G Model
CCLET 5471 No. of Pages 4
2
Z. Li et al. / Chinese Chemical Letters xxx (2019) xxx–xxx
Table 1
a
The optimization of α,α-dichloroacetophenone.
Entry
Variation from standard condition
Yield (%)b
1
2
3
4
5
6
7
8
9
None
77
65
54
60
70
72
68
72
NaCl as chlorine source
NH
4
Cl as chlorine source
KCl as chlorine source
n
Bu
Bu
Bu
4
4
4
NBF
NHSO
NPF as electrolyte
4
as electrolyte
n
n
4
as electrolyte
6
10 mA as electric current
20 mA as electric current
54
1
0
Pt (+)-C (À) as electrode system
C (+)-Pt (À) as electrode system
C (+)-C (À) as electrode system
8 mL MeCN, 2 mL HCl (1.2 mol/L, aq.)
10 mL HCl (1.2 mol/L, aq.)
70
61
58
1
1
1
2
c
c
c
c
93(92)d
trace
74
1
3
1
4
1
5
7 mL MeCN, 3 mL HCl (1.2 mol/L, aq.)
9 mL MeCN, 1 mL HCl (1.2 mol/L, aq.)
16
82
a
4
0.5 mmol phenylacetylene, 0.5 mmol LiClO , 2 mL HCl (1.2 mol/L, aq.), 6 mL
MeCN were added in the anodic compartment of the electrolysis cell; 0.5 mmol
LiClO , 8 mL H SO (0.6 mol/L) were added in the cathodic compartment of the
4
2
4
electrolysis cell, r.t., 15 mA, Pt-Pt.
b
c
1
HNMR yield, MeNO
2
as internal standard.
Variation of anodic compartment, while 10 mL H
2
4
SO (0.6 mol/L) in the cathodic
compartment.
d
Isolated yield.
substrate, α,α-dibromoacetophenone was tried to be obtained
under the optimized condition (entry 13). However, only less than
3
0% of the desired product was obtained and 1,2-dibromophenyl-
ethylene was generated as the major product. The oxybromolation
can also be carried out smoothly to give the corresponding product
with moderate to good yields. Nevertheless, the solvent MeCN
disfavored this oxybromolation while water promoted this
transformation. After optimization, it was found that the acidic
water solution was benefit to this oxybromolation. For instance, α,
α-dibromoacetophenone can be obtained with the yield of 53%
Scheme 1. Synthesis of α,α-dihaloketones.
which contained 6 mL of MeCN and 2 mL of HCl (1.2 mol/L, aq.) as
solvent. The cathodic compartment was filled with 8 mL of H SO
0.6 mol/L). Then 0.5 mmol of LiClO was added as electrolyte in
2
4
(
4
both electrolysis compartments. The two cells were separated by a
membrane which can be selectively permeable for the positive
2 4
when MeCN:H SO (0.6 mol/L, total volume 10 mL) was 1:1, while
2
ions (TRJCM Type, 1.5 Â1.5 cm ).
the reaction yield achieved 63% when the ratio was changed to 1:9.
2
À
Initially, the reaction was carried out with a 10 mA/cm Pt-Pt
In order to avoid the interference of Cl , H
2
SO
4
(0.6 mol/L) was
electrode system at room temperature. As expected, 77% of the
used as the acid. Ultimately 10 mL of H
2
SO
4
(0.6 mol/L) was chosen
desired product was obtained (Table 1, entry 1). When NaCl, NH
4
Cl
as the solvent in the anodic compartment, and KBr was added as
the source of bromine (Table S2 in Supporting information). Under
this modified conditions, the yield of α,α-dibromoacetophenone
can reach 83%.
or KCl was employed to replace HCl (1.2 mol/L) as chlorine source,
the yield of the desired product was decreased, giving the reaction
yield 65%, 54% and 60%, respectively (entries 2–4). This indicated
that acidic environment at the anode favored the reaction. Then
various ammonium salt electrolytes were examined in place of
With the optimized conditions in hand, the scope of the
reaction substrates was investigated, as shown in Scheme 2. The
results showed that a variety of alkyne derivatives were suitable for
this electrochemical transformation, affording the α,α-dichloroa-
cetophenones with the yields of 31%–96% except for 2m, which
only generated in trace amount. This phenomenon was probably
due to the steric effect. Similar result was also observed when
diphenylacetylene was used as the reaction substrate. Compared
with 2d and 2f, 2e was obtained in lower yield, which maybe
resulted from the steric effect. When the phenyl group was
replaced by substituted phenyl, such as F-, Cl-, Br-phenyl (2b-2f),
the reaction still afforded satisfied results. Similarily, 4-cyanophe-
nylacetylene can be converted to 2l successfully. Except for 2p,
either electron-donating groups (2g-2k) or electron-withdrawing
groups (2n and 2o) had little influence on the reaction yields (65%–
94%). The lower yields of 2j and 2k (74% and 65%) were probably
due to the existence of methylene groups, which tended to occur
4
LiClO . The experimental results showed that the reaction still
proceeded smoothly in spite of a slight decrease in the reaction
yields (entries 5–7). Either the increase or decrease in the current
density can result in the lower yields (entries 8 and 9). The
electrode optimization showed that Pt-Pt electrode couple was the
optimal for the reaction, while the Pt electrode was replaced by a
graphite rod would lead to poor yield (entries 10–12). On the other
hand, the solvent in anodic compartment had a significant effect on
the reaction (entries 13–16). For instance, the reaction yield
achieved 93% when the ratio of MeCN and HCl (1.2 mol/L) was 4:1
(
total volume 10 mL) in the anodic compartment (entry 13). The
higher or lower of this ratio would result in the low yield (entries
5 and 16). The addition of MeCN was necessary since a trace
1
amount of the desired product was generated when water was the
only solvent (entry 14). To extend the scope of the reaction