Transesterification of ketoesters using Amberlyst-15

Article abstract of DOI:10.1081/SCC-100000212

A facile one-to-one transesterification of ketoesters by Amberlyst-15 is described.

Full text of DOI:10.1081/SCC-100000212

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TRANSESTERIFICATION OF KETOESTERS USING
AMBERLYST-15
Subhash P. Chavan a , Y. Tripura Subbarao a , Shubhada W. Dantale a & R. Sivappa a
a Division of Organic Chemistry: Technology , National Chemical Laboratory , Pune, 411
008, India
Published online: 16 Aug 2006.
To cite this article: Subhash P. Chavan , Y. Tripura Subbarao , Shubhada W. Dantale & R. Sivappa (2001)
TRANSESTERIFICATION OF KETOESTERS USING AMBERLYST-15, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 31:2, 289-294, DOI: 10.1081/SCC-100000212
To link to this article: http://dx.doi.org/10.1081/SCC-100000212
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SYNTHETIC COMMUNICATIONS, 31(2), 289–294 (2001)
TRANSESTERIFICATION OF KETOESTERS
USING AMBERLYST-15
Subhash P. Chavan,∗ Y. Tripura Subbarao,
Shubhada W. Dantale, and R. Sivappa
Division of Organic Chemistry: Technology, National
Chemical Laboratory, Pune 411 008, India
ABSTRACT
A facile one-to-one transesterification of ketoesters by
Amberlyst-15 is described.
Ketoesters are multi-coupling reagents with electrophilic and nucleophilic
sites and are proven to be valuable tools in a wide variety of molecular systems.
Especially, the transesterification of β-ketoesters has received a great deal of atten-
tion and various catalysts (1–8) have been investigated in the attempt to effect this
interconversion. These β-ketoesters are important by virtue of their facile bond
formation at all four carbon atoms that feature in their structural unit and also due
to their ease of transformation to chiral building blocks and use in chain extension
reactions.
Although well-known using conventional acidic and basic catalysts, a need
for new catalysts has arisen in order to meet the requirement for this transesterifi-
cation to be highly efficient and chemo- and regioselective.
Heterogeneous catalysts have in some cases replaced conventional reagents
due to their practical utility. We have reported (9) one such catalyst, viz., sulfated tin
∗ To whom correspondence should be addressed.
289
Copyright ꢀ 2001 by Marcel Dekker, Inc.
www.dekker.com
C

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CHAVAN ET AL.
Table 1.
S. No.
Substrate
Alcohol
Product
Time (h) Yield (%)
1
2
3
10.0
5.5
85
85
89
2.0
4
5
6
7
3.0
3.0
4.0
2.0
90
75
88
64
8
6.0
94
9
10
11
6.0
8.0
2.0
65
42
86∗
12
10.0
54
∗ Combined yields; ∗∗2 eq of alcohol. # 1:1 ratio of products.
oxide, which has been effectively utilized for transesterification of β-ketoesters
with excellent results, and, as part of our continued interest in finding cheaper
alternatives for effecting this transesterification, we found that Amberlyst-15 was
more effective with primary, secondary, and allylic alcohols (see Table 1). Several
related reports have also appeared (10,11).
Amberlyst-15 is a macro reticular ion exchange resin that contains strongly
acidic sulfonic groups and has been widely used for a variety of reactions: prepa-
ration of acetals from carbonyls and alcohols (12); esters from alcohols and acids
(13); tetrahydropyranylation of alcohols and phenols (14); hydrolysis of acetals to
carbonyls (15); and dethioacetalization (16). In this communication, a facile inter
conversion of β-ketoesters using Amberlyst-15 is described.

