Cyclopentyl methyl ether: An alternative solvent for palladium-catalyzed direct arylation of heteroaromatics

Article abstract of DOI:10.1002/cssc.201000405

Some ethers, such as cyclopentyl methyl ether and di-n-butyl ether, which can be considered as "greener" solvents than N,N-dimethylacetamide (DMAc) or DMF, can be advantageously employed for the palladium-catalyzed direct arylation of heteroaromatics. In the presence of such ethers and only 0.5-1 mol% of palladium catalysts at 125-150°C, the direct 5-arylation of thiazoles, thiophenes, or furans by using aryl bromides as coupling partners proceeds in moderate to high yields.

Full text of DOI:10.1002/cssc.201000405

DOI: 10.1002/cssc.201000405
Cyclopentyl Methyl Ether: An Alternative Solvent for
Palladium-Catalyzed Direct Arylation of Heteroaromatics
Kassem Beydoun and Henri Doucet*[a]
Some ethers, such as cyclopentyl methyl ether and di-n-butyl
ether, which can be considered as “greener” solvents than N,N-
dimethylacetamide (DMAc) or DMF, can be advantageously
employed for the palladium-catalyzed direct arylation of heter-
oaromatics. In the presence of such ethers and only 0.5–
1 mol% of palladium catalysts at 125–1508C, the direct 5-aryla-
tion of thiazoles, thiophenes, or furans by using aryl bromides
as coupling partners proceeds in moderate to high yields.
The direct arylation of heteroaromatics is an important field for
research in organic synthesis due to the biological or physical
properties of the aryl heteroaryl derivatives. Ohta and co-work-
ers reported in 1990 that the direct 2- or 5-arylation of several
heteroaromatics with aryl halides proceeded in moderate to
good yields by using [Pd(PPh3)4] as the catalyst and DMAc
(N,N-dimethylacetamide) as the solvent.[1] Since these exciting
results, the palladium-catalyzed direct arylation of heteroaryl
derivatives with aryl halides or triflates has proven to be a very
powerful method for the synthesis of a wide variety of arylated
heterocycles. This reaction provides a cost-effective and envi-
ronmentally attractive access for the preparation of such com-
pounds. Indeed, the major by-product of the reaction is a base
associated to HX, instead of the transition metal salts produced
under classical cross-coupling procedures, such as Suzuki, Ne-
gishi, or Stille reactions.[2] Moreover, the method avoids the
preliminary preparation of a requisite organometallic reagent,
which reduces the number of steps required to prepare these
compounds. However, these reactions are currently performed,
in most cases, by using relatively toxic solvents, such as DMF,
DMAc, N-methylpyrrolidone (NMP), or dioxane.[3–10] Some palla-
dium-catalyzed direct arylations of heteroaromatics have also
been performed by using toluene, xylene or mesitylene.[3]
Recently, a few solvents that can be considered as “green-
er”,[11] according to Anastas principles, have been employed for
direct arylations. For example, the direct arylation of oxazoles,
thiazoles, indazoles or indoles by using water as the solvent
was reported by the groups of Greaney and Djakovitch.[12]
Renꢀ and Fagnou developed biphasic conditions using water
and EtOAc for the direct arylation of thiophenes.[13a] Polyethy-
lene glycol (PEG 20000) is a useful solvent for the direct aryla-
tion of triazoles.[13b] Carbonates, such as diethylcarbonate, have
also been used successfully for the direct arylation of some
heteroaromatics such as oxazole or thiazole derivatives.[14] Fi-
nally, the ruthenium-catalyzed direct arylation of 2-arylpyri-
dines in carbonates or water has been recently reported by
Fischmeister and co-workers.[15]
enes. CPME presents several advantageous features, such as
high hydrophobicity; its limited miscibility in water allows easy
separation and recovery from water and reduces the waste
stream. Other preferable characteristics are low formation of
peroxides (compared with THF or diisopropyl ether), relative
stability under acidic and basic conditions and a narrow explo-
sion range. CPME can be manufactured by the addition of
MeOH to cyclopentene. This process produces no apparent
waste.[16] Therefore, the use of CPME as a solvent is in agree-
ment with green chemistry principles 1, 5, and 12.[11a]
CPME has already been employed for some metal-catalyzed
reactions, such as iridium-catalyzed multi-component coup-
lings.[17a] Some examples of palladium-catalyzed reactions, such
as allylic alkylations;[17b] ring opening;[17h] or couplings with thi-
ols,[17c] boron derivatives[17d–f] or amines, have also been descri-
bed.[17f] On the other hand, to the best of our knowledge, this
solvent has not been employed for direct arylations. Herein,
we report on the use of CPME for palladium-catalyzed direct
arylations of a wide range of heteroaromatic derivatives.
To determine the suitability of this solvent for palladium-cat-
alyzed direct arylations, a set of reactions with benzoxazole
and 4-bromobenzonitrile as the coupling partners were carried
out under previously reported reaction conditions, but using
CPME as the solvent (Scheme 1).[14] In the presence of polar
solvents, such as DMF, NMP, dioxane or diethylcarbonate, high
yields of coupling product 1 have been obtained.[9e,14] In CPME
only low yields of 1 were obtained, mainly as a result of low
conversion of the aryl bromide and also the formation of bi-
phenyl-4,4’-dicarbonitrile.
Then, we examined the reactivity of 2-n-propylthiazole in
CPME. Since the 2-arylation of benzoxazole and the 5-arylation
of thiazoles proceed by different mechanisms, we expected dif-
ferent reactivities for these two heteroarenes. The direct 2-ary-
lation of oxazoles seemed to proceed through a simple depro-
tonation of the oxazole by the base,[18] whereas the 5-arylation
[a] K. Beydoun, Dr. H. Doucet
To the best of our knowledge, so far, ethers such as cyclo-
pentyl methyl ether (CPME) or di-n-butyl ether have not been
employed as solvents for palladium-catalyzed direct arylations.
The use of such solvents would provide an environmentally at-
tractive procedure for the preparation of arylated heteroar-
Institut Sciences Chimiques de Rennes
UMR 6226 CNRS-Universitꢀ de Rennes 1
“Catalyse et Organometalliques”, Campus de Beaulieu
35042 Rennes (France)
Fax: (+33)0223236939
E-mail: henri.doucet@univ-rennes1.fr
526
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ChemSusChem 2011, 4, 526 – 534

Cyclopentyl Methyl Ether as Alternative Solvent
or PPh3) were also added to the reaction mixture with
Pd(OAc)2 as the palladium source. With these catalysts, good
conversions were generally obtained when 0.5 mol% catalyst
was employed. On the other hand, in the presence of
0.1 mol% catalyst, the yield was not improved (Table 1, en-
tries 14–18). Therefore, we employed Pd(OAc)2 as the catalyst
for the arylation of 2-n-propylthiazole with other aryl bro-
mides.
