Sodium hydride catalyzed Tishchenko reaction

Article abstract of DOI:10.1002/ejoc.201001294

A convenient and practical method for the dimerization of aldehydes is described. The conversion of aromatic and even heteroaromatic aldehydes in the presence of catalytic amounts of sodium hydride leads to the corresponding Tishchenko esters in high yields (up to 95 %). The reaction can be performed under standard laboratory conditions and on a multigram scale (up to 10 g). The use of catalytic amounts of sodiumhydride as an efficient promoter for the dimerization of aromatic and even heteroaromatic aldehydes under standard laboratory conditions is reported. A range of substituted aromatic and heteroaromatic aldehydes was converted, and the corresponding esters were obtained in good to excellent yields even on a multigram scale. Copyright

Full text of DOI:10.1002/ejoc.201001294

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201001294
Sodium Hydride Catalyzed Tishchenko Reaction
[a]
[a]
Thomas Werner* and Juliane Koch
Dedicated to Professor Uwe Rosenthal on the occasion of his 60th birthday
Keywords: Tishchenko Reaction / Dimerization / Sodium hydride / Aldehydes / Synthetic methods
A convenient and practical method for the dimerization of
aldehydes is described. The conversion of aromatic and even
heteroaromatic aldehydes in the presence of catalytic
amounts of sodium hydride leads to the corresponding Tish-
chenko esters in high yields (up to 95%). The reaction can
be performed under standard laboratory conditions and on a
multigram scale (up to 10 g).
Introduction
hyde to benzyl benzoate, have also been reported, including
[
7]
[8]
[9]
boric acid, transition-metal catalysts based on Fe, Ru,
The development of novel, efficient and environmentally
benign reactions and catalysts that make those processes
possible are constant challenges for synthetic organic chem-
ists. The atom economic conversion of aldehydes 1 to the
analogous carboxylic esters 2 through dimerization, better
known as the Tishchenko (or Claisen–Tishchenko) reac-
[10]
[11]
[12]
Os,
Zr, and Hf.
More recently iridium
and lantha-
[13]
nide complexes,
amides,
as well as heavier alkaline earth
have been reported as active catalysts for the
[14]
Tishchenko reaction and mediate the dimerization of ali-
phatic and aromatic aldehydes to the carboxylic esters.
However, these catalysts are either not commercially avail-
able, expensive, difficult to prepare, air- and moisture sensi-
tive, slow, only reactive under extreme conditions, or give
small yields. Especially, heteroaromatic aldehydes are
known to be difficult to dimerize. The heteroatom of the
substrate can form hemilabile Lewis acid/Lewis base ad-
ducts with the Lewis acid metal center of the catalyst, which
thus hampers the Tishchenko reaction. To the best of our
knowledge, only a very few examples of metal hydride me-
diated Tishchenko reactions have been reported. In those
cases, yields for the desired esters were only moderate or
even low, the scope was very limited, or high-speed ball
tion, has been known for more than
a
century
[
1,2]
(Scheme 1).
This well-known reaction is industrially rel-
evant as the homodimers of aldehydes have found numer-
ous applications in e.g. the fragrance and food indus-
[
2c,3]
tries.
For example, the homodimer of 3-cyclohexene-
carbaldehyde is a precursor for the formation of durable
epoxy resins, whereas benzyl benzoate is used as a dye car-
rier.
[
15]
milling was required.
Scheme 1. Tishchenko reaction.
Sodium-[1a,4] and, in particular, aluminium[5] alkoxides
Results and Discussion
are traditionally employed as catalysts in the Tishchenko
reaction. Many efforts have been made to develop more ef-
ficient aluminium-based catalysts.[ However, many of
those catalysts react sluggishly with aromatic aldehydes
We are interested in the development of novel organocat-
[
16]
alysts for redox reactions. While studying the reaction of
benzaldehyde (1a) in the presence of stoichiometric
amounts of various organic and inorganic bases, we ob-
served that sodium hydride acts as an efficient promoter
for the dimerization of 1a. Herein we report that catalytic
amounts of inexpensive and commercially available sodium
hydride effectively promote the Tishchenko reaction of aro-
matic and heteroaromatic aldehydes. The reaction is easily
performed on a preparative scale of up to several grams of
reactant aldehyde under standard laboratory conditions. We
initially studied the conversion of benzaldehyde (1a) to
6]
such as benzaldehyde or provide the corresponding ester
product in low yields.[
5,6]
Other catalytic systems, which
show moderate activity for the dimerization of benzalde-
[
a] Leibniz-Institut für Katalyse e. V. an der Universität Rostock,
Albert-Einstein-Str. 29a, 18059 Rostock, Germany
Fax: +49-381-1281-51326
E-mail: Thomas.Werner@catalysis.de
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001294.
6904
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 6904–6907

