Synthesis of esters from aldehydes or carboxylic acids with dichloromethane, dichloroethane or dichloropropane under mild conditions

Article abstract of DOI:10.1039/c3ra43615b

Dichloromethane (DCM) as a C1 source has been discovered: methylene diesters from DCM and carboxylic acids or aldehydes with TBHP in water were efficiently synthesized. The reactions proceed under mild conditions and afford both aliphatic and aromatic met

Full text of DOI:10.1039/c3ra43615b

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Synthesis of esters from aldehydes or carboxylic acids
with dichloromethane, dichloroethane or
dichloropropane under mild conditions†
Cite this: RSC Adv., 2013, 3, 20246
*
*
Feng Lin, Qiang Feng, Xiuling Cui and Qiuling Song
Dichloromethane (DCM) as a C1 source has been discovered: methylene diesters from DCM and carboxylic
acids or aldehydes with TBHP in water were efficiently synthesized. The reactions proceed under mild
conditions and afford both aliphatic and aromatic methylene diesters in good to excellent yields (up to
>99%). 2-Chloroethyl benzoates and 3-chloropropyl benzoates are easily obtained in the same way
from 1,2-dichloroethane and 1,3-dichloropropane, respectively, in good to excellent yields.
Received 15th July 2013
Accepted 19th August 2013
DOI: 10.1039/c3ra43615b
www.rsc.org/advances
Methylene diesters are very important scaffolds in pharmaceu-
tical1,2 and material science.3 Various methylene diester deriv-
atives have been found to possess anti-inammatory, analgesic
and other biological properties.1,2,4,5 The general route for
construction of symmetric methylene diesters is the reaction of
either CH2I2 (ref. 6) or CH2Br2 (ref. 7) with a carboxylic acid [eqn
(1)]. For unsymmetric methylene diesters, a common route
employs acyl chlorides, which react with aldehydes to give an a-
chloro esters in the presence of ZnCl2,5 and these further react
with different carboxylic acids to afford the unsymmetric dies-
ters [eqn (2)]. Alternatively, CH2IBr can be employed in two step
pathway.5 Compared with CH2I2, CH2Br2, and CH2IBr, DCM is
much less expensive, and even though it is a widely used
solvent, it is seldom8 used as a reagent, especially to serve as a
C1 source (Scheme 1).
Aldehydes are cheap, commercially available, and widely
used organic compounds. The oxidation of aldehydes to
carboxylic acids is a well-known transformation, but although
many efficient methods have been developed, most involve
transition metals. We found that in the presence of base, TBHP
in water–DMSO readily converts aldehydes into the corre-
sponding carboxylic acids in good to high yield. Herein we
describe a novel methylene diester synthesis that starts with
aldehydes and uses DCM as the C1 source. This transformation
is highly efficient for symmetric methylene diester formation.
The same procedure was also adapted to utilize 1,2-dichloro-
ethane and 1,3-dichloropropane, but instead of yielding the
corresponding diesters, monoesters were formed in most cases.
Our studies commenced with the reaction of benzoic acid (1)
and DCM in the presence of K2CO3 in DMSO solvent at 60 ꢀC in
Scheme 1 Symmetric and unsymmetric methylene diester syntheses.
air (Table 1). Most gratifyingly, methylene diester 2 was obtained
in 80% yield! Solvent screening showed that both DMSO and
DMF are good solvents for this reaction, while 1,4-dioxane,
toluene, THF and water gave no reaction. In term of bases, both
K2CO3 and Cs2CO3 gave excellent yields, but KHCO3, Na2CO3 and
NaHCO3 produced only trace amounts of diester. In the presence
of pyridine, triethylamine, NaOH, KOH or sodium tert-butoxide,
there was no reaction at all. The amount of base was also inves-
tigated and it appears that 1 equivalent of K2CO3 in DMSO and
0.5 mL of DCM gives the best results, with isolated yields of up to
99% (entry 6, Table 1), and Cs2CO3–DMSO is also an acceptable
system for the reaction (entry 15, Table 1).
School of Biomedical Sciences, Huaqiao University, Xiamen, Fujian, China. E-mail:
qsong@hqu.edu.cn; cuixl@hqu.edu.cn
With the optimized protocol in hand, we next set out to
explore the scope and limitations of the reaction (Table 2). As
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c3ra43615b
20246 | RSC Adv., 2013, 3, 20246–20253
This journal is ª The Royal Society of Chemistry 2013

View Article Online
Paper
RSC Advances
Table 1 Reaction condition screening for methylene diester synthesisa
Table 2 Methylene diester formation from various carboxylic acidsab
Entry 1
1
Carboxylic acid
Benzoic add
Product
Yield (%)
99%
Entry Bases (equiv.) Solvent
DCM (mL) T (h) T (ꢀC) Yieldb%
1
2
3
4
4
5
6
7
K2CO3(3)
K2CO3(2)
K2CO3(1)
K2CO3(0.5)
K2CO3(0.25)
K2CO3(1)
K2CO3(1)
K2CO3(1)
K2CO3(1)
K2CO3(1)
K2CO3(1)
Pyridine
Triethylamine
KHCO3(2)
Na2CO3(1)
NaHCO3(2)
Cs2CO3(1)
NaOH(2)
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
1,4-Dioxane 0.5
Toluene
THF
—
—
1
1
1
1
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
>99%
>99%
>99%
80%
34%
>99%
80%
>99%
NRc
95%
(0.5 mmol)
96%
2
3
1
(gram scale)
0.5
0.2
0.5
93%
8
9
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
NRc
10
11
12
13
14
15
16
17
18
19
NRc
4
5
6
7
8
9
10
11
12
o-Br (2d)
m-Br (2e)
p-Br (2f)
o-F (2g)
m-F (2h)
p-F (2i)
o-NO2 (2j)
m-NO2 (2k)
p-NO2 (2l)
94%
84%
89%
99%
97%
99%
94%
96%
92%
NRc
NRc
DMSO
DMSO
DMSO
DMF
H2O
Trace
Trace
Trace
>99%
NRc
KOH(2)
Sodium-tert-
butoxide(2)
H2O
DMSO
NRc
NRc
20
Potassium-tert- DMSO
0.5
3
60
NRc
13
14
99%
98%
butoxide(2)
a
Reaction conditions: substrate (0.5 mmol), base, DCM and solvent (2.5
b
mL) stirred under air for the indicated time. Yield of the isolated
product. c NR ¼ no reaction.
