PEG400-enhanced synthesis of gem-dichloroaziridines and gem-dichlorocyclopropanes via in situ generated dichlorocarbene

Article abstract of DOI:10.1039/c3ra43307b

PEG₄₀₀ is employed as an efficient phase transfer catalyst for the cycloaddition reaction of imines with dichlorocarbene, which is generated in situ from chloroform and sodium hydroxide, to give gem-dichloroaziridines in moderate to excellent yields at ambient temperature. This protocol is also extended to the synthesis of cyclopropanes from a variety of alkenes. In this study, PEG₄₀₀ behaves as a phase transfer reagent thanks to its ability to coordinate with alkali metal cations. Notably, the one-pot synthesis of gem-dichloroaziridines from benzaldehyde and aromatic amines has also been successfully performed. The in situ generated acid, derived from CO₂ and H₂O, can also be effectively applied to promote the amide synthesis via the gem-dichloroaziridine pathway. The application of the gem-dichlorocyclopropane as a platform chemical is also briefly demonstrated, to afford the 2-phenylacrylaldehyde derivative via a ring-opening reaction. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3ra43307b

RSC Advances
View Article Online
View Journal | View Issue
PAPER
PEG400-enhanced synthesis of gem-dichloroaziridines
and gem-dichlorocyclopropanes via in situ generated
dichlorocarbene 3
Cite this: RSC Advances, 2013, 3,
19009
Qing-Wen Song, Bing Yu, An-Hua Liu, Ying He, Zhen-Zhen Yang, Zhen-Feng Diao,
Qing-Chuan Song, Xue-Dong Li and Liang-Nian He*
PEG400 is employed as an efficient phase transfer catalyst for the cycloaddition reaction of imines with
dichlorocarbene, which is generated in situ from chloroform and sodium hydroxide, to give gem-
dichloroaziridines in moderate to excellent yields at ambient temperature. This protocol is also extended to
the synthesis of cyclopropanes from a variety of alkenes. In this study, PEG400 behaves as a phase transfer
reagent thanks to its ability to coordinate with alkali metal cations. Notably, the one-pot synthesis of gem-
dichloroaziridines from benzaldehyde and aromatic amines has also been successfully performed. The in
situ generated acid, derived from CO2 and H2O, can also be effectively applied to promote the amide
synthesis via the gem-dichloroaziridine pathway. The application of the gem-dichlorocyclopropane as a
platform chemical is also briefly demonstrated, to afford the 2-phenylacrylaldehyde derivative via a ring-
opening reaction.
Received 1st July 2013,
Accepted 5th August 2013
DOI: 10.1039/c3ra43307b
www.rsc.org/advances
appealing.14 Consequently, the development of an effective
greener PTC is highly desirable.
Introduction
gem-Dichloroaziridines have broad application as significant
intermediates in pharmacological and organic synthesis.1–4
Most importantly, gem-dihalocyclopropanes are valuable sub-
strates in the preparation of cyclopropane and allene
derivatives, which are fine chemicals with functional groups
for further derivatization.5,6
Poly(ethylene glycol) (PEG) has a flexible chain structure
with a hydrophobic ether chain and hydrophilic hydroxyl side
groups.15 Accordingly, it is assumed to not only be a phase
transfer reagent, but also to have the ability to coordinate with
alkali metal cations.16 In particular, PEG shows higher stability
in acidic or basic conditions in comparison with the
quaternary onium salts.17 Indeed, PEG and its derivatives
have been extensively investigated as PTCs in many industrial
processes, as replacements for otherwise necessary hazardous
compounds.15,18 Linear PEG is much cheaper than commonly
used analagous crown ether and cryptand PTCs.19 In addition,
PEG and its derivatives have also been used as either
catalysts20,21 or solvents22 for the chemical transformation of
carbon dioxide, and in carbon capture and storage processes.
In this work, we would like to report a simple and effective
PEG400-promoted process for the synthesis of gem-dichloroa-
ziridines/gem-dichlorocyclopropanes from imines/olefins and
There are three main routes to the gem-dichloroaziridine
when utilizing dichlorocarbene as the starting material,7 i.e.
generation from chloroform,8,9 hexachloroacetone,10 or ethyl
trichloroacetate.11 Dichlorocarbene generated in situ from
readily available chloroform is frequently used for the
preparation of gem-dichloroaziridines under mild conditions.
Several strong bases such as potassium t-butoxide12 and
sodium methoxide2 are employed in the generation of
dichlorocarbene, while anhydrous conditions are also
required. Al2O3-supported KF8 also works well for this
purpose. Moreover, quaternary onium salts as phase transfer
catalysts (PTCs) are found to be highly efficient for the
synthesis of gem-dichloroaziridines, even in water-bearing
media compatible with common inorganic bases.13
Nonetheless, the use of a biodegradable PTC without the
necessity of introducing a hazardous halogen species could be
chloroform. Of particular note,
a one-pot protocol was
successfully utilized for the preparation of gem-dichloroazir-
idines from benzaldehyde and aromatic amines. Moreover,
gem-dichloroaziridines and gem-dichlorocyclopropanes were
then employed as platform chemicals, being readily converted
to the amide and 2-phenylacrylaldehyde derivatives through a
ring-opening reaction.
