Amidation of aryl halides with isocyanides using a polymer-supported palladium-n-heterocyclic carbene complex as an efficient, phosphine-free and heterogeneous recyclable catalyst

Article abstract of DOI:10.1055/s-0033-1340733

The amidation of aryl halides with alkyl/aryl isocyanides to give the corresponding amides using polymer-supported palladium-N-heterocyclic carbene complex (PS-Pd-NHC) as an efficient heterogeneous recyclable catalyst is described. The catalytic system was optimized with respect to various reaction parameters giving excellent yields of the desired products. The catalyst can be easily separated by a simple filtration process and recycled further for up to four consecutive recycle without any loss of activity and selectivity. The protocol is advantageous due to the ease in handling of the catalyst, simple workup procedure, phosphine-free, and effective catalyst recyclability. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1340733

1236▌
PAPER
paper
Amidation of Aryl Halides with Isocyanides Using a Polymer-Supported
Palladium–N-Heterocyclic Carbene Complex as an Efficient, Phosphine-Free
and Heterogeneous Recyclable Catalyst
Amidation of Aryl Halides
Bhikan J. Khairnar, Bhalchandra M. Bhanage*
Department of Chemistry, Institute of Chemical Technology, N. Parekh Marg, Matunga, Mumbai 400 019, India
Fax +91(22)33611020; E-mail: bm.bhanage@gmail.com; E-mail: bm.bhanage@ictmumbai.edu.in
Received: 16.11.2013; Accepted after revision: 12.01.2014
to employ a heterogeneous catalyst for this transforma-
Abstract: The amidation of aryl halides with alkyl/aryl isocyanides
tion. In this respect N-heterocyclic carbene ligands have
to give the corresponding amides using polymer-supported palladi-
found potential applications in homogeneous catalysis
um–N-heterocyclic carbene complex (PS-Pd-NHC) as an efficient
heterogeneous recyclable catalyst is described. The catalytic system
due to their effective binding ability to any transition met-
was optimized with respect to various reaction parameters giving al irrespective of their oxidation state.7 Theoretical calcu-
excellent yields of the desired products. The catalyst can be easily
separated by a simple filtration process and recycled further for up
lations showed that NHC ligands have very high
dissociation energies compared to phosphine ligands.
to four consecutive recycle without any loss of activity and selectiv-
Therefore, the coordination between NHC and transition
ity. The protocol is advantageous due to the ease in handling of the
metal is much stronger. They are chemically and thermal-
catalyst, simple workup procedure, phosphine-free, and effective
ly more inert towards cleavage than other metal complex-
es and they are also air- and moisture-stable. Recently,
polymer-supported palladium–N-heterocyclic carbene
(PS-Pd-NHC) catalyst has been explored for various cou-
pling reactions, as it offers several advantages such as the
reuse of expensive palladium and ligands with the possi-
bility of preventing contaminating ligand residue in the
product.8
catalyst recyclability.
Key words: amides, heterogeneous catalysis, palladium, cross-
coupling, phosphine-free
The amide functional group is important in synthetic or-
ganic chemistry; it plays a major role in the elaboration
and composition of biological and chemical systems and
polymer compounds.1 While amide bond formation re-
mains a fundamental reaction in organic chemistry, it is
usually created by the reactions of carboxylic acids with
amines using coupling reagents, or by prior conversion of
carboxylic acids to derivatives such as acid chlorides or
anhydrides.2 Alternative strategies for the synthesis of
amides have been explored, which include metal-cata-
lyzed aminocarbonylation of aryl halides,3 or transition-
metal-catalyzed oxidative coupling between benzyl alco-
hols and amines using silver-, ruthenium-, and rhodium-
based catalytic systems. However, the use of lethal carbon
monoxide gas and use of various oxidants limits the appli-
cation of such methods.4
Jiang and co-workers5 reported a new methodology for
the synthesis of amides through the coupling of aryl ha-
lides and isocyanides, as the amide source, using a homo-
geneous palladium–triphenylphosphine catalytic system.
However, the principal drawbacks of this homogeneous
method are stability, cost of palladium and the phosphine
ligand, and its lack of reusability. Heterogeneous phos-
phine ligand-free cross-coupling reactions have been en-
thusiastically investigated because of easy product
separation from the reaction mixture and low cost bur-
den.6 One method used to develop an atom-economic pro-
cess that can minimize the loss of expensive palladium is
We have developed a PS-Pd-NHC catalyzed protocol for
the synthesis of amides by coupling between aryl halides
and isocyanides (Scheme 1). Isocyanides are important
synthons in various organic transformations.9,10 We found
that the isocyanide acts as source of the amide function in
such transformations. However, to the best of our knowl-
edge, no such heterogeneous/polymer-supported phos-
phine-free catalytic system has been explored for the
amidation of aryl halides with isocyanides.
