6
806 Ge et al.
Asian J. Chem.
solid. The product was further purified by recrystalization from
mixed solution of ethanol and water.Yield, 56 %, m.p. 126.1-
EXPERIMENTAL
-1
1
Boric acid was purchased fromAlfaAesar China (Tianjin)
126.5 ºC. IR (KBr, νmax, cm ): 3380, 3332, 1646, 1599. H
NMR (300 MHz, DMSO-d ) δ : 9.87 (1H, s, NH), 7.90-7.92
Co., Ltd.All the other reagents were obtained from Sinopharm
Chemical Reagent Co., Ltd.All reagents were used as received
without further purify.
6
H
(2H, d,ArH), 7.47-7.57 (3H, m,ArH), 7.36-7.38 (2H, d,ArH),
6.53-6.56 (2H, d, ArH), 4.95(2H, s, NH).
IR spectra were measured as KBr pellets on a Perkin Elmer
-
1
Specture one FT-IR Spectrometer in the 4000-400 cm region.
Routine NMR spectra were recorded on aVarian Mercury 300
RESULTS AND DISCUSSION
1
spectrometer with H NMR operating at 300 MHz. Melting point
Direct amide formation between carboxylic acids and
13
were recorded on a WRS-1B digital melting point apparatus
(
amines an important phenomena in organic chemistry . In
this study, the most common aromatic amines and benzoic
acid were screened. The results are summarized in Table-1. A
classical synthetic procedure involves benzoic acid, aromatic
amines and boric acid in the flask, equipped with a Dean-
Stark apparatus and either toluene or toluene-ethanol as
solvent, heated to reflux. In some cases, the addition of ethanol
is in order to increase the solubility of certain reactants.Azeo-
trope was continuously removed from the reaction system.
The mechanism of boronic acid catalysis in amide coupling
Shanghai precision & scientific instrument Co., Ltd.).
Procedure for the synthesis of the amides
N-phenylbenzamide (1): To a solution of benzoic acid
10 mmol) in toluene (30 mL), boric acid (0.6 mmol) was
(
added. After heated to 100 ºC, aniline (16 mmol) was added
to the mixture in portions. Then, other 20 mL of toluene was
added. The above reaction mixture was refluxed for 16 h and
water was collected azeotropically in the Dean-Stark trap. The
mixture was allowed to cool to room temperature, leading to
the precipitation of needle-like solid. The collected solid was
successively washed with warm water and dried at room
temperature to afford 1 in 47 %, m.p. 162.8-163.5 ºC. IR (KBr,
14
reactions was suggested by Yamamoto et al. . It can be also
applied in explanation of the catalytic behaviour of boric acid
(
Scheme-IIIa). Taking into account the condensation of
9
aromatic aldehydes and amides in the presence of boric acid
as a catalyst, another plausible reaction mechanism for the
synthesis under boric acid as an electron acceptor is also
supposed (Scheme-IIIb). Entries 1 and 4 show that boric acid
is capable of catalysis albeit at a lower rate (4 %). Boric acid
is mildly successful at producing the desired product (N-
phenylbenzamide, 47 % yield). This catalytic protocol was
successfully applied in amidation of other aromatic diamines.
The addition of massive boric acid (75 % mole fraction of
diamine) provided the amides in 63 % yield (N,N'-1,3-pheny-
lenebisbenzamide) and 76 % yield (N,N'-1,4-phenylene-
bisbenzamide). Considering the aromatic amine is less
nucleophilic, yields are acceptable.
-
1
1
ν
max, cm ): 3345, 1653, 1600. H NMR (300 MHz, DMSO-
) δ : 10.27 (1H, s, NH), 7.95-7.97 (2H, d, ArH), 7.78-7.80
2H, d, ArH), 7.50-7.62 (3H, m, ArH), 7.33-7.38 (2H, t, ArH),
d
6
H
(
7
.08-7.13 (1H, t, NH).
N,N'-1,4-phenylenebisbenzamide (2): The mixture of
benzoic acid (13 mmol) and boric acid (7 mmol) in 30 mL
toluene was heated to 60 ºC. Then 1,4-phenylenediamine (4
mmol), ethanol (5 mL) and toluene (25 mL) were added. The
reaction mixture was refluxed for 72 h and water was collected
azeotropically in the Dean-Stark trap. The collected solid was
successively washed with warm water and ethanol, then dried
at room temperature to afford 2 in 76 %, m.p. 342.2-345.1 ºC.
-1
1
IR (KBr, νmax, cm ): 3333, 1650, 1602. H NMR (300 MHz,
DMSO-d ) δ : 10.26 (2H, s, NH), 7.95-7.98 (4H, d, ArH),
.56 (4H, s, ArH), 7.49-7.62 (6H, m, ArH).
6
H
H
7
O
O
B
N,N'-1,3-phenylenebisbenzamide (3): The mixture of
Ar or R
1
,3-phenylenediamine (4 mmol) and boric acid (3 mmol) in
O
OH
OH
mixed 30 mL toluene and 5 mL ethanol was heated to 50 ºC.
After the solid dissolved, benzoic acid (13 mmol) was added.
The reaction mixture was refluxed for 48 h and water was
collected azeotropically in the Dean-Stark trap. Then, a large
number of light gray solid were found in the solution. The
collected solid was successively washed with warm water and
ethanol. And then dried at room temperature to afford 3 in
a
O
HO
OH
B
Ar or R
HO
+
B
OH
OH
b
O
OH
-1
Ar or R
6
1
8
3 %, m.p. 244.2-245.1 ºC. IR (KBr, νmax, cm ): 3263, 1648,
1
602. H NMR (300 MHz, DMSO-d
OH
6 H
) δ : 10.32 (2H, s, NH),
.34 (1H, s, ArH), 7.96-7.99 (4H, d, ArH), 7.49-7.60 (8H, m,
Scheme-III: Catalytic behaviour of boric acid
ArH), 7.29-7.35 (1H, t, ArH).
N-4-aminophenylbenzamide (4): A solution of 1,4-
phenylenediamine (10 mmol) and boric acid (0.4 mmol) in
toluene (30 mL) was heated to 100 ºC. Then, benzoic acid (10
mmol) and toluene (20 mL) was added to the mixture. The
above reaction mixture was refluxed for 16 h and water was
collected azeotropically in the Dean-Stark trap. The mixture
was allowed to cool to ambient temperature, filtered to get
Conclusion
We have developed an amidation that allows employing
aromatic amine and benzoic acid directly under boric acid
catalytic conditions. It is a simple procedure under mild reac-
tion condition and green catalyst, which can be extended to
various amidation of aromatic derivative.
Ge, Chunhua