State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin,
300071, P. R. China. E-mail: heln@nankai.edu.cn; Fax: (+86)-22-2350-3878;
Tel: (+86)-22-2350-3878
Electronic supplementary information (ESI) available: 1H NMR and 13C NMR
3
spectra of all products. See DOI: 10.1039/c3ra43307b
This journal is ß The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 19009–19014 | 19009

View Article Online
Paper
RSC Advances
Table 1 The effects of PEG molecular weight and solvent typea
(entries 2–6). In particular, PEG400 exhibited the best perfor-
mance (entry 3), probably due to its proper coordination with
K+.23 This excellent performance enabled 2a to be obtained in
almost quantitative yield using PEG400 as a PTC, even within 1
h (entry 7). On the other hand, the reaction was severely
retarded in high polarity solvents such as C2H5OH, H2O and
DMSO (entries 8–10). The use of low polarity solvents such as
THF and ClCH2CH2Cl also gave poor results (entries 11 and
12). PhCH3, CH2Cl2 and CH3CN were much more effective in
comparison with THF and ClCH2CH2Cl (entries 13–15 vs. 11
and 12). As a result of its dual role as a reagent and solvent, an
excess of CHCl3 gave 97% yield (entry 3).
In order to optimize the reaction conditions, other reaction
parameters including the PEG400 loading, choice of base,
amount of chloroform and reaction time were further
investigated as listed in Table 2. It became evident that the
reaction ran best in the presence of NaOH out of the selection
of screened bases (entries 1–6, Table 2). The organic base,
DBU, and the inorganic base, Na2CO3, were both inactive
(entries 1 and 2). Even the use of a strong base such as t-BuOK
only gave very low conversion and yield (entry 3). CsOH?H2O
led to the formation of unknown byproducts, thus resulting in
poor selectivity (entry 4). Gratifyingly, NaOH afforded an
almost quantitative yield and performed even better than KOH
in the case of 0.5 h (entries 5 vs. 6). Reducing the PEG400
loading resulted in the decline of both the conversion and
yield (entries 6 vs. 7). No distinct effect arising from the
amount of CHCl3 was observed on the reaction in a range of
0.5–5 mL (entries 6, 8–10). Furthermore, the use of less than 3
equiv. NaOH or shortening the reaction time resulted in a
sharp decrease in both the conversion and yield (entries 11
and 12).
Entry PEG
Solvent
CHCl3
Time (h) Conversionb (%) Yieldc (%)
1
2
3
4
5
6
7
8
—
1.5
1.5
1.5
1.5
1.5
1.5
1.0
1.0
1.0
1.0
1.0
27
86
98
90
79
60
99
6
10
8
17
20
88
93
89
14
80
97
88
78
46
97
0
0
0
13
12
72
89
86
PEG200 CHCl3
PEG400 CHCl3
PEG800 CHCl3
PEG2000 CHCl3
PEG6000 CHCl3
PEG400 CHCl3
PEG400 C2H5OH
PEG400 H2O
9
10
11
12
13
14
15
PEG400 DMSO
PEG400 THF
PEG400 ClCH2CH2Cl 1.0
PEG400 PhCH3
PEG400 CH2Cl2
PEG400 CH3CN
1.0
1.0
1.0
a
Reaction conditions: 1a (90.6 mg, 0.5 mmol), KOH (168 mg, 3
mmol), PEG (20 mol%), CHCl3 (241.3 mL, 3 mmol), solvent (5.0 mL),
b
c
25 uC. Based on the recovery of 1a. NMR yield.
Results and discussion
Initially, N-benzylideneaniline 1a was selected as a model
substrate to investigate the effects of the solvent and PEG
molecular weight on the reaction outcome. The results are
listed in Table 1. The PEG molecular weight obviously had a
significant impact on the reaction (entries 1–6, Table 1). A poor
result was obtained in the absence of PEG (entry 1). However,
the presence of PEG greatly improved the reaction outcome
To investigate the generality of the reaction, various typical
imine substrates were tested under the optimal conditions as
Table 2 Optimization of the reaction conditionsa
Entry
PEG400 (mol%)
Base
CHCl3 (mL)
Time (min)
Conversionb (%)
Yieldc (%)
1d
2d
3
4
5
6
7
8
9
15
15
15
15
15
15
10
15
15
15
15
15
DBU
5.0
5.0
5.0
5.0
5.0
5.0
5.0
3.0
1.0
0.5
1.0
1.0
60
60
60
60
30
30
30
30
30
30
30
20
13
8
0
0
Na2CO3
t-BuOK
CsOH?H2O
KOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
38
78
73
98
66
98
99
87
73
86
20
44
60
97
64
97
98
85
70
86
10
11e
12
a
b
c
d
Reaction conditions: 1a (90.6 mg, 0.5 mmol), base (1.5 mmol, 3 equiv.). Based on the recovery of 1a. NMR yield. No product detected by
1H NMR. 2 equiv. NaOH.