15
39%
a
Reaction conditions: carboxylic acid (0.5 mmol), K2CO3 (0.5 mmol),
summarized in Table 2, both aromatic and aliphatic carboxylic
acids could be smoothly transformed into the desired products
(2a–2n in Table 2). Halo-substituted aromatic carboxylic acids
survived well, leading to halo-substituted products (2d–2i), and
b
DMSO (2.5 mL), DCM (0.5 mL), air. Isolated yield.
substituents on the aromatic ring at different positions (ortho-, worked well with both aromatic and aliphatic carboxylic acids
meta- and para-) did not affect the efficiency (2d–2f and 2g–2i). (3a–4g, Table 3). It is easily scaled up to gram quantities without
Similar reactivity was observed with both electron-donating and loss of yield (3b). For aromatic acids, ring substituents at
electron-withdrawing groups on the aromatic rings (2a, 2c, 2d, different positions (ortho-, meta- and para-) did not affect the
2h and 2j), and the reaction can tolerate many functional efficiency (3a, 3c–3e and 4a, 4c–4e), and the reaction tolerated
groups, including methyl, benzyl ether, halo and nitro groups. many functional groups, including uoro, bromo, nitro, methyl,
The procedure can readily be scaled up to gram quantities, and and anisyl groups. However, when the reaction temperature was
there is no decrease in yield between 0.5 mmol and gram scale raised to 90 ꢀC, both mono- and di-esters were formed, and the
(95% in 0.5 mmol and 96% in gram scale; entry 2b in Table 2). ethylene diester (3f) was obtained in 49% isolated yield.
Besides the symmetric examples above, an unsymmetric
Aldehydes are readily available and widely used organic
methylene diester (2o) was also formed under the standard compounds, and they can be considered precursors of carbox-
conditions in 39% isolated yield. This result is not inferior to the ylic acids via oxidation. Numerous methods have been devel-
common methods for unsymmetric diester formation, which oped for aldehyde oxidation,9–15 yet most are either transition
usually require two steps and give overall yields of 30–50%.1
metal-catalyzed9,10,15,16 or catalyzed by highly complex organo-
1,2-Dichloroethane and 1,3-dichloropropane are also catalysts.11 Current environmental concerns necessitate greener
common solvents. Interestingly, when the standard conditions reactions free of any transition metal involvement, and water is
were applied to these dichloro alkanes, none of the expected the preferred medium. When 4-chlorobenzaldehyde was treated
diesters were formed. Instead, monoesters were formed exclu- with TBHP in aqueous DMSO, we found that bases could
sively (Table 3). This is a highly efficient method for synthesis of promote the conversion of aldehyde to acid without any tran-
2-chloroethyl and 3-chloropropyl benzoates, and the reaction sition metal present. Since methylene diester formation is a
This journal is ª The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 20246–20253 | 20247

View Article Online
RSC Advances
Paper
Table 3 2-Chloroethyl and 3-chloropropyl ester formation from DCE and DCP
and various carboxylic acidsab
Table 5 Methylene diester formation from various aldehydesa
Entry
1
Aldehyde
Product
Yieldb (%)
75
2
3
4
5
56
55
50
70
6
58
56
62
54
62
a
Reaction conditions: carboxylic acid (0.5 mmol), K2CO2 (0.5 mmol),
b
c
DMSO (2.5 mL), DCE or DCP (1.0 mL), air. Isolated yield. Reaction
d
e
temp: 35 ꢀC. Reaction temp: 45 ꢀC. Reaction temp: 60 ꢀC.
f
Reaction temp: 90 ꢀC.
7
8
base-mediated reaction, addition of DCM to the reaction
mixture directly leads to methylene diester formation. Condi-
tion screening showed that 2.5 equivalents of TBHP in water at
120 ꢀC in the presence of K2CO3 could convert 1 equivalent of 2-
chlorobenzaldehyde into carboxylic acid smoothly, and
furthermore, DCM addition at 90 ꢀC gave a 75% yield of the
corresponding methylene diester (entry 4, Table 4).
9
10
11
71
Table 4 Reaction condition screening for methylene diester formation from
aldehydesa
a
Reaction conditions: step 1: aldehyde (1 mmol), TBHP in water (0.34
mL), DMSO (1.75 mL), 5–6 h, 120 ꢀC, air, reux; step 2: 0.8 mL DCM,
3 h, 60–90 ꢀC. b Yield of the isolated product.
A variety of benzaldehydes were subjected to the standard
conditions, and as shown in Table 5, all gave fair to good results.
Many functional groups were tolerated in this reaction (5a–5j,
Table 5), and the same functional group at a different positions
on the aromatic ring had little effect on the efficiency of the
reaction (5b, 5h and 5i, 5d and 5f). In the case of aliphatic alde-
hydes, however, only trace amounts of product were obtained.
When DCE and DCP were used instead of DCM under the
above conditions, the corresponding monoesters were formed
in good yield as well (Table 6).
Entry Oxidant (equiv.)
T1 (ꢀC) t1 (h) T2 (ꢀC) t2 (h) Yieldb%
1
2
3
4
4
5
TBHP in hexane (2.5) 120
DTBP (2.5) 120
TBHP in toluene (2.5) 120
TBHP in H2O (2.5)
TBHP in H2O (1.4)
TBHP in H2O (3.2)
5
5
5
5
5
5
90
90
90
90
90
90
2.5
2.5
2.5
2.5
2.5
2.5
58
43
43
75
32
75
120
120
120
a
Reaction conditions: substrate (0.5 mmol), oxidant and DMSO (2.5 mL)
and DCM (0.5 mL) with stirring under air for the indicated time. b Yield
of the isolated product.
20248 | RSC Adv., 2013, 3, 20246–20253
This journal is ª The Royal Society of Chemistry 2013

View Article Online
Paper
RSC Advances
Cs2CO3 and DMF, an N-substituted product was obtained;21 and
the chlorine can easily be converted into iodine in the presence
of sodium iodide (Scheme 2).22
Table 6 2-Chloroethyl and 3-chloropropyl ester formation from various alde-
hydes and DCE and DCPa
In summary, we have demonstrated direct methylene diester
formation from carboxylic acids with DCM (dichloromethane),
as well as a methylene diester preparation from aldehydes and
DCM in a basic TBHP aqueous system. DCM is much cheaper
than DBM (dibromomethane), DIM (diiodomethane) or bro-
moiodomethane and the reaction proceeds smoothly to give
good to excellent yields. If DCE (1,2-dichloroethane) or DCP
(1,3-dichloropropane) is used instead of DCM, monoester is
formed in good to excellent yield. This method affords a cheap
and efficient route for synthesis of methylene diesters and 2-
chloroethyl benzoates and 3-chloropropyl benzoates. The scope,
mechanism and synthetic applications of these reactions are
under investigation in our lab.
Entry
1
Aldehyde
Product
Yieldb (%)
74
2
3
4
60
62
74
Experimental section
General method
5
77
74
All manipulations were conducted with a trace reaction tube
under air. 1H-NMR spectra were recorded on a Bruker AVIII-
400M spectrometers. Chemical shis (in ppm) were referenced
to tetramethylsilane (d ¼ 0 ppm) in CDCl3 as an internal stan-
dard. 13C-NMR spectra were obtained by using the same NMR
spectrometers and were calibrated with CDCl3 (d ¼ 77.00 ppm).
