Lithium bromide as a flexible, mild, and recyclable reagent for solvent-free cannizzaro, tishchenko, and meerwein-ponndorf-verley reactions

Article abstract of DOI:10.1021/ol070894t

A room temperature convenient disproportionation or reduction of aldehydes prompted by lithium bromide and triethylamine is described in a solvent-free environment. Distribution of the products to selectively direct the process toward Cannizzaro or Tishchenko reactions is controlled by the type of workup selection. The presence of hydrogen donor alcohols in the mixture completely diverts the process toward the MeerweinPonndorf-Verley reaction.

Full text of DOI:10.1021/ol070894t

ORGANIC
LETTERS
2
007
Vol. 9, No. 15
791-2793
Lithium Bromide as a Flexible, Mild, and
Recyclable Reagent for Solvent-Free
Cannizzaro, Tishchenko, and
2
Meerwein−Ponndorf−Verley Reactions
Mohammad M. Mojtahedi, Elahe Akbarzadeh, Roholah Sharifi, and
M. Saeed Abaee*
Organic Chemistry Department, Chemistry & Chemical Engineering Research Center
of Iran, P.O. Box 14335-186, Tehran, Iran
abaee@ccerci.ac.ir
Received April 17, 2007
ABSTRACT
A room temperature convenient disproportionation or reduction of aldehydes prompted by lithium bromide and triethylamine is described in
a solvent-free environment. Distribution of the products to selectively direct the process toward Cannizzaro or Tishchenko reactions is controlled
by the type of workup selection. The presence of hydrogen donor alcohols in the mixture completely diverts the process toward the Meerwein
Ponndorf Verley reaction.
−
−
3
With increasing global environmental concerns, design of
green processes with no use of hazardous and expensive
solvents, e.g., “solvent-free” reactions, has gained special
carboxylic acids. For many decades, the reaction was
generally conducted under strong basic conditions or at
4
elevated temperatures, and is in competition with other
parallel carbonyl group transformations. Two of the most
closely related processes to the Cannizzaro reaction are the
Tishchenko dimerization of aldehydes to form the corre-
1
attention from synthetic organic chemists. As a result, many
5
reactions are newly found to proceed cleanly and efficiently
2
6
in the solid state or under solvent-free conditions. Less
chemical pollution, lower expenses, and easier procedures
are the main reasons for the recent increase in the popularity
of solvent-free reactions.
The classical Cannizzaro reaction involves the red-ox
conversion of aldehydes into their respective alcohols and
sponding ester compounds and the Meerwein-Ponndorf-
Verley (MPV) reduction of carbonyl moieties to produce
7
their analogous alcohols. Both reactions are usually con-
ducted under the influence of stoichiometric or excessive
8
amounts of trivalent aluminum-based catalysts. Recent
developments in this area involve the use of various Lewis
(
1) (a) Tanaka, K. SolVent-Free Organic Synthesis; Wiley-VCH: Wein-
heim, Germany, 2003. (b) Tanaka, K.; Toda, F. Chem. ReV. 2000, 100,
025-1074.
2) For some recent examples of solvent-free reactions see: (a) Zhao, J.
L.; Liu, L.; Sui, Y.; Liu, Y. L.; Wang, D.; Chen, Y. J. Org. Lett. 2006, 8,
127-6130. (b) Castrica, L.; Fringuelli, F.; Gregoli, L.; Pizzo, F.; Vaccaro,
(3) (a) Cannizzaro, S. Justus Liebigs Ann. Chem. 1853, 88, 129-130.
(b) For a recent example of Cannizzaro reaction see: Basavaiah, D.; Sharada,
D. S.; Veerendhar, A. Tetrahedron Lett. 2006, 47, 5771-5774.
(4) (a) Maruyama, K.; Murakami, Y.; Yoda, K.; Mashino, T.; Nishinaga,
A. J. Chem. Soc., Chem. Commun. 1992, 1617-1618. (b) Jin, S. J.; Arora,
P. K.; Sayre, L. M. J. Org. Chem. 1990, 55, 3011-3018.
(5) Smith, M. B.; March, J. AdVanced Organic Chemistry; John Wiley
& Sons: New York, 2001; pp 1564-1566.
