One-step for the preparation of α-haloacetal of ketones with N-bromosuccinimide/N-chlorosuccinimide (NBS/NCS) and ethylene glycol

Article abstract of DOI:10.1016/j.tet.2016.05.064

A new process that could directly prepare α-haloacetal of ketones from various ketones with N-halosuccinimide (NBS/NCS) and ethylene glycol in one step without any other catalysts was reported. The effects of solvents, NBS/NCS and reaction temperature were investigated. Under the optimal condition, most of α-haloacetals of ketones were obtained in 90–100% yield.

Full text of DOI:10.1016/j.tet.2016.05.064

Accepted Manuscript
One-step for the preparation of α-haloacetal of ketones with N-bromosuccinimide/N-
chlorosuccinimide (NBS/NCS) and ethylene glycol
Zubiao Zheng, Bingbing Han, Fang Wu, Tengfei Shi, Jie Liu, Yong Zhang, Jialong
Hao
PII:
S0040-4020(16)30481-1
10.1016/j.tet.2016.05.064
TET 27791
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 9 February 2016
Revised Date: 22 May 2016
Accepted Date: 24 May 2016
Please cite this article as: Zheng Z, Han B, Wu F, Shi T, Liu J, Zhang Y, Hao J, One-step for the
preparation of α-haloacetal of ketones with N-bromosuccinimide/N-chlorosuccinimide (NBS/NCS) and
ethylene glycol, Tetrahedron (2016), doi: 10.1016/j.tet.2016.05.064.
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ACCEPTED MANUSCRIPT
Graphical Abstract
One-step for the preparation of α-haloacetal of ketones Leave this area blank for abstract info.
with N-bromosuccinimide/N-chlorosuccinimide
(
NBS/NCS) and ethylene glycol
*
Zubiao Zheng , Bingbing Han, Fang Wu, Tengfei Shi, Jie Liu, Yong Zhang, Jialong Hao
Department of Chemistry, Huangshan University, Anhui 245041, China.
O
O
O
NBS or NCS
X
R
ethylene glycol
R
1
X: 2 -Br; 3 -Cl.
2
or 3
R : H, p-Br, p-Cl, p-F, m-Br, o-Cl, p-CF , p-NO , m-NO , 2,4-Cl, 3,4-Cl,
3
2
2
biphenyl, 4'-Br-biphenyl, p-Me, p-MeO.
cyclohexanone, 3-pentanone, 2-pentanone, methyl-2-thienyl ketone

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
One-step for the preparation of α-haloacetal of ketones with N-bromosuccinimide/N-
chlorosuccinimide (NBS/NCS) and ethylene glycol
*
Zubiao Zheng , Bingbing Han, Fang Wu, Tengfei Shi, Jie Liu, Yong Zhang, Jialong Hao
Department of Chemistry, Huangshan University, AnHui 245041, China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A new process that could directly prepare α-haloacetal of ketones from various ketones with N-
halosuccinimide (NBS/NCS) and ethylene glycol in one step without any other catalysts was
reported. The effects of solvents, NBS/NCS and reaction temperature were investigated. Under
the optimal condition, most of α-haloacetals of ketones were obtained in 90–100% yield.
Available online
2
009 Elsevier Ltd. All rights reserved.
Keywords:
Ketones,
α-Haloacetalization,
N-Halosuccinimide,
α-Haloacetals of ketones ,
One-step.
1
. Introduction
N-Halosuccinimides represent an important class of
halogenating reagents, especially N-bromosuccinimide (NBS),
which has been widely researched in bromination of ketones to
Simultaneous installation of two different functional groups in
one-step into the organic framework is a remarkable fundamental
1,2
process in organic synthesis. Halogenation and acetalization
26-32
prepare α-bromoketones with various reaction conditions.
3-9
are two kinds of important process in organic synthesis. α-
The halogenation would be not reactive enough without a Lewis
haloacetals of ketones are valuable synthetic intermediates used
30
acid or a Bronsted acid as catalyst. a-Monohalogenated ketals
10
for medicine and agriculture, particularly in triazole fungicides ,
could always be found as by-products when acetophenones with
11-16
14
α,β-unsaturated ketones , and enol ethers . Previous methods
to prepare α-haloacetals of ketones are always based on two
separate steps, sequences on α-halogenation of ketones followed
by acetalization of the α-halogenation products. One of the
effective methods for preparation of α-haloacetals of ketones is
one-step α-haloacetalization of ketones with halogenating reagent
and alcohol or glycol. There are a few examples have been
an electron-withdrawing groups(-NO ) on the benzene ring was
2
refluxed with halogenating reagents and acidic catalysts in
24,33
methanol during our research.
Herein, we decided to develop and optimize a one-step method
for preparation of α-haloacetalization of ketones with NBS/NCS
in glycol without any other catalysts based on our studies.
17-19
previously reported solving this challenge,
employing
2. Results and discussion
20
21
compounds, such as liquid bromine , copper(II) bromide ,
22
In the preliminary experiments, acetophenone 1a which is the
simplest aromatic ketone was chosen as a model for α-
bromoacetalization with various alcohol or glycol in one step.
