3-Butyl-1-methylimidazolinium borohydride ([bmim][BH4])-a novel reducing agent for the selective reduction of carbon-carbon double bonds in activated conjugated alkenes

Article abstract of DOI:10.1016/j.tetlet.2008.08.110

A novel ionic reducing reagent, 3-butyl-1-methylimidazolium borohydride ([bmim][BH₄]), was synthesized and successfully used for the selective reduction of carbon-carbon double bonds in conjugated alkenes as well as the α,β-carbon-carbon double bonds in highly activated α,β,γ,δ-unsaturated alkenes. The reagent can be regenerated and reused several times without losing its activity.

Full text of DOI:10.1016/j.tetlet.2008.08.110

Tetrahedron Letters 49 (2008) 6518–6520
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Tetrahedron Letters
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3-Butyl-1-methylimidazolinium borohydride ([bmim][BH4])—a novel
reducing agent for the selective reduction of carbon–carbon double
bonds in activated conjugated alkenes
*
Jiayi Wang, Gonghua Song , Yanqing Peng, Yidong Zhu
Shanghai Key Laboratory of Chemical Biology, Institute of Pesticides and Pharmaceuticals, East China University of Science and Technology, Shanghai 200237, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel ionic reducing reagent, 3-butyl-1-methylimidazolium borohydride ([bmim][BH4]), was synthe-
sized and successfully used for the selective reduction of carbon–carbon double bonds in conjugated
Received 19 May 2008
Revised 27 August 2008
Accepted 29 August 2008
Available online 3 September 2008
alkenes as well as the
a,b-carbon–carbon double bonds in highly activated a,b,c,d-unsaturated alkenes.
The reagent can be regenerated and reused several times without losing its activity.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Reduction
Double bond
Ionic reducing reagent
Selective
The selective reduction of carbon–carbon double bonds,
especially conjugated double bonds, is a real challenge in organic
synthesis. Typically, either a metal-containing catalyst or a com-
plex reducing reagent is needed to obtain the target product in
acceptable yield and selectivity. Examples of such reducing sys-
tems include resin supported formates-Pd catalyst,1 combination
of a formate reagent and palladium catalyst,2 1,4-dihydropyridine
ester,3 combination of sodium cyanoborohydride and acid,4 indium
metal,5 combination of sodium borohydride and indium(III)
chloride,6 ruthenium complexes7 and copper hydride complex.8,9
Unfortunately, these methods are rather expensive and some
may also have a negative environmental impact. Sodium boro-
hydride has been traditionally used as a reducing agent for
ketones,10 aldehydes,10 C–N double bonds,11 alkenes,12 esters,13
carboxyls,14 alkynes,15 oximes16 and nitryls.17 It was reported that
a few electron-deficient alkenes could also be reduced by sodium
borohydride without any catalyst.7d But it required an extended
reaction time (22 h) at 100 °C, which is obviously unsuitable for
alkenes with sensitive groups. During our research on functional-
ized ionic liquids, a novel ionic reducing reagent, 3-butyl-1-
methyl-imidazolium borohydride ([bmim][BH4]), was synthesized
and successfully applied to the reduction of carbon–carbon double
bonds in conjugated alkenes as well as to the selective reduction of
ture without any catalyst (Scheme 1). The reagent can be regener-
ated and recycled several times without losing its activity.
As shown in Scheme 2, 1-methylimidazole and 1-bromobutane
were reacted at 80 °C for 3 h to form 3-butyl-1-methyl-imidazoli-
um bromide. [bmim][BH4] was then afforded by anion metathesis
between 1-butyl-3-methylimidazolium bromide and sodium boro-
hydride in anhydrous acetonitrile.18 To avoid degradation, caution
needs to be exercised to exclude moisture from [bmim][BH4] in
storage.
