Heterogeneous Catalysis with Basic Compounds to Achieve the Synthesis and C-N Cleavage of Azetidin-2-ones under Microwave Irradiation

Article abstract of DOI:10.1055/s-0037-1611851

The synthesis of azetidin-2-ones with a completely heterogeneous catalysis is reported. The use of basic compounds as solid catalysts allowed for the synthesis of azetidin-2-ones under microwave irradiation without organic additives such as triethylamine. An excellent catalyst for this transformation was Mg-Al hydroxide (MAH). The present methodology offers the advantages of non-hazardous reaction conditions, short reaction times, high yields, and catalyst reusability. Different substitution groups were tested on the imines and acyl chlorides to explore the scope of the reaction. Unconventional N-C4 bond cleavage was detected in azetidin-2-ones. MAH was characterized by N ₂ adsorption-desorption, X-ray diffraction (XRD), scanning electron microscopy (SEM), and high-resolution transmission electron microscopy (HR-TEM).

Full text of DOI:10.1055/s-0037-1611851

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–M
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A
en
A. Galván et al.
Paper
Synthesis
Heterogeneous Catalysis with Basic Compounds to Achieve the
Synthesis and C–N Cleavage of Azetidin-2-ones under Microwave
Irradiation
Adriana Galvána
Fabiola N. de la Cruzb
Francisco Cruza
Merced Martíneza
Clarisa Villegas Gomeza
Yolanda Alcarazc
José Manuel Domínguezd
Francisco Delgadoe
Miguel A. Vázquez*a
a Departamento de Química, Universidad de Guanajuato, Noria
Alta S/N, 36050, Guanajuato, Gto., México
mvazquez@ugto.mx
b Departamento de Química Orgánica, Universidad Autónoma
de Coahuila, Blvd. V. Carranza e Ing. José Cárdenas, 25280,
Saltillo, Coahuila, México
c Departamento de Farmacia, Universidad de Guanajuato, Noria
Alta S/N, 36050, Guanajuato, Gto., México
d Instituto Mexicano del Petróleo, Eje Central Lázaro Cárdenas
152, 07730, Ciudad de México, México
e Departamento de Química Orgánica, Escuela Nacional de
Ciencias Biológicas-IPN, Prolongación Carpio y Plan de Ayala
S/N, 11340, Ciudad de México, México
Received: 01.03.2019
OH
O
O
Accepted after revision: 10.05.2019
Published online: 28.05.2019
DOI: 10.1055/s-0037-1611851; Art ID: ss-2019-m0136-op
OH
CO2H
F
N
N
O
Abstract The synthesis of azetidin-2-ones with a completely heteroge-
neous catalysis is reported. The use of basic compounds as solid cata-
lysts allowed for the synthesis of azetidin-2-ones under microwave irra-
diation without organic additives such as triethylamine. An excellent
catalyst for this transformation was Mg-Al hydroxide (MAH). The pres-
ent methodology offers the advantages of non-hazardous reaction con-
ditions, short reaction times, high yields, and catalyst reusability. Differ-
ent substitution groups were tested on the imines and acyl chlorides to
explore the scope of the reaction. Unconventional N–C4 bond cleavage
was detected in azetidin-2-ones. MAH was characterized by N2 adsorp-
tion–desorption, X-ray diffraction (XRD), scanning electron microscopy
(SEM), and high-resolution transmission electron microscopy (HR-TEM).
O
F
O
1
2
BuO2C
OEt
O
Me
N
O
OMe
H
N
N
Key words heterogeneous catalyst, Mg-Al hydroxide, azetidin-2-
ones, ring opening, microwave irradiation
O
OMe
O
OMe
4
3
Figure 1 Structures with an azetidine-2-one nucleus that have biologi-
cal activity
Many antibiotics, including penicillin, have the azeti-
din-2-one (-lactam) structure, which has been known in
the field of medicinal chemistry since 1940.1,2 Considerable
research efforts have focused on this kind of heterocycle3 to
develop potent cholesterol absorption inhibitor 1,4,5 pros-
tate-specific antigen inhibitor 2,6,7 antiproliferative agent 3
that acts by inhibition of tubulin polymerization,8–10 and in-
hibitor 4 of the human cytomegalovirus protein11 (Figure
1).
Given the relevance of this structure, the development
of new procedures for the creation of azetidin-2-one-based
series of synthetic compounds should certainly be instru-
mental in the search for novel drugs. Several methodologies
have been developed for the construction of four-mem-
bered nitrogen heterocycles.12–21 The Staudinger synthesis,
starting from ketene-imine, has been one the most popular
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–M

B
A. Galván et al.
Paper
Synthesis
classical methods.22 Among other methodologies are the
[2+2] cycloaddition of isocyanates to vinyl ethers,23 the es-
ter or amide enolate-imine condensations,24 and recently
the Kinugasa reaction.25 Each of these methodologies has
been developed and implemented to improve selectivity,
increase yield, and attain shorter reaction times. However,
most of them are based on homogeneous catalysis with or-
ganic bases, representing an important drawback.
Heterogeneous catalysis is desirable in industry because
the product purification process is simplified, in part by the
ease of handling solid catalysts. Moreover, the catalysts can
be recovered and reused.26–30 Basic compounds such as
Al2O3, MgO, basic zeolites, and laminar hydroxides have
been successfully employed in heterogeneous catalysis to
achieve various organic transformations, including decar-
boxylation reactions,31 pyranpyrazole synthesis,32 methyla-
tion reactions,33 and condensations.34 In this context, ex-
tensive research on Mg-Al hydroxide (MAH) has led to its
application in the synthesis of amides35 and coumarins,36 as
well as in a variety of fundamental reactions: oxidation,37
hydroxylation,38 olefin epoxidation,39 and transesterifica-
tion.40
It is possible to synthesize azetidin-2-ones in the pres-
ence of diverse solid materials, including MS 3Å,41
Fe2O3/SiO2,42,43 and Al2O344 (Scheme 1).
Azetidin-2-ones have been synthesized with inorganic
materials and homogeneous catalysis, using compounds
such as triethylamine45 (Scheme 1a, c, d) and K2CO3
44
(Scheme 1b). To the best of our knowledge, their synthesis
with a purely heterogeneous methodology has yet to be re-
ported. We presently describe reactions between imines
and acyl chlorides carried out with heterogeneous catalysis
and microwave irradiation (Scheme 1e).
As a model system for optimizing the synthesis of azeti-
din-2-ones, N-(4-nitrobenzylidene)-4-methoxyaniline (5j)
and 2-chloroacetyl chloride (6a) were reacted under micro-
wave irradiation (Table 1). Evaluation was made of the ef-
fect of various solvents, including MeCN, PhMe, DMF, and
THF (Table 1, entries 1–4), all at 150 °C except the latter.
Performing the reaction in MeCN or PhMe afforded the de-
sired product in low yield (entries 1 and 3). With DMF (en-
try 4), a moderate yield was obtained for 7j (65%). This
compound was also achieved in a lower yield (37%) by re-
a) Isonicotinic acid hydrazide analogues (Thomas, 2010)
O
O
O
Cl
O
Cl
Cl
N
Ar
N
N
N
H
MS 3Å, Et3N
DCE, 0 °C
H
N
Ar
N
b) Derivatives containing aryl sulfonate (Kendre, 2012)
O
R1
R2
OTs
Cl
R1
R2
OTs
R
Cl
N
N
Al2O3/K2CO3
MW (5 min)
solvent-free
R
O
Cl
c) 4-Aminopyridine derivatives (Avasthi, 2014)
O
O
Cl
NH2
O
N
Ar
Cl
Cl
Fe2O3/SiO2
70 °C, 6–8 h
N
+
N
N
Ar
H
Et3N, EtOH, 6 h
Ar
N
d) 1,2,4-Triazole derivatives (Avasthi, 2015)
O
O
S
NH2
S
N
Ar
N
N
O
Cl
Cl
Fe2O3/SiO2
MW (2 min)
N
H
N
Cl
N
N
S
N
H
N
+
N
N
O
N
O
Ar
H
N
H
Et3N, EtOH, 6 h
Ar
N
O
e) This work
O
N
R2
R1
O
MAH
DMF, MW (150 °C, 2 min)
R2
R1
R3
+
N
Cl
R3
Scheme 1 Approaches for the synthesis of azetidin-2-ones with solid materials
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–M

C
A. Galván et al.
Paper
Synthesis
acting 5j and 6a under neat conditions (entry 5). As a refer-
ence, triethylamine was used under similar conditions (en-
try 6), giving 7j in a low yield (33%).
All the imines were excellent substrates regardless of the
presence of electron-donating or electron-withdrawing
groups on the benzene rings. The yields found with differ-
ent derivatives of acetyl chloride depended on the electro-
negativity of the substituent at the -position to the car-
bonyl group. With the presence of two chlorines, the trans-
formation towards azetidine-2-one was quantitative (Table
2, entries 18–20). The yield decreased when using the ace-
tyl chloride with an acetoxy group as a substituent. This
transformation required prolonged reaction times (10 min),
which led to the hydrolysis of the imine and the generation
of by-products (entry 22).
Table 1 Optimization of the Synthesis of Azetidin-2-one 7ja
OMe
OMe
O
O
N
+
Cl
N
Cl
Cl
O2N
NO2
There was also a low yield for entries 2, 5, 6, 8, 9, 11, and
15, attributed to ring-opened product 8 (discussed in detail
later). A mixture of cis/trans-isomers was formed in all ex-
periments, in agreement with the literature.46 The cis/trans
ratio was determined by NMR and GC-MS analysis of the re-
action crude. Overall, slightly lower diastereoselectivity was
observed for reactions with electron-donating groups on
the trans-isomer. On the other hand, the presence of elec-
tron-withdrawing groups on the aryl moiety afforded the
cis-isomer as the major product. Likewise, N-acetate- and
N-hexanoate-substituted azetidin-2-ones were obtained in
good yield and, surprisingly, with only one isomer (Table 2,
entries 16 and 17). The structural description for the cis-
isomer (J = ~5.0 Hz; dihedral angle 0°) and trans-isomer (J =
~2.0 Hz; dihedral angle 139.9°) is given as a coupling con-
stant, provided by NMR and X-ray crystal structure analysis
of product 7j (Figure 2).
Another compound was isolated in some experiments.
After characterization and confirmation by X-ray structural
analysis (Figure 2c), it was identified as the ring-opened
product (Figure 3). The well-known core reactivity of azeti-
din-2-one23 owes itself to its strain energy, which results in
four reactive positions on the nucleus of these compounds.
