Synthesis of E/Z N-(1-Chlorovinyl)formamide Using Vilsmeier–Haack Reaction

Article abstract of DOI:10.1002/bkcs.11673

Synthesis of a variety of novel Z/E N-(1-chlorovinyl)formamides through Vilsmeier–Haack reaction starting from 2-phenoxyethanamides with POCl₃/DMF has been accomplished. The reactions introduced chlorine atom to the C_α-position and p

Full text of DOI:10.1002/bkcs.11673

Article
DOI: 10.1002/bkcs.11673
BULLETIN OF THE
L. Tang et al.
KOREAN CHEMICAL SOCIETY
Synthesis of E/Z N-(1-Chlorovinyl)formamide Using Vilsmeier–Haack
Reaction
‡
‡,
Linlin Tang,† Jingtao Wang,† Xiaojiao Xia,† Hua Zuo,†, Kyung-Min Choi, and Dong-Soo Shin
*
*
†College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China.
*E-mail: zuohua@swu.edu.cn
‡Department of Chemistry, Changwon National University, Changwon 51140, South Korea.
*E-mail: dsshin@changwon.ac.kr
Received November 24, 2018, Accepted January 3, 2019
Synthesis of a variety of novel Z/E N-(1-chlorovinyl)formamides through Vilsmeier–Haack reaction start-
ing from 2-phenoxyethanamides with POCl3/DMF has been accomplished. The reactions introduced chlo-
rine atom to the Cα-position and phenoxy substitutions to the Cβ-position of N-vinylformamides, and the
Z/E isomers of N-(1-chlorovinyl)formamide were isolated and characterized. In most cases, Z/E N-
(1-chlorovinyl)formamides were both obtained; however, for the steric hindrance reason, the reaction
starting from cyclohexylamine afforded sole Z isomer of N-(1-chloro-2-(2,4-dichlorophenoxy)vinyl)-N-
cyclohexylformamide as the highly regioselective product.
Keywords: Vilsmeier–Haack reaction, N-(1-chlorovinyl)formamide, Z/E isomers, 2-phenoxyethanamide
derivatives, Regioselective
Introduction
position of NVFs and the Z/E isomers of NVF greatly
enrich the substrate versatility of enamides.
Enamide moieties are an important functional group
involved in the synthesis of natural products and bioactive
molecules.1–4 Enamides contain nitrogen atom, and such
building blocks represent a powerful platform to produce
many complex nitrogen-containing compounds. Therefore,
the functionalized enamides provide key intermediates in
the organic synthesis community. Metal-catalyzed regiose-
lective functionalization of enamides represents a rapid
method to synthesize useful enamides for further synthesis
of heterocycle-containing compounds.5–11 Such effective
pathways avoid tedious and expensive substrate preactiva-
tion steps. N-Vinylformamides (NVFs), the simplest mem-
ber of the enamide family, are stable enamide or enamine
surrogates and have been endowed with fine physical and
chemical characteristics which make them highly attractive
on both commercial and scientific perspectives.12 In this
context, various methods for the preparation of N-
vinylenamide derivatives have been developed13–19 even to
the commercial scale.20 Among these derivatives, α-halo
eneformamides are good substrates for α- and
α,β-functionalization to afford functionalized heterocycles
via coupling reactions,21 which avoid the lability of the
substrates under the coupling conditions.22,23 We therefore
focus on the synthesis of Z/E N-(1-chlorovinyl)formamide
derivatives through Vilsmeier–Haack reaction.24,25 Such
simple and effective route does not require the use of metal
catalysts. Furthermore, the introduction of chlorine atom to
the Cα-position and phenoxy substitutions to the Cβ-
Result and Discussions
In our initial study, 2-(2-chlorophenoxy)-N-propylacetamide
4a, obtained by first acylation of n-propyl amine and subse-
quent O-alkylation of 2-chlorophenol 3, was used to react
with Vilsmeier reagent (DMF/POCl3) at 0–40 ꢀC
(Scheme 1). The reaction was monitored by thin-layer chro-
matography. Interestingly, two major products less polar than
the intermediate 4 were afforded. The two products were
then isolated by silica gel column and further characterized
by 1H NMR (Figure S1, S4), 13C NMR (Figure S2, S5), and
HRMS (Figure S3, S6). Much to our surprise, the two com-
pounds represented identical 1H NMR and 13C NMR spectra
and mass spectra. Note that odd molecular mass was found
in mass spectroscopy, and it was reasoned that both the two
new products contained nitrogen atom with odd number.
