Palladium-catalysed direct heteroarylation of bromobenzenes bearing SO 2R substituents at C2 or C4

Article abstract of DOI:10.1039/c3ra40769a

Palladium-catalysed direct arylation of 4- or 2-bromobenzenesulfonic acid derivatives in the presence of a variety of heteroaromatics was found to proceed using 0.1-0.5 mol% palladium acetate as the catalyst. However, both the nature and position of the SO₂R substituent on such bromobenzenes has an influence on the reaction rates and yields. The presence of SO₂Et or SO₂NEt₂ at the C2 or C4 position of bromobenzene is tolerated. Good results were also obtained from bromobenzene substituted at C4 by SO₂NHPh or SO₂OPh. On the other hand, the reactions of bromobenzenes bearing either SO₂N(Me)CH₂Ph or SO ₂OAr at C2 led in some cases to intramolecular reactions instead of the desired intermolecular couplings. Some reactions were performed in cyclopentyl methyl ether, which can be considered as a green solvent.

Full text of DOI:10.1039/c3ra40769a

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Palladium-catalysed direct heteroarylation of
bromobenzenes bearing SO2R substituents at C2 or C43
Cite this: RSC Advances, 2013, 3,
5987
Charles Beromeo Bheeter,a Rongwei Jin,a Jitendra K. Berab and Henri Doucet*a
Palladium-catalysed direct arylation of 4- or 2-bromobenzenesulfonic acid derivatives in the presence of a
variety of heteroaromatics was found to proceed using 0.1–0.5 mol% palladium acetate as the catalyst.
However, both the nature and position of the SO2R substituent on such bromobenzenes has an influence
on the reaction rates and yields. The presence of SO2Et or SO2NEt2 at the C2 or C4 position of
bromobenzene is tolerated. Good results were also obtained from bromobenzene substituted at C4 by
SO2NHPh or SO2OPh. On the other hand, the reactions of bromobenzenes bearing either SO2N(Me)CH2Ph
or SO2OAr at C2 led in some cases to intramolecular reactions instead of the desired intermolecular
couplings. Some reactions were performed in cyclopentyl methyl ether, which can be considered as a
green solvent.
Received 12th December 2012,
Accepted 14th February 2013
DOI: 10.1039/c3ra40769a
www.rsc.org/advances
tallic derivative, reducing the number of steps needed to
prepare such compounds.
1. Introduction
The ArSO2 motif is a ubiquitous building block found in many
bioactive compounds. For example, Sildenafil makes the blood
vessels become wider, Celecoxib and Valdecoxib are anti-
inflammatory drugs, Etoricoxib is employed for the treatment
of rheumatoid arthritis and Furosemide is used in the
treatment of congestive heart failure and edema (Fig. 1).
Suzuki, Stille or Negishi palladium-catalysed cross-coupling
reactions are valuable methods to form carbon–carbon bonds,
allowing us to modify the substituents of bi(hetero)aryl
derivatives quite easily.1 However, they require the preliminary
preparation of a requisite organometallic species. Ohta and co-
workers reported in 1990 that the direct 2- or 5-arylation of
several heteroaromatics with aryl halides via C–H bond
activation proceeded in moderate to good yields using a
palladium catalyst.2 Since this report, the palladium-catalysed
direct arylation of heteroaryl derivatives with aryl halides has
proven to be a cost-effective and environmentally attractive
method for the synthesis of a wide variety of arylated
heterocycles.3–8 Indeed, the major by-products of the reaction
are a base associated to HX, instead of metallic salts produced
under more classical cross-coupling procedures. Moreover, the
method avoids the preliminary preparation of an organome-
So far, very few examples of palladium-catalysed intermo-
lecular direct arylations of heteroaromatics using benzenesul-
fonic acid derivatives have been described.9,10 Moreover, in
most cases large amounts of catalyst (5–10 mol%) have been
employed. For example, in 2006, Van der Eycken et al.
described the coupling of 2-arylimidazo[1,2-a]pyrimidines with
1-bromo-4-methanesulfonylbenzene using 8 mol% Pd(OAc)2
a
´
Institut Sciences Chimiques de Rennes, UMR 6226 CNRS-Universite de Rennes 1,
´
‘‘Organometalliques: Materiaux et Catalyse’’, Campus de Beaulieu, 35042 Rennes,
France. E-mail: henri.doucet@univ-rennes1.fr; Fax: +(33) 0223236939.;
Tel: +(33) 0223236384
bDepartment of Chemistry, Indian Institute of Technology Kanpur, 208016 Kanpur,
India
Electronic supplementary information (ESI) available. See DOI: 10.1039/
3
Fig. 1
c3ra40769a
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associated to 16 mol% PPh3.9 Moreover, to our knowledge, no
example of palladium-catalysed intermolecular direct aryla-
tions using halobenzenes substituted by sulfonamides or
sulfonates has been reported. Therefore, the influence of both
the nature and position of the SO2R substituent on haloben-
zenes for such couplings needs to be investigated. Moreover,
the discovery of effective conditions, using low catalyst loading
and a non-toxic base and solvent, could be a considerable
advantage for industrial applications and for sustainable
development.
Table 1 Palladium catalysed reaction of 1-bromo-4-ethanesulfonylbenzene
with heteroaromatics
Entry Heteroarene
Product
Yield (%)
Herein, we report a general access to heteroaryl-benzene-
sulfonic acid derivatives by the regioselective palladium-
catalysed arylation of heterocycles with various benzenesulfo-
nic acid derivatives using economically viable (low catalyst
loading, cheap base) and environmentally attractive condi-
tions. The influence of the position of the bromide on the
benzenesulfonic acid derivatives, and of the nature of the SO2R
substituent are reported.
1
2
3
4
5
6
94a
93
82a, b
14c
0d
87
7
82
2. Results and discussion
8
9
80
81
For this study, based on previous results,11 DMAc was initially
chosen as the solvent and KOAc as the base. The reactions
were performed at 130 uC under argon in the presence of 0.5
mol% Pd(OAc)2 as the catalyst. Using these conditions, the
coupling of 1-bromo-4-ethanesulfonylbenzene
1 with 2-
i-butylthiazole gave 2 in a very high 94% yield (Table 1, entry
1). In the presence of a lower catalyst loading (0.1 mol%), a
very similar yield of 2 was obtained (Table 1, entry 2). It should
be noted that this reaction also proceeded nicely using
cyclopentyl methyl ether (CPME) as the solvent and 0.5
mol% Pd(OAc)2 catalyst (Table 1, entry 3). The use of this
solvent for such couplings provides a more environmentally
attractive procedure, as CPME presents several advantageous
features, such as a limited miscibility in water, allowing an
easy separation and recovery from water. Another preferable
characteristic is the low formation of peroxides (compared to
THF or diisopropyl ether).12 Moreover, CPME can be manu-
factured by the addition of MeOH to cyclopentene. This
process produces no apparent waste. On the other hand, 2 was
only obtained in 14% yield using diethylcarbonate as the
solvent (Table 1, entry 4).7c Then, several heteroarenes were
coupled with 1-bromo-4-ethanesulfonylbenzene 1. From
2-methylthiophene, 1-(furan-2-yl)butan-1-one or 1-methylpyr-
role-2-carbaldehyde, the desired products 3–5 were obtained in
high yields using again only 0.1 mol% catalyst (Table 1, entries
6–8). It should be noted that no decarboxylation was observed
in the course of the reaction of 1-bromo-4-ethanesulfonylben-
zene 1 with methyl 1-methylpyrrole-2-carboxylate, producing 6
in 81% yield (Table 1, entry 9). Finally, 3,5-dimethylisoxazole
gave the product 7 in 80% yield in the presence of 0.5 mol%
catalyst (Table 1, entry 11).
