Solvent-Free Condensation of Carboxylic Acids with Alcohols
COMMUNICATIONS
Table 2 (cont.)
Entry
R in RCOOH
R1-OH
Time [h]
18
Temp. [ 8C]
Product
Yield [%]
92
23
80
24
CH3(CH2)7-
CH3(CH2)21-OH
12
80
n-C8H17COOC22H45 26
95
Reaction conditions: 1 mmol of alcohol, 1.1 mmol of carboxylic acid, 0.05 mmol of Zn(ClO4)2 ·6 H2O, 1 mmol of MgSO4; the
yields reported refer to isolated products.
[a]
10% of dibenzyl ether was obtained.
10 mol % of catalyst were used.
10% of deprotected product was observed.
A mixture of tri- and diesters of glycerol was recovered.
10% of ethyl 3-phenylpropionate was observed.
15 mol % of catalyst were used.
[b]
[c]
[d]
[e]
[f]
(s, 3H), 2.55 (t, 2H, JH,H ¼6.5 Hz), 2.74 (t, 2H, JH,H ¼6.5 Hz),
4.80–4.95 (m, 1H); 13C NMR (100 MHz, CDCl3): d¼14.0
(CH3), 19.8 (CH3), 22.5 (CH2), 25.2 (CH2), 28.3 (CH2), 29.2
(CH2), 29.9 (CH3), 31.7 (CH2), 36.0 (CH2), 38.1 (CH2), 71.7
(CH), 172.3 (C), 206.6 (C).
by Ishihara, Yamamoto et al.,[12] which appeared during
the revision of the present manuscript.
We can assert that the present protocol for the
Zn(ClO4)2 ·6 H2O-catalysed esterification joins the
practical and environmental advantages of heterogene-
ous catalysis with a fair applicability to several sub-
strates, typical of a homogeneous Lewis acid catalysis.
Acknowledgements
This work was carried out in the framework of the National
Project “Stereoselezione inSintesi Organica. Metodologiee Ap-
plicazioni” supported by MIUR, Rome, by the University of Bo-
logna, in the framework of “Progetto di Finanziamento Plurien-
nale, Ateneo di Bologna”, and by National project FIRB “Pro-
gettazione, preparazione e valutazione biologica e farmacolog-
ica di nuove molecole organiche quali potenziali farmaci”.
Experimental Section
Typical Experimental Procedure
An oven-dried Schlenk tube was charged with Zn(ClO4)2 ·
6 H2O (18.6 mg, 0.05 mmol), MgSO4 (120 mg, 1 mmol), 1-octa-
nol (157 mL, 1 mmol), 3-phenylpropionic acid (165 mg,
1.1 mmol), and immersed up to the top in an oil bath at 808C.
The mixture was stirred for 8 hours, then cooled to room tem-
perature, and diluted with CH2Cl2. The catalyst was filtered off,
and the organic layer was washed with water, then aqueous
NaHCO3. After drying with MgSO4 and evaporation of the sol-
vent, the crude product was purified by flash chromatography
on a silica gel column (petroleum ether:diethyl ether, 4:1) to
give the desired carboxylic ester; yield: 249 mg (95%).
The filtered catalyst was reactivated by heating in oven at
608C overnight and reused.
References and Notes
[1] a) T. W. Greene, P. G. M. Wuts, Protective Groups in Or-
ganic Synthesis, Wiley, New York, 3rd edn., 1999, pp. 369
–427; b) P. J. Kocienski, Protecting Groups, 3rd edn.,
Thieme, Stuttgart, 2004, pp. 323–325, 394–444; c) R. C.
Larock, Comprehensive Organic Transformations, 2nd
edn., Wiley-VCH, New York, 1999, pp. 1932–1941;
d) H. E. Hoydonckx, D. E. De Vos, S. A. Chavan, P. A.
Jacobs, Top. Cat. 2004, 27, 83–95.
[2] For recent examples, see: a) J. Xiang, A. Orita, J. Otera
Angew. Chem. Int. Ed. 2002, 41, 4117–4119; b) J. Otera
Acc. Chem. Res. 2004, 37, 288–296; c) K. Ishihara, S.
Ohara, H. Yamamoto Science 2000, 290, 1140–1142;
d) K. Wakasugi, T. Misaki, K. Yamada, Y. Tanabe, Tetra-
hedron Lett. 2000, 41, 5249–5252; e) Y. Q. Li, Synth.
Commun.1999, 29, 3901–3903; f) T. Kawabata, T. Mizu-
gaki, K. Ebitani, K. Kaneda, Tetrahedron Lett. 2003, 44,
9205–9208; g) L. J. Gooben, A. Dçhring, Synlett 2004,
263–266.
Spectroscopic data of two representative unknown products
are as follows:
(Z)-3-Hexenyl 3-phenylpropanoate (5): 1H NMR
(400 MHz, CDCl3): d¼0.96 (t, 3H, JH,H ¼7.5 Hz), 2.00–2.05
(m, 2H), 2.15–2.20 (m, 2H), 2.61 (t, 2H, JH,H ¼7.8 Hz), 2.94
(t, 2H, JH,H ¼7.8 Hz), 4.06 (t, 2H, JH,H ¼6.0 Hz), 5.10–5.15
(m, 1H), 5.20–5.25 (m, 1H), 7.05–7.10 (m, 3H), 7.10–7.15
(m, 2H); 13C NMR (75 MHz, CDCl3): d¼14.0 (CH3), 20.4
(CH2), 26.8 (CH2), 30.8 (CH2), 35.8 (CH2), 63.5 (CH2), 123.7
(CH), 126.3 (CH), 128.2 (CH), 128.4 (CH), 134.5 (C), 140.5
(C), 172.9 (C).
2-Methylheptyl 4-oxopentanoate (14): 1H NMR (300 MHz,
CDCl3): d¼0.88 (t, 3H, JH,H ¼6.8 Hz), 1.21 (d, 3H, J¼6.0 Hz),
1.20–1.35 (m, 8H), 1.35–1.45 (m, 1H), 1.50–1.60 (m, 1H), 2.20
[3] a) B. M. Trost, Science 1991, 254, 1471; b) B. M. Trost,
Angew. Chem. Int. Ed. Engl. 1995, 34, 259–281.
Adv. Synth. Catal. 2005, 347, 33–38
asc.wiley-vch.de
ꢀ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
37