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291
Mixing an equimolar mixture of ketoester and alcohol in the presence of 10%
Amberlyst-15, heating in toluene, while removing the methanol/ethanol formed,
led to the formation of the transesterified β-ketoesters in good to excellent yields.
A noteworthy feature of the present protocol is that not only β-ketoesters but also
a γ -ketoester (entry 12) can be transesterified. Another example of interest is the
transesterification of N-(2-hydroxy ethyl)phthalimide to furnish the 2-phthalimido
ethyl acetoacetate ester (entry 1). This product is an important reagent for the syn-
thesis of 1,4-dihydropyridine derivatives (17), which are effective calcium channel
blockers and have antihypertensive activities. Another point worth mentioning is
that only a 1:1 ratio of ketoester and alcohol is required for a facile exchange to
occur. Chiral alcohols also participate efficiently in this reaction, giving access
to chiral ketoesters. Interestingly, when mercapto ethanol is used, an equimolar
amount of thio ester and ester are obtained in good yields.
This catalyst, being heterogeneous in nature, offers advantages over conven-
tional methods, not only in terms of yields and reaction times, but also in ease of
work-up and retrieval of products, in addition to the reusability of catalyst, which
can be of tremendous commercial importance. The short reaction times and high
yields emphasize the attractive feature of this protocol.
The ready availability of this catalyst commercially and its superiority over
the existing methods (1) should make the present protocol an attractive addition
to conventional methods.
EXPERIMENTAL
General Procedure for Transesterification
A mixture of ketoester (1 eq), alcohol (1 eq), and catalyst (100 mg, 10%
by weight of ketoester) in toluene (20 mL) was heated to 110◦C in a two-necked
round-bottom flask provided with a distillation condenser to remove MeOH/EtOH.
After completion of the reaction (as monitored by TLC), the catalyst was filtered
and the filtrate concentrated and chromatographed on SiO2 (95:5 pet.ether: ethyl
acetate) to afford the ester as a viscous liquid in excellent yields.
1. N-(2-Phthalimidoethyl)-3-oxo Butanoate (17)
M.p.: 88◦–89◦C. IR (neat) cm−1: 3022, 1755, 1744, 1712, 1428, 1395, 1365,
1319, 1216, 754, 720. 1H NMR (200 MHz) CDCl3 (δ): 2.25 (s, 3H); 3.45 (s, 2H);
4.0 (t, J = 5.4 Hz, 2H); 4.4 (t, J = 5.4 Hz, 2H); 7.7–7.9 (m, 4H, aromatic). Mass
(m/z): 275 (M+). Analysis: Calculated C = 61.09; H = 4.83; N = 5.05. Found
C = 60.82; H = 4.76; N = 4.65.

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CHAVAN ET AL.
2. Butyl-3-oxo Butanoate (18)
IR (neat) cm−1: 2980, 2950, 1750, 1730, 1650, 1420, 1350, 1320, 1250,
1180, 1150, 1050, 1020, 950, 820, 750. 1H NMR (200 MHz) CDCl3 (δ): 0.9 (t, 3H,
-CH3); 1.35 (m, 2H, -CH2-); 1.6 (m, 2H, CH2-); 2.25 (s, 3H, -CH2-); 3.4 (s, 2H,
-CH2-), 4.1 (t, 2H, -OCH2-). Mass (m/z): 158 (M+).
3. Octyl-3-oxo Butanoate (18)
IR (neat) cm−1: 2950, 2850, 1750, 1720, 1650, 1450, 1400, 1350, 1300,
1
1220, 1150, 1020. H NMR (200 MHz) CDCl3 (δ): 0.9 (t, 3H); 1.3 (m, 10H,
-CH2-); 1.6 (t, 2H); 2.6 (s, 3H); 3.4 (S, 2H); 4.1 (t, 2H). Mass (m/z): 214 (M+).
4. Butyl-2-oxo Cyclopetanecarboxylate (18)
IR (neat) cm−1: 2950, 2850, 1750, 1720, 1640, 1610, 1450, 1350, 1250,
1180, 1050, 920. 1H NMR (200 MHz) CDCl3 (δ) : 0.9 (t, 3H); 1.3 (m, 2H); 1.6
(m, 2H); 2.1 (m, 2H); 2.3 (m, 4H); 3.15 (t, 1H); 4.2 (t, 2H). Mass (m/z): 184 (M+).
5. 2-Chloroethyl-3-oxo Butanoate (18)
IR (neat) cm−1: 2950, 1750, 1720, 1650, 1450, 1420, 1350, 1320, 1250,
1
1150, 1020, 780, 650. H NMR (200 MHz) CDCl3 (δ): 2.1 (s, 3H); 3.4 (s, 2H);
3.6 (t, 2H); 4.3 (t, 2H). Mass (m/z): 167 (M + 2), 165 (M+).
6. 2-Phenyl Ethyl-3-oxo Butanoate (18)
IR (neat) cm−1: 3020, 2900, 1750, 1720, 1620, 1400, 1300, 1250, 1200,
1050, 1020, 920, 810, 720, 580, 550. 1H NMR (200 MHz) CDCl3 (δ): 2.15 (s, 3H);
3.0 (t, 2H); 3.4 (s, 2H); 4.4 (t, 2H), 7.5 (m, 5H). Mass (m/z): 206 (M+).
7. 3-Phenyl Propyl-3-oxo Butanoate (18)
IR (neat) cm−1: 3030, 2860, 1740, 1720, 1650, 1600, 1500, 1455, 1360,
1260, 1170, 1150, 1030, 750, 700. 1H NMR (200 MHz) CDCl3 (δ): 2.0 (m, 2H);
2.2 (s, 3H); 2.7 (t, 2H); 3.5 (s, 2H); 4.2 (t, 2H); 7.25 (m, 5H). Mass (m/z): 220 (M+).
8. 5-Methyl-2-(1-methylethyl)cyclohexyl-3-oxo Butanoate (18)
IR (neat) cm−1: 2980, 2820, 1740, 1700, 1650, 1450, 1400, 1350, 1300,
1240, 1120, 1080, 1020, 980, 950, 900, 850. 1H NMR (200 MHz) CDCl3 (δ): 0.80

