Ultrasound-assisted tandem reaction of alkynes and trihaloisocyanuric acids by thiourea as catalyst in water

Article abstract of DOI:10.1016/j.tet.2017.05.075

With water as the sole solvent, a green and efficient method has been developed for the synthesis of various α,α-dihaloketones via ultrasound assisted p-tolylthiourea catalyzed tandem reaction of alkynes with trihaloisocyanuric acids. This synthetic route

Full text of DOI:10.1016/j.tet.2017.05.075

Accepted Manuscript
Ultrasound-assisted tandem reaction of alkynes and trihaloisocyanuric acids by
thiourea as catalyst in water
Xingyu Zhang, Yundong Wu, Ya Zhang, Huilan Liu, Ziyu Xie, Shengmin Fu, Fang Liu
PII:
S0040-4020(17)30576-8
10.1016/j.tet.2017.05.075
TET 28741
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 27 February 2017
Revised Date: 20 May 2017
Accepted Date: 23 May 2017
Please cite this article as: Zhang X, Wu Y, Zhang Y, Liu H, Xie Z, Fu S, Liu F, Ultrasound-assisted
tandem reaction of alkynes and trihaloisocyanuric acids by thiourea as catalyst in water, Tetrahedron
(2017), doi: 10.1016/j.tet.2017.05.075.
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Ultrasound-assisted tandem reaction of
alkynes and trihaloisocyanuric acids by
thiourea as catalyst in water
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a,‡
b,‡
a
a
a
a
a,∗
Xingyu Zhang , Yundong Wu , Ya Zhang , Huilan Liu , Ziyu Xie , Shengmin Fu and Fang Liu
a
Key Laboratory of Comprehensive Utilization of Advantage Plants Resources in Hunan South, College of Chemistry and
Bioengineering, Hunan University of Science and Engineering, Yongzhou 425100, China
School of Material and Chemical Engineering, Tongren University, Tongren, Guizhou, 554300, P.R.C.
b

1
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Tetrahedron
journal homepage: www.elsevier.com
Ultrasound-assisted tandem reaction of alkynes and trihaloisocyanuric acids by
thiourea as catalyst in water
a,‡
b,‡
a
a
a
a
a,∗
Xingyu Zhang , Yundong Wu , Ya Zhang , Huilan Liu , Ziyu Xie , Shengmin Fu and Fang Liu
a
Key Laboratory of Comprehensive Utilization of Advantage Plants Resources in Hunan South, College of Chemistry and Bioengineering, Hunan University of
Science and Engineering, Yongzhou 425100, China
School of Material and Chemical Engineering, Tongren University, Tongren, Guizhou, 554300, P.R.C.
b
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
With water as the sole solvent, a green and efficient method has been developed for the
synthesis of various α,α-dihaloketones via ultrasound assisted p-tolylthiourea catalyzed tandem
reaction of alkynes with trihaloisocyanuric acids. This synthetic route could effectively avoid the
use of toxic organic solvents and transition metal catalysts, and the products could be obtained
in a very short time at room temperature with good to excellent yields.
Available online
Keywords:
ultrasound
alkyne
thiourea
trihaloisocyanuric acid
α,α-dihaloketones
2
017 Elsevier Ltd. All rights reserved.
1
. Introduction
bleaching agent. In contrast to common halogenating
reagents, TXCA has no irritating odor and is able to
transfer most part of their mass to the substrates.
Furthermore, in these reactions, cyanuric acid precipitates
α,α-Dihaloketones are important structural motifs and
intermediates for pharmaceuticals, agrochemicals and
natural products, and their high reactivity makes them react
with a large number of nucleophiles to provide a variety of
useful compounds. Consequently, the development of
as a by-product, which can be recovered by filtration and
5
reused to prepare trihaloisocyanuric acid.
1
Ultrasound-assisted organic synthesis has proved as a clean
and advantageous mothed method in organic synthesis.
When ultrasonic waves are passed through a solvent
medium, vibrational motions are induced. As the cycle
exceeds the compression cycle, it breaks through the
intermolecular forces of attraction maintaining the
cohesion of the medium causing a sudden drop in pressure,
resulting in the production of micro oscillating cavitation
bubbles of gaseous substances. The bubbles then enlarge to
an unstable size with each succession of applied ultrasonic
energy causing instantaneous asymmetric violent
implosion of the bubbles in less than a microsecond at the
interface, resulting in the formation of high pressure micro-
jets and high energetic shockwaves that aid in triggering
the solid catalyst, causing the interfacial boundary to
destruct and thereby intensifying adequate contact by
means of efficient turbulent mixing and acoustic streaming.