Compound 1a was treated with 2.3 equiv of NBS in 6 mL of
various alcohols or glycols, and the results were summarized in
Table 1. When ethylene glycol was used as a reagent and solvent
without any other catalyst, the α-bromoacetal of acetophenone(2-
bromomethyl-2-phenyl-1,3-dioxolane, 2a) could be precipitated
from the reaction system as a white solid. After filtration, the
yield of 2a could reach 98% (entry 1, Table 1). When 1,2-
propanediol was selected, the two isomers of 2-bromomethyl-4-
methyl-2-phenyl-1,3-dioxolane could also be obtained with 96%
poly(diallyldimethylammonium
chloride) ,
1,3-dihalo-5,5-dimehtylhydantoin
DBDMH/DCDMH) . However, most of the studies suffer for
iodobenzene
23
dichloride
and
24,25
(
one or more disadvantages such as use of hazardous reagents,
cost of metallic or strongly acids as catalyst, work up procedures,
and moderate yields. Hence, the development of a safer, greener,
and efficient procedure for α-haloacetalization of ketones with
excellent yields remains a major challenge for synthetic organic
chemists.
.
∗
Corresponding author. Tel.: +86-0559-2546554; fax: +86-0559-2546554;
E-mail: zenzuobiao@126. com.
1
yield(entry 2, Table 1), and the ratio determined by H NMR was

2
Tetrahedron
Table 5 α-haloacetalization of various acetophenones with DBDMH/DCDMH in
3
:2. When the reaction performed in
A
1
C
,3
C
-p
E
rop
P
a
TED
ne
di
ol, MANUSCRIPT
a
ethylene glycol
bromination of 1a was the main reaction, and the α-bromoacetal
product determined by GC was only 20%(entry 3, Table 1). Both
α-bromoacetalization and bromination could not take place any
more in methanol or ethanol at room temperature (entries 4, and
O
O
O
NXS
X
R
ethylene glycol
R
1
X: 2 -Br; 3 -Cl.
2
or 3
5
, Table 1); however, when the reaction was performed under
b
Entry
1
Substrate
Product
Yield (%)
reflux in methanol, the main product 3 was 2-bromo-1-
phenylethanone and the yield could reach 80% (entry 6, Table 1).
So, ethylene glycol was the first choice for the acetalization.
2
O
O
O
Br
98
1a
2
a
2
2
O
O
O
O
O
O
Table 1 Effect of various solvents on the α-bromoacetalization of 1a with
Br
2
99
96
92
a
NBS
Br
1b
Br
Cl
b
c
Entry
Solvent
ethylene glycol
1,2-propanediol
1,3-propanediol
methanol
Time(h)
yield (%)
O
O
Br
b
3
4
5
6
1
2
3
4
5
6
24
24
24
8
98
Cl
1c
96
O
c
Br
20
F
1d
F
0
0
2d
O
O
O
ethanol
8
Br
91
93
d
methanol
8
0(80 )
Cl 1e
O
Cl
O
2e
a
The reaction was performed with 2 mmol of acetophenone(1a), 4.6 mmol
O
O
O
of NBS(2.3 equiv), and 6 mL of alcohols or glycols at room temperature;
Br
Br
2
Br
Br
Br
b
α-bromoacetal of acetophenone(2a) was filtrated directly from the reaction
1f
2f
system as a white solid;
O
O
O
O
c
O N
c
2
O N
The ratio of α-bromoacetal product was determined by GC;
2
7
8
9
ꢀ100
98
d
-bromo-1-phenylethanone was obtained with 80% yield.
1g
2
g
a
c
c
Table 2 Effect of NBS on α-bromoacetalization of 1a with ethylene glycol
b
O
2
N
1h
O
2
N
2h
2i
Entry
NBS (mmol)
Yield (%)
O
O
O
O
O
1
2
3
4
5
3.0
4.0
4.6
5.0
5.5
40
85
98
93
90
Br
Br
Br
97
96
94
F
3
C
3
F C
1
i
O
c
1
0
Cl
Cl 1j
O
Cl
Cl
2
j
O
O
a
Cl
Cl
Cl
Cl
The reaction was performed with 2 mmol of acetophenone(1a), and 6 mL
1
1
1
2
of ethylene glycol at room temperature for 24 h;
1
k
2k
b
the α-bromoacetal of acetophenone(2a) was filtrated directly from the
O
O
O
Br
reaction system as a white solid.
91
1
l
Table 3. Effect of the dosage of ethylene glycol on α-bromoacetalization of
2l
O
a
O
O
1
a
Br
b
13
92
85
Entry
Ethylene glycol (mL)
Yield (%)
Br
1m
Br
2
m
1
2
3
4
5
6
2
3
4
5
6
7
79
90
O
O
O
Br
O
1
4
92
1n
2
n
95
O
O
Br
d
98
15
52
MeO
MeO
1o
98.7
Br
2o
O
O
a
The reaction was performed with 2 mmol of acetophenone(1a), and 4.6 mmol of
O
1
1
6
7
96
82
1
p
q
NBS(2.3 equiv) at room temperature for 24 h.
Br
2
p
b
isolated yield.
O
O
O
1
Br 2q
a
Table 4 Effect of NCS on α-chloroacetalization of 1a with ethylene glycol
b
O
O
O
O
O
e
Entry
NCS (mmol)
Ratio of 3a (%)
18
19
Br
,
87
1
1
r
s
Br
2r
1
2
3
4
5
4.6
6.0
7.0
8.0
9.0
62
73
79
90
89
O
S
O
O
S
Br
Br
45
2s
O
O
O
f
f
2
2
0
1
-
-
-
1t
-
a
N
The reaction was performed with 2 mmol of acetophenone(1a), and 6 mL
1u
O
O
O
of ethylene glycol at room temperature for 24 h;
b
22
20, 43
The ratio of α-chloroacetal product was determined by GC.
