G Model
CCLET-2895; No. of Pages 4
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Y.-B. Jiang et al. / Chinese Chemical Letters xxx (2014) xxx–xxx
3. Results and discussion
The reaction of p-tolylboronic acid 1a (0.5 mmol), ammonia 2
(25% aqueous solution), propargyl bromide 3 (0.5 mmol), base
(1 mmol), Cu2O, and 2 mL of solvent under microwave-assisted
conditions was chosen as the model reaction for the preparation of
the N-monopropargylated product, 4-methyl-N-(prop-2-ynyl)-
aniline 4a, in which 5 min were allocated respectively in each
step (Table 1).
Scheme 1. One-pot synthesis of N-aryl propargylamine 4.
an internal standard. IR spectra were performed on a Nexus FT-IR
spectrophotometer. Commercially available reagents were used
without further purification. All reactions were monitored by TLC
with Huanghai GF254 silica gel-coated plates. Column chromatog-
raphy was carried out using 300–400 mesh silica gel at medium
pressure.
The realized yield of the product 4a was only 32% when the
system was heated to 70 8C for 3 h in each step without MW energy
(Table 1, entry 1), but increased to 61% when a microwave power of
5 W was used (entry 2). The reaction favored polar solvents, such
as DMSO, DMF, and H2O, and satisfactory yields were observed
(entries 2 and 5–16), whereas no product was detected when DCE,
or PhMe, was used as the solvent (entries 3 and 4). The reaction can
work smoothly in H2O, generating an excellent yield of 87% when
4 equiv. of ammonia and 0.1 equiv. of Cu2O were used (entry 7). A
higher or lower loading of ammonia or Cu2O will decrease the yield
(entries 8, 9, 15, and 16). The base, K2CO3, is more efficient than
others, such as Cs2CO3, KOAc, and Et3N in this reaction (entries 11–
14). A microwave power of 5 W was better than a lower, or higher,
one (entries 7, 10, and 11). The reaction proceeded more efficiently
when promoted by a microwave power of 5 W in 2 mL of H2O for
5 min in each step respectively using p-tolylboronic acid 1a
General procedure for the synthesis of 4: The microwave
reaction tube was charged with boronic acid 1 (0.5 mmol),
ammonia
2 (2 mmol, 25% aqueous solution), Cu2O (8 mg,
0.05 mmol), and H2O (2 mL). After the mixture was exposed to
5 W microwaves for 5 min, propargyl bromide 3 (59 mg, 0.5 mmol)
was added. The mixture was then irradiated under 5 W micro-
waves for another 5 min. The system was diluted with 30 mL of
H2O after the reaction was completed, and the mixture was then
extracted three times with EtOAc. The organic layer was separated,
washed with water and saturated brine, and dried over anhydrous
Na2SO4. The evaporation of the solvent provided the crude product,
which was subjected to column chromatography (silica gel, EtOAc-
petroleum ether 1:8–1:3) to yield N-aryl propargylamine 4.
4-Methyl-N-(prop-2-ynyl)aniline (4a) [11]: Yellow oil; 1H NMR
(0.5 mmol), ammonia
2
(4 equiv.), propargyl bromide
3
(0.5 mmol), Cu2O (0.1 equiv.), and K2CO3 as the base. The product,
4-methyl-N-(prop-2-ynyl)aniline 4a, was isolated with 87% yield
when this optimum reaction condition was used (entry 7).
A series of aromatic boronic acid 1 were then subjected to this
reaction under optimized reaction conditions. All the reactions
were completed within the total 10 min, and moderate to excellent
yields of N-aryl propargylamine 4 were achieved, as shown in
Table 2. The reaction of aromatic boronic acids containing electron-
donating groups, such as methyl and methoxyl, proceeded with
higher yields (Table 2, 4a and 4c) compared to anilines containing
electron-withdrawing groups, such as nitryl, bromo, chloro, and
iodo (Table 2, 4d–4k). Notably, aromatic boronic acids containing
either, an electron-donating, or an electron-withdrawing group at
the para position can provide excellent yields (Table 2, 4a, 4c, 4d,
4h, and 4i). Although the substrates containing the o-substituent
provided lower yields, the reactions can also be completed
smoothly within total 10 min (Table 2, 4f and 4j).
(400 MHz, CDCl3):
J = 8.27 Hz), 3.91 (d, 2H, J = 2.22 Hz), 3.73 (s, 1H), 2.25 (s, 3H),
2.20 (s, 1H).
d 7.03 (d, 2H, J = 8.18 Hz), 6.62 (d, 2H,
General procedure for the synthesis of 5: The tube was charged
with AgSbF6 (17 mg, 0.05 mmol) after the propargylation process
was completed. The mixture was irradiated by 5 W microwaves for
5 min. The system was diluted with 30 mL of H2O after completion
of the reaction, and the mixture was then extracted with EtOAc
three times. The organic layer was separated, washed with water
and saturated brine, and dried over anhydrous Na2SO4. Evapora-
tion of the solvent provided the crude product, which was then
subjected to column chromatography (silica gel, EtOAc-petroleum
ether 1:5–1:2) to obtain the quinoline derivatives 5.
6-Methylquinoline (5a) [12]: Light green oil; IR (KBr, cmÀ1):
3398, 3014, 1594, 1501, 1373, 1119, 829; 1H NMR (400 MHz,
CDCl3):
d 8.85 (dd, 1H, J = 1.44, 4.12 Hz), 8.07 (d, 1H, J = 8.28 Hz),
8.00 (d, 1H, J = 8.6 Hz), 7.58 (m, 1H), 7.55 (dd, 1H, J = 1.88, 8.6 Hz),
7.37 (dd, 1H, J = 4.24, 8.28 Hz), 2.54 (s, 3H).
Moreover, this procedure can be used as a facile method for the
synthesis of potential bioactive quinoline derivatives through a
Table 1
Optimization of the synthesis to 4-methyl-N-(prop-2-ynyl)aniline 4a.
Entry
Solvent
Equiv. of NH3ÁH2O
Base
Equiv. of Cu2O
MW (W)
Yield of 4aa
1b
2
3c
4c
5
DMSO
DMSO
DCE
2
2
2
2
2
2
4
3
5
4
4
4
4
4
4
4
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
KOAc
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.05
0.2
70 8C
5
32%
61%
N.R.
N.R.
60%
81%
87%
80%
82%
75%
79%
75%
45%
23%
78%
63%
5
PhMe
DMF
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
5
5
6
5
7
5
8
5
9
5
10
11
12
13
14
15
16
8
3
5
5
Et3N
5
K2CO3
K2CO3
5
5
a
Isolated yields.
b
c
This reaction was conducted by heating to 70 8C without microwave.
The reaction did not work.
Please cite this article in press as: Y.-B. Jiang, et al., One-pot synthesis of N-aryl propargylamine from aromatic boronic acid, aqueous
Jiang, Yu-Bo