As a result of this, the rate of the reaction increases by
many times as the rate of mass transfer across the
general and efficient methods for synthesis of α,α-
dihaloketone is an active research topic in modern organic
synthesis and medicinal chemistry. Traditionally, α,α-
dihaloketones have been synthesized through halogenation
2
3
of α-methylketones,
acylation of arenes
and
4
oxyhalogenation of alkynes . Although these methods are
favorable, there are still some limitations as follows: (i)
these methods are usually restricted to synthesis of α,α-
dichloroketones and α,α-dibromoketones; (ii) the non-
methyl phenylketone and internal alkyne substrates show
low selectivity; and (iii) hazardous or toxic reagents and
solvents, metallic or acidic catalyst, and high reaction
temperatures for long reaction times are required. Novel
methods of halogenation with high selectivity that satisfy
the requirements of green chemistry are still desirable.
Trihaloisocyanuric acids (TXCA) are stable and
inexpensive solids, easily available in pool supplies and
frequently used as swimming-pool disinfectant and
—
——
∗
Corresponding author. Tel.86-7466381164; fax: 86-7466381165; e-mail:hnkjxy2017@163.com (Fang Liu)
Contribute equally
‡

2
Tetrahedron
6
interfacial surface increases. The u
A
ltr
C
as
C
on
E
icPTef
E
fe
D
ct MANUSCRIPT
1
2
3
4
5
6
7
8
9
None
30 min
30 min
30 min
30 min
30 min
30 min
12 h
94%
81%
84%
89%
53%
74%
34%
59%
85%
94%
induces very high local pressure and temperatures inside
the bubbles and enhances mass transfer and turbulent flow
in the liquid. This unique property of ultrasonic decisively
affects the chemical reactivity through dissipation of
energy. Compared with the traditional heating, ultrasound
Thioure instead of p-tolylthiourea
N-Methylthiourea instead of p-tolylthiourea
N,N'-Diphenylthiourea instead of p-
Without p-tolylthiourea
irradiation
has
some
significant
advantages:
ultrasonification largely enhances the reaction rate,
improves yields, minimizes side-product formation by
providing the activation energy in micro environment. It
offers environmentally friendly and sustainable synthetic
processes by means of using small amounts of solvents,
mild reaction condition, and easier manipulation. To the
best of our knowledge, there is no report in the literature on
the preparation of α,α-dihaloketone from alkynes and
trihaloisocyanuric acids using ultrasound irradiation in
water. We purpose in this work an improved synthesis of
α,α-dihaloketone using an catalytic amount of p-
tolylthiourea in water under ultrasound irradiation. This
method allows for high yields in a short time at room
temperature.
TCCA (0.5 equiv.) instead of (1.0 equiv.)
Stirring at 50ꢀinstead of ultrasonic
Stirring at 100ꢀinstead of ultrasonic
sonicated at 40 W power instead of 60 W
sonicated at 100 W power instead of 60 W
12 h
50 min
30 min
7
1
0
a
Reaction conditions: 1a (0.1 mmol), TCCA (1.0 equiv.) p-tolylthioure (2.5
mmol %), water (1.5 ml) in vial was sonicated at 60 W power.
b
Determined by GC-MS using ethylbenzene as the internal standard.
With the optimal reaction conditions in hand, we
investigated various alkynes so as to gauge the scope of
this ultrasound-assisted tandem reaction. As shown in
Table 2, phenylacetylenes bearing both electron-donating
groups and electron-withdrawing groups at the para-,
meta-, and ortho-positions of the phenyl ring could furnish
the desired α,α-dihaloketones in high yields (2a – 2n).
