A facile and selective procedure for transesterification of β-keto esters promoted by yttria-zirconia based lewis acid catalyst

Article abstract of DOI:10.1055/s-2000-6496

An yttria-zirconia based strong Lewis acid efficiently catalyses the transesterification of β-keto esters under environmentally safe, heterogeneous reaction conditions with high selectivity and in good to excellent yields.

Full text of DOI:10.1055/s-2000-6496

LETTER
251
A Facile and Selective Procedure for Transesterification of b-Keto Esters
Promoted by Yttria-Zirconia Based Lewis Acid Catalyst
Pradeep Kumar,* Rajesh Kumar Pandey
Division of Organic Chemistry: Technology, National Chemical Laboratory, Pune-411008, India
Fax +91-20-5893614, E-mail: tripathi@dalton.ncl.res.in
Received 18 November 1999
such as open chain, cyclic and aromatic ones underwent
transesterification with a variety of alcohols. The reaction
proceeds smoothly with primary and secondary alcohols
in excellent yields; while transesterification to t-butyl es-
ter (Table 1, entry 3) which is often problematic in acid
catalyzed reactions, is also realized by this reagent though
in moderate yield. Another noteworthy feature of this
methodology is that unsaturated alcohols like propargyl
and allylic alcohols underwent transesterification reaction
smoothly affording the corresponding products in excel-
lent yields (Table 1, entries 4 & 7). It should be pointed
out that transesterification of β-keto esters with unsaturat-
ed alcohols is rather difficult as it is offset by facile decar-
boxylated rearrangement.14 The superiority of this
procedure can be clearly visualized in transesterification
reactions leading to the synthesis of b-keto esters with an
aromatic moiety in excellent yields (Table 1, entries 5 &
9). In this connection it should be mentioned that a recent
literature report9 which describes synthesis of alkyl b-keto
esters employing a tin-based superacid catalyst, failed
with aromatic substrates. It is clear from Table 1 that
while conversion from methyl / ethyl ester to higher ho-
mologues appears to be efficient by this procedure, the re-
verse transformation such as menthyl ester to ethyl ester
(Table 1, entry 10) could be achieved only in moderate
yield. It is important to mention that the reaction appears
to be specific only for the transesterification of β-keto es-
ters. Other esters like a-keto esters, g-keto esters, unsatur-
ated esters as well as normal esters failed to undergo the
reaction. The difference in the reactivity of b-keto esters
from other esters in transesterification may probably be
due to the formation of acyl ketene intermediate in the
former as proposed by Campbell and Lawrie.15
Abstract: An yttria-zirconia based strong Lewis acid efficiently ca-
talyses the transesterification of β-keto esters under environmental-
ly safe, heterogeneous reaction conditions with high selectivity and
in good to excellent yields.
Key words: transesterification, β-keto esters, alcohols, yttria-zirco-
nia based Lewis acid, heterogeneous catalysis
Transesterification is an important reaction which has
wide applications both in academic and industrial re-
search.1 In general, the transesterification reaction is ac-
celerated by protic acids,2 Lewis acids3 and basic catalysts
such as 4-(dimethylamino)pyridine,4 metal alkoxides,5
metal carbonates6 etc. Recently, an efficient method of
transesterification employing t-butyl acetoacetate has
been reported which is restricted only to t-butyl esters thus
lacking generality.7 Otera et.al.8 have shown that keto-
esters can be smoothly transesterified by tetrabutyldi-
stannoxanes as catalyst under mild condition. More re-
cently use of sulfated tin oxide,9 zeolites10 and kaolinitic
clay11 has been reported to effect transesterification. Nev-
ertheless there are sufficient drawbacks to most of these
procedures to justify the need for a general, selective and
practical method of transesterification. During our recent
endeavor with yttria-zirconia based Lewis acid mediated
synthesis of acetals12 from carbonyl compounds, interest-
ingly we observed an efficient transesterification instead
of carbonyl protection when the reaction was applied to
b-keto esters. This prompted us to initiate a systematic in-
vestigation on yttria-zirconia based Lewis acid catalyzed
transesterification of β-keto esters and herein we wish to
disclose our results.
In order to explore the generality and scope of yttria-zir-
conia based Lewis acid catalyzed transesterification reac-
tion, the procedure has been extended to a variety of other
nucleophiles such as thiols and amines. The conversion of
b-keto ester to its thio analogue which is often problemat-
ic due to its facile decarboxylation upon hydrolysis, was
achieved by this procedure in moderate yield (Table 2, en-
try 1). In a similar manner aniline reacted smoothly with
b-keto ester to afford the corresponding amidation prod-
uct in good yield (Table 2, entry 2). Encouraged by this
finding, it was felt worthwhile to study the reactivity pat-
tern of different kind of diols, mercapto alcohols, and ami-
no alcohols towards b-keto ester over yttria-zirconia
based Lewis acid catalyst and results of such study
are presented in Table 2. Thus it was observed that the
Scheme
In a typical experimental procedure,13 when the b-keto es-
ters were treated with alcohols in the presence of catalytic
amount of yttria-zirconia catalyst, the corresponding
transesterified products were obtained in good to excel-
lent yields (Table 1). The present procedure is quite gen-
eral as a wide range of structurally varied b-keto esters
Synlett 2000, No. 2, 251–253 ISSN 0936-5214 © Thieme Stuttgart · New York