(6) (a) Tischtschenko, W. J. Russ. Phys. Chem. 1906, 38, 355. (b) Ogata,
Y.; Kawasaki, A.; Kishi, I. Tetrahedron 1967, 23, 825-830.
(7) Meerwein, H.; Schmidt, R. Justus Liebigs Ann. Chem. 1925, 444,
221-238.
1
(
6
L. J. Org. Chem. 2006, 71, 9536-9539. (c) Azizi, N.; Aryanasab, F.; Saidi,
M. R. Org. Lett. 2006, 8, 5275-5277. (d) Lofberg, C.; Grigg, R.; Whittaker,
M. A.; Keep, A.; Derrick, A. J. Org. Chem. 2006, 71, 8023-8027. (e)
Hosseini-Sarvari, M.; Sharghi, H. J. Org. Chem. 2006, 71, 6652-6654. (f)
Mojtahedi, M. M.; Abaee, M. S.; Heravi, M. M.; Behbahani, F. K. Monatsh.
Chem. 2007, 138, 95-99. (g) Choudhary, V. R.; Jha, R.; Jana, P. Green
Chem. 2007, 9, 267-272.
1
0.1021/ol070894t CCC: $37.00
© 2007 American Chemical Society
Published on Web 06/20/2007

9
,10
11,12
acidic reagents, heterogeneous catalytic systems,
and
form of esters, we replaced water with methanol in the
workup procedure. Therefore, when the same reaction
mixtures were treated with methanol, respective methyl esters
of the starting aldehydes were obtained in excellent amounts
along with equivalent quantities of their analogous alcohols
(Table 1). After completion of the reactions, LiBr was
supercritical solvents.1 Nevertheless, design of new pro-
cedures to improve the conditions for these reactions in a
milder and less expensive environment would be of interest.
During our recent investigations on Lewis acid-catalyzed
carbonyl chemistry, we communicated a room temperature
version of the Cannizzaro reaction that could conveniently
convert aldehydes to their corresponding alcohols and
carboxylic acids under very mild conditions consisting of
3,14
18
15
Table 1. Cannizzaro Reactions of Aromatic Aldehydes under
LiBr Catalysis
16
MgBr
2
2 3
‚OEt and triethylamine (Et N). As a consequence
of our attempts to apply these mild and convenient conditions
to other red-ox reactions of carbonyl compounds, we would
like to report a flexible protocol by which selective conver-
sion of aldehydes with no R-hydrogen to their respective
alcohols and/or carboxylic functionalities of choice is practi-
cally attainable under catalysis of lithium bromide (LiBr)
and in the absence of any solvent.
We first optimized the conditions for Cannizzaro reactions
of three representative model aldehydes using various
quantities of LiBr. The optimum results were obtained by
entry
products
yield (%)a
1
7
1
2
3
4
5
C6H5CH2OH; C6H5COOMe
97
98
98
96
94
(m-MeO)C6H4CH2OH; (m-MeO)C6H4COOMe
(m-F)C6H4CH2OH; (m-F)C6H4COOMe
(p-Cl)C6H4CH2OH; (p-Cl)C6H4COOMe
â-naphthyl-CH2OH; â-naphthyl-COOMe
a
1
Yields of isolated products characterized by H NMR analysis.
3
using Et N and half equivalents of LiBr when reactions were
conducted at room temperature in a solvent-free environment.
After complete consumption of the starting aldehydes,
treatment of the mixtures with excessive water for about 2
h led to more than 85% formation of the respective alcohols
and carboxylic acids (Scheme 1).
recovered by a simple filtration and reused efficiently in the
next reactions.
1
9
Having these promising results in hand, we next decided
to extend this chemistry to Tishchenko dimerization of
aldehydes as one the most practical tools to synthesize esters
2
0
21
Scheme 1
and lactones which have many industrial applications as
synthetic precursors for durable epoxy resins, dye carriers,
solvents, plasticizers, and artificial flavor. The Tishchenko
reaction is classically conducted in solution under catalysis
of aluminum or magnesium alkoxides, transitional metal
8
a,9a
9b,c
complexes,
or rare earth elements. Very recently, Hill
and co-workers reported a catalytic Tishchenko reaction for
electron deficient aldehydes promoted by alkaline earth metal
complexes.
