Heck reactions with very low ligandless catalyst loads accelerated by microwaves or simultaneous microwaves/ultrasound irradiation

Article abstract of DOI:10.1002/adsc.200700098

Heck couplings were carried out ligandless in air with very low catalyst loads under microwave or simultaneous microwave/ultrasound irradiation. Using ligand-free palladium(II) acetate [Pd(OAc)₂] in the range of 0.01-0.1 mol% or palladium-oncarbon (Pd/C) 10% in the range of 1.0-2.0 mol%, most aryl iodides and bromides gave high yields under conventional heating (120 °C) in 18 h. MicroWave irradiation alone or, better still, combined with high-intensity ultrasound, strongly promotes the reaction, generally decreasing reaction times to 1 h. Electron-poor aryl chlorides such as 4-chloroacetophenone and l-chloro-4-nitrobenzene reacted with styrene to afford high product yields in the presence of 0.25 mol% Pd(OAc)₂ or 2.0-3.0 mol% Pd/C. In several cases the addition of a co-catalyst, either rhodium tris(triphenylphosphine) chloride, 0.005 mol%, or a copper(I) salt (iodide or bromide), 2.0-4.0 mol %, proved very advantageous. 4-Bromo- and 4-chloroacetophenone afforded up to 15 % of oxidation products, namely the corresponding 4-halobenzoic acid and 4-styrylbenzoic acid, a drawback that was avoid ed by working under a nitrogen atmosphere.

Full text of DOI:10.1002/adsc.200700098

FULL PAPERS
DOI: 10.1002/adsc.200700098
Heck Reactions with Very Low Ligandless Catalyst Loads Accel-
erated by Microwaves or Simultaneous Microwaves/Ultrasound
Irradiation
Giovanni Palmisano,a Werner Bonrath,b Luisa Boffa,c Davide Garella,c
Alessandro Barge,c and Giancarlo Cravottoc,*
a
Dipartimento di Scienze Chimiche e Ambientali, Università dell’Insubria, Via Valleggio 11, 22100 Como, Italy
DSM – Nutritional Products, Research and Development, P.O. Box 3255, 4002 Basel, Switzerland
Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Via Giuria 9, 10235 Torino, Italy
b
c
Fax : (+39)-011-670-7687; e-mail: giancarlo.cravotto@unito.it
Received: February 13, 2007; Revised: May 28, 2007
Abstract: Heck couplings were carried out ligandless styrene to afford high product yields in the presence
in air with very low catalyst loads under microwave of 0.25 mol% Pd
or simultaneous microwave/ultrasound irradiation. several cases the addition of a co-catalyst, either rho-
Using ligand-free palladium(II) acetate [Pd(OAc)2] dium tris(triphenylphosphine) chloride, 0.005 mol%,
A
AHCTREUNG
in the range of 0.01–0.1 mol% or palladium-on- or a copper(I) salt (iodide or bromide), 2.0–4.0 mol%,
carbon (Pd/C) 10% in the range of 1.0–2.0 mol%, proved very advantageous. 4-Bromo- and 4-chloro-
most aryl iodides and bromides gave high yields acetophenone afforded up to 15% of oxidation prod-
under conventional heating (1208C) in 18 h. Micro- ucts, namely the corresponding 4-halobenzoic acid
wave irradiation alone or, better still, combined with and 4-styrylbenzoic acid, a drawback that was avoid-
high-intensity ultrasound, strongly promotes the re- ed by working under a nitrogen atmosphere.
action, generally decreasing reaction times to 1 h.
Electron-poor aryl chlorides such as 4-chloroaceto- Keywords: Heck reaction; ligand-free; microwaves;
phenone and 1-chloro-4-nitrobenzene reacted with palladium; ultrasound
Introduction
Using ligand-free Pd
and 0.10 mol% De Vries and co-workers observed
A
In the last years the Heck (or Mizoroki–Heck) reac- very acceptable rates in the Heck reaction of bromo-
tion,[1–3] one of the most useful syntheses in organic benzene with butyl acrylate. Under their conditions
chemistry, has become a veritable classic. Not only the addition of ligands or preformed palladacycles
has it been thoroughly studied in the laboratory;[4]
a
often had a retarding effect. When the catalyst-to-sub-
myriad of important applications and related patents strate ratio was further lowered to 0.00125 mol%, cat-
testify to its fundamental role in the preparation of a alysis still occurred, but conversion was too slow to be
wide range of products.[5–7] Its scope has been further practical.
