A Simple and Efficient Method for Transesterification of β-Ketoesters Catalysed by Iodine

Article abstract of DOI:10.1055/s-2003-42433

A facile transesterification of β-ketoesters using catalytic iodine is described.

Full text of DOI:10.1055/s-2003-42433

PAPER
2695
A Simple and Efficient Method for Transesterification of -Ketoesters
Catalysed by Iodine
A
S
S
imple and
uE fficient Me
b
thodfor Tra
h
nsesterificati
a
on of
-
Ket
s
oesters h P. Chavan,* Ramesh R. Kale, K. Shivasankar, Sanjay I. Chandake, Swapnanjali B. Benjamin
Division of Organic Chemistry Technology, National Chemical Laboratory, Pune- 411 008, India
Fax +91(20)5893614; E-mail: spchavan@dalton.ncl.res.in
Received 3 July 2003; revised 11 September 2003
Abstract: A facile transesterification of -ketoesters using catalytic
iodine is described.
Key words: transesterification -ketoesters, iodine, alcohols
Scheme 1
The transesterification of -ketoesters has been found to
be a very useful tool in organic synthesis having wide ap- The noteworthy feature of our protocol is that -ketoesters
plications in academic as well as industrial research. A like ethyl acetoacetate and ethyl cyclopentanone-2-car-
number of methods have been reported to effect transes- boxylate underwent transesterification with benzyl alco-
terification of -ketoesters. Although uncatalysed transes- hol to furnish the transesterified products in good yields
terification of -ketoesters is reported in the literature1
–3
(83% and 88% respectively). In most of the cases only 1.2
they require the use of either an excess of ketoester or equivalents of alcohols were required for efficient conver-
longer reaction times and employ high boiling alcohols or sions. However, in the case of volatile alcohols like 2-pro-
utilise unconventional energy sources thus limiting their panol, 1-propanol and propargyl alcohol, 2 equivalents of
usage. Similarly uncatalysed transesterification of tert- alcohol are required to obtain good yields of the corre-
4
butyl acetoacetate is also reported in the literature. How- sponding ester. The other important feature of this proto-
ever, this method is confined to tert-butyl acetoacetate col is that transesterification of -ketoesters by various
which itself is not readily available thus limiting its usage. alcohols like benzyl, allylic, propargyl alcohols has been
Transesterification of -ketoesters has been reported us- effectively catalysed by iodine giving products with mod-
5
6
ing reagents like DMAP, DBU, titanium tetraalkoox- erate to high yields in comparatively reduced reaction
7
8,9
10
ide, tetrabutyl distannoxanes, p-TSA. However, most times. Although several aliphatic esters underwent
of these reagents are toxic, expensive or difficult to pre- smooth transesterification, phenols did not undergo trans-
pare. We have already described the utility of heteroge- esterification with either methyl acetoacetate or ethyl ac-
1
1
12
neous catalysts like S–SnO2 and Amberlyst-15 as etoacetate to furnish the coumarins in the presence of
efficient catalysts for transesterification of -ketoesters. iodine as the catalyst. This result may be contrasted with
Several other catalysts have also been shown to be effec- the reactions mediated by zinc and iodine, which fur-
1
3,14
tive for transesterification of -ketoesters.
In recent nished the coumarins. This clearly indicates that most
1
5
years reagents like indium triiodide, iodotrimethylsi- likely a complex of zinc and iodine is responsible for the
lane/I2 have been used for transesterification. A recent transesterification.
1
6
1
7
report on the use of iodine for transesterification of es-
ters shows that iodine acts as an efficient catalyst to effect
the transesterification. It has limitations, as benzyl alcohol
fails to undergo transesterification with normal esters. Ad-
ditionally the iodine-catalysed protocol involves the use
of excess alcohol to push the equilibrium driven reaction
in the desired direction and requires longer reaction times.
Recently we have demonstrated that zinc can be activated
by iodine and this reagent was shown to effect transes-
terification with normal alcohols as well as phenols to fur-
nish coumarins. In this communication we wish to report
that even iodine acts as an efficient catalyst to effect trans-
esterification (Scheme 1). The results of this protocol are
summarised in Table 1.
In conclusion, the present protocol describes a simple and
efficient method for the transesterification of -ketoesters
by different alcohols catalysed by iodine. The ready avail-
ability of iodine along with its efficiency, simplicity and
superiority over the existing methods should make this
protocol an attractive addition to the arsenal of synthetic
chemists.
1
8
Transesterification; Typical Procedure
Methyl acetoacetate (1.004 g, 8.655 mmol, 1 equiv), menthol (1.620
g, 10.386 mmol, 1.2 equiv), iodine (66 mg, 0.26 mmol, 3 mol%) and
toluene (10 mL) were placed in a 50 mL round bottom flask fitted
with a condenser. The reaction mixture was heated to 115–120 °C
(oil bath temperature) for 4 h. The reaction was monitored by TLC
and after completion the reaction mixture was cooled, washed with
sodium thiosulfate solution and subsequently with water and brine.
The organic layer was separated, dried over sodium sulfate, filtered
SYNTHESIS 2003, No. 17, pp 2695–2698
x
x.
x
x
.
2
0
0
3
Advanced online publication: 14.10.2003
DOI: 10.1055/s-2003-42433; Art ID: Z09503SS
Georg Thieme Verlag Stuttgart · New York
©