These results indicated that neither electronic effect nor
steric hindrance of phenylacetylenes significantly
influences the efficiency of this method. Thioether group
2
. Results and Discussion
We initiated our investigations with phenylacetylene 1a as
the model substrate. After scrupulous evaluation of all of
the reaction parameters, we found that a cocktail consisting
8
of trichloroisocyanuric acid (TCCA, 1.0 equiv.) and p-
tolylthiourea (2.5 mol %) as the catalyst in water (1.5 ml)
was sonicated at 60 W power for 30 min delivered α,α-
dichloroketone 2a in 94% GC yield (Table 1, entry 1). It is
worth noting that α-monochloro ketone was not detected in
the crude mixtures. As expected, the nature of the catalyst
played a critical role on the reaction outcome; while
otherwise related thioureas provided inferior results
(
2e), which may not be used in oxyhalogenation of alkynes
is compatible. Halogen substituents such as F, Cl, Br and I
were all well tolerated (2f – 2i), which made this
methodology more useful for further transformations.
Diethylnylbenzene proceeded smoothly to give the double
chlorination product 2o in 85 % yield. Polycyclic and
heteroaromatic substituted acetylenes could also be
transformed into the corresponding products in good yields
(
entries 2 - 4). A complicated reaction mixture of
chlorination products (2a, 2-chloroacetophenone 3a and
,2-dichloro-vinyl)-benzene 4a) was detected in the
(2p and 2q). In addition, aliphatic terminal alkynes were
1
good substrates (2r – 2s). Notably, the reaction could be
extended to thermodynamically more stable internal
alkynes.
absence of thioureas (entry 5). Decreasing the amount of
TCCA from 1.0 equiv. to 0.5 equiv. resulted in the
formation of product 2a with only a 74% GC yield (entry
Subjecting
the
substrate
6
). In order to verify the effect of ultrasound irradiation, we
performed the halogenation reaction of 1a by stirring at
0ꢀ and 100ꢀ for 12 hours in the absence of ultrasonic
wave. The yields of 2a were 34% and 59% (entries 7 and
), respectively, which were less than that obtained via
trimethyl(phenylethynyl)silane 1t to the standard reaction
conditions could successfully afford the 2t in 88% yield,
allowing access to phenylacetylene via deprotection of the
TMS group. Phenylpropyne was good for the reaction to
deliver product 2u. However, the diphenylacetylene
substrate only provided a trace amount of the desired
product 2v in the present catalytic system. Gratifyingly, the
present ultrasound promoted halogenation reaction was
also successfully applied to produce α,α-dibromoketones
5
8
ultrasonic-assisted synthesis. Encouraged by these results,
various ultrasonic powers were screened to optimize the
reaction conditions. Decreasing the ultrasonic powers
resulted in slightly lower yields (entry 9). No benefit was
obtained by increasing the ultrasonic power (entry 10).
Thus, it was clear from the data that ultrasound can
accelerate the halogenation reaction affording higher yield
than thermal conditions and significantly reducing the
reaction time and temperature.
(2w – 2y) and α,α-diiodoketones (2z – 2ab) and afford the
corresponding products in good yields.
a
Table 1. Optimization Studies
b
Entry
Variation from standard conditions above
Time
Yield

3
a,b
Table 2. Reaction Scopes
reaction process involved a build-up of positive charge in
ACCEPTED MANUSCRIPT
the transition state, with the positive charge on the α-
carbon atom adjacent to the phenyl ring, that is, a
9
chloronium ion.
Figure 1. Hammett Equation
To further verify the tandem reaction mechanism, several
control experiments were performed and the results were
1
0
shown in Scheme 2. α-Chloroacetophenone 3a, 1-
1
1
phenylethanone 6a and (1,2-dichlorovinyl)benzene 4a,
which could be generated from alkyne 1a, failed to afford
a under the present conditions (Scheme 2, eqn. 1-3).
These results ruled out the possibility of 3a, 4a and 6a as
intermediates of the transformation. Subsequently, the
reaction 1a with TCCA in the presence of 2,6-di-tertbutyl-
2
a
Reaction conditions: 1 (0.3 mmol), TCCA (0.3 mmol) p-tolylthioure
2.5 mmol %), water (1.5 ml) in vial was sonicated at 60 W power.
b
(
isolated yield.
4
-methylphenol
(BHT)
or
2,2,6,6-tetramethyl-1-
Further, the scalability of our catalytic system was
examined. Phenylacetylene 1a with TCCA could be
performed on the 6 mmol scale. After 30 min, an insoluble
gum-like substance of a yellowish colour formed in water.