For more convenient fractionation of the reaction mixtures
and in order to directly obtain the carboxylic moieties in the
9
d
When we mixed various aldehydes with LiBr and Et
3
N
(
8) (a) Seki, T.; Nakajo, T.; Onaka, M. Chem. Lett. 2006, 35, 824-829.
under solvent-free conditions at room temperature, formation
of dimeric esters of the starting substrates was observed in
high yields as represented in Table 2. Notably, the conditions
employed here were the same as those used for the
Cannizzaro reactions in Scheme 1 except that the aqueous
(
b) Cha, J. S. Org. Process Res. DeV. 2006, 10, 1032-1053. (c) Campbell,
E. J.; Zhou, H.; Nguyen, S. T. Org. Lett. 2001, 3, 2391-2393 and references
therein.
(
9) (a) Ogata, Y.; Kawasaki, A. Tetrahedron 1969, 25, 929-955. (b)
Burgstein, M. R.; Berberich, H.; Roesky, P. W. Chem. Eur. J. 2001, 7,
3
078-3085. (c) Suzuki, T.; Yamada, T.; Matsuo, T.; Watanabe, K.; Katoh,
T. Synlett 2005, 1450-1452. (d) Crimmin, M. R.; Barrett, G. M.; Hill, M.
S.; Procopiou, P. A. Org. Lett. 2007, 9, 331-333.
(10) (a) Boronat, M.; Corma, A.; Renz, M. J. Phys. Chem. B 2006, 110,
(17) For some recent synthetic applications of LiBr see: (a) Chakraborti,
A. K.; Rudrawar, S.; Kondaskar, A. Eur. J. Org. Chem. 2004, 3597-3600.
(b) Maiti, G.; Kundu, P.; Guin, C. Tetrahedron Lett. 2003, 44, 2757-2758.
(c) Roy, S. C.; Guin, C.; Maiti, G. Tetrahedron Lett. 2001, 42, 9253-
9255. (d) Rudrawar, S. Synlett 2005, 1197-1198 and references cited
therein.
(18) To the best of our knowledge, direct synthesis of nondimeric esters
via disproportionation of aldehydes is only reported in intramolecular
reactions of aryl glyoxals. For a recent example see: Curini, M.; Epifano,
F.; Genovese, S.; Marcotullio, M. C.; Rosati, O. Org. Lett. 2005, 7, 1331-
1333.
2
1168-21174. (b) Zhu, Y.; Liu, S.; Jaenicke, S.; Chuah, G. Catal. Today
2
004, 97, 249-255.
(11) (a) Chen, Y.; Zhu, Z.; Zhang, J.; Shen, J.; Zhou, X. J. Organomet.
Chem. 2005, 690, 3783-3789. (b) Tsuji, H.; Hattori, H. ChemPhysChem.
004, 5, 733-736.
12) (a) Zapilko, C.; Liang, Y.; Nerdal, W.; Anwander, R. Chem. Eur.
2
(
J. 2007, 13, 3169-3176. (b) Samuel, P. P.; Shylesh, S.; Singh, A. P. J.
Mol. Catal. A: Chem. 2007, 266, 11-20.
(
13) (a) Seki, T.; Onaka, M. J. Phys. Chem. B 2006, 110, 1240-1248.
(
b) Seki, T.; Onaka, M. Chem. Lett. 2006, 34, 262-263.
14) Kamitanaka, T.; Matsuda, T.; Harada, T. Tetrahedron 2007, 63,
429-1434.
15) (a) Abaee, M. S.; Mojtahedi, M. M.; Zahedi, M. M. Synlett 2005,
(
(19) Upon completion of each reaction, the mixture was diluted by
toluene and LiBr was separated by filtration. The separated LiBr was washed
with toluene, dried under vacuum, and used in the next reactions without
significant loss of activity. For further details see the Supporting Information.
(20) (a) Ooi, T.; Ohmatsu, K.; Sasaki, K.; Miura, T.; Maruoka, K.
Tetrahedron Lett. 2003, 44, 3191-3193. (b) Seki, T.; Hattori, H. Chem.
Commun. 2001, 2510-2511.