10
11
68
80a
Conditions: Pd(OAc)2 (0.001 eq.), 1-bromo-4-ethanesulfonylbenzene
(1 eq.), heteroaromatic (1.5 eq.), KOAc (2 eq.), DMAc, 130 uC, 20
a
b
c
h. P(OAc)2 d(0.005 eq.). CPME as the solvent. Diethylcarbonate as
the solvent. Pentan-1-ol as the solvent.
reactivity to 1 in DMAc. From 2-i-butylthiazole and 8 as the
coupling partners, 9 was obtained in 93% yield using 0.1
mol% Pd(OAc)2 catalyst (Table 2, entry 1). It should be noted
that this reaction performed in CPME led to 9 in only 52%
yield (Table 2, entry 2). Good yields were also obtained for the
reaction of 8 using 2-n-butylthiophene, 1-methylpyrrole-2-
carbaldehyde or 3,5-dimethylisoxazole as the reactants
(Table 2, entries 3, 5 and 6). 2-Chlorothiophene coupled with
8 gave 11 in 84% yield (Table 2, entry 4). In the course of this
reaction no cleavage of the C–Cl bond of the chlorothiophene
derivative was detected, allowing further transformations.
The
secondary
sulfonamide,
4-bromo-
N-phenylbenzenesulfonamide 14 was found to be less reactive
than the tertiary sulfonamide 8. With this substrate, 0.5 mol%
catalyst had to be employed to observe a high conversion of
the aryl bromide (Table 3). From 2-i-butylthiazole,
Then, we studied the reactivity of 4-bromobenzenesulfona-
mides (Tables 2 and 3). The tertiary sulfonamide, 4-bromo-
N,N-diethylbenzenesulfonamide 8, was found to have a similar
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Table 2 Palladium catalysed reaction of 4-bromo-
N,N-diethylbenzenesulfonamide with heteroaromatics
Table 3 Palladium catalysed reaction of 4-bromo-N-phenylbenzenesulfonamide
with heteroaromatics
Entry Heteroarene Product
Yield (%)
Entry
Heteroarene
Product
Yield (%)
1
2
92
1
2
93
83a
52a
3
4
68
66
3
4
5
91
84
78
Conditions: Pd(OAc)2 (0.005 eq.), 4-bromo-
N-phenylbenzenesulfonamide (1 eq.), heteroaromatic (1.5 eq.), KOAc
a
(2 eq.), DMAc, 130 uC, 20 h. CPME as the solvent.
6
86
0.5 mol% Pd(OAc)2 catalyst; only decomposition of the starting
material 22 was observed (Scheme 1).
Then, we examined the reactivity of bromobenzenes
bearing various SO2R substituents at C2 (Tables 5 and 6 and
Conditions: Pd(OAc)2 (0.001 eq.), 4-bromo-
N,N-diethylbenzenesulfonamide (1 eq.), heteroaromatic (1.5 eq.),
a
KOAc (2 eq.), DMAc, 130 uC, 20 h. P(OAc)2 0.5 mol%, CPME as the
solvent.
Table 4 Palladium catalysed reaction of phenyl 4-bromobenzenesulfonate with
heteroaromatics
2-methylthiophene or ethyl 2-methylfuran-3-carboxylate, the
products 15–17 were obtained in 66–92% yields. Similar yields
of 15 were obtained for the reactions of 14 with 2-i-
butylthiazole using DMAc or CPME as the solvents (Table 3,
entries 1 and 2).
The arylations using phenyl 4-bromobenzenesulfonate 18
might have produced side-products, as the palladium-cata-
lyzed direct arylation of heteroaromatics using tosylates or
mesylates, via C–O bond cleavage, is possible in the presence
of K2CO3/tBuCO2H.13 However, phenyl 4-bromobenzenesulfo-
nate 18 reacts nicely with heteroarenes using again only 0.1
mol% Pd(OAc)2 as the catalyst (Table 4). The desired products
19–21 were obtained in 79–90% yields using 2-n-propylthia-
zole, 2-methylthiophene or 1-methylpyrrole-2-carbaldehyde as
the coupling partners. A slightly lower yield was obtained for
the synthesis of 19 in CPME (Table 4, entry 2). In the course of
these reactions no clevage of the Ph–O bond was observed.
On the other hand, from methyl 4-bromobenzenesulfonate
22 and 2-i-butylthiazole, no formation of target compound 23
was detected using either DMAc or CPME as the solvents and
Entry
Heteroarene
Product
Yield (%)
1
2
90
75a
3
4
85
79
Conditions: Pd(OAc)2 (0.001 eq.), phenyl 4-bromobenzenesulfonate (1
eq.), heteroaromatic (1.5 eq.), KOAc (2 eq.), DMAc, 130 uC, 20
a
h. P(OAc)2 0.5 mol%, CPME as the solvent.
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Table 6 Palladium catalysed reaction of 2-bromo-
N,N-diethylbenzenesulfonamide with heteroaromatics
Scheme 1
Entry
1
Heteroarene
Product
Yield (%)
95
Schemes 2–5). First, we investigated the reaction of 1-bromo-2-
ethanesulfonylbenzene 24 with three heteroaromatics
(Table 5). Using 0.1 mol% Pd(OAc)2, the reaction with 2-
i-butylthiazole led to a low yield of desired product 25 due to a
poor conversion of 24. On the other hand, 2-i-butylthiazole,
2-methylthiophene or ethyl 2-methylfuran-3-carboxylate in the
presence of 0.5 mol% Pd(OAc)2 gave the desired products 25–
27 in very good yields (Table 5, entries 1, 3 and 4). Under the
same conditions, but using CPME as the solvent, the
formation of 25 in 90% yield was observed (Table 5, entry 2).
The lower reactivity of 24 (Table 5) compared to 1 (Table 1)
might be due to the steric hindrance of the SO2Et substituents
at C2 of 24.
2
3
92
82
The tertiary sulfonamide, 2-bromo-N,N-diethylbenze-
nesulfonamide 28, also gave the desired coupling products
4
41
Table 5 Palladium catalysed reaction of 1-bromo-2-ethanesulfonylbenzene
with heteroaromatics
Conditions: Pd(OAc)2 (0.005 eq.), of 2-bromo-
N,N-diethylbenzenesulfonamide (1 eq.), heteroaromatic (1.5 eq.),
KOAc (2 eq.), DMAc, 130 uC, 20 h.