The reaction mixture was extracted with ether and then
crude 2a could be purified simply by recrystallization from
hexanes and ether to give the desired product 2a in 88%
yield (Scheme 1a). Notably, the developed process avoids
piperidinyloxy (TEMPO) as a radical scavenger gave the
corresponding products in good yields, thus suggesting that
a radical mechanism or single-electron-transfer (SET)
might not be involved in these reaction processes (Scheme
2
, eqn. 4). Furthermore, deuterium labeling experiment was
performed (Scheme 2, eqn.5). Treating 1a with TCCA in
the presence of p-tolylthiourea (2.5 mmol%) in D O (0.5
mL), deuterated products [D]-2a could be formed,
implying that the α-hydrogen atom of 2a originated from
water .
2
using column chromatography. Finally,
a
one-pot,
sequential reaction followed by Et NH mediated
2
cyclization to provide 5a has been demonstrated (see
1
e
Scheme 1b) . Although moderate yields are obtained, the
one-pot methodology is expected to be of high synthetic
utility.
Scheme 2. Control Experiments
O
(
1)
Cl standard conditions
2a
Ph
Scheme 1 Gram scale synthesis and Application
3
O
a
a
N.D
(2)
standard conditions
2a
Ph
Me
N.D
6
Cl
standard conditions
(3)
2
N.D
a
Ph
Cl
4a
standard conditions
(4) Ph
2a
TEMPO 2 equiv.
BHT 2 equiv.
88%
85%
Given this departure from our initial expectation, a
Hammett plot was constructed for the migration of para-
substituted phenylacetylene 1. In this way, we hoped to
gain an understanding of the type of intermediates that
were involved in the reaction. Figure 1 shows a reasonable
linearity between the log(k /k ) and Brown–Okamoto
O
p-tolylthiourea (2.5 mmol %)
Cl
D
(5)
Ph
+ TCCA
ultrasonic
Ph
D O
2
Cl
D]-2a
[
X
H
12
+
On the basis of all these results and previous reports , a
possible reaction pathway was proposed as depicted in
Scheme 3. First, a dihalo monoxide (X O) is in situ
constant (δ ) value of the respective substituents. This
+
negative slope (Hammett ρ value: -1.35.) suggests that the
2

4
Tetrahedron
us MATh
production of tricyanic acid. Initially, TXCA reacts with
generated from TXCA and water wi
A
th
C
s
C
im
E
ul
P
ta
T
ne
E
o
D
N
e
U
res
S
id
C
ue
R
w
I
as purified by column chromatography on silica gel
P
T
(eluent: hexanes/ethyl acetate) to afford 2a – 2aa.
1
2a, 13
water to give the HXO
Then, hypohalous acid converts into dihalo monoxide
and release tricyanic acid.
4
.3. Characterization of the compounds
1
2b
4e
(X O) and reacts with alkyne 1 to yield the halonium ion
4.3.1. 2,2-dichloro-1-phenylethanone (2a) : Yellow oil (52.1
2
1
intermediate A. Then, A is trapped by p-tolylthiourea to
afford the key intermediate haloenamine B, followed by
intermolecular nucleophilic attack with XO¯ to form the
intermediate C, which converts to more stable product 2
via enol keto tautomerism.
mg, 92%). H NMR (400 MHz, CDCl ): δ = 6.69 (s, 1 H), 7.53
(t, J = 7.6 Hz, 2H), 7.66 (t, J = 7.6 Hz, 1 H), 8.09 (d, J = 7.6 Hz,
2 H). C NMR (100 MHz, CDCl ): δ = 67.81, 128.98, 129.80,
131.32, 134.63, 185.95.
3
13
3
2c
4
.3.2. 2,2-dichloro-1-(p-tolyl)ethanone (2b) : Colorless oil
1
Scheme 3. Plausible Mechanism
(
55.4 mg, 91%). H NMR (400 MHz, CDCl ): δ = 2.35 (s, 3 H),
3
13
X
H
6.61 (s, 1 H), 7.22 (d, J = 8 Hz, 2H), 7.88 (t, J = 8 Hz, 2 H).
C
O
N
O
O
X
N
O
X
NMR (100 MHz, CDCl ): δ = 21.91, 67.68, 128.74, 129.72,
3
+
H2O
+
HXO
HN
NH
N
N
1
29.88, 145.97, 185.62.