High-resolution mass spectra (HRMS) were recorded on a FTMS
mass spectrometer using ESI (electrospray ionization) and
FT-ICR mass analyser or mass spectrometer using EI (electro-
ionization). Unless otherwise noted, materials obtained from
commercial suppliers were used without further purication.
6
a
Reaction conditions: step 1: aldehyde (1 mmol), TBHP in water (0.34
mL), DMSO (1.75 mL), 5–6 h, 120 ꢀC, air, reux; step 2: 0.8 mL DCE
b
(entry 1–3) or DCP (entry 4–6), 2.5 h, 60 ꢀC. Yield of the isolated
product.
2-Chloroethyl benzoates and 3-chloropropyl benzoates are
versatile intermediates and building blocks in organic
synthesis.17 For example, a Sonogashira reaction could take
place between a terminal alkyne and a 2-chloroethyl benzoate or
3-chloropropyl benzoate to give a useful product;17 a tandem
reaction between sodium azide, acetylene, 4-bromopyridine and
2-chloroethyl benzoate or 3-chloropropyl benzoate might give a
click type product;18 in the presence of strong base, the ester can
be hydrolyzed to 2-chloroethanol;19 and the chlorine might be
replaced by hydroxide to give 2-hydroxyethyl benzoate;20 when
treated with a nitrogenous organic base in the presence of
A typical procedure for preparation of methylene diester from
carboxylic acid and DCM (1,1-dichloromethane)
2-Methylbenzoic acid (69 mg, 0.5 mmol), K2CO3 (69 mg, 0.5
mmol), DCM (0.5 mL), and DMSO (2.5 mL) were stirred at 60 ꢀC
under air for 3 hours. Aer cooling to r.t., EtOAc (20 mL) was
added, and the reaction solution was washed with saturated
NaHCO3 solution (20 mL), water (20 mL ꢁ 3) and brine
sequentially. Then the organic layer was dried over anhydrous
MgSO4. Aer ltration, the solvent was removed under vacuum.
At last, the reaction affords 71.5 mg of 2a as a white solid.
A typical procedure for preparation of 2-chloroethyl benzoate
from carboxylic acid and DCE (1,2-dichloroethane)
2-Methylbenzoic acid (100 mg, 0.5 mmol), K2CO3 (69 mg,
0.5 mmol), DMSO (2.5 mL) and DCE (1.0 mL) were stirred at
35 ꢀC under air for 4 hours. Aer cooling to r.t., EtOAc (20 mL)
was added, and the reaction solution was washed with saturated
NaHCO3 solution (20 mL), water (20 mL ꢁ 3) and brine
sequentially. Then the organic layer was dried over anhydrous
MgSO4. Aer ltration, the solvent was puried by ash chro-
matography on silica gel (eluent: petroleum ether–ethyl
acetate ¼ 15 : 1) to afford 95 mg of 3a as yellow oil.
Scheme 2 Literature transformations of 2-chloroethyl benzoates and 3-chlor-
opropyl benzoates.
This journal is ª The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 20246–20253 | 20249

View Article Online
RSC Advances
Paper
A typical procedure for preparation of 3-chloropropyl benzoate
from carboxylic acid and DCP (1,3-dichloropropane)
Bis(3-bromobenzoyloxy)methane (2e)
89 mg (84%), a white solid. Mp: 100–102 ꢀC. 1H NMR (400 MHz,
2-Methylbenzoic acid (100 mg, 0.5 mmol), K2CO3 (69 mg, 0.5 CDCl3): d 8.22 (t, J ¼ 1.6 Hz, 2H), 8.02 (d, J ¼ 7.8 Hz, 2H), 7.72 (d,
mmol), DMSO (2.5 mL) and DCP (1.0 mL) were stirred at 45 ꢀC J ¼ 8.0 Hz, 2H), 7.34 (t, J ¼ 7.9 Hz, 2H), 6.24 (s, 2H); 13C NMR
under air for 3 hours. Aer cooling to r.t., EtOAc (20 mL) was (100 MHz, CDCl3): d 163.89, 136.71, 132.98, 130.73, 130.08,
added, and the reaction solution was washed with saturated 128.63, 122.61, 80.30; HRMS calcd for C15H10Br2NaO4 [M + Na]+
NaHCO3 solution (20 mL), water (20 mL ꢁ 3) and brine 434.8838, found 434.8841.
sequentially. Then the organic layer was dried over anhydrous
MgSO4. Aer ltration, the solvent was puried by ash chro-
matography on silica gel (eluent: petroleum ether–ethyl acetate
¼ 20 : 1) to afford 96.5 mg of 4a as yellow oil.
Bis(4-bromobenzoyloxy)methane (2f)
92.2 mg (89%), a white solid. Mp: 119–121 ꢀC. 1H NMR (400
MHz, CDCl3): d 7.94 (d, J ¼ 8.7 Hz, 4H), 7.59 (d, J ¼ 8.7 Hz, 4H),
6.22 (s, 2H); 13C NMR (100 MHz, CDCl3): d 164.49, 131.90,
131.51, 129.04, 127.75, 80.17; HRMS calcd for C15H10Br2NaO4
[M + Na]+ 434.8838, found 434.8843.
Bis(2-methylbenzoyloxy)methane (2a)
71.5 mg (99%), a white solid. Mp: 62–63 ꢀC. 1H NMR (400 MHz,
CDCl3): d 8.03–7.97 (m, 2H), 7.43 (td, J ¼ 7.5, 1.4 Hz, 2H), 7.25
(dd, J ¼ 8.1, 6.4 Hz, 4H), 6.21 (s, 2H), 2.63 (s, 6H); 13C NMR (100
MHz, CDCl3): d 165.88, 141.11, 132.70, 131.81, 131.09, 128.16,
125.81, 79.71, 21.82; HRMS calcd for C17H16NaO4 [M + Na]+
307.0941, found 307.0939.
Bis(2-uorobenzoyloxy)methane (2g)
72.3 mg (99%), a white solid. Mp: 61–63 ꢀC. 1H NMR (400 MHz,
CDCl3): d 7.99 (td, J ¼ 7.6, 1.7 Hz, 2H), 7.56 (dddd, J ¼ 8.3, 7.4,
4.8, 1.8 Hz, 2H), 7.18 (dddd, J ¼ 10.7, 9.2, 8.1, 0.9 Hz, 4H), 6.25
(s, 2H); 13C NMR (100 MHz, CDCl3): d 163.63, 162.61 (d, J ¼ 3.8
Hz), 161.03, 135.28 (d, J ¼ 9.2 Hz), 132.33, 124.02 (d, J ¼ 4.1 Hz),
117.45 (d, J ¼ 9.0 Hz), 117.08 (d, J ¼ 22.0 Hz), 80.10; HRMS calcd
for C15H10F2NaO4 [M + Na]+ 315.0439, found 315.0437.