252
P. Kumar, R. K. Pandey
LETTER
Table 1 Transesterification of various β-keto esters with different alcohols catalyzed by yttria-zirconia based Lewis acid catalyst16
aAll products were characterized by their IR, 1H NMR and Mass spectroscopic data.17 bYields refer to isolated pure products.
cAs the reaction did not proceed in toluene as solvent, excess of ethanol was used to effect reverse transesterification.
Table 2 Selective transesterification of β-keto ester with thiol, amine, diol, mercapto alcohol and amino alcohol catalyzed by yttria-
zirconia based Lewis acid catalyst
aAll products were characterized by their IR, 1H NMR and Mass spectroscopic data.17 bYields refer to isolated pure products.
cThe formation of ketone protected product was not observed. dOnly the transaminated product was isolated.
Synlett 2000, No. 2, 251–253 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
A Facile and Selective Procedure for Transesterification of b-Keto Esters
253
(11) Ponde, D. E.; Deshpande, V. H.; Bulbule, V. J.; Sudalai, A.;
Gajare, A. S. J. Org. Chem. 1998, 63, 1058.
(12) Pais, G. C. G.; Keshavaraja, A.; Saravanan, K.; Kumar, P. J.
Chem Res. (S) 1996, 426.
(13) General experimental procedure for transesterification :
A mixture of ketoester (1 equiv), alcohol (1 equiv), and
catalyst (20% by weight) in toluene (10 equiv) was refluxed
for the indicated length of time (Table 1). The reaction was
monitored by TLC. After completion of the reaction, the
catalyst was filtered and the filtrate was concentrated to get the
crude product which was purified by silica gel column
chromatography using petroleum ether/ethyl acetate as eluent
to afford the pure transesterified product.
reaction is selective for the primary alcohol over second-
ary in the case of 1,2-diol; however a mixture of mono-
and di-transesterified products was obtained (Table 2, en-
try 3). Similarly hydroxyl group of 2-mercapto ethanol re-
acts preferentially over thiol affording the corresponding
product in excellent yield (Table 2, entry 4). In the case of
aliphatic amino alcohols, amine being more nucleophilic
than alcohol, it reacts faster with ester giving the corre-
sponding amidation product in excellent yield (Table 2,
entry 5).
In conclusion, we have demonstrated that yttria-zirconia
based Lewis acid serves as an efficient and selective cata-
lyst to effect transesterification of b-keto esters by a vari-
ety of alcohols. The obvious advantages of heterogeneous
catalysis in terms of simple operation coupled with the
ease of work-up and recyclability of the catalyst are note-
worthy. We believe this will present a better and more
practical alternative to the existing methodologies and
should find widespread applications in organic synthesis.
(14) (a) Carrol, M. F. J. Chem. Soc. 1940, 704. (b) Kimel, W.;
Cope, A. C. J. Am. Chem. Soc. 1943, 65, 1992.
(15) Campbell, D. S.; Lawrie, C. W. J. Chem. Soc., Chem.
Commun. 1971, 355.
(16) Procedure for the preparation of the catalyst : The catalyst
was prepared by mixing aqueous solutions of yttrium nitrate
and zirconyl nitrate in the mole ratio 16:84, to which aqueous
ammonia (28%) was added under vigorous stirring until a pH
of 8.5 was reached. Washing with deionized water, drying at
110°C for 24 h, treating with sulfuric acid (4 M), drying at
120°C and subsequent programmed calcination at 500°C for 3
h at a heating rate of 2°C min-1 resulted in a highly acidic
material. The chemical composition of the final catalyst