O
O
2
HXO
X2O + H2O
2c
S
4.3.3. 1-([1,1'-biphenyl]-4-yl)-2,2-dichloroethanone (2c) :
Colorless solid (69.9 mg, 88%). H NMR (400 MHz, CDCl
S
NHTol
X
XO
R
O
R
X
X
1
X2O
XO
TolHN
NH2
): δ
3
R
XO
R
HN
R
S
X
=
6.71 (s, 1 H), 7.46 (m, J = 8.4 Hz, 3H), 7.64 (d, J = 8.4 Hz, 2
H), 7.74 (d, J = 8.4 Hz, 2 H), 8.17 (d, J = 8.4 Hz, 2 H). C NMR
100 MHz, CDCl ): δ = 67.91, 127.38, 127.54, 128.74, 129.13,
X
1
3
TolHN
NH2
1
A
B
C
2
(
3
3
. Conclusion
129.89, 130.45, 139.39, 147.33, 185.59.
In conclusion, we have developed an ultrasound assisted
one-pot three-component procedure for the preparation of
α,α-dihaloketone starting with commercially available
alkynes, green halogenating reagent and water using
common and cheap p-tolylthiourea as a catalyst. Utilizing
ultrasonic irradiation techniques provided dramatic
improvements in terms of higher yields and shorter
reaction times compared with conventional heating method.
The advantages of this ultrasonic promoted approach
involve the mild reaction conditions, low catalyst loading,
ease of operation, the simplicity of separation, no
requirement for any matel salt and oxidant, excellent
chemoselectivity, and good functional-group tolerance. To
the best of our knowledge, this method is the first example
of synthesis of α,α-dihaloketone through ultrasonic
irradiation utilizing p-tolylthiourea as a catalyst.
2c
4
.3.4.
2,2-dichloro-1-(4-methoxyphenyl)ethanone
(2d) :
1
Yellow solid (56.4 mg, 86%). H NMR (400 MHz, CDCl ): δ
3.89 (s, 3 H), 6.64 (s, 1H), 6.97 (t, J = 8.4 Hz, 2 H), 8.06 (d, J =
13
.4 Hz, 2 H). C NMR (100 MHz, CDCl ): δ = 55.71, 67.91,
3
=
8
1
3
14.24, 123.91, 132.32, 164.67, 184.65.
2
b
4
.3.5. 2,2-dichloro-1-(4-(methylthio)phenyl)ethanone (2e) :
1
Colorless oil (26.1 mg, 37%). H NMR (400 MHz, CDCl ): δ =
2.53 (s, 3H), 6.68 (s, 1H), 7.28 (d, J = 8.4 Hz, 2H), 8.01 (d, J =
8.4 Hz, 2H). C NMR (100 MHz, CDCl ) δ 14.62, 39.13,
3
13
3
124.91,126.57, 130.03, 148.32, 184.97.
2b
4.3.6 2,2-dichloro-1-(4-fluorophenyl)ethanone (2f) : Colorless
1
oil (46.6 mg, 75%). H NMR (400 MHz, CDCl ): δ = 6.60 (s, 1
3
1
3
H), 7.20 (t, J = 8.4 Hz, 2H), 8.16 (dd, J = 8.4, 5.2 Hz, 2 H).
C
NMR (100 MHz, CDCl ): δ = 67.84, 116.18, 116.40, 127.51,
3
1
32.84, 167.76, 184.60.
4
4
. Experimental Section
2
b
.1. General methods and materials
4.3.6.
2,2-dichloro-1-(4-chlorophenyl)ethanone
(2g) :
1
Colorless solid (50.9 mg, 76%). H NMR (400 MHz, CDCl ): δ
6.60 (s, 1 H), 7.50 (t, J = 8.4 Hz, 2 H), 8.05 (d, J = 8.4 Hz, 2 H).
C NMR (100 MHz, CDCl ): δ = 67.80, 128.94, 129.34, 131.09,
3
All organic solvents were purchased from commercial sources
=
and used as received unless otherwise stated. All other chemicals
were purchased from 9dingchem and used without further
purification. Reactions were monitored by thin-layer
chromatography (TLC) using silicycle pre-coated silica gel plates.
Chromatographic purifications were carried out on a Biotage
13
3
1
31.28, 141.29, 184.97.