Selectivity depends on the electronic effects of substituents
and the reaction conditions. The cleavage of the N–C4 bond
is typically carried out by hydrogenolysis when the C-4
substituent is an aryl group.47 The photo-induced electron
transfer methodology has been applied as well.48 Cleavage
is also found when the substituent is other than an aryl
group, as in the reaction between 4-formyllactams and 2-
(trimethylsilyl)thiazole.49 The behavior observed presently
is distinct from that reported previously. MAH herein cata-
lyzed the ring opening, leading to different yields of the C4–
N cleavage derivatives 8 (Figure 3). Unfortunately, no ten-
dency was detected in the reaction conditions or for the
electronic nature of substituents.
5j
6a
7j (cis/trans)
Entry Solvent Catalyst Temp
(°C)
Time
(min)
Ratiob
(cis/trans)
Yield (%)
1
MeCN
THF
–
150
65
120
30
41/59
trace
49
2
–
trace
38
3
PhMe
DMF
–
–
150
150
150
150
150
150
150
150
100
70
120
150
180
120
120
120
120
2
47/53
46/54
22/78
45/55
52/48
trace
4
–
65
5
–
37
6c
7d
8d
9d
10e
11e
12e
DMF
DMF
DMF
DMF
DMF
DMF
DMF
Et3N
MgO
-Al2O3
MAH
MAH
MAH
MAH
33
61
trace
76
53/47
52/48
52/48
52/48
95
2
50
2
30
a Reaction conditions: 5j (0.2 mmol), 6a (0.21 mmol), sealed vessel, and
microwave irradiation.
b The cis/trans ratio was calculated from the 1H NMR spectrum of the reac-
tion crude and GC-MS.
c In open vessel with 10% mol of base.
d In open vessel with 10% w/w of inorganic material.
e In sealed vessel with 10% w/w of inorganic material.
The next step was the examination of catalytic materials
(Table 1, entries 7–12), finding pure magnesium oxide
(MgO, entry 7) slightly active and aluminum oxide (-Al2O3,
entry 8) inactive. Testing MAH under the same reaction
conditions increased the yield to 76% (entry 9), and then to
95% by shortening the reaction time from 2 hours to 2 min-
utes (entry 10). When conducting the reaction at different
temperatures, a significantly reduced yield was observed
below 150 °C (entries 11 and 12). Finally, the azetidin-2-
one 7j (entry 10) was purified by column chromatography
with a hexane/EtOAc mixture.
After optimizing the reaction conditions, the scope of
the reaction was explored with a variety of imines (Table 2).
The presence of an aromatic moiety did not affect the yield.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–M

D
A. Galván et al.
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Synthesis
Table 2 Synthesis of Azetidin-2-ones 7 by Using Heterogeneous Catalysis with MAH
O
O
R2
R1
N
R4
R1
R2
MAH
O
R2
N
+
R3
R1
R3
+
H
N
DMF, MW (150 °C, 300 W, 2 min)
Cl
R4
R4
7 (cis), 7' (trans)
5
6
8
Entry
R1
Ph
R2
Ph
R3
R4
Cl
Ratioa (cis/trans)
7a (43/57)
Yield (cis/trans, %)b
8 (%)c
1
H
40/52
36/53
47/38
39/54
29/29
25/33
55/32
22/22
0/0
n.d.
10
2
4-MeOC6H4
4-O2NC6H4
4-FC6H4
Ph
Ph
Ph
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Cl
Cl
Cl
H
H
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
OAc
7b (40/60)
7c (55/45)
7d (42/58)
7e (49/51)
7f (43/57)
7g (63/37)
7h (51/49)
7i (0/0)
3
n.d.
n.d.
25
4
5
Ph
4-O2NC6H4
4-BrC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
6
Ph
34
7
3-ClC6H4
2-thienyl
2-furanyl
4-O2NC6H4
4-MeOC6H4
4-MeOC6H4
4-O2NC6H4
2,4-ClC6H3
C6H5CH=CH
4-FC6H4
n.d.
39
8
9
40
10
11
12
13
14
15
16
17
18
19
20
21
22
4-MeOC6H4
4-MeOC6H4
4-ClC6H4
7j (59/41)
7k (40/60)
7l (53/47)
7m (65/35)
7n (74/26)
7o (47/53)
7p (0/100)
7q (0/100)
7r (99)
55/40
46/31
46/40
55/0
n.d.
12
n.d.
n.d.
n.d.
38
4-MeOC6H4
4-ClC6H4
42/43
26/32
0/82
4-MeOC6H4
MeO2CCH2
n.d.
n.d.
0
4-FC6H4
MeO2C(CH2)5
4-MeOC6H4
4-MeOC6H4
4-ClC6H4
0/80
4-O2NC6H4
4-MeOC6H4
2,4-ClC6H3
2,4-ClC6H3
4-O2NC6H4
91/0
7s (99)
83/0
0
7t (98)
89/0
0
4-ClC6H4
7u (55/45)
7v (54/46)
38/32
12/10
n.d.
n.d.
4-MeOC6H4
a The cis/trans ratio was ascertained by GC-MS analysis of the reaction crude.
b Isolated yield.
c n.d.: Not detected.
Thus, several experiments were performed to gain in-
sight into the reactivity of azetidin-2-ones and MAH. A
mixture of stereoisomers of 7e (cis/trans) was used under
the same reaction conditions (Table 2), monitoring reaction
crudes with GC-MS. The analysis revealed that MAH induc-
es the opening of the heterocycle to provide 8e in moderate
yield (50%). A proposal for the mechanism is outline in
Scheme 2. The basic characteristics of MAH are responsible
for activating the -proton to the carbonyl group, which
may be stabilized by resonance structures (A ↔ B) to later
generate the ring-opened product.
R2
HN
R2
R1
O
R2
R1
O
R2
R1
O
R2
R1
O
N
Cl
R1
N
N
N
MAH
O
DMF
MW (150 °C)
Cl
Cl
Cl
Cl
A
B
C
7e
8e
Scheme 2 Azetidin-2-one ring opening catalyzed by MAH
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–M

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Synthesis
Figure 2 ORTEP drawing of compound 7j for the: a) trans-isomer, b) cis-isomer, and c) ring-opened product 8b
NO2
Br
O
Cl
O
O
O
Cl
Cl
Cl
N
H
Cl
S
N
N
N
H
H
H
MeO
8b, 10%
8e, 25%
8f, 34%
8h, 39%
OMe
O
OMe
Cl
Cl
O
N
O
H
Cl
Cl
O
N
H
N
H
MeO
8i, 40%
8k, 12%
8o, 38%
Figure 3 The products isolated and corresponding yield that resulted from the ring opening
The test of catalyst reuse was conducted with the imine
5j (Scheme 3) under the previously established optimal
conditions (vide supra). Once the first run was completed,
the MAH catalyst was filtered in vacuo and then washed
with dichloromethane. The recovered catalyst was reused
directly (without the need for stove drying) in further cy-
cles under the same conditions. The MAH catalyst could be
recovered and reused up to 6 times without any significant
loss of catalytic activity. According to the monitoring of the
reaction crude by GC-MS, an 89% yield of 7j was obtained
on the 6th run (Scheme 3). The catalytic activity decreased
dramatically by the 9th cycle, giving only a 40% yield. How-
ever, it could be recovered by washing the catalyst with wa-
ter and drying it at 120 °C for 10 minutes, resulting in 91%
yield.
The synthesis of MAH was carried out by the typical co-
precipitation procedure.50 The textural properties of MAH
were characterized by N2 physisorption analysis at 77 K
(Figure 4a). The measured surface area of BET (232 m2/g)
was superior to that of MgO (45 m2/g), with a pore volume
of 0.60 cm3/g and a pore diameter of 7.5 nm. According to
the powder X-ray analysis, the predominant phase in MAH
is boehmite (JCPDS card 21-1307), which is an aluminum
oxyhydroxide (Figure 4b). The scanning electron micro-
scope (SEM) and transmission electron microscopy (TEM)
analyses revealed that MAH had an amorphous character, a
fibrillar shape, and a particle size under 1 m (Figure 4c, d).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–M

F
A. Galván et al.
Paper
Synthesis
activity. Subsequently, catalyst recovery was characterized
by effortless regeneration of activity. Azetidin-2-one ring-
opened products were formed through N–C4 bond cleavage
promoted by the MAH catalyst.
OMe
OMe
O
O
MAH
N
+
Cl
N
DMF
MW (150 °C)
Cl
Cl
O2N
7j
Microwave irradiation was conducted in a Discover SP CEM micro-
wave apparatus. The progress of the reaction was monitored by TLC
(aluminum sheets, silica gel 60 F/UV254), using a hexane/EtOAc mix-
ture as eluent. Visualization was carried out with UV light and I2. The
products were purified by column chromatography over silica gel
(MN Kieselgel 60, 230–400 mesh). 1H and 13C NMR spectra were re-
corded on a Varian Gemini 200 MHz, Varian Gemini 300 MHz, or
Bruker Ultrashield 500 and 600 MHz spectrometer in CDCl3. Chemical
shifts are reported in ppm, relative to TMS and CHCl3 as the internal
standard. Melting points were determined on a digital Electrothermal
90100 melting point apparatus. High-resolution mass spectra (HRMS)
were obtained with electrospray ionization on a Bruker QTOF mass
spectrometer. X-ray data were collected on an Oxford Diffraction
Gemini ‘A’ diffractometer with a CCD area detector. N2 physisorption
samples were dried overnight at 120 °C, degassed at 200 °C under N2
flow for 3 h and examined at 77 K in Micromeritics Tristar II Plus
3030. The BET surface was measured in the relative pressure range of
0.05–0.3. Powder X-ray diffraction was obtained in a PANalytical X
Pert Pro MRD diffractometer with Cu K radiation. Particle morphol-
ogy was analyzed by TEM on a JEOL JEM-100S and by SEM on a JEOL
5900 LV.
6a
5j
NO2
Scheme 3 Recycling the MAH catalyst. Reagents and conditions: 5j (0.2
mmol), 6a (mmol), MAH (10% w/w), DMF (3 mL) in open vessel and mi-
crowave irradiation at 150 °C. The conversion was calculated from GC-
MS of the reaction crude.
1H and 13C NMR Spectra: For the numbering of carbon atoms, see the
Supporting Information.
Preparation of Catalysts; General Procedure
-Al2O3
-Al2O3 was synthesized by the precipitation method. A solution of
Al2(SO4)3·17H2O in deionized H2O was prepared in a 1:12 mass/vol-
ume ratio. This solution was added dropwise into a 3 L glass reactor
containing a mixture of deionized H2O and NH3 gas at 70 °C. The sus-
pension formed was filtered in vacuo and washed twice with a
H2O/NH3 mixture. The washed powder was dried at 110 °C for 12 h
and calcined at 500 °C for 4 h under air at 5 °C/min.
