Na-promoted aerobic oxidation of alcohols to ketones

Article abstract of DOI:10.1016/j.tetlet.2009.11.079

Aerobic oxidation of a number of diaryl and arylalkyl carbinols to ketones was promoted by Na in THF at room temperature with up to 99% yield. This new oxidation method is also selective with good efficiency for the oxidation of benzylic secondary alcohols but not for a primary alcohol or nonbenzylic secondary alcohols. Under nitrogen, a catalytic amount of Ni or transition metal halides such as CoCl₃, FeCl₃, and NiCl₃ in combination with Na was also found to conduct a dehydrogenation of a secondary alcohol to the corresponding ketone in high yield at room temperature.

Full text of DOI:10.1016/j.tetlet.2009.11.079

Tetrahedron Letters 51 (2010) 475–477
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Tetrahedron Letters
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Na-promoted aerobic oxidation of alcohols to ketones
a,
Li-Hong Zhou a,b, Xiao-Qi Yu b, , Lin Pu
*
*
a Department of Chemistry, University of Virginia, Charlottesville, VA 22904 4319, USA
b Department of Chemistry, Key Laboratory of Green Chemistry and Technology (Ministry of Education), Sichuan University, Chengdu 610064, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Aerobic oxidation of a number of diaryl and arylalkyl carbinols to ketones was promoted by Na in THF at
room temperature with up to 99% yield. This new oxidation method is also selective with good efficiency
for the oxidation of benzylic secondary alcohols but not for a primary alcohol or nonbenzylic secondary
alcohols. Under nitrogen, a catalytic amount of Ni or transition metal halides such as CoCl3, FeCl3, and
NiCl3 in combination with Na was also found to conduct a dehydrogenation of a secondary alcohol to
the corresponding ketone in high yield at room temperature.
Received 23 October 2009
Revised 16 November 2009
Accepted 17 November 2009
Available online 22 November 2009
Keywords:
Na
Ó 2009 Elsevier Ltd. All rights reserved.
Oxidation
Alcohols
Ketones
Aerobic
Anaerobic
Oxidation of alcohols is one of the most fundamental reactions
in organic chemistry. A great variety of metal and non-metal-based
stoichiometric reagents have been developed to oxidize primary
and secondary alcohols to the corresponding aldehydes, ketones,
and carboxylic acids.1–3 These processes generally produce signifi-
cant amount of inorganic or organic wastes that are of environ-
mental concern. Aerobic4–7 and anaerobic8 oxidations of alcohols
in the presence of transition metal catalysts and/or other catalysts
have also been investigated extensively. Although these processes
are more environmentally benign, they often need expensive met-
als and/or other reagents. Thus, the search for environmentally
friendly as well as economical oxidation processes continues. Re-
cently, Wang and coworkers reported a practically useful oxidation
of secondary alcohols to ketones catalyzed by NaH under nitro-
gen.9 Herein, we report our finding of an aerobic oxidation of sec-
ondary alcohols to ketones promoted by the commercially cheaper
Na at room temperature.
We first studied the conversion of diphenylmethanol to benzo-
phenone (Scheme 1). The results for the screening experiments are
summarized in Table 1. No oxidation of the alcohol under nitrogen
in the presence of Na (10 mg, 2 equiv) in THF was observed (entry
1). However, addition of a catalytic amount of the transition metal
salts such as CoCl3, FeCl3, and NiCl2 in combination with Na
(2 equiv) led to high conversions of the alcohol to the ketone (en-
tries 2–4). Using a catalytic amount of Na in combination with the
transition metal salts led to incomplete conversions (entries 5–7).
We also found that the transition metal salts alone could not cata-
lyze the oxidation of the alcohol under nitrogen (entries 8–10). The
combination of Na (2 equiv) with a small amount of Ni also led to
complete conversion of the alcohol to ketone (entry 11) but the
combination of Na with Fe did not oxidize the alcohol (entry 12).
Using Ni alone under nitrogen only led to 10% conversion of the
alcohol to the ketone over 40 h (entry 13) and Fe could not pro-
mote this reaction (entry 14). Finally, when the reaction was con-
ducted in the presence of Na (2 equiv) and air in THF at room
temperature without any transition metal additive, a complete
conversion of the alcohol to the ketone was observed (entry 15).
The above-mentioned screening experiments demonstrate that
(1) in the presence of air, Na can promote an efficient oxidation of
the alcohol; (2) without air, Na cannot promote the oxidation; and
(3) without air, a catalytic amount of transition metal salts or Ni
combined with Na can promote the oxidation of the alcohol. These
observations present intriguing questions that remain to be an-
swered for the mechanisms of these oxidation processes.
Encouraged by the high conversion and mild reaction condi-
tions for the Na-promoted aerobic oxidation of diphenylmethanol,
we have applied this method for the oxidation of a number of
alcohols. The results are summarized in Table 2. These oxidations
OH
O
Na
THF, rt
other
conditions
* Corresponding authors.
E-mail address: lp6n@virginia.edu (L. Pu).
Scheme 1. Oxidation of diphenylmethanol to benzophenone.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.11.079