Scheme 1. Coupling of benzoxazole with 4-bromobenzonitrile in CPME;
dppb=1,4-bis(diphenylphosphino)butane.
The reaction of other para-substituted, electron-deficient
aryl bromides, such as 4-bromoacetophenone, 4-bromobenzal-
dehyde or 4-bromonitrobenzene, with 2-n-propylthiazole gave
the expected products 3, 5 and 8 in 75–83% yields (Table 2,
entries 1, 3 and 7). Slower reactions were observed when using
4-(trifluoromethyl)bromobenzene or methyl 4-bromobenzoate.
However, with longer reaction times (48 h), high conversions
of these aryl bromides and high yields of coupling products 6
and 7 were obtained (Table 2, entries 4–6). By using the elec-
tron-rich aryl bromide, 4-bromotoluene, product 10 was ob-
tained in only 20% yield. With this reactant, even long reaction
times (48 h) or the use of Pd(OAc)2/dppe or [Pd(C3H5)Cl(dppb)]
as the catalysts did not result in high conversions and yields
(Table 2, entries 12–15). This is certainly due to a slow oxidative
addition of this slightly deactivated aryl bromide to palladium.
Next, the reactivity of four meta-substituted aryl bromides
was examined (Table 2, entries 16–19). As expected, similar re-
sults to those in the presence of para-substituted aryl bro-
mides were obtained. 3-Bromoacetophenone, 3-bromobenzal-
dehyde, 3-(trifluoromethyl)bromobenzene or 3,5-bis(trifluoro-
methyl)bromobenzene gave 11–14 in 62–87% yields.
of thiazoles appeared to occur through a concerted metalla-
tion–deprotonation (CMD) mechanism.[8b]
By employing 2-n-propylthiazole and 4-bromobenzonitrile as
the coupling partners, at 1008C for 19 h, in the presence of
KOAc as the base and Pd(OAc)2 (1 mol%) in CPME, the corre-
sponding 5-arylation product 2 was obtained in good yield
(Table 1, entry 1). At a higher temperature (1258C) using as
little as 0.5 mol% Pd(OAc)2, product 2 was obtained in 88%
yield (Table 1, entry 3). The use of other bases, such as NaOAc,
CsOAc or carbonates, gave only partial conversion of the aryl
bromide (Table 1, entries 5–8). Then, we studied the reaction
1
using = [{PdCl(C3H5)}2] or PdCl2 as the catalysts precursors with
2
substrate/catalyst ratios of 200 (Table 1, entries 9 and 10).
Slightly lower conversions were observed than in the presence
of Pd(OAc)2. In the presence of 0.5 mol% [Pd(C3H5)Cl(dppb)] as
the catalyst, product 2 was obtained in only 72% conversion
(Table 1, entry 13). A few other phosphine ligands (dppe, dppb
Due to their steric or coordination properties, ortho substitu-
ents on aryl halides generally have more influence on the
yields of palladium-catalyzed reactions.[19] 2-Bromobenzalde-
hyde, 2-bromobenzonitrile or 2-bromobenzotrifluoride gave
15, 17 and 18 in 77–91% yields (Table 2, entries 20, 22, and
23). The reaction was also successfully realised with methyl 2-
bromobenzoate to give 16, albeit in moderate 58% yield due
to the formation of several side products (Table 2, entry 21).
We also explored the reactivity of 2-n-propylthiazole with
some heteroaryl bromides (Table 2, entries 24–27). Good per-
formances of this novel friendly protocol in direct couplings
with 4-bromopyridine, 3-bromoquinoline, 4-bromoisoquinoline
or 5-bromopyrimidine were observed. With these substrates,
the target products 19–22 were obtained in 56–74% yields.
For all of these reactions, very high selectivity in favour of the
formation of the 5-arylation products, 2–22, was observed. No
formation of 4-arylated or 4,5-diarylated thiazoles was detect-
ed.
Table 1. Influence of the reaction conditions for palladium-catalyzed
direct coupling of 2-n-propylthiazole with 4-bromobenzonitrile in CPME.[a]
Entry
Catalyst
S/C[b]
ratio
Base
T
[8C]
t
[h]
Conv.[c]
[%]
1
2
3
4
5
6
7
8
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
100
100
200
1000
200
200
200
200
200
200
100
100
200
200
200
1000
200
1000
KOAc
KOAc
KOAc
KOAc
NaOAc
CsOAc
K2CO3
Cs2CO3
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
100
125
125
125
125
125
125
125
125
125
110
125
125
125
125
125
125
120
19
17
19
18
19
19
19
19
19
19
16
18
19
19
19
19
19
19
79 (70)
99
99 (88)
6
5
68
50
31
65
95
50
99
72
75
100
0
100
5
9
1= [{PdCl(C3H5)}2]
2
10
11
12
13
14
15
16
17
18
PdCl2
[Pd(C3H5)Cl(dppb)]
[Pd(C3H5)Cl(dppb)]
[Pd(C3H5)Cl(dppb)]
Pd(OAc)2/dppb
Pd(OAc)2/dppe
Pd(OAc)2/dppe
Pd(OAc)2/2PPh3
Pd(OAc)2/2PPh3
Then, we studied the reactivity of several other heteroaro-
matics by using CPME as the solvent (Tables 3–6). The 4-aryla-
tion of 3,5-dimethylisoxazole was found to be more difficult.
We had previously observed that, in DMAc, the direct 5-aryla-
tion of thiazoles is easier than the 4-arylation of isoxazoles.[8d,10]
The use of Pd(OAc)2 as the catalyst gave only traces of desired
product 23 (Table 3, entry 2). On the other hand, product 23
was obtained in 40% yield when [Pd(C3H5)Cl(dppb)] was em-
ployed as the catalyst (Table 3, entry 1). With this reactant, the
use of di-n-butyl ether instead of CPME as the solvent and a
[a] Conditions: 2-n-propylthiazole (2 equiv), 4-bromobenzonitrile (1 equiv),
base (2 equiv), CPME; dppe=1,2-bis(diphenylphosphino)ethane. [b] Sub-
strate/catalyst ratio. [c] Conversion of 4-bromobenzonitrile; yields in pa-
rentheses are isolated yields.
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527

H. Doucet and K. Beydoun
Table 2. Palladium-catalyzed coupling of 2-n-propylthiazole with aryl bro-
mides in CPME.[a]
Table 2. (Continued)
Entry
Aryl bromide
Product
Yield [%][b]
90
Entry
1
Aryl bromide
Product
Yield [%][b]
75
23
18
3
4
5
24
25
61[c]
56[c]
2
3
70
83
19
20
26
27
74[c]
4
5
62
78[c]
21
6
7
8
73[c]
6
7
71[c]
82
22
[a] Conditions: Pd(OAc)2 (0.005 equiv), 2-n-propylthiazole (2 equiv), aryl
bromide (1 equiv), KOAc (2 equiv), CPME, 1258C, 24 h. [b] Isolated yields.
