Selective hydrolysis of 1-cyanocyclopropane-1-carboxylates: Concise preparation of 1-carbamoylcyclopropane-1-carboxylates

Article abstract of DOI:10.3184/174751916X14768938598056

An efficient and straightforward method has been developed for the preparation of 1-carbamoylcyclopropane-1-carboxylate derivatives selective hydrolysis of 1-cyanocyclopropane-1-carboxylates by using hydroxylamine and sodium acetate system strategy. The of 1-carbamoylcyclopropane-1-carboxylate 2a was further confirmed by X-ray single crystal analysis.

Full text of DOI:10.3184/174751916X14768938598056

694 RESEARCH PAPER
VOL. 40 NOVEMBER, 694–697
JOURNAL OF CHEMICAL RESEARCH 2016
Selective hydrolysis of 1-cyanocyclopropane-1-carboxylates: concise
preparation of 1-carbamoylcyclopropane-1-carboxylates
Jiaming Liu, Feixiang Zhang, Ting Wang, Xushun Qing and Cunde Wang*
School of Chemistry and Chemical Engineering, Yangzhou University, 180 Siwangting Street, Yangzhou 225002, P.R. China
An efficient and straightforward method has been developed for the preparation of 1-carbamoylcyclopropane-1-carboxylate derivatives
via selective hydrolysis of 1-cyanocyclopropane-1-carboxylates by using hydroxylamine and sodium acetate system strategy. The
structure of 1-carbamoylcyclopropane-1-carboxylate 2a was further confirmed by X-ray single crystal analysis.
Keywords: cyclopropane, 1-cyanocyclopropane-1-carboxylate, 1-carbamoylcyclopropane-1-carboxylate, selective hydrolysis, neighbouring-group
participation
Amides are important building blocks that are widely found
in numerous natural products, as well as in a vast array of
useful industrially important compounds.1,2 Additionally,
some amide derivatives are also used widely in applications in
supramolecular and polymer chemistry.3–6 Due to the important
biological and pharmaceutical activities of these compounds
containing amide cores, the construction of the amide bonds has
become a topic of great interest among synthetic chemists, and
as a consequence, many studies have been directed at increasing
synthetic access to this structural subunit. Typical methods for
the construction of amide cores deal with the approaches based
on both the direct amidation of carboxylic acids7 and controllable
hydrolysis of nitriles. Recently improved protocol involved the
condensation between a carboxylic acid and an amine promoted
by alkylboronic acids or alkylphosphonic acid anhydride.8–11 In
addition to the conventional dehydrative amide synthesis,7 there
were also methods via oxidative amidation reactions employing
alcohol or aldehyde precursors.12 The use of nitrile-based
starting materials for direct amidation has attracted significant
attention. In a report on the Ritter reaction between alcohols
and nitriles at room temperature in a solvent-free or low-solvent
environment by using a Brønsted acid catalyst, a wide range
of functionalised nitriles as well as secondary and tertiary
alcohols were noted.13 Selective hydrolysis of nitriles for the
preparation of amides has also been described. Although this
approach is very attractive, due to the use of stronger Brønsted
acid catalysts such as trifluoroacetic acid and sulfuric acid14,15
or alkaline reagents such as aqueous potassium carbonate and
hydrogen peroxide,16 high reaction temperatures are required
and the substrate scope is limited in comparison with that of the
direct amidation of carboxylic acids with amines.
that 1-carbamoylcyclopropane-1-carboxylates should not be
prepared via selective hydrolysis of 1-cyanocyclopropane-1-
carboxylates in the presence of conventional acidic and basic
conditions. To avoid the ring opening of cyanocyclopropanes, we
proposed that a controlled hydrolysis of 1-cyanocyclopropane-
1-carboxylates could be carried out via neighbouring-group
participation. In this communication, we report a novel selective
hydrolysis of 1-cyanocyclopropane-1-carboxylates using
hydroxylamine and sodium acetate. This protocol provides a
simple and direct way to convert a nitrile group to an amide.