Br Br
Br
1
v

3
O
O
O
ACCEPTED MAac
N
ety
U
lfu
S
r
C
an
R
. T
I
he results were listed in Table 5. When 1b, 1c,
P
T
Cl
O
2
2
3
4
90
and 1d with a halogen atom on the para-position of benzene ring
were selected, the yields of 2b, 2c, and 2d were 99%, 96%, and
2%(entries 2, 3, and 4, Table 5), respectively. When 2-
chloroacetophenone (1e) and 3-bromoacetophenone (1f) were
used as the tested substrates, the yields were also good, could
reach 91% and 93%(entries 5, and 6, Table 5), respectively.
However, when 2g was prepared at room temperature from 1g
1
a
3a
O
O
O
O
9
Cl
91
Br
Cl
1b
1c
Br
3b
O
O
Cl
2
5
95
ꢀ100
97
Cl
3c
3g
with a strong electron-withdrawing group (-NO ) on the benzene
2
O
O
c
O
2
N
2
O N
Cl
ring, the yield was only 76%; when the reaction temperature was
increased to 45ꢁ, 2g could be obtained with excellent yields (ꢀ
100%)(entry 7, Table 5); the same process was also used to
prepared 2h, 2i and 2j, the yields were 98%, 97%, and
2
6
7
1
g
O
O
O
c
Cl
2
9
6%(entries 8, 9, and 10, Table 5), respectively. When 1l, and
O
2
N
2
O N
1
h
3h
O
1m with bulky groups on the benzene ring were tested, the yields
of 2l and 2m could also reach 91% and 92%(entries 12 and 13,
Table 5), respectively. The yield of 2n with a methyl on the
benzene ring was 85% (entry 14, Table 5). Substrates with a
O
2
8
O
Cl
92
76
1
p
3
p
q
O
O
O
2
3
9
0
strong electron-donation group (-OCH ), such as 1o, 2-
3
1
q
Cl
3
bromomethyl-2-(3-bromo-4-methoxyphenyl)-1,3-dioxolane(2o)
was isolated as the main product and the yield was only
52%(entry 15, Table 5). In our new chemical process of a-
bromination and acetalization in one-step, acetophenones with
electron-withdrawing groups on the benzene ring seem to offer
products with excellent yields, and the yields of the substrates
with strong electron-donating groups were less than others.
Aliphatic ketones, cyclohexanone(1p), 3-pentanone(1q), and 2-
pentanone(1r) were selected as test substrates, 2p, 2q, and 2r
could be obtained with 96%, 82%, and 87% yields(entry 16, 17
and 18, Table 5), respectively. 2r was a mixture of 2-
(bromomethyl)-2-propyl-1,3-dioxolane and 2-(1-bromopropyl)-
O
O
O
Br
96
a
The reaction was performed with 2 mmol of ketone, 4.6 mmol (2.3
equiv) of NBS(entries 1-15) or 8.0 mmol (4.0 equiv) of NCS(entries 14-20),
and 6 mL of ethylene glycol at room temperature for 24 h;
b
isolated yield;
c
the reaction was carried at 45ꢀ;
d
2
-bromomethyl-2-(3-bromo-4-methoxyphenyl)-1,3-dioxolane(2m) was
isolated as the main product;
a mixture of 2-(bromomethyl)-2-propyl-1,3-dioxolane and 2-(1-
bromopropyl)-2-methyl-1,3-dioxolane was obtained, and the ratio determined
e
1
2-methyl-1,3-dioxolane, and the ratio determined by H NMR
was 3 : 2. When
1
by H NMR was 3 : 2;
2-acetylthiophene(1s) was tested, 2-
f
the products was too complex to further separation.
(bromomethyl)-2-(5-bromothiophen-2-yl)-1,3-dioxolane(2s) was
OH
obtained with only 45% yield(entry 19, Table 5). However, the α-
bromoacetalization of 2-acetylfuran(1t) and 4-acetylpyridine(1u)
was too complex to further separation(entry 20, and 21, Table 5).
When 1-phenylpropan-1-one(1v) was selected, 2-bromo-1-
phenylpropan-1-one and 2,2-dibromo-1-phenylpropan-1-one
were obtained with 20% and 43% yields(entry 22, Table 5),
respectively.
N-Chlorosuccinimide (NCS) which is an analogue of NBS
could be used as a chlorinated reagent to produce α-chloroacetal
of acetophenone and other conditions remained. The conversion
of 1a could reach 100%, the yield of 3a was only 62% (entry 1,
Table 4), and α-chloroacetophenone was the main by-product
with 38% yield. When the dosage of NCS was adjusted to 8.0
mmol, the yield of 3a could increase to 90% (entry 4, Table 4).
When 1b and 1c were tested, 3b and 3c could be obtained with
91% and 95% (entries 24, and 25, Table 5), respectively. The α-
chloroacetalization of 1g and 1h must be carried at 45ꢁ, the
yields of 3g and 3h were 100% and 97% (entry 26, and 27, Table
5) , respectively. Cyclohexanone(1p), and 3-pentanone(1q) were
tested, 3p, and 3q could be obtained in 92%, and 76% yields,
respectively(entry 28, and 29, Table 5). When N-iodosuccinimide
(NIS) was selected to replace NBS or NCS, no iodoacetalization
was detected.