O
X
PS-Pd-NHC (1 mol%)
R2
N
R2
+
N
H
CsF, DMSO–H2O
R1
X = I, Br, Cl
R1
N
N
N
N
Me
Pd
AcO
Me
OAc
PS-Pd-NHC
Scheme 1 PS-Pd-NHC catalyzed amidation of aryl halides with iso-
cyanides
SYNTHESIS 2014, 46, 1236–1242
Advanced online publication: 10.03.2014
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DOI: 10.1055/s-0033-1340733; Art ID: SS-2013-Z0750-OP
© Georg Thieme Verlag Stuttgart · New York

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Amidation of Aryl Halides
1237
At the onset of the research, we made a conscious effort to (entries 5, 10–14, and 19). Dimethyl sulfoxide–water
develop a catalytic system that would address the limita- (9:1) was the best combined solvent system for synthesis
tions of the previously reported palladium-catalyzed ami- of 3a (entry 5). Dry dimethyl sulfoxide provided trace
dation reaction. During the preliminary studies amounts of 3a (entry 14). Water is necessary for this reac-
iodobenzene (1a) was reacted with tert-butyl isocyanide tion because water is the source of the carbonyl oxygen
(2a) used as the model system. A series of experiments and the hydrogen atom on the nitrogen of the amide func-
were performed to optimize various reaction parameters, tion. A study of the effects of temperature (entries 5, 15,
such as the catalyst, catalyst loading, base, solvent, tem- and 16) showed that the yield of 3a increased with in-
perature, and time (Tables 1 and 2). Initially we screened creasing reaction temperature (from 80 °C to 90 °C), but
various heterogeneous palladium catalyst such as 5% there was a slight decrease when the temperature was fur-
Pd/C, 10% Pd/C, polymer-supported triphenylphosphine– ther increased to 100 °C, thus 90 °C is the optimum tem-
palladium (PS-TPP-Pd), and PS-Pd-NHC (Table 1, en- perature. The reaction time was optimized at nine hours
tries 1–4).
(entries 5, 17, and 18).
Table 1 Effect of Catalyst Screening and Loading on the Amidation
Table 2 Effect of Reaction Parameters on the Amidation Reactiona
Reactiona
O
O
I
PS-Pd-NHC
N
+
I
N
H
Pd catalyst
N
base, solvent
N
H
+
Entry Base
Solvent
Temp (°C) Yieldb (%)
Entry
Catalyst
Catalyst loading (mol%) Yieldb (%)
1
K2CO3
DMSO–H2O (9:1)
DMSO–H2O (9:1)
DMSO–H2O (9:1)
DMSO–H2O (9:1)
DMSO–H2O (9:1)
DMSO–H2O (9:1)
DMSO–H2O (9:1)
DMSO–H2O (9:1)
DMSO–H2O (9:1)
1,4-dioxane
90
90
90
90
90
90
90
90
90
90
90
90
90
90
100
80
90
90
90
58
52
64
86
96
8
1
2
3
4
5
6
7
Pd/C (5%)
5
12
2
K3PO4
NaHCO3
Cs2CO3
CsF
Pd/C (10%)
PS-TPP-Pd
PS-Pd-NHC
PS-Pd-NHC
PS-Pd-NHC
PS-Pd-NHC
5
18 (24)c
72
3c
4
2
1
96
5
0.5
0.72
1.5
84
6
KF
86
7
t-BuOK
Et3N
Cs2CO3
CsF
26
32
88
18
34
16
76
6
97
8
a Reaction conditions: PhI (1 mmol), t-BuNC (1.2 mmol), CsF (1
mmol), DMSO–H2O (9:1, 2 mL), 90 °C, 9 h.
b GC yields.
9c
10
c Reaction catalyst loading 10 mol%.
11
12
13
14
15
16
17d
18e
19
CsF
DMF
Among the catalysts examined, polymer-supported het-
erogeneous PS-Pd-NHC complex was found to be the
best, providing excellent yields of the desired product 3a.
We further studied catalyst loadings ranging from 0.5 to
1.5 mol%; increasing the catalyst concentration from 0.5
to 1.0 mol% increased the yield of 3a to 96%, a further in-
crease to 1.5 mol% did not improve the yield further (Ta-
ble 1, entries 4–7). As the base will have an impact on the
overall process, the effects of various bases (Table 2, en-
tries 1–8) were examined; the best results was obtained
with cesium fluoride which afforded 3a in 96% yield (en-
try 5). Cesium carbonate also gave 3a in 86% yield (entry
4), which increased to 88% when two equivalents of cesi-
um carbonate were used (entry 9). To design a reaction
that is both efficient and tolerant of functional groups, the
correct choice of base, one that is not too strong or too
weak, is essential. Experiments have shown that both ce-
sium carbonate or cesium fluoride provide this balance.