Results and discussion
We explored the selective hydrolysis reaction of ethyl
2- (4-bromobenzoyl) -1-cyano-3- (4-chlorobenzoyl)
cyclopropane-1-carboxylate (1a) by using hydroxylamine and
sodium acetate system. Our initial experiments focused on
the appropriate amounts of hydroxylamine hydrochloride and
sodium acetate. The reaction of 1a (1.0 equiv.), hydroxylamine
hydrochloride (1.0 equiv.) and sodium acetate (1.0 equiv.) was
performed in ethanol under ambient conditions, as a result,
the product 2a was not isolated. However, while the resulting
mixture was stirred under reflux for 18 h, this reaction afforded
product 2a in 63% yield. The further investigation found that
the yield of product 2a could be substantially increased by
employing two equivalents of hydroxylamine hydrochloride
and sodium acetate and heating the reaction mixture under
refluxing for 18 h. Thus the product 2a was now isolated in
87% yield. Further increase of the amount of hydroxylamine
hydrochloride and sodium acetate had no significant beneficial
effect on the hydrolysis reaction. Additionally, we studied the
effect of solvent on the reaction. The reaction was carried
out with different solvents such as THF, DMF and dioxane
only gave the desired product 2a in low yields, however
ethanol gave good yields. Thus, we defined the reaction of
the 1-cyanocyclopropanecarboxylate 1a with hydroxylamine
Cyclopropanes with an amide moiety exhibit potent biological
and pharmacological activity. Due to their high π character and
intrinsic ring strain, they undergo a variety of ring-opening
reactions under acidic and basic conditions.17–19 It is quite evident
R2
R2
O
O
HONH2 HCl (2.0 equiv.)
NaOAc (2.0 equiv.)
EtOH, reflux
CONH2
Et
CO2
CN
Et
10 examples, 82–89%
CO2
R1
R1
2a j
–
1a j
–
Scheme 1 Selective hydrolysis of 1-cyanocyclopropanecarboxylates.
* Correspondent. E-mail: wangcd@yzu.edu.cn

JOURNAL OF CHEMICAL RESEARCH 2016 695
Table 1 Substrate scope of 1-cyanocyclopropanecarboxylatesa
Table 2 Crystallographic data of 2a
Entry R1
R2
Product
2a
2b
2c
2d
2e
2f
2g
2h
Yield/%b
87
84
83
86
85
89
88
Entry
Molecular formula
Formula weight
T/K
Wavelength/nm
Crystal system
Space group
a/Å
2a
1
2
3
4
5
6
7
8
9
10
p-Br
p-I
p-Cl
p-Br
p-COOMe
m-Me
m-Br
o-I
o-I
p-Cl
p-Br
H
H
H
p-Cl
H
p-Cl
H
C20H17BrClNO4
450.70
296(2)
0.71073
Triclinic
Pbca
17.340(5)
24.663(6)
9.304(3)
90
82
86
87
b/Å
c/Å
2i
2j
3,4-OCH2CH2O
H
a/°
aReaction conditions: 1a–j (2 mmol); hydroxylamine hydrochloride (278 mg, 4 mmol); and
sodium acetate (328 g, 4 mmol); 95% EtOH (15 mL); reflux; 18 h.
bIsolated yields.
90
b/°
90
3979(2)
8
g/°
V/Å3
Z
F (000)
Dcalc/mg m–3
1824
1.505
Absorption coefficient/mm–1 2.225
2.35–27.71
–22 < = h < = 22, –32 < = k < = 31, –12 < = l< =11
q range/°
Limiting indices
Reflections collected/unique 54035/4667, [R(int) = 0.0933]
Completeness to theta
Data/restraints/parameters
Refinement method
99.6%
4649/0/245
Full-matrix least-squares on F^2
R1 = 0.0687, wR2 = 0.1717
R1 = 0.1365, wR2 = 0.2008
1.040
Final R indices[I>2s(I)]
R indices (all data)
Goodness-of-fit on F2
Largest diff. peak and hole/(e.Å–3) 0.742 and –0.833
can be obtained free of charge from the CCDC via http://www.
ccdc.cam.ac.uk/.
