A method for the cyanation of alkenes using nitromethane as a source of cyano group mediated by proton-exchanged montmorillonite

Article abstract of DOI:10.1016/j.tetlet.2014.10.127

A novel method for the cyanation of alkenes using nitromethane as a source of the cyano group is described. H⁺-montmorillonite mediates the cyanation through the in situ formation of trimethylsilanecarbonitrile oxide from nitromethane and allylsilane, followed by 1,3-dipolar cycloaddition and subsequent rearrangement to afford the corresponding nitriles.

Full text of DOI:10.1016/j.tetlet.2014.10.127

Tetrahedron Letters xxx (2014) xxx–xxx
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A method for the cyanation of alkenes using nitromethane
as a source of cyano group mediated by proton-exchanged
montmorillonite
⇑
Ken Motokura, Kenta Matsunaga, Akimitsu Miyaji, Sho Yamaguchi, Toshihide Baba
Department of Environmental Chemistry and Engineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8502, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel method for the cyanation of alkenes using nitromethane as a source of the cyano group is
described. H+-montmorillonite mediates the cyanation through the in situ formation of trimethylsilane-
carbonitrile oxide from nitromethane and allylsilane, followed by 1,3-dipolar cycloaddition and subse-
quent rearrangement to afford the corresponding nitriles.
Received 19 September 2014
Revised 17 October 2014
Accepted 24 October 2014
Available online xxxx
Ó 2014 Published by Elsevier Ltd.
Keywords:
Cyanation
Nitromethane
Alkene
Proton-exchanged montmorillonite
Heterogeneous catalysis
Introduction
During the course of our research regarding the activation of
silyl groups by proton-exchanged montmorillonite (H+-montmoril-
Nitriles are important building blocks for pharmaceuticals and
agrochemicals.1 They also receive much attention as useful
precursors of amides, ketones, esters, and others.1 Since cyanation
of organic compounds is one of the most useful methods for the
synthesis of target nitriles, the discovery of novel cyanation
procedures is the key to access a variety of nitriles from diverse
substrates.
lonite) as a solid acid,6 nitromethane was found to be a precursor
of trimethylsilanecarbonitrile oxide. Herein, we report the in situ
formation of trimethylsilanecarbonitrile oxide from commonly
available chemicals for a novel cyanation of alkenes using nitro-
methane as a source of the cyano group (Eq. 2).7 This overcomes
the problems regarding instability of trimethylsilanecarbonitrile
oxide and does not require the use of highly toxic materials.
CN sources for cyanations are broadly classified as either, nucle-
ophilic2 or electrophilic.3 Alternatively, trimethylsilanecarbonitrile
oxide (Me3SiCN?O) as a 1,3-dipole can provide CN through
1,3-dipolar cycloaddition.4 De Sarlo et al. reported the synthesis
of nitriles in this way from the reaction of trimethylsilanecarbonit-
rile oxide and several alkenes, such as styrene and norbornene
(Eq. 1).4 This procedure is potentially applicable to the cyanation
of more varied alkenes. However, the use of an instable trimeth-
ylsilanecarbonitrile oxide as a starting compound and the necessity
of using a highly toxic Hg compound for its preparation5 have
restricted its application.
Hg(CNO)2
Me3SiBr
+
De Sarlo et al. (1983)
Me3Si C N O
+
N
Me3Si
NC
1,3-dipolar addition
rearrangement
O
ð1Þ
R
R
OSiMe3
R
⇑
Corresponding author.
E-mail address: tbaba@chemenv.titech.ac.jp (T. Baba).
http://dx.doi.org/10.1016/j.tetlet.2014.10.127
0040-4039/Ó 2014 Published by Elsevier Ltd.
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2
K. Motokura et al. / Tetrahedron Letters xxx (2014) xxx–xxx
OSiMe3
SiMe3
N
Me3Si N C O
This Work
Me3Si
N O
SiMe3
H+-montmorillonite
CH3NO2
+
3
1
2
SiMe3
Chart 1.
N
C
13C
ð2Þ
SiMe3
(8.7 mmol)
H3NO2
(9.3 mmol)
+
C
O
N
Me3Si
R'
R
in-situ formation
OSiMe3
R'
N
H+-montmorillonite (0.10 g)
ð3Þ
N
C
13C
chlorobenzene (5 mL)
80 oC, 5 h
R
0.08 mmol
13C content >95%
During the cyanation of allyltriemthylsilane, a trace amount of
trimethylsilyl isocyanate (1) (Chart 1) was detected by GCMS
analysis. The amount of 1 was less than 1%. The incorporation
of a 13C atom into 1 was also detected in the reaction using
13C-nitromethane (Figure S2), indicating that nitromethane is
transformed to 1. It was reported that trimethylsilanecarbonitrile
oxide (2) (Chart 1) is readily transformed to 1 upon heating,5
Results and discussion
First, we attempted the cyanation of allyltrimethylsilane
using nitromethane as the solvent and H+-montmorillonite as the
acid. The reaction conditions and result are shown in Table 1.