e
19010 | RSC Adv., 2013, 3, 19009–19014
This journal is ß The Royal Society of Chemistry 2013

View Article Online
RSC Advances
Paper
Table 3 Effect of varying imine substratea
Entry Substrate R1
R2
Product (2 or 4) Yieldb (%)
Scheme 1 One-pot synthesis of gem-dichloroaziridines from aromatic alde-
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
3a
3b
3c
3d
3e
3f
Ph
Ph
Ph
Ph
2a
97(90)
95
89
75
81
65
83
80
88
hydes and amines.
p-CH3OC6H4 2b
1-naphthyl 2c
p-CH3C6H4 Ph
p-ClC6H4 Ph
p-NO2C6H4 Ph
2d
2e
2f
4a
4b
4c
4d
4e
4f
preparation of the amide compound.11 On the other hand, the
reversible reaction between CO2 and water could form
carbonic acid in situ, which is able to serve as an acidic
Ph
H
H
H
p-ClC6H4
p-CH3C6H4
–CH2(CH2)2CH2–
PhS
n-hexyl
9
catalyst. Such
a CO2–H2O system could be inherently
10
11
12
89
52
78
H
H
neutralized by the removal of CO2, thus resulting in self-
neutralization producing easily disposable waste salt-water.27
This in situ CO2–H2O acidic system can be applied instead of
traditional acids for the hydrolysis of the gem-dichloroazir-
idine to form the amide derivative, as depicted in Scheme 2. As
a consequence, PEG400 and CO2 smoothly promoted the one-
pot synthesis of amide 2aa from 1a in 86% yield.
a
Reaction conditions: 1 or 3 (1.0 mmol), PEG400 (60.0 mg, 15
b
mol%), NaOH (120 mg, 3 mmol), CHCl3 (2.0 mL), 30 min, rt. NMR
yield, value in parentheses refers to isolated yield.
summarized in Table 3. A variety of aromatic imines, 1, reacted
smoothly with chloroform to afford the desired products
(entries 1–6, Table 3). The dichloroaziridination of 1a, derived
from unsubstituted benzaldehyde and aniline, was accom-
plished with high reactivity (entry 1). The substrates with
different R2 substituents and R1 fixed as phenyl gave
dichloroaziridines 2b and 2c in excellent yields (entries 2
and 3). By changing R1, imines including 1d, 1e, and 1f
provided 2d, 2e, and 2f respectively in good yields (entries 4–
6). Accordingly, this protocol offers an efficient route to
synthesize the gem-dichloroaziridines from aromatic imines.
Furthermore, olefins also worked well with this protocol. As
summarized in Table 3, both internal and terminal olefins
could be converted to their corresponding gem-dichlorocyclo-
propanes in good to excellent yields (entries 7–12, Table 3). In
particular, the presence of electron-donating substituents is
shown to be beneficial to the desired reaction (entries 7, 10
and 12).
Besides, gem-dihalocyclopropanes also play an important
role in organic synthesis, such as in the conversion of 1,1-
dihalo-2-phenylcyclopropanes into a,b-unsaturated acetals.28
4a was selected as a typical representative substrate with which
to perform the transformation in 66% yield as shown in
Scheme 3.
It can reasonably be assumed that the process for the
formation of dichlorocarbene goes through the phase transfer
mechanism. The sodium cation is likely coordinated by PEG400
and the hydroxyl ion is then transferred from the aqueous
phase into the organic phase. The hydroxide anion reacts with
chloroform to produce the chloroform anion and water which
plays a similar role as the PTC.29 The chloroform anion yields
a chlorine anion to form dichlorocarbene. Accordingly, the
products, including gem-dichloroaziridine and gem-dichloro-
cyclopropane, are obtained by the addition of dichlorocarbene
to the imine or olefin.
In this work, imines were derived from their corresponding
aldehydes and amines. Specifically, the facile synthesis of gem-
dichloroaziridines directly from aromatic aldehydes and
amines in a one-pot procedure has been studied, and to our
delight, successfully achieved with reasonable efficiency, as
shown in Scheme 1.
Conclusions
In summary, we have developed a simple and efficient system
for the synthesis of gem-dichloroaziridines/gem-dichlorocyclo-
The biological effectiveness of many pharmaceutically
active compounds (e.g. anaesthetic lidocaine)24 stems from
the amide group. In addition, a-halogen-substituted amides
are important synthetic intermediates.25 Generally, the acidic
hydrolysis of the gem-dichloroaziridine results in the forma-
tion of the a-chloroacetamide,26 thus offering a route for the
Scheme 2 One-pot synthesis of 2aa from 1a.
This journal is ß The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 19009–19014 | 19011

View Article Online
Paper
RSC Advances
152.0, 136.2, 131.4, 129.1, 128.82, 128.75, 125.9, 120.8 ppm;
GC-MS (EI, 70 eV) m/z (%) 182 (12), 181 (M+, 88), 180 (100).
General procedure for the synthesis of gem-dichloroaziridines
To a mixture of PEG400 (60.0 mg, 15 mol%), sodium hydroxide
powder (120.0 mg, 3.0 mmol) and imines 1 (1.0 mmol),
chloroform (2.0 mL) was added. The reaction mixture was
stirred for 30 min at room temperature and the mixture was
then washed with ether. The combined solvent was concen-
trated by rotary evaporation to afford the crude product.