widened by the introduction of new generations of
If a soluble, ligand-free Pd catalyst could be in-
catalysts, comprising palladacycles, pincers and bulky duced to work effectively at a significantly lower
electron-rich ligands for coupling reactions on aryl level, its marginal cost and simplified work-up proce-
chlorides. As phosphine ligands are often difficult to dures would make its industrial use more advanta-
separate from products, greener procedures now geous than heterogeneous catalysis. Several reports
resort to “ligand-free” palladium catalysis, using describe Heck reactions carried out in the presence of
either simple palladium salts, metallic palladium, or Pd/C or a palladium catalyst dispersed on other sup-
palladium nanoclusters immobilized on inorganic sup- porting materials; their major drawbacks are the need
ports. Some recent reports even describe Heck reac- for
a high temperature and a longer reaction
tions catalyzed by ligand-free palladium in trace time.[11,12] Although high turnover numbers (TONs)
amounts, an improvement to which such eminent au- have been attained using heterogeneous catalysts cou-
thors as Beletskaya,[4] Reetz and de Vries[8,9] refer by pled with elaborate recycling strategies, a great
the term “homeopathic catalyst quantities” to cover simplification would result from the use of catalysts
concentrations ranging from a few ppm to a few ppb. that are effective at such low levels that, in principle,
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Adv. Synth. Catal. 2007, 349, 2338 – 2344

Heck Reactions with Very Low Ligandless Catalyst Loads
FULL PAPERS
they may not have to be recovered and recycled at Results and Discussion
all. As highlighted by Farina,[5] besides considerations
of cost, an important concern is product contamina- The present study was prompted by the excellent re-
tion by the metallic catalyst, which in the case of sults we had achieved with the Suzuki reaction, that
pharmaceuticals must to be strictly controlled, usually was greatly accelerated by combined MW/US irradia-
not to exceed 10 ppm. It is easy to see that both the tion as compared to either treatment used by itself or
problems of cost and contamination will be automati- to conventional heating.[30] We developed two types
cally eliminated with catalysts that display TONs of of combined MW/US reactors.[32] The first uses two
105 or higher. Thus any Pd-based technique with reaction cells (one for each kind of irradiation) joined
TONs of 105–106 and adequate turnover frequency by short lengths of tubing to allow the reacting liquid
(TOF) will be of great practical interest for pharma- to circulate between them, while the second uses a
ceutical and fine chemical production.[10] A recent single reaction cell for simultaneous irradiation with
review by Jones and co-workers summarized the pres- both energy sources. For the present work we em-
ent knowledge on a much debated issue that is actual- ployed the latter reactor, featuring a Pyrexꢁ US horn
ly the main crux in this field of research: the true inserted in a professional multimode MW oven
nature of catalytic species generated from different (Figure 1).[33]
types of precatalysts and reaction conditions.[13]
To begin with, couplings of styrene with 4-iodoani-
The Heck reaction has been carried out in all possi- sole (Table 1, entries 1–8), 4-bromoanisole (entries 9–
ble reaction media (organic solvents, water, supercriti- 16) and 4-bromoacetophenone (entries 17–28) were
cal CO2, ionic liquids) and under such unconventional carried out in the presence of Pd
conditions as ultrasound (US) and microwave (MW) C; the amounts of catalyst were in the ranges of 0.01–
irradiation. For example, Srinivasan employed Pd- 0.1 mol% for Pd(OAc)2 and 1.0–2.0 mol% for Pd/C
(OAc)2 in an ionic liquid under US;[14] in other studies (Scheme 1). All reactions were carried out in parallel
(OAc)2 or 10% Pd/
AHCTREUNG
ACHTREUNG
the sonochemical approach was used with Pd/C in under the following conditions: 1) under stirring and
NMP[15] or to form palladium nanoparticles at room conventional heating in an oil bath; 2) under MW
temperature in an aqueous reaction medium.[16] Ge- alone; 3) under combined MW/US irradiation. In
danken exploited power US to generate in situ amor- order to improve yields, in certain cases we also stud-
phous carbon-activated palladium metallic clusters
that proved an efficient catalyst for the Heck reac-
tion.[17] In the last ten years more than 50 papers have
appeared describing the advantages of MW heating
when applied to the Heck reaction;[18,19] particular at-
tention was paid to the vinylation of both electron-
poor and electron-rich aryl chlorides. Reaction times
were generally reduced from many days or hours
down to few minutes.[20] MW heating[21,22] and US
waves[23,24] are among the most simple, inexpensive
and valuable tools in applied chemistry. Beside saving
energy, these green techniques promote faster and
more selective transformations. Recent develop-
ments[25–27] evidence that their combination (simulta-
neous or sequential) is possible, safe and well suited
for automation and scaling-up.[28]
Ligand-free Pd-catalyzed homo- and cross-cou-
plings of boronic acids with aryl halides have been
successfully performed by our group in aqueous
media under high-intensity US and MW, either alone
or in a combined fashion.[29,30] We carried out com-
bined irradiation in a flow reactor, obtaining the ex-
pected biaryls in higher yields and shorter time than
using sonication or microwaves separately.[30] Proceed-
ing from our previous experience on the catalysis of
Suzuki[29,30] and Heck reactions[31] we present here our
recent results on reactions carried out with a very low
ligandless catalyst load under MW or simultaneous
US/MW irradiation.