[c] 48 h. [d] Pd(OAc)2 (0.005 equiv), dppe (0.005 equiv) as the catalyst.
[e] [Pd(C3H5)Cl(dppb)] (0.005 equiv) as the catalyst.
8
9
10
11
25
31[c]
45[d]
43[e]
9
12
13
14
15
15
20[c]
24[d]
34[e]
higher reaction temperature (1508C) gave 23 in 89% yield
(Table 3, entry 4). Di-n-butyl ether is also considered to be a
greener solvent than DMAc due to its low environmental
impact, relatively high flash point (258C) and the formation of
a limited amount of waste after recycling or incineration. It is
already used as a solvent in the manufacturing of pharmaceuti-
cal intermediates. By using this solvent, low to moderate yields
10
11
16
64[c]
17
18
19
68[c]
62[c]
87[c]
Table 3. Palladium-catalyzed coupling of 3,5-dimethylisoxazole with aryl
bromides in CPME or di-n-butyl ether.[a]
12
13
Entry
Aryl bromide
Product
Yield [%][b]
1
2
3
4
40
5[c]
10[d]
89[d,e]
23
24
25
52[d,e]
62[d,e]
38[d,e]
14
15
5
6
7
20
77[c]
21
22
58[c]
16
17
26
91
[a] Conditions: [Pd(C3H5)Cl(dppb)] (0.005 equiv), 3,5-dimethylisoxazole
(2 equiv), aryl bromide (1 equiv), KOAc (2 equiv), CPME, 1258C, 48 h.
[b] Isolated yields. [c] Pd(OAc)2 (0.005 equiv). [d] 1508C in autoclave.
[e] Di-n-butyl ether instead of CPME.
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Cyclopentyl Methyl Ether as Alternative Solvent
Table 4. Palladium-catalyzed coupling of thiophene derivatives with aryl
bromides in CPME.[a]
Table 4. (Continued)
Entry
Aryl bromide
Product
Yield [%][b]
41
17
78
Entry
Aryl bromide
Product
Yield [%][b]
42
43
44
1
2
77
2[c]
18
19
20
77
27
28
3
88
70
4
5
81
56
29
30
77[d]
6
7
62
71
45
46
31
32
33
21
22
23
48[e]
56
47
48
8
73
53
9
81
47
76
[a] Conditions: [Pd(C3H5)Cl(dppb)] (0.01 equiv), thiophene derivative
(2 equiv), aryl bromide (1 equiv), KOAc (2 equiv), CPME, 1308C, 48 h.
[b] Isolated yields. [c] Pd(OAc)2 (0.01 equiv). [d] 16 h. [e] 72 h.
34
35
10
11
of 24–26 were obtained with 4-bromobenzaldehyde, 4-bromo-
nitrobenzene or 2-bromobenzonitrile (Table 3, entries 2–4).
High yields were generally obtained for the coupling of thio-
phene derivatives with aryl bromides in CPME (Table 4). How-
ever, again the use of Pd(OAc)2 as the catalyst gave only traces
of desired product 27, whereas [Pd(C3H5)Cl(dppb)] gave 27 in
77% yield (Table 4, entries 1 and 2). A wide range of electron-
deficient aryl bromides were coupled with thiophene 2-carbon-
itrile and the products 27–34 and 36–38 were obtained in 52–
88% yield. A lower yield (47%) was obtained in the presence
of 2-bromonaphthalene (Table 4, entry 10). Highly functional-
ized thiophene derivatives were also employed successfully.
For example, 2-acetyl-4-chlorothiophene reacted with electron-
deficient aryl bromides, such as 4-bromobenzonitrile, 4-bromo-
benzaldehyde or 4-bromonitrobenzene, to give 39–44 in 70–
82% yields (Table 4, entries 14–19). In the course of this reac-
tion no cleavage of the CÀCl bond of the chlorothiophene de-
rivative was detected. The reaction of 2-(4-bromothiophen-2-
yl)-1,3-dioxolane with 4-bromobenzonitrile also proceeded
nicely in CPME to give 45 in 77% yield without cleavage of the
CÀBr bond (Table 4, entry 20). In the presence of 2-formyl- or
36
12
13
67
52
37
38
14
15
16
74
81
82
39
40
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529

H. Doucet and K. Beydoun
2-acetylthiophene and 4-bromobenzonitrile as the coupling
partners, products 46 and 48 were obtained in moderate
yields due to partial decomposition (Table 4, entries 21 and
23).
eral para-, meta- or ortho-substituted aryl bromides and also
heteroaryl bromides were coupled with 1-(furan-2-yl)butan-1-
one (Table 5, entries 1–9). Again, for these reactions, [Pd-
(C3H5)Cl(dppb)] was employed as the catalyst because
Pd(OAc)2 was found to be ineffective. In all cases, the reaction
was very regioselective in favor of 5-arylation and 49–56 were
obtained in 51–78% yields. 2-n-Butylfuran and methyl 2-meth-
ylfuran-3-carboxylate were found to be less reactive. With
these two substrates the use of di-n-butyl ether instead of
CPME gave higher yields (Table 5, entries 11–14).
The direct use of furan derivatives is an important field for
research in green chemistry, since some of them can be ob-
tained from agricultural wastes rich in pentosan polymers. Sev-
Table 5. Palladium-catalyzed coupling of furan derivatives with aryl bro-
mides in CPME.[a]
Slow reactions were observed in the presence of 1,2-dime-
thylimidazole in CMPE (Table 6). A low yield of 30% of product
60 was obtained by using 0.5 or 2 mol% of Pd(OAc)2 as the
catalyst at 1258C (Table 6, entries 1 and 2). On the other hand,
the use of 2 mol% of [Pd(C3H5)Cl(dppb)] as the catalyst with
di-n-butyl ether as the solvent at 1508C gave 60 in 70% yield
(Table 6, entry 5).
Entry
Aryl bromide
Product
Yield [%][b]
1
2
78
8[c]
49
50
Table 6. Coupling of 1,2-dimethylimidazole with 4-bromobenzonitrile.
3
4
5
6
72
75
65
51
Entry
Catalyst ([mol%])
T [8C]
Yield [%]
51
52
1
2
3
4
5
Pd(OAc)2 (0.5)
Pd(OAc)2 (2)
[Pd(C3H5)Cl(dppb)] (1)
[Pd(C3H5)Cl(dppb)] (1)
[Pd(C3H5)Cl(dppb)] (2)
125
125
125
150
150
30
30
17
38[a]
70[a]
[a] Di-n-butyl ether instead of CPME as the solvent.