The mechanism proposed for the reaction is illustrated in
Scheme 2. Firstly, in the presence of weak basic sodium acetate,
the reaction of 1-cyanocyclopropane-1-carboxylates and
hydroxylamine hydrochloride generated a stable intermediate
1-cyano-2-[(hydroxyimino)methyl]cyclopropane-1-carboxylate
[A]. Then, the intramolecular nucleophilic addition of oxime
[A] to cyano group formed the bicyclic 2-imino-3-oxa-4-
Fig. 1 Molecular structure of 1-carbamoylcyclopropane-1-carboxylate
2a. Non-hydrogen atoms are shown at the 30% probability level.
hydrochloride (2 equiv.) and sodium acetate (2 equiv.) in
ethanol under reflux for 18 h as the standard conditions. We
explored the scope of this selective hydrolysis reaction with
various 1-cyanocyclopropanecarboxylates (Scheme 1). To our
satisfaction, the reaction took place easily to give a good yield
and was applicable to a broad range of 1-cyanocyclopropane-
1-carboxylates. The results were summarised in Table 1.
Both electron-rich and electron-deficient aromatic groups
were similarly viable affording the products in good yields
(82−89%). Substrates bearing chloro, bromo, iodo, methyl,
and ethoxycarbonyl of the aryl displayed similar reactivity,
but substrates bearing iodo at the 2-position of the aryl showed
slightly lower activities to furnish the products in good yields.
All 1-carbamoylcyclopropane-1-carboxylates were analysed
azabicyclo[4.1.0]hept-4-ene-1-carboxylate
intermediate
[B]. Nucleophilic addition of water to the C=N of O-imino
oxime afforded intermediate 5-hydroxy-2-imino-3-oxa-4-
azabicyclo[4.1.0]heptane-1-carboxylate [C]. The opening ring
of 6-imino-1,2-oxazinan-3-ol skeleton of intermediate [C]
gave the intermediate 1-[(aminooxy)(imino)methyl]-2-aroyl-
3-arylcyclopropane-1-carboxylate [D]. Then, the nucleophilic
addition of water to the C=N of 1-[(aminooxy)(imino)methyl]
cyclopropane-1-carboxylate formed the intermediate 1-amino-
1-(aminooxy)-1-cyclopropylmethan-1-ol [E] again. Finally,
removal of hydroxylamine mediated by sodium acetate
produced the 1-carbamoylcyclopropane-1-carboxylates.
1
1
by their H NMR, 13C NMR and HRMS. Characteristic H
chemical shift of CONH2 at δ ca 7.08 ppm (s), and 5.69 ppm (s),
unequivocally indicated the exclusive chemical environment of
amide protons. Two doublet peaks at δ ca 4.26 ppm (s), and 3.70
ppm (s) were assigned to C(2) and C(3) protons of cyclopropane.
Unambiguous evidence for the structure and stereochemistry of
2a was obtained from a single crystal X-ray analysis. ORTEP
diagram of 2a was shown in Fig. 1. The crystallographic data of
2a are listed in Table 2. Crystallographic data for 2a have been
deposited with the Cambridge Crystallographic Data Centre
(CCDC) with the deposition number CCDC 1402516. The data
In conclusion, we have successfully developed
a
hydroxylamine-mediated selective hydrolysis of 1-cyanocyclo-
propane-1-carboxylates. This reaction involved the sequential
the nucleophilic addition reaction of 2-aroyl-3-aryl-1-
cyanocyclo-propanecarboxylates with hydroxylamine to give
the corresponding oximes, the formation of bicyclic 3-oxa-4-
azabicyclo[4.1.0]heptanes via the intramolecular nucleophilic
addition, ring opening of heterobicycles and removal of
hydroxylamine. With this new and simple method, we can
synthesise a series of 1-carbamoylcyclo-propane-1-carboxylates.

696 JOURNAL OF CHEMICAL RESEARCH 2016
NH
N
NH
EtO
Ar1
2C
EtO
2C
H
EtO
Ar1
EtO
2C
2C CN
O
N
O
HONH2HCl
O
N
O
Ar1
Ar1
NH
H
OH
H
H
OH
OH
Ar2
Ar2
[ ]
Ar2
H
O
Ar2
[ ]
A
[ ]
C
B
H
OH
NH2
H2N
NH2
HN
2C
H2N
2C
EtO
2C
O
O
O
H
O
OH
EtO
EtO
+
HONH2
H
O
H
2O
Ar1
O
O
Ar1
Ar1
Ar2
Ar2
Ar2
[ ]
E
[ ]
D
Scheme 2 Tentative reaction mechanism.