The reaction afforded 0.23 mmol of allylnitrile and almost all of
the allylsilane (94% conversion) was converted to propylene and
hexamethyldisiloxane (Table 1, entry 1). No allylnitrile was
obtained when other acids, such as H2SO4 and Amberlyst, were
used.
indicating that
2 is most likely formed initially during the
cyanation of allyltrimethylsilane with nitromethane using
H+-montmorillonite.
Allylnitrile was hardly obtained when using sodium-exchanged
montmorillonite (Na+-montmorillonite) instead of H+-montmoril-
lonite (Table 1). This result indicates that the H+ site of montmoril-
lonite is necessary for the cyanation reaction. Other Brønsted acids,
such as Amberlyst, Nafion, and H2SO4, were completely inactive for
the reaction of nitromethane with allyltrimethysilane (Table 1).
Our group has previously reported the use of H+-montmorillonite
as a catalyst for the allylsilylation of alkenes with allylsilanes, for
which other Brønsted acids were also inactive.6 The catalytic
activity of H+-montmorillonite is derived from the formation of
active cationic Si species through the reaction between allylsilane
and the H+ site on the montmorillonite surface. Therefore, a
proposed mechanism for the formation of 2 from nitromethane
and allylsilane mediated by H+-montmorillonite is shown in
Scheme 1. The cationic Si species ([Si]+) interacts with the oxygen
atom of nitromethane to promote deoxygenation of nitromethane
and generate fulminic acid (HCNO) and silanol. A cation exchange
reaction between HCNO and another [Si]+ may afford 2. As shown
in Table 1, 0.23 mmol of allylnitrile was obtained using 0.10 g of
H+-montmorillonite. Since the amount of the H+ site in the
H+-montmorillonite is 0.86 mmol gꢀ1, the H+ site on the montmo-
rillonite may act as a catalyst.
To confirm that nitromethane is truly the source of the cyano
group in allylnitrile product, the reaction of 13C-nitromethane with
allylsilane using H+-montmorillonite was conducted, as shown in
Eq. 3. The incorporation of a13C atom in the CN group of allylnitrile
was determined by GCMS (Figure S1) and 13C NMR analyses.
Table 1
Screening of Brønsted acids for allylnitrile synthesis from nitromethane and
allyltrimethylsilane
Acid
80 oC, 5 h
N
SiMe3
CH3NO2
+
Brønsted acid
Acid
Conv. of
Allylnitrile
amount (g)
allylsilane (%)
produced (mmol)
H+-montmorillonite
H+-montmorillonite
Na+-montmorillonite
montK10
H2SO4
p-TsOH
0.10
0.05
0.05
0.05
0.05
0.05
0.05
0.05
94
93
8
29
86
77
28
60
0.23
0.08
<0.00
<0.00
<0.00
<0.00
<0.00
<0.00
Nafion
Amberlyst
Reaction conditions: nitromethane (3.0 mL, 56 mmol), allyltrimethylsilane
(3.0 mmol), acid (0.05–0.10 g), 80 °C, 5 h, under Ar. Conversion and product amount
were determined by 1H NMR analysis on the CDCl3 solution of the reaction mixture
using 1,4-dioxane as an internal standard.
During the reaction of nitromethane with allyltrimethysilane
using H+-montmorillonite, the formation of 4-(trimethylsilyl)-3-
((trimethylsilyl)oxy)butanenitrile (3) (Chart 1) was observed. The
H
H
H
HO SiMe3
O
N
H
H
H
O
M3Si
N
O
H
N
H
O
N
O
N
O
2
O
SiMe3
H
O
[Si]
O
H+
O
[Si]
O
O
SiMe3
SiMe3
H+
O
H+-montmorillonite
Scheme 1. Proposed mechanism for the formation of 2 from nitromethane and allylsilane mediated by H+-montmorillonite.