O
OH
O
HO
OH
X
N
X
O
OH
OH
-H
HO
O
O
O
O
X
X
X
2
O
OH
OH
OH
2
X
Scheme 1 Possible mechanism for one-step α-haloacetalization of acetophenone
with NXS in glycol.
Secondly, the effect of NBS on the α-bromoacetalization of 1a
was further investigated (Table 2). When 3.0 mmol (1.5 equiv) of
NBS was added to the reaction system, 2a was obtained with
only 40% yield(entry 1, Table 2). Increased the amount of NBS
to 4.6mmol (1.5 equiv) could result in an increase of the yield to
9
8%(entry 3, Table 2). However, larger amount of NBS was not
necessary and helpful for the reaction.
Effect of the dosage of ethylene glycol on α-
bromoacetalization of 1a was also investigated (Table 3). Less
amount of ethylene glycol (2 mL) resulted low yield of
a(79%)(entry 1, Table 3). When the amount of ethylene glycol
was increased to 6 mL, the yield could also increase to
8%( entry 5, Table 3). The major reason may be attributed to the
2
9
3
. Conclusion
dilution of ethylene glycol on the water formed in the
acetalization process.
In summary, we developed a simple and efficient method to
The optimal reaction condition in terms of yield required 2
mmol of 1a, 4.6 mmol of NBS, 6 mL of ethylene glycol at room
temperature for 24h. To further examine the scope of this
protocol, the optimized conditions were then applied to the
synthesis of a variety of α-bromoacetal of substituted ketones,
such as acetophenones, aliphatic ketones, acetylthiophene, and
synthesis α-haloacetal of ketones directly from various ketones in
one-step by the application of NBS/NCS in glycols as reaction
reagent and solvent under mild reaction without any other
catalysts. Chen et al. suggested the mechanism of keto-enol
tautomerism in the process of the chlorination of acetophenones
24,33
using DCDMH.
Analogously, we proposed the following

4
Tetrahedron
α- MA
1
haloacetalization mechanism. In the propos
A
ed
C
sy
C
st
E
em
P
,
T
th
E
e
D
Y
N
iel
3.96(m, 2H, OCH
OCH CH O), 7.28-7.31(m, 2H, ArH), 7.41-7.43(m, 1H, ArH),
7.71-7.72(m, 1H); C NMR(125 MHz, CDCl
U
d 9
S
1
C
%
R
, c
I
o
P
lo
T
rless oil; H NMR (500 MHz, CDCl
3
) δ 3.93-
halogenation of ketone generates acid in situ, which catalyzes the
ketals formation (Scheme 1). Major advantageous of the present
protocol include a wide range of substrates, mild reaction
conditions, ease and safety of operation, and high yields, which
have provided a novel route to α-haloacetal of ketones in the
methodology of organic synthesis.
2
CH O), 3.97 (s, 2H, CH Br), 4.22-4.25(m, 2H,
2
2
2
2
13
) δ 36.2, 65.9,
-1
3
107.2, 126.7, 128.7, 130.2, 131.5, 132.1, 136.3. IR (KBr, cm ):
3065, 2892, 1591, 1466, 1434, 1210, 1177, 1037, 762.
2
5
4
.2.6. 2-bromomethyl-2-(3-bromophenyl)-1,3-dioxolane (2f)
1
4
4
. Experimental
Yield 93%, colorless oil; H NMR (500 MHz, CDCl ) δ 3.63 (s,
3
2
H, CH Br), 3.90-3.91(m, 2H, OCH CH O), 4.17-4.20(m, 2H,
2
2
2
.1. General
OCH CH O), 7.23-7.28(m, 1H, ArH), 7.45-7.48(m, 2H, ArH),
2
2
13
7
1
.68(s, 1H, ArH); C NMR(125 MHz, CDCl ) δ 37.8, 66.0,
3
-1
All required chemicals were used directly without purification
06.7, 122.5, 124.8, 129.2, 129.9, 131.9, 142.2. IR (KBr, cm ):
unless mentioned. Melting points (mp) were recorded on a
Yanano MP500 apparatus and are uncorrected. H NMR spectra
1
3026, 2892, 1566, 1466, 1426, 1211, 1030.
were recorded on a Varian INOVA-500 (500 MHz) spectrometer
2
5
4
.2.7. 2-bromomethyl-2-(3-nitrophenyl)-1,3-dioxolane (2i)
with CDCl as the solvent and TMS as the internal standard.
3
1
Yield 100%, white solid, m.p.: 84-86 ꢁ, H NMR (500 MHz,
CDCl ) δ 3.63(s, 2H, CH Br), 3.90-3.93(m, 2H, OCH CH O),
Capillary GC was performed on GC2014 with a RTX-1 (Restek,
ø 0.25 mm–30 m) column (Inj. 250 ꢁ, Det. 250 ꢁ).
