 28, 1603 (b) Tidwell, T. T. Org. React. 1998, 39, 297-
72. (c) Pfitzner, K. E.; Moffat, J . G. J . Am. Chem. Soc. 1963, 85, 3027.
d) Kornblum, N.; J ones, W. J .; Anderson G. J . J . Am. Chem. Soc. 1959,
(6) Marx, M.; Tidwell, T. T. J . Org. Chem. 1984, 49, 788-793.
(7) Boruah, M.; Konwar, D. Synlett 2001, 6, 795-796.
(8) Boruah, M.; Konwar, D. J . Org. Chem. 2002, 67, 7138-7139.
(9) Greenwood, N. N.; Earnshaw, A. Chemistry of the Elements;
Pergamon Press: New York, 1984; p 948.
5
(
8
1, 4113-4114.
(
5) Omura, K.; Sharma, A. K.; Swern, D. J . Org. Chem. 1976, 41,
9
57-962.
(10) Parham, W. E.; Sayed, Y. A. Synthesis 1976, 116.
1
0.1021/jo0494984 CCC: $27.50 © 2004 American Chemical Society
Published on Web 06/30/2004
J . Org. Chem. 2004, 69, 5153-5154
5153

TABLE 1. Oxid a tion of Secon d a r y Alcoh ols
SCHEME 2
tions. It has been found that the system oxidized benzyl
alcohol to benzaldehyde (3.7%) [2,4-dinitrophenyl hydra-
.
12
zone derivative, mp 236 °C (lit
mp 237 °C)] when
refluxed for 30 h. DMSO is the oxidizing agent, which
was confirmed by carrying out the oxidation under a
1
1
nitrogen atmosphere, and it was found that air did not
affect the acid-catalyzed oxidation. Also, the dimethyl
sulfide formed in the reaction mixture reacted with
mercuric chloride to give the mercuric chloride derivativ,e
147-49 °C (lit.1
313-14
mp150-51 °C). On the basis of
mp
.
these results, a plausible mechanism is proposed (Scheme
).
In conclusion, a new, selective, and efficient alternate
2
method has been developed for the oxidation of secondary
alcohols to ketones in moderate to very good yields in
hydrated media. It does not involve moisture-sensitive
and toxic reagents and bases in the reaction mixture. In
addition, it can selectively oxidize only the secondary
alcoholic groups in the presence of primary alcohols
present within the same molecule and it does not reduce
the alcohols to the corresponding saturated compounds.
a
Isolated yield. b Reflux temperature (80 °C). The structures
c
1
of the compounds were determined by using H NMR, FTIR, and
C NMR analyses and comparison with authentic samples.
1
3
14
TABLE 2. Selective Oxid a tion of Secon d a r y Alcoh ols
Exp er im en ta l Section :
Gen er a l P r oced u r e for t h e Oxid a t ion of Secon d a r y
Alcoh ols. Hydrazine monohydrate (51 mg, 1 mmol) and iodine
(
[
506 mg, 2 mmol) were stirred in aqueous acetonitrile (10 mL)
CH CN/H O 5:1] for 15 min under a nitrogen atmosphere, and
3
2
secondary alcohol (1 mmol) was added to it. The reaction mixture
was stirred for another 5 min at room temperature. DMSO (390
mg, 5 mmol) was added to the reaction mixture and refluxed at
8
0 °C under nitrogen. The solvent was distilled off to half of its
volume under reduced pressure, poured into water (100 mL),
and extracted with diethyl ether (2 × 25 mL). The organic layer
was washed with 5% sodium thiosulfate solution (20 mL) and
then with water (2 × 50 mL) and dried over Na
2 4
SO . The residue
was purified by preparative TLC and gave the analytically pure
ketones. All of the products were commercially available and
identified by comparison of the isolated products with authentic
samples.
a
Isolated yield. b Reflux temperature (80 °C). The structures
c
Ack n ow led gm en t. We acknowledge Dr. P. G. Rao,
Director, and Dr. N. Borthakur, Senior Scientist, RRL,
J orhat-6, Assam, India, for their help. P.G. thanks
CSIR, New Delhi, for a J RF fellowship.
1
of the compounds were determined by using H NMR, FTIR, and
C NMR analyses and comparison with authentic samples.
1
3
14
both yields and rates of the reaction, in contrast to CHCl
and CH Cl
While the exact mechanism of selective oxidation is not
clear at present and we propose that hydrazine reduces
to HI, HI reacts with the hydroxyl group of secondary
3
2
2
.
Su p p or tin g In for m a tion Ava ila ble: Characterization
1
13
data including H and C NMR and FTIR of all compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
9
I
2
alcohols to generate carbocations to produce ketones in
the presence of DMSO. The secondary carbocation is
more stable than primary carbocation in the transition
state,11 which may facilitate the faster oxidation of
secondary alcohol to ketones under the reaction condi-
J O0494984
(
12) Buckingham, J .; Macdonald, F. Dictionary of Organic Com-
pounds, 6th ed.; Chapman and Hall: London, 1996; Vol. 1, p 558.
13) Faragher, W. F.; Morrell, J . C.; Comay, S. J . Am. Chem. Soc.
929, 51, 2781.
(
1
(
14) (a) Ueno, Y.; Okawara, M. Tetrahedron Lett. 1976, 50, 4597-
(11) March, J . Advanced Organic Chemistry, Reactions, Mechanisms
4600. (b) Dictionary of Organic Compounds, 6th ed.; Chapman and
and Structure, 4th ed.; J ohn Wiley & Sons: New York, 1999; p 166.
Hall: London, 1996.
5
154 J . Org. Chem., Vol. 69, No. 15, 2004