29–31 in high yields using 0.5 mol% Pd(OAc)2 catalyst
(Table 6). For example, from 2-i-butylthiazole and 2-
n-butylthiophene, the products 29 and 30 were obtained in
95% and 92% yields, respectively. A lower yield was obtained
when 1-methylpyrrole-2-carbaldehyde was employed, due to a
moderate conversion of the aryl bromide (Table 6, entry 4).
Entry
Heteroarene
Product
Yield (%)
1
2
91
90a
3
4
82
76
Conditions: Pd(OAc)2 (0.005 eq.), 1-bromo-2-ethanesulfonylbenzene
(1 eq.), heteroaromatic (1.5 eq.), KOAc (2 eq.), DMAc, 130 uC, 20
a
Scheme 2
h. CPME as the solvent.
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Scheme 3
Next, the reactivity of secondary sulfonamide, 2-bromo-
N-ethyl-benzenesulfonamide 33 was examined (Scheme 2). In
the presence of 0.1 mol% Pd(OAc)2 at 130 uC, a very low yield
in 34 was obtained. On the other hand, at 150 uC using 1 mol%
Pd(OAc)2 34 was obtained in 30% yield. This might be due to
the formation of stable palladacycles via oxidative addition of
2-bromo-N-ethyl-benzenesulfonamide followed by sulfona-
mide deprotonation.
We then investigated the reactivity of 2-bromo-
N-phenylbenzenesulfonamide 35. However, the use of 35 in
the presence of 2-i-butylthiazole gave no intermolecular direct
arylation product 36 (Scheme 3, top). We had previously
observed that, with the secondary sulfonamide 35 and 1 mol%
Pd(OAc)2, no trace of intramolecular direct arylation to form
product 37 was detected.11 The primary sulfonamide 38 was
Scheme 5
also found to be completely unreactive in the presence of
2-methylthiophene (Scheme 3, bottom). For these two reac-
tions, the starting materials 35 and 38 were recovered
unreacted. The difference of reactivity between 35 and 14
might again come from the formation of a stable palladacycle
with 35.
Then, we performed a competition reaction to probe the
preference of this catalyst system for inter molacular arylation
vs. intra molecular reaction to form a seven membered ring.
From N-benzyl-2-bromo-N-methylbenzenesulfonamide 40 in
the presence of 1 mol% Pd(OAc)2, the formation of the
intramolecular reaction product 42 has already been
reported.11 The reaction of 40 with 1.5 equiv. 2-i-butylthiazole
and KOAc as the base led to an equimolar mixture of 41 and 42
(Scheme 4). The ratio of products 41 : 42 depends on the
nature of the base and also on the excess amount of thiazole
derivative. In the presence of CsOAc using a larger excess of 2-
i-butylthiazole, 41 was formed in 75% selectivity and 52%
yield. For these reactions, 2 mol% PdCl(C3H5)(dppb) catalyst
was employed, as the use of 1 mol% Pd(OAc)2, which is a less
stable catalyst, led to a poor conversion of 40.
We also performed competition reactions using aryl
2-bromobenzenesulfonates 43 and 46. We have recently
reported that from 43, an intramolecular direct arylation gives
45 in good yield; whereas, from 46 no formation of 48 was
detected.11 We observed that using a mixture of 43 and 2-
i-butylthiazole as reaction partners, no formation of 44 was
Scheme 4
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the solvent, the product was purified by silica gel column
chromatography.
detected by GC-MS analysis and only 45 was produced
(Scheme 5, top). On the other hand, from 46 and 2-
i-butylthiazole only the intermolecular reaction to give 47 in
72% yield was observed (Scheme 5, bottom).
5-(4-Ethanesulfonylphenyl)-2-isobutylthiazole (2). From
1-bromo-4-ethanesulfonylbenzene (0.249 g, 1 mmol) and 2-
i-butylthiazole (0.212 g, 1.5 mmol), product 2 was obtained in
1
93% (0.287 g) yield. H NMR (300 MHz, DMSO-d6) d 8.28 (s,
1H), 7.95–7.85 (m, 4H), 3.33 (q, J = 7.4 Hz, 2H), 2.87 (d, J = 7.2
Hz, 2H), 2.10–2.00 (m, 1H), 1.11 (t, J = 7.4 Hz, 3H), 0.94 (d, J =
7.2 Hz, 6H). 13C NMR (75 MHz, DMSO-d6) d 170.6, 140.4, 137.3,
136.1, 135.9, 128.7, 126.7, 49.2, 41.6, 29.1, 21.9, 7.1. Elemental
analysis: calcd (%) for C15H19NO2S2 (309.45): C 58.22, H 6.19;
found: C 58.31, H 6.01.
Conclusion
In summary, we report here conditions for the palladium-
catalyzed intermolecular direct arylation at C4 or C5 of a range
of heteroarenes using bromobenzenes bearing SO2Et, SO2NEt2
or SO2Ph substituents either at C2 or C4. As low as 0.5–0.1
mol% phosphine-free Pd(OAc)2 catalyst associated to KOAc
promotes the arylation of thiazole, thiophene, furan, pyrrole or
oxazole derivatives. In some cases, CPME, which can be
considered as a green solvent, was successfully employed. The
major by-product of these couplings is the salt arising from the
trapping of the released HBr by the base, instead of metallic
salts with more classical coupling procedures. For these
reasons, this novel process should give an economically viable
and environmentally attractive access to several arylated
heteroaromatics bearing SO2-substituents useful to bioche-
mists.
2-(4-Ethanesulfonylphenyl)-5-methylthiophene (3). From
1-bromo-4-ethanesulfonylbenzene (0.249 g,
2-methylthiophene (0.147 g, 1.5 mmol), product
1
mmol) and
was
3
obtained in 87% (0.231 g) yield. 1H NMR (300 MHz, DMSO-
d6) d 7.90–7.80 (m, 4H), 7.55 (d, J = 3.6 Hz, 1H), 6.90 (d, J = 3.6
Hz, 1H), 3.31 (q, J = 7.4 Hz, 2H), 2.50 (s, 3H), 1.11 (t, J = 7.4 Hz,
3H). 13C NMR (75 MHz, DMSO-d6) d 141.7, 138.8, 138.7, 136.3,
128.7, 127.4, 126.1, 125.3, 49.2, 15.1, 7.1. Elemental analysis:
calcd (%) for C13H14O2S2 (266.38): C 58.61, H 5.30; found: C
58.70, H 5.47.
1-[5-(4-Ethanesulfonylphenyl)-furan-2-yl]-butan-1-one (4).
From 1-bromo-4-ethanesulfonylbenzene (0.249 g, 1 mmol)
and 1-(furan-2-yl)butan-1-one (0.207 g, 1.5 mmol), product 4
was obtained in 82% (0.251 g) yield. 1H NMR (300 MHz,
DMSO-d6) d 8.09 (d, J = 8.4 Hz, 2H), 7.97 (d, J = 8.4 Hz, 2H),
7.58 (d, J = 3.8 Hz, 1H), 7.42 (d, J = 3.8 Hz, 1H), 3.35 (q, J = 7.4
Hz, 2H), 2.86 (t, J = 7.5 Hz, 2H), 1.63 (m, 2H), 1.11 (t, J = 7.4 Hz,
3H), 0.92 (t, J = 7.5 Hz, 3H). 13C NMR (75 MHz, DMSO-d6) d
188.5, 154.5, 152.0, 138.2, 133.4, 128.7, 125.2, 120.0, 111.0,
49.1, 39.5, 17.3, 13.5, 7.0. Elemental analysis: calcd (%) for
C16H18O4S (306.38): C 62.72, H 5.92; found: C 62.80, H 6.05.