3
2
2
2
4
.21-4.24(m, 2H, OCH CH O), 7.55(dd, 1H, J = 7.7 Hz, J = 8.2
2 2 1 2
Hz, ArH), 7.85(d, 1H, J = 7.7 Hz, ArH), 8.20(d, 1H, J = 8.2 Hz,
4
.2. General procedure for preparation of α-haloacetal of
13
ArH), 8.38(s, 1H, ArH); C NMR(125 MHz, CDCl ) δ 37.2,
acetophenones from acetophenons
3
6
6.1, 106.7, 121.4, 123.7, 129.3, 132.2, 142.2, 148.4. IR (KBr,
-1
cm ): 3026, 2880, 1616, 1525, 1474, 1349, 1227, 1142, 1042.
A mixture of 2 mmol of substrate, and 6 mL ethylene glycol
was stirred for 5 min, and then 4.6 mmol of NBS or 8 mmol of
NCS was added by 5 times in one hour, and the mixture was
stirred 24 h at room temperature or 45ꢁ. Afterward, the mixture
was extracted with ether(10 mL × 3). The combined organic
layer was washed twice by water(20 mL), and dried over
anhydrous Na SO . After filtration, the solvent was removed
under reduced pressure, and the residual was treated with
alumina chromatography (Petroleum ether/AcOEt=20/1,V/V) to
generate the product.
2
2
4
.2.8. 2-bromomethyl-2-(4-nitrophenyl)-1,3-dioxolane (2h)
1
Yield 98%, white solid, m.p.: 126-129 ꢁ, H NMR (500 MHz,
CDCl ) δ 3.62 (s, 2H, CH Br), 3.89-3.93(m, 2H, OCH CH O),
3
2
2
2
4
8
3
3
.21-4.23(m, 2H, OCH CH O), 7.71 (d, 2H, J = 8.5 Hz, ArH),
2 2
13
.21 (d, 2H, J = 8.5 Hz, ArH); C NMR(125 MHz, CDCl ) δ
3
2
4
-
1
7.1, 66.1, 106.9, 123.5, 127.3, 146.7, 148.4. IR (KBr, cm ):
109, 2897, 1608, 1519, 1473, 1347, 1220, 1171, 1038, 854.
4
.2.9. 2-bromomethyl-2-(4-trifluoromethylphenyl)-1,3-
25
22
dioxolane (2g)
4
.2.1. 2-bromomethyl-2-phenyl-1,3-dioxolane(2a)
1
1
Yield 97%, colorless oil; H NMR (500 MHz, CDCl ) δ 3.66 (s,
Yield 98%, white solid, m.p.: 56-58 ꢁ, H NMR (500 MHz,
CDCl ) δ 3.66 (s, 2H, CH Br), 3.88-3.91(m, 2H, OCH CH O),
4
2
1
1
3
2
H, CH Br), 3.91-3.93(m, 2H, OCH CH O), 4.21-4.24(m, 2H,
2 2 2
13
3
2
2
2
OCH CH O), 7.64-7.68(m, 4H, ArH); C NMR(125 MHz,
2
2
.17-4.20(m, 2H, OCH CH O), 7.32-7.38(m, 3H, ArH), 7.52(d,
2 2
13
CDCl ) δ 37.6, 66.0, 106.9, (120.73, 122.90, 125.06, 127.22, q ),
3
H, J = 7.5 Hz, ArH); C NMR (125 MHz, CDCl ) δ 38.2, 65.8,
3
-
1
(125.27, 125.30,125.33, 125.36, q), 126.58, (130.60, 130.86,
07.3, 126.0, 128.3, 128.7, 139.8. IR (KBr, cm ): 3011, 2885,
627, 1485, 1470, 1447, 1220, 1169, 1039, 1029, 997.
-
1
1
1
31.12, 131.38, q), 143.7. IR (KBr, cm ): 2970, 2895, 1619,
409, 1326, 1222, 1167, 1043, 847.
25
4.2.10. 2-bromomethyl-2-(2,4-dichlorophenyl)-1,3-dioxolane
(2j)
4
.2.2. 2-bromomethyl-2-(4-bromophenyl)-1,3-dioxolane (2b)
Yield 99%, white solid, m.p.: 67-70 ꢁ, H NMR (500 MHz,
CDCl ) δ 3.63 (s, 2H, CH Br), 3.89-3.90(m, 2H, OCH CH O),
4
7
3
2
1
1
Yield 96%, white solid, m.p.: 57-58ꢁ; H NMR (500 MHz,
3
2
2
2
CDCl ) δ 3.90-3.93(m, 4H, CH Br, OCH CH O), 4.18-4.25(m,
3
2
2
2
.18-4.21(m, 2H, OCH CH O), 7.40(d, 2H, J = 8.5 Hz, ArH),
2 2
13
2H, OCH CH O), 7.26(d, 2H, J = 8.5 Hz, ArH), 7.42(s, 1H, ArH),
2 2
13
.51(d, 2H, J = 8.5 Hz, ArH); C NMR(125 MHz, CDCl ) δ
3
-
1
7.63(d, 1H, J = 8.5 Hz, ArH); C NMR(125 MHz, CDCl ) δ 35.8,
3
7.8, 65.9, 107.0, 123.1, 127.9, 131.5, 138.8. IR (KBr, cm ):
957, 2874, 1585, 1481, 1413, 1221, 1171, 1039, 831.
6
5.9, 107.0, 126.9, 129.9, 131.2, 132.0, 135.1, 135.4.