Sodium Hydride Catalyzed Tishchenko Reaction
benzyl benzoate (2a) at 95 °C and room temperature using Table 1. Sodium hydride mediated Tishchenko reaction of aromatic
aldehydes.[
a]
1
to 5 mol-% of sodium hydride as the catalyst (Scheme 2).
In all cases, the conversion was quantitative after 18 h, even
with 1 mol-% catalyst at 23 °C. The only observed by-prod-
uct was alcohol 3, which is formed by the reduction of 1a
with sodium hydride.
Scheme 2. Sodium hydride catalyzed Tishchenko reaction.
We further investigated the reaction of a range of
aromatic aldehydes. In order to achieve full conversion,
5
mol-% sodium hydride was employed. The results are
summarized in Table 1. As expected from trial experiments,
the conversion of benzaldehyde (1a) gave the corresponding
product 2a in an excellent isolated yield of 95% (Entry 1)
even on a 10-g scale. Several 4-substituted benzaldehyde de-
rivatives were also converted, and the corresponding di-
meric esters 2b–e were obtained in good to excellent yields
(
(
Entries 2–5). If 2-chloro- (1f) or 3-chloro benzaldehyde
1g) is used instead of the 4-isomer 1d the conversion is
Ͻ40% at 23 °C. An increase in the reaction temperature to
5 °C leads to quantitative conversion, and 2f and 2g were
obtained in 95% and 88% yield, respectively (Entries 6 and
). Under these conditions, very good yields were also ob-
tained for the dimerization products of 4-phenyl- (1h) and
-methoxy benzaldehyde (1i) (Entries 8 and 9). Further-
9
7
4
more sodium hydride also effectively mediated the intramo-
lecular Tishchenko reaction of 2-phthalaldehyde (1j). The
ester product 2j was isolated in 95% yield after 24 h at
23 °C (Entry 10). When sodium hydride is employed as a
60% dispersion in mineral oil, comparable yields were ob-
tained.
We then turned our attention to the conversion of more
challenging heteroaromatic substrates. The results are sum-
marized in Table 2. The conversion of 2-thiophenecarboxal-
dehyde (1k) in the presence of 5 mol-% sodium hydride in [a] Reaction conditions: 5 mol-% NaH, toluene, 23 °C, 18 h. [b] Iso-
lated yield. [c] 1 mol-% NaH was employed. [d] 95 °C. [e] 24 h.
toluene at 95 °C gave the corresponding ester 2k in good
yield (Entry 1). Under these conditions, very slow conver-
sion was observed for reactants 1l–p. However, in the pres- are obtained e.g. benzyl alcohol (3). Moreover, sodium al-
ence of 10 mol-% sodium hydride, the dimerization of coholates, such as the sodium salt of benzyl alcohol, un-
2
7
-furaldehyde (1l) was quantitative, and 2l was isolated in dergo Tishchenko reaction in the presence of benzalde-
4% yield (Entry 2). Furthermore, the Tishchenko reaction hyde. On the basis of those facts, we propose a catalytic
[
4]
of picoline- (1m), nicotine- (1n), isonicotine- (1o), and chin- cycle for the sodium hydride mediated Tishchenko reaction
oline-2-aldehyde (1p) gave esters 2m–p in 77, 88, 87, and shown in Scheme 3. The first step is the reduction of alde-
86% yield (Entries 3–6), respectively. However, because of hyde 1 by sodium hydride, followed by the addition of the
the basicity of sodium hydride, this protocol is restricted to formed alcoholate 4 to the carbonyl group of a second alde-
aldehydes without an acidic proton in the α-position to the hyde 1. A subsequent hydride transfer from intermediate 5
carbonyl group.
liberates the desired ester 2 and regenerates alcoholate 4.
Even though sodium hydride is generally thought of as Thus, sodium hydride might rather be considered as a pre-
a base, it has been demonstrated that it reduces aldehydes to catalyst. The proposed mechanism is in agreement with our
the corresponding alcoholate in the absence of α-hydrogen findings that the corresponding alcohols are formed as a
[
15a,15b]
atoms.
After aqueous work up, the primary alcohols by-product under our reaction conditions.
Eur. J. Org. Chem. 2010, 6904–6907
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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6905

T. Werner, J. Koch
SHORT COMMUNICATION
Table 2. Sodium hydride mediated Tishchenko reaction of hetero- Experimental Section
[
a]
aromatic aldehydes.
A Typical Procedure: Benzaldehyde (1a) (9.62 g, 90.7 mmol) was
added to a suspension of NaH (22.9 mg, 0.907 mmol) in absolute
toluene (15 mL) at 23 °C. After the reaction mixture was stirred for
1
(
8 h at 23 °C, it was diluted with CH
1 m, 35 mL) was added, and the aqueous phase was extracted with
CH Cl (3ϫ 60 mL). The combined organic layers were dried with
MgSO . After the removal of all volatiles in vacuo, the crude prod-
2 2
Cl (60 mL), HCl solution
2
2
4
uct was purified by Kugelrohr distillation (160 °C, 2.1 mbar) to ob-
1
tain 2a as a pale yellow liquid (9.20 g, 43.3 mmol, 95%). H NMR
(
(
=
1
300 MHz, CDCl
m, 1 H), 8.12–8.15 (m, 2 H) ppm. C NMR (75 MHz, CDCl
66.56, 128.06, 128.13, 128.27, 128.49, 129.59, 130.01, 132.92,
35.95, 166.29 ppm. C14 (212.24): calcd. C 79.22, H 5.70;
3
): δ = 5.41 (s, 2 H), 7.38–7.52 (m, 7 H), 7.56–7.62
1
3
3
): δ
12 2
H O
found C 79.35, H 5.68.
Supporting Information (see footnote on the first page of this arti-
cle): General procedures, experimental details, and compound
characterization data are presented.
Acknowledgments
Financial support from the Deutsche Forschungsgemeinschaft
(
WE 3605/3-1) and the Leibniz-Institut für Katalyse e. V. an der
Universität Rostock, as well as support and advice from Prof. M.
Beller, are gratefully acknowledged.
[
a] Reaction conditions: 10 mol-% NaH, toluene, 95 °C, 18 h. [b]
Isolated yield. [c] 5 mol-% NaH was employed.
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lyzed Tishchenko reaction.
[
[
Conclusions
[
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dimerization of aromatic and even heteroaromatic alde-
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hydride. The reaction can be performed under standard lab-
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Received: September 16, 2010
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Published Online: November 17, 2010
Eur. J. Org. Chem. 2010, 6904–6907
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6907