Figure 1. Standard set-up for simultaneous MW/US irradia-
tion.
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ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
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Giovanni Palmisano et al.
FULL PAPERS
Table 1.
Entry[a] Aryl halide
Catalyst (mol%) Method
Time[b] [h] Yield[c] [%] Product[d] E/Z Conversion
ratio
[%]
1
2
3
4-iodoanisole
4-iodoanisole
4-iodoanisole
Pd
Pd(OAc)2 0.01
Pd(OAc)2 0.01,
CuI 2.0
Pd(OAc)2 0.05
Pd(OAc)2 0.05
Pd/C 1.0
Pd/C 1.0
Pd/C 1.0
C
Oil bath
Oil bath
Oil bath
18
18
18
94
88
91
1a/1b, 1:6
1a/1b, 2:13
1a/1b, 1:7
96
89
100
4
5
6
7
8
9
10
11
4-iodoanisole
4-iodoanisole
4-iodoanisole
4-iodoanisole
4-iodoanisole
4-bromoanisole
4-bromoanisole
4-bromoanisole
MW
1.5
0.5
18
3
1.5
18
18
18
97
99
97
98
99
95
32
66
1a/1b, 2:9
1a/1b, 1:9
1a/1b, 1:7
1a/1b, 1:5
1a/1b, 1:5
1a/1b, 1:12
1a/1b, 1:13
1a/1b, 1:16
100
100
100
100
100
100
40
MW/US
Oil bath
MW
MW/US
Oil bath
Oil bath
Oil bath
Pd
Pd(OAc)2 0.01
Pd(OAc)2 0.01,
Wilkinson 0.005
Pd(OAc)2 0.01
Pd(OAc)2 0.01
A
ACHTREUNG
N
86
12
13
14
15
16
17
18
19
4-bromoanisole
4-bromoanisole
4-bromoanisole
4-bromoanisole
H
MW
3
29
39
92
89
96
95
31
39
1a/1b, 1:13
1a/1b, 1:14
1a/1b, 1:16
1a/1b, 1:12
1a/1b, 1:13
2b
35
43
94
96
98
100
40
56
R
MW/US
Oil bath
MW
MW/US
Oil bath
Oil bath
Oil bath
1.5
18
3
1.5
18
18
18
Pd/C 2.0
Pd/C 1.5
Pd/C 1.5
4-bromoanisole
4-bromoacetophenone
4-bromoacetophenone
4-bromoacetophenone
Pd
Pd(OAc)2 0.01
Pd(OAc)2 0.01,
CuBr 3.0
Pd(OAc)2 0.01,
Wilkinson 0.005
Pd(OAc)2 0.01,
CuBr 3.0
Pd(OAc)2 0.01
Pd(OAc)2 0.01
Pd(OAc)2 0.01,
CuBr 3.0
Pd(OAc)2 0.01,
A
H
2b
2b
N
20
20
4-bromoacetophenone
4-bromoacetophenone
U
Oil bath
Oil bath
18
18
76
39
2b
2b
95
56
AHCTREUNG
21
22
23
4-bromoacetophenone
4-bromoacetophenone
4-bromoacetophenone
T
MW
MW/US
MW/US
3
1.5
1.5
29
41
51
2b
2b
2b
35
55
64
R
AHCTREUNG
24
4-bromoacetophenone
A
MW/US
(N2)
Oil bath
MW
MW/US
MW/US
(N2)
1.5
59
2b
67
CuBr 3.0
Pd/C 2.0
Pd/C 1.5
Pd/C 1.5
Pd/C 1.5
25
26
27
28
4-bromoacetophenone
4-bromoacetophenone
4-bromoacetophenone
4-bromoacetophenone
18
3
1.5
1.5
90
93
81
96
1a/1b, 1:68
97
99
100
100
2b
2b
2b
[a]
All reactions were carried out at 1208C in DMA in the presence of TBAB (1 equiv.); TEA (1.5 equivs.) was used for en-
tries 1–8, K2CO3 (1.5 equivs.) for entries 9–28.