5-(4-Ethanesulfonylphenyl)-1-methylpyrrole-2-carbaldehyde
(5). From 1-bromo-4-ethanesulfonylbenzene (0.249 g, 1 mmol)
and 1-methylpyrrole-2-carbaldehyde (0.164 g, 1.5 mmol),
Experimental section
All reactions were run under argon in Schlenk tubes using
vacuum lines. DMAc (analytical grade), cyclopentyl methyl
ether 99+%, and KOAc (99%) were used. Commercial aryl
bromides, heteroarenes and solvents were used without
purification. The reactions were followed by GC and NMR
spectroscopic analysis. H and 13C spectra were recorded with
Bruker 300 or 400 MHz spectrometers. Chemical shifts are
1
1
reported in ppm relative to CDCl3 (7.25 for H NMR and 77.0
1
for 13C NMR). Flash chromatography was performed on silica
gel (230–400 mesh). Reactants 1,15 8,16 14,17 18,18 22,19 28,20
35,21 40,22 43,11 and 46,11 were prepared according to reported
product 5 was obtained in 80% (0.222 g) yield. H NMR (300
MHz, DMSO-d6) d 9.63 (s, 1H), 7.99 (d, J = 8.4 Hz, 2H), 7.83 (d, J
= 8.4 Hz, 2H), 7.15 (d, J = 4.1 Hz, 1H), 6.55 (d, J = 4.1 Hz, 1H),
3.92 (s, 3H), 3.35 (q, J = 7.4 Hz, 2H), 1.14 (t, J = 7.4 Hz, 3H). 13C
NMR (75 MHz, DMSO-d6) d 180.2, 141.2, 138.1, 135.6, 133.5,
129.7, 128.1, 123.7, 111.7, 49.1, 34.0, 7.1. Elemental analysis:
calcd (%) for C14H15NO3S (277.34): C 60.63, H 5.45; found: C
60.51, H 5.60.
Methyl 5-(4-ethanesulfonylphenyl)-1-methylpyrrole-2-carbox-
ylate (6). From 1-bromo-4-ethanesulfonylbenzene (0.249 g, 1
mmol) and methyl 1-methylpyrrole-2-carboxylate (0.209 g, 1.5
mmol), product 6 was obtained in 81% (0.249 g) yield. 1H NMR
(300 MHz, DMSO-d6) d 7.96 (d, J = 8.4 Hz, 2H), 7.78 (d, J = 8.4
Hz, 2H), 6.98 (d, J = 4.1 Hz, 1H), 6.42 (d, J = 4.1 Hz, 1H), 3.87 (s,
3H), 3.78 (s, 3H), 3.35 (q, J = 7.4 Hz, 2H), 1.14 (t, J = 7.4 Hz, 3H).
13C NMR (75 MHz, CDCl3) d 161.4, 139.6, 138.1, 136.9, 130.1,
128.6, 124.6, 117.9, 110.8, 51.6, 49.6, 34.8, 7.6. Elemental
analysis: calcd (%) for C15H17NO4S (307.37): C 58.61, H 5.57;
found: C 58.40, H 5.68.
procedures.
14
Preparation of the PdCl(C3H5)(dppb) catalyst:
An oven-
dried 40 mL Schlenk tube equipped with a magnetic stirring
bar under an argon atmosphere was charged with
[Pd(C3H5)Cl]2 (182 mg, 0.5 mmol) and dppb (426 mg, 1 mmol).
10 mL anhydrous dichloromethane was added, then, the
solution was stirred at room temperature for twenty minutes.
The solvent was removed in vacuo. The yellow powder was used
without purification. 31P NMR (81 MHz, CDCl3) d = 19.3 (s).
General procedure
In a typical experiment, the aryl bromide (1 mmol), hetero-
aromatic derivative (1.5 mmol), KOAc (0.196 g, 2 mmol) and
Pd(OAc)2 (0.23 mg, 0.001 mmol), (1.1 mg, 0.005 mmol) or
PdCl(C3H5)(dppb) (12.0 mg, 0.02 mmol) (see tables or
schemes) were dissolved in DMAc or CPME (4 mL) under an
argon atmosphere. The reaction mixture was stirred at 130 uC
or 150 uC (see Tables or Schemes) for 20 h. After evaporation of
4-(4-Ethanesulfonylphenyl)-3,5-dimethylisoxazole (7). From
1-bromo-4-ethanesulfonylbenzene (0.249 g, 1 mmol) and 3,5-
dimethylisoxazole (0.146 g, 1.5 mmol), product 7 was obtained
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in 80% (0.212 g) yield. 1H NMR (300 MHz, DMSO-d6) d 7.97 (d,
J = 8.4 Hz, 2H), 7.70 (d, J = 8.4 Hz, 2H), 3.35 (q, J = 7.4 Hz, 2H),
2.46 (s, 3H), 2.27 (s, 3H), 1.15 (t, J = 7.4 Hz, 3H). 13C NMR (75
MHz, CDCl3) d 166.3, 157.9, 137.3, 135.4, 129.6, 128.2, 114.7,
49.1, 11.4, 10.4, 7.0. Elemental analysis: calcd (%) for
C13H15NO3S (265.33): C 58.85, H 5.70; found: C 58.69, H 5.44.
N,N-Diethyl-4-(2-isobutylthiazol-5-yl)-benzenesulfonamide
(9). From 4-bromo-N,N-diethylbenzenesulfonamide (0.292 g, 1
mmol) and 2-i-butylthiazole (0.212 g, 1.5 mmol), product 9 was
obtained in 93% (0.327 g) yield. 1H NMR (300 MHz, DMSO-d6)
d 8.23 (s, 1H), 7.90–7.80 (m, 4H), 3.15 (q, J = 7.3 Hz, 4H), 2.84
(d, J = 7.3 Hz, 2H), 2.10–2.00 (m, 1H), 1.03 (t, J = 7.3 Hz, 6H),
0.94 (d, J = 7.3 Hz, 6H). 13C NMR (75 MHz, DMSO-d6) d 170.2,
140.0, 138.7, 136.0, 135.0, 127.6, 126.7, 41.8, 41.6, 29.1, 21.9,
14.0. Elemental analysis: calcd (%) for C17H24N2O2S2 (352.52):
C 57.92, H 6.86; found: C 57.99, H 6.74.