For the reduction of a conjugated alkene or an
a,b,c,d-unsatu-
rated alkene, 1.2 equiv [bmim][BH4] was stirred with an alkene
in the mixed solvent of acetonitrile and water (6:1) for a certain
R1
R2
E1
E2
R1
R2
E1
E2
[bmim][BH4]
E1
CH3CN:Water (6:1)
rt, 0.25-2 h
E1
R3
R3
E2
E2
R1 = Ph, p-(MeO)-C6H4, m-(NO2)-C6H4...
R2 = H, alkyl.
R3 = Ph, p-(MeO)-C6H4.
E1 = CN, COOEt,COOBun
E2 = H, CN, COOEt.
[bmim][BH4]:
a
,b-carbon–carbon double bonds in a,b,c,d-unsaturated dicyano
compounds, cyanoesters and dicarboxylic esters at room tempera-
N
N
-
BH4
* Corresponding author. Fax: +86 21 64252603.
E-mail address: ghsong@ecust.edu.cn (G. Song).
Scheme 1. Reduction of carbon–carbon bonds.
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.08.110

J. Wang et al. / Tetrahedron Letters 49 (2008) 6518–6520
6519
H2O
N
N
N
N
1-bromobutane
80 oC, 3 h
excess
-
BH4
NaBH4
N
N
N
N
anhydrous CH3CN
rt ,1 d
OH-
-
N
N
BH4
Br-
Scheme 2. Synthesis of ionic reducing reagent.
diluted HCl solution
NaBH4
CH3CN
period of time (monitored by TLC) at room temperature. After
removing the solvent in vacuo, the reaction mixture was quenched
with water and the aqueous solution was extracted with ether.
After removing the ether, the crude reduction product obtained
was purified by column chromatography over silica gel.19,20
As shown in Table 1, a wide range of electron-deficient alkenes
N
N
Cl-
Scheme 3. Regeneration of reducing reagent.
a
-substituted by dicyano olefins, cyanoesters or dicarboxylic
esters, could be reduced to their corresponding alkanes by
[bmim][BH4] in good yields (84–92%). While the carbon–carbon
double bonds were efficiently reduced, sensitive groups such as
NO2 (entry 4), Cl (entry 5), MeO (entries 2, 8 and 9), methylenedi-
oxy (entries 3 and 10) on phenyl, as well as the sensitive furan (en-
try 11) remained unaffected. Butyl acrylate (entry 18) can also be
reduced to butyl propionate without any difficulty. [bmim][BH4]
was also applied to the reduction of highly activated
urated dienes ( -substituted by dicyano compounds, cyanoesters
or dicarboxylic esters). Only the ,b-carbon–carbon double bond
was reduced, and the corresponding ,d-unsaturated derivations
was treated with sodium borohydride in the solution of [bmim]Cl
(2 mmol) in acetonitrile (1 ml) to demonstrate the possible activa-
tion of [bmim]Cl. The yield of product was only 42%. The high
activity of [bmim][BH4] may be due to its high solubility in organic
solvents and good affinity for substrates.
The reducing agent [bmim][BH4] can be regenerated conve-
niently (Scheme 3). After extracting the reduction product from a
quenched reaction mixture, the residue was neutralized with
a,b,c,d-unsat-
a
a
c
Table 2
were accessed in moderate to good yields (69–84%).
Reducing with regenerated [bmim][BH4]
In a comparative study, butyl acrylate (entry 18) was treated
with sodium borohydride in the mixed solvent of acetonitrile and
water (6:1) at room temperature for 2 h. The yield of product
was only 23%. 2-(3-phenylallylidene) malononitrile (entry 13)
Cycle no.
Yielda (%)
1
86
2
84
3
85
a
Isolated yields.