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K. Motokura et al. / Tetrahedron Letters xxx (2014) xxx–xxx
3
73
147
N
OSiMe3
SiMe3
13C
101
45
114
189
59
131
215
171
147
73
OSiMe3
N
SiMe3
101
45
189
113
59
131
214
170
50
100
150
200
m / z
Figure 1. Mass spectra of intermediate 3 and 13C-3 during allylnitrile synthesis from nitromethane/13C-nitromethane and allyltrimethylsilane.
mass spectrum of 3 is shown in Figure 1. The incorporation of the
13C atom in the CN group of 3 when using 13C-nitromethane was
detected by GC–MS analysis (Fig. 1). Figure 2A represents the 1H
NMR spectrum of the CDCl3 solution of the concentrated reaction
mixture after removal of H+-montmorillonite by filtration and sub-
sequent evaporation. Other products, such as allylnitrile and hex-
amethyldisiloxane, could be selectively removed during the
evaporation due to the higher boiling point of compound 3, allow-
ing the signals assigned to 3 (1–5) to be clearly observed.8 Next, the
solution was treated with H+-montmorillonite, and the 1H NMR
measurement of the resulting product was conducted (Fig. 2B).
The signals corresponding to 3 had disappeared and the signals
assigned as allylnitrile (a–c) and hexamethyldisiloxane had
increased. This result clearly indicates that compound 3 is an inter-
mediate in the formation of allylnitrile from nitromethane and
allyltrimethylsilane.
The overall formation route of allylnitrile from nitromethane
and allylsilane is shown in Scheme 2. First, 2 is generated by
*
nitromethane
(SiMe3)2O
c
H
N
H
H
a
H
H
b
a
*
b
c
(B)
1
2
2
5
H OSiMe3
N
SiMe3
1
H
H
H
H
4
3
4
5
(A)
0.2
-0.2
6
5
4
3
2
1
1H Chemical Shift / ppm
⁄
Figure 2. 1H NMR spectra of the CDCl3 solution of (A) the concentrated reaction mixture containing 3 and (B) after treatment of the mixture with H+-montmorillonite.
indicates H2O as a contaminant. Spectra (A) and (B) show the transformation of 3 to allylnitrile and hexamethyldisiloxane.
-
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K. Motokura et al. / Tetrahedron Letters xxx (2014) xxx–xxx
H+-montmorillonite
1,3-dipolar addition
rearrangement
pathway. Further efforts toward the improvement of the reaction
efficiency as well as the scope of the substrates10 are now underway.
SiMe3
+
CH3NO2
Me3Si
N O
2
Experimental section
Me3Si
N O
N
Me3Si
O
2
+
Characterization procedures
SiMe3
SiMe3
1H and 13C NMR were recorded in CDCl3 with a Bruker AVANCE
III 400 or AVANCE III 500 spectrometer. 1H–1H COSY and 13C–1H
HMBC NMR were also recorded in CDCl3 with a Bruker AVANCE
III 500 spectrometer. A Shimadzu QP2010 Plus spectrometer
equipped with a DB-1 column was used for GC–MS analysis. The
product and the intermediate were identified by 1H and 13C NMR
and/or MS data.
OSiMe3
SiMe3
N
3
H+-montmorillonite
- (Me3Si)2O
N
Scheme 2. Overall formation route of allylnitrile from nitromethane and allylsilane.
Materials
Na+-montmorillonite
(Na0.66(OH)4Si8(Al3.34Mg0.66Fe0.19)O20;
Kunipia F) was obtained from Kunimine Industries Co. Ltd.
H+-montmorillonite was prepared from Na+-montmorillonite
using the reported ion exchange procedure with aqueous hydrogen
chloride.11 The parent H+-montmorillonite was stored under ca.
30% humidity for at least one week, and then dried under vacuum
(ca. 1 mmHg) at 120 °C for 1 h before the catalytic reaction.
MontK10 was purchased from Aldrich. Amberlyst was purchased
from Organo Co. as AmberlystÒ 15DRY. Nafion was purchased from
Aldrich as NafionÒ NR50. Unless otherwise noted, materials were
purchased from Wako Pure Chemicals, Tokyo Kasei Kogyo Co.,
Kanto Kagaku Co., and Aldrich Inc.
the reaction between nitromethane and allyltrimethylsilane. This
is followed by the 1,3-dipolar cycloaddition of 2 and another
allyltrimethylsilane and subsequent rearrangement to afford 3.
The 1,3-dipolar addition and rearrangement occur in without
catalyst.4,9 Finally, 3 is converted to allylnitrile and hexame-
thyldisiloxane in the presence of H+-montmorillonite.