53
54
55
Conclusion
7
62
56
60
41
These results demonstrate that some ethers, such as CPME and
in some cases di-n-butyl ether, which can be considered as
greener solvents than DMAc or DMF, can be advantageously
employed for the direct arylation of heteroaromatics. In the
presence of CPME and palladium catalysts (0.5–1 mol%) at
125–1508C, the direct 5-arylation of thiazoles, thiophenes or
furans with aryl bromides as coupling partners proceeds in
moderate to high yields. For all these reactions, CPME >99%
was used without any purification. Because this solvent is hy-
drophobic, there is no need to dry it before use. It should be
noted that a wide range of functional groups, such as acetyl,
propionyl, formyl, ester, nitro, nitrile, trifluoromethyl, or fluoro,
on the aryl bromide is tolerated. The major by-product of
these couplings is CsBr or KBr instead of the transition metal
salts obtained with more classical coupling procedures. For
these reasons, this novel process should give an economically
viable and environmentally attractive access to several arylated
heteroaromatics.
8
9
56
10
57
58
11
12
0
57[d]
13
14
41
50[d,e]
59
[a] Conditions: [Pd(C3H5)Cl(dppb)] (0.01 equiv), furan derivative (2 equiv),
aryl bromide (1 equiv), KOAc (2 equiv), CPME, 1308C, 48 h. [b] Isolated
yields. [c] Pd(OAc)2 (0.01 equiv). [d] Di-n-butyl ether instead of CPME as
the solvent. [e] 1508C.
Experimental Section
CPME >99%, di-n-butyl ether >99%, and Pd(OAc)2 were pur-
chased from Acros Organics and were not purified before use. Het-
530
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ChemSusChem 2011, 4, 526 – 534

Cyclopentyl Methyl Ether as Alternative Solvent
eroarenes, KOAc and Cs2CO3 were purchased from Alfa Aesar and
were not purified before use. NMR measurements were performed
by using a Bruker instrument, at 200 Mhz. Elemental analyses were
performed by using a Thermo-Finnigan Flash EA 1112 instrument.
3-(2-Propylthiazol-5-yl)benzaldehyde (12):[8d] 3-Bromobenzaldehyde
(0.184 g, 1 mmol) and 2-n-propylthiazole (0.254 g, 2 mmol) afford-
ed 12 (0.157 g, 68%).
2-Propyl-5-(3-trifluoromethylphenyl)thiazole (13):[8d] 3-(Trifluorome-
thyl)bromobenzene (0.225 g, 1 mmol) and 2-n-propylthiazole
(0.254 g, 2 mmol) afforded 13 (0.168 g, 62%).
Preparation of the [Pd(C3H5)Cl(dppb)] catalyst[20]
5-[3,5-Bis(trifluoromethyl)phenyl]-2-propylthiazole (14):[8d] 3,5-Bis(tri-
fluoromethyl)bromobenzene (0.293 g, 1 mmol) and 2-n-propylthia-
zole (0.254 g, 2 mmol) afforded 14 (0.295 g, 87%).
An oven-dried 40 mL Schlenk tube equipped with a magnetic stir-
ring bar was charged with [{Pd(C3H5)Cl}2] (182 mg, 0.5 mmol) and
dppb (426 mg, 1 mmol) under an argon atmosphere. Anhydrous
dichloromethane (10 mL) was added and the solution was stirred
at room temperature for 20 min. The solvent was removed in
vacuo and the yellow powder was used without purification.
31P NMR (81 MHz, CDCl3): d=19.3 ppm (s).
2-(2-Propylthiazol-5-yl)benzaldehyde (15):[8d] 2-Bromobenzaldehyde
(0.185 g, 1 mmol) and 2-n-propylthiazole (0.254 g, 2 mmol) afford-
ed 15 (0.178 g, 77%).
Methyl 4-(2-propylthiazol-5-yl)benzoate (16): Methyl 2-bromoben-
zoate (0.205 g, 1 mmol) and 2-n-propylthiazole (0.254 g, 2 mmol)
afforded 16 (0.151 g, 58%). 1H NMR (200 MHz, CDCl3, 258C): d=
7.80 (d, J=8.2 Hz, 1H), 7.60–7.30 (m, 4H), 3.78 (s, 3H), 3.01 (t, J=
7.5 Hz, 2H), 1.89 (sextet, J=7.5 Hz, 2H), 1.05 ppm (t, J=7.5 Hz,
3H); 13C NMR (50 MHz, CDCl3, 258C): d=171.7, 168.3, 140.3, 135.7,
131.6, 131.5, 131.3, 131.2, 129.9, 128.3, 52.2, 35.4, 23.3, 13.7 ppm;
elemental analysis calcd (%) for C14H15NO2S (261.34): C 64.34, H
5.79; found: C 64.47, H 5.61.
Typical experiment for coupling reactions
The reaction of the aryl bromide (1 mmol), heteroaromatic
(2 mmol) and Cs2CO3 (0.651 g, 2 mmol) or KOAc (0.196, 2 mmol) at
125–1508C in CPME or di-n-butyl ether (5 mL) in the presence of
[Pd(C3H5)Cl(dppb)] or Pd(OAc)2 under argon afforded the corre-
sponding product after evaporation of the solvent and filtration
through silica gel (pentane/ether) (see Tables 1–6 and Scheme 1
for conditions).
2-(2-Propylthiazol-5-yl)benzonitrile (17):[8d] 2-Bromobenzonitrile
(0.182 g, 1 mmol) and 2-n-propylthiazole (0.254 g, 2 mmol) afford-
ed 17 (0.207 g, 91%).
4-Benzoxazol-2-yl-benzonitrile (1):[14] 4-Bromobenzonitrile (0.182 g,
1 mmol) and benzoxazole (0.238 g, 2 mmol) afforded 1 (0.099 g,
45%).
2-Propyl-5-(2-trifluoromethylphenyl)thiazole (18):[8d] 2-(Trifluorome-
thyl)bromobenzene (0.225 g, 1 mmol) and 2-n-propylthiazole
(0.254 g, 2 mmol) afforded 18 (0.244 g, 90%).
2-(2-Propylthiazol-5-yl)benzonitrile
(2):[8d]
4-Bromobenzonitrile
(0.182 g, 1 mmol) and 2-n-propylthiazole (0.254 g, 2 mmol) afford-
ed 2 (0.201 g, 88%).
5-(2-Propylthiazol-5-yl)pyrimidine
(19):[8d]
5-Bromopyrimidine
4-(2-Propylthiazol-5-yl)acetophenone (3):[8d] 4-Bromoacetophenone
(0.199 g, 1 mmol) and 2-n-propylthiazole (0.254 g, 2 mmol) afford-
ed 3 (0.184 g, 75%).
(0.159 g, 1 mmol) and 2-n-propylthiazole (0.254 g, 2 mmol) afford-
ed 19 (0.125 g, 61%).
