3-Nitrobenzeneboronic acid as an efficient and environmentally benign catalyst for the selective transesterification of β-keto esters

Article abstract of DOI:10.1055/s-2006-932454

An efficient and high-yielding procedure for the selective transesterification of various β-keto esters using 3-nitrobenzeneboronic acid as a catalyst in an environmentally acceptable process is described. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-932454

LETTER
415
3-Nitrobenzeneboronic Acid as an Efficient and Environmentally Benign
Catalyst for the Selective Transesterification of b-Keto Esters
Catalyst for the
S
.
elective Tra
n
H
sesterification of
.
b
-KetoEster
T
s
ale,* A. D. Sagar, H. D. Santan, R. N. Adude
Organic Chemical Research Laboratory, School of Chemical Sciences, S. R. T. M. University, Nanded 431606, Maharashtra, India
Fax +91(2462)229245; E-mail: rkht2002@yahoo.com
Received 5 October 2005
tive catalyst for the azidation14 and reduction15 of carbox-
ylic acids. In this paper, in continuation of our interest in
the applications of arylboronic acids in organic synthe-
sis,14–16 we wish to report another remarkable catalytic
activity of arylboronic acid, this time that of 3-nitro-
benzeneboronic acid 1 (Figure 1) for selective transester-
ification of b-keto esters. We show that easily available
and relatively inexpensive boronic acid 1 was found to be
a mild and versatile catalyst to develop an efficient and
high-yielding protocol for the transesterification of b-keto
esters in a selective manner.
Abstract: An efficient and high-yielding procedure for the selec-
tive transesterification of various b-keto esters using 3-nitroben-
zeneboronic acid as a catalyst in an environmentally acceptable
process is described.
Key words: b-keto esters, 3-nitrobenzeneboronic acid, environ-
mentally benign, selective reaction
With the increasing environmental concerns and the regu-
latory constraints faced in the chemical and pharmaceuti-
cal industries, development of the environmentally benign
organic reactions has become a crucial and demanding re-
search area in modern organic chemical research.1 There-
fore, more and more chemists’ synthetic endeavors are
devoted towards green synthesis, which means that the
reagents, solvents, and catalysts are environmentally
friendly. Transesterification is an important process as it
has wide applications in both academic and industrial
research.2 b-Keto esters represent an important class of
organic building blocks3 and are used for the efficient syn-
thesis of many complex natural products. In general, the
use of protic acids,4 Lewis acids,5 and basic catalysts6
accelerates the transesterification process. An efficient
method of transesterification employing the tert-butyl
acetoacetate, which is limited only to the tert-butyl esters,
has been reported. In recent years, various catalysts have
been reported to effect the transterification of b-keto
esters.7–13 Although some of these methods are efficient
and provide the practical means for the synthesis of b-keto
esters, many of these procedures suffer from one or more
limitations such as: 1) most of the reported methods of
transesterification are not general and those which are
equilibrium-driven reactions essentially required an ex-
cess use of one of the reactants, alcohol or ester to obtain
good yield, or 2) use of the catalysts which are toxic, ex-
pensive and difficult to prepare and 3) lack of selectivity.
B(OH)2
NO2
1
Figure 1
Thus when b-keto esters were allowed to react with alco-
hols in the presence of catalytic amount (2.5 mol%) of 1,
the corresponding transesterified products were obtained
in good to high yields (Table 1). As can be seen from
Table 1, the present procedure is general as the structural-
ly diverse b-keto esters such as open-chain, cyclic and
aromatic ones underwent transesterification smoothly
with primary, secondary, cyclic, allylic and benzylic alco-
hols. It is to be noted that the transestrerification of b-keto
esters with tertiary alcohols, such as tert-butyl alcohol
leading to tert-butyl ester, is problematic in acid-catalysed
reactions. However, by our method transesterification
with tert-butyl alcohol (Table 1, entry 9) proceeded
smoothly giving good yield of the corresponding product.
Remarkably, the method is also applicable to the trans-
esterification of b-keto esters with unsaturated alcohols,
which is otherwise difficult due to the facile decarboxyla-
tive rearrangement.17 However, under the present reaction
conditions, the corresponding transesterified product was
obtained in high yield (Table 1, entries 10 and 11). More-
over, in contrast to the reported methods (for instance, the
transesterification catalysed by tin-based superacid18
failed with aromatic b-keto esters), the present catalyst
was found to be effective for the transesterification with
aromatic b-keto esters (Table 1, entries 5 and 8) giving ex-
cellent yields of the product. This can be considered as the
significant advantage of our method over the existing one.
The most striking feature of the present method is that the
transesterification is specific only to b-keto esters as other
Thus there are sufficient drawbacks to the most of these
procedures that clearly justify the need for the develop-
ment of general, selective and practical method of transes-
terification. The arylboronic acids, particularly those with
electron-withdrawing substituents on the aromatic ring
behave as an efficient Lewis acid catalyst. We previously
reported 3,4,5-trifluoro benzeneboronic acid as an effec-
SYNLETT 2006, No. 3, pp 0415–0418
1
5.
0
2.
2
0
0
6
Advanced online publication: 06.02.2006
DOI: 10.1055/s-2006-932454; Art ID: D30605ST
© Georg Thieme Verlag Stuttgart · New York

