Shaken not stirred; Oxidation of alcohols with sodium dichromate

Article abstract of DOI:10.1016/j.tetlet.2005.11.024

Efficient and selective oxidation of primary alcohols to the corresponding aldehydes with sodium dichromate at room temperature under solvent-free conditions by shaking is described. This new procedure can also successfully oxidise secondary alcohols.

Full text of DOI:10.1016/j.tetlet.2005.11.024

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 311–313
Shaken not stirred; oxidation of alcohols with sodium dichromate
Ji-Dong Lou,a Chun-Ling Gao,b,* Yi-Chun Ma,a Li-Hong Huanga and Li Lic
aCollege of Life Sciences, China Institute of Metrology, Hangzhou, Zhejiang 310018, China
bCenter for Prostate Disease Research, Uniformed Service University of Health Science,
4301 Johns Bridge Road, Bethesda, MD 20814, USA
cInstituto Superior Tecnico, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
Received 30 September 2005; revised 3 November 2005; accepted 3 November 2005
Available online 22 November 2005
Abstract—Efficient and selective oxidation of primary alcohols to the corresponding aldehydes with sodium dichromate at room
temperature under solvent-free conditions by shaking is described. This new procedure can also successfully oxidise secondary
alcohols.
ꢀ 2005 Elsevier Ltd. All rights reserved.
1. Introduction
tion, the oxidising reagent can further oxidise the
aldehyde to the acid, since in an aqueous medium, the
aldehyde product can be hydrated to the geminal diol,
which is further oxidised. To avoid further oxidation
to the corresponding acid, the aldehyde has to be
removed as rapidly as possible, for example, by distilla-
tion through a fractionating column. In addition, under
acidic medium, the aldehyde product and unreacted
alcohol react to give a hemiacetal that is rapidly oxidised
to an ester. The most important problem in sodium
dichromate dihydrate oxidations is that overoxidation
can occur during the reaction process. In an attempt
to circumvent this problem the main trend has been to
develop the use of non-aqueous complexes, for instance,
the Collins reagent6 [(C5H5N)2CrO3], pyridinium chlo-
rochromate7 [PCC, (C5H5NH)ClCrO3] and pyridinium
dichromate8 [PDC, (C5H5NH)2+Cr2O72À]. The latter
two are currently the reagents of choice, particularly
for the oxidation of a,b-unsaturated primary and sec-
ondary alcohols to the corresponding unsaturated alde-
hydes and ketones. Furthermore, most of improved
Na2Cr2O7-based oxidants previously reported are per-
formed at vigorous conditions.9,10
The oxidation of alcohols to the carbonyl compounds is
an important reaction in synthetic organic chemistry.
Sodium dichromate dihydrate (Na2Cr2O7Æ2H2O), an
oxidising agent used in organic chemistry for over a cen-
tury, is one of the most versatile and vigorous of the
commonly used oxidants for the above transforma-
tion.1–4
Over the years, sodium dichromate dihydrate has been
continually developed and modified to overcome the
typical problems that occur for the reactions, for exam-
ple, especially to overoxidation that exist during the
selective preparation of aldehydes from the correspond-
ing alcohols.
2. Results and discussion
Sodium dichromate in aqueous sulfuric acid under
rather vigorous conditions (high temperature and/or
an aqueous strongly acidic environment) is used for a
variety of oxidations including some primary alcohols
to aldehydes5 and secondary alcohols to ketones. Acidic
dichromate is not a generally useful reagent for the oxi-
dation of primary alcohols. Under the reaction condi-
We now report here that the oxidation of primary alco-
hols with Na2Cr2O7 at room temperature under solvent-
free conditions11 by shaking, is a new system that offers
a very simple, efficient, and selective oxidation method
for the preparation of aldehydes. In the present method,
overoxidation and formation of an ester can be pre-
vented by the use of solvent-free conditions under which
the aldehyde produced is stable. On the other hand, in
Keywords: Aldehydes; Ketones; Sodium dichromate; Solvent free;
Shaking.
*
Corresponding author. Tel./fax: +1 240 453 8943; e-mail: gao-cl@
sohu.com
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.11.024