N,N-Diethyl-4-(5-n-butylthiophen-2-yl)-benzenesulfonamide
(10). From 4-bromo-N,N-diethylbenzenesulfonamide (0.292 g)
and 2-n-butylthiophene (0.210 g, 1.5 mmol), product 10 was
obtained in 91% (0.319 g) yield. 1H NMR (300 MHz, DMSO-d6)
d 7.80–7.70 (m, 4H), 7.48 (d, J = 3.6 Hz, 1H), 6.87 (d, J = 3.6 Hz,
1H), 3.14 (q, J = 7.3 Hz, 4H), 2.79 (t, J = 7.5 Hz, 2H), 1.68–1.62
(m, 2H), 1.35–1.30 (m, 2H), 1.05 (t, J = 7.3 Hz, 6H), 0.88 (t, J =
7.5 Hz, 3H). 13C NMR (75 MHz, DMSO-d6) d 147.1, 138.6, 137.7,
137.6, 137.5, 126.1, 125.4, 125.2, 41.7, 33.1, 29.1, 21.5, 14.0,
13.5. Elemental analysis: calcd (%) for C18H25NO2S2 (351.53): C
61.50, H 7.17; found: C 61.67, H 7.12.
4-(5-Chlorothiophen-2-yl)-N,N-diethylbenzenesulfonamide
(11). From 4-bromo-N,N-diethylbenzenesulfonamide (0.292 g)
and 2-chlorothiophene (0.178 g, 1.5 mmol), product 11 was
obtained in 84% (0.277 g) yield. 1H NMR (300 MHz, DMSO-d6)
d 7.85–7.75 (m, 4H), 7.58 (d, J = 4.0 Hz, 1H), 7.22 (d, J = 4.0 Hz,
1H), 3.17 (q, J = 7.3 Hz, 4H), 1.04 (t, J = 7.3 Hz, 6H). 13C NMR
(75 MHz, DMSO-d6) d 140.2, 138.7, 136.4, 129.3, 128.6, 127.7,
125.7, 125.6, 41.8, 14.1. Elemental analysis: calcd (%) for
C14H16ClNO2S2 (329.87): C 50.98, H 4.89; found: C 50.79, H
5.09.
N,N-Diethyl-4-(5-formyl-1-methylpyrrol-2-yl)-benzenesulfo-
namide (12). From 4-bromo-N,N-diethylbenzenesulfonamide
(0.292 g) and 1-methylpyrrole-2-carbaldehyde (0.164 g, 1.5
mmol), product 12 was obtained in 78% (0.249 g) yield. 1H
NMR (300 MHz, DMSO-d6) d 9.61 (s, 1H), 7.89 (d, J = 8.4 Hz,
2H), 7.77 (d, J = 8.4 Hz, 2H), 7.14 (d, J = 4.1 Hz, 1H), 6.52 (d, J =
4.1 Hz, 1H), 3.90 (s, 3H), 3.20 (q, J = 7.3 Hz, 4H), 1.07 (t, J = 7.3
Hz, 6H). 13C NMR (75 MHz, DMSO-d6) d 180.1, 141.3, 139.4,
134.5, 133.4, 129.7, 127.0, 123.7, 111.5, 41.9, 34.0, 14.2.
Elemental analysis: calcd (%) for C16H20N2O3S (320.41): C
59.98, H 6.29; found: C 60.14, H 6.11.
4-(2-Isobutylthiazol-5-yl)-N-phenylbenzenesulfonamide (15).
From 4-bromo-N-phenylbenzenesulfonamide (0.312 g,
1
mmol) and 2-i-butylthiazole (0.212 g, 1.5 mmol), product 15
was obtained in 92% (0.342 g) yield. 1H NMR (400 MHz,
DMSO-d6) d 8 .07 (s, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.4
Hz, 2H), 7.18 (t, J = 8.4 Hz, 2H), 7.09 (d, J = 8.4 Hz, 2H), 6.98 (t, J
= 8.4 Hz, 1H), 2.80 (d, J = 7.3 Hz, 2H), 2.10–1.90 (m, 1H), 0.90
(d, J = 7.3 Hz, 6H). 13C NMR (100 MHz, DMSO-d6) d 170.6,
139.5, 138.3, 137.3, 136.0, 135.2, 128.8, 127.5, 126.2, 124.0,
120.1, 41.4, 29.1, 21.4. Elemental analysis: calcd (%) for
C19H20N2O2S2 (372.51): C 61.26, H 5.41; found: C 61.04, H 5.56.
4-(5-Methylthiophen-2-yl)-N-phenylbenzenesulfonamide
(16). From 4-bromo-N-phenylbenzenesulfonamide (0.312 g, 1
mmol) and 2-methylthiophene (0.147 g, 1.5 mmol), product 16
was obtained in 68% (0.224 g) yield. 1H NMR (300 MHz,
DMSO-d6) d 10.32 (s, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.71 (d, J =
8.4 Hz, 2H), 7.43 (d, J = 3.6 Hz, 1H), 7.23 (t, J = 8.4 Hz, 2H), 7.13
(d, J = 8.4 Hz, 2H), 7.02 (t, J = 8.4 Hz, 1H), 6.84 (d, J = 3.6 Hz,
1H), 2.45 (s, 3H). 13C NMR (75 MHz, DMSO-d6) d 141.4, 138.7,
137.9, 137.6, 137.3, 129.1, 127.6, 127.2, 125.8, 125.1, 124.0,
120.0, 15.1. Elemental analysis: calcd (%) for C17H15NO2S2
(329.44): C 61.98, H 4.59; found: C 61.80, H 4.74.
Ethyl 2-methyl-5-(4-phenylsulfamoylphenyl)-furan-3-carbox-
ylate (17). From 4-bromo-N-phenylbenzenesulfonamide (0.312
g, 1 mmol) and ethyl 2-methylfuran-3-carboxylate (0.231 g, 1.5
mmol), product 17 was obtained in 66% (0.254 g) yield. 1H
NMR (300 MHz, DMSO-d6) d 10.31 (s, 1H), 7.80 (d, J = 8.4 Hz,
2H), 7.77 (d, J = 8.4 Hz, 2H), 7.26 (s, 1H), 7.22 (t, J = 8.4 Hz, 2H),
7.12 (d, J = 8.4 Hz, 2H), 7.01 (t, J = 8.4 Hz, 1H), 4.21 (q, J = 7.5
Hz, 2H), 2.55 (s, 3H), 1.26 (t, J = 7.5 Hz, 3H). 13C NMR (75 MHz,
DMSO-d6) d 162.6, 159.5, 149.4, 138.0, 137.6, 132.9, 129.1,
127.4, 124.1, 123.7, 120.2, 115.3, 108.6, 60.0, 14.1, 13.5.
Elemental analysis: calcd (%) for C20H19NO5S (385.43): C
62.32, H 4.97; found: C 62.52, H 4.69.
Phenyl 4-(2-propylthiazol-5-yl)-benzenesulfonate (19). From
phenyl 4-bromobenzenesulfonate (0.313 g, 1 mmol) and
2-propylthiazole (0.190 g, 1.5 mmol), product 19 was obtained
in 90% (0.323 g) yield. 1H NMR (300 MHz, DMSO-d6) d 8.29 (s,
1H), 7.93–7.82 (m, 4H), 7.45–7.25 (m, 3H), 7.05 (d, J = 8.0 Hz,
2H), 2.95 (t, J = 7.4 Hz, 2H), 1.80–1.70 (m, 1H), 0.94 (t, J = 7.2
Hz, 3H). 13C NMR (75 MHz, DMSO-d6) d 172.6, 149.5, 141.4,
137.7, 135.9, 133.4, 130.5, 129.6, 128.0, 127.3, 122.5, 35.2, 23.1,
13.8. Elemental analysis: calcd (%) for C18H17NO3S2 (359.46): C
60.14, H 4.77; found: C 60.04, H 5.02.