416
R. H. Tale et al.
LETTER
Table 1 Transesterification of b-Keto Esters with Various Alcohols Catalysed by 1a
O
O
O
O
cat. 1
R3OH
+
R1
OR2
toluene, ∆
R1
OR3
Entry
1
b-Keto ester
Alcohol
Time (h)
10
Product
Yield (%)b
O
O
O
O
O
O
O
O
O
O
O
O
O
O
n-BuOH
78
71
74
92
Me
O
Me
Me
Me
Me
Ph
OEt
OEt
OEt
OEt
OEt
OBu
2
3
4
n-C6H13OH
16
14
10
Me
O
OC6H13
OC10H21
n-C10H21OH
Me
O
OH
O
O
Me
O
O
OH
5
6
7
12
16
18
95
87
67
O
Ph
O
O
O
O
O
O
O
O
O
OH
O
Me
Me
Ph
OEt
OEt
OEt
Me
Cl
Cl
O
OH
Cl
O
Me
Cl
O
O
OH
8
16
75
O
Ph
NO2
NO2
O
O
O
O
O
O
O
9
10
11
t-BuOH
19
15
12
59
64
89
Me
Me
OEt
OEt
Me
O
Ot-Bu
HC
OH
Me
O
HC
O
O
O
O
OH
Ph
Me
OEt
Me
O
Ph
a All the products were characterised by their spectroscopic data (IR, 1H NMR).
b Yields refer to the pure isolated products.
esters like a-keto esters, g-keto esters as well as the nor- another significant advantage as the transesterification of
mal esters failed to undergo transesterificton. We attribute b-keto esters with thiols is often problematic due to facile
the difference in the reactivity of b-keto esters over other decarboxylation of the thio analogue on hydrolysis.17
esters in tranesterification most probably to the activation Moreover, the method can be used successfully for the
of the former by the catalyst to form an acylketene inter- transamidation as aniline reacted smoothly with b-keto
mediate which is not possible in other esters as proposed esters to afford the corresponding transamidation product
by Campbell and Lawrie.19 In order to expand the scope in high yield. Prompted by the above results, we thought
of our methodology further, we studied the transesterifica- it was worthwhile to look closely at the reactivity pattern
tion with other nucleophiles such as thiols and amines. of diol, mercapto alcohol and amino alcohol towards the
The results, summarised in Table 2, clearly show that the tranesterification process. We performed the transesterifi-
b-keto ester can be smoothly converted to its thio cation with these nucleophiles in the presence of catalyst
anologue in good yield. Thus the present method offers 1 and the results of our study are collected in Table 2. As
Synlett 2006, No. 3, 415–418 © Thieme Stuttgart · New York