It was further observed that the intensities of the peaks m/z
M: (M + 2): (M + 4) (Figure S3, S6) followed the ratio of
9:6:1, we, therefore, speculated that both the two compounds
contained two chlorine atoms. Overall, the results proved that
the Vilsmeier–Haack reaction of 2-(2-chlorophenoxy)-N-
propylacetamide 4a afforded two novel N-(1-chlorovinyl)
formamides isomers, (E)-N-propyl-N-(1-chloro-2-(2-chloro-
phenoxy)vinyl)form amide (E)-5a and (Z)-N-propyl-N-
(1-chloro-2-(2-chlorophenoxy)vinyl)formamide (Z)-5a, both
in good yields. The hydrogen atom in the aldehyde group of
E isomer (E)-5a may have formed a hydrogen bond with the
oxygen atom attached to the vinyl group.
Bull. Korean Chem. Soc. 2019
© 2019 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Wiley Online Library
1

Article
BULLETIN OF THE
ISSN (Print) 0253-2964 | (Online) 1229-5949
KOREAN CHEMICAL SOCIETY
structure of the product 5f was further confirmed by single-
crystal through X-ray diffraction (Figure 1). Based on
single-crystal X-ray diffraction analysis, both the chlorine
on the vinyl and oxygen are located to the same side of
carbon–carbon double bond of vinyl group, which con-
firmed the formation of Z isomer.
Overall, the method for the preparation of Z/E N-
(1-chlorovinyl)formamide isomers by Vilsmeier-Haack
reaction has been well established. However, the cyclo-
hexyl group (R1 = cyclohexyl) with steric hindrance in
compounds 4e and 4f led to relatively low yield to N-
vinylenamide 5 but with an excellent regioselectivity.
To point out, the introduction of chlorine atom to the
Cα-position and phenoxy substitutions to the Cβ-position of
N-vinylenamide derivatives via our protocol extended the
versatility of N-vinylenamides.
Scheme 1. Synthesis of novel N-(1-chlorovinyl)formamide iso-
mers through Vilsmeier–Haack reaction. Reagents and conditions:
(a) K2CO3, CH2Cl2, 0–25 ꢀC; (b) NaH/DMF, 150 ꢀC; (c) 4,
POCl3/DMF, 4–40 ꢀC.
Following
this
attractive
discovery,
various
Possible mechanism of Vilsmeier–Haack reaction for the
synthesis of novel Z/E N-(1-chlorovinyl)formamide isomers
was proposed, as shown in Scheme 2. Vilsmeier reagent,
an iminium salt with weak electrophilic activity, can be
obtained from the reaction between an acid chloride and an
amide.26,27 The Vilsmeier reagent 6, used in our studies
was generated from the reaction of POCl3 and DMF. The
nitrogen atom in compound 7 showed stronger electrophilic
activity than the benzene moiety and therefore, attacked the
substituted chloroiminium ion 6, to afford the addition
product 8, which then gave the intermediate 13 after the
leaving of chloride, hydrolysis of iminium, and the release
of dimethylamine. Further nucleophilic addition of Cl and
subsequent release of water afforded the Z/E N-(1-chlorovi-
nyl)formamide isomer.
2-(2-chlorophenoxy)ethanamide derivatives were used to
react with Vilsmeier reagent to explore the feasibility and
scope of the Vilsmeier–Haack reaction. As shown in
Scheme 1, the synthetic method for 2-(2-chlorophenoxy)
ethanamide derivatives 4 is simple, as expected, such easily
accessible starting materials could react with Vilsmeier
reagent under mild reaction conditions to prepare the corre-
sponding Z/E N-(1-chlorovinyl)formamide products. We
designed and synthesized set of substrates 4 (R1 = n-pro-
pyl, n-butyl, cyclohexyl, and phenylethyl, and R2 = Cl, H)
(Table 1), and investigated their reactivity with Vilsmeier
reagent. In most cases, the desired Z/E isomers of N-
(1-chlorovinyl)formamide were generated in good yields
of 70–80%.