An investigation of the strength of some common bases in
aprotic solvents support these findings. We also studied
the effects of various solvents on the amidation reaction
CsF
MeCN
CsF
DMSO–H2O (4:1)
DMSO
CsF
CsF
DMSO–H2O (9:1)
DMSO–H2O (9:1)
DMSO–H2O (9:1)
DMSO–H2O (9:1)
H2O
92
74
84
98
–
CsF
CsF
CsF
CsF
a Reaction conditions: PhI (1 mmol), t-BuNC (1.2 mmol), PS-Pd-
NHC (1 mol%), base (1 mmol), solvent (2 mL), 9 h.
b Conversion based on GC analysis.
c Base (2 mmol).
d Time 8 h.
e Time 12 h.
Having optimized reaction conditions in hand, we ex-
plored the substrate scope of the PS-Pd-NHC catalyzed
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1236–1242

1238
B. J. Khairnar, B. M. Bhanage
PAPER
amidation. Various aryl halides containing different func- aryl chlorides. Aryl bromides were well tolerated and
tional groups were investigated (Scheme 2). Products con- gave 3a–c,l,m in slightly lower yields, but aryl chlorides
taining electron-donating 3b–e as well as electron- gave 3a–c,l,m in moderate yields only after increasing the
withdrawing groups 3f–p were obtained. Gratifyingly a catalyst loading up to 2 mol% and increasing the reaction
variety of common functional group, such as alkyl, ether, temperature to 120 °C for 12 hours.
hydroxy, halo, nitro, cyano, and acetyl, were tolerated re-
gardless of the meta- or para-position, however ortho-
substituted iodobenzenes gave lower yields of 3q,r, pos-
A small number of aryl- and alkyl-substituted isocyanides
were examined and these provided the corresponding am-
ides 3s–u in good yields.
sibly due to steric hindrance. Next we widened the scope
In order to make our catalytic system more economical,
of the PS-Pd-NHC catalyst by utilizing aryl bromides and
we focused on the reusability of the PS-Pd-NHC catalyst
in this amidation reaction. As shown in Scheme 3, the cat-
alyst exhibited remarkable activity in the first two consec-
utive recycles, while a slight decrease in conversion was
O
R2
X
PS-Pd-NHC (1 mol%)
CsF, DMSO–H2O
observed during the third and fourth recycle. The leaching
of palladium in solution was checked by ICP-AES analy-
sis of the reaction mixture and the palladium content was
found to be below detectable level (0.01 ppm), which re-
vealed no significant leaching of palladium catalyst.
N
R1
H
R1
C
N
2
R2
+
1
3
HN t-Bu
MeO
HN t-Bu
HN t-Bu
O
O
O
I
3a, X = I, 92%
3b, X = I, 88%
3c, X = I, 82%
= Br, 84%
= Br, 78%
= Br, 76%
+
N
= Cl, 48%
= Cl, 44%
= Cl, 38%
MeO
1a
2a
HN t-Bu
HN t-Bu
HN t-Bu
1st run
nd run
3rd run
th run
96%
96%
94%
88%
HO
Cl
CsF
O
O
O
2
MeO
Cl
PS-Pd-NHC
DMSO–H2O
3d, X = I, 84%
3e, X = I, 78%
3f, X = I, 86%
F
HN t-Bu
HN t-Bu
HN t-Bu
4
F
O
O
O
O
3g, X = I, 76%
3h, X = I, 90%
3i, X = I, 87%
F
NC
N
H
HN t-Bu
HN t-Bu
HN t-Bu
NC
3a
O
O
O
F
Scheme 3 Recycle study of amidation reaction; conversion based on
GC analysis
3j, X = I, 72%
3k, X = I, 88%
3l, X = I, 83%
= Br, 72%
= Cl, 36%
O2N
O2N
In summary, the present study reports an efficient method
for the amidation of aryl halides using a stable heteroge-
neous PS-Pd-NHC complex as a versatile phosphine-free
recyclable catalyst. The present protocol tolerates a wide
range of functional groups and it was applicable to a vari-
ety of aryl halides (I, Br, Cl) furnishing good to excellent
yields of the corresponding products. Furthermore, the
catalytic system was also recycled for up to four consecu-
tive recycles with maintenance of the catalytic activity.
This protocol provides an alternative route for the carbon-
ylation and oxidative amidation reaction under heteroge-
neous conditions. Thus, we believe that the present
protocol will be a useful contribution in the amidation of
aryl halides using isocyanide as amide source with the use
of a heterogeneous recyclable catalyst.