Experimental
by TLC (hexanes/EtOAc, 2/1). Subsequently, the mixture was poured
directly into ice-water (20 mL), and the crude product was obtained
by filtering and then recrystallised from ethyl acetate and petroleum
ether to the purified products 2a–f in yields of 83–89%; afterwards
the mixture was poured directly into ice-water (20 mL), the residue
was extracted with dichloromethane (10 mL × 2). The organic phase
was washed with water (10 mL) and brine (15 mL), and dried over
anhydrate sodium sulfate. After removal of dichloromethane, the crude
product was purified by flash chromatography (silica gel, EtOAc/
hexanes, 1/3) and recrystallisation to give the desirable products 2g–j
of 82–88% in yields.
All melting points were determined in a Yanaco melting point
apparatus and are uncorrected. IR spectra were recorded in a Nicolet
FTIR 5DX spectrometer. The 1H NMR (400 or 600 MHz) and
13C NMR (100 or 150 MHz) spectra were recorded in a Bruker AV-
400 or 600 spectrometer with TMS as internal reference in CDCl3 or
DMSO-d6 solutions. The J values are given in hertz. High-resolution
ESI mass spectra were obtained on a UHR-TOF maXis (ESI) mass
spectrometer. X-ray crystallographic analysis was performed with a
Smart Apex-II diffractometer. Flash chromatography was performed
on silica gel (230–400 mesh) eluting with ethyl acetate–hexanes
mixture. All reactions were monitored by thin layer chromatography
(TLC). All reagents and solvents were purchased from commercial
sources and purified commonly before used.
Ethyl 2-(4-bromophenyl)-1-carbamoyl-3-(4-chlorobenzoyl)cyclopropane
-1-carboxylate (2a)
White solid, 87%; m.p. 247.8–248.2 °C (EA/PE); IR (KBr, cm–1):
Synthesis of substituted 1-cyanopropane-1-carboxylates 1a–j
ν = 3447, 3315, 3185, 2984, 1722, 1670, 1599, 1488, 1442, 1399, 1281,
1216, 1133, 1092, 1010, 825, 778; H NMR (400 MHz, DMSO-d6) δ
1
The
starting
materials,
2-aroyl-3-aryl-1-cyanocyclopropane-
(ppm): 8.07 (d, J = 8.0 Hz, 2H), 7.65 (d, J = 8.0 Hz, 2H), 7.59 (s, 1H),
7.49 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 7.28 (s, 1H), 4.14 (d,
J = 8.0 Hz, 1H), 3.93–3.82 (m, 2H), 3.50 (d, J = 8.0 Hz, 1H), 0.82 (t,
J = 6.8 Hz, 3H);13C NMR (DMSO-d6, 100 MHz) δ (ppm): 197.2, 171.7,
169.8, 143.9, 140.0, 138.9, 136.1, 136.0, 135.4, 134.1, 125.8, 66.3, 51.8,
40.5, 38.3, 18.7; HRMS (ESI) for C20H17BrClNNaO4 [M + Na]+ calcd
471.9927; found: 471.9920.
1-carboxylates, were prepared via a modified method from the
corresponding 1-(2-oxo-2-arylethyl)pyridin-1-ium salt and 2-cyano-
3-arylacrylates in good yields under mild conditions according to the
reported procedure.20
The synthesis of pyridinium salt was carried out by mixing
substituted 2-bromo-1-phenylethan-1-one (2.2 mmol) and pyridine
(10 mL) at about 100 °C under conventional heating for 0.5 h. The
resulting precipitate was collected with filtration. The residue of
the filtrate was washed by dichloromethane (10 mL) and then dried
over air.
Ethyl 2-(4-bromobenzoyl)-1-carbamoyl-3-(4-iodophenyl)cyclopropane
-1-carboxylate (2b)
White solid, 84%; m.p. 244.3–244.7 °C (EA/PE); IR (KBr, cm–1):
ν = 3474, 3326, 3178, 2989, 1724, 1673, 1584, 1481, 1391, 1273, 1115,
1005, 894, 820, 771; 1H NMR (600 MHz, DMSO-d6) δ (ppm): 8.00 (s,
2H), 7.80 (s, 2H), 7.67 (s, 2H), 7.56 (s, 1H), 7.26 (s, 1H), 7.16 (s, 2H),
4.13 (s, 1H), 3.92-3.88 (m, 2H), 3.51 (s, 1H), 0.86 (s, 3H); 13C NMR
(DMSO-d6, 150 MHz) δ (ppm): 192.3, 166.5, 164.5, 136.8, 135.1,
134.0, 131.8, 131.0, 130.3, 127.9, 93.4, 61.1, 46.6, 35.2, 33.3, 13.5;
HRMS (ESI) for C20H17BrINNaO4 [M + Na]+ calcd 563.9283; found:
563.9283.