(determined by XRF technique) was found to be 82.6 mol%
Zr, 15.6 mol% Y and 1.8 mol% S. The physicochemical
characterization of the catalyst was carried out by X-ray
powder diffraction, FTIR, potentiometric titrations,
temperature programmed desorption (TPD), scanning
electron microscopy (SEM) and N2 adsorption techniques. For
details, see : Keshavaraja, A.; Hegde, V. R.; Pandey, B.;
Ramaswamy, A. V.; Kumar, P.; Ravindranathan, T. Angew.
Chem. Int. Ed. Engl. 1995, 34, 2143; U. S. Patent 5,932,752
(1999)
Acknowledgement
RKP thanks Director, NCL for allowing him to work as a guest wor-
ker. We are grateful to Dr. T. Ravindranathan, Head, Organic Che-
mistry : Technology Division for his constant encouragement and
support.
References and Notes
This is NCL Communication No. 6579.
(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,
1203. (b) Rehberg, C. E.; Faucette, W. A.; Fisher, C. H. J. Am.
Chem. Soc. 1944, 66, 1723. (c) Rehberg, C. E. Organic
Synthesis; Wiley: New York 1955; Collect. Vol. 3, p 146. (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.; Neckers, D. C.
Tetrahedron Lett. 1973, 1823.
(4) Taber, D. F.; Amedio, J. C., Jr.; Patel, Y. K. J. Org. Chem.
1985, 50, 3618.
(5) (a) Taft, R. W., Jr; Newman, M. S.; Verhoek, F, H. J. Am.
Chem. Soc. 1950, 72, 4511. (b) Billman, J. H.; Smith, W. T.,
Jr.; Rendall, J. L. J. Am. Chem. Soc. 1947, 69, 2058.
(6) (a) Osipow, L.; Snell, F. D.; Finchler, A. J. Am. Oil Chem.
Soc. 1957, 34, 185. (b) Komori, S.; Okahara, M.; Okamoto, K.
J. Am. Oil Chem. Soc. 1960, 37, 468.
(7) Witzeman, J. S.; Nottingham, W. D. J. Org. Chem.1991, 56,
1713.
(8) (a) Otera, J.; Yano, T.; Kawabata, A.; Hitoshi, N. Tetrahedron
Lett. 1986, 27, 2383. (b) Otera, J.; Danoh, N.; Nozaki, H. J.
Org. Chem. 1991, 56, 5307.
(17) Selected spectroscopic data:
9: colorless liquid; IRνmax / cm-1 (Neat): 2920, 1735, 1710,
1640, 1140, 1030; 1H NMR(CDCl3) d: 2.25 (s, 3H), [3.45,
4.95, 12.25] (s, 2H), 5.2 (s, 2H), 7.4 (s, 5H); MS (m/z, rel.
int%): M+192 (2.39), 164 (5.99), 107 (64.07), 98 (20.36), 91
(100), 79 (29.95), 65 (15.57), 58 (2.99).
11: colorless liquid; IRνmax / cm-1 (Neat): 2900, 2680, 2325,
1740, 1710, 1670, 1640, 1120, 1020; 1H NMR(CDCl3) d: 1.65
(s, 3H), 1.75 (s, 3H), 1.8-2.24 (m, 6H), 3.15 (t, J = 8.3 Hz,
1H), 4.65 (d, J = 8.3 Hz, 2H), 5.35 (t, J = 8.3 Hz, 1H); MS (m/
z, rel. int%): M+196 (1.49), 178 (2.09), 168 (2.99), 143 (6.88),
129 (19.76), 111 (46.70), 85 (76.65), 69 (100), 59 (9.88), 55
(32.34).
19: colorless liquid; IRνmax / cm-1 (Neat): 3441, 2926, 2868,
1729, 1680, 1618, 1403, 1189, 1085, 831; 1H NMR(CDCl3) d:
1.63 (t, J = 7.6 Hz, 1H), 2.25 (s, 3H), 2.72 (m, 2H), 3.13 (m,
2H), [3.67, 5.42, 12.58] (s, 2H); MS (m/z, rel. int%): M+178
(4.79), 160 (3.59), 119 (63.47), 85 (100), 77 (2.9), 69 (8.08),
61 (8.98).
20: colorless liquid; IRνmax / cm-1 (Neat): 3352, 3317, 1713,
1651, 1551, 1458, 1055; 1H NMR(CDCl3) d: 1.3 (s, 6H), 2.26
(s, 3H), 3.39 (s, 2H), 3.58 (s, 2H), 4.5 (br s, 1H), 7.15 (br s,
1H); MS (m/z, rel. int%): M+173 (2.39), 143 (100), 135 (1.8),
100 (8.38), 85 (14.97), 74 (6.59), 74 (6.29), 58 (40.72).
(9) Chavan, S. P.; Zubaidha, P. K.; Dantale, S. W.; Keshavaraja,
A.; Ramaswamy, A. V.; Ravindranathan, T. Tetrahedron Lett.
1996, 37, 233.
Article Identifier:
1437-2096,E;2000,0,02,0251,0253,ftx,en;L18599ST.pdf
(10) (a) Balaji, B. S.; Sasidharan, M.; Kumar, R.; Chanda, M.
Chem. Commun. 1996, 707. (b) Balaji, B. S.; Chanda, M.
Tetrahedron 1998, 54, 13237.
Synlett 2000, No. 2, 251–253 ISSN 0936-5214 © Thieme Stuttgart · New York