HN t-Bu
Cl
HN t-Bu O
HN t-Bu
O
O
MeO
O
3m, X = I, 86%
= Br, 74%
3n, X = I 80%
3o, X = I 78%
= Cl, 32%
HN t-Bu
HN t-Bu
HN t-Bu
S
O
O
3p, X = I, 86%
O
O
NO2
3q, X = I, 14%
O
HN
N
N
H
H
O
3s, X = I, 79%
3t, X = I, 82%
3u, X = I, 74%
Scheme 2 PS-Pd-NHC catalyzed synthesis of secondary amides. Re-
action conditions: aryl iodide or bromide (1.0 mmol), isocyanide (1.2
mmol), PS-Pd-NHC (1 mol%), CsF (1.0 equiv), DMSO–H2O (9:1, 2
mL), 90 °C, 9 h; aryl chloride (1.0 mmol), isocyanide (1.2 mmol), PS-
Pd-NHC (2 mol%), 120 °C, 12 h. Yields are isolated yields based on
the aryl halide.
All chemicals and reagents were purchased from commercial sup-
pliers. Polymer-supported palladium–N-heterocyclic carbene com-
plex (PS-Pd-NHC) was prepared according to our previously
reported procedure.8a Loading of palladium catalyst on chlorometh-
yl polystyrene resin support was evaluated by ICP-AES analysis
Synthesis 2014, 46, 1236–1242
© Georg Thieme Verlag Stuttgart · New York

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Amidation of Aryl Halides
1239
and was found to be about 0.29 mmol·g–1 of support.8 The progress
of the reaction was monitored by gas chromatograph. The product
was purified by column chromatography on silica gel (100–200
GC-MS (EI): m/z (%) = 207 (11.6, M+), 192 (6.2), 151 (22.6), 136
(8.7), 135 (100), 107 (7.3), 92 (9.1), 77 (14), 64 (5.3), 41 (3.7).
N-tert-Butyl-3,5-dimethoxybenzamide (3d)1e
Light yellow solid; yield: 199 mg (84%); mp 114–116 °C. (Lit.1e
115.28 °C).
1
mesh). H NMR spectra were recorded on Varian-300/400 MHz
and the 13C NMR spectra were recorded on a 75/100 MHz NMR
spectrometer in CDCl3 or DMSO-d6 using TMS as the internal stan-
dard. Melting point ranges were determined in open capillaries and
are uncorrected.
IR (KBr): 3337, 2964, 2934, 1639, 1595, 1534, 1456, 1390, 1351,
1315, 1228, 1204, 1155, 1066, 925, 850, 801, 769, 735 cm–1.
1H NMR (300 MHz, CDCl3): δ = 6.85 (s, 2 H), 6.54 (s, 1 H), 6.01
(br s, 1 H), 3.80 (s, 6 H), 1.46 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 166.58, 160.67, 138.07, 104.61,
102.95, 55.42, 51.51, 28.69.
GC-MS (EI): m/z (%) = 237 (38.4, M+), 222 (7.2), 207 (3.3), 181
(37.1), 180 (10.6), 166 (12.8), 165 (100), 151 (4.4), 149 (4.8), 137
(25.9), 122 (16.9), 107 (10.6), 77 (10.8), 63 (6.3), 57 (6.7), 44
(11.0), 41 (9.0).
Benzamides 3; General Procedure
A mixture of aryl halide (1.0 mmol), CsF (1.0 mmol), PS-Pd-NHC
(1 mol%), and DMSO–H2O (9:1) (2 mL) were added successively
to a 10-mL round-bottom flask. The mixture stirred at r.t. for 10
min. Then isocyanide (1.2 mmol) was added and the mixture was
stirred with a magnetic stirrer at 90 °C for 9 h. The mixture was fil-
tered to separate the catalyst and the filtrate was extracted with
EtOAc (3 × 5 mL). The combined organic layers were dried (anhyd
Na2SO4), filtered, and concentrated in vacuo. The residue was puri-
fied by column chromatography (petroleum ether–EtOAc, 10:1) to
give the final pure product.
N-tert-Butyl-4-hydroxybenzamide (3e)12
White solid; yield: 150 mg (78%); mp 188–190 °C (Lit.12 mp 189–
192 °C).
Reuse of PS-Pd-NHC; Typical Procedure
After the reaction mixture had been passed through a filter paper,
the crude PS-Pd-NHC was washed with distilled H2O (3 × 5 mL)
and MeOH (3 × 5 mL) to remove trace amounts of organic material
if present. The filtered washed catalyst was then dried under re-
duced pressure and activated at 80 °C for a period of 4 h prior to the
next recycle. The dried catalyst was then used in catalyst recyclabil-
ity experiments and it was observed that the recovered catalyst
could be reused up to 4 consecutive cycles affording good to appre-
ciable yield of the desired product.
IR (KBr): 3338, 2972 (broad), 2780, 1611, 1550, 1509, 1455, 1393,
1362, 1325, 1283, 1218, 1168, 1150, 1105, 965, 915, 881, 845, 772,
710 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.60 (d, J = 8.4 Hz, 2 H), 7.26 (s,
1 H), 6.85–6.76 (m, 2 H), 5.91 (br s, 1 H), 1.46 (s, 9 H).
GC-MS (EI): m/z (%) = 193 (15.9, M+), 178 (13.3), 156 (1.8), 137
(15.3), 121 (100), 89 (21.2), 58 (45.0), 45 (63.6), 44 (50.1).