2
b
4
.3.7.
1-(4-bromophenyl)-2,2-dichloroethanone
(2h) :
1
1
13
Colorless solid (57.9 mg, 72%). H NMR (400 MHz, CDCl ): δ =
.59 (s, 1 H), 7.67(d, J = 8.4 Hz, 2H), 7.96 (d, J = 8.4 Hz, 2 H).
C NMR (100 MHz, CDCl ): δ = 67.77, 129.89, 130.13, 131.30,
Isolera instrument. H NMR and C NMR spectra were recorded
on 400 MHz NMR plus spectrometer using residue solvent peaks
as internal standards. Infrared spectra were recorded with IR
3
6
13
3
-
1
1
32.34, 185.19.
spectrometer and are reported in reciprocal centimeter (cm ).
High resolution mass spectra were obtained using GCT-TOF
instrument with EI or ESI source. Sonication was performed by
K1000E-type sonicator (with a frequency of 40 kHz and
ultrasonic peak max. 100 W).
2c
4.3.8. 2,2-dichloro-1-(4-iodophenyl)ethanone (2i) : Colorless
1
solid (69.6 mg, 79%). H NMR (400 MHz, CDCl
H), 7.48 (d, J = 8.0 Hz, 2H), 7.79 (d, J = 8.0 Hz, 2 H), 7.88 (d, J
): δ = 6.60 (s, 1
3
13
=
8.0 Hz, 2 H), 8.04 (d, J = 8.0 Hz, 2 H). C NMR (100 MHz,
CDCl ): δ = 67.82, 103.22, 129.35, 129.49, 130.46, 131.03,
4
.2.1 General Procedure for the Synthesis of 2
3
Procedure for 2: To a solution of alkyne (0.3 mmol) in water
138.33, 141.27, 184.51.
(
1.5 mL) in sealed tube was added TXCA (0.3 mmol) and p-
2
c
tolylthiourea (0.075 mmol, 12 mg), the reaction mixture was
ultrasonic at room temperature under and the reaction was
monitored by TLC. The reaction typically took 20 mins. Upon
completion, the mixture was concentrated under reduced pressure.
4.3.9. 2,2-dichloro-1-(4-(trifluoromethyl)phenyl)ethanone(2j) :
1
Colorless oil (67.1 mg, 87%). H NMR (400 MHz, CDCl ): δ =
6.62 (s, 1 H), 7.79 (d, J = 8.4 Hz, 2H), 8.23 (d, J = 8.4 Hz, 2H).
3

5
1
3
4e
C NMR (100 MHz, CDCl ): δ = 67.81, 125.9
A
4,
C
12
C
5.
E
98
P
, 1
T
2
E
8.3
D
6, MAN4.
U
3.2
S
0
C
. 2
R
,2
I
-d
P
ib
T
romo-1-phenylethanone (2w) : Colorless oil
3
1
1
28.62, 133.99, 135.48, 185.15.
(69.3 mg, 83%) . H NMR (400 MHz, CDCl ): δ = 6.65 (s, 1H),
3
7
.43 (t, J = 7.8 Hz, 2H), 7.57 (t, J = 7.8 Hz, 1H), 8.01 (d, J = 8.0
13
2
c
4
.3.10. 2,2-dichloro-1-(4-nitrophenyl)ethanone (2k) : Yellow
Hz, 2H). C NMR (100 MHz, CDCl
130.85, 134.53, 186.01.
): δ = 39.74, 129.00, 129.76,
3
1
oil (50.6 mg, 72%). H NMR (400 MHz, CDCl ): δ = 6.59 (s, 1
H), 7.50 (d, J = 8.4 Hz, 2H), 8.05 (d, J = 8.4 Hz, 2 H). C NMR
100 MHz, CDCl ): δ = 67.80, 129.34, 131.27, 141.29, 147.81,
3
1
3
4
e
(
1
4.3.21.
2,2-dibromo-1-(4-fluorophenyl)ethanone
(2x) :
3
1
85.05.
Yellow oil (72.0 mg, 81%) . H NMR (400 MHz, CDCl ): δ =
3
6.56 (s, 1H), 7.12 (t, J = 7.8 Hz, 2H), 8.08 (m, J = 7.8 Hz, 2H).