Purification was by column chromatography with neutral
Al2O3 media and eluting with petroleum ether–ethyl acetate,
yielding the desired products.
2,2-Dichloro-1,3-diphenylaziridine (2a)9. Pale yellow solid,
mp 98.5–100 uC (lit.,9 mp 100–102 uC; lit.,37 mp 98–99 uC); IR
(KBr) n/cm21 3035, 2921, 1603, 1526 (CLC, Ar), 693, 574; 1H
NMR (400 MHz, CDCl3) d 7.56–7.55 (m, 2H), 7.49–7.45 (m, 3H),
7.42–7.38 (m, 2H), 7.21–7.18 (m, 1H), 7.11 (d, J = 8.0 Hz, 2H),
3.75 (s, 1H); 13C NMR (100.6 MHz, CDCl3) d 144.9 132.9, 129.1,
128.9, 128.4, 127.8, 124.3, 119.7, 75.2, 54.6 ppm; GC-MS (EI, 70
eV) m/z (%) 230 (7), 229 [(C14H1137ClN)+, 32], 228 (16), 227
[(C14H1135ClN)+, 99], 194 (9), 193 [(C14H11N)2+, 60].
Scheme 3 Preparation of (3,3-diethoxyprop-1-en-2-yl)benzene 4aa (a isolated
yield)
propanes under mild conditions. The results disclosed herein
represent several impressive features consistent with the
principles of green chemistry and improved economics: (I)
no hazardous halogen species are generated, PEG400 is
biodegradable and a highly effective PTC; (II) PEG400 is an
efficient PTC for the cyclization reaction of CLN and CLC with
chloroform with the assistance of NaOH; (III) the one-pot
synthesis of gem-dichloroaziridines from benzaldehyde and
aromatic amines proceeds smoothly in the presence of PEG400
.
Notably, the acid derived in situ from CO2 and H2O could also
be effectively applied to promote the amide synthesis, with
profound advantages with regard to simple post-reaction
disposal. The present approach represents an effective and
clean route for the preparation of three-membered (hetero)-
cycles, and will also open up possibilities for turning
traditional reactions into environmentally benign chemical
processes.
2,2-Dichloro-1-(4-methoxyphenyl)-3-phenylaziridine (2b).
1
Colorless solid, mp 86–87 uC (lit.,38 mp 90 uC); H NMR (400
MHz, CDCl3) d 7.54–7.51 (m, 2H), 7.45–7.41 (m, 3H), 7.03–7.00
(d, J = 2.6 Hz, 2H), 6.93–6.89 (d, J = 2.6 Hz, 2H), 3.81 (s, 3H),
3.67 (s, 1H) ppm; 13C NMR (100.6 MHz, CDCl3) d 156.6, 138.2,
133.0, 128.8, 128.4, 127.8, 120.7, 114.4, 75.9, 55.5, 54.5 ppm;
GC-MS (EI, 70 eV) m/z (%) 259(20), 258 [(C15H1337ClNO)2+, 11],
257 (59), 223 [(C15H13NO)2+, 100], 222 (47).
2,2-Dichloro-1-phenyl-3-(p-tolyl)aziridine (2d)11. Light yellow
solid, mp 74.5–76 uC (lit.,11 mp 75–76 uC); IR (KBr) n/cm21
2922, 2857, 2025, 1506, 1462, 1389, 1277, 1135, 1007, 835, 540;
1H NMR (400 MHz, CDCl3) d 7.42–7.34 (m, 4H), 7.24 (m, 1H),
7.18–7.14 (m, 1H), 7.08–7.06 (m, 2H), 3.68 (s, 1H), 2.40 (s, 3H)
ppm; 13C NMR (100.6 MHz, CDCl3) d 145.0 138.9, 130.0,
129.14, 129.06, 127.7, 124.2, 119.7, 75.4, 54.6, 21.3 ppm; GC-
MS (EI, 70 eV) m/z (%) 243 (33), 242 [(C15H1335ClN)+, 18], 241
(100), 207 [(C15H13N)2+, 32], 206 (38).
Experimental
General methods
All reactions were carried out at ambient temperature.
Standard column chromatography was performed using
neutral Al2O3 or silica gel media and flash column chromato-
graphy techniques. Infrared spectra (IR) of liquid or solid
compounds were measured as thin films on KBr plates. 1H
NMR spectra were recorded on a Bruker 400 MHz spectro-
meter using CDCl3 as solvent, referenced to TMS (0 ppm) or
CHCl3 (7.26 ppm). 13C NMR spectra were recorded at 100.6
MHz in CDCl3 using CDCl3 (77.0 ppm) as an internal
reference. Melting points were measured on an X4 apparatus
and were uncorrected. All of the products were characterized
2,2-Dichloro-3-(4-nitrophenyl)-1-phenylaziridine (2f)11
.
