4
Tetrahedron
References and notes
1
2
3
4
5
.
.
.
.
.
Lednicer, D.; Mitscher, L. A. In The Organic Chemistry of Drug
Synthesis; John Wiley: New York, 1980; Vol. 2, p 62.
Zeevaart, J. G.; Parkinson, Ch. J.; de Koning, Ch. B. Tetrahedron
Lett. 2007, 48, 3289-3293.
Yip, S. F.; Cheung, H. Y.; Zhou, Zh.; Kwong, F. Y. Org. Lett.
2
007, 9, 3469-3472.
Deng, W.;Wang, Y. F.; Liu, L.; Xiang, Q. Chinese Chem. Lett.
006, 17, 595-598.
Ke, J.; He, Ch.; Liu, H.; Xu, H.; Lei, A. Chem. Commun. 2013,
9, 6767-6769.
2
4
Figure 6
Interestingly, by-products 10a and 10b (Figure 7) were
6.
Fodor, A.; Kiss, Á; Debreczeni, N.; Hell, Z.; Gresits, I. Org.
Biomol. Chem. 2010, 8, 4575-4581.
Debreczeni, N.; Fodor, A.; Hell, Z. Cat. Lett. 2014, 144, 1547-
7
.
1551.
observed from the reactions of 3- and 4-iodotoluene,
respectively, in very small amounts (approximately 1%). The
proposed mechanism of their formation is shown using the
example of 4-iodotoluene (Figure 8). In the presence of water,
iodotoluene can form the appropriate phenol (6b) which then
reacts with iodine (originating from oxidation of the formed CsI)
yielding the intermediate benzyl iodide 11 which then alkylates
the acetoacetate yielding 10b (Figure 7).
8.
Zeevaart, J. G.; Parkinson, Ch. J.; de Koning, Ch. B. Tetrahedron
Lett 2004, 45, 4261-4264.
Hurtley, R. H. J. Chem. Soc. 1929, 1870.
9
1
.
0. Adams, R; Blomstrom, D. C. J. Am. Chem. Soc. 1953, 75, 3403.
11. Hell Z.; Kiss Á. Synth. Commun. 2013, 43, 1778-1786.
1
2. Hell Z.; Kiss Á. Tetrahedron Lett. 2011, 52, 6021-6023.
1
3. Nakamura, S.; Hirao, H.; Ohwada, T. J. Org. Chem. 2004, 69,
4
309-4316.
1
1
4. Hell Z.; Finta Z.; Tőke L. Synth. Commun. 1997, 27, 405-408.
5. GC-MS measurements were performed on an Agilent 6890 N-
GC-5973 N-MSD chromatograph, using a 30 m × 0.25 mm
Restek, Rtx-5SILMS column with a film layer of 0.25 µm. The
initial temperature of column was 45 °C for 1 min, followed by
programming at 10 °C/min up to 310 °C and a final period at 310
°C (isothermal) for 17 min. The temperature of the injector was
2
50 °C. The carrier gas was He and the operation mode was
1
splitless. H NMR spectra were made on BRUKER Avance-300
instrument using TMS as an internal standard in CDCl
6. Preparation and characterization of the catalyst: 4Å molecular
sieves (2 g) and CuCl .2H O (0.34 g, 2 mmol) in deionized water
200 mL) were stirred at room temperature for 12 h. The light
3
.
1
2
2
(
Figure 7
green solid was filtered, washed with deionized water (50 mL)
and acetone (20 mL), then dried in an oven at 120 °C for 1 h. The
copper content was experimentally determined as 5.8 wt% (by
ICP-OES). 4ÅMS are
a
synthetic microporous sodium
aluminosilicate (zeolite) having sodalite structure. During the
impregnation copper ions can replace the sodium ions in the
zeolite. Surface analysis by scanning electron microscope (SEM)
showed cubic zeolite crystals (see picture below), most of the
particles were in the 2.5–5 µm range. Energy-Dispersive X-ray
Spectroscopy (EDS) showed that copper evenly covered the
support’s surface. Nitrogen adsorption measurements showed
2
Figure 8
that the surface area of the original molecular sieves (810 m /g)
2
dropped to 360 m /g after impregnation.
The reusability of the catalyst was also investigated. The solid
filtered from the reaction mixture was washed with water then
dichloromethane and heated at 150 °C for 2 h. Use of the
recovered catalyst in the reaction of iodobenzene with ethyl
acetoacetate yielded 60% of product. The large decrease in the
yield could be explained by the precipitation of caesium iodide
onto the surface of the catalyst. During the workup of the
reaction this inorganic salt may not be removed completely from
the surface, and thus it can cover and block the metal particles,
decreasing the number of active sites.
17. General procedure: A mixture of aryl iodide (5 mmol), ethyl
2
+
acetoacetate (7.5 mmol), Cu /4A (0.5 g, 0.1 mol% copper), and
Cs CO (12.5 mmol) in dioxane (10 ml) was stirred at 100 °C for
2 hours. The solid was filtered and the filtrate was evaporated in
vacuo. The products were purified by column chromatography
silica gel, hexane:acetone 4:1 eluent). The products were
2
3
1
Conclusion
(
In summary, a heterogeneous catalytic method has been
developed for the selective preparation of arylacetic esters from
ethyl acetoacetate and aryl iodides in the presence of copper(II)
on 4Å molecular sieves. The catalyst can be easily removed from
the reaction mixture, with no appreciable copper contamination
of the product. The reaction time was considerably shorter than in
the previously published homogeneous catalytic processes (12 h
vs. 48 h).
1
characterized by H-NMR and GC-MS.
1
8. Selected analytical data: Ethyl phenylacetate (3a): colourless
liquid, 1H NMR (300 MHz, CDCl ) δ (ppm): 1.21 (t, 3H), 3.58
3
+
(s, 2H), 4.12 (q, 2H), 7.19-7.33 (m, 5ArH); MS: m/z: 164 (M ),
136, 119, 105, 91(100%), 77. Diphenylether (7a): MS: m/z:
+
1
70(M , 100%), 94, 77. Ethyl 2-acetyl-3-hydroxy-3-methyl-4-
phenylbutanoate (8a): MS: m/z: 248, 219, 203, 175(100%), 147,
1
31, 119, 102, 91, 77. Ethyl 3-hydroxy-3-methyl-4-phenyl-
+
butanoate (9a): MS: m/z: 222(M ), 176, 149, 135, 107(100%),
1, 77. Ethyl (4-hydroxybenzyl)acetoacetate (10b): MS: m/z:
9