4-(2-Propylthiazol-5-yl)pyridine (20):[8e] 4-Bromopyridine hydrochlo-
ride (0.195 g, 1 mmol) and 2-n-propylthiazole (0.254 g, 2 mmol) af-
forded 20 (0.114 g, 56%).
4-(2-Propylthiazol-5-yl)propiophenone (4):[8d] 4-Bromopropiophe-
none (0.213 g, 1 mmol) and 2-n-propylthiazole (0.254 g, 2 mmol)
afforded 4 (0.181 g, 70%).
3-(2-Propylthiazol-5-yl)quinoline (21):[8d] 3-Bromoquinoline (0.208 g,
1 mmol) and 2-n-propylthiazole (0.254 g, 2 mmol) afforded 21
(0.188 g, 74%).
4-(2-Propylthiazol-5-yl)benzaldehyde (5):[8d] 4-Bromobenzaldehyde
(0.184 g, 1 mmol) and 2-n-propylthiazole (0.254 g, 2 mmol) afford-
ed 5 (0.192 g, 83%).
4-(2-Propylthiazol-5-yl)isoquinoline (22):[8d] 4-Bromoisoquinoline
(0.208 g, 1 mmol) and 2-n-propylthiazole (0.254 g, 2 mmol) afford-
ed 22 (0.186 g, 73%).
Methyl 4-(2-propylthiazol-5-yl)benzoate (6):[8d] Methyl 4-bromoben-
zoate (0.205 g, 1 mmol) and 2-n-propylthiazole (0.254 g, 2 mmol)
afforded 6 (0.204 g, 78%).
4-(3,5-Dimethylisoxazol-4-yl)benzonitrile (23):[10] 4-Bromobenzoni-
trile (0.182 g, 1 mmol) and 3,5-dimethylisoxazole (0.192 g, 2 mmol)
afforded 23 (0.176 g, 89%).
5-[4-(Trifluoromethyl)phenyl]-2-propylthiazole (7):[8d] 4-Trifluorome-
thylbromobenzene (0.225 g, 1 mmol) and 2-n-propylthiazole
(0.254 g, 2 mmol) afforded 7 (0.192 g, 71%).
4-(3,5-Dimethylisoxazol-4-yl)benzaldehyde (24):[10] 4-Bromobenzal-
dehyde (0.187 g, 1 mmol) and 3,5-dimethylisoxazole (0.192 g,
2 mmol) afforded 24 (0.105 g, 52%).
5-(4-Nitrophenyl)-2-propylthiazole (8):[8d] 4-Bromonitrobenzene
(0.202 g, 1 mmol) and 2-n-propylthiazole (0.254 g, 2 mmol) afford-
ed 8 (0.203 g, 82%).
3,5-Dimethyl-4-(4-nitrophenyl)isoxazole (25):[10] 4-Bromonitroben-
zene (0.202 g, 1 mmol) and 3,5-dimethylisoxazole (0.192 g, 2 mmol)
afforded 25 (0.135 g, 62%).
5-(4-Fluorophenyl)-2-propylthiazole (9):[8d] 4-Fluorobromobenzene
(0.175 g, 1 mmol), and 2-n-propylthiazole (0.254 g, 2 mmol) afford-
ed 9 (0.069 g, 31%).
2-(3,5-Dimethylisoxazol-4-yl)benzonitrile (26):[10] 2-Bromobenzoni-
trile (0.182 g, 1 mmol) and 3,5-dimethylisoxazole (0.192 g, 2 mmol)
afforded 26 (0.075 g, 38%).
2-Propyl-5-p-tolylthiazole (10):[8d] 4-Bromotoluene (0.171 g, 1 mmol)
and 2-n-propylthiazole (0.254 g, 2 mmol) afforded 10 (0.044 g,
20%).
1-[3-(2-Propylthiazol-5-yl)phenyl]ethanone (11):[8d] 3-Bromoaceto-
phenone (0.199 g, 1 mmol) and 2-n-propylthiazole (0.254 g,
2 mmol) afforded 11 (0.157 g, 64%).
5-(4-Cyanophenyl)thiophene-2-carbonitrile (27):[4h] 4-Bromobenzo-
nitrile (0.182 g, 1 mmol) and thiophene 2-carbonitrile (0.218 g,
2 mmol) afforded 27 (0.162 g, 77%).
ChemSusChem 2011, 4, 526 – 534
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemsuschem.org
531

H. Doucet and K. Beydoun
5-(4-Acetylphenyl)thiophene-2-carbonitrile (28):[4h] 4-Bromoaceto-
phenone (0.199 g, 1 mmol) and thiophene 2-carbonitrile (0.218 g,
2 mmol) afforded 28 (0.200 g, 88%).
137.6, 125.9, 124.5, 112.4, 110.1 ppm; elemental analysis calcd (%)
for C9H5N3S (187.22): C 57.74, H 2.69; found: C 57.84, H 2.54.
5-Pyridin-4-yl-thiophene-2-carbonitrile (38): 4-Bromopyridine hydro-
chloride (0.195 g, 1 mmol) and thiophene 2-carbonitrile (0.218 g,
2 mmol) afforded 38 (0.097 g, 52%). 1H NMR (200 MHz, CDCl3,
258C): d=8.70 (d, J=4.5 Hz, 2H), 7.67 (d, J=3.6 Hz, 1H), 7.55–
7.40 ppm (m, 3H); 13C NMR (50 MHz, CDCl3, 258C): d=149.9,
147.1, 138.2, 137.4, 124.3, 119.2, 112.6, 109.7 ppm; elemental analy-
sis calcd (%) for C10H6N2S (186.23): C 64.49, H 3.25; found: C 64.51,
H 3.41.
5-(4-Formylphenyl)thiophene-2-carbonitrile (29):[4h] 4-Bromobenzal-
dehyde (0.185 g, 1 mmol) and thiophene 2-carbonitrile (0.218 g,
2 mmol) afforded 29 (0.173 g, 81%).
5-(4-Nitrophenyl)thiophene-2-carbonitrile (30): 4-Bromonitroben-
zene (0.202 g, 1 mmol) and thiophene 2-carbonitrile (0.218 g,
2 mmol) afforded 30 (0.129 g, 56%). 1H NMR (200 MHz, CDCl3,
258C): d=8.32 (d, J=8.2 Hz, 2H), 7.80 (d, J=8.2 Hz, 2H), 7.68 (d,
J=3.6 Hz, 1H), 7.46 ppm (d, J=3.6 Hz, 1H); 13C NMR (50 MHz,
CDCl3, 258C): d=148.8, 148.3, 139.0, 138.5, 127.4, 126.0, 125.1,
114.1, 111.3 ppm; elemental analysis calcd (%) for C11H6N2O2S
(230.24): C 57.38, H 2.63; found: C 57.41, H 2.50.