2
5
4.2.11. 2-bromomethyl-2-(3,4-dichlorophenyl)-1,3-dioxolane
4
.2.3 2-bromomethyl-2-(4-chlorophenyl)-1,3-dioxolane (2c)
25
1
(2k)
Yield 86%, colorless oil; H NMR (500 MHz, CDCl ) δ 3.62 (s,
Yield 96%, white solid, m.p.: 56-59 ꢁ, H NMR (500 MHz,
CDCl ) δ 3.64 (s, 2H, CH Br), 3.90-3.91(m, 2H, OCH CH O),
.18-4.21(m, 2H, OCH CH O), 7.35(d, 2H, J = 8.5 Hz, ArH),
1
3
3
2
2
2
2
H, CH Br), 3.91-3.93(m, 2H, OCH CH O), 4.19-4.22(m, 2H,
2
2
2
4
7
3
2
2
13
OCH
2
CH
2
O), 7.35-7.37(dd, 1H, J
1
= 8.3Hz, J
2
= 2.0 Hz, ArH),
.46(d, 2H, J = 8.5 Hz, ArH); C NMR(125 MHz, CDCl ) δ
3
13
7
.46(d, 1H, J = 8.3 Hz, ArH), 7.62(d, 1H, J = 2.0 Hz, ArH);
C
1
7.9, 65.9, 107.0, 127.6, 128.5, 134.8, 138.3.
NMR(125 MHz, CDCl ) δ 37.5, 66.0, 106.5, 125.6, 128.3, 130.4,
3
-
1
2
5
132.6, 133.0, 140.1. IR (KBr, cm ): 3068, 2893, 1585, 1561,
1468, 1416, 1379, 1216, 1174, 1035, 822.
4
.2.4. 2-bromomethyl-2-(4-fluorophenyl)-1,3-dioxolane (2d)
1
Yield 92%, colorless oil; H NMR (500 MHz, CDCl ) δ 3.65 (s,
3
2
H, CH Br), 3.90-3.92(m, 2H, OCH CH O), 4.19-4.22(m, 2H,
2
2
2
4
.2.11. 2-bromomethyl-2-(4-biphenylyl)-1,3-dioxolane(2l)
OCH CH O), 7.04-7.09(m, 2H, ArH), 7.49-7.53(m, 2H, ArH);
2
2
1
13
Yield 91%, white solid, m.p.: 74-76ꢁ; H NMR (500 MHz,
CDCl ) δ 3.74(s, 2H, CH Br), 3.96-4.00(m, 2H, OCH CH O),
4
7
ArH); C NMR(125 MHz, CDCl ) δ 39.2, 65.9, 107.3, 126.5,
1
C NMR(125 MHz, CDCl ) δ 38.1, 65.9, 107.0, 115.1, 115.3,
3
-
1
3
2
2
2
1
1
28.0, 135.6. IR (KBr, cm ): 2969, 2893, 1600, 1560, 1412,
222, 1160, 1042, 839.
.21-4.28(m, 2H, OCH CH O), 7.38(t, 1H, J = 7.3 Hz, ArH),
2 2
.47(t, 2H, J = 7.5 Hz, J = 7.7 Hz, ArH), 7.60-7.63(m, 6H,
1
2
13
25
3
4
.2.5. 2-bromomethyl-2-(2-chlorophenyl)-1,3-dioxolane(2e)
27.12, 127.17, 127.6, 128.8, 138.6, 140.5, 141.8.

5
ACCEPTED MANUSCRIPT
25
4
.2.13.
2-bromomethyl-2-[4-(4-bromophenyl)phenyl]-1,3-
4.2.21. 2-chloromethyl-2-phenyl-1,3-dioxolane(3a)
25
1
dioxolane(2m)
Yield 90%, white solid, m.p.: 62-64 ꢁ, H NMR (500 MHz,
CDCl ) δ 3.76 (s, 2H, CH Cl), 3.90-3.93(m, 2H, OCH CH O),
4.17-4.20(m, 2H, OCH CH O), 7.32-7.39(m, 3H, ArH), 7.52(d,
2H, J = 7.3 Hz, ArH); C NMR(125 MHz, CDCl ) δ 49.4, 65.8,
107.9, 126.0, 128.2, 128.7, 139.8. IR (KBr, cm ): 3066, 2887,
1
Yield 92%, white solid, m.p.: 91-95 ꢁ, H NMR (500 MHz,
CDCl ) δ 3.69 (s, 2H, CH Br), 3.92-3.95(m, 2H, OCH CH O),
3
2
2
2
3
2
2
2
2
2
1
3
4
7
1
(
1
.20-4.23(m, 2H, OCH CH O), 7.44-7.45(m, 2H, ArH), 7.54-
2
2
3
13
-1
.59(m, 6H, ArH); C NMR(125 MHz, CDCl ) δ 38.0, 65.9,
3
07.3, 121.8, 126.6, 126.9, 128.7, 131.9, 139.1, 139.5, 140.5. IR
1481, 1467, 1446, 1225, 1179, 1024.
-
1
KBr, cm ): 3021, 2891, 1671, 1479, 1384, 1224, 1167, 1072,
2
5
039, 817.
