Tr ich lor oisocya n u r ic/TEMP O Oxid a tion of
Alcoh ols u n d er Mild Con d ition s: A Close
In vestiga tion
SCHEME 1
Lidia De Luca, Giampaolo Giacomelli,*
Simonetta Masala, and Andrea Porcheddu
Dipartimento di Chimica, Universit a` degli Studi di Sassari,
Via Vienna 2, I-07100 Sassari, Italy
piperidinyloxy (TEMPO).10 In particular, this last system
operates rapidly, at room temperature, and in an organic
solvent such as dichloromethane. However, the resulting
aldehyde has to be oxidized in a second step.
Received March 3, 2003
Oxidation of primary alcohols to carboxylic acids
through TEMPO-catalyzed procedures was recently re-
Abstr a ct: Efficient oxidation of primary alcohols to the
corresponding carboxylic acids can be carried out at room
temperature and in acetone/water, using trichloroisocyanuric
acid (TCCA) in the presence of catalytic TEMPO. The mild
conditions of this procedure and the total absence of any
transition metal make this reaction suitable for safe labora-
tory use. A possible mechanism is presented and discussed.
1
1, 12
ported.
Bleach and sodium chlorite solution have to
be used as oxidants at 35 °C in MeCN in an economical
and practical methodology. The reaction is efficient but
the procedure employed is quite complicated, as caution
has to be taken in the mixing of bleach and NaClO2.
Within this context, we report here a safe and efficient
one-pot oxidation of primary carbinols to their carboxylic
acids, using the same trichloroisocyanuric acid/TEMPO
couple, simply using acetone as solvent. In this case, the
reaction proceeds more slowly than the oxidation carried
The development of oxidation processes constitutes an
1
active area of both academic and industrial research and
is a topic of current interest. However, direct conversion
of primary alcohols to the corresponding carboxylic acids
is still a challenge, and the most commonly used methods
1
1
out in CH
2
Cl
2
and the entire process requires from 20
1
min to several hours to completion in relation to the
structure of the alcohol. Nevertheless the yields are
quantitative, and the acids can be recovered without any
additional purification (Scheme 1).
include transition-metal-assisted oxidations. Only a few
2
3
examples of reactions with chromium, ruthenium, or
4
tungsten catalysts for the synthesis of carboxylic acids
have been reported up to now.
5
The procedure is based on the addition of 2 molar
equiv13 of 1,3,5-trichloro-2,4,6-triazinetrione (trichlor-
oisocyanuric acid), a very cheap and nontoxic reagent,
to an acetone solution of the alcohol followed by catalytic
amounts (0.1 equiv) of TEMPO and of NaBr1 and then
In the area of metal-free alcohol oxidations, Swern
6
oxidation has emerged, along with the use of TEMPO-
7
based ones, as an important reaction to be used under
8
mild conditions too. During our program on the use of
4
9
1
,3,5-triazine derivatives in organic synthesis, we have
1
3
equiv of aq NaHCO . This system operates at room
reported a very mild and chemoselective oxidation of alco-
hols to carbonyl compounds that uses trichloroisocyanuric
acid in the presence of catalytic 2,2,6,6-tetramethyl-1-
temperature, the oxidation of the primary alcoholic group
being practically quantitative (Table 1).
The reaction is reasonably fast (generally less than 6
h) and only in a few cases requires up to 24 h for
completion (e.g., run 13). Moreover, this method can be
successfully applied on a large scale. On examination of
Table 1, some observations can be made.
(1) Sheldon, R. A.; Kochi, J . K. Metal-Catalyzed Oxidation of Organic
Compounds; Academic Press: New York, 1984. (b) Hudlicky, M.
Oxidation in Organic Chemistry; ACS Monograph 186; American
Chemical Society: Washington, DC, 1990.
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The reaction rate is related to the structure of the
primary alcohol employed, apparently to its steric hin-
drance. Under the usual conditions, even N-protected
â-amino alcohols are oxidized to N-protected R-amino
acids, with slightly reduced rates (entries 9-14); how-
(
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(
(
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1
Bull. Chem. Soc. J pn. 1999, 72, 2287.
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(
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2
480.
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1
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(14) Using 1 equiv of TCCA the reaction is very slow and requires
longer reaction time for completion.
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6
6, 7907.
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0.1021/jo034276b CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/13/2003
J . Org. Chem. 2003, 68, 4999-5001
4999