4-(5-Acetyl-3-chlorothiophen-2-yl)benzonitrile (39): 4-Bromobenzo-
nitrile (0.182 g, 1 mmol) and 2-acetyl-4-chlorothiophene (0.321 g,
2 mmol) afforded 39 (0.193 g, 74%). 1H NMR (200 MHz, CDCl3,
258C): d=7.84 (d, J=8.2 Hz, 2H), 7.77 (d, J=8.2 Hz, 2H), 7.62 (s,
1H), 2.60 ppm (s, 3H); 13C NMR (50 MHz, CDCl3, 258C): d=190.0,
142.8, 142.3, 136.2, 134.2, 133.0, 129.7, 123.7, 118.7, 113.2,
26.8 ppm; elemental analysis calcd (%) for C13H8ClNOS (261.73): C
59.66, H 3.08; found: C 59.49, H 2.89.
5-(3-Cyanophenyl)thiophene-2-carbonitrile (31):[4h] 3-Bromobenzo-
nitrile (0.182 g, 1 mmol) and thiophene 2-carbonitrile (0.218 g,
2 mmol) afforded 31 (0.130 g, 62%).
5-(3-Acetylphenyl)thiophene-2-carbonitrile (32): 3-Bromoacetophe-
none (0.199 g, 1 mmol) and thiophene 2-carbonitrile (0.218 g,
2 mmol) afforded 32 (0.161 g, 71%). 1H NMR (200 MHz, CDCl3,
258C): d=8.18 (s, 1H), 7.97 (d, J=7.8 Hz, 1H), 7.78 (d, J=7.8 Hz,
1H), 7.62 (d, J=3.6 Hz, 1H), 7.55 (t, J=7.5 Hz, 1H), 7.37 (d, J=
3.6 Hz, 1H), 2.66 ppm (s, 3H); 13C NMR (50 MHz, CDCl3, 258C): d=
196.2, 149.4, 137.5, 136.9, 131.8, 129.7, 128.7, 128.2, 124.9, 123.0,
113.1, 107.9, 25.7 ppm; elemental analysis calcd (%) for C13H9NOS
(227.28): C 68.70, H 3.99; found: C 68.73, H 4.14.
1-[4-(5-Formyl-3-chlorothiophen-2-yl)-phenyl]ethanone (40): 4-Bro-
mobenzaldehyde (0.187 g, 1 mmol) and 2-acetyl-4-chlorothiophene
(0.321 g, 2 mmol) afforded 40 (0.214 g, 81%). 1H NMR (200 MHz,
CDCl3, 258C): d=10.08 (s, 1H), 7.99 (d, J=8.4 Hz, 2H), 7.90 (d, J=
8.4 Hz, 2H), 7.61 (s, 1H), 2.59 ppm (s, 3H); 13C NMR (50 MHz,
CDCl3, 258C): d=190.4, 188.6, 141.7, 141.1, 136.1, 135.3, 132.8,
129.0, 128.2, 122.1, 25.4 ppm; elemental analysis calcd (%) for
C13H9ClO2S (264.73): C 58.98, H 3.43; found: C 59.10, H 3.42.
5-(3-Formylphenyl)thiophene-2-carbonitrile (33): 3-Bromobenzalde-
hyde (0.185 g, 1 mmol) and thiophene 2-carbonitrile (0.218 g,
2 mmol) afforded 33 (0.156 g, 73%). 1H NMR (200 MHz, CDCl3,
258C): d=10.08 (s, 1H), 8.11 (s, 1H), 7.95–7.80 (m, 2H), 7.70–7.60
(m, 2H), 7.39 ppm (d, J=3.6 Hz, 1H); 13C NMR (50 MHz, CDCl3,
258C): d=191.8, 150.3, 138.9, 137.6, 133.7, 132.3, 131.1, 130.6,
127.2, 124.7, 114.4, 109.7 ppm; elemental analysis calcd (%) for
C12H7NOS (213.26): C 67.58, H 3.31; found: C 67.51, H 3.39.
1-[4-(5-Acetyl-3-chlorothiophen-2-yl)-phenyl]ethanone (41): 4-Bro-
moacetophenone (0.199 g, 1 mmol) and 2-acetyl-4-chlorothio-
phene (0.321 g, 2 mmol) afforded 41 (0.228 g, 82%). 1H NMR
(200 MHz, CDCl3, 258C): d=8.03 (d, J=8.2 Hz, 2H), 7.80 (d, J=
8.2 Hz, 2H), 7.59 (s, 1H), 2.64 (s, 3H), 2.57 ppm (s, 3H); 13C NMR
(50 MHz, CDCl3, 258C): d=197.6, 190.1, 143.5, 142.2, 137.5, 136.2,
134.2, 129.2, 129.1, 123.7, 27.1, 26.8 ppm; elemental analysis calcd
(%) for C14H11ClO2S (278.75): C 60.32, H 3.98; found: C 60.40, H 3.90.
5-[3-(Trifluoromethyl)phenyl]thiophene-2-carbonitrile (34): 3-(Tri-
1-[4-Chloro-5-(4-trifluoromethylphenyl)thiophen-2-yl]ethanone (42):
4-Trifluoromethylbromobenzene (0.225 g, 1 mmol) and 2-acetyl-4-
chlorothiophene (0.321 g, 2 mmol) afforded 42 (0.237 g, 78%).
1H NMR (200 MHz, CDCl3, 258C): d=7.83 (d, J=8.2 Hz, 2H), 7.74
(d, J=8.2 Hz, 2H), 7.61 (s, 1H), 2.59 ppm (s, 3H); 13C NMR (50 MHz,
CDCl3, 258C): d=189.6, 142.6, 141.9, 134.8, 133.6, 131.0 (q, J=
32.5 Hz), 129.1, 125.8 (q, J=3.8 Hz), 124.0 (q, J=273.0 Hz), 122.9,
26.3 ppm; elemental analysis calcd (%) for C13H8ClF3OS (304.72): C
51.24, H 2.65; found: C 51.30, H 2.57.
fluoromethyl)bromobenzene (0.225 g, 1 mmol) and thiophene 2-
1
carbonitrile (0.218 g, 2 mmol) afforded 34 (0.205 g, 81%). H NMR
(200 MHz, CDCl3, 258C): d=7.85 (s, 1H), 7.79 (d, J=8.2 Hz, 1H),
7.75–7.55 (m, 3H), 7.37 ppm (d, J=3.6 Hz, 1H); 13C NMR (50 MHz,
CDCl3, 258C): d=148.6, 137.4, 132.0, 131.2 (q, J=33.2 Hz), 128.9,
128.7, 124.9 (q, J=3.7 Hz), 123.4 (q, J=272.0 Hz), 123.3, 122.1 (q,
J=3.8 Hz), 112.9, 108.4 ppm; elemental analysis calcd (%) for
C12H6F3NS (253.24): C 56.91, H 2.39; found: C 56.78, H 2.55.