MAH and MgO
MAH was prepared by the co-precipitation method. First, MgSO4 and
Al2(SO4)3 were dissolved in deionized H2O (200 mL) with an
Mg/(Mg+Al) ratio of 0.75. The resulting solution was added dropwise,
under constant stirring at 60 °C, into a 3-L glass reactor containing aq
0.5 M Na2CO3 (500 mL) and the pH was adjusted to 11. Subsequently,
the temperature was increased to 80 °C and stirring continued for 18
h. The solid formed was filtered in vacuo, washed with H2O, and then
dried at 80 °C for 2 h at 3 °C/min. MgO was prepared in a similar pro-
cedure.
Figure 4 MAH characterization by: a) an N2 adsorption–desorption
graph, b) an X-ray diffractogram, and images from c) scanning electron
microscopy (SEM) and d) transmission electron microscopy (TEM).
In conclusion, the use of heterogeneous catalysis with
MAH resulted in the development of an efficient and envi-
ronmentally benign strategy for synthesizing azetidin-2-
one derivatives without the aid of organic bases. This meth-
odology offers several advantages, including high yields,
short reaction times, low cost, and a relatively clean reac-
tion profile. The catalyst could be synthesized simply and
recycled up to six times without any significant decrease in
Imines and Iminoesters 5; General Procedure
In a 25 mL round-bottomed flask were mixed the corresponding ani-
line (4.0 mmol), aldehyde (4.4 mmol, 1.1 equiv), and MeOH (ca. 3.0
mL). The reaction mixture was irradiated by microwave energy in an
open vessel (150 W) at 60 °C for 30 min. The reaction progress was
monitored by TLC. Upon completion, the mixture was cooled to r.t.
and MeOH was removed under reduced pressure. The pure product
was precipitated with a DCM/hexane mixture (5:95).
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G
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Synthesis
N-Benzylidenaniline (5a)
13C NMR (125 MHz, CDCl3):  = 160.7 (C=N), 160.0 (C-1), 136.1 (C-7),
132.3 (C-3, C-5), 131.8 (C-10), 129.1 (C-8, C-12), 129.0 (C-9, C-11),
122.8 (C-2, C-6), 119.5 (C-4).
Yellow solid; yield: 1.088 g (93%); mp 51–52 °C.
1H NMR (500 MHz, CDCl3):  = 8.28 (1 H, s, HC=N), 7.82–7.80 (2 H, m,
H-8, H-12), 7.33–7.29 (5 H, m, H-2, H-6, H-9, H-10, H-11), 7.27–7.13
(3 H, m, H-3, H-4, H-5).
Spectral data are consistent with the literature.53
N-(3-Chlorobenzylidene)-4-chloroaniline (5g)
13C NMR (125 MHz, CDCl3):  = 160.5 (C=N), 152.2 (C-1), 136.4 (C-7),
131.6 (C-10), 129.4 (C-8, C-12), 129.1 (C-3, C-5), 129.0 (C-9, C-11),
126.2 (C-4), 121.2 (C-2, C-6).
Green liquid; yield: 1.050 g (89%).
1H NMR (500 MHz, CDCl3):  = 8.31 (1 H, s, HC=N), 7.86 (1 H, s, H-8),
7.54 (1 H, ddd, J = 8.0, 2.1, 1.1 Hz, H-12), 7.44–7.38 (3 H, m, H-3, H-5,
H-10), 7.38–7.29 (3 H, m, H-2, H-6, H-11).
Spectral data are consistent with the literature.51
N-(4-Methoxybenzylidene)aniline (5b)
13C NMR (125 MHz, CDCl3):  = 158.9 (C=N), 149.8 (C-1), 137.8 (C-7),
135.3 (C-9), 134.9 (C-10), 134.3 (C-4), 130.4 (C-11), 129.3 (C-3, C-5),
129.1 (C-8), 128.0 (C-12), 122.3 (C-2, C-6).
White solid; yield: 1.224 g (90%); mp 61–62 °C.
1H NMR (500 MHz, CDCl3):  = 8.35 (1 H, s, HC=N), 7.84 (2 H, d, J = 8.8
Hz, H-8, H-12), 7.37 (2 H, t, J = 7.9 Hz, H-2, H-6), 7.20–7.15 (3 H, m, H-
3, H-4, H-5), 6.95 (2 H, d, J = 8.8 Hz, H-9, H-11), 3.82 (3 H, s, OCH3).
N-(Thiophen-2-ylmethylene)-4-chloroaniline (5h)
Brown solid; yield: 821.6 mg (79%); mp 72–73 °C.
13C NMR (125 MHz, CDCl3):  = 162.3 (C-10), 159.7 (C=N), 152.4 (C-1),
130.6 (C-8, C-12), 129.3 (C-3, C-5), 129.2 (C-7), 125.6 (C-4), 120.9 (C-
2, C-6), 114.2 (C-9, C-11), 55.4 (OCH3).
1H NMR (500 MHz, CDCl3):  = 8.49 (1 H, s, HC=N), 7.48 (1 H, d, J = 4.8
Hz, H-9), 7.45 (1 H, d, J = 3.0 Hz, H-11), 7.30 (2 H, d, J = 8.4 Hz, H-3, H-
5), 7.18–7.07 (3 H, m, H-2, H-6, H-10).
13C NMR (125 MHz, CDCl3):  = 153.3 (C=N), 149.9 (C-1), 142.6 (C-7),
132.7 (C-8), 131.5 (C-4), 130.8 (C-10), 129.3 (C-3, C-5), 127.9 (C-9),
122.4 (C-2, C-6).
Spectral data are consistent with the literature.51
N-(4-Nitrobenzylidene)aniline (5c)
Orange oil; yield: 1.226 g (84%).
Spectral data are consistent with the literature.51
1H NMR (500 MHz, CDCl3):  = 8.51 (1 H, s, HC=N), 8.26 (2 H, d, J = 8.6
Hz, H-9, H-11), 8.03 (2 H, d, J = 8.6 Hz, H-8, H-12), 7.46–7.35 (2 H, m,
H-2, H-6), 7.31–7.18 (3 H, m, H-3, H-4, H-5).
N-(Furan-2-ylmethylene)-4-chloroaniline (5i)
Black oil; yield: 735.0 mg (76%).
13C NMR (125 MHz, CDCl3):  = 157.4 (C=N), 150.9 (C-10), 149.3 (C-1),
141.6 (C-7), 129.4 (C-8, C-12), 129.4 (C-3, C-5), 127.1 (C-4), 124.0 (C-
9, C-11), 121.1 (C-2, C-6).
1H NMR (500 MHz, CDCl3):  = 8.26 (1 H, s, HC=N), 7.62 (1 H, d, J = 1.7
Hz, H-9), 7.34 (2 H, d, J = 8.8 Hz, H-3, H-5), 7.17 (2 H, d, J = 8.7 Hz, H-2,
H-6), 6.98 (1 H, d, J = 3.0 Hz, H-8), 6.57 (1 H, dd, J = 3.5, 1.8 Hz, H-9).
13C NMR (125 MHz, CDCl3):  = 151.9 (C-1), 149.8 (C-7), 148.0 (C=N),
(C-7), 146.0 (C-9), 131.8 (C-4), 129.3 (C-3, C-5), 122.3 (C-2, C-6), 116.9
(C-11), 112.3 (C-10).
Spectral data are consistent with the literature.52
N-(4-Fluorobenzylidene)aniline (5d)
Beige solid; yield: 1.114 g (87%); mp 45–46 °C.
Spectral data are consistent with the literature.54
1H NMR (500 MHz, CDCl3):  = 8.32 (1 H, s, HC=N), 7.83 (2 H, m, H-8,
H-12), 7.38–7.31 (2 H, m, H-2, H-6), 7.21–7.14 (3 H, m, H-3, H-4, H-5),
7.11–7.06 (2 H, m, H-9, H-11).
N-(4-Nitrobenzylidene)-4-methoxyaniline (5j)
Golden solid; yield: 1.175 g (94%); mp 131–132 °C.
13C NMR (125 MHz, CDCl3):  = 165.8 (J = 252.1 Hz, C-10), 158.8 (C=N),
151.9 (C-1), 132.7 (J = 3.0 Hz, C-7), 130.9 (J = 8.8 Hz, C-8, C-12), 129.3
(C-3, C-5), 126.1 (C-4), 121.0 (C-2, C-6), 115.9 (J = 22.0 Hz, C-9, C-11).
1H NMR (500 MHz, CDCl3):  = 8.57 (1 H, s, HC=N), 8.30 (2 H, d, J = 8.3
Hz, H-9, H-11), 8.04 (2 H, d, J = 8.3 Hz, H-8, H-12), 7.30 (2 H, d, J = 8.4
Hz, H-2, H-6), 6.96 (2 H, d, J = 8.4 Hz, H-3, H-5), 3.85 (3 H, s, OCH3).
13C NMR (125 MHz, CDCl3):  = 159.3 (C-4), 154.8 (C=N), 149.0 (C-10),
143.6 (C-1), 142.0 (C-7), 129.1 (C-8, C-12), 124.0 (C-9, C-11), 122.6 (C-
2, C-6), 114.6 (C-3, C-5), 55.5 (OCH3).
Spectral data are consistent with the literature.52
N-(Benzylidene)-4-nitroaniline (5e)
Golden solid; yield: 1.285 g (88%); mp 79–80 °C.
Spectral data are consistent with the literature.52,53
1H NMR (500 MHz, CDCl3):  = 8.51 (1 H, s, HC=N), 8.26 (2 H, d, J = 8.6
Hz, H-3, H-5), 8.03 (2 H, d, J = 8.6 Hz, H-2, H-6), 7.42–7.39 (2 H, m, H-
8, H-12), 7.29–7.24 (3 H, m, H-9, H-10, H-11).
N-(4-Methoxybenzylidene)-4-methoxyaniline (5k)
Olive green solid; yield: 1.049 g (89%); mp 145–146 °C.
13C NMR (125 MHz, CDCl3):  = 157.4 (C=N), 150.9 (C-4), 149.3 (C-7),
141.6 (C-1), 129.4 (C-2, C-6), 129.4 (C-9, C-11), 127.1 (C-10), 124.0 (C-
3, C-5), 121.1 (C-8, C-12).
1H NMR (500 MHz, CDCl3):  = 8.39 (1 H, s, HC=N), 7.82 (2 H, d, J = 4.9
Hz, H-8, H-12), 7.20 (2 H, d, J = 4.8 Hz, H-2, H-6), 6.94 (2 H, d, J = 5.5
Hz, H-3, H-5), 3.84 (3 H, s, OCH3), 3.81 (3 H, s, OCH3).
