Eco-friendly conjugate hydrocyanation of α-cyanoacrylates using potassium hexacyanoferrate(II) as cyanating reagent

Article abstract of DOI:10.1515/chempap-2015-0055

The conjugate hydrocyanation of α-cyanoacrylates through chemoselective 1,4-addition to synthesise α,β-dicyanopropanoates by one-pot two-step procedure using potassium hexacyanoferrate(II) as an eco-friendly cyanide source, benzoyl chloride as a promoter

Full text of DOI:10.1515/chempap-2015-0055

Chemical Papers 69 (4) 596–603 (2015)
DOI: 10.1515/chempap-2015-0055
ORIGINAL PAPER
Eco-friendly conjugate hydrocyanation of α-cyanoacrylates using
potassium hexacyanoferrate(II) as cyanating reagent
b
a
aYu-Peng Zhang, Xiao-Chun Hu, Zheng Li*
aCollege of Chemistry and Chemical Engineering, bEditorial Department of the University Journal, Northwest Normal
University, Lanzhou, Gansu 730070, China
Received 30 April 2014; Revised 27 August 2014; Accepted 28 August 2014
The conjugate hydrocyanation of α-cyanoacrylates through chemoselective 1,4-addition to synthe-
sise α,β-dicyanopropanoates by one-pot two-step procedure using potassium hexacyanoferrate(II)
as an eco-friendly cyanide source, benzoyl chloride as a promoter and potassium carbonate as a
catalyst is described. The advantages of this protocol are use of a non-toxic, non-volatile and inex-
pensive cyanating reagent, high product yields and simple working procedure.
c
ꢀ 2014 Institute of Chemistry, Slovak Academy of Sciences
Keywords: conjugate hydrocyanation, α-cyanoacrylate, “green chemistry”, potassium hexacyano-
ferrate(II)
Introduction
for TMSCN and CNCOOEt. To overcome these prob-
lems, the development of alternative cyanide sources
that are relatively cheap, less toxic, and easier to han-
dle has attracted attention.
The conjugate additions of cyanide to α,β-unsatu-
rated carbonyl compounds, such as α,β-unsaturated
ketones (Yang et al., 2009, 2010), amides (Sammis et
al., 2004) and esters (Liu et al., 2013), are useful re-
actions in organic synthesis, especially in asymmetric
synthesis (Liu et al., 2013; Mita et al., 2005; Sammis
et al., 2004; Yang et al., 2010). The conjugate addi-
tion of cyanide to α-cyano acrylate is an important
example. The resulting α,β-dicyanopropanoates are
valuable intermediates for the synthesis of medicines
and can be readily transformed into acids, esters,
amides and amines (Rappoport, 1970). To date, many
cyanating reagents have been used as additions to
α,β-unsaturated esters, such as HCN (Griffiths et al.,
1991), KCN (Aizencang et al., 1995; Sammelson et al.,
2004), NaCN (Das et al., 2008; Rajib et al., 2012),
TMSCN (Mazet & Jacobsen, 2008; Sammis et al.,
2004), CNCOOEt (Wang et al., 2010) and acetone
cyanohydrins (Wakita et al., 1990). However, some
problems continue to be associated with the use of
the existing cyanating reagents, including strong toxi-
city for KCN and NaCN, volatility for HCN, instabil-
ity for acetone cyanohydrins, and moisture sensibility
Potassium hexacyanoferrate(II) (K4[Fe(CN)6]) is
mainly used as carburising reagent in the iron and
steel industry; it is also used in the food indus-
try for metal precipitation and it has been de-
scribed as an anti-agglutinating auxiliary for table salt
(NaCl). K4[Fe(CN)6] is a by-product of the coal chem-
ical industry and commercially available by the tonne;
it is even cheaper than KCN. Recently, K4[Fe(CN)6]
has been used as a cyanide source for some substitu-
tion reactions to synthesise benzonitriles (Schareina et
al., 2004), aroyl cyanides (Li et al., 2006), arylsulpho-
nyl cyanide (Li & Xu, 2014), benzyl cyanides (Ren et
al., 2012) and cinnamonitriles (Saha et al., 2012). The
present work focused on the cyanation of unsaturated
—
—
—
compounds including C O, C N or C C bonds by
—
—
—
nucleophilic addition reactions using K4[Fe(CN)6] as
an eco-friendly cyanide source (Li et al., 2010, 2012,
2013). An efficient method for the conjugate hydro-
cyanation of α-cyanoacrylates through chemoselective
1,4-addition using K4[Fe(CN)6] as a novel eco-friendly
cyanide source is reported.