5-Naphthalen-2-ylthiophene-2-carbonitrile (35): 2-Bromonaphtha-
lene (0.207, 1 mmol) and thiophene 2-carbonitrile (0.218 g,
2 mmol) afforded 35 (0.111 g, 47%). 1H NMR (200 MHz, CDCl3,
258C): d=8.07 (s, 1H), 7.95–7.80 (m, 3H), 7.75–7.50 (m, 4H),
7.39 ppm (d, J=3.6 Hz, 1H); 13C NMR (50 MHz, CDCl3, 258C): d=
152.3, 138.9, 133.9, 133.7, 129.9, 129.6, 128.7, 128.2, 127.5, 127.4,
125.9, 124.3, 123.9, 114.9, 108.7 ppm; elemental analysis calcd (%)
for C15H9NS (235.30): C 76.56, H 3.86; found: C 76.41, H 3.89.
1-[4-Chloro-5-(4-nitrophenyl)thiophen-2-yl]ethanone (43): 4-Bromo-
nitrobenzene (0.202 g, 1 mmol) and 2-acetyl-4-chlorothiophene
(0.321 g, 2 mmol) afforded 43 (0.217 g, 77%). 1H NMR (200 MHz,
CDCl3, 258C): d=8.32 (d, J=8.2 Hz, 2H), 7.90 (d, J=8.2 Hz, 2H),
7.62 (s, 1H), 2.60 ppm (s, 3H); 13C NMR (50 MHz, CDCl3, 258C): d=
188.6, 146.8, 141.6, 140.4, 136.6, 132.7, 128.5, 123.0, 122.6,
25.4 ppm; elemental analysis calcd (%) for C12H8ClNO3S (281.72): C
51.16, H 2.86; found: C 51.07, H 2.80.
5-(2-Cyanophenyl)thiophene-2-carbonitrile (36):[4h] 2-Bromobenzo-
nitrile (0.182 g, 1 mmol) and thiophene 2-carbonitrile (0.218 g,
2 mmol) afforded 36 (0.160 g, 76%).
1-(4-Chloro-5-pyridin-4-ylthiophen-2-yl)ethanone (44): 4-Bromopyri-
dine hydrochloride (0.195 g, 1 mmol) and 2-acetyl-4-chlorothio-
phene (0.321 g, 2 mmol) afforded 44 (0.166 g, 70%). 1H NMR
(200 MHz, CDCl3, 258C): d=8.73 (d, J=4.7 Hz, 2H), 7.63 (d, J=
4.7 Hz, 2H), 7.28 (s, 1H), 2.59 ppm (s, 3H); 13C NMR (50 MHz,
CDCl3, 258C): d=189.6, 150.4, 142.5, 140.9, 138.9, 133.8, 123.8,
122.5, 26.4 ppm; elemental analysis calcd (%) for C11H8ClNOS
(237.71): C 55.58, H 3.39; found: C 55.40, H 3.31.
5-Pyrimidin-5-ylthiophene-2-carbonitrile (37): 5-Bromopyrimidine
(0.159 g, 1 mmol) and thiophene 2-carbonitrile (0.218 g, 2 mmol)
afforded 37 (0.125 g, 67%). 1H NMR (200 MHz, CDCl3, 258C): d=
9.25 (s, 1H), 8.99 (s, 2H), 7.70 (d, J=3.6 Hz, 1H), 7.42 ppm (d, J=
3.6 Hz, 1H); 13C NMR (50 MHz, CDCl3, 258C): d=157.8, 153.0, 142.3,
532
www.chemsuschem.org
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemSusChem 2011, 4, 526 – 534

Cyclopentyl Methyl Ether as Alternative Solvent
4-(3-Bromo-5-[1,3]dioxolan-2-ylthiophen-2-yl)benzonitrile (45): 4-
Bromobenzonitrile (0.182 g, 1 mmol) and 2-(4-bromothiophen-2-
yl)-1,3-dioxolane (0.470 g, 2 mmol) afforded 45 (0.259 g, 77%).
1H NMR (200 MHz, CDCl3, 258C): d=7.86 (d, J=8.1 Hz, 2H), 7.77
(d, J=8.1 Hz, 2H), 7.37 (s, 1H), 6.08 (s, 1H), 4.11 ppm (m, 4H);
13C NMR (50 MHz, CDCl3, 258C): d=151.6, 144.9, 133.4, 129.5,
128.6, 118.5, 115.4, 113.8, 107.5, 99.5, 66.0 ppm; elemental analysis
calcd (%) for C14H10BrNO2S (336.20): C 50.01, H 3.00; found: C
50.13, H 2.89.
2 mmol) afforded 55 (0.120 g, 56%). 1H NMR (200 MHz, CDCl3,
258C): d=8.70 (d, J=4.5 Hz, 2H), 7.65 (d, J=4.5 Hz, 2H), 7.28 (d,
J=3.6 Hz, 1H), 6.99 (d, J=3.6 Hz, 1H), 2.89 (t, J=7.5 Hz, 2H), 1.81
(sextet, J=7.5 Hz, 2H), 1.03 ppm (t, J=7.5 Hz, 3H); 13C NMR
(50 MHz, CDCl3, 258C): d=189.9, 154.5, 153.3, 150.9, 136.6, 119.0,
118.8, 110.8, 40.9, 18.1, 14.3 ppm; elemental analysis calcd (%) for
C13H13NO2 (215.25): C 72.54, H 6.09; found: C 72.41, H 6.23.
1-(5-Pyrimidin-4-yl-furan-2-yl)butanone (56): 5-Bromopyrimidine
(0.159 g, 1 mmol) and 1-(furan-2-yl)butan-1-one (0.276 g, 2 mmol)
afforded 56 (0.130 g, 60%). 1H NMR (200 MHz, CDCl3, 258C): d=
9.21 (s, 1H), 9.14 (s, 2H), 7.30 (d, J=3.6 Hz, 1H), 6.97 (d, J=3.6 Hz,
1H), 2.89 (t, J=7.5 Hz, 2H), 1.81 (sextet, J=7.5 Hz, 2H), 1.03 ppm
(t, J=7.5 Hz, 3H); 13C NMR (50 MHz, CDCl3, 258C): d=188.3, 157.2,
152.2, 151.7, 149.9, 123.0, 117.4, 108.7, 39.5, 16.7, 12.8 ppm; ele-
mental analysis calcd (%) for C12H12N2O2 (216.24): C 66.65, H 5.59;
found: C 66.41, H 5.74.
4-(5-Acetylthiophen-2-yl)benzonitrile (46):[4h] 4-Bromobenzonitrile
(0.182 g, 1 mmol) and 2-acetylthiophene (0.252 g, 2 mmol) afforded
46 (0.109 g, 48%).