This does not include the ramp time (5 min) required to reach the temperature of 1208C.
These yields were calculated from calibration curves obtained with pure products; they include both stereoisomers E/Z.
Product numbers refer to Scheme 1.
[b]
[c]
[d]
ied the effect of adding a co-catalyst such as CuI or The co-catalyst combination Pd(II)-Rh(I) it is not un-
CuBr (2–4 mol%) or rhodium tris(triphenylphos- precedented;[37] Bankston et al. first described the use
phine) chloride (Wilkinsonꢂs catalyst, 0.005 mol%).
of Pd(II) acetate in association with Wilkinsonꢂs cata-
The beneficial effect of copper(I) on cross-cou- lyst.[38]
plings (e.g., the Stille, Sonogashira, Glaser and Suzuki
Except for entries 1–8 where the base was TEA, for
reactions) is well known.[34] Its catalytic effect was all the other reactions we used K2CO3 in the presence
also exploited in the Heck reaction[35] and a possible of TBAB. Results are summarized in Table 1. With
mechanism for it was recently proposed by Li et al.[36] 0.01–0.05 mol% Pd
(OAc)2 and 1–2 mol% Pd/C
A
The role of CuI as cocatalyst is still unclear. After ox- respectively, reactions with 4-iodoanisole and 4-bro-
idation to Cu(II) it probably favours the oxidative ad- moanisole gave very good results even under conven-
dition of Pd(0) to the alkene; this could explain why tional heating (1208C), although the starting material
we observed a co-catalytic effect only with Pd(II). had not reacted completely after 10 h. MW and com-
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Heck Reactions with Very Low Ligandless Catalyst Loads
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Scheme 1.
bined MW/US strongly accelerated the reaction; the spectively) critically affected the reaction of 4-chloro-
effect was more striking with 0.1–0.05 mol% Pd- nitrobenzene (98 vs. 12% yield). This precipitous fall
ACHTREUNG
ACHTREUNG
tion 4-iodoanisole gave a 99% yield in 30 min MW/US irradiation as before; the resulting yield was
(entry 5). Combined irradiation was extremely effec- 58% after 1.5 h (entry 45).
tive in the case of heterogeneous catalysis with 1–1.5
In order to strictly compare performances under
mol% Pd/C, giving quantitative yields after 1.5 h irra- the three energy sources (oil bath, MW and MW/US)
diation (entries 8, 16). In the coupling of 4-bromoace- we carried out additional experiments with 4-bromo-
tophenone a catalyst load reduction from 0.05 to 0.01 acetophenone and styrene using the same volumes of
mol% Pd
ACHTREUNG
heating (oil bath 1208C, 18 h) the yield fell from 95% catalyst load was uniformly Pd
AHCTREUNG
(entry 17) to 31% with only 40% conversion CuBr 3 mol%. Table 3 shows the dramatic increase of
(entry 18). The addition of a co-catalyst was surpris- reaction rates caused by MW and MW/US irradiation.
ingly effective: CuBr 3.0 mol% (entry 19) raised the
yield to 39%; better still, a very small amount of rho-
dium tris(triphenylphosphine) chloride (0.005 mol%) Conclusions
sufficed to bring the reaction close to completion
(entry 20). As shown in the tables, the favorable ef- In summary, we showed that Heck reactions can con-
fects of the co-catalyst and MW or MW/US irradia- veniently be carried out under simultaneous MW/US
tion were additive. With 1.5 mol% Pd/C under com- irradiation to afford high product yields while using
bined MW/US irradiation, 4-bromoacetophenone also very low ligandless catalyst loads. With styrene, elec-
gave a good yield (81%) after only 1.5 h (entry 27). tron-poor aryl chlorides, such as 4-chloroacetophe-
GC-MS analyses of the reacted mixtures showed in none and 4-chloronitrobenzene, gave good yields in
all cases the presence of two side products: 4-bromo- 1 h in the presence of 0.25 mol% Pd(OAc)2 and a co-
A
benzoic acid (1–9%) and 4-styrylbenzoic acid (1– catalyst (Wilkinsonꢂs 0.005 mol% or CuBr 4.0 mol%)
4%), respectively arising from the oxidation of the or 2.0–3.0 mol% Pd/C. In most cases MW heating
starting material and of the Heck coupling product. gave comparable results (although yields were 5-20%
The same by-processes were observed with 4-chloro- lower) in somewhat longer times, whereas under con-
acetophenone, yielding 4-chlorobenzoic acid (1–10%) ventional heating acceptable yields were achieved
and 4-styrylbenzoic acid (1–5%). The highest percen- only after 18 h. A possible scale-up of this protocol
tages of these undesired products resulted from com- will require a careful analysis of costs, including
bined MW/US irradiation; however their formation energy consumption besides the cost of reactors.
