Condensation of orthoacetates with aldehydes: A new strategy for the preparation of α,β-unsaturated esters

Article abstract of DOI:10.1016/S0040-4039(03)00815-3

α,β-Unsaturated esters are formed in good yields when aldehydes are heated with orthoacetates in the presence of a catalytic amount of phenol.

Full text of DOI:10.1016/S0040-4039(03)00815-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 4287–4289
Condensation of orthoacetates with aldehydes: a new strategy for
the preparation of a,b-unsaturated estersꢀ
H. M. Sampath Kumar,* M. Shesha Rao, Sipak Joyasawal and J. S. Yadav
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 14 October 2002; revised 11 March 2003; accepted 21 March 2003
Abstract—a,b-Unsaturated esters are formed in good yields when aldehydes are heated with orthoacetates in the presence of a
catalytic amount of phenol. © 2003 Elsevier Science Ltd. All rights reserved.
a,b-Unsaturated esters are useful chemical entities
which are accessible through condensation reactions
involving aldehydes, viz. (i) Knoevenagel condensations
of active methylene esters with aldehydes,1 (ii) conden-
sations of alkyl acetates with aldehydes followed by
dehydration,2 (iii) Reformatsky reactions with alde-
hydes followed by b-elimination of the ensuing hydroxy
esters,3 (iv) Wadsworth–Emmons olefination of car-
bonyl compounds.4 Even though some of the above
methods have advantages, the Knoevenagel condensa-
tion route, particularly for cinnamic esters, involves two
separate steps, i.e. the preparation of the cinnamic acid
followed by its esterification and the Reformatsky reac-
tion has the limitation2 of not being suitable for the
preparation of cinnamic acids with halo, phenoxy or
nitro substituents on the aromatic moiety.
Various aldehydes and ketones were heated with
orthoacetates at elevated temperatures in the presence
of a catalytic quantity of phenol. The reactions were
conducted in the absence of any solvent by simply
heating (120–130°C) the reactants under an inert atmo-
sphere (see Table 1). The progress of the reaction could
be monitored by thin layer chromatography (TLC) and
after the appropriate time, the reaction was cooled to
room temperature and treated with dilute HCl to
remove excess orthoacetate and the residual crude a,b-
unsaturated ester was purified by column chromatogra-
phy (purity >90%, GC). This reaction is general with
regard to various aldehydes such as aliphatic, aromatic,
heterocyclic and a,b-unsaturated aldehydes.7 However,
in the case of ketones, cyclohexanone gave only trace
amounts of the corresponding unsaturated ester,
whereas acetophenone failed to react under identical
reaction conditions. Aromatic aldehydes generally
required 12 h or more heating whereas heterocyclic
aldehydes such as furfural required only 6 h for com-
plete conversion. This reaction was also found to be
general with regard to different orthoesters, e.g. both
trimethyl and triethyl orthoacetates gave comparable
yields of the corresponding a,b-unsaturated esters
under identical experimental conditions (Scheme 1).
Reactions of orthoesters with various carbonyl com-
pounds are well documented in the literature.5 Alde-
hydes and ketones form acetals when heated with
orthoformates and an acidic catalyst, whereas esters are
formed when acids react with orthoacetates or for-
mates. Recently we reported an O-alkylation reaction
of benzylic and allylic alcohols using orthoesters which
has been applied to the total synthesis of various natu-
ral products.6 In continuation of our interest in explor-
ing new synthetic uses of orthoesters, we herein report
a new application which describes the condensation of
orthoacetates with aldehydes to generate a,b-unsatu-
rated esters in high yields.
Keywords: orthoesters; aldehydes; a,b-unsaturated esters.
ꢀ IICT Communication No. 030104.
* Corresponding author. Fax: +91-40-27160512; e-mail: hmskumar@
yahoo.com
Scheme 1.
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00815-3

