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Citation: Chen, J.; Duan, L.; Liu, K.;
Liu, J.-B. A Convenient Synthesis
towards 2-Bromo-2-
(methoxy(phenyl)methyl)malononitrile
and 2-Iodo-2-
(methoxy(phenyl)methyl)malononitrile.
Molbank 2022,2022, M1373. https://
doi.org/10.3390/M1373
Academic Editor: Ian R. Baxendale
Received: 30 April 2022
Accepted: 27 May 2022
Published: 30 May 2022
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molbank
Communication
A Convenient Synthesis towards
2-Bromo-2-(methoxy(phenyl)methyl)malononitrile and
2-Iodo-2-(methoxy(phenyl)methyl)malononitrile
Jialuo Chen, Lili Duan, Kunming Liu * and Jin-Biao Liu *
Jiangxi Provincial Key Laboratory of Functional Molecular Materials Chemistry, Faculty of Materials,
Metallurgy and Chemistry, Jiangxi University of Science and Technology, 86 Hongqi Road, Ganzhou 341000,
China; cjl2710722009@163.com (J.C.); dll1320191269@163.com (L.D.)
*Correspondence: liukunming@jxust.edu.cn (K.L.); liujinbiao@jxust.edu.cn (J.-B.L.)
Abstract:
This short note elaborates a concise protocol for the synthesis of two novel vicinal haloethers
bearing a malonontrile group, 2-bromo-2-(methoxy(phenyl)methyl)malononitrile (1) and 2-iodo-2-
(methoxy(phenyl)methyl)malononitrile (2). The structures of the synthesized compounds were
confirmed by 1H, 13C-NMR spectroscopy. The final products indicate that methanol not only acts as
solvent but also participates in and dominates the reaction result.
Keywords: β;β-dicyanostyrene; difunctionalization; vicinal haloether
1. Introduction
The difunctionalization of olefins has become an attractive strategy for rapidly increasing
molecular complexity from abundant and cheap feedstock [
1
–
4
]. Up to now, much work
on difunctionlization has been reported, such as the representative aminohalogenation reac-
tion, which provides an effective platform to convert simple
olefins [5–7]
,
α
,
β
-unsaturated
ketones [
8
–
10
], and
β
-nitrostyrene derivatives [
11
–
13
] into vicinal haloamine compounds.
β
,
β
-
Dicyanostyrene derivatives are a kind of reaction raw material containing a multifunctional
group which can be converted into the skeleton structures in drugs and natural products, via di-
functionalization, such as enamine [
14
],
β
-hydroxy sulfide [
15
], dicyanocyclobutane [
16
], and
so on. Recently, an unexpected vicinal bromoether product was obtained when we performed
an aminobromination reaction of
β
,
β
-dicyanostyrene. On this basis, we developed a synthetic
protocol for vicinal haloethers, including 2-bromo-2-(methoxy(phenyl)methyl)malononitrile
(
1
) and 2-iodo-2-(methoxy(phenyl)methyl)malononitrile (
2
), which are verified to be novel
compounds and to possess the potential to be building blocks in organic synthesis by easy
conversion into amounts of useful functional derivatives via intermolecular or intramolecular
nucleophilic substitution of halogens.
2. Results
Many synthetic methods are available for the aminobromination reaction of
β
,
β
-
dicyanostyrene; most of them require catalysts such as Na
2
CO
3
[
14
], K
3
PO
4
[
17
], and
NaHCO
3
[
18
]. In 2012, Chen reported a NaOAc-catalyzed aminobromination of
β
,
β
-
dicyanostyrene, with NBS as nitrogen/bromine source, to yield N-[2-Bromo-2,2-dicyano-
1-phenylethyl]pyrrolidine-2,5-dione [
19
]. Recently, we slightly modified this reaction by
replacing CH
3
CN with methanol as the solvent and abandoning the catalyst. Surprisingly,
the expected product was not observed in the reaction. Alternatively,
β
,
β
-dicyanostyrene
was converted into 2-bromo-2-(methoxy(phenyl)methyl)malononitrile (
1
) in moderate yield
(Scheme 1). Subsequently, we also tried ethanol, isopropyl alcohol, and tert-butanol as sol-
vents, but none of the reactions formed 2-bromo-2-(methoxy (phenyl)methyl)malononitrile
Molbank 2022,2022, M1373. https://doi.org/10.3390/M1373 https://www.mdpi.com/journal/molbank
Molbank 2022,2022, M1373 2 of 4
or N-[2-bromo-2,2-dicyano-1-phenylethyl]pyrrolidine-2,5-dione. Most of the starting mate-
rial,
β
,
β
-dicyanostyrene, was recovered, and some was converted to benzaldehyde. The
relative mechanism is still under further study.
Scheme 1. Synthesis of compound 1and 2.