could easily be avoided by working under nitrogen at-
mosphere (entries 24, 28 and 38).
In general under conventional heating 4-chloroace-
tophenone and 4-chloronitrobenzene reacted with sty-
ExperimentalSection
rene (18 h) in the presence of catalyst loads exceeding
0.25 mol% for Pd(OAc)2 (entries 29 and 39) or 3
GeneralRemarks
AHCTREUNG
Commercially available reagents and solvents were used
without further purification unless otherwise noted. Stock
solutions in DMA of Pd(OAc)2 (1 mg/mL) and Wilkinsonꢂs
catalyst (1 mg/10 mL) were prepared just before use. Reac-
tions were monitored by TLC on Merck 60 F254 (0.25 mm)
plates, which were visualized by UV inspection and/or by
heating after a spray with phosphomolybdic acid. Merck
mol% for Pd/C. In these cases also, adding 0.005
mol% of Wilkinsonꢂs catalyst ( entries 32, 42 and 45)
or 4 mol% CuBr (entries 31, 34 and 41) considerably
increased yields; moreover MW or combined MW/US
irradiation strongly accelerated the reaction in all
cases (see Table 2). Lowering the catalyst load from
A
0.5 to 0.25 mol% Pd(OAc)2 (entries 39 and 40, re- silica gel was used for column chromatography (CC). IR
G
Adv. Synth. Catal. 2007, 349, 2338 – 2344
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Giovanni Palmisano et al.
FULL PAPERS
Table 2.
Entry[a] Aryl halide
Catalyst (mol%) Method
Time[b] [h]
Yield[c] [%] Product[d]
Conversion
[%]
29
30
31
4-chloroacetophenone
4-chloroacetophenone
4-chloroacetophenone
Pd
Pd(OAc)2 0.25
Pd(OAc)2 0.25,
CuBr 4.0
Pd(OAc)2 0.25,
Wilkinson 0.005
Pd(OAc)2 0.25
Pd(OAc)2 0.25,
G
Oil bath
Oil bath
Oil bath
18
18
18
95
51
92
2b
2b
2b
100
71
95
32
4-chloroacetophenone
Oil bath
18
75
2b
94
33
34
4-chloroacetophenone
4-chloroacetophenone
MW
MW/US
3
1.5
47
90
2b
2b
65
100
CuBr 4.0
Pd/C 2.0
Pd/C 2.0
Pd/C 2.0
Pd/C 2.0
35
36
37
38
4-chloroacetophenone
4-chloroacetophenone
4-chloroacetophenone
4-chloroacetophenone
Oil bath
MW
MW/US
MW/US
(N2)
18
3
1.5
1.5
75
61
87
94
2b
2b
2b
2b
100
72
100
100
39
40
41
4-chloronitrobenzene
4-chloronitrobenzene
4-chloronitrobenzene
Pd
Pd(OAc)2 0.25
Pd(OAc)2 0.25,
CuBr 4.0
Pd(OAc)2 0.25,
Wilkinson 0.005
Pd(OAc)2 0.25
Pd(OAc)2 0.25
Pd(OAc)2 0.25,
G
Oil bath
Oil bath
Oil bath
18
18
18
98
12
20
3b
3b
3b
100
25
37
42
4-chloronitrobenzene
Oil bath
18
25
3b
45
43
44
45
4-chloronitrobenzene
4-chloronitrobenzene
4-chloronitrobenzene
MW
MW/US
MW/US
3
1.5
1.5
29
35
58
3b
3b
3b
38
45
69
Wilkinson 0.005
Pd/C 3.0
Pd/C 3.0
46
47
48
4-chloronitrobenzene
4-chloronitrobenzene
4-chloronitrobenzene
Oil bath
MW
MW/US
18
3
1.5
66
85
84
3b
3b
3b
73
95
96
Pd/C 3.0
[a]
[b]
[c]
[d]
All reactions were carried out in DMA at 1208C in the presence of K2CO3 (1.5 equivs.) and TBAB (1 equiv.).
