Bismuth(III) chloride-catalyzed highly efficient transesterification of β-keto esters

Article abstract of DOI:10.1002/hlca.201000113

Bismuth(III) chloride was found to be an efficient catalyst for the transesterification of a variety of β-keto esters with a wide range of alcohols to afford transesterified products in good to high yields in short reaction times (see Table). Copyright

Full text of DOI:10.1002/hlca.201000113

Helvetica Chimica Acta – Vol. 94 (2011)
119
Bismuth(III) Chloride-Catalyzed Highly Efficient Transesterification of
b-Keto Esters
by Gowravaram Sabitha*, Rangavajjula Srinivas, Peddabuddi Gopal, M. Bhikshapathi, and
Jhillu Singh Yadav
Organic Division I, Indian Institute of Chemical Technology, Hyderabad 500007, India
(phone: þ 91-40-27191629; fax: þ 91-40-27160512; e-mail: gowravaramsr@yahoo.com)
Bismuth(III) chloride was found to be an efficient catalyst for the transesterification of a variety of
b-keto esters with a wide range of alcohols to afford transesterified products in good to high yields in
short reaction times (see Table).
Introduction. – Bismuth(III) halides are inexpensive, relatively nontoxic, fairly
water-insensitive, and environmentally benign reagents, which have been used as mild
Lewis acid catalysts for an array of synthetic transformations [1][2]. Bismuth has the
electron configuration [Xe]4f14 5d106s26p3. Due to the weak shielding of the 4f electrons
(lanthanide contraction), bismuth(III) compounds exhibit Lewis acidity. Earlier, we
have shown the catalytic activity of BiCl3 [3] in synthetic methodology. As a part of our
research program, we were in need of benzyl esters, which can be cleaved by
hydrogenolysis. The hydrolysis of alkyl such as methyl or ethyl esters requires base,
which may pose some unavoidable side reactions like ring opening or decomposition of
the material in lactones and macrolides or in the presence of base-sensitive functional
groups. Therefore, we developed a method using BiCl3 as a catalyst by which alkyl
esters are converted to the benzyl esters in very high yields in pure form. We studied the
generality of the catalyst action, and the results are presented here.
Results and Discussion. – The transesterification reaction of ethyl acetoacetate
(¼ethyl 3-oxobutanoate) with benzyl alcohol was studied in the presence of a catalytic
amount of BiCl3 as a model reaction. The reaction smoothly proceeded in refluxing
toluene in a DeanꢀStark apparatus to give transesterified product in 90% yield in 2 h.
Under similar conditions, b-keto esters such as methyl, ethyl, and cycloalkyl
acetoacetates underwent smooth transesterification with alcohols like butanol and
allyl, propargyl, and homoallyl alcohol (¼ prop-2-en-1-ol, prop-2-yn-1-ol, and but-3-en-
1-ol) giving good yields of transesterification products. Similarly, ethyl benzoylacetate
(¼ethyl 3-oxo-3-phenylpropanoate) (Table, Entries 6 and 10) underwent a clean
transesterification with benzyl and homopropargyl alcohol, respectively. The trans-
esterification reaction ran equally well with enantiomerically pure (þ)- or (ꢀ)-menthol
(¼(1S,2R,5S)- and (1R,2S,5R)-2-isopropyl-5-methylcyclohexanol) (Entries 3 and 9)
giving the products in good yields. It is important to note that with BiCl3 as catalyst,
methyl (cyclopropylcarbonyl)acetate (Entry 2) cleanly reacted with benzyl alcohol
ꢀ 2011 Verlag Helvetica Chimica Acta AG, Zꢁrich