However, it was worth noting that the cyclohexyl group
on nitrogen atom (R1 = cyclohexyl) in substrate 4 hindered
the reaction, so the reaction resulted in relatively low yields
(about 40%) but gave only one of the two desired Z/E N-
(1-chlorovinyl)formamide isomers as the highly regioselec-
tive product (Table 1, entry 5 and 6). The molecular
Conclusion
The classical Vilsmeier–Haack reaction is the chemical
reaction to produce aldehyde derivatives by using a
Table 1. Vilsmeier–Haack reaction assisted conversion of (2-(2-chlorophenoxy)ethanamide derivatives 4 to Z/E N-(1-chlorovinyl)
formamides 5.a
Entry
Substrate
Product
Yieldb (%) (E/Z)
1
2
3
4
5
6
a
4a: R1 = n-propyl, R2 = H
4b: R1 = n-butyl, R2 = H
4c: R1 = phenylethyl, R2 = H
4d: R1 = n-propyl, R2 = Cl
4e: R1 = cyclohexyl, R2 = H
4f: R1 = cyclohexyl, R2 = Cl
(E)-5a/(Z)-5a: R1 = n-propyl, R2 = H
(E)-5b/(Z)-5b: R1 = n-butyl, R2 = H
(E)-5c/(Z)-5b: R1 = phenylethyl, R2 = H
(E)-5d/(Z)-5d: R1 = n-propyl, R2 = Cl
5e: R1 = cyclohexyl, R2 = H
73 (55/45)
72 (49/51)
77 (53/47)
80 (47/53)
40 (0/100)
37 (0/100)
5f: R1 = cyclohexyl, R2 = Cl
Reaction conditions: 4 (15.0 mmol), POCl3 (45.0 mmol), DMF (60 mL) at 0–5 ꢀC for 1 h, and then heated to 40 ꢀC for 5 h.
b
Isolated yields.
Bull. Korean Chem. Soc. 2019
© 2019 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de
2

BULLETIN OF THE
Article E/Z N-(1-Chlorovinyl)formamide Synthesized Using Vilsmeier–Haack Reaction KOREAN CHEMICAL SOCIETY
Figure 1. X-ray molecular structure of compound 5f.
traditional Vilsmeier–Haack reagent, DMF and phosphorus
oxychloride. However, we herein developed an approach to
the synthesis of Z/E N-(1-chlorovinyl)formamide via
Vilsmeier–Haack reaction. In most cases, a mixture of
regioisomeric Z/E N-(1-chlorovinyl)formamides were both
obtained, however, for the steric hindrance reason, the reac-
tion starting from cyclohexylamine afforded the sole
Z isomer as highly regioselective product. We expect that
this method can be extended to allow the synthesis of more
functionalized NVFs and the scope of this method will be
applicable to a variety of substrates.
Scheme 2. Possible mechanism for Vilsmeier-Haack reaction for
the synthesis of Z/E N-(1-chlorovinyl)formamide derivatives.
water (50 mL) was added. The mixture was then extracted
by ethyl acetate (50 mL × 3), and the combined organic
layers were evaporated at reduced pressure to give the
crude product. The purification by column chromatography
on silica gel (elute: ethyl acetate: petroleum ether = 1:4
(V: V)) gave N-alkyl-2-(2-chloro-4-substituted-phenoxy)
ethanamide 4 as the final product.