*Corresponding author, e-mail: lizheng@nwnu.edu.cn
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Table 1. Characterisation data of prepared compounds
597
wi(calc.)/%
wi(found)/%
Yield
M.p.
Compound
Formula
Mr
Appearance
C
H
N
%
90
87
89
86
85
88
84
84
83
85
86
89
82
89
91
77
87
85
90
89
88
◦C
IIa
IIb
IIc
IId
IIe
IIf
C13H12N2O2
C14H14N2O2
C14H14N2O2
C14H14N2O3
C14H14N2O3
C14H12N2O4
228.25
242.27
242.27
258.27
258.27
272.26
246.24
262.69
262.69
296.24
273.24
273.24
218.21
194.23
208.26
304.34
242.27
276.72
180.20
206.24
220.27
68.41
68.27
5.30
5.28
12.27
12.31
57–58
white solid
69.41
69.59
5.82
5.80
11.56
11.59
–
oil
69.41
69.23
5.82
5.83
11.56
11.53
73–74
white solid
65.11
64.99
5.46
5.45
10.85
10.88
–
oil
65.11
65.18
5.46
5.48
10.85
10.81
61–62
white solid
61.76
61.57
4.44
4.43
10.29
10.32
84–86
white solid
IIg
IIh
IIi
C
13H11FN2O2
63.41
63.55
4.50
4.49
11.38
11.40
64–65
white solid
C13H11ClN2O2
C13H11ClN2O2
C14H11F3N2O2
C13H11N3O4
C13H11N3O4
C11H10N2O3
C10H14N2O2
C11H16N2O2
C19H16N2O2
C14H14N2O2
C14H13ClN2O2
C9H12N2O2
59.44
59.60
5.22
5.21
10.66
10.70
49–50
white solid
59.44
59.39
5.22
5.24
10.66
10.63
57–58
white solid
IIj
56.76
56.87
3.74
3.75
9.46
9.43
67–68
white solid
IIk
IIl
57.14
57.00
4.06
4.07
15.38
15.43
–
oil
57.14
57.26
4.06
4.05
15.38
15.34
91–92
white solid
IIm
IIn
IIo
IIp
IIq
IIr
IIs
IIt
60.55
60.59
4.62
4.63
12.84
12.82
–
–
–
–
–
–
–
–
–
oil
oil
oil
oil
oil
oil
oil
oil
oil
61.84
61.96
7.27
7.30
14.42
14.37
63.44
63.57
7.74
7.76
13.45
13.48
74.98
75.09
5.30
5.32
9.20
9.17
69.41
69.33
5.82
5.81
11.56
11.60
60.77
60.90
4.74
4.75
10.12
10.09
59.99
60.18
6.71
6.73
15.55
15.57
C11H14N2O2
C12H16N2O2
64.06
63.97
6.84
6.82
13.58
13.61
IIu
65.43
65.36
7.32
7.30
12.72
12.68
Experimental
in δ relative to Me4Si. Elemental analyses were per-
formed on a Vario El (Elementar, Germany) elemen-
tal analysis instrument. Melting points were observed
in an electrothermal melting point apparatus. Potas-
sium hexacyanoferrate(II) was dried at 80◦C under
vacuum for 24 h and pulverised prior to use. Var-
ious α-cyanoacrylates were prepared in accordance
with procedures in the literature (Das et al., 2008;
Griffiths et al., 1991). The characterisation and spec-
tral data for all products are given in Tables 1
and 2.