N-(Benzylidene)-4-bromoaniline (5f)
13C NMR (125 MHz, CDCl3):  = 162.0 (C=N), 158.0 (C-10), 145.2 (C-4),
130.3 (C-8, C-12), 129.5 (C-1), 122.1 (C-2, C-6), 114.4 (C-3, C-5), 114.2
(C-9, C-11), 55.5 (OCH3), 55.5 (OCH3).
Silver solid; yield: 1.529 g (91%); mp 65–66 °C.
1H NMR (500 MHz, CDCl3):  = 8.42 (1 H, s, HC=N), 7.93 (2 H, d, J = 7.5
Hz, H-3, H-5), 7.54–7.46 (5 H, m, H-8, H-9, H-10, H-11, H-12), 7.13 (2
H, d, J = 5.5 Hz, H-2, H-6).
Spectral data are consistent with the literature.52,53
N-(4-Methoxybenzylidene)-4-chloroaniline (5l)
Beige solid; yield: 881.6 mg (76%); mp 89–90 °C.
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1H NMR (500 MHz, CDCl3):  = 8.29 (1 H, s, HC=N), 7.79 (2 H, d, J = 8.8
Hz, H-8, H-12), 7.29 (2 H, d, J = 8.6 Hz, H-3, H-5), 7.09 (2 H, d, J = 8.6
Hz, H-2, H-6), 6.98–6.89 (2 H, m, H-9, H-11), 3.81 (3 H, s, OCH3).
ter removing DCM under reduced pressure, the crude mixture was
purified by column chromatography over 230–400 mesh SiO2 and
EtOAc/hexane (5:95) as eluent.
13C NMR (125 MHz, CDCl3):  = 162.5 (C-10), 160.0 (C=N), 150.8 (C-1),
132.0 (C-4), 131.0 (C-8, C-12), 130.7 (C-3, C-5), 129.2 (C-7), 122.8 (C-
2, C-6), 114.3 (C-9, C-11), 55.4 (OCH3).
For catalyst recycling, the reaction mixture was filtered in vacuo be-
fore extraction and washed with DCM. For catalyst reactivation, it was
additionally washed with H2O and stove-dried at 120 °C for 10 min.
Spectral data are consistent with the literature.55
cis-3-Chloro-1,4-diphenylazetidin-2-one (7a)
Orange crystals; yield: 284.4 mg (40%); mp 179–180 °C.
N-(2,4-Dichlorobenzylidene)-4-chloroaniline (5n)
White solid; yield: 1.112 g (83%); mp 127–128 °C.
1H NMR (500 MHz, CDCl3):  = 7.41–7.35 (5 H, m, H-2′, H-3′, H-4′),
7.33-7.30 (3 H, m, H-2, H-4), 7.29–7.25 (2 H, m, H-3), 5.41 (1 H, d, J =
5.3 Hz, Ha), 5.26 (1 H, d, J = 5.4 Hz, Hb).
13C NMR (125 MHz, CDCl3):  = 161.2 (C=O), 136.8 (C-1), 132.7 (C-1′),
129.2 (C-3′), 128.7 (C-2′), 127.8 (C-3), 124.9 (C-4′), 120.2 (C-4), 117.6
(C-2), 60.8 (Cb), 60.5 (Ca).
1H NMR (500 MHz, CDCl3):  = 8.82 (1 H, s, HC=N), 8.18 (1 H, d, J = 8.4
Hz, H-12), 7.45 (1 H, s, H-9), 7.36 (3 H, m, H-11, H-2, H-6), 7.18 (2 H,
d, J = 7.7 Hz, H-5, H-4).
13C NMR (125 MHz, CDCl3):  = 156.0 (C=N), 150.0 (C-1), 138.0 (C-4),
136.7 (C-7), 132.4 (C-12), 131.7 (C-10), 129.9 (C-11), 129.6 (C-8),
129.5 (C-3, C-5), 127.9 (C-9), 122.6 (C-2, C-6).
HRMS (ESI+): m/z [M + H]+ calcd for [C15H13ClNO]+: 258.0685; found:
258.0681.
N-[(E)-Cinnamylidene]-4-methoxyaniline (5o)
trans-3-Chloro-1,4-diphenylazetidin-2-one (7a′)
Silver solid; yield: 904.8 mg (78%); mp 119–120 °C.
Red oil; yield: 369.7 mg (52%).
1H NMR (500 MHz, CDCl3):  = 8.34–8.23 (1 H, m, HC=N), 7.52 (2 H, d,
J = 7.3 Hz, H-8, H-12), 7.37 (2 H, t, J = 7.3 Hz, H-9, H-11), 7.33 (1 H, d,
J = 7.1 Hz, H-14), 7.20 (2 H, d, J = 8.7 Hz, H-2, H-6), 7.09 (2 H, s, H-10,
H-13), 6.91 (2 H, d, J = 8.7 Hz, H-3, H-5), 3.80 (3 H, s, OCH3).
1H NMR (500 MHz, CDCl3):  = 7.38–7.34 (5 H, m, H-2′, H-3′, H-4′),
7.29–7.27 (3 H, m, H-2, H-4), 7.26–7.21 (2 H, m, H-3), 5.00 (1 H, d, J =
1.9 Hz, Ha), 4.58 (1 H, d, J = 1.9 Hz, Hb).
13C NMR (125 MHz, CDCl3):  = 159.5 (C=N), 158.4 (C-4), 144.6 (C-1),
143.1 (C-13), 135.8 (C-7), 129.4 (C-10), 128.9 (C-14), 128.8 (C-9, C-
11), 127.4 (C-8, C-12), 122.3 (C-2, C-6), 114.5 (C-3, C-5), 55.5 (OCH3).
13C NMR (125 MHz, CDCl3):  = 160.7 (C=O), 136.9 (C-1), 135.0 (C-1′),
129.5 (C-3′), 127.5 (C-2′), 126.2 (C-3), 124.9 (C-4′), 124.8 (C-4), 114.9
(C-2), 66.1 (Cb), 63.3 (Ca).
Spectral data are consistent with the literature.53
cis-3-Chloro-4-(4-methoxyphenyl)-1-phenylazetidin-2-one (7b)
Yellow crystals; yield: 245.2 mg (36%); mp 173–174 °C.
Methyl N-[(4-Fluorobenzylidene)amino]acetate (5p)
Amber oil; yield: 1.297 g (99%).
1H NMR (500 MHz, CDCl3):  = 7.32 (2 H, dd, J = 8.6, 1.1 Hz, H-2′), 7.27
(2 H, dd, J = 15.0, 2.8 Hz, H-2), 7.24 (2 H, d, J = 8.7 Hz, H-3), 7.13–7.07
(1 H, m, H-4), 6.93 (2 H, d, J = 8.7 Hz, H-3′), 5.37 (1 H, d, J = 5.3 Hz, Ha),
5.24 (1 H, d, J = 5.3 Hz, Hb), 3.81 (3 H, s, OCH3).
13C NMR (125 MHz, CDCl3):  = 161.4 (C=O), 160.2 (C-4′), 136.8 (C-1),
130.7 (C-2′), 124.8 (C-4), 124.4 (C-1′), 120.1 (C-3), 117.6 (C-2), 114.1
(C-3′), 60.8 (Cb), 60.5 (Ca), 55.3 (OCH3).
1H NMR (300 MHz, CDCl3):  = 8.25 (1 H, s, H-1′), 7.78–7.75 (2 H, m,
H-3′), 7.13–7.06 (2 H, td, J = 8.6, 1.7 Hz, H-4′), 4.40 (2 H, s, H-2), 3.77
(3 H, s, CO2CH3).
13C NMR (75 MHz, CDCl3):  = 170.5 (C-1), 166.3 (J = 249.7 Hz, C-5′),
163.9 (C-1′), 132.1 (C-2′), 130.5 (J = 8.2 Hz, C-3′), 115.7 (J = 21.7 Hz, C-
4’), 61.7 (C-2), 52.1 (CO2CH3).
trans-3-Chloro-4-(4-methoxyphenyl)-1-phenyazetidin-2-one
(7b′)
Methyl N-[(4-Fluorobenzylidene)amino]hexanoate (5q)
White oil; yield: 778.6 mg (86%).
Yellow solid; yield: 360.9 mg (53%); mp 89–90 °C.
1H NMR (500 MHz, CDCl3):  = 9.98 (1 H, s, H-1′), 7.94–7.91 (2 H, m,
H-3′), 7.24–7.21 (2 H, m, H-4′), 3.66 (3 H, s, CO2CH3), 3.65 (2 H, s, H-6),
2.34 (2 H, t, J = 7.4 Hz, H-2), 1.84 (2 H, dt, J = 15.4, 7.7 Hz, H-3), 1.66 (2
H, dt, J = 15.2, 7.5 Hz, H-5), 1.45 (2 H, dt, J = 15.4, 7.8 Hz, H-4).
13C NMR (125 MHz, CDCl3):  = 190.5 (C-1), 173.9 (C-1′), 166.5 (J =
256.6 Hz, C-5′), 132.9 (J = 2.7 Hz, C-2′), 132.2 (J = 9.7 Hz, C-3′), 116.3
(J = 22.3 Hz, C-4′), 51.5 (CO2CH3), 39.7 (C-6), 33.6 (C-2), 27.1 (C-5),
25.9 (C-4), 24.2 (C-3).
1H NMR (500 MHz, CDCl3):  = 7.30 (4 H, d, J = 8.7 Hz, H-2′, H-2), 7.26–
723 (2 H, m, H-3), 7.09–7.06 (1 H, m, H-4), 6.91 (2 H, d, J = 8.7 Hz, H-
3′), 4.96 (1 H, d, J = 1.9 Hz, Ha), 4.58 (1 H, d, J = 1.9 Hz, Hb), 3.79 (3 H, s,
OCH3).
13C NMR (125 MHz, CDCl3):  = 160.9 (C=O), 160.5 (C-4′), 136.9 (C-1),
129.2 (C-2′), 127.5 (C-3), 124.8 (C-4), 120.3 (C-1′), 117.6 (C-2), 114.9
(C-3′), 65.8 (Cb), 63.3 (Ca), 55.4 (OCH3).
HRMS (ESI+): m/z [M + H]+ calcd for [C16H15ClNO2]+: 288.7508; found:
288.0778.