LETTER
Catalyst for the Selective Transesterification of b-Keto Esters
417
Table 2 Transesterification of b-Keto Esters with Thiols, Amines, Diols and Amino Alcohols Catalysed by 1a
Entry
1
b-Keto ester
Alcohol
Time (h)
10
Product
Yield (%)b
78
O
O
O
O
O
SH
Me
Me
S
OEt
OEt
Me
O
O
O
NH2
2
16
87
Me
NH
O
O
O
O
O
O
O
O
O
O
3
4
5
14
13
12
74
90
67
OH OH
SH OH
Me
Me
Me
O
OH
Me
O
OEt
OEt
OEt
O
Me
O
SH
OH
OH NH2
Me
NH
a All the products were characterised by their spectroscopic data (IR, 1H NMR).
b Yields refer to the pure isolated products.
shown in Table 2, the hydroxy group of mercapto alcohol
reacted preferentially over thiol affording the correspond-
ing product in good yield. The selective mono-transester-
ification of diol was achieved using the present catalyst to
afford the corresponding mono-esterified product in high
yield. In case of amino alcohol (Table 2, entry 5), the
corresponding transamidation product was obtained in
good yield as the amino group is more nucleophilic than
the hydroxy one.
References and Notes
(1) (a) Fujita, T.; Tanaka, M.; Norimine, Y.; Suemune, H. J.
Org. Chem. 1997, 62, 3824. (b) Shapiro, G.; Marzi, M. J.
Org. Chem. 1997, 62, 7096.
(2) (a) Rehberg, C. E.; Fisher, C. H. J. Am. Chem. Soc. 1944, 66,
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Am. Chem. Soc. 1944, 66, 1723. (c) Rehberg, C. E. Org.
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(d) Haken, J. K. J. Appl. Chem. 1963, 13, 168.
(3) (a) Yazawa, H.; Tanaka, K.; Kariyone, K. Tetrahedron Lett.
1974, 3995. (b) Blossey, E. C.; Turner, L. M.; Neckersw, D.
C. Tetrahedron Lett. 1973, 1823.
The reaction is general as a wide range of b-keto esters
and alcohols participated successfully in the transesterifi-
cation process. It is important to note that boronic acids,
RB(OH)2, are usually crystalline solids, stable to air and
moisture. The evidence that exists indicates that the
boronic acids are of relatively low toxicity [benzene-
boronic acid:20 LD50 oral, rat = 740 mg/kg] and environ-
mental impact. Furthermore, small amount of 3-
nitrobenzeneboronic acid was found to be effective for
catalysing the selective transesterification of b-keto es-
ters. Thus it is evident that the present method represents
a novel and environmentally benign approach, which not
only preserves the simplicity but consistently provides
good to high yields of the corresponding transesterified
products.21
(4) Taber, D. F.; Amedio, J. C. Jr.; Patel, Y. K. J. Org. Chem.
1985, 50, 3618.
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Lett. 1996, 37, 233.
In conclusion, we have demonstrated that the novel 3-ni-
trobenzeneboronic acid effectively catalysed the selective
transesterification of b-keto esters in an environmentally
acceptable process. In view of the applications of b-keto
esters in various areas, we believe that the present method
will certainly find widespread use in organic synthesis.
(10) (a) Balaji, B. S.; Sasidharan, M.; Kumar, R.; Chanda, M.
Chem. Commun. 1996, 707. (b) Balaji, B. S.; Chanda, M.
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Cope, A. C. J. Am. Chem. Soc. 1943, 65, 1992.
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2002, 43, 3427.
Acknowledgment
Authors are grateful to University Grant Commission (UGC), New
Delhi, India for financial support.
Synlett 2006, No. 3, 415–418 © Thieme Stuttgart · New York

418
R. H. Tale et al.
LETTER
(16) Sagar, A. D.; Tale, R. H.; Adude, R. N. Tetrahedron Lett.
2003, 44, 70.
(17) (a) Carool, M. F. J. Chem. Soc. 1940, 784. (b) Kimel, W.;
Cope, A. J. Am. Chem. Soc. 1943, 65.
(18) Chavan, S. P.; Zubaidha, P. K.; Dhantale, S. W.;
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(19) Camppbell, D. S.; Lawrie, C. W. J. Chem. Soc., Chem.
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(20) Boron, Metallo-Boron Compounds and Boranes; Adams, R.
M., Ed.; Wiley: New York, 1964, 693; data quoted in
Registry of Toxic Effects of Chemical Substances, NIOSH,
2001.
(21) Typical Procedure (Table 1, entry 8): Ethyl acetoacetate (5
mmol), 3-nitrobenzyl alcohol (5 mmol) and 3-nitro-
benzeneboronic acid (21 mg, 2.5 mol%) in 20 mL of toluene
was heated at reflux for the time allotted (Table 1) with
removal of toluene–ethanol azeotrope by distillation. The
progress of the reaction was monitored by TLC. After
completion of the reaction, the mixture was concentrated and
the residue was chromatographed on silica gel (elution with
EtOAc–hexane; 20:80) to afford the pure 3-nitrobenzyl
acetoacetate.
Synlett 2006, No. 3, 415–418 © Thieme Stuttgart · New York