This does not include the ramp time (5 min) required to reach 1208C.
These yields were calculated from calibration curves obtained with pure products.
Product numbers refer to Scheme 1.
used for combined MW/US irradiation after
a probe
Table 3.
equipped with a Pyrexꢁ horn was inserted in it (Figure 1).
Method[a] Time
[min]
Yield[%] Products[b] Conversion
[%]
GeneralProcedure
Oil bath 15
Oil bath 30
2
44
2b
4
45
2b (2a
traces)
2b (2a
traces)
2b (2a 3%) 92
2b (2a
The aryl halide (1 mmol), styrene (1.5 mmol) and the base
(1.5 mmol) were dissolved in DMA (1 mL) in a Pyrexꢁ pres-
sure-resistant tube (for reactions under conventional heat-
ing); in DMA (10 mL) in a two-necked round-bottomed
flask equipped either with a condensing tube for reactions
under MW or with a elastomeric sleeve (Figure 1) to seal
the system for reactions under combined MW/US. The base
was TEA in the case of 4-iodoanisole, K2CO3 in the pres-
ence of TBAB (1 mmol) with all other substrates. Pd/C
MW
MW
15
30
68
69
87
88
MW/US 15
90
traces)
2b (2a 3%) 100
MW/US 30
99
[a]
Reacting mixture: 4-bromoacetophenone (1 mmol), sty-
rene (1.5 mmol), Pd(OAc)2 0.5 mol%, CuBr 3 mol%,
10% or Pd(OAc)2 and, in some cases, a co-catalyst were
A
AHCTREUNG
added to the mixture in the molar ratios indicated in Table 1
and Table 2. The mixtures were heated in an oil bath or in
the MW oven under magnetic stirring or by simultaneous
MW/US irradiation. The temperature, measured with an op-
tical-fibre thermometer, was always kept constant at 1208C;
the reaction outcome was monitored by TLC (hexane/
EtOAc, 9:1, as eluent) and GC.[39] Finally the reacted mix-
ture was poured into 2N H2SO4 (50 mL) and extracted with
EtOAc (2”50 mL). The combined organic layers were
K2CO3 (1.5 mmol), TBAB (1 mmol), DMA (10 mL). The
temperature was, for all entries, 1208C.
Product numbers that refer to Scheme 1.
[b]
spectra were recorded with a Shimadzu FT-IR 8001 spectro-
photometer, NMR spectra with a Bruker 300 Avance at
258C. MW-promoted reactions were carried out in a profes-
sional oven, Microsynth-Milestone (Italy); this was also
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Heck Reactions with Very Low Ligandless Catalyst Loads
FULL PAPERS
washed with brine, dried with anhydrous Na2SO4 and con-
centrated under vacuum.
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The better to compare results obtained under MW alone
and combined MW/US irradiation, we used the same oven
in combination with a Pyrexꢁ horn (20.3 kHz, 35 W). MW
maximum power was in all cases 200 W for the temperature
ramp up to 1208C, while MW average power during the re-
action time was 70 W when applied alone and 50 W when
used in combination with US. After evaporation of the sol-
vent from the reacted mixture, products were easily isolated
by silica-gel column chromatography, using hexane/EtOAc
mixtures in different ratios. Yields and conversion percents
determined by GC analyses[40] were comparable to the iso-
lated yields.
[21] Microwaves in Organic Synthesis, (Ed.: A. Loupy),
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Acknowledgements
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196.
This work has been carried out under the European Union
COST Action D32/006/04. We thank the University of Turin
and DSM – Nutritional Products (Basel – CH) for financial
support.
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ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Mass Selective Detector, using capillary column (length
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250 8C, detector temperature 280 8C; temperature pro-
gram: from 50 8C (3 min) to 80 8C at 3 8C/min, 80 8C to
[40] Retention times of starting materials and products
were: 4-iodoanisole, 19.28 min; 4-bromoanisole,
17.22 min; 4-bromoacetophenone, 19.67 min; 4-chloro-
acetophenone,
18.06 min;
4-nitrochlorobenzene,
18.14 min; 1a, 25.55 min; 1b, 27.74 min; 2a, 27.26 min,
2b, 29.40 min; 3a, 27.70 min; 3b, 29.76 min.
2344
asc.wiley-vch.de
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 2338 – 2344