General
All chemicals and solvents were purchased from
Aladdin (China). The IR spectra were recorded us-
ing KBr pellets on an Alpha Centauri FTIR (Bruker,
Germany) spectrophotometer. The H NMR and 13C
1
NMR spectra were recorded on a Mercury-400BB
(Varian, USA) instrument using CDCl3 as solvent and
Me4Si as internal standard. Chemical shifts are given
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Y. P. Zhang et al./Chemical Papers 69 (4) 596–603 (2015)
Table 2. Spectral data of prepared compounds
Compound
Spectral data
—
IIa
IIb
IIc
IId
IIe
IIf
IR, (KBr) ν˜/cm−1: 2252 (C—N), 1749 (C O)
—
—
—
1H NMR (CDCl3), δ: 7.44–7.47 (m, 5H), 4.60 (d, J = 5.2 Hz, 1H), 4.33 (q, J = 7.2 Hz, 2H), 3.89 (d, J = 5.2 Hz,
1H), 1.32 (t, J = 7.2 Hz, 3H)
13C NMR (CDCl3), δ: 162.8, 130.6, 130.0, 129.9, 128.0, 116.5, 113.1, 64.4, 43.9, 37.9, 14.1
IR, (KBr) ν˜/cm−1: 2252 (C—N), 1749 (C O)
—
—
—
—
1H NMR (CDCl3), δ: 7.63–7.66 (m, 1H), 7.25–7.35 (m, 3H), 4.80 (d, J = 4.8 Hz, 1H), 4.34 (q, J = 7.2 Hz, 2H), 3.80
(d, J = 4.8 Hz, 1H), 2.37 (s, 3H), 1.34 (t, J = 7.2 Hz, 3H)
13C NMR (CDCl3), δ: 162.8, 134.8, 131.3, 129.8, 128.3, 128.1, 127.3, 116.5, 112.8, 64.1, 42.1, 34.5, 18.7, 13.8
IR, (KBr) ν˜/cm−1: 2252 (C—N), 1749 (C O)
—
—
—
—
1H NMR (CDCl3), δ: 7.31 (d, J = 8.4 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 4.53 (d, J = 5.2 Hz, 1H), 4.30 (q, J =
7.2 Hz, 2H), 3.84 (d, J = 5.2 Hz, 1H), 2.34 (s, 3H), 1.30 (t, J = 7.2 Hz, 3H)
13C NMR (CDCl3), δ: 162.6, 139.9, 130.2, 127.5, 127.3, 116.3, 112.9, 64.1, 43.7, 37.2, 21.1, 13.8
IR, (KBr) ν˜/cm−1: 2247 (C—N), 1743 (C O)
—
—
—
—
1H NMR (CDCl3), δ: 7.61 (d, J = 7.6 Hz, 1H), 7.40–7. 44 (m, 1H), 7.07–7.09 (m, 1H), 6.94 (d, J = 8.4 Hz, 1H),
4.94 (d, J = 4.8 Hz, 1H), 4.36 (q, J = 7.2 Hz, 2H), 4.16 (d, J = 4.8 Hz, 1H), 3.89 (s, 3H), 1.36 (t, J = 7.2 Hz, 3H)
13C NMR (CDCl3), δ: 163.0, 155.5, 131.1, 129.4, 121.4, 118.2, 116.3, 113.0, 110.8, 63.9, 55.6, 40.8, 33.0, 13.8
IR, (KBr) ν˜/cm−1: 2251 (C—N), 1748 (C O)
—
—
—
—
1H NMR (CDCl3), δ: 7.37 (d, J = 8.8 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 4.55 (d, J = 5.6 Hz, 1H), 4.33 (q, J =
7.2 Hz, 2H), 3.86 (d, J = 5.6 Hz, 1H), 3.82 (s, 3H), 1.33 (t, J = 7.2 Hz, 3H)