Phenyl 4-(5-methylthiophen-2-yl)-benzenesulfonate (20).
From phenyl 4-bromobenzenesulfonate (0.313 g, 1 mmol)
and 2-methylthiophene (0.147 g, 1.5 mmol), product 20 was
obtained in 85% (0.280 g) yield. 1H NMR (300 MHz, DMSO-d6)
d 7.90–7.80 (m, 4H), 7.57 (d, J = 3.6 Hz, 1H), 7.45–7.25 (m, 3H),
7.05 (d, J = 8.0 Hz, 2H), 6.90 (d, J = 3.6 Hz, 1H), 2.49 (s, 3H). 13C
NMR (75 MHz, DMSO-d6) d 149.0, 142.4, 139.8, 138.2, 131.7,
130.0, 129.1, 127.5, 127.4, 126.8, 125.3, 122.0, 15.1. Elemental
analysis: calcd (%) for C17H14O3S2 (330.42): C 61.79, H 4.27;
found: C 61.89, H 4.05.
4-(3,5-Dimethylisoxazol-4-yl)-N,N-diethyl-benzenesulfona-
mide (13). From 4-bromo-N,N-diethylbenzenesulfonamide
(0.292 g) and 3,5-dimethylisoxazole (0.146 g, 1.5 mmol),
product 13 was obtained in 86% (0.265 g) yield. 1H NMR
(300 MHz, DMSO-d6) d 7.87 (d, J = 8.4 Hz, 2H), 7.63 (d, J = 8.4
Hz, 2H), 3.20 (q, J = 7.3 Hz, 4H), 2.44 (s, 3H), 2.26 (s, 3H), 1.07
(t, J = 7.3 Hz, 6H). 13C NMR (75 MHz, DMSO-d6) d 166.0, 157.9,
138.6, 134.2, 129.5, 127.1, 114.7, 41.9, 14.2, 11.4, 10.4.
Elemental analysis: calcd (%) for C15H20N2O3S (308.40): C
58.42, H 6.54; found: C 58.58, H 6.72.
Phenyl 4-(5-formyl-1-methylpyrrol-2-yl)-benzenesulfonate
(21). From phenyl 4-bromobenzenesulfonate (0.313 g, 1 mmol)
and 1-methylpyrrole-2-carbaldehyde (0.164 g, 1.5 mmol),
product 21 was obtained in 79% (0.269 g) yield. 1H NMR
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(400 MHz, DMSO-d6) d 9.57 (s, 1H), 7.89 (d, J = 7.8 Hz, 2H),
7.75 (d, J = 7.8 Hz, 2H), 7.33 (t, J = 7.6 Hz, 2H), 7.27 (t, J = 7.6
Hz, 1H), 7.08 (d, J = 3.6 Hz, 1H), 7.02 (d, J = 7.6 Hz, 2H), 6.49 (d,
J = 3.6 Hz, 1H), 3.88 (s, 3H). 13C NMR (100 MHz, DMSO-d6) d
179.9, 149.0, 140.8, 136.6, 133.9, 133.7, 129.6, 129.4, 128.3,
127.1, 123.4, 121.7, 111.4, 22.5. Elemental analysis: calcd (%)
for C18H15NO4S (341.38): C 63.33, H 4.43; found: C 63.12, H
4.54.
Methyl 4-(2-isobutylthiazol-5-yl)-benzenesulfonate (23).
From methyl 4-bromobenzenesulfonate (0.251 g, 1 mmol)
and 2-i-butylthiazole (0.212 g, 1.5 mmol), product 23 was not
detected.
(t, J = 7.4 Hz, 3H). 13C NMR (75 MHz, DMSO-d6) d 162.8, 159.3,
148.0, 135.7, 133.9, 131.3, 130.6, 129.4, 128.7, 114.8, 111.3,
60.0, 48.8, 14.2, 13.5, 6.9. Elemental analysis: calcd (%) for
C16H18O5S (322.38): C 59.61, H 5.63; found: C 59.79, H 5.29.
N,N-Diethyl-2-(2-isobutylthiazol-5-yl)-benzenesulfonamide
(29). From 2-bromo-N,N-diethylbenzenesulfonamide (0.292 g,
1 mmol) and 2-i-butylthiazole (0.212 g, 1.5 mmol), product 29
was obtained in 95% (0.334 g) yield. 1H NMR (300 MHz,
DMSO-d6) d 8.10–8.05 (m, 1H), 7.71 (s, 1H), 7.70–7.57 (m, 2H),
7.55–7.45 (m, 1H), 3.00 (q, J = 7.4 Hz, 4H), 2.92 (d, J = 7.2 Hz,
2H), 2.20–2.00 (m, 1H), 1.05–0.98 (m, 12H). 13C NMR (75 MHz,
DMSO-d6) d 172.0, 141.9, 140.0, 134.2, 133.6, 132.2, 129.8,
129.7, 128.9, 41.4, 41.1, 29.8, 21.2, 13.1. Elemental analysis:
calcd (%) for C17H24N2O2S2 (352.52): C 57.92, H 6.86; found: C
57.87, H 6.97.
N,N-Diethyl-2-(5-butylthiophen-2-yl)-benzenesulfonamide
(30). From 2-bromo-N,N-diethylbenzenesulfonamide (0.292 g,
1 mmol) and 2-n-butylthiophene (0.210 g, 1.5 mmol), product
30 was obtained in 92% (0.323 g) yield. 1H NMR (300 MHz,
DMSO-d6) d 7.98 (d, J = 7.4 Hz, 1H), 7.63 (t, J = 7.4 Hz, 1H), 7.55
(t, J = 7.4 Hz, 1H), 7.45 (d, J = 7.4 Hz, 1H), 7.07 (d, J = 3.5 Hz,
1H), 6.82 (d, J = 3.5 Hz, 1H), 2.96 (q, J = 7.4 Hz, 4H), 2.78 (t, J =
7.5 Hz, 2H), 1.68–1.57 (m, 2H), 1.40–1.28 (m, 2H), 0.95–0.85
(m, 9H). 13C NMR (75 MHz, DMSO-d6) d 146.8, 139.8, 136.5,
134.4, 133.8, 132.7, 129.9, 129.5, 128.7, 124.8, 41.2, 33.9, 29.3,
21.9, 14.4, 14.0. Elemental analysis: calcd (%) for C18H25NO2S2
(351.53): C 61.50, H 7.17; found: C 61.41, H 7.30.
2-(5-Butyrylfuran-2-yl)-N,N-diethylbenzenesulfonamide (31).