Bis(benzoyloxy)methane (2b), 0.5 mmol scale
60.8 mg (95%), a white solid. Mp: 100–102 ꢀC. 1H NMR (400
MHz, CDCl3): d 8.10 (dd, J ¼ 8.4, 1.3 Hz, 4H), 7.61–7.56 (m, 2H),
7.47–7.42 (m, 4H), 6.26 (s, 2H); 13C NMR (100 MHz, CDCl3): d
165.38, 133.80, 130.20, 129.13, 128.62, 80.19; HRMS calcd for
Bis(3-uorobenzoyloxy)methane (2h)
1
ꢀ
70 mg (97%), a white solid. Mp: 45–46 C. H NMR (400 MHz,
CDCl3): d 7.91–7.87 (m, 2H), 7.80–7.73 (m, 2H), 7.47–7.40 (m,
2H), 7.33–7.26 (m, 2H), 6.25 (s, 2H); 13C NMR (100 MHz, CDCl3):
d 164.05 (d, J ¼ 3.3 Hz), 163.74, 161.28, 130.97 (d, J ¼ 7.6 Hz),
130.18 (d, J ¼ 7.8 Hz), 125.79 (d, J ¼ 3.1 Hz), 120.83 (d, J ¼ 21.3
C
15H12NaO4 [M + Na]+ 279.0628, found 279. 0624.
Bis(benzoyloxy)methane (2b), gram scale
Benzoic acid (1.098 g, 9 mmol), K2CO3 (1.242ꢀg, 9 mmol), DCM
(4 mL), and DMSO (6 mL) were stirred at 90 C under air for 5
hours. Aer cooling to r.t., EtOAc (60 mL) was added, and the
reaction solution was washed with saturated NaHCO3 solution
(60 mL), water (60 mL ꢁ 3) and brine sequentially. Then the
organic layer was dried over anhydrous MgSO4. Aer ltration,
the solvent was removed under vacuum. At last, the reaction
affords 1.106 g (96%) of 2b as a white solid.
Hz), 116.90 (d,
C
J
¼
23.3 Hz), 80.32; HRMS calcd for
15H10F2NaO4 [M + Na]+ 315.0439, found 315.0438.
Bis(4-uorobenzoyloxy)methane (2i)
1
ꢀ
72.3 mg (99%), a white solid. Mp: 97–98 C. H NMR (400 MHz,
CDCl3): d 8.14–8.09 (m, 4H), 7.16–7.10 (m, 4H), 6.23 (s, 2H); 13C
NMR (100 MHz, CDCl3): d 167.48, 164.94, 164.23, 132.70 (d, J ¼ 9.5
Hz), 125.15 (d, J ¼ 3.1 Hz), 115.73 (d, J ¼ 22.1 Hz), 80.05; HRMS
calcd for C15H10F2NaO4 [M + Na]+ 315.0439, found 315.0439.
Methylene bis(2-(benzyloxy)benzoate) (2c)
106 mg (93%), brown oil. 1H NMR (400 MHz, CDCl3): d 7.89 (dd,
J ¼ 7.8, 1.2 Hz, 2H), 7.51–7.40 (m, 6H), 7.27 (ddd, J ¼ 10.3, 7.5,
3.8 Hz, 6H), 7.02–6.92 (m, 4H), 6.23 (s, 2H), 5.15 (s, 4H); 13C
NMR (100 MHz, CDCl3): d 164.42, 158.77, 136.55, 134.13,
132.33, 128.47, 127.67, 126.79, 120.47, 119.33, 113.80, 79.93,
70.53; HRMS calcd for C29H24NaO6 [M + Na]+ 491.1465, found
491.1456.
Bis(2-nitrobenzoyloxy)methane (2j)
81.3 mg (94%), a light yellow solid. Mp: 87–89 ꢀC. 1H NMR (400
MHz, CDCl3): d 7.99 (dd, J ¼ 7.9, 0.7 Hz, 2H), 7.87–7.83 (m, 2H),
7.71 (dtd, J ¼ 17.0, 7.6, 1.3 Hz, 4H), 6.16 (s, 2H); 13C NMR (100
MHz, CDCl3): d 164.14, 147.82, 133.28, 132.22, 130.08, 126.60,
124.06, 80.40; HRMS calcd for C15H10N2NaO8 [M + Na]+
369.0329, found 369.0333.
Bis(2-bromobenzoyloxy)methane (2d)
Bis(3-nitrobenzoyloxy)methane (2k)
97.3 mg (94%), a white solid. Mp: 57–59 ꢀC. 1H NMR (400 MHz, 83.9 mg (96%), a white solid. Mp: 83–85 ꢀC. 1H NMR (400 MHz,
CDCl3): d 7.94–7.87 (m, 2H), 7.73–7.65 (m, 2H), 7.41–7.33 (m, CDCl3): d 9.04–8.79 (m, 2H), 8.50–8.42 (m, 4H), 7.71 (t, J ¼ 8.0
4H), 6.24 (s, 2H); 13C NMR (100 MHz, CDCl3): d 164.31, 134.64, Hz, 2H), 6.35 (s, 2H); 13C NMR (100 MHz, CDCl3): d 163.09,
133.32, 131.94, 130.35, 127.23, 122.40, 80.29; HRMS calcd for 148.36, 135.62, 130.48, 129.89, 128.20, 125.00, 80.80; HRMS
C
15H10Br2NaO4 [M + Na]+ 434.8838, found 434.8842.
calcd for C15H10N2NaO8 [M + Na]+ 369.0329, found 369.0323.
20250 | RSC Adv., 2013, 3, 20246–20253
This journal is ª The Royal Society of Chemistry 2013

View Article Online
Paper
RSC Advances
(60 mL), water (60 mL ꢁ 3) and brine sequentially. Then the
organic layer was dried over anhydrous MgSO4. Aer ltration,
the solvent was puried by ash chromatography on silica gel
(eluent: petroleum ether–ethyl acetate ¼ 15 : 1) to afford 1.639 g
(99%) of 3b as yellow oil.
Bis(4-nitrobenzoyloxy)methane (2l)
1
ꢀ
79.6 mg (92%), a light yellow solid. Mp: 181–183 C. H NMR
(400 MHz, CDCl3): d 8.47–8.22 (m, 8H), 6.31 (s, 2H); 13C NMR
(100 MHz, CDCl3): d 163.34, 151.07, 133.97, 131.25, 123.72,
80.72; HRMS calcd for C15H10N2NaO8 [M + Na]+ 369.0329, found
369.0326.