The substituted ethyl 2-cyano-3-phenylacrylate was obtained by the
piperidine (2.0 mmol) promoted condensation of aromatic aldehydes
(2.0 mmol) and ethyl cyanoacetate (2.0 mmol) in ethanol (10 mL)
stirred at 0 °C for about 10 min. The resulting precipitate was collected
with filtration. The residue of the filtrate was washed by water (10 mL)
and then dried over air.
A mixture of pyridinium salt and substituted ethyl 2-cyano-3-
phenylacrylate and triethylamine (0.2 g) in N,N-dimethylformamide
(15 mL) was stirred at room temperature for 12 h, the reaction was
completed by TLC analysis. The reaction mixture was extracted with
ethyl acetate (3 × 10 mL) and dried using sodium sulfate anhydrous and
then evaporated. The residue was recrystallised from ethanol to yield
substituted 1-cyanocyclopropane-1-carboxylates 1a–j in 58–72%.
Ethyl 2-benzoyl-1-carbamoyl-3-(4-chlorophenyl)cyclopropane-1-
carboxylate (2c)
White solid, 83%; m.p. 210.1–211.0 °C (EA/PE); IR (KBr, cm–1):
ν = 3441, 3302, 3187, 2981, 1722, 1670, 1603, 1494, 1448, 1404, 1280,
1135, 1091, 1056, 1013, 830, 749, 692; 1H NMR (400 MHz, CDCl3) δ
(ppm): 8.07 (d, J = 7.6 Hz, 2H), 7.58 (dd, J = 7.6 Hz and 7.2 Hz, 1H),
7.47 (dd, J = 7.6 Hz and 7.2 Hz, 2H), 7.26–7.20 (m, 4H), 7.08 (s, 1H),
5.69 (s, 1H), 4.26 (d, J = 8.4 Hz, 1H), 4.02–3.93 (m, 2H), 3.70 (d,
J = 8.4 Hz, 1H), 0.94 (t, J = 7.2 Hz, 3H);13C NMR (CDCl3, 100 MHz) δ
(ppm): 193.2, 168.7, 165.0, 136.4, 133.7, 131.8, 130.1, 128.8, 128.5, 62.3,
Synthesis of substituted 1-carbamoylcyclopropane-1-carboxylates 2a–j
The mixture of appropriate substituted 1-cyanopropane-1-carboxylates
(2.0 mmol), hydroxylamine hydrochloride (278 mg, 4 mmol), and
sodium acetate (328 g, 4 mmol) in the solution of 95% EtOH (15 mL)
was stirred at room temperature. The resultant mixture was stirred
under reflux for 18 h, and the completion of reaction was confirmed

JOURNAL OF CHEMICAL RESEARCH 2016 697
44.7, 36.7, 35.6, 13.3; HRMS (ESI) for C20H18ClNNaO4 [M + Na]+ calcd
394.0822; found: 394.0825.
Ethyl 2-benzoyl-1-carbamoyl-3-(2-iodophenyl)cyclopropane-1-
carboxylate (2i)
White solid, 86%; m.p. 188.5–189.6 °C (EA/PE); IR (KBr, cm–1):
ν = 3442, 3331, 3184, 3044, 3015, 1722, 1674, 1582, 1429, 1375, 1263,
1222 1133 1012, 898, 825, 746; 1H NMR (600 MHz, CDCl3) δ (ppm):
8.00 (d, J = 7.8 Hz, 2H), 7.76 (d, J = 7.8 Hz, 1H), 7.52 (dd, J = 7.8
Hz and 7.2 Hz, 2H), 7.41 (dd, J = 7.8 Hz and 7.2 Hz, 2H), 7.24 (dd,
J = 7.8 Hz and 7.2 Hz, 1H), 7.14 (d, J = 7.2 Hz, 1H), 6.93 (dd, J = 7.2 Hz
and 7.2 Hz, 1H), 5.61 (s, 1H), 4.31 (d, J = 9.0 Hz, 1H), 4.01–3.95 (m,
1H), 3.90–3.85 (m, 1H), 3.72 (d, J = 9.0 Hz, 1H), 0.92 (t, J = 6.6 Hz,
3H); 13C NMR (CDCl3, 150 MHz) δ (ppm): 191.6, 167.9, 164.2, 137.9,
135.5, 135.2, 132.6, 129.1, 128.6, 127.8, 127.4, 126.9, 101.3, 61.1, 42.8,
42.3, 36.6, 12.5; HRMS (ESI) for C20H18INNaO4 [M + Na]+ calcd
486.0178; found: 486.0183.