Methods
Representative Procedure for Preparation of the
2-phenoxyethanamides 4. The substituted primary amine
1 (60 mmol, 1.0 equiv.) and K2CO3 (75.0 mmol, 1.5
Representative Procedure for the Synthesis of Z/E Iso-
mers of N-(1-chlorovinyl)formamide Derivatives. To a
magnetically stirred solution of the product 4 (15.0 mmol,
1.0 equiv.) in DMF (60 mL) cooled in an ice bath, the
phosphorus oxychloride, POCl3 (45.0 mmol, 3.0 equiv.)
was ꢀadded dropwise. The mixture was further stirred at
ꢀ
equiv.) were mixed in CH2Cl2 (80 mL) and cooled to 0 C
in an ice bath, to which the chloroacetyl chloride
(72.0 mmol, 1.2 equiv.) was added dropwise. The reaction
mixture was then stirred at room temperature and moni-
tored by thin-layer chromatography (TLC, eluent: 25%
ethyl acetate in petroleum ether). After the completion of
the reaction, the solvent was removed under vacuum and
water (50 mL) was added into the residue. The mixture
was then extracted with ethyl acetate (50 mL × 3). The
organic layers were combined, which was then washed with
the saturated aqueous NaCl (100 mL), and dried over anhy-
drous Na2SO4. Then, the Na2SO4 was filtered, and the fil-
trate was evaporated under vacuum to give the crude
product 2 (N-substituted-2-chloroacetamide) without further
purification. The mixture of crude N-substituted-
2-chloroacetamide 2 (24 mmol, 1.2 equiv.), 2-chloro-
4-substituted-phenol 3 (20 mmol, 1.0 equiv.), and sodium
hydride (30 mmol, 1.5 equiv.) in DMF (60 mL) was
refluxed and monitored by TLC (eluent: 25% ethyl acetate
in petroleum ether). When the reaction was complete, the
solvent was removed under vacuum and to the residue
ꢀ
0–5 C for 1 h, and then heated to 40 C, which was moni-
tored by TLC (eluent: 25% ethyl acetate in petroleum ether
(V: V)). After the completion of the reaction, the reaction
mixture was cooled to room temperature, and saturated
aqueous NaHCO3 was added till the solution became neu-
tral. The mixture was extracted with dichloromethane
(30 mL × 3). The combined organic phases were washed
with the saturated aqueous NaCl (100 mL), dried over
anhydrous Na2SO4, and filtered. The filtrate was evaporated
under vacuum to give the crude product. The purification
by silica gel chromatography (eluent: 12% ethyl acetate in
petroleum ether) gave product 5 as isomers.
(E)-5a: (E)-N-propyl-N-(1-chloro-2-(2-chlorophenoxy)
1
vinyl)formamide, yellow oil; H NMR (400 MHz, CDCl3)
δ 8.33 (s, 1H), 7.41 (dd, J = 7.9, 1.6 Hz, 1H), 7.28–7.24
(m, 1H), 7.11–7.07 (m, 1H), 7.04 (dd, J = 8.1, 1.4 Hz,
1H), 6.81 (s, 1H), 3.55 (t, J = 8.0 Hz, 2H), 1.67–1.62 (m,
2H), 0.96 (t, J = 7.4 Hz, 3H) ppm. 13C NMR (100 MHz,
Bull. Korean Chem. Soc. 2019
© 2019 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de
3

BULLETIN OF THE
Article E/Z N-(1-Chlorovinyl)formamide Synthesized Using Vilsmeier–Haack Reaction KOREAN CHEMICAL SOCIETY
CDCl3) δ 162.74, 151.96, 139.48, 138.35, 131.00, 127.98,
125.20, 119.72, 117.15, 43.82, 20.86, 11.16 ppm. ESI-
HRMS: m/z (%): 274.0416 [M + H]+ (calc. C12H14Cl2NO2:
274.0396).
δ 8.30 (s, 1H), 7.43 (d, J = 2.5 Hz, 1H), 7.24 (dd, J = 8.7,
2.5 Hz, 1H), 6.98 (d, J = 8.7 Hz, 1H), 6.77 (s, 1H), 3.55 (t,
J = 7.3 Hz, 2H), 1.65–1.62 (m, 2H), 0.95 (t, J = 7.4 Hz,
3H) ppm. 13C NMR (100 MHz, CDCl3) δ 162.57, 150.68,
137.79, 130.76, 129.94, 128.02, 125.01, 120.45, 117.71,
43.79, 20.87, 11.14 ppm. ESI-HRMS: m/z (%): 308.0020
[M + H]+ (calc. C12H13Cl3NO2: 308.0006).