2
696
S. P. Chavan et al.
PAPER
Table 1 Iodine-Catalysed Transesterification of -Ketoestersa,e
Entry
1
-Ketoester
Alcoholb
Product
Time (h)
4
Isolated Yields (%)
96
2
6.5
87
3
4
5
7
5
5
79c
86
81
6
7
8
7
7
5
65d
63d
89
9
4
74
1
1
0
1
6.5
5
80d
83
1
1
2
3
5
88
92
4.5
14
4
96
a
b
c
d
e
3
1
0
2
mol% of iodine used.
.2 Equivalents of alcohol used.
.5 Equivalents of alcohol used.
Equivalents of alcohol used.
All the compounds were characterised by physical and spectroscopic methods (IR, H NMR, 13C NMR, MS etc.) and by comparison with
1
authentic samples.
Synthesis 2003, No. 17, 2695–2698 © Thieme Stuttgart · New York

PAPER
A Simple and Efficient Method for Transesterification of -Ketoesters
2697
and the solvent was removed under vacuum. The residue was puri-
fied by column chromatography to give the transesterified product.
Propargyl 3-Oxobutanoate14
Yield: 80%.
1
H NMR (CDCl , 200MHz): = 4.70 (d, J = 2.4 Hz, 2 H), 3.46 (s,
H), 2.48 (t, J = 2.4 Hz, 1 H), 2.24 (s, 3 H).
1
2
3
Menthyl 3-Oxobutanoate
Yield: 96%; [ ]D25 –72.00 (c = 10.24, benzene) {lit. [ ] –69.3,
2
2
20
D
(
c = 10, benzene)}.
Benzyl 3-Oxobutanoate12
Yield: 83%.
1
H NMR(CDCl , 200MHz): = 4.75 (dt, J = 4.4, 10.7 Hz, 1 H),
3
3
1
.45 (s, 2 H), 2.25 (s, 3 H), 1.9–2.1 (m, 2H), 1.65–1.75 (m, 2 H),
.4–1.5 (m, 2 H), 0.9–1.2 (m, 9 H), 0.85 (d, J = 6 Hz, 3 H).
1
H NMR (CDCl , 200MHz): = 7.36 (s, 5 H), 5.18 (s, 2 H), 3.50 (s,
H), 2.25 (s, 3 H).
3
2
1
2
N-(2-Pthalimido)ethyl 3-Oxobutanoate
Benzyl 2-Oxocyclopentanecarboxylate13f
Yield: 88%.
1
2
Yield: 87%; mp 87–88 °C (lit. mp 88–89 °C).
IR (CHCl ): 3022, 1775, 1746, 1717, 1616, 1469, 1429, 1395, 1035,
1
3
H NMR (CDCl , 200MHz): = 7.32 (s, 5 H), 5.14 (s, 2 H), 3.16 (t,
–1
3
7
59 cm .
J = 8.8Hz, 1 H), 2.25–2.33 (m, 4 H), 2.15 (m, 1 H), 1.87 (m, 1 H).
13
1
H NMR(CDCl , 200MHz): = 7.85 (dd, J = 2.9, 8.3 Hz, 2 H), 7.75
3
C NMR (CDCl , 50MHz): = 211.3 (s), 168.9 (s), 135.5 (s), 128.3
3
(
dd, J = 2.9, 8.3 Hz, 2 H), 4.38 (t, J = 4.9 Hz, 2 H), 3.97 (t, J = 4.9
(
d), 128.0 (d), 127.8 (d), 66.7 (t), 54.4 (d), 37.7 (t), 27.2 (t).
Hz, 2 H), 3.42 (s, 2 H), 2.25 (s, 3 H).
+
(–)-Menthyl 2-Oxacyclopentanecarboxylate13f
ESI-MS (CH CN–H O–CH COONH ): m/z = 293.02 (M + NH ),
3
2
3
4
4
2
76.02 (M + 1).
Yield: 92%.
1
H NMR (CDCl , 200MHz): = 4.75 (m, 1 H), 3.11 (m, 1 H), 2.14–
.43 (m, 4 H), 1.75–2.14 (m, 4 H), 1.55–1.75 (m, 2 H), 1.23–1.55
m, 3 H), 0.65–1.05 (m, 11 H).
Decane-1,10-diyl Bis(3-oxobutanoate)13e
Yield: 79%.
3
2
(
1
H NMR (CDCl , 200MHz): = 4.09 (t, J = 6.4 Hz, 4 H), 3.40 (s, 4
13
3
C NMR (CDCl , 50MHz, mixture of two diasterisomers, partly
3
H), 2.24 (s, 6 H), 1.50–1.65 (m, 4 H), 1.10–1.40 (m, 12 H).
doubled signals): = 211.1 (s), 168.5 (s), 74.6 (d), 54.6 (d), 54.3 (d),