Yellow solid, mp 104 uC (lit.,11 mp 104.5–106 uC); IR (KBr) n/
cm21 3041, 2945, 1599, 1521, 1494 (CLC), 1348, 891, 815, 758,
693, 566; 1H NMR (400 MHz, CDCl3) d 8.31–8.28 (d, J = 2.0 Hz,
2H), 7.73–7.69 (d, J = 2.0 Hz, 2H), 7.42–7.37 (m, 2H), 7.23–7.19
(m, 1H), 7.08–7.05 (d, J = 1.6 Hz, 2H), 3.80 (s, 1H) ppm; 13C
NMR (100.6 MHz, CDCl3) d 148.3 144.1, 140.1, 129.3, 128.9,
124.8, 123.7, 119.7, 74.7, 53.5 ppm; GC-MS (EI, 70 eV) m/z (%)
274 (C14H937ClN2O2, 25), 272 (C14H935ClN2O2, 63), 209 (26),
208 (100), 207 (39).
1
by H NMR, 13C NMR, GC-MS and IR spectroscopy, and were
identified by comparison of their characterized data with
those reported in the literature.
Typical procedure for the preparation of imines30–36
Benzaldehyde (3.18 g, 30 mmol) and aniline (2.79 g, 30 mmol)
were dissolved in ethanol (50 mL). After completion of the
reaction (monitored by TLC), the solvent was removed under
reduced pressure. Purification of the residue was by recrys-
General procedure for the synthesis of gem-
dichlorocyclopropanes 4
To a mixture of PEG400 (60.0 mg, 15 mol%), sodium hydroxide
powder (120.0 mg, 3.0 mmol) and olefin 3 (1.0 mmol),
chloroform (2.0 mL) was added. The reaction mixture was
stirred for 30 min at room temperature and the mixture was
then washed with ether. The combined solvent was concen-
trated by rotary evaporation to afford the crude product.
Purification was by column chromatography with silica gel
tallization
from
Et2O/hexane,
giving
pale-yellow
N-benzylideneaniline (2a); yield: 4.35 g (80%).
N-Benzylideneaniline (1a)30. Pale yellow solid, mp 50–51 uC
1
(lit.,30 mp 51–52 uC); H NMR (400 MHz, CDCl3) d 8.47 (s, 1H,
CH), 7.94–7.91 (m, 2H), 7.50–7.41 (m, 3H), 7.43–7.39 (m, 2H),
7.27–7.22 (m, 3H) ppm; 13C NMR (100.6 MHz, CDCl3) d 160.4,
19012 | RSC Adv., 2013, 3, 19009–19014
This journal is ß The Royal Society of Chemistry 2013

View Article Online
RSC Advances
Paper
media and eluting with petroleum ether–ethyl acetate, yielding
the target products.
introduced into the autoclave and the pressure was adjusted
to 2 MPa, after which the mixture was stirred continuously for
5 h at 100 uC. After completion of the reaction, the reactor was
cooled to room temperature and the remaining CO2 was
carefully vented out. The product was extracted with diethyl
ether (3 6 5 mL). The solvent was evaporated under reduced
pressure to obtain the crude product. Further purification by
column chromatography using silica gel media and eluting
with petroleum ether–ethyl acetate afforded the pure product.
N-Phenyl-a-chlorophenylacetamide (2aa)37. White solid, mp
148–149 uC, (lit.,10 mp 148–149 uC); IR (KBr) n/cm21 2920 (N–
H), 2856, 1668 (CLO), 1598, 1540, 1494, 1451 (CLC), 1374, 722,
1,1-Dichloro-2-phenylcyclopropane (4a)39. Colorless oil; IR
(KBr) n/cm21 2923, 2858, 1501, 1457, 1374, 1229, 1114, 1047,
769, 742, 694, 587, 545; 1H NMR (400 MHz, CDCl3) d 7.38–7.24
(m, 5H), 2.92 (d, J = 10.4 Hz, 1H), 1.98 (d, J = 10.5 Hz, 1H), 1.86
(t, J = 8.4 Hz, 1H) ppm; 13C NMR (100.6 MHz, CDCl3) d 134.6,
128.8, 128.3, 127.6, 60.7, 35.4, 25.6 ppm; GC-MS (EI, 70 eV) m/z
(%) 188 [(M + H)+, 7], 186 (10), 153 (13), 152 [(M-35Cl)+, 5], 151
(43), 116 (20), 115 [(C9H7)+, 100].
1,1-Dichloro-2-(4-chlorophenyl)cyclopropane (4b)40
.
Colorless oil; IR (KBr) n/cm21 3741, 2926, 1494, 1431, 1228,
1
1
688; H NMR (400 MHz, CDCl3) d 8.40 (s, 1H, N–H), 7.18–7.15
1105, 1048, 1014, 941, 878, 827, 762, 711, 561; H NMR (400
(m, 1H), 7.41–7.33 (m, 5H), 7.51–7.49 (m, 2H), 7.57–7.55 (m, 2H)
5.50 (s, 1H, C–H) ppm; 13C NMR (100.6 MHz, CDCl3) d
165.3(CLO), 136.8, 136.6, 129.3, 129.1, 129.0, 127.8, 125.2,
120.0, 62.1 ppm; GC-MS (EI, 70 eV) m/z (%) 247 [(C14H1237ClNO),
30), 245 [(C14H1235ClNO), 13], 211 [(C14H13NO)2+, 27], 126 (22),
125 (12), 120 (59), 119 (47), 118 (12), 93 (C6H7N, 100), 92 (48), 91
(71).