From 2-bromo-N,N-diethylbenzenesulfonamide (0.292 g, 1
mmol) and 1-(furan-2-yl)butan-1-one (0.207 g, 1.5 mmol),
product 31 was obtained in 82% (0.286 g) yield. 1H NMR
(300 MHz, DMSO-d6) d 7.92 (d, J = 7.4 Hz, 1H), 7.78–7.60 (m,
3H), 7.53 (d, J = 3.5 Hz, 1H), 7.02 (d, J = 3.5 Hz, 1H), 3.15 (q, J =
7.4 Hz, 4H), 2.84 (t, J = 7.5 Hz, 2H), 1.72–1.57 (m, 2H), 1.03 (t, J
= 7.5 Hz, 6H), 0.91 (t, J = 7.5 Hz, 3H). 13C NMR (75 MHz,
DMSO-d6) d 188.6, 153.6, 151.7, 138.7, 132.5, 132.1, 130.1,
128.6, 128.0, 119.0, 113.5, 41.3, 17.3, 14.0, 13.5. Elemental
analysis: calcd (%) for C18H23NO4S (349.45): C 61.87, H 6.63;
found: C 61.80, H 6.48.
N,N-Diethyl-2-(5-formyl-1-methylpyrrol-2-yl)-benzenesulfo-
namide (32). From 2-bromo-N,N-diethylbenzenesulfonamide
(0.292 g, 1 mmol) and 1-methylpyrrole-2-carbaldehyde (0.164
g, 1.5 mmol), product 32 was obtained in 41% (0.131 g) yield.
1H NMR (300 MHz, DMSO-d6) d 9.58 (s, 1H), 8.02 (d, J = 7.5 Hz,
1H), 7.80–7.68 (m, 2H), 7.47 (d, J = 7.5 Hz, 1H), 7.10 (d, J = 4.0
Hz, 1H), 6.25 (d, J = 4.0 Hz, 1H), 3.55 (s, 3H), 2.97 (q, J = 7.5 Hz,
4H), 0.95 (t, J = 7.5 Hz, 6H). 13C NMR (75 MHz, DMSO-d6) d
180.3, 141.0, 140.0, 134.1, 132.9, 132.2, 130.5, 129.7, 129.5,
123.3, 112.5, 41.3, 34.0, 14.7. Elemental analysis: calcd (%) for
C16H20N2O3S (320.41): C 59.98, H 6.29; found: C 59.84, H 6.47.
2-Bromo-N-propylbenzenesulfonamide (33). The reaction of
1-Bromo-2-ethanesulfonylbenzene (24). The 4-bromosulfo-
nyl chloride (0.511 g, 2.0 mmol), sodium sulfite (0.504 g, 4.0
mmol) and sodium bicarbonate (1.34 g, 16.0 mmol) were
dissolved in distilled water (15 mL) under an argon atmo-
sphere and heated at 100 uC for three hours. After cooling to
room temperature, ethyliodide (1.0 mL, 6.0 mmol) and the
phase transfer catalyst tetra-N-butyl ammonium bromide
(0.970 g, 0.3 mmol) were added under an argon flow. The
reaction mixture was stirred overnight at 70 uC. After cooling to
room temperature, 24 was purified by silica column chroma-
tography 3 : 7 (diethylether : pentane) with 76% (0.379 g)
1
yield. H NMR (300 MHz, DMSO-d6) d 8.06 (d, J = 7.4 Hz, 1H),
7.91 (d, J = 7.4 Hz, 1H), 7.70–7.60 (m, 2H), 3.50 (q, J = 7.4 Hz,
2H), 1.11 (t, J = 7.4 Hz, 3H). 13C NMR (75 MHz, DMSO-d6) d
137.2, 135.5, 135.4, 131.7, 128.5, 120.0, 47.6, 6.8. Elemental
analysis: calcd (%) for C8H9BrO2S (249.13): C 38.57, H 3.64;
found: C 38.41, H 3.58.
5-(2-Ethanesulfonylphenyl)-2-isobutylthiazole (25). From
1-bromo-2-ethanesulfonylbenzene (0.249 g, 1 mmol) and 2-
i-butylthiazole (0.212 g, 1.5 mmol), product 25 was obtained in
91% (0.281 g) yield. 1H NMR (300 MHz, DMSO-d6) d 8.10 (d, J =
7.4 Hz, 1H), 7.80 (t, J = 7.4 Hz, 1H), 7.78 (s, 1H), 7.73 (t, J = 7.4
Hz, 1H), 7.60 (d, J = 7.4 Hz, 1H), 2.98 (q, J = 7.4 Hz, 2H), 2.90 (d,
J = 7.2 Hz, 2H), 2.10–2.00 (m, 1H), 0.99 (t, J = 7.4 Hz, 3H), 0.96
(d, J = 7.2 Hz, 6H). 13C NMR (75 MHz, DMSO-d6) d 170.9, 142.9,
137.6, 134.2, 133.6, 131.9, 130.1, 129.7, 129.5, 48.5, 41.2, 29.2,
21.9, 6.8. Elemental analysis: calcd (%) for C15H19NO2S2
(309.45): C 58.22, H 6.19; found: C 58.03, H 6.10.
2-(2-Ethanesulfonylphenyl)-5-methylthiophene (26). From
1-bromo-2-ethanesulfonylbenzene (0.249 g,
1 mmol) and
2-methylthiophene (0.147 g, 1.5 mmol), product 26 was
obtained in 82% (0.218 g) yield. 1H NMR (300 MHz, DMSO-
d6) d 8.09 (d, J = 7.4 Hz, 1H), 7.76 (t, J = 7.4 Hz, 1H), 7.67 (t, J =
7.4 Hz, 1H), 7.55 (d, J = 7.4 Hz, 1H), 7.16 (d, J = 3.5 Hz, 1H),
6.87 (d, J = 3.5 Hz, 1H), 2.90 (q, J = 7.4 Hz, 2H), 2.50 (s, 3H),
0.95 (t, J = 7.4 Hz, 3H). 13C NMR (75 MHz, DMSO-d6) d 141.6,
137.1, 135.2, 133.7, 133.5, 133.4, 129.9, 129.3, 128.7, 125.8,
47.5, 14.8, 7.0. Elemental analysis: calcd (%) for C13H14O2S2
(266.38): C 58.61, H 5.30; found: C 58.51, H 5.09.