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H. M. Sampath Kumar et al. / Tetrahedron Letters 44 (2003) 4287–4289
Table 1. Preparation of a,b-unsaturated esters

H. M. Sampath Kumar et al. / Tetrahedron Letters 44 (2003) 4287–4289
4289
Scheme 2.
This condensation may proceed through the attack of
an enol ether, generated by acid catalyzed degradation
of the orthoacetate, on the oxonium ionfollowed by
b-elimination to afford the trans a,b-unsaturated ester.
Finally, when we attempted the direct condensation of
ethyl acetate with aldehydes in the presence of a cata-
lytic quantity of phenol under analogous experimental
conditions, i.e. heating at 130°C for 12 h (a sealed tube
was used on this occasion in order to prevent evapora-
tion of ethyl acetate) no a,b-unsaturated ester could be
detected in the reaction mixture. Thus, the reaction is
unlikely to proceed through the direct condensation of
the acetic acid ester generated in situ as the by-product
of acid catalyzed degradation of the orthoacetate. This
augments our proposed mechanism for the formation
of a,b-unsaturated esters from the interaction of
orthoacetates and aldehydes (Scheme 2, Table 1).
2. Galat, A. J. Am. Chem. Soc. 1946, 68, 376.
3. (a) Shriner, R. L. Org. React. 1942, 1; (b) Hauser, C. R.;
Breslow, D. S. Org. Synth. Coll. Vol. 1955, 3, 408; (c)
Rinehart, K. L.; Perkins, E. G. Org. Synth. Coll. Vol.
1963, 4, 444.
4. (a) Wadsworth, W. S.; Emmons, W. D. J. Am. Chem. Soc.
1961, 83, 1733; (b) Wadsworth, W. S. Org. React. 1977,
25, 73; (c) Wadsworth, W. S. Acc. Chem. Res. 1983, 16,
1411; (d) Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989,
89, 863.
5. Sampath Kumar, H. M.; Subba Reddy, B. V.; Mohanty,
P. K.; Yadav, J. S. Tetrahedron Lett. 1997, 37, 3619 and
references cited therein.
6. Nishimata, T.; Mori, M. J. Org. Chem. 1998, 63, 7586.
7. Experimental: Typical procedure for the preparation of h,i-
unsaturated esters: A mixture of furfural (0.968 g, 10
mmol) and triethyl orthoacetate (3.24 g, 20 mmol) and
phenol (0.2 g, 20% w/w of aldehyde) was heated at 130°C
under a nitrogen atmosphere for 6 h at the end of which
time the complete conversion could be ascertained by the
total disappearance of aldehyde on TLC. The reaction
mass was cooled to rt and washed with portions of cold
dilute hydrochloric acid to remove any excess orthoac-
etate. This was followed by extraction with ether (2×25 ml)
and the combined organic extracts washed with brine (10
ml) and dried (Na2SO4). Evaporation of the ether afforded
a crude residue, which after column chromatography (sil-
ica gel, EtOAc–hexane, gradient) gave 1.59 g (92%) of
product (entry 9, GC purity, 97%) as a viscous liquid;8 bp
In conclusion, we have presented in this paper, a novel
and efficient acid catalyzed condensation of orthoac-
etates with various aldehydes to generate a,b-unsatu-
rated esters in good yields. The above method may find
utility as an alternative to the currently available proce-
dures for the preparation of these compounds.
Acknowledgements
S.J. thanks the CSIR, New Delhi for the award of a
research fellowship.
1
230°C; IR (CHCl3): 1712 cm−1; H NMR (CDCl3): l 1.3
(t, 3H, J=7.4 Hz), 4.2 (q, 2H, J=7.4 Hz), 6.3 (d, 1H,
J=15.7 Hz), 6.43 (m, 1H), 6.56 (d, 1H, J=3.4 Hz), 7.39
(d, 1H, J=15.7 Hz), 7.45 (d, 1H, J=1.6 Hz).
References
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