3-Chloroazetidin-2-ones 7a–s and 8b–o; General Procedure
The imine 5 (2 mmol), the solid catalyst (5% w/w), DMF (21.0 mmol,
10.5 equiv, ca. 1.8 mL), and acyl chloride 6 (2.4 mmol, 1.2 equiv) were
placed in a 25 mL round-bottomed flask under N2 atmosphere. The
mixture was stirred at r.t. for 5 min and then irradiated by micro-
waves (300 W) in an open vessel at 180 °C for 2 min. The reaction
progress was monitored by TLC and GC-MS. Upon completion of the
reaction, the crude was extracted with DCM (3 × 10 mL) and the com-
bined organic extracts were washed with H2O, and dried (Na2SO4). Af-
cis-3-Chloro-4-(4-nitrophenyl)-1-phenylazetidin-2-one (7c)
Red solid; yield: 314.4 mg (47%); mp 152–153 °C.
1H NMR (500 MHz, CDCl3):  = 8.26 (2 H, d, J = 8.7 Hz, H-3′), 7.50 (2 H,
d, J = 8.6 Hz, H-2′), 7.33–7.25 (4 H, m, H-2, H-3), 7.18–7.11 (1 H, m, H-
4), 5.55 (1 H, d, J = 5.4 Hz, Ha), 5.36 (1 H, d, J = 5.4 Hz, Hb).
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13C NMR (125 MHz, CDCl3):  = 160.5 (C=O), 148.5 (C-4′), 140.2 (C-1′),
136.2 (C-1), 129.5 (C-2), 128.8 (C-2′), 125.4 (C-4), 124.0 (C-3′), 117.3
(C-3), 60.2 (Cb), 59.9 (Ca).
cis-3-Chloro-1-(4-bromophenyl)-4-phenylazetidin-2-one (7f)
Yellow solid; yield: 161.8 mg (25%); mp 179–180 °C.
1H NMR (500 MHz, CDCl3):  = 7.42–7.38 (5 H, m, H-3′, H-4′, H-3),
7.29–7.26 (2 H, m, H-2′), 7.20 (2 H, d, J = 8.8 Hz, H-2), 5.40 (1 H, d, J =
5.3 Hz, Ha), 5.28 (1 H, d, J = 5.3 Hz, Hb).
trans-3-Chloro-4-(4-nitrophenyl)-1-phenylazetidin-2-one (7c′)
Red oil; yield: 254.2 mg (38%).
13C NMR (125 MHz, CDCl3):  = 161.1 (C=O), 135.7 (C-1), 132.3 (C-3),
132.1 (C-1′), 129.4 (C-4′), 128.8 (C-3′), 127.8 (C-2′), 119.1 (C-2), 117.8
(C-4), 60.9 (Cb), 60.6 (Ca).
HRMS (ESI+): m/z [M + H]+ calcd for [C15H12BrClNO]+: 335.9791;
found: 335.9758.
1H NMR (500 MHz, CDCl3):  = 8.29–8.27 (2 H, m, H-3′), 7.59–7.58 (2
H, m, H-2′), 7.57–7.30 (2 H, m, H-2), 7.28–7.25 (2 H, m, H-3), 7.23–
7.14 (1 H, m, H-4), 5.14 (1 H, d, J = 1.9 Hz, Ha), 4.63 (1 H, d, J = 2.0 Hz,
Hb).
13C NMR (125 MHz, CDCl3):  = 159.9 (C=O), 148.6 (C-4′), 142.0 (C-1′),
136.3 (C-1), 129.5 (C-2), 127.1 (C-2′), 125.4 (C-4), 124.8 (C-3′), 117.4
(C-3), 64.9 (Cb), 63.0 (Ca).
trans-3-Chloro-1-(4-bromophenyl)-4-phenylazetidin-2-one (7f′)
Red solid; yield: 213.5 mg (33%); mp 140–142 °C.
HRMS (ESI+): m/z [M + H]+ calcd for [C15H12ClN2O3]+: 303.0536;
found: 303.0530.
1H NMR (500 MHz, CDCl3):  = 7.40–7.38 (3 H, m, H-4′, H-3), 7.35–
7.33 (4 H, m, H-2′, H-3′), 7.32–7.14 (2 H, m, H-2), 4.99 (1 H, d, J = 2.0
Hz, Ha), 4.60 (1 H, d, J = 2.0 Hz, Hb).
13C NMR (125 MHz, CDCl3):  = 160.7 (C=O), 135.8 (C-1), 134.5 (C-1′),
132.3 (C-3), 129.7 (C-4′), 129.6 (C-3′), 126.1 (C-2′), 119.1 (C-2), 117.8
(C-4), 66.2 (Cb), 63.4 (Ca).
cis-3-Chloro-4-(4-fluorophenyl)-1-phenylazetidin-2-one (7d)
White solid; yield: 269.9 mg (39%); mp 174–175 °C.
1H NMR (500 MHz, CDCl3):  = 7.31–7.25 (6 H, m, H-2′, H-2, H-3),
7.13–7.07 (3 H, m, H-3′, H-4), 5.41 (1 H, d, J = 5.3 Hz, Ha), 5.26 (1 H, d,
J = 5.3 Hz, Hb).
13C NMR (125 MHz, CDCl3):  = 162.2 (J = 248.4 Hz, C-4′), 161.1 (C=O),
136.6 (C-1), 129.6 (J = 8.4 Hz, C-2′), 129.3 (C-3), 128.5 (J = 2.8 Hz, C-1′),
125.0 (C-4), 117.5 (C-2), 115.8 (J = 21.9 Hz, C-3′), 60.5 (Cb), 60.2 (Ca).
cis-3-Chloro-1-(4-chlorophenyl)-4-(3-chlorophenyl)azetidin-2-
one (7g)
White crystals; yield: 359.0 mg (55%); mp 177–178 °C.
1H NMR (500 MHz, CDCl3):  = 7.39–7.33 (2 H, m, H-3), 7.29–7.23 (4
H, m, H-5′, H-2′, H-2), 7.17 (1 H, d, J = 7.4 Hz, H-6′), 5.37 (1 H, d, J = 5.3
Hz, Ha), 5.28 (1 H, d, J = 5.4 Hz, Hb).
HRMS (ESI+): m/z [M + H]+ calcd for [C15H12ClFNO]+: 276.0591; found:
276.0554.
13C NMR (125 MHz, CDCl3):  = 160.8 (C=O), 135.0 (C-1′), 134.9 (C-1),
134.4 (C-3′), 130.3 (C-6′), 130.2 (C-4), 129.7 (C-2′), 129.5 (C-3), 127.9
(C-5′), 125.9 (C-4′), 118.6 (C-2), 60.5 (Cb), 60.3 (Ca).
trans-3-Chloro-4-(4-fluorophenyl)-1-phenylazetidin-2-one (7d′)
Yellow solid; yield: 373.6 mg (54%); mp 117–118 °C.
1H NMR (500 MHz, CDCl3):  = 7.39–7.33 (2 H, m, H-2′), 7.29–7.22 (4
H, m, H-2, H-3), 7.12–7.05 (3 H, m, H-3′, H-4), 5.01 (1 H, d, J = 1.8 Hz,
Ha), 4.58 (1 H, d, J = 1.9 Hz, Hb).
trans-3-Chloro-1-(4-chlorophenyl)-4-(3-chlorophenyl)azetidin-2-
one (7g′)
13C NMR (125 MHz, CDCl3):  = 163.3 (J = 249.0 Hz, C-4′), 160.6 (C=O),
136.7 (C-1), 130.9 (J = 3.2 Hz, C-1′), 129.3 (C-3), 128.1 (J = 8.4 Hz, C-2′),
125.0 (C-4), 117.6 (C-2), 116.6 (J = 21.9 Hz, C-3′), 65.3 (Cb), 63.2 (Ca).
Dark yellow liquid; yield: 208.9 mg (32%).
1H NMR (CDCl3, 500 MHz):  = 7.40–7.35 (3 H, m, H-2′, H-3), 7.26–
7.20 (5 H, m, H-6′, H-5′, H-4′, H-2), 4.96 (1 H, d, J = 1.9 Hz, Ha), 4.62 (1
H, d, J = 2.0 Hz, Hb).
cis-3-Chloro-1-(4-nitrophenyl)-4-phenylazetidin-2-one (7e)
13C NMR (125 MHz, CDCl3):  = 160.3 (C=O), 136.7 (C-1′), 135.7 (C-1),
135.0 (C-3′), 131.0 (C-6′), 130.4 (C-4), 130.0 (C-2′), 129.5 (C-3), 126.3
(C-5′), 124.1 (C-4′), 118.7 (C-2), 65.5 (Cb), 63.3 (Ca).
HRMS (ESI+): m/z [M + H]+ calcd for [C15H11Cl3NO]+: 325.9906; found:
325.9878.
Red solid; yield: 194.0 mg (29%); mp 140–142 °C.
1H NMR (500 MHz, CDCl3):  = 8.26 (2 H, d, J = 8.7 Hz, H-3), 7.50 (2 H,
d, J = 8.6 Hz, H-3′), 7.33–7.25 (4 H, m, H-2′, H-2), 7.18–7.11 (1 H, m, H-
4′), 5.55 (1 H, d, J = 5.4 Hz, Ha), 5.36 (1 H, d, J = 5.4 Hz, Hb).
13C NMR (125 MHz, CDCl3):  = 160.5 (C=O), 148.5 (C-4), 140.2 (C-1′),
136.2 (C-1), 129.5 (C-4′), 128.8 (C-3′), 125.4 (C-2), 124.0 (C-2′), 117.3
(C-3), 60.2 (Cb), 59.9 (Ca).
cis-3-Chloro-1-(4-chlorophenyl)-4-(2-thiophen-2-yl)azetidin-2-
one (7h)
Yellow solid, yield: 147.9 mg (22%); mp 71–72 °C.
trans-3-Chloro-1-(4-nitrophenyl)-4-phenylazetidin-2-one (7e′)
1H NMR (CDCl3, 500 MHz):  = 7.39 (1 H, dd, J = 5.0, 1.2 Hz, H-3′),
7.32–7.27 (2 H, m, H-3), 7.27–7.22 (2 H, m, H-2), 7.12–7.09 (1 H, m,
H-4′), 7.06 (1 H, dd, J = 5.0, 3.6 Hz, H-5′), 5.65 (1 H, d, J = 5.2 Hz, Ha),
5.28 (1 H, d, J = 5.2 Hz, Hb).
13C NMR (125 MHz, CDCl3):  = 160.9 (C=O), 135.3 (C-1′), 135.1 (C-1),
130.2 (C-4), 129.4 (C-3), 128.2 (C-3′), 127.4 (C-4′), 127.1 (C-5′), 118.7
(C-2), 61.2 (Cb), 57.3 (Ca).