4.2.22. 2-chloromethyl-2-(4-bromophenyl)-1,3-dioxolane(3b)
1
Yield 91%, white solid, m.p.: 58-61 ꢁ, H NMR (500 MHz,
CDCl ) δ 3.72 (s, 2H, CH Cl), 3.90-3.92(m, 2H, OCH CH O),
4.17-4.20(m, 2H, OCH CH O), 7.40(d, 2H, J = 8.6 Hz, ArH),
25
4
.2.14. 2-bromomethyl-2-(4-methylphenyl)-1,3-dioxolane(2n)
3
2
2
2
1
Yield 85%, colorless oil; H NMR (500 MHz, CDCl ) δ 2.38 (s,
3
2
2
13
3
4
7
H, CH Br), 3.61 (s, 2H, CH ), 3.90-3.92(m, 2H, OCH CH O),
7.51(d, 2H, J = 8.6 Hz, ArH); C NMR(125 MHz, CDCl ) δ
2
3
2
2
3
.18-4.21(m, 2H, OCH CH O), 7.20(d, 1H, J = 7.9 Hz, ArH),
49.1, 65.9, 107.6, 123.1, 127.9, 131.5, 138.8.
4.2.23 2-chloromethyl-2-(4-chlorophenyl)-1,3-dioxolane(3c)
2
2
13
25
.42(d, 1H, J = 7.9 Hz, ArH); C NMR(125 MHz, CDCl ) δ
3
-
1
2
1.2, 38.3, 65.8, 107.3, 125.9, 129.4, 136.7, 138.7. IR (KBr, cm
Yield 95%, white solid, m.p.: 54-58 ꢁ, H NMR (500 MHz,
CDCl ) δ 3.71 (s, 2H, CH Cl), 3.88-3.91(m, 2H, OCH CH O),
1
)
: 3029, 2891, 1606, 1412, 1226, 1182, 1043, 819.
3
2
2
2
4
7
.15-4.18(m, 2H, OCH CH O), 7.33(d, 2H, J = 8.3 Hz, ArH),
2 2
13
2
5
4
.2.15 2-bromomethyl-2-(4-methoxyphenyl)-1,3-dioxolane (2o)
.45(d, 2H, J = 8.3 Hz, ArH); C NMR(125 MHz, CDCl ) δ
3
1
-
1
Yield 52%, mushy oil; H NMR (500 MHz, CDCl ) δ 3.61 (s, 2H,
CH Br), 3.87-3.90(m, 5H, OCH CH O, OCH ), 4.16-4.18(m, 2H,
OCH CH O), 6.88(d, 1H, J = 8.5 Hz, ArH), 7.41(d, 1H, J = 8.5
Hz, ArH), 7.69(s, 1H, ArH); C NMR(125 MHz, CDCl ) δ 38.0,
3
49.1, 65.8, 107.6, 127.6, 128.5, 134.8, 138.3. IR (KBr, cm ):
2982, 1592, 1488, 1431, 1220, 1178, 1090, 1034, 833, 761.
2
2
2
3
2
2
13
25
3
4.2.24. 2-chloromethyl-2-(3-nitrophenyl)-1,3-dioxolane(3g)
Yield 100%, white solid, m.p.: 78-80 ꢁ, H NMR (500 MHz,
CDCl ) δ 3.74 (s, 2H, CH Cl), 3.92-3.95(m, 2H, OCH CH O),
5
6.3, 65.9, 106.6, 111.5, 126.4, 131.1, 133.3, 135.4, 156.2. IR
1
-
1
(
KBr, cm ): 3068, 2894, 1596, 1495, 1252, 1182, 1049, 814.
3
2
2
2
4
.20-4.23(m, 2H, OCH CH O), 7.55(dd, 1H, J = 7.7 Hz, J = 8.2
2 2 1 2
4
.2.16 2-bromocyclohexanone ethylene glycol ketal(2p)
Hz, ArH), 7.85(d, 1H, J = 7.7 Hz, ArH), 8.20(d, 1H, J = 8.2 Hz,
ArH), 8.39(s, 1H, ArH); C NMR(125 MHz, CDCl ) δ 27.4,
6
1
Yield 96%, colorless oil; H NMR (500 MHz, CDCl ) δ 1.35-
1
CH ), 2.18-2.25(m, 1H), 3.97-4.00(m, 2H, OCH CH O), 4.09-
4
2
13
3
3
.38 (m, 1H), 1.51-1.64(m, 4H, CH CH ), 1.98-2.05(m, 2H,
2 2
6.1, 107.3, 121.4, 123.7, 129.3, 132.3, 142.1, 148.4. IR (KBr,
-1
2
2
2
cm ): 3075, 2890, 1615, 1525, 1475, 1422, 1353, 1229, 1042.
13
.15(m, 3H, OCH CH O, CHBr); C NMR(125 MHz, CDCl ) δ
2
2
3
3.1, 34.9, 57.2, 65.5, 65.7, 107.9.
4
.2.25. 2-chloromethyl-2-(4-nitrophenyl)-1,3-dioxolane (3h)
1
Yield 97%, white solid, m.p.: 103-105ꢁ; H NMR (500 MHz,
CDCl
4
8
4
.2.17. 2-(1-bromoethyl)-2-ethyl-1,3-dioxolane(2q)
1
3
) δ 3.75(s, 2H, CH
2
Cl), 3.92-3.97(m, 2H, OCH CH O),
2 2
Yield 82%, colorless oil; H NMR (500 MHz, CDCl ) δ 0.92(t,
3
.19-4.27(m, 2H, OCH CH O), 7.26(d, 2H, J = 8.7 Hz, ArH),
2
2
3
1
4
7
H, J = 7.4 Hz, CH ), 1.68(d, 3H, J = 6.9 Hz, CH ), 1.75-1.82(m,
13
3
3
.24(d, 2H, J = 8.7 Hz, ArH); C NMR(125 MHz, CDCl ) δ 48.8,
3
H, CH ), 1.95-2.03(m, 1H, CH ), 4.00-4.05(m, 4H, OCH CH O),
2
2
2
2
13
66.1, 107.4, 123.5, 127.4, 146.6, 148.3.