After optimization of the experimental conditions (details of the condition optimiza-
tion are shown in Table S1), the reaction was performed in methanol at room tempera-
ture by using
β
,
β
-dicyanostyrene/NBS (1:1 ratio) as the starting materials. Compound
1
was obtained in 76.8% yield and confirmed by NMR. Firstly, the
1
H-NMR spectrum
(
Supplementary Materials
) exhibits the typical signals for the methoxy and methyne group
as a single peak at 3.47 and 4.67 ppm, respectively. The chemical shifts of the five hydrogen
atoms on the substituted benzene ring are concentrated in the range of 7.45 to 7.55 ppm.
The
13
C-NMR spectrum exhibits nine peaks which fully agree with the proposed structure
for 1(Supplementary Materials).
As an expansion of the reaction, N-iodosuccinimide (NIS) was selected as the iodine
source, and we obtained 2-iodo-2-(methoxy(phenyl)methyl)malononitrile (
2
) in 70.5% yield
under the same reaction conditions. The molecular structure of compound
2
was also
unambiguously confirmed by
1
H-NMR and
13
C-NMR, with the peak at 1.02 ppm in the
13C-NMR spectrum representing the typical chemical shift of C–I bond.
3. Discussion
All reagents were purchased from Shanghai Aladdin Bio-Chem Technology Co., Ltd.
(Shanghai, China) and used without further purification. The starting
β
,
β
-dicyanostyrene
was synthesized according to the literature [
17
]. NMR spectra were recorded on a Bruker
Avance AV400 (400/100 MHz
1
H/
13
C) spectrometer (Bruker, Billerica, MA, USA), and
chemical shifts (δ, ppm) were down field from TMS.
2-Bromo-2-(methoxy(phenyl)methyl)malononitrile (
1
): in a 100 mL three-neck flask,
N-bromosuccinimide (0.35 g, 2 mmol) was added to the solution of
β
,
β
-dicyanostyrene
(0.31 g; 2 mmol) in absolute methanol (10 mL). The reaction mixture was stirred at room
temperature for 24 h, and then the excess methanol was removed by rotary evaporation. The
residue was purified by column chromatography over silica gel (
EtOAc/petroleum = 1/10
)
to yield a yellow oil (0.34 g, 76.8%).
1
H NMR (400 MHz, CDCl
3
):
δ
7.55 (dd,
J= 7.4
, 2.1 Hz,
2H), 7.52–7.45 (m, 3H), 4.64 (s, 1H), 3.47 (s, 3H);
13
C NMR (100 MHz, CDCl
3
):
δ
131.38 (s),
130.94 (s), 128.96 (s), 128.60 (s), 111.11 (s), 110.81 (s), 86.05 (s), 58.74 (s), 30.54 (s).
2-Iodo-2-(methoxy(phenyl)methyl)malononitrile (
2
): in a 100 mL three-neck flask,
N-iodosuccinimide (0.45 g, 2 mmol) was added to the solution of
β
,
β
-dicyanostyrene
(0.31 g; 2 mmol) in absolute methanol (10 mL). The reaction mixture was stirred at room
temperature for 24 h, and then the excess methanol was removed by rotary evaporation. The
residue was purified by column chromatography over silica gel (
EtOAc/petroleum = 1/10
)
to yield a brown oil (0.44 g, 70.5%).
1
H NMR (400 MHz, CDCl
3
)
δ
7.58–7.54 (m, 2H),
7.53–7.48 (m, 3H), 4.45 (s, 1H), 3.48 (s, 3H);
13
C NMR (100 MHz, CDCl3)
δ
131.83 (s), 130.80
(s), 129.00 (s), 128.38 (s), 112.87 (s), 112.66 (s), 86.21 (s), 58.61 (s).
4. Conclusions
Two novel vicinal haloether compounds, 2-bromo-2-(methoxy(phenyl)methyl)
malononitrile (
1
) and 2-iodo-2-(methoxy(phenyl)methyl)malononitrile (
2
), were handily
synthesized from
β
,
β
-dicyanostyrene and characterized by NMR. Future work will
Molbank 2022,2022, M1373 3 of 4
emphasize exploring the scope of
β
,
β
-dicyanostyrene derivatives and illustrating the
reaction mechanism.
Supplementary Materials:
The following supporting information can be downloaded online,
1
H-
NMR and
13
C-NMR spectra of compounds
1
,
2
. Reference [
17
] is cited in Supplementary Materials.
Table S1. condition optimization. Figure S1. H-NMR and 13C-NMR spectra of compound
1
.
Figure S2
.
1H NMR and 13C NMR spectra of compound 2.
Author Contributions:
Investigation, J.C. and L.D.; writing—original draft preparation, K.L.; writing—
review and editing, J.-B.L. All authors have read and agreed to the published version of the manuscript.
Funding:
This research was funded by the Jiangxi Provincial Natural Science Foundation
(20202BABL213007, 20212BAB203013), National College Students’ Innovation and Entrepreneurship
Training Program (202110407006). The Youth Jinggang Scholars Program in Jiangxi Province is
gratefully acknowledged.
Data Availability Statement:
The data from this study are available in this paper and in its
Supplementary Materials.
Conflicts of Interest: The authors declare no conflict of interest.
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