312
J.-D. Lou et al. / Tetrahedron Letters 47 (2006) 311–313
comparison with the complexes described above, the
main advantage of the present method is that no prepa-
ration of the complexes is needed. Convenient opera-
tion, high yield, and simple work-up are additional
benefits of the present method. In addition, the shaking
machine is first employed for this reaction, which is very
easy for performance. We find that shaking is much
more effective than using a stirrer for this kind of reac-
tions. For example, some other previously reported
chromium(VI) oxidation methods, sometimes, are
needed to be heated and/or with a long reaction time.1
In the present work, heating is unnecessary and the reac-
tion time is quite short. The present method is the first
letter to report using shaking in oxidations of alcohols
under solvent-free conditions. It offers special promise
for the preparation of aldehydes by the oxidation of
alcohols, but can be also successfully employed in the
oxidation of secondary alcohols to the corresponding
ketones.
applicable to a wide range of alcohols, and gives the cor-
responding products in high yield.
In conclusion, this solvent-free oxidation of alcohols
using Na2Cr2O7 as an oxidant at room temperature by
shaking is a new and efficient method for the prepara-
tion of the corresponding aldehydes and ketones.
3. Experimental
Oxidation of benzyl alcohol to benzaldehyde. Typical
procedure: a mixture of benzyl alcohol (108 mg,
1 mmol) and Na2Cr2O7Æ2H2O (298 mg, 1 mmol; finely
and carefully to grind into around 200–300 mesh in
advance) in a normal test tube is shaken mechanically
(Oscillation frequency: 220 times per minute; Horizontal
oscillator, Model: HY-2, Zhengji Instrument Co. Ltd) at
room temperature for 20 min. The progress of the reac-
tion is monitored by TLC (plates: aluminium-backed sil-
ica gel Merck 60 GF254) using hexane–ethyl acetate (8:2)
as eluent. The reaction mixture is then washed with
dichloromethane (3 · 5 mL). The combined filtrates are
evaporated to give crude product, which is purified by
preparative TLC with hexane–ethyl acetate (8:2) to
afford 103 mg (97%) benzaldehyde.
O
OH
R2
Na2Cr2O7
R1
R.T. Shaking
R1
R2
In the present procedure, commercial Na2Cr2O7 by
grinding to a fine power and a 1:1 molar ratio of Na2-
Cr2O7 to substrate are employed with shaking machine
at room temperature for the oxidation. The reaction
progress is monitored by TLC. In general, the oxida-
tions are complete within 30 min. The product is of
acceptable purity for most purposes. The results, which
are shown in Table 1, show that the method is generally
4. Note
This oxidation is exothermic, and precautions should be
taken to avoid it running amuck. Even though we have
Table 1. Solvent-free sodium dichromate oxidations by shaking
Substratea
Scale
(mg/
mmol)
Reaction
time (min)
Productb
Yieldc
(%)
Bp (ꢁC/mm)
Mp (ꢁC) of 2,4-DNP
Reported13
Found
Reported13 Found
n-CH3(CH2)4CH2OH
CH3CCl@CHCH2OH
PhCH2OH
PhCH@CHCH2OH
p-H3CO–C6H4–CH2OH
CH2@CHCH(OH)CH3
CH3CH2CH(OH)CH3
306/3 30
320/3 20
108/1 20
134/1 20
138/1 20
144/2 20
222/3 30
n-CH3(CH2)4CHO
CH3CCl@CHCHO
PhCHO
PhCH@CHCHO
p-H3CO–C6H4–CHO
CH2@CHC(O)CH3
CH3CH2C(O)CH3
83
91
97
95
95
87d
90
130–131/760 131
34–35/10
104–105 104
130
129–13014
238–239 237
255–257 255
252–254 254
14514
57–58/10
121–122/10
122–123/10
178–179
248
248
140–141 139.5–140.5
113–115 115
79–80/760
80
OH
O
501/5 30
95
153–155/760 155
161–162 161–162
48–49.5e 48–49e
PhCH(OH)Ph
PhCH(OH)COOC2H5
C15H31CH(OH)CH2COOC2H5 329/1 30
PhCH(OH)CH2OH
184/1 20
180/1 20
PhC(O)Ph
PhCOCOOC2H5
C15H31COCH2COOC2H5 90
PhCOCH2OH
97
95
117–118/0.9 305
127–129/10
110–113/10
130/10
36–38f
37–38f
138/1 20
93
118–120/11 233–234 233–236
216/3 30
89
106–109/760 97–100/740 185–186 182–185
CH2OH
CHO
OH
C
O
C
336/3 30
96
60–63/10
162.5–163
192–194 193–194
H
a All the substrates are commercially available.
b All the aldehydes and ketones have been described previously in the literature and were identified by their IR spectra or by the IR spectra and
melting points of their 2,4-dinitrophenylhydrazones.
c Yield of isolated product.
d Isolated as the 2,4-dinitrophenylhydrazone.
e Mp of benzophenone.
f Mp of ethyl 3-oxooctadecylate.

J.-D. Lou et al. / Tetrahedron Letters 47 (2006) 311–313
313
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run each reaction at least three times on the amounts
ranging from 100 to 1000 mg in high yields without
encountering any problem, we nevertheless advise that
any user should certainly never run on a large scale.
Sodium dichromate dihydrate is a highly toxic agent.
All chromium(VI) reagents must be handled with care.
The mutagenicity of chromium(VI) compounds is well
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in adding sodium dichromate dihydrate to organic
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