MHz, CDCl3) d 7.33–7.17 (m, 4H, CH), 2.90 (d, J = 10.4 Hz, 1H),
2.01–1.80 (m, 2H, CH2) ppm; 13C NMR (100.6 MHz, CDCl3) d
133.5, 133.2, 130.2, 128.5, 60.4, 34.8, 25.9 ppm; GC-MS (EI, 70
eV) m/z (%) 187 (37), 185 [(M-H35Cl), 61], 151 (34), 150 (21), 149
(C9H6Cl+, 100), 115 (39).
1,1-Dichloro-2-(4-methylphenyl)cyclopropane (4c)40
.
Colorless oil; IR (KBr) n/cm21 3742, 2923, 2858, 2025, 1515,
1
1459, 1378, 1117, 996, 818, 756, 562, 536; H NMR (400 MHz,
Procedure for the one-pot synthesis of gem-dichloroaziridines
CDCl3) d 7.19–7.14 (m, 5H), 2.90 (d, J = 10.4 Hz, 1H), 2.37 (s,
3H), 1.99–1.83 (m, 2H) ppm; 13C NMR (100.6 MHz, CDCl3) d
137.3, 131.6, 129.0, 128.7, 60.9, 35.1, 25.6, 21.1 ppm; GC-MS
(EI, 70 eV) m/z (%) 202 [(M + H)+, 11], 200 (17), 167 (20), 165
[(M-H35Cl), 62], 149 (16), 130 (25), 129 [(C10H9)+, 100], 128 (33),
127 (14).
from aromatic aldehydes and amines
To a mixture of PEG400 (60.0 mg, 15 mol%), benzaldehyde
(106.1 mg, 1.0 mmol), aromatic amines (1.0 mmol, 1.0 equiv.)
and CHCl3 (2.0 mL), NaOH powder (4 equiv. or 5 equiv.) was
added. The reaction mixture was stirred for 1 h at room
temperature and the mixture was then washed with ether. The
combined solution was then evaporated under reduced
pressure to yield the crude product which was further
quantified by 1H NMR using mesitylene as the internal
standard.
7,7-Dichlorobicyclo[4.1.0]heptane (4d)39. Colorless oil; IR
(KBr) n/cm21 3741, 2941, 2864, 2025, 1449, 1340, 1226, 1168,
1027, 796; 1H NMR (400 MHz, CDCl3) d 1.97–1.90 (m, 2 H),
1.73–1.64 (m, 4H), 1.37–1.29 (m, 2H), 1.23–1.14 (m, 2H) ppm;
13C NMR (100.6 MHz, CDCl3) d 67.4, 25.8, 20.2, 18.8 ppm; GC-
MS (EI, 70 eV) m/z (%) 124 (26), 122 [(M-C3H7)+, 42], 81 (21), 68
(C5H82+, 100).
Procedure for (3,3-diethoxyprop-1-en-2-yl)benzene synthesis
from 1,1-dichloro-2-phenylcyclopropane
(2,2-Dichlorocyclopropyl)-phenylsulfane (4e)41. Colorless oil;
IR (KBr) n/cm21 3741, 2924, 1745, 1702, 1154, 1013, 936, 823,
To a stirred solution of 1,1-dichloro-2-phenylcyclopropane
(206.3 mg, 1.0 mmol) in 2 mL dry EtOH, NaOH powder (160.0
mg, 4.0 mmol) was added and the mixture was then refluxed
for 12 h. The reaction mixture was then washed with ether.
The organic layer was then evaporated under reduced pressure
to yield the crude product which was purified by column
chromatography.
1
751, 684; H NMR (400 MHz, CDCl3) d 7.41–7.22 (m, 5H), 2.95
(d, J = 10.4 Hz, 1H), 2.05 (d, J = 10.5, 1H), 1.55 (t, J = 7.6 Hz, 1H)
ppm; 13C NMR (100.6 MHz, CDCl3) d 135.4, 129.19, 129.15,
127.6, 126.2, 61.8, 32.6, 27.3 ppm; GC-MS (EI, 70 eV) m/z (%)
220 [(M + H)+, 16), 218 (23), 185 (21), 183 (60), 147 (91), 111
(48), 109 (C6H5S+, 100).