6.6 (d), 40.4 (t), 37.4 (t), 33.9 (t), 31.0 (d), 27.7 (t), 26.9 (t), 25.8
t), 25.3 (t), 23.1 (t), 22.8 (t), 21.7 (q), 20.7 (q), 15.9 (q), 15.6 (q).
4
(
Decyl 3-Oxobutanoate12
Yield: 86%.
1
H NMR (CDCl , 200MHz): = 4.06 (t, J = 6.4 Hz, 2 H), 3.37(s, 2
Menthyl 5-Hydroxy-2,2-dimethyl-4H-1,3-dithiine-6-carboxy-
3
H), 2.21 (s, 3 H), 1.51–1.61 (m, 2 H), 1.14–1.40 (m, 14 H), 0.82 (t,
J = 6.4 Hz, 3 H).
late
2
5
Yield: 96%; [ ]D –76.30 (c = 2.2, benzene).
–
1
IR (CHCl ): 2958, 2925, 2871, 1717, 1632, 1587, 758 cm .
Butyl 3-Oxobutanoate12
Yield: 81%.
3
1
H NMR (CDCl , 200MHz): = 12.81 (s, 1 H), 4.78 (dt, J = 3.9,
0.4 Hz, 1 H), 3.45 (d, J = 8.6 Hz, 2 H), 1.79–2.08 (m, 2 H), 1.70
s, 3 H), 1.66 (s, 3 H), 1.47–1.60 (m, 2H), 1.07–1.27 (m, 2 H), 0.89–
3
1
(
1
H NMR (CDCl , 200MHz): = 4.11 (t, J = 6.8 Hz, 2 H), 3.42 (s, 2
3
H), 2.24 (s, 3 H), 1.60 (quintet, J = 6.8 Hz, 2 H), 1.35 (tq, J = 6.8,
0
.95 (m, 9 H), 0.76 (d, J = 7.4, 3 H).
7
.3 Hz, 2 H), 0.91 (t, J = 6.8 Hz, 3 H).
1
3
C NMR (CDCl , 50MHz): = 174.3 (s), 170.0 (s), 95.8 (s), 75.30
3
Propyl 3-Oxobutanoate14
Yield: 65%.
(d), 55.9 (s), 46.4 (d), 40.4 (t), 33.9 (t), 32.1 (q), 31.8 (t), 31.1 (d),
6.0 (d), 23.2 (t), 21.7 (q), 20.4 (q), 16.1 (q).
2
+
1
ESI-MS (CH CN–H O–CH COONH ): m/z = 362.05 (M + NH ),
H NMR (CDCl , 200MHz): = 4.06 (t, J = 6.8 Hz, 2 H), 3.42 (s, 2
3
2
3
4
4
3
3
45.05 (M + 1).
H), 2.24 (s, 3 H), 1.65 (tq, J = 6.8, 7.3 Hz, 2 H), 0.93 (t, J = 6.8 Hz,
3
H).
Methyl 5-Hydroxy-2,2-dimethyl-4H-1,3-dithiine-6-carboxy-
late
Mp 49 °C (pale yellow solid).
1
9
Isopropyl 3-Oxobutanoate14
Yield: 63%.
1
IR (CHCl ): 3194, 3168, 3099, 2959, 2907, 2850, 1653, 1571, 1434,
3
H NMR (CDCl , 200MHz): = 4.99 (m, 1 H), 3.33 (s, 2 H), 2.19
s, 3 H), 1.20 (d, J = 6.4 Hz, 6 H).
3
–
1
1
311, 1203, 1141, 1062, 775 cm .
(
1
H NMR (CDCl , 200MHz): = 12.60 (s, 1 H), 3.84 (s, 3 H), 3.46
3
Cycloheptyl 3-Oxobutanoate12
Yield: 89%.
(s, 2 H), 1.70 (s, 6 H).
1
3
C NMR (CDCl , 50MHz): = 31.9 (q), 32.0 (t), 52.0 (q), 55.8 (s),
3
1
H NMR (CDCl , 200MHz): = 4.97 (m, 1 H), 3.39 (s, 2 H), 2.25
3
95.8 (s), 171.0 (s), 174.4 (s).
(
s, 3 H), 1.86–1.98 (m, 2 H), 1.42–1.73 (m, 10 H).
MS: m/z = 220 (34), 188 (20), 170 (18), 160 (28), 146 (21), 127 (60),
Prenyl 3-Oxobutanoate4
114 (82), 103 (21), 86 (100), 74 (90), 69 (15), 59 (43).
Yield: 74%.
1
H NMR (CDCl , 200MHz): = 5.29 (t, J = 7.3Hz, 1 H), 4.57 (d, Acknowledgement
3
J = 7.3 Hz, 2 H), 3.38 (s, 2 H), 2.21 (s, 3 H), 1.72 (s, 3 H), 1.67 (s,
The authors RRK, KS thank CSIR New Delhi (India) for the award
of fellowships. Funding under the YSA (SPC) scheme from CSIR,
India is gratefully acknowledged.
3
H).
Synthesis 2003, No. 17, 2695–2698 © Thieme Stuttgart · New York