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L.-H. Zhou et al. / Tetrahedron Letters 51 (2010) 475–477
Table 1
Table 2
Oxidation of diphenylmethanol to benzophenone in THF at room temperaturea
Aerobic oxidation of various alcohols to ketones promoted by Na in THF at room
temperature
Entry Metal reagents
N2 or air Time (h) Conversion
to ketoneb
Entry
Alcohol
Ketone
Timea (h)
Isolated yield (%)
1
2
3
4
Na (2 equiv)
N2
N2
N2
N2
16
40
16
40
16
40
16
40
40
40
40
40
40
40
40
16
40
40
40
16
40
None
None
6
100
15
78
20
92
18
OH
O
1
20
95
Na (2 equiv) + CoCl3 (0.03 equiv)
Na (2 equiv) + FeCl3 (0.03 equiv)
Na(2 equiv) + NiCl2 (0.04 equiv)
OH
O
O
S
S
2
3
48
46
92
72
OH
5
6
7
8
9
10
11
12
Na (0.4 equiv) + CoCl3 (0.03 equiv) N2
Na (0.4 equiv) + FeCl3 (0.03 equiv) N2
Na (0.4 equiv) + NiCl2 (0.04 equiv) N2
CoCl3 (0.03 equiv)
FeCl3 (0.03 equiv)
NiCl2 (0.04 equiv)
Na (2 equiv) + Ni (0.085 equiv)
Na (2 equiv) + Fe (0.09 equiv)
OCH3
OH
OCH3
O
0
40
4
5
6
7
46
44
23
10
99
90
79
69
N2
N2
N2
N2
N2
None
None
None
100
None
None
10%
None
67
OH
O
O
O
OH
13
14
15
Ni (0.085 equiv)
Fe (0.09 equiv)
Na (2 equiv)
N2
N2
Air
OH
100
OH
O
a
Conditions: Diphenylmethanol (36.8 mg, 0.2 mmol), THF (3 mL), rt.
Estimated by using 1H NMR spectroscopy.
8
9
36
16
20
82
65
61
b
MeO
MeO
OH
O
O
Br
Br
were conducted by first stirring an alcohol with 1 equiv Na in THF
in air for 4 h at room temperature. Then second equivalent of Na
was added to continue the reaction. As shown in Table 2, good
yields are obtained for the oxidation of a variety of diaryl and aryl-
alkyl carbinols. This reaction tolerates functional groups such as
thiophenyl, methoxy, bromo, and nitrile. Lower yields were ob-
served for the oxidation of several sterically hindered alcohols (en-
tries 11–13). Oxidation of a primary alcohol, p-phenylbenzylic
alcohol, was also tested which gave only ꢀ1% conversion to the
corresponding aldehyde after 16–40 h (entry 17). Thus, this meth-
od is highly selective for the oxidation of the secondary alcohols.
Inactivity of nonbenzylic secondary alcohols was also observed un-
der the reaction conditions (entries 18 and 19). This Na-promoted
oxidation could potentially be used to selectively oxidize the ben-
zylic secondary alcohols in the presence of these inactive alcohols.
The general experimental procedure for the Na-promoted aero-
bic oxidation is given here. To a flame-dried round-bottomed flask
were added an alcohol (0.2 mmol) and THF (dry, 3 mL). Sodium
(0.2 mmol, 1.0 equiv) was cut into small pieces under nitrogen
and added to the alcohol solution. The reaction mixture exposed
to air through a drying tube (anhydrous CaSO4) was stirred at room
temperature for 4 h. Additional sodium (0.2 mmol, 1.0 equiv) was
added and the stirring continued. [Note: Slow stirring was neces-
sary to allow the Na chips to be always covered by the solvent.]
The reaction was monitored with TLC. The solvent was then evap-
orated and a 5% HCl solution was added until pH 7. The solution
was extracted with EtOAc, and the combined organic phase was
washed with brine, dried over androus Na2SO4, and concentrated
under vacuum. The crude product was purified by flash chroma-
tography on silica gel eluted with EtOAc/hexane (1:6) to give the
desired ketone product.
OH
10
Br
Br
OH
O
11
12
13
14
20
20
24
24
46
41
38
71
OMe
OMe
O
OH
OMe
OHOMe
OMe
O
OMe
OMe
OH
OMe
O
CN
O
CN
OH
15
16
18
20
62
70
OH
O
OH
O
H
17
18
19
16–40
20
ꢀ1b
Ph
Ph
OH
OH
O
Noneb
Noneb
O
20
7
7
a
The total reaction time for the oxidation promoted by the first and second
equivalents of Na.
Observed by using 1H NMR spectroscopy.
b
In summary, we have discovered a Na-promoted aerobic oxida-
tion of a number of diaryl and arylalkyl carbinols at room temper-
ature. The simple and mild reaction conditions and the easily
available reagent make this new method synthetically useful. This
method is also selective with good efficiency for the oxidation of
benzylic secondary alcohols but not for a primary alcohol or nonb-
enzylic secondary alcohols. In the absence of air, a catalytic amount
of Ni or transition metal halides in combination with Na can also
convert a secondary alcohol to the corresponding ketone. These
findings present interesting mechanistic questions that require
further investigation.
Acknowledgments
Partial supports of this work from the US National Science
Foundation (CHE-0717995), the donors of the Petroleum Research

L.-H. Zhou et al. / Tetrahedron Letters 51 (2010) 475–477
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Fund-administered by the American Chemical Society, the National
Science Foundation of China (Nos. 20725206 and 20732004), and
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(2007)3020]. We thank Albert Deberardinis for providing some of
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