Ethyl 2-benzoyl-3-(4-bromophenyl)-1-carbamoylcyclopropane-1-
carboxylate (2d)
White solid, 86%; m.p. 217.3–217.9 °C (EA/PE); IR (KBr, cm–1):
ν = 3438, 3327, 3186, 3048, 3004, 1718, 1669, 1589, 1427, 1377, 1263,
1221, 1136, 1016, 897, 825, 749; 1H NMR (400 MHz, CDCl3) δ (ppm):
8.02 (d, J = 8.4 Hz, 2H), 7.53 (dd, J = 7.6 Hz and 7.2 Hz, 1H), 7.42 (dd,
J = 6.8 Hz and 6.8 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.11 (d, J = 7.6 Hz,
2H), 6.99 (s, 1H), 5.45 (s, 1H), 4.21 (d, J = 8.0 Hz, 1H), 3.96–3.90
(m, 2H), 3.63 (d, J = 8.4 Hz, 1H), 0.90 (t, J = 7.6 Hz, 3H); 13C NMR
(CDCl3, 100 MHz) δ (ppm): 193.1, 168.7, 164.9, 136.5, 133.6, 132.4,
131.4, 130.4, 128.8, 128.4, 121.9, 62.3, 44.8, 36.8, 35.6, 13.3; HRMS
(ESI) for C20H18BrNNaO4 [M + Na]+ calcd 438.0317; found: 438.0314.
Ethyl 2-benzoyl-1-carbamoyl-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-
yl)cyclopro pane-1-carboxylate (2j)
Methyl 4-(3-benzoyl-2-carbamoyl-2-(ethoxycarbonyl)cyclopropyl)
benzoate (2e)
White solid, 87%; m.p. 176.1–176.8 °C (EA/PE); IR (KBr, cm–1):
ν = 3442, 3335, 3217, 3043, 2989, 1730, 1672, 1599, 1428, 1389, 1284,
1215, 1132, 1012, 895, 821, 749; 1H NMR (600 MHz, CDCl3) δ (ppm):
8.03 (d, J = 7.8 Hz, 2H), 7.51 (dd, J = 7.8 Hz and 7.2 Hz, 1H), 7.41 (dd,
J = 7.8 Hz and 7.2 Hz, 2H), 6.92 (s, 1H), 6.74 (s, 1H), 6.70 (s, 2H), 5.56
(s, 1H), 4.15 (s, 5H), 3.96–3.89 (m, 2H), 3.58 (d, J = 8.4 Hz, 1H), 0.89
(t, J = 7.2 Hz, 3H);13C NMR (CDCl3, 150 MHz) δ (ppm): 192.6, 167.8,
164.3, 142.2, 135.6, 132.5, 127.7, 127.5, 125.4, 120.7, 116.6, 116.1, 63.3,
63.2, 61.1, 44.1, 36.1, 34.7, 12.4; HRMS (ESI) for C22H21NNaO6 [M +
Na]+ calcd 418.1267; found: 418.1265.