2-Chloroethyl 4-bromobenzoate (3c)
105 mg (80%), a white solid. Mp: 56–58 ꢀC. 1H NMR (400 MHz,
CDCl3): d 7.93 (dd, J ¼ 8.6, 1.9 Hz, 2H), 7.60 (dd, J ¼ 8.7, 2.1 Hz,
2H), 4.565 (t, J ¼ 6.0 Hz, 2H), 3.81 (t, J ¼ 4.0 Hz, 2H); 13C NMR
(100 MHz, CDCl3): d 165.43, 131.81, 131.24, 128.51, 128.45,
64.65, 41.57; HRMS calcd for C9H9BrClO2 [M + H]+ 262.9469,
found 262.9476.
Bis(cyclohexanecarbonyloxy)methane (2m)
1
66.2 mg (99%), a light yellow oil. H NMR (400 MHz, CDCl3): d
5.74 (s, 1H), 2.34 (tt, J ¼ 11.2, 3.7 Hz, 2H), 1.95–1.85 (m, 4H),
1.78–1.71 (m, 4H), 1.68–1.59 (m, 2H), 1.53–1.36 (m, 4H), 1.35–
1.17 (m, 6H); 13C NMR (100 MHz, CDCl3): d 174.69, 78.93, 42.79,
28.67, 25.62, 25.24; HRMS calcd for C15H24NaO4 [M + Na]+
291.1567, found 291.1568.
2-Chloroethyl 2-uorobenzoate (3d)
95.1 mg (94%), a yellow oil. 1H NMR (400 MHz, CDCl3): d 7.99–
7.92 (m, 1H), 7.62–7.46 (m, 1H), 7.25–7.11 (m, 2H), 4.58 (t, J ¼
5.7 Hz, 2H), 3.815 (t, J ¼ 6.0 Hz, 2H). 13C NMR (100 MHz,
CDCl3): d 63.74 (d, J ¼ 3.7 Hz), 163.30, 160.71, 134.75 (d, J ¼ 9.2
Hz), 132.07, 123.94 (d, J ¼ 4.0 Hz), 118.10 (d, J ¼ 9.7 Hz), 116.97
(d, J ¼ 22.2 Hz), 64.59, 41.39; HRMS calcd for C9H8ClFNaO2 [M +
Na]+ 225.0089, found 225.0091.
Bis(pentanoyloxy)methane (2n)
105 mg (98%), a yellow oil. 1H NMR (400 MHz, CDCl3): d 5.75 (s,
2H), 2.36 (t, J ¼ 7.5 Hz, 4H), 1.72–1.53 (m, 4H), 1.42–1.30 (m,
4H), 0.92 (t, J ¼ 7.4 Hz, 6H); 13C NMR (100 MHz, CDCl3): d
172.44, 76.68, 33.64, 26.62, 22.07, 13.59; HRMS calcd for
C
11H20NaO4 [M + Na]+ 239.1254, found 239.1255.
((3-Bromobenzoyl)oxy)methyl 2-uorobenzoate (2o)
2-Chloroethyl 3-nitrobenzoate (3e)
68.9 mg (39%), a light yellow solid. Mp: 39–40 ꢀC. 1H NMR (400
MHz, CDCl3): d 8.22 (t, J ¼ 1.8 Hz, 1H), 8.04–7.94 (m, 2H), 7.70
(ddd, J ¼ 8.0, 2.0, 1.1 Hz, 1H), 7.62–7.51 (m, 1H), 7.33 (t, J ¼ 7.9
Hz, 1H), 7.24–7.09 (m, 2H), 6.24 (s, 2H); 13C NMR (100 MHz,
CDCl3): d 163.82, 163.63, 162.62 (d, J ¼ 3.8 Hz), 161.02, 136.59,
135.37 (d, J ¼ 9.1 Hz), 132.92, 132.32, 130.79, 130.02, 128.58,
124.04 (d, J ¼ 3.9 Hz), 122.54, 117.31 (d, J ¼ 9.3 Hz), 117.11 (d, J
¼ 22.0 Hz), 80.17; HRMS calcd for C15H10BrFNaO4 [M + Na]+
374.9639, found 374.9647.
108.8 mg (95%), a yellow oil. 1H NMR (400 MHz, CDCl3): d 8.88
(s, 1H), 8.47–8.38 (m, 2H), 7.69 (t, J ¼ 8.0 Hz, 1H), 4.655 (t, J ¼
6.0 Hz, 2H), 3.865 (t, J ¼ 6.0 Hz, 2H); 13C NMR (100 MHz,
CDCl3): d 164.03, 148.29, 135.33, 131.34, 129.71, 127.64, 124.65,
65.18, 41.36; HRMS calcd for C9H9ClNO4 [M + H]+ 230.0215,
found 230.0220.
1,2-Bis(2-nitrobenzoyl)ethane (3f)
1
ꢀ
44.1 mg (49%), a brown solid. Mp: 132–133 C. H NMR (400
MHz, CDCl3): d 7.92 (dd, J ¼ 7.9, 1.3 Hz, 2H), 7.81 (dd, J ¼ 7.6,
2-Chloroethyl 2-methylbenzoate (3a)
1.5 Hz, 2H), 7.67 (dtd, J ¼ 17.1, 7.6, 1.4 Hz, 4H), 4.64 (s, 4H); 13
C
95 mg (96%), a yellow oil. 1H NMR (400 MHz, CDCl3): d 7.96 (dd,
J ¼ 8.1, 1.4 Hz, 1H), 7.41 (td, J ¼ 7.5, 1.5 Hz, 1H), 7.28–7.22 (m,
2H), 4.545 (t, J ¼ 6.0 Hz, 2H), 3.805 (t, J ¼ 6.0 Hz, 2H), 2.61 (s,
3H); 13C NMR (100 MHz, CDCl3): d 167.00, 140.39, 132.23,
131.69, 130.75, 128.93, 125.72, 64.23, 41.71, 21.72; HRMS calcd
for C10H11ClNaO2 [M + Na]+ 221.0340, found 221.0342.
NMR (100 MHz, CDCl3): d 165.10, 148.12, 132.98, 131.87,
130.06, 127.16, 123.87, 63.51; HRMS calcd for C16H13N2O8[M +
H]+ 361.0666, found 361.0678.
2-Chloroethyl 2-(4-methoxyphenyl)acetate (3g)
108.3 mg (95%), a yellow oil. 1H NMR (400 MHz, CDCl3): d 7.23–
7.19 (m, 2H), 6.88–6.85 (m, 2H), 4.335 (t, J ¼ 6.0 Hz, 2H), 3.79 (s,
3H), 3.665 (t, J ¼ 6.0 Hz, 2H), 3.61 (s, 2H); 13C NMR (100 MHz,
CDCl3): d 171.50, 158.77, 130.27, 125.62, 114.02, 64.26, 55.24,
41.45, 40.14; HRMS calcd for C11H13ClNaO3 [M + Na]+ 251.0445,
found 251.0449.