Table 1
Reduction of conjugated alkenes by [BMIM]BH4
R1
R2
E1
R1
R2
E1
E2
E1
E2
E1
[BMIM]BH4
CH3CN:Water (6:1)
R3
R3
E2
E2
Entry
R1
R2
R3
E1
E2
Time (min)
Yielda (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
Ph
H
H
H
H
H
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
COOEt
CN
CN
CN
CN
CN
CN
CN
COOEt
COOEt
COOEt
COOEt
COOEt
COOEt
CN
30
20
20
15
15
50
40
30
20
30
30
60
50
45
70
70
90
120
86 (0b,6b
92
88
85
84
88
85
90
85
)
p-(MeO)-Ph
3,4-Methylenedioxy-Ph
m-(NO2)-Ph
2,4-Dichloro-Ph
Cyclohexylidene
Ph
p-(MeO)-Ph
3,4-Dimethyloxy-Ph
3,4-Methylenedioxy-Ph
H
H
H
H
H
H
H
H
H
H
H
H
87
86
85
a-Furanyl
2,4-Dichloro-Ph
Ph
82 (42,c 70d)
p-(MeO)-Ph
Ph
p-(MeO)-Ph
Ph
CN
CN
CN
COOEt
H
CN
84
75
78
69
COOEt
COOEt
COOEt
H
COO-n-Butyl
88e (23e,f
)
a
Isolated yields, all products were identified by 1H NMR, 13C NMR and GC–MS/HRMS.
Reaction was conducted with sodium borohydride in acetonitrile.6b
Reaction was conducted with sodium borohydride in the solution of [bmim]Cl (2 mmol) in acetonitrile (1 ml) for 50 min at room temperature.
Reaction was conducted with [bmim]BH4 in acetonitrile for 50 min at room temperature.
Determined by GC.
b
c
d
e
f
Reaction was conducted with sodium borohydride in CH3CN/Water (6:1) for 2 h at room temperature.

6520
J. Wang et al. / Tetrahedron Letters 49 (2008) 6518–6520
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diluted HCl solution to afford an aqueous solution of 3-butyl-1-
methylimidazolinium chloride. The solution was then dehydrated
in vacuo, followed by anion exchange with sodium borohydride
in anhydrous acetonitrile to give the regenerated [bmim][BH4]. In
the demonstration reduction of 2-benzylidenemalono-nitrile, the
regenerated [bmim][BH4] can be reused at least three times with-
out losing its activity (Table 2).
In conclusion, a new reducing reagent, 3-butyl-1-methylimida-
zolium borohydride ([bmim][BH4]), has been synthesized and
successfully applied to the chemoselective reduction of carbon–
carbon double bonds in conjugated alkenes as well as to the selec-
13. (a) Boechat, N.; Costa, J. C. S.; Mengdonca, J. S.; Oliveria, P. S. M.; Souza, M. V. N.
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tive reduction of the
a,b-carbon–carbon double bonds in highly
activated ,b, ,d-unsaturated alkenes. This method has the advan-
a
c
16. Bandgar, B. P.; Wadgaonkar, P. P. Synth. Commun. 1995, 25, 863–869.
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tage of good reductive activity, room temperature reaction, no
need for catalyst and easy reagent regeneration. Further work to
apply this reducing reagent to other substrates is in progress.
18. General procedure for synthesis of [bmim][BH4]: A mixture of 1-methylimidazole
(4.1 g, 0.05 mol) and 1-bromobutane (6.85 g, 0.05 mol) in absence of solvent
was heated with stirring at 80 °C for 3 h. Then, the product was washed with
dimethyl ether and dried in vacuum to afford [bmim]Br. On completion, 50 ml
of CH3CN and 2.28 g NaBH4 (0.06 mol) were added in sequence. The mixture
was stirred for 24 h at room temperature under nitrogen. After filtrating, the
filtrate was evaporated in vacuo to get [bmim][BH4] (7.39 g, 0.048 mol, yield
96%) as a viscous liquid: 1H NMR (CDCl3, 400 MHz): d 9.85 (s, 1H), 7.46 (s, 1H),
7.38 (s. 1H), 4.27 (t, J = 7.2 Hz, 2H), 4.05 (s, 3H), 1.85–1.92 (m, 2H), 1.32–1.41
(m, 2H), 0.94 (t, J = 7.6 Hz, 3H), ꢀ0.21–0.41 (4H); 13C NMR (CDCl3, 100 MHz): d
137.29, 123.60, 122.12, 49.73, 36.52, 32.08, 19.36, 13.36; HRMS (ESI) calcd for
C16H34BNþ4 (2 M-BHꢀ4 ) 293.2871, found 293.2897.