White solid, 85%; m.p. 158.4–159.1 °C (EA/PE); IR (KBr, cm–1):
ν = 3440, 3314, 3187, 2989, 1722, 1674, 1607, 1441, 1279, 1184, 1112,
1
1017, 852, 766, 696; H NMR (600 MHz, CDCl3) δ (ppm): 8.03 (d,
J = 8.4 Hz, 2H), 7.90 (d, J = 7.8 Hz, 2H), 7.53 (dd, J = 7.8 Hz and 7.2
Hz, 1H), 7.42 (dd, J = 7.8 Hz and 7.2 Hz, 2H), 7.31 (d, J = 7.8 Hz, 2H),
6.95 (s, 1H), 5.54 (s, 1H), 4.26 (d, J = 7.8 Hz, 1H), 3.99–3.89 (m, 2H),
3.82 (s, 3H), 3.72 (d, J = 8.4 Hz, 1H), 0.90 (t, J = 7.2 Hz, 3H);13C NMR
(CDCl3, 150 MHz) δ (ppm): 192.6, 168.1, 166.2, 164.4, 138.2, 136.0,
133.2, 129.1, 128.3, 128.0, 61.9, 51.6, 44.5, 36.5, 35.2, 12.8; HRMS
(ESI) for C22H21NNaO6 [M + Na]+ calcd 418.1267; found: 418.1266.
Ethyl 1-carbamoyl-2-(4-chlorobenzoyl)-3-(m-tolyl)cyclopropane-1-
carboxylate (2f)
Acknowledgements
Financial support of this research by the National Natural
Science Foundation of China (NNSFC 21173181) is gratefully
acknowledged by authors. This project was funded by the
Priority Academic Program Development of Jiangsu Higher
Education Institutions.
White solid, 89%; m.p. 171.7–172.5 °C (EA/PE); IR (KBr, cm–1):
ν = 3449, 3342, 3287, 3059, 3017, 1719, 1676, 1592, 1441, 1403, 1285,
1214, 1133, 1018, 889, 826, 756; 1H NMR (600 MHz, CDCl3) δ (ppm):
8.00 (d, J = 7.8 Hz, 2H), 7.81 (d, J = 7.8 Hz, 2H), 7.13 (dd, J = 7.8 Hz and
7.8 Hz, 1H), 7.02 (dd, J = 7.2 Hz and 7.2 Hz, 3H), 6.84 (s, 1H), 5.39 (s,
1H), 4.16 (d, J = 8.4 Hz, 1H), 4.00–3.91 (m, 2H), 3.64 (d, J = 8.4 Hz,
1H), 2.26 (s, 3H), 0.92 (t, J = 7.2 Hz, 3H);13C NMR (CDCl3, 100 MHz)
δ (ppm): 191.5, 168.6, 165.0, 140.1, 138.9, 136.2, 134.6, 130.0, 129.8,
129.7, 129.2, 127.9, 102.3, 62.2, 43.7, 37.3, 13.6; HRMS (ESI) for
C21H20ClNNaO4 [M + Na]+ calcd 408.0979; found: 408.0980.
Received 16 August 2016; accepted 7 October 2016
Paper 1604259 doi: 10.3184/174751916X14768938598056
Published online: 24 October 2016
References
Ethyl 2-benzoyl-3-(3-bromophenyl)-1-carbamoylcyclopropane-1-
carboxylate (2g)
1
2
3
A.K. Ghose, V.N. Viswanadhan and J.J. Wendoloski, J. Comb. Chem.,
1999, 1, 55.
D.Y. Hu, Q.Q. Wan, S. Yang, B.A. Song, P.S. Bhadury, L.H. Jin, K. Yan, F.
Liu, Z. Chen and W. Xue, J. Agric. Food Chem., 2008, 56, 998.
L. Crespo, G. Sanclimens, M. Pons, E. Giralt, M. Royo and F. Albericio,
Chem. Rev., 2005, 105, 1663.
White solid, 88%; m.p. 181.8–182.4 °C (EA/PE); IR (KBr, cm–1):
ν = 3435, 3310, 3187, 3013, 1716, 1670, 1601, 1447, 1405, 1287, 1216,
1136, 1057, 1010, 852, 774, 690; 1H NMR (400 MHz, CDCl3) δ (ppm):
8.07 (d, J = 7.2 Hz, 2H), 7.58 (dd, J = 7.6 Hz and 7.2 Hz, 1H), 7.47
(dd, J = 7.6 Hz and 7.2 Hz, 2H), 7.45 (s, 1H), 7.38 (d, J = 8.0 Hz, 1H),
7.21 (d, J = 8.4 Hz, 1H), 7.15 (dd, J = 8.0 Hz and 8.0 Hz, 1H), 7.02 (s,
1H), 5.70 (s, 1H), 4.25 (d, J = 8.4 Hz, 1H), 4.06–3.93 (m, 2H), 3.70 (d,
J = 8.4 Hz, 1H), 0.95 (t, J = 7.2 Hz, 3H);13C NMR (CDCl3, 100 MHz)
δ (ppm): 193.1, 168.5, 164.9, 136.5, 135.7, 133.6, 131.9, 130.9, 129.7,
128.8, 128.5, 127.3, 122.2, 62.3, 44.8, 36.5, 33.5, 13.3; HRMS (ESI) for
C20H18BrNNaO4 [M + Na]+ calcd 438.0317; found: 438.0315.