2-Chloroethyl benzoate (3b), 0.5 mmol scale
92.5 mg (99%) of 3b as yellow oil. 1H NMR (400 MHz, CDCl3): d
8.07 (dd, J ¼ 8.3, 1.2 Hz, 2H), 7.61–7.55 (m, 1H), 7.45 (t, J ¼ 7.7
Hz, 2H), 4.575 (t, J ¼ 6.0 Hz, 2H), 3.815 (t, J ¼ 6 Hz, 2H); 13C NMR
(100 MHz, CDCl3): d 166.13, 133.22, 129.71, 129.61, 128.40,
64.42, 41.63; HRMS calcd for C9H9ClNaO2 [M + Na]+ 207.0183,
found 207.0183.
2-Chloroethyl benzoate (3h)
1
88.4 mg (93%), a light yellow oil. H NMR (400 MHz, CDCl3): d
4.315 (t, J ¼ 6 Hz, 2H), 3.68 (t, J ¼ 6 Hz, 2H), 2.35 (tt, J ¼ 11.3, 3.6
2-Chloroethyl benzoate (3b), gram scale
Hz, 1H), 1.93 (ddd, J ¼ 11.8, 6.3, 3.6 Hz, 2H), 1.80–1.72 (m, 2H),
Benzoic acid (1.098 g, 9 mmol), K2CO3 (1.242 g, 9 mmol), DMSO 1.70–1.61 (m, 1H), 1.54–1.40 (m, 2H), 1.38–1.19 (m, 4H); 13C
(6 mL) and DCE (5 mL) were stirred at 60 ꢀC under air for 5 NMR (100 MHz, CDCl3): d 175.66, 63.63, 42.99, 41.72, 28.92,
hours. Aer cooling to r.t., EtOAc (60 mL) was added, and the 25.68, 25.34; HRMS calcd for C9H15ClNaO2 [M + Na]+ 213.0653,
reaction solution was washed with saturated NaHCO3 solution found 213.0658.
This journal is ª The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 20246–20253 | 20251

View Article Online
RSC Advances
Paper
13C NMR (100 MHz, CDCl3, TMS): d 175.87, 60.77, 43.13, 41.21,
31.65, 28.98, 25.70, 25.39; HRMS calcd. for C10H17ClNaO2 [M +
Na]+ 227.0809, found 227.0814.
2-Chloropropyl 2-methylbenzoate (4a)
1
96.5 mg (90%), a yellow oil. H NMR (400 MHz, CDCl3): d 7.90
(dd, J ¼ 8.1, 1.3 Hz, 1H), 7.39 (td, J ¼ 7.5, 1.3 Hz, 1H), 7.31–7.16
(m, 2H), 4.44 (t, J ¼ 6.1 Hz, 2H), 3.69 (t, J ¼ 6.5 Hz, 2H), 2.60 (s,
3H), 2.22 (p, J ¼ 6.3 Hz, 2H); 13C NMR (100 MHz, CDCl3): d
167.26, 140.13, 131.99, 131.67, 130.46, 129.38, 125.66, 61.39,
41.29, 31.68, 21.66; HRMS calcd for C11H13ClNaO2 [M + Na]+
235.0496, found 235.0495.
Typical procedure for preparation of methylene diester from
aldehydes and DCM
4-Chlorobenzaldehyde (140 mg, 1 mmol), K2CO3 (166 mg, 1.2
mmol), TBHP in H2O (0.34 mL, 2.5 mmol), DMSO (1.75 mL)
ꢀ
were stirred at 120 C under air for 5 hours. Then the solvent
was charged with 0.8 mL DCM and stirred for 3 more hours.
Aer cooling to r.t., the reaction solution was washed with
saturated Na2S2O3 solution (20 mL), water (20 mL ꢁ 2) and
brine sequentially. Then the organic layer was dried over
anhydrous MgSO4. Aer ltration, the solvent was puried by
ash chromatography on silica gel (eluent: petroleum ether–
ethyl acetate ¼ 70 : 1) to affords 120 mg of 2p as a white solid.
2-Chloropropyl benzoate (4b)
88.1 mg (89%), a yellow oil. 1H NMR (400 MHz, CDCl3): d 8.07–
8.01 (m, 2H), 7.60–7.52 (m, 2H), 7.48–7.41 (m, 2H), 4.66 (t, J ¼
6.1 Hz, 2H), 3.70 (t, J ¼ 6.4 Hz, 2H), 2.23 (p, J ¼ 6.2 Hz, 2H); 13
C
NMR (100 MHz, CDCl3): d 166.26, 132.95, 129.97, 129.47,
128.31, 61.59, 41.20, 31.68; HRMS calcd for C10H11NaClO2 [M +
Na]+ 221.0340, found 221.0344.
Typical procedure for preparation of methylene diester from
aldehydes and DCE
2-Chloropropyl 2-bromobenzoate (4c)
125 mg (90%), a yellow oil. 1H NMR (400 MHz, CDCl3): d 7.81–
7.75 (m, 1H), 7.67–7.63 (m, 1H), 7.41–7.30 (m, 2H), 4.49 (t, J ¼
6.0 Hz, 2H), 3.72 (t, J ¼ 6.4 Hz, 2H), 2.27–2.20 (m, 2H); 13C NMR
(100 MHz, CDCl3): d 165.94, 134.21, 132.51, 132.08, 131.21,
131.20, 127.10, 121.38, 62.23, 41.20, 31.44; HRMS calcd for
4-Chlorobenzaldehyde (140 mg, 1 mmol), K2CO3 (166 mg, 1.2
mmol), TBHP in H2O (0.34 mL, 2.5 mmol), DMSO (1.75 mL)
ꢀ
were stirred at 120 C under air for 5 hours. Then the solvent
was charged with 0.8 mL DCE and stirred for 2.5 more hours.
Aer cooling to r.t., the reaction solution was washed with
saturated Na2S2O3 solution (20 mL), water (20 mL ꢁ 2) and
brine sequentially. Then the organic layer was dried over
anhydrous MgSO4. Aer ltration, the solvent was puried by
ash chromatography on silica gel (eluent: petroleum ether–
ethyl acetate ¼ 70 : 1) to afford 161 mg of 3i as yellow oil.
C
10H11BrClO2 [M + H]+ 276.9626, found 276.9633.