120
Helvetica Chimica Acta – Vol. 94 (2011)
giving 75% yield of transesterified product. In all the cases, the reactions were
completed within 3 – 4.5 h. The present protocol is general since a variety of structurally
different b-keto esters underwent transesterification with various alcohols. In all the
cases, 10 mol-% of the catalyst was used to drive the reaction to completion. These
transesterified esters can be utilized in organic synthesis and in industry.
Table. BiCl3-Catalyzed Transesterification of b-Ketoesters
Entry
R
R1
R2
Time [h]
Yield of 3a)b) [%]
1
2
3
4
5
6
7
8
9
Me
Me
Me
Et
Et
Et
Et
Et
Et
Et
Et
Et
Et
Bu
PhCH2
3
4
4.5
3
3.5
3
85
75
71
72
78
81
79
84
73
85
82
85
cyclopropyl
tBu
(þ)-menthyl
iPr
PhCH2
tBu
PhCH2
Ph
HCꢁCCH2
H2C¼CHCH2CH2
PhCH2CH2CH2
(ꢀ)-menthyl
PhCH2
PhCH2
H2C¼CHCH2
iPr
3
iPr
2.5
4.5
3
4
4.5
iPr
10
11
12
Ph
2-oxocyclopentyl
2-oxocyclopentyl
a) All products were characterized by spectroscopic data. b) Yield after chromatography.
In summary, we established BiCl3 as a novel catalyst for the rapid and efficient
transesterification of b-keto esters with a variety of alcohols.
R. S. and P. G. thank CSIR, and M. B. thanks UGC, New Delhi, for the award of fellowships.
Experimental Part
Transesterification: General Procedure. A mixture of b-keto ester 1 (1 equiv.), alcohol 2 (2 equiv.),
and the catalyst BiCl3 (10 mol-% of b-keto ester) in toluene (ca. 20 ml) was refluxed in a DeanꢀStark
apparatus to remove the alcohol formed (TLC monitoring). After the consumption of 1, the catalyst was
filtered and the filtrate concentrated. The residue was purified by chromatography (silica gel, hexane/
AcOEt in different proportions): b-keto ester 3. Isolated yields are indicated in the Table. All products
were analyzed by NMR, IR, and GC/MS, and the spectra were consistent with the structure of the desired
products.
REFERENCES
[1] Y. Matano, T. Ikegami, ꢂOrganobismuth(III) Compoundsꢃ, in ꢂOrganobismuth Chemistryꢃ, Eds. H.
Suzuki, Y. Matano, Elsevier, New York, 2001, Chapt. 2, pp. 21 – 245.
[2] S. K. De, R. A. Gibbs, Tetrahedron Lett. 2004, 45, 7407; N. M. Leonard, L. C. Wieland, R. S. Mohan,
Tetrahedron 2002, 58, 8373.

Helvetica Chimica Acta – Vol. 94 (2011)
121
[3] G. Sabitha, R. S. Babu, E. V. Reddy, R. Srividya, J. S. Yadav, Adv. Synth. Catal. 2001, 343, 169; G.
Sabitha, E. V. Reddy, J. S. Yadav, Synthesis 2001, 1979; G. Sabitha, E. V. Reddy, J. S. Yadav, K. V. S.
Ramakrishna, A. R. Sankar, Tetrahedron Lett. 2002, 43, 4029; G. Sabitha, E. V. Reddy, C. Maruthi,
J. S. Yadav, Tetrahedron Lett. 2002, 43, 1573; G. Sabitha, E. V. Reddy, J. S. Yadav, Synthesis 2002, 409;
G. Sabitha, E. V. Reddy, R. Swapna, N. M. Reddy, J. S. Yadav, Synlett 2004, 1276; G. Sabitha, C. S.
Reddy, C. Maruthi, E. V. Reddy, J. S. Yadav, Synth. Commun. 2003, 33, 3063; G. Sabitha, C. Maruthi,
E. V. Reddy, C. Srinivas, J. S. Yadav, S. K. Dutta, A. C. Kunwar, Helv. Chim. Acta 2006, 89, 2728; G.
Sabitha, R. S. Babu, E. V. Reddy, J. S. Yadav, Chem. Lett. 2000, 29, 1074.
Received March 22, 2010