Ethyl 5-(2-ethanesulfonylphenyl)-2-methylfuran-3-carboxy-
late (27). From 1-bromo-2-ethanesulfonylbenzene (0.249 g, 1
mmol) and ethyl 2-methylfuran-3-carboxylate (0.231 g, 1.5
mmol), product 27 was obtained in 76% (0.245 g) yield. 1H
NMR (300 MHz, DMSO-d6) d 8.07 (d, J = 7.4 Hz, 1H), 7.85–7.75
(m, 2H), 7.75–7.65 (m, 1H), 7.13 (s, 1H), 4.27 (q, J = 7.4 Hz, 2H),
2.90 (q, J = 7.4 Hz, 2H), 2.62 (s, 3H), 1.30 (t, J = 7.4 Hz, 3H), 1.13
2-bromobenzenesulfonyl chloride (0.255 g,
N-propylamine (0.071 g, 1.2 mmol) and triethylamine (0.7
mL, mmol) at room temperature over 12 in dry
dichloromethane (10 mL) affords the coupling product 33
after the addition of water (20 mL), extraction with dichlor-
omethane (20 mL), drying on MgSO4, evaporation and
purification on silica gel in 75% (0.208 g) yield. 1H NMR
1
mmol),
5
h
5994 | RSC Adv., 2013, 3, 5987–5996
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(300 MHz, MeOD) d 8.09 (d, J = 7.7 Hz, 1H), 7.81 (d, J = 7.7 Hz,
1H), 7.55–7.43 (m, 2H), 2.86 (t, J = 7.3 Hz, 2H), 1.47 (sext., J =
7.3 Hz, 2H), 0.85 (t, J = 7.3 Hz, 3H). 13C NMR (75 MHz, DMSO-
d6) d 139.9, 135.2, 133.7, 130.5, 128.1, 119.2, 44.3, 22.5, 11.0.
Elemental analysis: calcd (%) for C9H12BrNO2S (278.17): C
38.86, H 4.35; found: C 38.67, H 4.55.
(q, J = 273.1 Hz), 121.7 (m), 41.1, 29.2, 21.8. Elemental analysis:
calcd (%) for C21H17F6NO3S2 (509.49): C 49.51, H 3.36; found:
C 49.64, H 3.17.
Acknowledgements
N-Propyl-2-(2-isobutylthiazol-5-yl)-benzenesulfonamide (34).
From 2-bromo-N-propylbenzenesulfonamide (0.278 g, 1 mmol)
and 2-i-butylthiazole (0.212 g, 1.5 mmol), product 34 was
obtained in 30% (0.101 g) yield. 1H NMR (300 MHz, DMSO-d6)
d 7.98–7.92 (m, 1H), 7.71 (s, 1H), 7.70–7.49 (m, 3H), 2.87 (d, J =
7.4 Hz, 2H), 2.73 (q, J = 7.4 Hz, 2H), 2.15–2.00 (m, 1H), 1.38–
1.30 (m, 2H), 0.98 (d, J = 7.5 Hz, 6H), 0.76 (t, J = 7.5 Hz, 3H). 13C
NMR (75 MHz, DMSO-d6) d 169.9, 142.0, 140.2, 133.9, 133.1,
132.0, 129.4, 129.0, 128.2, 44.3, 41.3, 29.2, 22.7, 22.0, 11.0.
Elemental analysis: calcd (%) for C16H22N2O2S2 (338.49): C
56.77, H 6.55; found: C 56.67, H 6.48.
2-(2-Isobutylthiazol-5-yl)-N-phenylbenzenesulfonamide (36)
and 10H-9-thia-10-aza-phenanthrene 9,9-dioxide (37). From
2-bromo-N-phenylbenzenesulfonamide (0.312 g, 1 mmol) and
2-i-butylthiazole (0.212 g, 1.5 mmol), products 36 and 37 were
not detected.
This research was supported by a CEFIPRA fellowship. We
thank the Centre National de la Recherche Scientifique and
‘‘Rennes Metropole’’ for providing financial support.
References
1 (a) J. J. Li and G. W. Gribble, Palladium in Heterocyclic
Chemistry, Pergamon: Amsterdam, 2000; (b) E. Negishi, Ed.
Handbook of Organopalladium Chemistry for Organic
Synthesis; Wiley-Interscience: New York, 2002; Part III, p
213.
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2-(5-Methylthiophen-2-yl)-benzenesulfonamide (39). From
2-bromobenzenesulfonamide (0.236 g,
1 mmol) and 2-
i-butylthiazole (0.212 g, 1.5 mmol), product 39 was not
detected.
N-Benzyl-2-(2-isobutylthiazol-5-yl)-N-methylbenzenesulfonamide
(41) and 6-methyl-6,7-dihydro-5-thia-6-aza-dibenzo[a,c]cycloheptene
5,5-dioxide (42)11. From N-benzyl-2-bromo-N-methylbenzenesulfo-
namide (0.340 g, 1 mmol) and 2-i-butylthiazole (0.212 g, 1.5 mmol),
using CsOAc (0.384 g, 2 mmol) as the base, product 41 was obtained
in 52% (0.208 g) yield, and product 42 was also obtained in 12%
(0.031 g) yield. 41 1H NMR (300 MHz, DMSO-d6) d 8.04 (d, J = 7.7 Hz,
1H), 7.78–7.68 (m, 3H), 7.57 (d, J = 7.7 Hz, 1H), 7.40–7.25 (m, 3H), 7.18
(d, J = 7.7 Hz, 2H), 4.04 (s, 2H), 2.88 (d, J = 7.6 Hz, 2H), 2.47 (s, 3H),
2.07–2.02 (m, 1H), 0.96 (d, J = 7.6 Hz, 6H). 13C NMR (75 MHz, DMSO-
d6) d 170.2, 142.4, 138.7, 135.9, 134.5, 132.7, 132.6, 129.6, 129.4, 129.3,
128.5, 127.9, 127.6, 52.3, 41.2, 33.3, 29.2, 21.9. Elemental analysis:
calcd (%) for C22H25NO2S2 (400.56): C 62.97, H 6.04; found: C 62.64,
H 6.17.
3,5-Dimethylphenyl 2-(2-isobutylthiazol-5-yl)-benzenesulfo-
nate (44) and 1,3-dimethyldibenzo[1,2]oxathiine 6,6-dioxide
(45)11. From 3,5-dimethylphenyl 2-bromobenzenesulfonate
(0.341 g, 1 mmol) and 2-i-butylthiazole (0.212 g, 1.5 mmol),
product 45 was obtained in 90% (0.234 g) yield; whereas,
product 44 was not detected.
3,5-Bis(trifluoromethyl)phenyl 2-(2-isobutylthiazol-5-yl)-ben-
zenesulfonate (47) and 2,4-bis-trifluoromethyl-dibenzo[1,2]ox-
athiine 6,6-dioxide (48). From 2-bromobenzenesulfonic acid
3,5-bis-trifluoromethylphenyl ester (0.449 g, 1 mmol) and 2-
i-butylthiazole (0.212 g, 1.5 mmol), product 47 was obtained in
72% (0.367 g) yield; whereas, product 48 was not detected. 47
1H NMR (300 MHz, DMSO-d6) d 8.19 (s, 1H), 8.09 (d, J = 8.0 Hz,
1H), 7.92 (t, J = 8.0 Hz, 1H), 7.81 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H),
7.74 (t, J = 8.0 Hz, 1H), 7.65 (s, 2H), 2.88 (d, J = 7.7 Hz, 2H),
2.10–2.00 (m, 1H), 0.94 (d, J = 7.7 Hz, 6H). 13C NMR (75 MHz,
DMSO-d6) d 170.9, 148.7, 142.8, 135.4, 134.7, 133.0, 132.4 (q, J
= 34.0 Hz), 131.4, 131.1, 130.9, 129.9, 123.5 (q, J = 3.4 Hz), 122.2
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5996 | RSC Adv., 2013, 3, 5987–5996
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