(Z)-5a: (Z)-N-propyl-N-(1-chloro-2-(2-chlorophenoxy)
1
vinyl)formamide, yellow oil; H NMR (400 MHz, CDCl3)
δ 8.28 (s, 1H), 7.45 (dd, J = 8.0, 1.5 Hz, 1H), 7.30–7.26
(m, 1H), 7.15–7.11(m, 1H), 7.07 (dd, J = 8.1, 1.3 Hz, 1H),
6.78 (s, 1H), 3.54–3.50 (t, J = 8.0 Hz, 2H), 1.64–1.61 (m,
2H), 0.94 (t, J = 8.0 Hz, 3H) ppm. 13C NMR (100 MHz,
CDCl3) δ 162.47, 151.92, 139.65, 131.07, 128.07, 125.54,
124.55, 118.53, 118.19, 44.27, 20.52, 11.13 ppm. ESI-
HRMS: m/z (%): 274.0314 [M + H]+ (calc. C12H14Cl2NO2:
274.0396).
(Z)-5d: (Z)-N-propyl-N-(1-chloro-2-(2,4- dichlorophe-
noxy)vinyl)formamide, yellow oil; 1H NMR (400 MHz,
CDCl3) δ 8.26 (s, 1H), 7.46 (d, J = 2.4 Hz, 1H), 7.25 (dd,
J = 8.7, 2.5 Hz, 1H), 7.01 (d, J = 8.7 Hz, 1H), 6.74 (s,
1H), 3.52 (t, J = 7.4 Hz, 2H), 1.62–1.58 (m, 2H), 0.94 (t,
J = 7.4 Hz, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ
162.32, 150.65, 139.13, 130.79, 130.28, 128.12, 125.42,
119.29, 118.84, 44.27, 20.54, 11.14 ppm. ESI-HRMS: m/z
(%): 308.0003 [M + H]+ (calc. C12H13Cl3NO2: 308.0006).
5e: (Z)-N-cyclohexyl-N-(1-chloro-2-(2- chlorophenoxy)
(E)-5b: (E)-N-butyl-N-(1-chloro-2-(2-chlorophenoxy)
1
vinyl)formamide, yellow oil; H NMR (400 MHz, CDCl3)
δ 8.31 (s, 1H), 7.41 (dd, J = 7.9, 1.5 Hz, 1H), 7.28–7.24
(m, 1H), 7.11–7.07(m, 1H), 7.04 (dd, J = 8.2, 1.2 Hz, 1H),
6.81 (s, 1H), 3.59 (t, J = 8.0 Hz, 2H), 1.63–1.58 (m, 2H),
1.44–1.36 (m, 2H), 0.91 (t, J = 7.4 Hz, 3H) ppm. 13C
NMR (100 MHz, CDCl3) δ 162.69, 151.97, 138.38,
131.00, 127.97, 125.19, 124.18, 119.75, 117.15, 41.89,
29.59, 19.85, 13.70 ppm. ESI-HRMS: m/z (%): 288.0614
[M + H]+ (calc. C13H16Cl2NO2: 288.0553).
1
vinyl)formamide, yellow oil; H NMR (400 MHz, CDCl3)
δ 8.26 (s, 1H), 7.45 (dd, J = 8.0, 1.5 Hz, 1H), 7.31–7.28
(m, 1H), 7.16–7.12 (m, 1H), 7.08 (dd, J = 8.1, 1.3 Hz,
1H), 6.75 (s, 1H), 4.18–4.10 (m, 1H), 1.88–1.83 (m, 5H),
1.63–1.62 (m, 1H), 1.44–1.33 (m, 3H), 1.22–1.13 (m, 1H)
ppm. 13C NMR (100 MHz, CDCl3) δ 163.15, 151.87,
142.20, 131.07, 128.09, 125.62, 124.61, 118.36, 116.49,
54.07, 30.75, 25.71, 25.32 ppm. ESI-HRMS m/z (%):
found 314.0720 [M + H]+ (calc. C15H18Cl2NO2:
314.0709).