2-Chloropropyl 4-uorobenzoate (4d)
1
94 mg (87%), a yellow oil. H NMR (400 MHz, CDCl3): d 8.14–
7.94 (m, 2H), 7.15–7.07 (m, 2H), 4.47 (t, J ¼ 6.1 Hz, 2H), 3.70 (t, J
¼ 6.4 Hz, 2H), 2.28–2.19 (m, 2H); 13C NMR (100 MHz, CDCl3): d
166.96, 165.27, 164.44, 132.01 (d, J ¼ 9.4 Hz), 126.21 (d, J ¼ 3.0
Hz), 115.44 (d, J ¼ 22.0 Hz), 61.74, 41.13, 31.61; HRMS calcd for
Typical procedure for preparation of methylene diester from
aldehydes and DCP
C
10H10ClFO2 [M + H]+ 239.0215, found 239.0246.
4-Chlorobenzaldehyde (140 mg, 1 mmol), K2CO3 (166 mg, 1.2
mmol), TBHP in H2O (0.34 mL, 2.5 mmol), DMSO (1.75 mL)
2-Chloropropyl 3-nitrobenzoate (4e)
ꢀ
were stirred at 120 C under air for 5 hours. Then the solvent
107.2 mg (88%), a yellow oil. 1H NMR (400 MHz, CDCl3): d 8.84
(d, J ¼ 1.5 Hz, 1H), 8.48–8.33 (m, 2H), 7.68 (t, J ¼ 8.0 Hz, 1H),
4.56 (t, J ¼ 6.1 Hz, 2H), 3.73 (t, J ¼ 6.3 Hz, 2H), 2.30 (p, J ¼ 6.2 Hz,
2H); 13C NMR (100 MHz, CDCl3): d 164.20, 148.22, 135.17,
131.71, 129.63, 127.40, 124.43, 62.63, 41.04, 31.45; HRMS calcd
for C10H11ClNO4 [M + H]+ 244.0371, found 244.0378.
was charged with 0.8 mL DCP and stirred for 2.5 more hours.
Aer cooling to r.t., the reaction solution was washed with
saturated Na2S2O3 solution (20 mL), water (20 mL ꢁ 2) and
brine sequentially. Then the organic layer was dried over
anhydrous MgSO4. Aer ltration, the solvent was puried by
ash chromatography on silica gel (eluent: petroleum ether–
ethyl acetate ¼ 70 : 1) to afford 172 mg of 4h as yellow oil.
3-Chloropropyl 2-(4-methoxyphenyl)acetate (4f)
114.5 mg (96%), a yellow oil. 1H NMR (400 MHz, CDCl3, TMS): d
7.21–7.17 (m, 2H), 6.89–6.84 (m, 2H), 4.24 (t, J ¼ 6.1 Hz, 2H), 3.80
(s, 3H), 3.59–3.50 (m, 4H), 2.07 (p, J ¼ 6.3 Hz, 2H); 13C NMR (100
MHz, CDCl3, TMS): d 171.71, 158.74, 130.20, 125.94, 114.03,
61.46, 55.26, 41.09, 40.42, 31.54; HRMS calcd. for C12H15ClNaO3
[M + Na]+ 265.0602, found 265.0604.
Bis(4-Chlorobenzoyloxy)methane (2p)
122 mg (75%), a white solid. Mp: 68–70 ꢀC. 1H NMR (400 MHz,
CDCl3): d 8.02 (d, J ¼ 8.6 Hz, 4H), 7.43 (d, J ¼ 8.7 Hz, 4H), 6.23 (d,
J ¼ 6.7 Hz, 2H); 13C NMR (100 MHz, CDCl3): d 164.37, 140.34,
131.43, 128.91, 127.31, 80.15; HRMS calcd for C15H10Cl2NaO4
[M + Na]+ 346.9848, found 346.9852.
3-Chloropropyl cyclohexanecarboxylate (4g)
Methylene bis(4-(triuoromethyl)benzoate) (2q)
98.4 mg (95%), a yellow oil. 1H NMR (400 MHz, CDCl3, TMS): d 137.2 mg (70%), a white solid. Mp: 88–90 ꢀC. 1H NMR (400 MHz,
4.21 (t, J ¼ 6.0 Hz, 2H), 3.61 (t, J ¼ 6.5 Hz, 2H), 2.30 (tt, J ¼ 11.3, CDCl3): d 8.21 (ddd, J ¼ 7.6, 1.4, 0.7 Hz, 4H), 7.73 (ddd, J ¼ 6.2,
3.6 Hz, 1H), 2.15–2.04 (m, 2H), 1.96–1.86 (m, 2H), 1.79–1.71 (m, 1.5, 0.6 Hz, 4H), 6.30 (s, 2H); 13C NMR (100 MHz, CDCl3): d
2H), 1.69–1.60 (m, 1H), 1.51–1.38 (m, 2H), 1.35–1.17 (m, 3H); 164.01, 135.25 (q, J ¼ 32.9 Hz), 132.01 (d, J ¼ 1.5 Hz), 130.48,
20252 | RSC Adv., 2013, 3, 20246–20253
This journal is ª The Royal Society of Chemistry 2013

View Article Online
Paper
RSC Advances
125.59 (dd, J ¼ 7.9, 4.0 Hz), 122.09, 80.42; HRMS calcd for for Young Experts, Program for Minjiang Scholar program
C
17H10F6NaO4 [M + Na]+ 415.0383, found 415.0386.
(10BS216) and Research Funds of Huaqiao University.
Bis(4-methylbenzoyloxy)methane (2r)
88 mg (62%), a white solid. Mp: 98–100 ꢀC. 1H NMR (400 MHz,
CDCl3): d 7.98 (d, J ¼ 8.3 Hz, 4H), 7.23 (d, J ¼ 8.0 Hz, 4H), 6.22 (s,
2H), 2.39 (s, 6H); 13C NMR (100 MHz, CDCl3): d 165.29, 144.44,
130.06, 129.15, 126.24, 79.84, 21.66. HRMS calcd for
References
1 L. Lazzarato, M. Donnola, B. Rolando, K. Chegaev, E. Marini,
C. Cena, A. Di Stilo, R. Fruttero, S. Biondi, E. Ongini and
A. Gasco, J. Med. Chem., 2009, 52, 5058.
2 C. M. Svahn, F. Merenyi, L. Karlson, L. Widlund and
M. Grallst, J. Med. Chem., 1986, 29, 448.
C
17H16NaO4 [M + Na]+ 307.0941, found 307.0939; HRMS calcd
for C17H16NaO4 [M + Na]+ 307.0941, found 307.0949.
3 R. O. Al-Kaysi, R. J. Dillon, J. M. Kaiser, L. J. Mueller,
G. Guirado and C. J. Bardeen, Macromolecules, 2007, 40,
9040.