13
2
c
4
.3.11. methyl 4-(2,2-dichloroacetyl)benzoate (2l) : Colorless
C NMR (100 MHz, CDCl
): δ = 0.02, 38.37, 115.12, 115.34,
3
1
oil (54.1 mg , 73%). H NMR (400 MHz, CDCl ): δ = 3.94 (s, 3
H), 6.69 (s, 1 H), 8.13 (s, 4 H). C NMR (100 MHz, CDCl ): δ =
2.71, 67.83, 129.74, 129.97, 134.60, 135.05, 165.82, 185.51.
126.01, 126.05, 131.63, 131.73, 166.59, 183.55.
3
13
3
4e
5
4.3.22. 2,2-dibromo-1-p-tolylethanone (2y) : yellow solid
(
77.1 mg, 88%). δ = 2.37 (s, 3 H), 6.63 (s, 1 H), 7.23 (d, J = 8.4
1
4
13
4
.3.12. 2,2-dichloro-1-(m-tolyl)ethanone (2m) : Colorless oil
Hz, 2H), 7.90 (t, J = 8.4 Hz, 2 H). C NMR (100 MHz, CDCl
δ = 21.90, 39.94, 128.20, 129.72, 129.87, 145.81, 185.69.
3
):
1
(
48.8 mg, 80%). H NMR (400 MHz, CDCl ): δ = 2.43 (s, 3 H),
3
6
.72 (s, 1 H), 7.42 (m, J = 7.6 Hz, 2H), 7.87 (t, J = 3.8 Hz, 2 H).
1
3
4e
C NMR (100 MHz, CDCl ): δ = 21.42, 67.81, 126.89, 128.83,
4.3.23. 2,2-diiodo-1-phenylethanone (2z) : yellow solid (90.3
3
1
1
30.18, 131.41, 135.50, 139.01, 186.10.
mg, 81%). H NMR (400 MHz, CDCl ): δ = 6.53 (s, 1 H), 7.47 (t,
3
J = 7.6 Hz, 2H), 7.61 (t, J = 7.6 Hz, 1 H), 8.01 (d, J = 7.6 Hz, 2
1
4
13
4
.3.13. 2,2-dichloro-1-(o-tolyl)ethanone (2n) : Colorless oil
H). C NMR (100 MHz, CDCl
132.23, 186.34.
3
): δ = 126.59, 127.07, 131.67,
1
(
52.3 mg, 86%). H NMR (400 MHz, CDCl ): δ = 2.53 (s, 3 H),
3
6
7
2
1
.66 (s, 1 H), 7.32 (m, J = 8.4 Hz, 2H), 7.47 (t, J = 7.6 Hz, 1 H)
13
.73 (d, J = 7.6 Hz, 1 H). C NMR (100 MHz, CDCl ): δ =
4.3.24. 1-(4-fluorophenyl)-2,2-diiodoethanone (2aa): yellow
3
1.36, 68.97, 125.81, 128.56, 132.33, 132.47, 132.93, 140.75,
88.43.
solid (90.0 mg, 77%). IR (neat): 3461, 1693, 1599, 1508, 1410.5,
-
1 1
1264, 836, 768, 702 cm ; H NMR (400 MHz, CDCl ): δ = 6.45
3
13
(
s, 1 H), 7.15 (t, J = 7.6 Hz, 2H), 8.08 (m, J = 4 Hz, 2 H). C
1
4
4
.3.14. 1,1'-(1,4-phenylene)bis(2,2-dichloroethanone) (2o) :
NMR (100 MHz, CDCl ): δ = 115.18, 115.27, 115.40, 131.35,
3
+
1
White solid (65.0 mg, 85%). H NMR (400 MHz, CDCl ): δ =
6
6
131.45, 166.40, 185.82. HRMS (EI): m/z [M] calcd for
FI O: 389.8362, found: 389.8358.
3
13
.62 (s, 2 H), 8.24 (s, 4 H). C NMR (100 MHz, CDCl ): δ =
C
8
H
5
2
3
7.81, 130.18, 135.44, 185.24.
4
e
4
.3.25. 2,2-diiodo-1-p-tolylethanone (2ab) : Yellow solid
1
15
4
.3.15.