Red solid; yield: 194.0 mg (29%); mp 140–142 °C.
1H NMR (500 MHz, CDCl3):  = 8.16 (2 H, d, J = 9.1 Hz, H-3), 7.49–7.34
(7 H, m, H-2′, H-3′, H-4′, H-2), 5.10 (1 H, d, J = 2.0 Hz, Ha), 4.71 (1 H, d,
J = 2.1 Hz, Hb).
13C NMR (125 MHz, CDCl3):  = 161.3 (C=O), 144.1 (C-4), 141.8 (C-1),
133.9 (C-1′), 130.1 (C-4′), 129.8 (C-3′), 125.9 (C-2), 125.3 (C-2′), 117.5
(C-3), 66.7 (Cb), 63.5 (Ca).
trans-3-Chloro-1-(4-chlorophenyl)-4-(2-thiophen-2-yl)azetidin-
2-one (7h′)
HRMS (ESI+): m/z [M + H]+ calcd for [C15H12ClN2O3]+: 303.0536;
found: 303.0497.
Dark yellow solid, yield: 147.9 mg (22%); mp 95–96 °C.
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1H NMR (CDCl3, 500 MHz):  = 7.50 (1 H, d, J = 3.4 Hz, H-3′), 7.34–7.29
(2 H, m, H-3), 7.28–7.23 (2 H, m, H-2), 7.19 (1 H, d, J = 3.2 Hz, H-4′),
7.15 (1 H, dd, J = 5.0, 3.8 Hz, H-5′), 5.26 (1 H, d, J = 1.8 Hz, Ha), 4.74 (1
H, d, J = 1.9 Hz, Hb).
13C NMR (125 MHz, CDCl3):  = 159.9 (C=O), 136.6 (C-1′), 135.9 (C-1),
131.2 (C-4), 129.4 (C-3′), 129.2 (C-3), 128.9 (C-4′), 127.3 (C-5′), 121.5
(C-2), 64.0 (Cb), 62.0 (Ca).
cis-3-Chloro-1-(4-chlorophenyl)-4-(4-methoxyphenyl)azetidin-2-
one (7l)
White solid; yield: 301.5 mg (46%); mp 180–181 °C.
1H NMR (500 MHz, CDCl3):  = 7.24–7.09 (6 H, m, H-2′, H-2, H-3), 6.85
(2 H, d, J = 8.4 Hz, H-3′), 5.28 (1 H, d, J = 5.1 Hz, Ha), 5.17 (1 H, d, J = 5.2
Hz, Hb), 3.74 (3 H, s, OCH3).
13C NMR (125 MHz, CDCl3):  = 161.3 (C=O), 160.4 (C-4′), 135.3 (C-1),
130.0 (C-4), 129.3 (C-2′), 129.2 (C-3), 123.9 (C-1′), 118.8 (C-2), 114.2
(C-3′), 60.9 (Cb), 60.7 (Ca), 55.3 (OCH3).
HRMS (ESI+): m/z [M + H]+ calcd for [C13H10Cl2NOS]+: 297.9860;
found: 297.9837.
cis-3-Chloro-1-(4-methoxyphenyl)-4-(4-nitrophenyl)azetidin-2-
one (7j)
trans-3-Chloro-1-(4-chlorophenyl)-4-(4-methoxyphenyl)azeti-
din-2-one (7l′)
Red crystals; yield: 357.1 mg (55%); mp 136–137 °C.
White solid; yield: 262.2 mg (40%); mp 164–165 °C.
1H NMR (500 MHz, CDCl3):  = 8.25 (2 H, d, J = 8.4 Hz, H-3′), 7.49 (2 H,
d, J = 8.6 Hz, H-2′), 7.22 (2 H, d, J = 9.0 Hz, H-2), 6.82 (2 H, d, J = 9.0 Hz,
H-3), 5.53 (1 H, d, J = 4.9 Hz, Ha), 5.35 (1 H, d, J = 5.2 Hz, Hb), 3.75 (3 H,
s, OCH3).
13C NMR (125 MHz, CDCl3):  = 160.0 (C=O), 157.0 (C-4), 148.4 (C-1′),
140.4 (C-4′), 129.7 (C-1), 128.9 (C-2′), 123.9 (C-3′), 118.7 (C-2), 114.7
(C-3), 60.3 (Cb), 60.0 (Ca), 55.5 (OCH3).
1H NMR (500 MHz, CDCl3):  = 7.27 (2 H, d, J = 8.7 Hz, H-2), 7.23–7.18
(4 H, m, H-2′, H-3), 6.93 (2 H, d, J = 8.7 Hz, H-3′), 4.95 (1 H, d, J = 1.9
Hz, Ha), 4.60 (1 H, d, J = 1.9 Hz, Hb), 3.81 (3 H, s, OCH3).
13C NMR (125 MHz, CDCl3):  = 160.8 (C=O), 160.6 (C-4′), 135.3 (C-1),
130.0 (C-4), 129.3 (C-2′), 127.5 (C-3), 126.3 (C-1′), 118.8 (C-2), 114.9
(C-3′), 66.0 (Cb), 63.4 (Ca), 55.4 (OCH3).
HRMS (ESI+): m/z [M + Na]+ calcd for [C16H13Cll2NO2Na]+: 344.0221;
found: 344.0289.
HRMS (ESI+): m/z [M + H]+ calcd for [C16H13ClN2O4]+: 332.0564;
found: 332.0825.
cis-3-Bromo-1-(4-methoxyphenyl)-4-(4-nitrophenyl)azetidin-2-
one (7m)
trans-3-Chloro-1-(4-methoxyphenyl)-4-(4-nitrophenyl)azetidin-
2-one (7j′)
Brown solid; yield: 404.8 mg (55%); mp 129–130 °C.
Yellow crystals; yield: 259.7 mg (40%); mp 139–140 °C.
1H NMR (500 MHz, CDCl3):  = 8.25 (2 H, d, J = 8.4 Hz, H-3′), 7.49 (2 H,
d, J = 8.6 Hz, H-2′), 7.22 (2 H, d, J = 9.0 Hz, H-2), 6.82 (2 H, d, J = 9.0 Hz,
H-3), 5.53 (1 H, d, J = 4.9 Hz, Ha), 5.35 (1 H, d, J = 5.2 Hz, Hb), 3.75 (3 H,
s, OCH3).
13C NMR (125 MHz, CDCl3):  = 160.0 (C=O), 157.0 (C-4), 148.4 (C-1′),
140.4 (C-4′), 129.7 (C-1), 128.9 (C-2′), 123.9 (C-3′), 118.7 (C-2), 114.7
(C-3), 60.3 (Cb), 60.0 (Ca), 55.5 (OCH3).
1H NMR (500 MHz, CDCl3):  = 8.26 (2 H, d, J = 8.7 Hz, H-3′), 7.58 (2 H,
d, J = 8.7 Hz, H-2′), 7.19 (2 H, d, J = 9.0 Hz, H-2), 6.81 (2 H, d, J = 9.0 Hz,
H-3), 5.12 (1 H, d, J = 1.6 Hz, Ha), 4.64 (1 H, d, J = 1.8 Hz, Hb), 3.75 (3 H,
s, OCH3).
13C NMR (125 MHz, CDCl3):  = 159.4 (C=O), 157.1 (C-4), 148.6 (C-1′),
142.2 (C-4′), 129.6 (C-1), 127.3 (C-2′), 124.7 (C-3′), 118.9 (C-2), 114.7
(C-3), 65.0 (Cb), 63.0 (Ca), 55.5 (OCH3).
HRMS (ESI+): m/z [M + H]+ calcd for [C16H14BrN2O4]+: 377.0137;
found: 377.0095.
cis-3-Chloro-1-(4-methoxyphenyl)-4-(4-methoxyphenyl)azetidin-
2-one (7k)
cis-3-Chloro-N-(4-chlorophenyl)-4-(2,4-dichlorobenzyl)azetidin-
2-one (7n)
White solid; yield: 302.9 mg (46%); mp 165–166 °C.
1H NMR (500 MHz, CDCl3):  = 7.26 (2 H, d, J = 9.1 Hz, H-2′), 7.22 (2 H,
d, J = 8.7 Hz, H-2), 6.92 (2 H, d, J = 8.7 Hz, H-3), 6.79 (2 H, d, J = 9.1 Hz,
H-3′), 5.32 (1 H, d, J = 5.2 Hz, Ha), 5.22 (1 H, d, J = 5.2 Hz, Hb), 3.81 (3 H,
s, C4-OCH3), 3.74 (3 H, s, C4′-OCH3).
13C NMR (125 MHz, CDCl3):  = 160.8 (C=O), 160.2 (C-4′), 156.7 (C-4),
130.3 (C-1′), 129.2 (C-2′), 124.5 (C-1), 118.9 (C-2), 114.4 (C-3), 114.1
(C-3′), 60.9 (Cb), 60.6 (Ca), 55.4 (C4-OCH3), 55.3 (C4′-OCH3).
White crystals; yield: 266.4 mg (42%); mp 151–152 °C.
1H NMR (500 MHz, CDCl3):  = 7.52 (1 H, s, H-3′), 7.27 (5 H, m, H-5′, H-
3, H-2), 7.07 (1 H, d, J = 8.4 Hz, H-6′), 5.73 (1 H, d, J = 5.2 Hz, Ha), 5.38
(1 H, d, J = 5.2 Hz, Hb).
13C NMR (125 MHz, CDCl3):  = 160.8 (C=O), 135.8 (C-1′), 135.0 (C-1),
134.4 (C-4′), 130.6 (C-3′), 130.0 (C-4), 129.7 (C-2′), 129.3(C-3), 129.1
(C-5′), 127.6 (C-2), 118.7 (C-6′), 60.2 (Cb), 58.1 (Ca).
trans-3-Chloro-1-(4-methoxyphenyl)-4-(4-methoxyphenyl)azeti-
din-2-one (7k′)
trans-3-Chloro-1-(4-chlorophenyl)-4-(2,4-dichlorophenyl)azeti-
din-2-one (7n′)
White crystals; yield: 204.1 mg (31%); mp 112–113 °C.
White crystals; yield: 272.8 mg (43%); mp 131–132 °C.
1H NMR (500 MHz, CDCl3):  = 7.52 (1 H, s, H-3′), 7.24 (5 H, m, H-5′, H-
3, H-2), 7.11 (1 H, d, J = 8.4 Hz, H-6′), 5.73 (1 H, s, Ha), 5.38 (1 H, s, Hb).