4 L. Lazzarato, M. Donnola, B. Rolando, K. Chegaev, E. Marini,
C. Cena, A. Di Stilo, R. Fruttero, S. Biondi, E. Ongini and
A. Gasco, J. Med. Chem., 2009, 52, 5058.
Bis(3-methylbenzoyloxy)methane (2s)
76.7 mg (54%), a light yellow solid. gel (eluent: petroleum ether–
ethyl acetate ¼ 70 : 1) to affords 100.4 mg (62%) of 2t as a yellow
1
ꢀ
solid. Mp: 50–52 C. H NMR (400 MHz, CDCl3): d 7.90 (dt, J ¼
8.4, 4.2 Hz, 4H), 7.50–7.29 (m, 4H), 6.23 (s, 2H), 2.39 (s, 6H); 13
C
NMR (100 MHz, CDCl3): d 165.43, 138.31, 134.41, 130.52,
128.36, 127.22, 79.95, 21.19; HRMS calcd for C17H16NaO4 [M +
Na]+ 307.0941, found 307.0939.
5 A. Gasco, R. Fruttero, L. Lazzarato, B. Rolando, K. Chegaev,
M. Donnola, E. Ongini and S. Biondi, WO 2010/118968,
2010.
6 D. Mal, A. Jana, S. Ray, S. Bhattacharya, A. Patra and S. R. De,
Synth. Commun., 2008, 38, 3937.
Bis(3-Chlorobenzoyloxy)methane (2t)
100.4 mg (62%), a yellow solid. Mp: 69–71 ꢀC. 1H NMR (400
MHz, CDCl3): d 8.06 (t, J ¼ 1.8 Hz, 2H), 8.00–7.95 (m, 2H), 7.56
(ddd, J ¼ 8.0, 2.1, 1.1 Hz, 2H), 7.40 (t, J ¼ 7.9 Hz, 2H), 6.24 (s,
2H); 13C NMR (100 MHz, CDCl3): d 164.00, 134.73, 133.77,
130.54, 130.05, 129.83, 128.16, 80.28; HRMS calcd for
7 D. G. Salunkhe, M. H. Jagdale. and M. M. Salunkhe, Bull. Soc.
Chim. Belg., 1987, 96, 247.
8 K. Holmberg and B. Hansen, Tetrahedron Lett., 1975, 16,
2303.
9 D. Chakraborty, C. Majumder and P. Malik, Appl. Organomet.
Chem., 2011, 25, 487.
10 R. Das and D. Chakraborty, Appl. Organomet. Chem., 2011,
25, 437.
11 A. T. Murray, P. Matton, N. W. G. Fairhurst, M. P. John and
D. R. Carbery, Org. Lett., 2012, 14, 3656.
12 R. Shang, Z. Huang, X. Xiao, X. Lu, Y. Fu and L. Liu, Adv.
Synth. Catal., 2012, 354, 2465.
13 Y. Zhang and L. Gu, J. Am. Chem. Soc., 2009, 132, 914.
14 B. R. Travis, M. Sivakumar, G. O. Hollist and B. Borhan, Org.
Lett., 2003, 5, 1031.
15 M. Joseph, J. W. O. Grill and S. A. Miller, J. Org. Chem., 2006,
71, 9291.
16 V. R. Choudhary, D. K. Dumbre and V. S. Narkhede, J. Chem.
Sci., 2012, 124, 835.
17 O. Vechorkin, D. Barmaz, V. Proust and X. Hu, J. Am. Chem.
Soc., 2009, 131, 12078.
18 J. S. Tullis, J. C. V. Rens, M. P. Clark, B. E. Blass,
M. G. Natchus and B. De, US 2003/0013712 A1 2003, Jan.
16, 2003.
C
15H10Cl2NaO4 [M + Na]+ 346.9848, found 346.9852.
2-Chloroethyl 4-chlorobenzoate (3i)
161 mg (74%), a yellow oil. 1H NMR (400 MHz, CDCl3): d 8.00 (d,
J ¼ 8.6 Hz, 2H), 7.43 (d, J ¼ 8.5 Hz, 2H), 4.57 (t, J ¼ 6 Hz, 2H),
3.83–3.79 (t, J ¼ 4 Hz, 2H); 13C NMR (100 MHz, CDCl3): d 165.27,
139.74, 131.09, 128.78, 128.03, 41.57; HRMS calcd. for
C9H8Cl2NaO2 [M + Na]+ 240.9800, found 240.9802.
3-Chloropropyl 4-chlorobenzoate (4h)
172.4 mg (74%), a yellow oil. 1H NMR (400 MHz, CDCl3): d 7.96
(d, J ¼ 8.6 Hz, 2H), 7.41 (d, J ¼ 8.6 Hz, 2H), 4.48 (t, J ¼ 6.1 Hz,
2H), 3.69 (t, J ¼ 6.4 Hz, 2H), 2.24 (p, J ¼ 6.3 Hz, 2H); 13C NMR
(100 MHz, CDCl3): d 165.46, 139.48, 130.91, 128.71, 128.42,
61.91, 41.16, 31.62; HRMS calcd for C10H10Cl2NaO2 [M + Na]+
254.9950, found 254.9955.
3-Chloropropyl 4-(triuoromethyl)benzoate (4i)
193.3 mg (77%), a yellow oil. 1H NMR (400 MHz, CDCl3): d 8.15
(d, J ¼ 8.2 Hz, 2H), 7.71 (d, J ¼ 8.2 Hz, 2H), 4.53 (t, J ¼ 6.1 Hz,
2H), 3.70 (t, J ¼ 6.4 Hz, 2H), 2.32–2.22 (m, 2H); 13C NMR (100
MHz, CDCl3): d 165.16, 134.56 (d, J ¼ 32.8 Hz), 133.24, 129.96,
125.44 (dd, J ¼ 7.9, 4.0 Hz), 122.22, 62.27, 41.10, 31.58; HRMS
calcd for C11H10ClF3NaO2 [M + Na]+ 289.0220, found 289.0223.
19 E. Caselli, G. Tosi, A. Forni, M. Bucciarelli and F. Prati, IL
Farmaco, 2003, 58, 1029.
20 E. Santaniello, P. Ciuffred, S. Casati, L. Alessandrini and
A. Repetto, J. Mol. Catal. B: Enzym., 2006, 40, 81.
21 C. Nguyen, G. F. Ruda, A. Schipani, G. Kasinathan, I. Leal,
A. Musso-Buendia, M. Kaiser, R. Brun, L. M. Ruiz-Perez,
B.-L. Sahlberg, N. G. Johansson, D. Gonzalez-
Pacanowska and I. H. Gilbert, J. Med. Chem., 2006, 49,
4183.
Acknowledgements
We are grateful for nancial support from the National Science 22 C. K. Skepper, T. Quach and T. F. Molinski, J. Am. Chem. Soc.,
Foundation of China (21202049), Program for 1000 Talent Plan
2010, 132, 10286.
This journal is ª The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 20246–20253 | 20253