N-tert-Butyl-4-chlorobenzamide (3f)5,9f,13
Light yellow solid; yield: 181 mg (86%); mp 138–140 °C (Lit.5,9f
138–140 °C; Lit13 mp 136–137 °C).
N-tert-Butylbenzamide (3a)1e,5,11
White solid; yield (X = I): 163 mg (92%); mp 134–136 °C (Lit.1e
136.14 °C, Lit.5 134–136 °C).
IR (KBr): 3324, 3062, 2977, 2931, 1635, 1594, 1537, 1488, 1450,
1391, 1361, 1319, 1219, 1113, 1090, 1015, 971, 929, 872, 848, 762,
720 cm–1.
IR (KBr): 3323, 3064, 2978, 1635, 1539, 1491, 1451, 1365, 1312,
1218, 1079, 936, 877, 804, 719 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.64 (d, J = 8.6 Hz, 2 H), 7.32 (d,
J = 8.6 Hz, 2 H), 6.22 (br s, 1 H), 1.45 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 165.78, 136.92, 134.14, 128.38,
1H NMR (300 MHz, CDCl3): δ = 7.72 (d, J = 7.2 Hz, 2 H), 7.47–
7.38 (m, 3 H), 6.078 (br s, 1 H), 1.464 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 166.84, 135.78, 130.91, 128.3,
126.6, 51.41, 28.72.
128.1, 51.59, 28.63.
GC-MS (EI): m/z (%) = 213 (3.6), 211 (11.3, M+), 198 (5.4), 196
(16.7), 158 (4.0), 156 (12.4), 141 (31.4), 139 (100), 113 (9.4), 111
(24.8), 77 (1.9), 75 (13.7), 56 (5.6), 44 (3.8), 41 (8.1).
GC-MS (EI): m/z (%) = 177 (13.8, M+), 162 (18.9), 154 (6.9), 122
(12.7), 105 (100), 77 (34.7), 51 (12), 44 (32.5).
N-tert-Butyl-4-methylbenzamide (3b)1e,5,9f
White solid; yield (X = I): 168 mg (88%); mp 112–114 °C (Lit.1e
116.64 °C, Lit.5,9 114–116 °C).
N-tert-Butyl-3-chlorobenzamide (3g)9f,11,14
White solid; yield: 160 mg (76%); mp 102–104 °C (Lit.9f mp 99–
101 °C).
IR (KBr): 3354, 2980, 2962, 1636, 1611, 1547, 1506, 1478, 1454,
1387, 1362, 1320, 1307, 1222, 1119, 876, 836, 752 cm–1.
1H NMR (300 MHz, CDCl3): δ = 6.62 (d, J = 8.1 Hz, 2 H), 7.19 (d,
J = 7.5 Hz, 2 H), 5.99 (br s, 1 H), 2.37 (s, 3 H), 1.46 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 166.76, 141.24, 132.95, 128.97,
126.60, 51.37, 28.80, 21.27.
IR (KBr): 3275, 3071, 2963, 2929, 2869, 1640, 1597, 1453, 1362,
1318, 1276, 1216, 1096, 1077, 897, 809, 790, 756, 733 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.67 (s, 1 H), 7.56 (d, J = 7.6 Hz,
1 H), 7.38 (d, J = 8.2 Hz, 1 H), 7.28 (t, J = 7.7, 7.6 Hz, 1 H), 6.24
(br s, 1 H), 1.46 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ =165.53, 137.55, 134.27, 130.79,
129.52, 127, 124.74, 51.68, 28.6.
GC-MS (EI): m/z (%) = 213 (4.5), 211 (13.5, M+), 198 (7.2), 196
(21.3), 160 (1.6), 158 (5.5), 141 (31.3), 139 (100), 113 (12.6), 111
(30.2), 75 (16.6), 44 (5.5).
GC-MS (EI): m/z (%) = 191 (14.8, M+), 182 (20.2), 176 (11.5), 167
(10.5), 136 (6.3), 119 (100), 91 (27.9), 65 (13.9), 41 (5.7).
N-tert-Butyl-4-methoxybenzamide (3c)1e,5
White solid; yield (X = I): 170 mg (82%); mp 116–118 °C (Lit.1e
116.60 °C, Lit.5 118–120 °C).
N-tert-Butyl-4-fluorobenzamide (3h)5
White solid; yield: 175 mg (90%); mp 128–130 °C. (Lit.5 126–
128 °C).
