One-Pot Chemical Route in the Synthesis of Fragrances Based on the Heck Reaction
FULL PAPERS
clave was pressurized with H2 (5 bar) with a hydrogen flow
of 5 mLminÀ1, and the product from the first reaction step
was hydrogenated at 393 K to give compound 2a with a
raspberry fragrance. Samples were taken at a regular inter-
vals and analyzed by GC using an FID detector and a
column (EquiytTM-5 Fused Silica capillary column 30 mꢁ
0.25 mm, 0.25 mm film thicknesses). Reaction products were
identified by GC-MS (Hewlett–Packard 5988 A) and
accepted in the literature as being highly active for
performing Heck reactions.
The new catalytic route proposed here has the ad-
vantage of taking place in one-pot in which two reac-
tions taking place through consecutive steps are car-
ried out, in our case with very high yield, without the
necessity of intermediate separations and purifica-
tions.
1H NMR spectroscopy (Varian Gemenis-300 MHz, CDCl
3
as solvent).
Experimental Section
Study of Pd Leaching
Application of the hot filtration test in order to study Pd
leaching was carried out in the reaction of methoxyiodoben-
zene with methyl vinyl ketone at 393 K using Pd-TiO2 as cat-
alyst. After 15 min of reaction time the hot reaction mixture
was filtered and the solid catalyst removed. 5.39 mmol of
base were added to the liquid phase mixture and the reac-
tion was continued during 9 h with the composition of the
reaction mixture being analyzed at different time points.
The supports were supplied by Degussa (TiO2), Merck
(Al2O3), Aldrich (MgO), while hydrotalcite was prepared
according toRef[20] and hydroxyapatite was synthesized by
precipitation ccording to the literature procedure.[21]
Palladium on activated carbon (Pd/C) catalyst (Pd 5 wt%,
Degussa type E101NO/W, 50% water) was purchased from
Sigma–Aldrich.
Samples with 0.2 wt% of supported palladium were pre-
pared by impregnation of the support with an aqueous solu-
tion of dichlorobis(benzonitrile)palladium (28 mg) in ace-
tone (300 mL) which wasd added to 4.0 g of oxide support.
The mixture was stirred for 5 h at room temperature and
the solid was filtered and dried overnight under vacuum.
The samples were calcined 2 h at 673 K with an N2 flow of
100 mLminÀ1. Samples were activated after calcination at
723 K with a mixture of hydrogen and nitrogen (H2/N2: 90/
10) at a flow rate of 100 mLminÀ1 during 2 h. The main
characteristics of the catalysts are given in Table 1.
Recycling of Catalyst
After running the reaction of p-methoxyiodobenzene with
MVK according to the general procedure, the catalyst was
removed by filtration, washed several times with water to
remove the base and finally with dichloromethane. The cata-
lyst was dried at 523 K under vacuum (2 torr) during 2 h and
then activated at 723 K with a mixture of hydrogen and ni-
trogen (H2/N2: 90/10) at a flow rate of 100 mLminÀ1 during
2 h.
N2 adsorption/desorption isotherms were performed at
77 K in an ASAP 2010 apparatus from Micromeritics, after
Synthesis of Acetophenone Oxime-Palladium
pre-treating the samples under vacuum at 673 K overnight Complex (Pd-AO)
and the BET surfaces were obtained using the BET method-
ology. Physicochemical characteristics of the catalysts are
presented in Table 1.
The acetophenone oxime-derived palladacycle complexe
catalyst (Pd-AO) was synthesized according to reference.[19]
To a solution of Li2PdCl4 (1 mmol) in methanol (10 mL) a
methanolic solution (5 mL) of the acetophenone oxime
(5 mmol) and sodium acetate (0.1 mmol) were added, and
the solution was stirred for 3 days at room temperature.
After this time, the mixture was filtered, and after additon
of water to the liquid filtrate the cyclopalladate complexe
was precipitated. The palladium complex was recovered by
filtration and dried at room temperature under vacuum
during 4 h. The structure of the catalyst was confirmed by
1H NMR spectroscopy (Varian Gemenis 300 MHz, DMF-d
as solvent).
Reaction Procedure
The reaction was carried out as follows: a mixture of 4-me-
thoxyiodobenzene (4.4 mmol), methyl vinyl ketone
(8.8 mmol), Na2CO3 (5.39 mmol), in 4.5 mL of DMF and
catalyst (300 mg) were added to an autoclave. The resultant
suspension was heated a 393 K at atmospheric pressure
under vigorous stirring. The autoclave was heated with an
oil bath equipped with an automatic temperature control
system while the reaction temperature was measured in the
autoclave. When the Heck reaction was completed the auto-
Acknowledgements
Table 1. Main characteristics of different oxides used in the
preparation of 2a.
Financial support by CICyT MAT2006–14274-CO2–01 is ac-
knowledged. The contribution of Mr. Pablo Ramos in experi-
mental work is also gratefully acknowledged.
Catalysts
Surface area (m2 gÀ1) Pore volume (cm3 gÀ1)
0.2Pd-HA
0.2Pd-Al2O3 135
0.2Pd-MgO
0.2Pd-HT[a]
0.2Pd-TiO2
77
0.30
0.18
0.50
0.47
0.22
177
253
52
References
[1] R. Fischer, W. Koernig, (Badische-Anilin and Soda-
[a]
Relation molar Al/Al+Mg=0.25.
Fabrick AG), German Patent DE 2,145,308, 1973.
Adv. Synth. Catal. 2007, 349, 1949 – 1954
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1953