(3,3-diethoxyprop-1-en-2-yl)benzene (4aa)43. Light yellow oil;
1,1-Dichloro-2-hexylcyclopropane (4f)42. Colorless oil; IR
IR (KBr) n/cm21 3058, 2976 (LCH2), 2881, 1637, 1492, 1446,
(KBr) n/cm21 2928 (CH2), 2861, 1460, 1380 (CH3), 1225, 1123,
1
1381, 1126, 1058, 919, 776, 699; H NMR (400 HMz, CDCl3) d
1
748; H NMR (400 MHz, CDCl3) d 7.41–7.22 (12H, 5CH2, CH,
7.53–7.51 (m, 2H), 7.34–7.24 (m, 3H), 5.58–5.55 (m, 2H, LCH2),
5.25 (s, 1H, CH), 3.68–3.61 (m, 2H, CH2), 3.58–3.50 (m, 2H,
CH2), 1.21 (t, J = 7.0 Hz, 6H, 2CH3) ppm; 13C NMR (100.6 MHz,
CDCl3) d 144.9, 138.5, 128.1, 127.5, 126.7, 115.6, 101.8, 61.3,
15.1 ppm; GC-MS (EI, 70 eV) m/z (%) 207 [(M + H)+, 4], 162
(100), 161 [(M-C2H5O)+, 91], 105 (14), 104 (17), 103 (50).
CH2), 1.04 (m, 1H), 0.90 (t, J = 6.8 Hz, 3H, CH3) ppm; 13C NMR
(100.6 MHz, CDCl3) d 61.7, 31.7, 30.9, 30.4, 28.9, 28.6, 26.8,
22.6, 14.1 ppm; GC-MS (EI, 70 eV) m/z (%) 123 (11), 116 (11),
102 (17), 96 (14), 83 (26), 81 (28), 70 [(C5H10)2+, 100], 69 (85), 68
(12), 67 (25).
Procedure for a-chloro-a-phenylacetamide synthesis from
N-benzylideneaniline promoted by PEG400/CO2/H2O
Acknowledgements
To a mixture of PEG400 (60.0 mg, 15 mol%), sodium hydroxide
powder (120.0 mg, 3.0 mmol), and N-benzylideneaniline 1a
(181.2 mg, 1.0 mmol) in a stainless steel autoclave reactor,
chloroform (2.0 mL) was added. The reaction mixture was
stirred for 30 min at room temperature. CO2 gas was
Financial support from the National Natural Science
Foundation of China (Grants No. 21172125, 21121002), the
‘‘111’’ Project of the Ministry of Education of China (Project
No. B06005), and the Tianjin Co-Innovation Center of
This journal is ß The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 19009–19014 | 19013

View Article Online
Paper
RSC Advances
J.-S. Tian, C.-X. Miao, J.-Q. Wang, F. Cai, Y. Du, Y. Zhao and
L.-N. He, Green Chem., 2007, 9, 566–571.
Chemical Science and Engineering are gratefully acknowl-
edged.
21 (a) Z.-Z. Yang, Y.-N. Zhao, L.-N. He, J. Gao and Z.-S. Yin,
Green Chem., 2012, 14, 519–527; (b) Z.-Z. Yang, Y.-N. Zhao
and L.-N. He, RSC Adv., 2011, 1, 545–567; (c) Z.-Z. Yang, L.-
N. He, J. Gao, A.-H. Liu and B. Yu, Energy Environ. Sci.,
2012, 5, 6602–6639.
22 A.-H. Liu, R. Ma, C. Song, Z.-Z. Yang, A. Yu, Y. Cai, L.-N. He,
Y.-N. Zhao, B. Yu and Q.-W. Song, Angew. Chem., Int. Ed.,
2012, 51, 11306–11310.
References
1 A. F. Khlebnikov, T. Yu. Nikiforova, M. S. Novikov and R.
R. Kostikov, Synthesis, 1997, 677–680.
2 M. K. Meilahn, L. L. Augenstein and J. L. McManaman, J.
Org. Chem., 1971, 36, 3627–3629.
3 A. F. Khlebnikov, M. S. Novikov, P. P. Petrovskii, J. Magull
and A. Ringe, Org. Lett., 2009, 11, 979–982.
23 Y. R. Jorapur, G. Rajagopal, P. J. Saikia and R. R. Pal,
Tetrahedron Lett., 2008, 49, 1495–1497.
24 M. M. McNulty, G. B. Edgerton, R. D. Shah, D. A. Hanck, H.
A. Fozzard and G. M. Lipkind, J. Physiol., 2007, 581,
741–755.
4 A. F. Khlebnikov, M. S. Novikov, M. V. Golovkina, P.
P. Petrovskii, A. S. Konev, D. S. Yufit and H. S. Evans, Org.
Biomol. Chem., 2011, 9, 3886–3895.
´
25 W. Szymanski, A. Westerbeek, D. B. Janssen and B.
´
5 M. Fedorynski, Chem. Rev., 2003, 103, 1099–1132, and
L. Feringa, Angew. Chem., Int. Ed., 2011, 50, 10712–10715.
26 E. Y. Shinkevich, M. S. Novikov and A. F. Khlebnikov,
Synthesis, 2007, 225–230.
27 (a) A.-H. Liu, L.-N. He, F. Hua, Z.-Z. Yang, C.-B. Huang,
B. Yu and B. Li, Adv. Synth. Catal., 2011, 353, 3187–3195; (b)
A.-H. Liu, R. Ma, M. Zhang and L.-N. He, Catal. Today,
2012, 194, 38–43; (c) C.-X. Miao, L.-N. He, J.-L. Wang and
F. Wu, J. Org. Chem., 2010, 75, 257–260.
references cited therein.