IR (KBr): 3327, 2973, 1640, 1551, 1508, 1456, 1357, 1323, 1255,
1221, 1178, 1033, 842, 770 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.68 (d, J = 8.8 Hz, 2 H), 6.88 (d,
J = 8.2 Hz, 2 H), 5.95 (br s, 1 H), 3.82 (s, 3 H), 1.46 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 166.38, 161.72, 128.36, 128.09,
113.48, 55.25, 51.34, 28.83.
IR (KBr): 3315, 3079, 2968, 2935, 1636, 1550, 1504, 1454, 1392,
1358, 1321, 1294, 1225, 1157, 1096, 882, 847, 764 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.75–7.71 (m, 2 H), 7.07 (t, J = 8.6
Hz, 2 H), 6.02 (br s, 1 H), 1.46 (s, 9 H).
© Georg Thieme Verlag Stuttgart · New York
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B. J. Khairnar, B. M. Bhanage
PAPER
13C NMR (75 MHz, CDCl3): δ = 166.03, 165.83, 162.7, 132.0,
129.0, 128.88, 115.43, 115.16, 51.6, 28.7.
GC-MS (EI): m/z (%) = 195 (9.8, M+), 180 (17.5), 140 (11.3), 124
(7.7), 123 (100), 95 (27.9), 75 (9.2), 57 (3.9), 56 (4.8), 44 (6.5).
1H NMR (300 MHz, CDCl3): δ = 8.52 (s, 1 H), 8.31 (d, J = 8.1 Hz,
1 H), 8.11 (d, J = 7.6 Hz, 1 H), 7.61 (t, J = 8.1 Hz, 1 H), 6.22 (br s,
1 H), 1.50 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 164.4, 148.0, 137.5, 133.0, 129.7,
125.6, 121.5, 52.2, 28.6.
GC-MS (EI): m/z (%) = 222 (10.0, M+), 207 (40.8), 167 (31), 150
(100), 120 (5.0), 104 (27.1), 76 (25.5), 56 (18.3).
N-tert-Butyl-3-fluorobenzamide (3i)5
Light yellow solid; yield: 170 mg (87%); mp 108–110 °C. (Lit.5
108–110 °C).
IR (KBr): 3275, 3073, 2979, 2764, 1636, 1585, 1546, 1484, 1451,
1391, 1364, 1320, 1214, 1119, 1073, 939, 881, 826, 805, 757 cm–1.
N-tert-Butyl-4-chloro-3-nitrobenzamide (3n)
Yellow solid; yield: 205 mg (80%); mp 120–122 °C.
1H NMR (400 MHz, CDCl3): δ = 7.41 (m, 3 H), 7.16 (m, 1 H), 5.89
(br s, 1 H), 1.47 (s, 9 H).
IR (KBr): 3310, 3070, 2990, 2966, 2872, 1637, 1605, 1536, 1475,
1457, 1394, 1348, 1319, 1224, 1129, 1053, 923, 896, 843, 753 cm–1.
13C NMR (100 MHz, CDCl3): δ = 165.55, 163.90, 161.44, 138.25,
138.19, 130.05, 129.97, 122.12, 122.09, 118.04, 117.83, 114.23,
114, 51.76, 28.74.
1H NMR (400 MHz, CDCl3): δ = 8.91 (d, J = 2.08 Hz, 1 H), 7.91–
7.88 (dd, J = 2.12, 6.28, 2.12 Hz, 1 H), 7.61 (d, J = 8.36 Hz, 1 H),
5.93 (br s, 1 H), 1.48 (s, 9 H).
GC-MS (EI): m/z (%) = 195 (13.2, M+), 180 (20.4), 152 (1.1), 140
13C NMR (75 MHz, CDCl3): δ = 163.47, 147.56, 135.66, 132.07,
(17), 123 (100), 95 (13.7), 75 (8.6), 41 (7.6).
131.35, 129.58, 123.85, 52.36, 28.66.
GC-MS (EI): m/z (%) = 258 (3.0), 256 (9.7, M+), 243 (14.8), 241
(45.1), 226 (2.1), 203 (10.8), 201 (31.1), 185 (8.5), 186 (33.8), 184
(100), 156 (27.1), 154 (7.0), 140 (12.7), 138 (38.2), 128 (2.4), 126
(6.0), 112 (7.9), 110 (24.3), 75 (18.3), 57 (14.3), 56 (36.9).
HRMS (ESI): m/z calcd for [C11H13ClN2O3Na+]: 279.0507; found:
279.0506.
N-tert-Butyl-3,5-difluorobenzamide (3j)
White solid; yield: 153 mg (72%); mp 116–118 °C.
IR (KBr): 3298, 3079, 2980, 2930, 1642, 1606, 1549, 1513, 1458,
1364, 1324, 1216, 1104, 950, 880, 778 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.58 (t, J = 8.6, 10 Hz, 1 H), 7.44
(s, 1 H), 7.20 (m, 1 H), 5.94 (br s, 1 H), 1.46 (s, 9 H).