Acknowledgements
Financial support for this work from the NSFC (Grant
20676033), Shanghai Commission of Science and Technology and
Shanghai Leading Academic Discipline Project (Project Number:
B507) are gratefully acknowledged.
19. General procedure for reduction: (a) Representative procedure for the reduction
of 2-benzylidenemalononitrile (Table 1, entry 1): To a stirred solution of 2-
benzylidenemalononitrile (154 mg, 1 mmol) in acetonitrile (3 ml) and water
(0.5 ml), [bmim][BH4] (185 mg, 1.2 mmol) was added at room temperature.
Stirring was continued for another 0.5 h (monitored by TLC), and the solvent
was evaporated to leave water. Then, 10 ml water was added to the residue to
quench the remaining [bmim][BH4], and 10 ml diethyl ether was added to
extract the organic compound for three times. The combined ether extract was
washed with brine, dried (Na2SO4) and evaporated to leave the crude products
which were purified by column chromatography over silica gel to furnish the
pure 2-benzylmalononitrile (0.137 mg, 88%) as a white solid: 1H NMR(CDCl3,
400 MHz): d 7.33–7.43 (m, 5H), 3.92 (t, J = 7.0 Hz, 1H), 3.31 (d, J = 3.6 Hz, 2H);
13C NMR (CDCl3,100 MHz): d 132.91, 129.31 (2C), 129.11 (2C), 128.84, 112.11
(2C), 36.78, 24.99; MS (GC/MS) m/z: 156(M+), 91. This procedure was followed
for the reduction of all the substrates listed in Table 1. (b) Procedure for the
reduction of butyl acrylate (Table 1, entry 18,): To a stirred solution of butyl
acrylate (0.128 mg, 1 mmol) and water (0.2 ml), [bmim][BH4] (185 mg,
1.2 mmol) was added at room temperature. Stirring was continued for
another 2 h. Then 5 ml water was added to quench the reaction, and 5 ml
diethyl ether was added to extract the organic compound for three times. The
combined ether extract was washed with brine, dried (Na2SO4) and evaporated
to leave the crude products as a colourless liquid. The yield of product was 88%
(GC).
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2008.08.110.
References and notes
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20. Characterization of the products. Entry 14: 1H NMR (CDCl3, 400 MHz): d 7.34 (d,
J = 4.4 Hz, 2H), 6.88 (d, J = 4.4 Hz, 2H), 6.65 (d, J = 7.8 Hz, 1H), 6.01–6.08 (m,
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159.95, 136.71, 128.29, 127.95, 127.88 (2C), 117.30, 114.14 (2C), 112.19, 55.33,
34.41, 23.55; MS (GC/MS) m/z: 212(M+), 147, 132, 115, 103, 91; HRMS (EI)
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1H), 6.00–6.08 (m, 1H), 4.28 (q, J1 = 7.1 Hz, J2 = 3.6 Hz, 2H), 3.82 (s, 3H), 3.61 (t,
J = 6.4 Hz, 1H), 2.84 (t, J = 3.2 Hz, 2H), 1.32 (t, J = 6.8 Hz, 3H); 13C NMR (CDCl3,
100 MHz) d 165.57, 159.49, 134.42, 129.11, 127.63 (2C), 120.15, 116.19, 114.02
(2C), 62.88, 55.29, 38.06, 33.39, 14.03; MS (GC/MS) m/z: 259(M+), 147, 115, 91;
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