6 N. V. Zyk, O. B. Bondarenko, A. Y. Gavrilova, A. O. Chizhov
and N. S. Zefirov, Russ. Chem. Bull., 2011, 60, 328–333.
7 The method is similar to the synthesis of gem-dihalocyclo-
propanes and gem-dihaloaziridines, which proceeds mainly
through addition reaction of carbene, see ref. 5.
8 (a) M. Mihara, Y. Ishino, S. Minakata and M. Komatsu, J.
Org. Chem., 2005, 70, 5320–5322; (b) H. Naeimi and
K. Rabiei, Bull. Chem. Soc. Jpn., 2011, 84, 1112–1117.
9 H. Naeimi and K. Rabiei, Ultrason. Sonochem., 2012, 19,
130–135.
28 I. Crossland, Organic Synthesis, Wiley: New York, 1990.
29 E. V. Dehmlow, Angew. Chem., Int. Ed. Engl., 1977, 16,
493–505.
30 H. Naka, D. Koseki and Y. Kondo, Adv. Synth. Catal., 2008,
350, 1901–1906.
10 P. K. Kadaba and J. O. Edwards, J. Org. Chem., 1960, 25,
1431–1433.
31 P. Nongkunsarn and C. A. Ramsden, Tetrahedron, 1997, 53,
3805–3830.
32 Z.-H. Yu and X.-Q. Peng, J. Phys. Chem. A, 2001, 105,
8541–8553.
33 M. L. Crossley, P. F. Dreisbach, C. M. Hofmann and R.
P. Parker, J. Am. Chem. Soc., 1952, 74, 573–578.
34 A. Bolognese, M. V. Diurno, O. Mazzoni and F. Giordano,
Tetrahedron, 1991, 47, 7417–7428.
35 W. He, L.-D. Wang, C.-L. Sun, K.-K. Wu, S.-B. He, J.-P. Chen,
P. Wu and Z.-K. Yu, Chem.–Eur. J., 2011, 17, 13308–13317.
36 P. K. Kadaba, Tetrahedron, 1966, 22, 2453–2460.
11 (a) R. E. Brooks, J. O. Edwards, G. Levey and F. Smyth,
Tetrahedron, 1966, 22, 1279–1296; (b) H. Naeimi and
K. Rabiei, Helv. Chim. Acta, 2012, 95, 1102–1107.
12 A. G. Cook and E. K. Fields, J. Org. Chem., 1962, 27,
3686–3687.
13 (a) A. F. Khlebnikov, T. Y. Nikiforova and R. R. Kostikov,
Zh. Org. Khim., 1996, 32, 746–760; (b) A. F. Khlebnikov, M.
S. Novikov and R. R. Kostikov, Synlett, 1997, 8, 929–930.
14 Toxicological Evaluation of Certain Food Additives, World
Health Organization, Food Additives Series 14, 1979.
15 J. Chen, S. K. Spear, J. G. Huddleston and R. D. Rogers,
Green Chem., 2005, 7, 64–82, and references cited therein.
16 D.-L. Kong, L.-N. He and J.-Q. Wang, Synlett, 2010,
1276–1280.
17 S. D. Naik and L. K. Doraiswamy, AIChE J., 1998, 44,
612–646.
18 Z.-Z. Yang, Q.-W. Song and L.-N. He, Capture and Utilization
of Carbon Dioxide with Polyethylene Glycol, SpringerBriefs in
Molecular Science/SpringerBriefs in Green Chemistry for
Sustainability, 2012, ch. 3, pp. 23–25.
¯
37 M. Seno, S. Shiraishi, Y. Suzuki and T. Asahara, Bull. Chem.
Soc. Jpn., 1976, 49, 1893–1896.
38 T. Masanori and S. Minoru, Chem. Pharm. Bull., 1980, 28,
3098–3105.
39 C.-T. Chien, C.-C. Tsai, C.-H. Tsai, T.-Y. Chang, P.-K. Tsai, Y.-
C. Wang and T.-H. Yan, J. Org. Chem., 2006, 71, 4324–4327.
40 Y. Kusuyama, T. Kagosaku and T. Hasegawa, Bull. Chem.
Soc. Jpn., 1990, 63, 2836–2842.
41 W. E. Parham, L. Christensen, S. H. Groen and R. M. Dodson,
J. Org. Chem., 1964, 29, 2211–2214.
42 D. D. Tanner, L. Zhang, L. Q. Hu and P. Kandanarachchi, J.
Org. Chem., 1996, 61, 6818–6824.
43 Compared with the standard compound, reaxys registry
number: [3255896]; CAS number: [80234-04-4].
19 C. B. Dartt and M. E. Davis, Ind. Eng. Chem. Res., 1994, 33,
2887–2899.
20 (a) D.-L. Kong, L.-N. He and J.-Q. Wang, Synth. Commun.,
2011, 41, 3298–3307; (b) Z.-Z. Yang, L.-N. He, Y.-N. Zhao,
B. Li and B. Yu, Energy Environ. Sci., 2011, 4, 3971–3976; (c)
19014 | RSC Adv., 2013, 3, 19009–19014
This journal is ß The Royal Society of Chemistry 2013