Methyl 4-(tert-Butylcarbamoyl)benzoate (3o)1e
White solid; yield: 183 mg (78%); mp 124–126 °C. (Lit.1e
124.51 °C).
13C NMR (75 MHz, CDCl3): δ = 164.67, 153.86, 153.7, 151.82,
150.51, 150.34, 148.51, 148.34, 132.95, 123.08, 123.02, 122.97,
122.93, 117.28, 117.03, 116.65, 116.41, 51.88, 28.63.
IR (KBr): 3300, 3074, 2981, 2961, 1721, 1638, 1548, 1448, 1398,
1304, 1221, 1143, 1116, 1016, 870, 826, 795, 735 cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.03 (d, J = 8.5 Hz, 2 H), 7.77 (d,
J = 7.7 Hz, 2 H), 6.18 (br s, 1 H), 3.93 (s, 3 H), 1.48 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 166.24, 165.98, 139.8, 132.1,
129.6, 126.7, 52.2, 51.8, 28.66.
GC-MS (EI): m/z (%) = 235 (14.2, M+), 220 (24.1), 204 (6.7), 180
(20.3), 164 (10.6), 163 (100), 148 (6.2), 103 (13.9), 77 (8.5), 76
(10.5), 56 (6.5), 44 (6.6), 41 (7.2).
GC-MS (EI): m/z (%) = 213 (9.8, M+), 198 (22.0), 158 (14.6), 141
(100), 113 (30.3), 63 (10.8), 56 (9.6), 44 (4.7), 41 (8.7).
HRMS (ESI): m/z calcd for [C11H13F2NONa+]: 236.0857; found:
236.0869.
N-tert-Butyl-3-cyanobenzamide (3k)
White solid; yield: 178 mg (88%); mp 90–92 °C.
IR (KBr): 3329, 3065, 2973, 2930, 2234, 1643, 1582, 1540, 1478,
1451, 1361, 1304, 1219, 1218, 937, 815, 806, 745 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.99 (m, 2 H), 7.73 (d, J = 7.6 Hz,
1 H), 7.54 (t, J = 7.6, 8.1 Hz, 1 H), 6.25 (br s, 1 H), 1.48 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 164.69, 136.1, 134.1, 130.54,
129.34, 118.06, 112.46, 52.07, 28.63.
GC-MS (EI): m/z (%) = 202 (7.9, M+), 187 (25.5), 159 (1.0), 147
(23.6), 131 (8.9), 130 (100), 102 (33.2), 56 (13.3), 41 (9.8).
HRMS (ESI): m/z calcd for [C12H14N2ONa+]: 225.0998; found:
225.0996.
N-tert-Butylthiophene-3-carboxamide (3p)5
White solid; yield: 157 mg (86%); mp 160–162 °C. (Lit.5 159–
161 °C).
IR (KBr): 3318, 3082, 2973, 2930, 1627, 1550, 1510, 1475, 1453,
1392, 1361, 1305, 1218, 1070, 943, 846, 799, 754, 707 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.77 (s, 1 H), 7.31–7.25 (m, 2 H),
5.9 (br s, 1 H), 1.43 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 162.55, 138.9, 127.46, 126.21,
126.09, 51.57, 28.89.
GC-MS (EI): m/z (%) = 183 (17.8, M+), 168 (16.9), 128 (7.3), 111
(100), 85 (8.0), 83 (11.3), 57 (5.4), 44 (14.8), 39 (20.7).
N-tert-Butyl-4-cyanobenzamide (3l)5,9f
Yellow solid; yield: 168 mg (83%); mp 152–154 °C. (Lit.5 152–
153 °C; Lit.9f mp 151–153 °C).
IR (KBr): 3364, 3065, 2979, 2930, 2235, 1652, 1540, 1500, 1449,
1390, 1362, 1298, 1226, 874, 760 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.82 (d, J = 8.4 Hz, 2 H), 7.70 (d,
J = 8.1 Hz, 2 H), 6.07 (br s, 1 H), 1.48 (s, 9 H).
13C NMR (75 MHz, CDCl3): δ = 165.5, 139.79, 132.27, 127.46,
118.06, 114.55, 52.12, 28.68.
N-Cyclohexylbenzamide (3s)3f,5
White solid; yield: 160 mg (79%); mp 146–148 °C. (Lit.5 152–
154 °C).
IR (KBr): 3311, 3240, 3077, 2928, 2852, 1626, 1542, 1489, 1453,
1330, 1295, 1180, 1152, 1082, 1028, 970, 928, 891, 849, 808, 700
cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.75 (d, J = 7 Hz, 2 H), 7.50–7.40
(m, 3 H), 5.96 (br s, 1 H), 2.04 (d, 2 H), 1.78–1.73 (m, 2 H), 1.68–
1.62 (m, 1 H), 1.49–1.38 (m, 2 H), 1.29–1.17 (m, 3 H), 4.03–3.94
(m, 1 H).