13C NMR (125 MHz, CDCl3):  = 160.4 (C=O), 136.0(C-1′), 135.1 (C-1),
134.2(C-4′), 130.9 (C-3′), 130.6 (C-4), 130.5 (C-2′), 129.7 (C-3), 128.2
(C-5′), 127.8 (C-2), 118.8 (C-6′), 62.7 (Cb), 62.3 (Ca).
1H NMR (500 MHz, CDCl3):  = 7.26 (2 H, d, J = 8.7 Hz, H-2′), 7.22 (2 H,
d, J = 9.1 Hz, H-2), 6.90 (2 H, d, J = 8.7 Hz, H-3′), 6.76 (2 H, d, J = 9.1 Hz,
H-3), 4.90 (1 H, d, J = 1.7 Hz, Ha), 4.55 (1 H, d, J = 1.9 Hz, Hb), 3.78 (3 H,
s, C4-OCH3), 3.71 (3 H, s, C4′-OCH3).
13C NMR (125 MHz, CDCl3):  = 160.5 (C=O), 160.2 (C-4′), 156.7 (C-4),
130.3 (C-1′), 127.5 (C-2′), 126.9 (C-1), 118.9 (C-2), 114.8 (C-3), 114.4
(C-3′), 65.9 (Cb), 63.4 (Ca), 55.3 (C4-OCH3), 55.2 (C4′-OCH3).
cis-3-Chloro-1-(4-methoxyphenyl)-4-[(E)-styryl]azetidin-2-one
(7o)
HRMS (ESI+): m/z [M + H]+ calcd for [C17H17ClNO3]+: 318.0897; found:
318.1517.
Brown solid; yield: 171.9 mg (26%); mp 122–123 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–M

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1H NMR (500 MHz, CDCl3):  = 7.43 (2 H, dd, J = 16.5, 8.1 Hz, H-2), 7.35
(2 H, t, J = 7.3 Hz, H-5′), 7.31 (2 H, d, J = 7.2 Hz, H-4′), 6.88–6.81 (2 H,
m, H-2′, H-6′), 6.86–6.82 (2 H, m, H-3), 6.29 (1 H, dd, J = 15.9, 8.5 Hz,
H-1′), 5.17 (1 H, d, J = 5.2 Hz, Ha), 4.92 (1 H, dd, J = 8.4, 5.2 Hz, Hb), 3.76
(3 H, s, OCH3).
13C NMR (125 MHz, CDCl3):  = 164.4 (C=O), 156.8 (C-4), 137.5 (C-2′),
135.5 (C-3′), 130.8 (C-1), 128.8 (C-4′, C-6′), 126.9 (C-5′), 123.1 (C-1′),
118.8 (C-2), 114.5 (C-3), 60.3 (Cb), 59.8 (Ca), 55.5 (OCH3).
13C NMR (151 MHz, CDCl3)  = 157.7 (C=O), 157.2 (C-4), 148.9 (C-4′),
138.9 (C-1′), 128.9 (C-2′), 128.6 (C-1), 124.3 (C-3′), 119.4 (C-2), 114.9
(C-3), 83.8 (CCl2), 72.9 (Cb), 55.6 (OCH3).
HRMS (ESI+): m/z [M + H]+ calcd for [C16H12Cl2N2O4]+: 366.0174;
found: 366.0168.
3,3-Dichloro-1,4-bis(4-methoxyphenyl)azetidin-2-one (7s)
White solid; yield: 605.8 mg (83%); mp 128–130 °C.
HRMS (ESI+): m/z [M + H]+ calcd for [C18H17ClNO2]+: 314.0948; found:
314.0910.
1H NMR (600 MHz, CDCl3):  = 7.26 (4 H, dd, J = 12.9, 5.7 Hz, H-3, H-
3′), 6.95 (2 H, d, J = 8.7 Hz, H-2), 6.82 (2 H, d, J = 9.0 Hz, H-2′), 5.45 (1
H, s, Hb), 3.82 (3 H, s, C4′-OCH3), 3.76 (3 H, s, C4-OCH3).
13C NMR (151 MHz, CDCl3):  = 160.8 (C=O), 158.0 (C-4′), 157.2 (C-4),
129.3 (C-2′), 129.2 (C-1), 123.5 (C-1′), 119.5 (C-2), 114.6 (C-3), 114.4
(C-3′), 84.6 (CCl2), 73.8 (Cb) 55.5 (C4′-OCH3), 55.4 C4-OCH3).
trans-3-Chloro-1-(4-methoxyphenyl)-4-[(E)-styryl]azetidin-2-
one (7o′)
White crystals; yield: 211.6 mg (32%); mp 120–121 °C.
1H NMR (500 MHz, CDCl3):  = 7.40–7.38 (4 H, m, H-5′, H-2), 7.36–
7.30 (3 H, m, H-4′, H-6′), 6.90–6.87 (1 H, m, H-2′), 6.86–6.83 (2 H, m,
H-3), 6.23 (1 H, dd, J = 15.9, 8.4 Hz, H-1′), 4.65 (1 H, d, J = 1.9 Hz, Ha),
4.63 (1 H, ddd, J = 8.4, 1.9. 0.6 Hz, Hb), 3.76 (3 H, s, OCH3).
13C NMR (125 MHz, CDCl3):  = 159.9 (C=O), 156.8 (C-4), 136.4 (C-2′),
135.1 (C-3′), 130.7 (C-1), 128.9 (C-6′), 128.8 (C-4′), 126.9 (C-5′), 123.6
(C-1′), 118.9 (C-2), 114.5 (C-3), 65.3 (Cb), 61.4 (Ca), 55.5 (OCH3).
HRMS (ESI+): m/z [M + H]+ calcd for [C17H14Cl2NO3]+: 350.0351;
found: 351.0424.
3,3-Dichloro-1-(4-chlorophenyl)-4-(2,4-dichlorophenyl)azetidin-
2-one (7t)
Yellow oil; yield: 618.5 mg (89%).
1H NMR (600 MHz, CDCl3):  = 7.48–7.43 (1 H, m, H-3′), 7.41 (2 H, d,
J = 8.7 Hz, H-3), 7.31 (2 H, d, J = 5.6 Hz, H-5′, H-6′), 7.20 (2 H, d, J = 8.7
Hz, H-2), 5.50 (1 H, s, Hb).
13C NMR (151 MHz, CDCl3):  = 158.4 (C=O), 134.9 (C-2′), 132.5 (C-3),
131.2 (C-1), 130.2 (C-3′, C-4), 129.2 (C-5′, C-6′), 127.8 (C-1′), 119.7 (C-
2), 118.7 (C-4′), 84.2 (CCl2) 74.2 (Cb).
Methyl 2-[trans-3-Chloro-4-(4-fluorophenyl)-4-oxoazetidin-1-
yl]acetate (7p′)
Yellow oil; yield: 570.6 mg (82%).
1H NMR (500 MHz, CDCl3):  = 7.39–7.36 (2 H, m, H-2′), 7.14–7.11 (2
H, m, H-3′), 4.90 (1 H, d, J = 1.9 Hz, Ha), 4.60 (1 H, d, J = 1.9 Hz, Hb), 4.36
(1 H, d, J = 18.1 Hz, H-2, H-2), 3.72 (3H, s, OCH3), 3.58 (1 H, d, J =
18.0 Hz, H-2, H-2).
13C NMR (125 MHz, CDCl3):  = 167.7 (C-1), 164.3 (J = 248.9 Hz, C-4′),
163.8 (C=O), 130.3 (J = 3.8 Hz, C-1′), 128.7 (J = 8.5 Hz, C-2′), 116.3 (J =
21.8 Hz, C-3′), 65.2 (Cb), 63.5 (Ca), 52.4 (OCH3), 41.6 (C-2).
cis-3-Bromo-1-(4-chlorophenyl)-4-(2,4-dichlorophenyl)azetidin-
2-one (7u)
White solid; yield: 270.8 mg (38%); mp 186–187 °C.
1H NMR (300 MHz, CDCl3):  = 7.46–7.37 (3 H, m, H-3, H-3′), 7.30–
7.24 (2 H, m, H-5′, H-6′), 7.21 (2 H, d, J = 8.8 Hz, H-2), 5.39 (2 H, s, Ha,
Hb).
13C NMR (75 MHz, CDCl3):  = 161.1 (C=O), 135.9 (C-2′), 133.3 (C-1),
132.4 (C-3′, C-6′), 129.5 (C-5′), 128.9 (C-3), 127.7 (C-4, C-4′), 119.1 (C-
2), 117.8 (C-1′), 59.8 (Ca), 50.4 (Cb).
HRMS (ESI+): m/z [M + H]+ calcd for [C12H12ClFNO3]+: 272.0489;
found: 272.0461.
Methyl 6-[trans-3-Chloro-4-(4-fluorophenyl)-4-oxoazetidin-1-
yl]hexanoate (7q′)
Yellow oil; yield: 521.7 mg (80%).
trans-3-Bromo-1-(4-chlorophenyl)-4-(2,4-dichlorophenyl)azeti-
din-2-one (7u′)
1H NMR (500 MHz, CDCl3):  = 7.30 (2 H, dd, J = 8.6, 5.2 Hz, H-2′), 7.13
(2 H, t, J = 8.5 Hz, H-3′), 4.53 (1 H, d, J = 1.4 Hz, Ha), 4.47 (1 H, d, J = 1.1
Hz, Hb), 3.66 (3 H, s, OCH3), 3.24–3.13 (2 H, m, H-6), 2.59 (2 H, t, J = 7.4
Hz, H-2), 1.70–1.55 (4 H, m, H-3, H-5), 1.52 (2 H, dt, J = 14.8, 7.4 Hz, H-
4).
13C NMR (125 MHz, CDCl3):  = 173.8 (C-1), 161.7 (C=O), 160.3 (J =
246.4 Hz, C-4′), 131.0 (J = 2.6 Hz, C-1′), 128.4 (J = 8.4 Hz, C-2′), 116.4
(J = 21.9 Hz, C-3′), 65.4 (Cb), 63.1 (Ca), 51.6 (OCH3), 40.9 (C-6), 33.7 (C-
2), 27.1 (C-5), 26.3 (C-4), 24.3 (C-3).
Yellow oil; yield: 228.0 mg (32%).
1H NMR (600 MHz, CDCl3):  = 7.44–7.39 (2 H, m, H-5′, H-3′), 7.39–
7.34 (3 H, m, H-3, H-6′), 7.17 (2 H, d, J = 8.8 Hz, H-2), 5.09 (1 H, s, Ha),
4.64 (1 H, d, J = 1.9 Hz, Hb).