.17(q, 1H, J = 6.9 Hz, CHBr); C NMR(125 MHz, CDCl ) δ
3
.3, 20.8, 27.2, 52.7, 66.3, 111.48.
4
.2.26 2-chlorocyclohexanone ethylene glycol ketal(3p)
1
Yield 92%, colorless oil; H NMR (500 MHz, CDCl ) δ 1.13-
1
CHBr); C NMR(125 MHz, CDCl ) δ 22.96, 23.07, 33.7, 33.9,
6
3
4
.2.18. 2-(bromomethyl)-2-propyl-1,3-dioxolane and 2-(1-
.47 (m, 6H), 1.68-1.92(m, 2H), 3.73-3.97(m, 5H, OCH CH O,
2 2
13
bromopropyl)-2-methyl-1,3-dioxolane(2r)
Yield 86%, colorless oil; H NMR (500 MHz, CDCl ) δ 0.94(t,
2
1
3
3
3.4, 65.5, 107.9.
H, J = 7.4 Hz, CH ), 1.09(m, 1.2H, CH ), 1.39-1.43(m, 1.35H,
3
3
CH ), 1.48(s, 1.2H, CH ), 1.66-1.74(m, 0.66H, CH ), 1.79-
2
3
2
4
.2.27 2-(1-chloroethyl)-2-ethyl-1,3-dioxolane(3q)
1
5
1
.82(m, 1.35H, CH ), 2.04-2.08(m, 0.85H, CH ), 3.98-4.08(m,
1
2
2
13
Yield 76%, colorless oil; H NMR (500 MHz, CDCl
0
1
3
) δ 0.74-
H, OCH CH O, CHBr); C NMR(125 MHz, CDCl ) δ 12.9,
2
2
3
.83(m, 3H), 1.32-1.39(m, 3H), 1.46-1.60(m, 2H), 1.73-1.82(m,
4.2, 16.7, 20.7, 27.0, 35.7, 38.2, 62.6, 65.4, 65.7, 109.1, 109.9.
13
H), 3.83-3.92(m, 5H, OCH CH O, CHBr); C NMR(125 MHz,
2
2
CDCl ) δ 7.00, 19.5, 26.7, 60.0, 66.2, 111.5.
3
4
.2.19.
2-(bromomethyl)-2-(5-bromothiophen-2-yl)-1,3-
Dioxolane(2s)
1
4.2.28. cis and trans-2-bromomethyl-4-methyl-2-phenyl-1,3-
Yield 45%, colorless oil; H NMR (500 MHz, CDCl ) δ 4.02-
25
3
dioxolane
4
2
.08(m, 2H, OCH CH O), 4.16-4.23(m, 2H, OCH CH O), 4.30(s,
1
2
2
2
2
Yield 96%, colorless oil; H NMR (500 MHz, CDCl ) δ 1.22 (d,
3
H, CH Br), 6.88(d, 1H, J = 7.4 Hz, cyclo-H), 6.95(s, 1H, J = 7.4
2
13
0.64 H, J = 6.0 Hz, CH
3
4
3
), 1.40 (d, 0.90, J = 6.0 Hz, CH
.38(m, 0.23 H), 3.60-3.64 (m, 1.01 H), 3.66-3.71(m, 0.34 H),
.00-4.03 (m, 0.32 H), 4.13-4.17 (m, 0.32 H), 4.26-4.27 (m, 0.24
3
), 3.35-
Hz, cyclo-H); C NMR(125 MHz, CDCl ) δ 37.2, 66.3, 105.6,
3
1
26.0, 131.3, 132.6, 146.0.
H), 4.51-4.58 (m, 0.21H), 7.32-7.37 (m, 1.44 H), 7.50-7.55 (m,
4
.2.20 2-bromo-1-phenylpropan-1-one and 2,2-dibromo-1-
13
1
.00 H); C NMR(125 MHz, CDCl ) δ 17.7, 18.2, 38.6, 38.9,
3
phenylpropan-1-one
-bromo-1-phenylpropan-1-one: Yield 20%, colorless oil;
NMR (500 MHz, CDCl ) δ 1.89(d, 3H, CH ), 5.30(q, 1H, CHBr),
1
71.8, 72.2, 72.8, 74.9, 125.91, 125.94, 128.2, 128.3, 128.6, 128.7,
40.1, 140.9.
2
H
1
3
3
7
2
.43-7.49(m, 3H, ArH), 8.01-8.03(m, 2H, ArH);
,2-dibromo-1-phenylpropan-1-one: Yield 43%, colorless oil; H
1
Acknowledgments
NMR (500 MHz, CDCl ) δ 3.02(s, 3H, CH ), 7.34-7.39(m, 5H,
3
3
ArH).

6
Tetrahedron
ui MANUSCRIPT
The authors thank the Education Depa
A
rtm
C
e
C
nt
E
o
P
f
TED
A
nh
Province and Huangshan University for financial support (No.
KJ2016A684, and 2013xkjq005).
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