4
5
6
7
8
9
X. Guo, A. Facchetti and T.J. Marks, Chem. Rev., 2014, 114, 8943.
U. Boas, J. Brask and K.J. Jensen, Chem. Rev., 2009, 109, 2092.
D.W. Zhang, X. Zhao and Z.T. Li, Acc. Chem. Res., 2014, 47, 1961.
R.M. Lanigan and T.D. Sheppard, Eur. J. Org. Chem., 2013, 7453.
R. Yamashita, A. Sakakura and K. Ishihara, Org. Lett., 2013, 15, 3654.
T.M. El Dine, W. Erb, Y. Berhault, J. Rouden and J. Blanchet, J. Org.
Chem., 2015, 80, 4532.
10 J.R. Dunetz, Y. Xiang, A. Baldwin and J. Ringling, Org. Lett., 2011, 13,
5048.
11 C.M. Gabriel, M. Keener, F. Gallou and B.H. Lipshutz, Org. Lett., 2015,
17, 3968.
12 Z. Fu, J. Lee, B. Kang and S.H. Hong, Org. Lett., 2012, 14, 6028.
13 I. Dokli and M. Gredicak, Eur. J. Org. Chem., 2015, 2727.
14 V. Singh, G.P. Yadav, P.R. Maulik and S. Batra, Tetrahedron, 2006, 62,
8731.
15 M.C. Kozlowski, E.S. DiVirgilio, K. Malolanarasimhan and
C.A. Mulrooney, Tetrahedron Asymmetry, 2005, 16, 3599.
16 Y.S. Tran, T.J. Martin and O. Kwon, Chem. Asian J., 2011, 6, 2101.
17 M.A. Cavitt, L.H. Phun and S. France, Chem. Soc. Rev., 2014, 43, 804.
18 W. Ye, C. Tan, J. Yao, S. Xue, Y. Li and Wang, C. Adv. Synth. Catal., 2016,
358, 426.
19 S. Xue, J. Liu, X. Qing and C. Wang, RSC Adv., 2016, 6, 67724.
20 Q.F. Wang, X.K. Song, J. Chen and C.G. Yan, J. Comb. Chem., 2009, 11,
1007.
Ethyl 1-carbamoyl-2-(4-chlorobenzoyl)-3-(2-iodophenyl)cyclopropane
-1-carboxylate (2h)
White solid, 82%; m.p. 191.5–191.9 °C (EA/PE); IR (KBr, cm–1):
ν = 3431, 3328, 3189, 3059, 3001, 1714, 1666, 1596, 1431, 1397, 1283,
1216, 1135, 1013, 896, 824, 746; 1H NMR (400 MHz, CDCl3) δ (ppm):
8.00 (d, J = 8.0 Hz, 2H), 7.81 (d, J = 8.0 Hz, 1H), 7.50 (s, 1H), 7.44
(d, J = 8.0 Hz, 2H), 7.28 (dd, J = 7.6 Hz and 7.2 Hz, 1H), 7.16 (d,
J = 7.6 Hz, 1H), 6.98 (dd, J = 7.6 Hz and 7.2 Hz, 1H), 5.74 (s, 1H), 4.32
(d, J = 8.8 Hz, 1H), 4.08–3.90 (m, 2H), 3.75 (d, J = 8.8 Hz, 1H), 0.99
(t, J = 6.8 Hz, 3H);13C NMR (CDCl3, 100 MHz) δ (ppm): 191.5, 168.6,
165.0, 140.1, 138.9, 136.2, 134.6, 130.0, 129.8, 129.7, 129.2, 127.9,
102.3, 62.2, 43.7, 37.3, 13.6; HRMS (ESI) for C20H17ClINNaO4 [M +
Na]+ calcd 519.9788; found: 519.9783.