(Z)-5b:
(Z)-N-butyl-N-(1-chloro-2-(2-chlorophenoxy)
1
vinyl)formamide, yellow oil; H NMR (400 MHz, CDCl3)
δ 8.26 (s, 1H), 7.45 (dd, J = 8.0, 1.5 Hz, 1H), 7.30–7.28
(m, 1H), 7.15–7.11 (m, 1H), 7.08 (dd, J = 8.1, 1.4 Hz,
1H), 6.77 (s, 1H), 3.55 (t, J = 8.0 Hz, 2H), 1.60–1.53 (m,
2H), 1.40–1.31 (m, 2H), 0.95 (t, J = 8.0 Hz, 3H) ppm. 13C
NMR (100 MHz, CDCl3) δ 162.41, 151.93, 139.63,
131.08, 128.07, 125.54, 124.56, 118.54, 118.19, 42.40,
29.24, 19.89, 13.69 ppm. ESI-HRMS: m/z (%):288.0505
[M + H]+ (calc. C13H16Cl2NO2: 288.0553).
5f: (Z)-N-cyclohexyl-N-(1-chloro-2-(2,4-dichlorophenoxy)
1
vinyl)formamide. H NMR (400 MHz, CDCl3) δ 8.24 (s,
1H), 7.46 (d, J = 2.1 Hz, 1H), 7.25(dd, J = 8.7, 2.5 Hz,
1H), 7.01 (d, J = 8.7 Hz, 1H), 6.71 (s, 1H), 4.17–4.09 (m,
1H), 1.91–1.85 (m, 5H), 1.62–1.54 (m, 2H), 1.42–1.32 (m,
2H), 1.21–1.13 (m, 1H) ppm. 13C NMR (100 MHz,
CDCl3) δ 162.96, 150.60, 141.72, 130.79, 130.36, 128.14,
125.49, 119.03, 117.28, 54.10, 30.75, 25.70, 25.31 ppm.
ESI-HRMS: m/z (%): 348.0327 [M + H]+ (calc.
C15H17Cl3NO2: 348.0319).
(E)-5c: (E)-N-phenethyl-N-(1-chloro-2-(2-chlorophe-
noxy)vinyl)formamide, yellow oil; 1H NMR (400 MHz,
CDCl3) δ 8.34 (s, 1H), 7.41 (dd, J = 8.0, 1.6 Hz, 1H),
7.27–7.17 (m, 6H), 7.11–7.07 (m, 1H), 6.97 (dd, J = 8.2,
1.4 Hz, 1H), 6.78 (s, 1H), 3.84–3.80 (m, 2H), 2.97–2.93
(m, 2H) ppm. 13C NMR (100 MHz, CDCl3) δ 162.56,
151.84, 138.17, 130.98, 128.78, 128.47, 127.95, 126.48,
125.21, 124.17, 119.36, 117.13, 43.83, 33.96 ppm. ESI-
HRMS: m/z (%):336.0499 [M + H]+ (calc. C17H16Cl2NO2:
336.0553).
Acknowledgments. The authors would like to thank the
Fundamental Research Funds for the Central Universities,
P. R. China (XDJK2016A015 and XDJK2017B011),
Changwon National University (2017-2018) and the
National Research Foundation of Korea (NRF-
2016R1D1A1B1011019) for financial support.
(Z)-5c: (Z)-N-phenethyl-N-(1-chloro-2-(2-chlorophe-
noxy)vinyl)formamide, yellow oil; 1H NMR (400 MHz,
CDCl3) δ 8.24 (s, 1H), 7.43 (dd, J = 7.9, 1.6 Hz, 1H),
7.31–7.18 (m, 6H), 7.13–7.09 (m, 1H), 6.86 (dd, J = 8.1,
1.4 Hz, 1H), 6.46 (s, 1H), 3.85–3.81 (m, 2H), 2.97–2.93
(m, 2H) ppm. 13C NMR (100 MHz, CDCl3) δ 162.53,
151.82, 139.88, 137.93, 130.98, 128.85, 128.60, 127.95,
126.66, 125.47, 124.44, 118.37, 118.11, 43.99, 33.42 ppm.
Supporting Information. Additional supporting informa-
tion may be found online in the Supporting Information
section at the end of the article.