2,2-dichloro-1-(naphthalen-2-yl)ethanone
(2p) :
(99.6 mg, 86%). H NMR (400 MHz, CDCl
): δ = 2.34 (s, 3H),
3
1
White solid (56.7 mg, 79%). H NMR (400 MHz, CDCl ): δ =
7
6.61 (s, 1H), 7.23 (d, J = 8.0 Hz, 2H), 7.88 (d, J = 8.4 Hz, 2H).
3
13
.01 (s, 1 H), 7.35 (m, 3 H), 7.68 (m, 1 H), 7.95 (m, 1 H), 8.10
C NMR (100 MHz, CDCl
130.48, 146.57, 186.22.
): δ = 22.51, 68.48, 129.34, 130.32,
3
13
(m, 1 H), 8.63 (s, 1 H). C NMR (100 MHz, CDCl ): δ = 53.49,
3
1
1
25.89, 126.36, 127.16, 127.28, 128.39, 128.93, 131.07, 132.38,
35.91, 197.64.
1
e
4.3.26.
benzo[d]oxazol-2-yl(phenyl)methanone
(5a) :
1
Colorless solid (99.6 mg, 69%). H NMR (400 MHz, CDCl ): δ =
3
16
4
.3.16.
2,2-dichloro-1-(thiophen-3-yl)ethanone
(2q) :
7.48 (t, J = 7.6 Hz, 1H), 7.58 (t, J = 7.2 Hz, 3H), 7.69 (m, J = 8.0
1
13
Colorless oil (41.7 mg, 71%) . H NMR (400 MHz, CDCl ): δ =
Hz, 2H), 7.95 (d, J = 7.6 Hz, 1H), 8.54 (d, J = 8.0 Hz, 2H).
NMR (100 MHz, CDCl
C
3
6
8
6
.42 (s, 1 H), 7.39 (m, J = 4 Hz, 1H), 7.67 (d, J = 4.8 Hz, 1 H),
3
): δ = 111.82, 122.34, 125.69, 128.41,
128.58, 130.94, 134.28, 134.94, 140.68, 150.36, 157.03, 180.53.
13
.39 (d, J = 4.8 Hz, 1 H). C NMR (100 MHz, CDCl ): δ =
3
8.24, 126.77, 126.80, 135.56, 180.71
Acknowledgments
4
e
4
.3.17. 1,1-dichlorooctan-2-one (2r) : Colorless oil (32.7 mg,
1
7
1
5
2
7%) . H NMR (400 MHz, CDCl ): δ = 0.91 (t, J = 6.8 Hz, 3H),
.35 (m, 6H), 1.69 (t, J = 11.2 Hz, 2H), 2.94 (t, J = 7.5 Hz, 2H),
.81 (s, 1H). C NMR (100 MHz, CDCl ): δ = 14.07, 22.50,
4.34, 28.61, 31.49, 34.94, 43.03, 197.16.
This research was financially supported by Research
Foundation of Education Bureau of Hunan Province, China (No.
17A081) and Research Programs of Hunan University of Science
and Engineering (16XKY062).
3
13
3
4
.3.18. 1,1,5-trichloropentan-2-one (2s): Colorless oil (40.8
Supplementary data
mg, 84%). IR (neat): 3088.2, 2962.2, 1443.4, 1311.0, 1295.7,
-
1
1
1
=
6
2
071.2, 906.2, 800.4, 731.1 cm ; H NMR (400 MHz, CDCl ): δ
Supplementary data associated with this article can be found
in the online version, at http:// .
3
2.05 (t, J = 7.2 Hz, 2 H), 2.70 (t, J = 7.2 Hz, 2 H), 3.56 (t, J =
1
3
.4 Hz, 2 H), 6.21 (s, 1H). C NMR (100 MHz, CDCl ): δ =
3
+
9.39, 30.71, 43.52, 115.05, 134.68. HRMS (EI): m/z [M] calcd
References and notes
for C H Cl O: 187.9589, found: 187.9588.
5
7
3
1
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.3.19. 2,2-dichloro-1-phenylpropan-1-one (2u) : Yellow
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3
3
=
1
H), 7.49 (t, J = 8.4 Hz, 2H), 7.60 (t, J = 8.4 Hz, 1H), 8.32 (d, J
13
8.4 Hz, 2 H). C NMR (100 MHz, CDCl ): δ = 34.32, 82.72,
3
28.18, 131.25, 133.69, 188.13.

6
Tetrahedron
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