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(d, 3H); 1.1 (d, 6H); 1.2 (m, 4H); 1.35 (m, 2H); 1.55–1.85 (m, 3H), 2.3 (s, 3H),
3.5 (s, 2H), 4.7 (dt, J = 4.4 & 10.9, 1H). Mass (m/z): 240 (M+).
9. Cyclohexyl-3-oxo Butanoate (18)
IR (neat) cm−1: 3010, 2980, 1750, 1720, 1650, 1560, 1420, 1350, 1250,
1180, 1020, 920, 850, 780, 700. 1H NMR (200 MHz) CDCl3 (δ): 1.35 (m, 6H);
1.70 (m, 2H); 1.80 (m, 2H); 2.4 (s, 3H), 3.4 (s, 2H), 4.8 (m, 1H). Mass (m/z):
184 (M+).
10. Allyl-3-oxo Butanoate (18)
IR (neat) cm−1: 2950, 1750, 1720, 1640, 1420, 1380, 1280, 1020, 1000, 950,
1
780, 550. H NMR (200 MHz) CDCl3 (δ): 2.2 (s, 3H); 3.4 (s, 2H); 4.6 (d, 2H);
5.25 (d, 2H); 5.8 (m, 1H). Mass (m/z): 142 (M+).
11(a). 2-Mercapto Ethyl-3-oxo Butanoate (18)
IR (neat) cm−1: 1740, 1710, 1600, 1400, 1350, 1300, 1250, 1150, 1020.
1H NMR (200 MHz) CDCl3 (δ): 1.5 (t, -SH); 2.25 (s, 3H); 2.7 (dt, 2H); 3.5 (s, 2H);
4.3 (t, 2H). Mass (m/z): 162 (M+).
11(b). 2-Hydroxy Thio-3-oxo Butanoate (18)
IR (neat) cm−1: 3400, 1740, 1710, 1600, 1400, 1350, 1300, 1250, 1150,
1
1020. H NMR (200 MHz) CDCl3 (δ): 1.7 (s, 3H); 2.8 (s, -OH); 3.1 (t, 2H);
3.7 (s, 2H); 4.2 (t, 2H). Mass (m/z): 162 (M+).
12. Butyl-4-oxopentanoate (18)
IR(neat)cm−1:2950, 2800, 1740, 1720, 1620, 1450, 1350, 1180, 1150, 1050,
1020, 950, 780, 650. 1H NMR (200 MHz) CDCl3 (δ): 0.90 (t, 3H); 1.5 (m, 4H);
2.1 (s, 3H); 2.5 (t, 2H); 2.7 (t, 2H), 4.1 (t, 2H). Mass (m/z): 172 (M+).
ACKNOWLEDGMENTS
Y.T.S.R., S.R. thank CSIR for the award of fellowship. Funding from CSIR
under the Young Scientist Award (YSA) is also gratefully acknowledged.

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Received in the UK February 24, 1999

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