13C NMR (151 MHz, CDCl3):  = 160.7 (C=O), 136.0 (C-2′), 134.8 (C-1),
132.3 (C-3′, C-6′), 129.8 (C-5′), 129.7 (C-3), 126.1 (C-4, C-4′), 119.1 (C-
2), 117.8 (C-1′), 66.1 (Ca), 50.1 (Cb).
HRMS (ESI+): m/z [M + H]+ calcd for [C16H20ClFNO3]+: 328.1115;
found: 328.1078.
cis-1-(4-Methoxyphenyl)-2-(4-nitrophenyl)-4-oxoazetidin-3-yl
Acetate (7v)
Orange oil; yield: 83.4 mg (12%).
3,3-Dichloro-1-(4-methoxyphenyl)-4-(4-nitrophenyl)azetidin-2-
one (7r)
1H NMR (600 MHz, CDCl3):  = 8.23 (2 H, d, J = 8.8 Hz, H-3′), 7.50 (2 H,
d, J = 8.7 Hz, H-2′), 7.23 (2 H, d, J = 9.0 Hz, H-2), 6.82 (2 H, d, J = 9.1 Hz,
H-3), 6.00 (1 H, d, J = 5.0 Hz, Ha), 5.45 (1 H, d, J = 5.0 Hz, Hb), 3.76 (3 H,
s, OCH3), 1.74 (3 H, s, CO2CH3).
Yellow oil; yield: 651.9 mg (91%).
1H NMR (600 MHz, CDCl3):  = 8.28 (2 H, d, J = 6.6 Hz, H-3′), 7.52 (2 H,
d, J = 6.8 Hz, H-2′), 7.21 (2 H, d, J = 6.8 Hz, H-2), 6.84 (2 H, dd, J = 8.9,
2.1 Hz, H-3), 5.60 (1 H, s, Hb ), 3.76 (2 H, s, OCH3).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–M

L
A. Galván et al.
Paper
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13C NMR (151 MHz, CDCl3):  = 169.9 (CO2CH3), 160.2 (C=O), 142.3 (C-
4′), 129.9 (C-4), 127.5 (C-3′), 124.4 (C-2′), 122.2 (C-1′), 118.8 (C-2),
114.6 (C-3), 114.3 (C-1), 82.4 (Ca), 63.0 (Cb), 55.5 (OCH3), 20.4
(CO2CH3).
(Z)-2-Chloro-N-(4-chlorophenyl)-3-(2-thiophen-2-yl)acrylamide
(8h)
Brown crystals; yield: 262.3 mg (39%); mp 136–137 °C.
1H NMR (500 MHz, CDCl3):  = 8.31 (1 H, s, NH), 7.61–7.55 (3 H, m, H-
3, H-3′), 7.51 (1 H, d, J = 3.7 Hz, H-5′′), 7.35–7.30 (3 H, m, H-4′′, H-2′),
7.14 (1 H, td, J = 5.0, 2.1 Hz, H-3′′).
13C NMR (125 MHz, CDCl3):  = 159.9 (C-1), 136.6 (C-4′), 135.9 (C-5′′),
134.5 (C-1′′), 131.2 (C-3), 130.1 (C-1′), 129.2 (C-2′), 129.0 (C-4′′),
127.3 (C-3′′), 121.5 (C-3′), 119.6 (C-2).
trans-1-(4-Methoxyphenyl)-2-(4-nitrophenyl)-4-oxoazetidin-3-yl
Acetate (7v′)
Yellow oil; yield: 69.5 mg (10%).
1H NMR (600 MHz, CDCl3):  = 8.25 (2 H, d, J = 6.6 Hz, H-3′), 7.29–7.24
(2 H, m, H-2′), 7.19 (2 H, dd, J = 9.1, 2.3 Hz, H-2), 6.81 (2 H, dd, J = 9.2,
2.2 Hz, H-3), 5.28 (1 H, s, Ha), 5.00 (1 H, s, Hb), 3.76 (3 H, s, OCH3), 2.22
(3 H, s, CO2CH3).
HRMS (ESI+): m/z [M + H]+ calcd for [C13H10Cl2NOS]+: 297.9860;
found: 298.0480.
13C NMR (151 MHz, CDCl3):  = 169.1 (CO2CH3), 160.6 (C=O), 140.0 (C-
4), 129.7 (C-4′), 128.9 (C-3′), 123.7 (C-2′), 122.2 (C-1′), 118.7 (C-2),
114.7 (C-3), 114.3 (C-1), 76.4 (Ca), 60.7 (Cb), 55.5 (OCH3), 19.9
(CO2CH3).
HRMS (ESI+): m/z [M + H]+ calcd for [C18H16N2O6]+: 356.1008; found:
356.1006.
(Z)-2-Chloro-N-(4-chlorophenyl)-3-(2-furan-2-yl)acrylamide (8i)
Red solid; yield: 274.4 mg (40%); mp 140–141 °C.
1H NMR (500 MHz, CDCl3):  = 8.44 (1 H, s, NH), 8.02 (1 H, s, H-3),
7.60–7.58 (3 H, m, H-3′′, H-3′), 7.33 (2 H, d, J = 8.6 Hz, H-2′), 7.17 (1 H,
d, J = 3.2 Hz, H-4′′), 6.58 (1 H, s, H-5′′).
13C NMR (125 MHz, CDCl3):  = 159.7 (C-1), 149.4 (C-1′′), 145.0 (C-3′′),
135.8 (C-4′), 130.1 (C-2), 129.2 (C-3′), 123.6 (C-1′), 121.4 (C-3), 119.4
(C-2′), 116.6 (C-4′′), 112.6 (C-5′′).
(Z)-2-Chloro-3-(4-methoxyphenyl)-1-phenylacrylamide (8b)
White solid; yield: 68.1 mg (10%); mp 167–168 °C.
HRMS (ESI+): m/z [M + H]+ calcd for [C13H10Cl2NO2]+: 282.0089;
found: 282.0058.
1H NMR (200 MHz, CDCl3):  = 8.50 (1 H, s, NH), 8.07 (1 H, s, H-3), 7.82
(2 H, d, J = 8.8 Hz, H-2′), 7.64 (2 H, d, J = 7.5 Hz, H-2′′), 7.37 (2 H, t, J =
7.5 Hz, H-3′), 7.16 (1 H, t, J = 7.3 Hz, H-4′), 6.95 (2 H, dt, J = 8.9, 2.8 Hz,
H-3′′), 3.85 (3 H, s, OCH3).
13C NMR (50 MHz, CDCl3):  = 161.1 (C-1), 160.5 (C-4′′), 137.5 (C-1′),
134.5 (C-3), 132.6 (C-2′′), 129.2 (C-3′), 125.8 (C-1′′), 125.0 (C-4′),
120.6 (C-2), 120.4 (C-2′), 114.2 (C-3′′), 55.5 (OCH3).
(Z)-2-Chloro-N-(4-methoxyphenyl)-3-(4-methoxyphenyl)acryl-
amide (8k)
White crystals; yield: 79.0 mg (12%); mp 146–147 °C.
1H NMR (500 MHz, CDCl3):  = 8.42 (1 H, s, NH), 8.04 (1 H, s, H-3), 7.79
(2 H, d, J = 8.8 Hz, H-2′), 7.52 (2 H, d, J = 9.0 Hz, H-2′′), 6.93 (2 H, d, J =
8.9 Hz, H-3′), 6.88 (2 H, d, J = 9.0 Hz, H-3′′), 3.82 (3 H, s, C4′-OCH3),
3.78 (3 H, s, C4′′-OCH3).
HRMS (ESI+): m/z [M + H]+ calcd for [C16H15ClNO2]+: 288.0791; found:
288.1411.
13C NMR (125 MHz, CDCl3):  = 160.9 (C-1), 160.3 (C-4′′), 156.9 (C-4′),
134.0 (C-3), 132.4 (C-2′′), 130.5 (C-1′), 125.8 (C-1′′), 122.1 (C-2), 120.6
(C-2′), 114.2 (C-3′), 114.0 (C-3′′), 55.5 (C4′-OCH3), 55.3 (C4′′-OCH3) .
HRMS (ESI+): m/z [M + Na]+ calcd for [C17H16ClNO3Na]+: 340.0717;
found: 340.0778.
(Z)-2-Chloro-N-(4-nitrophenyl)-3-phenylacrylamide (8e)
White solid; yield: 167.3 mg (25%); mp 167–168 °C.
1H NMR (500 MHz, CDCl3):  = 8.80 (1 H, s, NH), 8.28 (2 H, d, J = 9.0 Hz,
H-3′), 8.16 (1 H, s, H-3), 7.84 (4 H, dd, J = 11.7, 8.5 Hz, H-2′′, H-2′), 7.46
(3 H, d, J = 6.8 Hz, H-3′′, H-4′′).
13C NMR (125 MHz, CDCl3):  = 162.4 (C-1), 144.2 (C-4′), 142.9 (C-1′),
136.3 (C-3), 132.7 (C-1′′), 130.6 (C-2′′), 130.5 (C-2), 128.7 (C-3′′),
125.1 (C-3′), 121.9 (C-4′′), 119.7 (C-2′).
Funding Information
HRMS (ESI+): m/z [M + H]+ calcd for [C15H12ClN2O3]+: 303.0536;
found: 303.0501.
The authors acknowledge financial support from CONACYT-SENER
(fellowship grant 177007). We recognize the spectroscopy services
provided by the National Laboratory of the Universidad de Guanajua-
to (UG-UAA-CONACYT Grant 260373). ACGC and FNCD received
(Z)-2-Chloro-N-(4-bromophenyl)-3-phenylacrylamide (8f)
scholarships from CONACYT (551221 and 366790, respectively).
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Yellow solid; yield: 219.9 mg (34%); mp 125–126 °C.
1H NMR (500 MHz, CDCl3):  = 8.51 (1 H, s, NH), 8.12 (1 H, s, H-3), 7.80
(2 H, d, J = 6.9 Hz, H-3′), 7.59–7.37 (7 H, m, H-2′′, H-3′′, H-4′′, H-2′).
13C NMR (125 MHz, CDCl3):  = 160.0 (C-1), 136.3 (C-4′′), 135.3 (C-3),
133.0 (C-1′), 132.1 (C-3′), 130.5 (C-2′′), 130.1 (C-2), 128.6 (C-3′′),
122.6 (C-1′′), 121.8 (C-2′), 117.8 (C-4′).
Acknowledgment
The authors wish to thank CONACYT as well as University of Guana-
juato (DAIP) for providing the financial support that enabled this proj-
ect to be carried out.
HRMS (ESI+): m/z [M + H]+ calcd for [C15H12BrClNO]+: 335.9791;
found: 335.9750.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1611851.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–M

M
A. Galván et al.
Paper
Synthesis
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–M