2
698
S. P. Chavan et al.
PAPER
References
(12) Chavan, S. P.; Rao, T. S.; Dantale, S. W.; Sivappa, R. Synth.
Commun. 2001, 31, 289.
(
(
1) Bader, A. R.; Cummings, L. O.; Vogel, H. A. J. Am. Chem.
Soc. 1951, 73, 4195.
2) Gianotti, M.; Martelli, G.; Spunta, G.; Campana, E.;
Panunzio, M.; Mendozza, M. Synth. Commun. 2000, 30,
(
13) (a) Balaji, B. S.; Sasidharan, M.; Kumar, R.; Chanda, B.
Chem. Commun. 1996, 707. (b) Balaji, B. S.; Chanda, B. M.
Tetrahedron 1998, 54, 13237. (c) Bandgar, B. P.; Uppalla,
L. S.; Sadavarte, V. S. Green Chem. 2001, 3, 39.
1725.
(
d) Bandgar, B. P.; Sadavarte, V. S.; Uppalla, L. S. J. Chem.
(
(
(
(
(
(
(
3) Mottet, C.; Hamelin, O.; Garavel, G.; Depres, J.; Greene, A.
E. J. Org. Chem. 1999, 64, 1380.
4) Witzeman, J. S.; Nottingham, W. D. J. Org. Chem. 1991, 56,
Res., Synop. 2001, 16. (e) Kumar, P.; Pandey, R. K. Synlett
2
2
000, 251. (f) Christoffers, J.; Onal, N. Eur. J. Org. Chem.
000, 1633. (g) Bandgar, B. P.; Uppalla, L. S.; Sadavarte, V.
1
713.
5) Taber, D. F.; Amedio, J. C. Jr.; Patel, Y. K. J. Org. Chem.
985, 50, 3618.
S. Synlett 2001, 1715.
(
(
(
(
(
(
14) Ponde, D. E.; Deshpande, V. H.; Bulbule, V. J.; Sudalai, A.;
Gajare, A. S. J. Org. Chem. 1998, 63, 1058.
15) Ranu, B. C.; Dutta, P.; Sarkar, A. J. Chem. Soc., Perkin 1
1
6) Seebach, D.; Thaler, A.; Blaser, D.; Ko, S. Y. Helv. Chim.
Acta 1991, 74, 1102.
7) Seebach, D.; Hungerbhler, E.; Naef, R.; Schnurrenberger,
D.; Weidmann, B.; Zügger, M. Synthesis 1982, 138.
8) Otera, J.; Yano, T.; Kawabata, A.; Hitoshi, N. Tetrahedron
Lett. 1986, 27, 2383.
2000, 2223.
16) Olah, G. A.; Narang, S. C.; Saleom, G. F.; Balaram Gupta,
B. G. Synthesis 1981, 142.
17) Ramalinga, K.; Vijayalakshmi, P.; Kaimal, T. N. B.
Tetrahedron Lett. 2002, 43, 879.
18) Chavan, S. P.; Shivasankar, K.; Sivappa, R.; Kale, R. R.
Tetrahedron Lett. 2002, 43, 8583.
19) von Luttringhaus, A.; Prinzbach, H. Liebigs Ann. Chem.
9) Otera, J.; Dan-ho, N.; Nozaki, H. J. Org. Chem. 1991, 56,
5
307.
10) Rehberg, C. E.; Fischer, C. H. J. Am. Chem. Soc. 1944, 66,
203.
11) Chavan, S. P.; Zubaidha, P. K.; Dantale, S. W.; Keshavaraja,
A.; Ramamswamy, A. V.; Ravindranathan, T. Tetrahedron
Lett. 1996, 37, 233.
(
(
1
1959, 624, 79.
Synthesis 2003, No. 17, 2695–2698 © Thieme Stuttgart · New York