1
(
2
2
317-2320. (b) Mojtahedi, M. M.; Abaee, M. S.; Abbasi, H. Can. J. Chem.
006, 429-432. (c) Mojtahedi, M. M.; Abaee, M. S.; Abbasi, H. J. Iran.
Chem. Soc. 2006, 3, 93-96. (d) Abaee, M. S.; Mojtahedi, M. M.; Zahedi,
M. M.; Sharifi, R. Heteroatom. Chem. 2007, 18, 44-49.
(16) Abaee, M. S.; Sharifi, R.; Mojtahedi, M. M. Org. Lett. 2005, 7,
(21) Ulmann’s Encyclopedia of Industrial Chemistry; Gerhartz, W., Ed.;
Wiley-VCH: Weinheim, Germany, 1985; Vol. A9, pp 565-585.
5
893-5895.
2792
Org. Lett., Vol. 9, No. 15, 2007

2
experiments showed that when 1:1:1 mixtures of LiBr:Me -
CHOH:aldehydes were mixed in the absence of any solvent,
quantitative reduction of the aldehydes to their respective
alcohols was observed (Table 3).
Table 2. Tishchenko Reactions of Aromatic Aldehydes under
LiBr Catalysis
1
9
Table 3. MPV Reactions of Aromatic Aldehydes under LiBr
Catalysis
entry
product
C6H5CH2OH
(m-Me)C6H4CH2OH
(m-MeO)C6H4CH2OH
(m-F)C6H4CH2OH
(p-Cl)C6H4CH2OH
(p-Br)C6H4CH2OH
thiophene-2-yl-CH2OH
pyridine-2-yl-CH2OH
trans-C6H5CHdCHCH2OH
yield (%)a
1
2
3
4
5
6
7
8
9
98
97
95
98
99
97
98
97
98
a
1
Yields of isolated esters characterized by GC-MS and H NMR.
workup was avoided and the products were obtained by
simple filtration of the solid fraction and removal of the
volatile portions of the mixtures.19
a
1
Yields of isolated alcohols characterized by GC-MS and H NMR.
This fact that both reactions proceed under the 2:1 ratio
of aldehyde:LiBr suggests the presence of a possible reacting
species consisting of two aldehyde molecules coordinated
through their carbonyl oxygen atoms to the lithium ion (a).
In summary, we demonstrated that LiBr, a very stable and
mild reagent to handle, can selectively and efficiently direct
aldehydes to undergo Cannizzaro, Tishchenko, or MPV
reactions with use of very inexpensive solvent-free conditions
at room temperature. Recycling of the catalyst and environ-
mental safety of the process are additional advantages of the
present method. Attempts to apply these mild conditions to
transesterification of esters are currently under investigation.
Acknowledgment. Partial financial support of this work
by the Ministry of Science, Research, and Technology of
Iran is gratefully acknowledged.
Such a reacting species which form a six-membered transi-
tion state could facilitate “intramolecular” hydride transfer
between the two aldehydes and has been previously reported
Supporting Information Available: Experimental pro-
cedures and spectral data. This material is available free of
charge via the Internet at http://pubs.acs.org.
9a,16
in the literature for Cannizzaro and Tishchenko reactions.
On the basis of this mechanism, we envisaged that
substitution of one of the two reacting aldehydes in the
discrete complex by a hydride donor alcohol could divert
the process toward the MPV reaction (via b), which is usually
OL070894T
(22) (a) Lebrun, A.; Namy, J.-L.; Kagan, H. B. Tetrahedron Lett. 1991,
8
b,c
conducted under aluminum
or other metal alkoxides
32, 2355-2358. (b) Ashby, E. C.; Argyropoulos, J. N. J. Org. Chem. 1986,
5
2
1, 3593-3597. (c) Zhu, Y.; Jaenicke, S.; Chuah, G. K. J. Catal. 2003,
18, 396-404. (d) Namy, J.-L.; Souppe, J.; Collin, J.; Kagan, H. B. J.
2
2
catalysis. Recent advancements to the MPV reaction still
involve the use of other basic reagents and catalysts. Our
8
b
Org. Chem. 1984, 49, 2045-2049.
Org. Lett., Vol. 9, No. 15, 2007
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