GC-MS (EI): m/z = 202 (M+), 187, 171, 159, 147, 130, 102, 75, 56,
41.
N-tert-Butyl-3-nitrobenzamide (3m)5,9f,11
Light yellow solid; yield (X = I): 191 mg (86%); mp 128–130 °C.
(Lit.1e,5 126–128 °C).
13C NMR (100 MHz, CDCl3): δ = 166.57, 135, 131.04, 128.31,
126.79, 48.61, 33.04, 25.44, 24.85.
IR (KBr): 3361, 3115, 3058, 2964, 2928, 1646, 1616, 1535, 1477,
1450, 1390, 1350, 1308, 1219, 1078, 918, 814, 775, 721, 705 cm–1.
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Amidation of Aryl Halides
1241
GC-MS (EI): m/z (%) = 203 (24.7, M+), 160 (4.6), 146 (1.8), 123
(6.1), 122 (70.8), 105 (100), 79 (14.1), 77 (56.9), 67 (5.5), 51 (13.1),
44 (7.1), 41 (7.3).
Stocks, M. J. Org. Lett. 2010, 12, 4280. (d) Wu, X. F.;
Neumann, H.; Beller, M. Chem. Eur. J. 2010, 16, 9750.
(e) Ju, J.; Jeong, M.; Moon, J.; Jung, H. M.; Lee, S. Org.
Lett. 2007, 9, 4615. (f) Sawant, D. N.; Wagh, Y. S.; Bhatte,
K. D.; Bhanage, B. M. J. Org. Chem. 2011, 76, 5489.
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2010, 5, 2168.
N-Phenylbenzamide (3t)3f,13,15
White solid; yield: 162 mg (82%); mp 160–162 °C (Lit.13 mp 162.7–
163.2 °C; Lit.15 mp 161 °C).
IR (KBr): 3344, 3052, 1654, 1600, 1579, 1525, 1438, 1322, 1260,
1179, 1114, 1075, 1028, 927, 885, 790, 750, 715 cm–1.
1H NMR (400 MHz, DMSO-d6): δ = 10.23 (br s, 1 H), 7.95 (d, J =
7 Hz, 2 H), 7.78 (d, J =7.6 Hz, 2 H), 7.61–7.51 (m, 3 H), 7.35 (t, J =
6.62, 8.36 Hz, 2 H), 7.10 (t, J = 7.36 Hz, 1 H).
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13C NMR (100 MHz, DMSO-d6): δ = 165.70, 139.11, 135.01,
(e) Zweifel, T.; Naubron, J. V.; Grutzmacher, H. Angew.
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131.69, 128.74, 128.52, 127.74, 123.85, 120.57, 120.46.
GC-MS (EI): m/z (%) = 197 (34.4, M+), 166 (1.8), 139 (01.4), 130
(01.0), 105 (100), 77 (56.7), 65 (6.8), 51 (16.2), 44 (6.0).
N-Benzylbenzamide (3u)3f,15
White solid; yield: 156 mg (74%); mp 104–106 °C (Lit.15 mp 104 °C).
IR (KBr): 3290, 3061, 3031, 2927, 1637, 1602, 1547, 1491, 1452,
1417, 1361, 1316, 1261, 1152, 1057, 1028, 987, 929, 805, 793, 725
cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.79 (d, J = 7.12 Hz, 2 H), 7.52–
7.40 (m, 3 H), 7.36–7.26 (m, 5 H), 6.45 (br s, 1 H), 4.64 (d, 2 H).
13C NMR (100 MHz, CDCl3): δ = 167.41, 135.22, 134.26, 131.34,
128.56, 128.38, 127.67, 127.33, 126.94, 43.87.
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GC-MS (EI): m/z (%) = 211 (67.5, M+), 210 (25.7), 192 (1.1), 181
(2.0), 165 (1.3), 132 (1.6), 106 (28.0), 105 (100), 91 (11.0), 77
(64.9), 65 (6.9), 51 (20.1).
Acknowledgment
The author B.J.K. is greatly thankful to Council of Scientific and In-
dustrial Research (CSIR), New Delhi, India for providing the re-
search fellowship.
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Bhanage, B. M. Green Chem. 2011, 13, 1490. (b) Qureshi,
Z. S.; Revankar, S. A.; Khedkar, M. V.; Bhanage, B. M.
Catal. Today 2012, 198, 148. (c) Qureshi, Z. S.; Deshmukh,
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2004, 45, 5827. (f) Khedkar, M. V.; Khan, S. R.; Dhake, K.
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see: (a) Sha, F.; Huang, X. Angew. Chem. Int. Ed. 2009, 48,
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Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
n
nfomartit
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© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1236–1242

1242
B. J. Khairnar, B. M. Bhanage
PAPER
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Synthesis 2014, 46, 1236–1242
© Georg Thieme Verlag Stuttgart · New York