4-[5-(2-Methyl-1,3-dioxolan-2-yl)thiophen-2-yl]benzonitrile (47):[4h]
4-Bromobenzonitrile (0.182 g, 1 mmol) and 2-acetylthiophene eth-
ylene acetal (0.340 g, 2 mmol) afforded 47 (0.152 g, 56%).
4-(5-Formylthiophen-2-yl)benzonitrile (48):[4h] 4-Bromobenzonitrile
(0.182 g, 1 mmol) and 2-formylthiophene (0.224 g, 2 mmol) afford-
ed 48 (0.113 g, 53%).
4-(5-Acetylthiophen-2-yl)benzonitrile (57):[5e] 4-Bromobenzonitrile
(0.182 g, 1 mmol) and 2-acetylfuran (0.220 g, 2 mmol) afforded 57
(0.087 g, 41%).
1-[5-(4-Cyanophenyl)furan-2-yl]butan-1-one (49):[5e] 4-Bromobenzo-
nitrile (0.182 g, 1 mmol) and 1-(furan-2-yl)butan-1-one (0.276 g,
2 mmol) afforded 49 (0.186 g, 78%).
2-n-Butyl-5-(4-cyanophenyl)furan
(0.182 g, 1 mmol) and 2-n-butylfuran (0.248 g, 2 mmol) afforded 58
(0.128 g, 57%).
(58):[5e]
4-Bromobenzonitrile
Methyl 2-methyl-5-(4-cyanophenyl)furan-3-carboxylate (59):[5e] 4-
Bromobenzonitrile (0.182 g, 1 mmol) and methyl 2-methylfuran-3-
carboxylate (0.280 g, 2 mmol) afforded 59 (0.121 g, 50%).
1-[5-(4-Acetylphenyl)furan-2-yl]butan-1-one (50): 4-Bromoacetophe-
none (0.199 g, 1 mmol) and 1-(furan-2-yl)butan-1-one (0.276 g,
2 mmol) afforded 50 (0.184 g, 72%). 1H NMR (200 MHz, CDCl3,
258C): d=8.01 (d, J=8.2 Hz, 2H), 7.87 (d, J=8.2 Hz, 2H), 7.27 (d,
J=3.6 Hz, 1H), 6.90 (d, J=3.6 Hz, 1H), 2.89 (t, J=7.5 Hz, 2H), 2.63
(s, 3H), 1.79 (sextet, J=7.5 Hz, 2H), 1.03 ppm (t, J=7.5 Hz, 3H);
13C NMR (50 MHz, CDCl3, 258C): d=196.2, 188.4, 154.8, 151.5,
135.9, 132.4, 127.9, 123.8, 117.8, 108.3, 39.4, 25.7, 16.8, 12.9 ppm;
elemental analysis calcd (%) for C16H16O3 (256.30): C 74.98, H 6.29;
found: C 75.11, H 6.34.
4-(2,3-Dimethylimidazol-4-yl)benzonitrile (60):[7f] 4-Bromobenzoni-
trile (0.182 g, 1 mmol) and 1,2-dimethylimidazole (0.192 g, 2 mmol)
afforded 60 (0.138 g, 70%).
Acknowledgements
1-[5-(4-Formylphenyl)furan-2-yl]butan-1-one (51):[5e] 3-Bromoben-
zaldehyde (0.185 g, 1 mmol) and 1-(furan-2-yl)butan-1-one (0.276 g,
2 mmol) afforded 51 (0.182 g, 75%).
K.B. is grateful to the CNRS and Region Bretagne for a grant. We
thank the CNRS and “Rennes Metropole” for providing financial
support.
1-[5-(4-Nitrophenyl)furan-2-yl]butan-1-one (52): 4-Bromonitroben-
zene (0.202 g, 1 mmol) and 1-(furan-2-yl)butan-1-one (0.276 g,
2 mmol) afforded 52 (0.168 g, 65%). 1H NMR (200 MHz, CDCl3,
258C): d=8.32 (d, J=8.2 Hz, 2H), 7.94 (d, J=8.2 Hz, 2H), 7.29 (d,
J=3.6 Hz, 1H), 6.99 (d, J=3.6 Hz, 1H), 2.89 (t, J=7.5 Hz, 2H), 1.79
(sextet, J=7.5 Hz, 2H), 1.03 ppm (t, J=7.5 Hz, 3H); 13C NMR
(50 MHz, CDCl3, 258C): d=188.3, 157.2, 155.6, 152.2, 151.7, 150.0,
143.9, 117.3, 108.7, 39.5, 16.7, 12.8 ppm; elemental analysis calcd
(%) for C14H13NO4 (259.26): C 64.86, H 5.05; found: C 64.98, H 5.14.
Keywords: aryl bromides
cyclopentyl methyl ether · heteroaromatics · palladium
·
homogeneous catalysis
·
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1-[5-(3-Formylphenyl)furan-2-yl]butan-1-one (53): 3-Bromobenzal-
dehyde (0.185 g, 1 mmol) and 1-(furan-2-yl)butan-1-one (0.276 g,
2 mmol) afforded 53 (0.124 g, 51%). 1H NMR (200 MHz, CDCl3,
258C): d=10.10 (s, 1H), 8.29 (s, 1H), 8.07 (d, J=7.7 Hz, 1H), 7.90
(d, J=7.7 Hz, 1H), 7.64 (t, J=7.5 Hz, 1H), 7.30 (d, J=3.6 Hz, 1H),
6.91 (d, J=3.6 Hz, 1H), 2.89 (t, J=7.5 Hz, 2H), 1.81 (sext., J=7.5 Hz,
2H), 1.03 ppm (t, J=7.5 Hz, 3H); 13C NMR (50 MHz, CDCl3, 258C):
d=192.1, 189.8, 156.1, 152.8, 137.3, 130.9, 130.8, 130.4, 130.2,
126.2, 119.3, 108.8, 40.8, 18.3, 14.3 ppm; elemental analysis calcd
(%) for C15H14O3 (242.27): C 74.36, H 5.82; found: C 74.54, H 5.97.
1-[5-(2-Cyanophenyl)furan-2-yl]butan-1-one (54):[5e] 2-Bromobenzo-
nitrile (0.182 g, 1 mmol) and 1-(furan-2-yl)butan-1-one (0.276 g,
2 mmol) afforded 54 (0.148 g, 62%).
1-(5-Pyridin-4-yl-furan-2-yl)butanone (55): 4-Bromopyridine hydro-
chloride (0.195 g, 1 mmol) and 1-(furan-2-yl)butan-1-one (0.276 g,
ChemSusChem 2011, 4, 526 – 534
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemsuschem.org
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Received: November 24, 2010
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Published online on February 18, 2011
534
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ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemSusChem 2011, 4, 526 – 534