Based on the reaction route shown in Scheme 2, b-siloxy nitriles
should be obtained as the major product if alkenes that do not con-
tain silyl groups are used. We attempted the cyano-siloxylation of
several alkenes using nitromethane and allyltrimethylsilane with
H+-montmorillonite. The reaction of p-chlorostyrene afforded the
cyano-siloxylation product in 18% yield (Eq. 4). The product yield
Typical procedure for allylnitrile synthesis
increased to 22% for norbornene (Eq. 5). 1H–1H COSY and 1H–13
C
HMQC NMR analyses indicated that both the CN and Me3SiO
groups were incorporated at the exo-positions of the norbornane
skeleton (see Supporting information). This stereoselectivity corre-
lates to a 1,3-dipolar cycloaddition mechanism. The synthesis of
nitriles from alkenes mediated by H+-montmorillonite is the first
cyanation of alkenes using nitromethane as a source of the cyano
group.7
The typical procedure for the cyanation of allyltrimethylsilane
using nitromethane is as follows: Into a glass reactor were placed
dried H+-montmorillonite (0.10 g), nitromethane (3.0 mL), and
allyltrimethylsilane (3.0 mmol) under a dry Ar atmosphere using
the Schlenk apparatus. The resulting mixture was vigorously
stirred at 80 °C. After 5 h, the catalyst was separated by filtration
and GC–MS analysis of the filtrate showed formation of allylnitrile.
The yield of allylnitrile and conversion of allyltrimethysilane were
determined by 1H NMR analysis of the filtrate dissolved in CDCl3
using 1,4-dioxane as an internal standard.
SiMe3
(3.0 mmol)
CH3NO2
(solvent: 2 mL)
+
+
Cl
(0.30 mmol)
Typical procedure for cyano-siloxylation of alkenes
ð4Þ
OSiMe3
CN
H+-montmorillonite (0.05 g)
80 oC, 3 days
The typical procedure for the cyano-siloxylation of alkenes using
nitromethane is as follows: Into a glass reactor were placed dried
H+-montmorillonite (0.10 g), nitromethane (3.0 mL), norbornene
(3.0 mmol), and allyltrimethylsilane (3.0 mmol) under a dry Ar
atmosphere using the Schlenk apparatus. The resulting mixture
was vigorously stirred at 80 °C. After 5 h, the catalyst was separated
by filtration and GC–MS analysis of the filtrate showed formation of
the cyano-siloxylated product. The yield of the nitrile product and
the conversion of substrates were determined by 1H NMR analysis
of the filtrate dissolved in CDCl3 using 1,4-dioxane as an internal
standard.
Cl
18%
SiMe3
+
CH3NO2
+
(3.0 mmol)
(3.0 mmol)
(solvent: 3 mL)
ð5Þ
H+-montmorillonite (0.10 g)
80 oC, 5 h
Me3SiO
NC
+
NC
Me3SiO
The filtrate was evaporated and the crude product was purified
by column chromatography using silica (n-hexane ? n-hexane/
ethyl acetate 9:1) to afford the pure product. The product was
identified by 1H and 13C NMR and mass data.
22% (racemic)
Summary
In summary, a novel cyanation of alkenes using nitromethane as a
source of the cyano group was disclosed. Among the heterogeneous
and homogeneous Brønsted acids tested, only H+-montmorillonite
could mediate the cyanation reaction. The in situ formation of tri-
methylsilanecarbonitrile oxide, followed by 1,3-dipolar cycloaddi-
tion and subsequent rearrangement, is proposed as the reaction
Acknowledgments
This study was supported by JSPS KAHENHI (grant nos.
24686092 and 25630362) and JSPS Grant-in-Aid for Scientific
Research on Innovative Areas ‘3D Active-Site Science’ (grant no.
26105003).
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K. Motokura et al. / Tetrahedron Letters xxx (2014) xxx–xxx
5
Tetrahedron Lett. 2011, 52, 6687; (c) Motokura, K.; Baba, T. Green Chem. 2012,
14, 565; (d) Motokura, K.; Matsunaga, S.; Noda, H.; Miyaji, A.; Baba, T. ACS Catal.
2012, 2, 1942.
Supplementary data
Supplementary data (copies of mass, 1H NMR, and 13C NMR
spectra of products and intermediates, and 1H–1H COSY and
1H–13C HMQC NMR spectra of the product from norbornene are
available free of charge at www.sciencedirect.com.) associated
with this article can be found, in the online version, at http://
dx.doi.org/10.1016/j.tetlet.2014.10.127.
7. Cyanation of heteroaromatics using nitromethane as a source of cyano group
has been reported: (a) Chen, X.; Hao, X.-S.; Goodhue, C. E.; Yu, J.-Q. J. Am. Chem.
Soc. 2006, 128, 6790; (b) Nagase, Y.; Sugiyama, T.; Nomiyama, S.; Yonekura, K.;
Tsuchimoto, T. Adv. Synth. Catal. 2014, 356, 347.
8. High resolution 1H NMR spectrum with enlarged view of intermediate 3 is
shown in Figure S4, Supplementary material.
9. Formation of 1 is an evidence for the existence of 2 during the reaction.
However, the reaction pathway through silylation of oxygen atom of HCNO (Eq.
6) cannot be excluded.
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H
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[Si]+
N
1,3-dipolar addition
SiMe3
O
ð6Þ
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