References
1. K. Gopalaiah, H.-B. Kagan, Chem. Rev. 2011, 111, 4599.
2. G.-R. Dake, Synlett 2012, 23, 814.
3. R. Matsubara, S. Kobayashi, Acc. Chem. Res. 2008, 41, 292.
4. D.-R. Carbery, Org. Biomol. Chem. 2008, 6, 3455.
5. N. Gigant, L. Chausset-Boissarie, I. Gillaizeau, Chem. Eur. J.
2014, 20, 7548.
ESI-HRMS:
m/z
(%):336.0631
[M + H]+
(calc.
C17H16Cl2NO2: 336.0553).
(E)-5d: (E)-N-propyl-N-(1-chloro-2-(2,4-dichlorophenoxy)
1
vinyl)formamide, yellow oil; H NMR (400 MHz, CDCl3)
Bull. Korean Chem. Soc. 2019
© 2019 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de
4

BULLETIN OF THE
Article E/Z N-(1-Chlorovinyl)formamide Synthesized Using Vilsmeier–Haack Reaction KOREAN CHEMICAL SOCIETY
6. J. Yamaguchi, A.-D. Yamaguchi, K. Itami, Angew. Chem. Int.
Ed. 2012, 51, 8960.
18. B. Gourdet, H.-W. Lam, J. Am. Chem. Soc. 2009, 131, 3802.
19. C.-S. Kuai, L.-H. Wang, H.-Y. Cui, J.-H. Shen, Y.-D. Feng,
X.-L. Cui, ACS Catal. 2016, 6, 186.
20. R. K. Pinschmidt, J. Polym. Sci. Part A: Polym. Chem. 2010,
48, 2257.
21. T. K. Beng, S. M. Wilkerson-Hill, R. Sarpong, Org. Lett.
2014, 16, 916.
22. E. G. Occhiato, A. Trabocchi, A. Guarna, J. Org. Chem.
2001, 66, 2459.
7. D. Y.-K. Chen, S.-W. Youn, Chem. Eur. J. 2012, 18, 9452.
8. B. Peng, N. Maulide, Chem. Eur. J. 2013, 19, 13274.
9. X. Shang, Z.-Q. Liu, Chem. Soc. Rev. 2013, 42, 3253.
10. L. Zhou, W. Lu, Chem. Eur. J. 2014, 20, 634.
11. J. Wencel-Delord, F. Glorius, Nat. Chem. 2013, 5, 369.
12. R.-K. Pinschmidt, W.-L. Renz, W.-E. Carroll, K. Yacoub,
J. Drescher, A.-F. Nordquist, N. Chen, J. Macromol. Sci.
Chem. 1997, 34, 1885.
23. B. Boren, J. S. Hirschi, J. H. Reibenspies, M. D. Tallant,
D. A. Singleton, G. A. Sulikowski, J. Org. Chem. 2003,
68, 8991.
13. H.-L. Liu, Y.-Q. Zhou, X.-Y. Yan, C. Chen, Q.-B. Liu,
C. J. Xi, Org. Lett. 2013, 15, 5174.
14. J. Xu, Y. Fu, B. Xiao, T.-J. Gong, Q.-X. Guo, Tetrahedron
Lett. 2010, 51, 5476.
24. O. Meth-Cohn, S.-P. Stanforth, Compr. Org. Synth. 1991,
2, 777.
15. A. Delforge, I. Georgiou, A. Kremer, J. Wouters, D. Bonifazi,
Org. Lett. 2016, 18, 4844.
16. S. Ahmad, S. Choudhury, F.-A. Khan, Tetrahedron 2015,
71, 4192.
17. L. Wang, C. Liu, R.-P. Bai, Y.-N. Pan, A.-W. Lei, Chem.
Commun. 2013, 49, 7923.
25. G. Jones, S.-P. Stanforth, Org. React. 2000, 56, 355.
26. A. Vilsmeier, A. Haack, Ber. Dtsch. Chem. Ges. 1927,
60, 119.
27. I.-M. Downie, M.-J. Earle, H. Heaney, K.-F. Shuhaibar, Tet-
rahedron 1993, 49, 4015.
Bull. Korean Chem. Soc. 2019
© 2019 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de
5