13C NMR (CDCl3), δ: 162.6, 160.5, 129.0, 122.1, 116.4, 114.9, 112.9, 64.1, 55.3, 43.8, 36.9, 13.8
IR, (KBr) ν˜/cm−1: 2254 (C—N), 1746 (C O)
—
—
—
—
1H NMR (CDCl3), δ: 6.88–6.93 (m, 2H), 6.82–6.85 (m, 1H), 6.01 (s, 2H), 4.51 (d, J = 5.2 Hz, 1H), 4.32 (q, J =
7.2 Hz, 2H), 3.85 (d, J = 5.2 Hz, 1H), 1.34 (t, J = 7.2 Hz, 3H)
13C NMR (CDCl3), δ: 162.5, 148.8, 148.6, 123.7, 121.7, 116.9, 112.8, 108.9, 107.9, 101.7, 64.1, 43.8, 37.3, 13.8
IIg
IIh
IIi
IR, (KBr) ν˜/cm−1: 2255 (C—N), 1745 (C O)
—
—
—
—
1H NMR (CDCl3), δ: 7.45–7.48 (m, 2H), 7.13–7.17 (m, 2H), 4.60 (d, J = 5.2 Hz, 1H), 4.35 (q, J = 7.2 Hz, 2H), 3.89
(d, J = 5.2 Hz, 1H), 1.33 (t, J = 7.2 Hz, 3H)
13C NMR (CDCl3), δ: 164.5, 162.4, 162.0, 129.8, 129.7, 126.2, 116.8, 116.6, 116.1, 112.7, 64.3, 43.6, 36.8, 13.8
IR, (KBr) ν˜/cm−1: 2256 (C—N), 1750 (C O)
—
—
—
—
1H NMR (CDCl3), δ: 7.79–7.81 (m, 1H), 7.40–7.48 (m, 3H), 5.09 (d, J = 4.0 Hz, 1H), 4.41 (q, J = 7.2 Hz, 2H), 4.07
(d, J = 4.0 Hz, 1H), 1.39 (t, J = 7.2 Hz, 3H)
13C NMR (CDCl3), δ: 162.4, 132.2, 131.3, 130.4, 130.3, 130.2, 128.2, 115.6, 112.4, 64.3, 41.3, 35.3, 13.8
IR, (KBr) ν˜/cm−1: 2256 (C—N), 1745 (C O)
—
—
—
—
1H NMR (CDCl3), δ: 7.40–7.45 (m, 4H), 4.58 (d, J = 5.2 Hz, 1H), 4.35 (q, J = 7.2 Hz, 2H), 3.88 (d, J = 5.2 Hz,
1H), 1.34 (t, J = 7.2 Hz, 3H)
13C NMR (CDCl3), δ: 162.4, 136.2, 129.9, 129.2, 128.9, 115.8, 112.6, 64.4, 43.5, 37.1, 13.8
IIj
IR, (KBr) ν˜/cm−1: 2256 (C—N), 1753 (C O)
—
—
—
—
1H NMR (CDCl3), δ: 7.74 (d, J = 6.8 Hz, 2H), 7.63 (d, J = 6.8 Hz, 2H), 4.69 (d, J = 4.8 Hz, 1H), 4.36 (q, J =
7.2 Hz, 2H), 3.92 (d, J = 4.8 Hz, 1H), 1.35 (t, J = 7.2 Hz, 3H)
13C NMR (CDCl3), δ: 162.2, 134.2, 132.3, 132.0, 128.4, 126.6, 124.7, 122.0, 115.6, 112.5, 109.7, 64.4, 43.2, 37.2, 13.7
IIk
IIl
IR, (KBr) ν˜/cm−1: 2253 (C—N), 1750 (C O)
—
—
—
—
1H NMR (CDCl3), δ: 8.20 (d, J = 8.0 Hz, 1H), 8.06 (d, J = 7.6 Hz, 1H), 7.85–7.92 (m, 1H), 7.68–7.72 (m, 1H),
5.41 (d, J = 3.6 Hz, 1H), 4.45 (q, J = 7.2 Hz, 2H), 4.39 (d, J = 3.6 Hz, 1H), 1.42 (t, J = 7.2 Hz, 3H)
13C NMR (CDCl3), δ: 162.2, 147.2, 135.0, 131.9, 131.2, 126.1, 125.7, 115.7, 112.5, 64.5, 42.4, 34.5, 13.9
IR, (KBr) ν˜/cm−1: 2256 (C—N), 1738 (C O)
—
—
—
—
1H NMR (CDCl3), δ: 8.32–8.34 (m, 2H), 7.93 (d, J = 8.0 Hz, 1H), 7.70–7.74 (m, 1H), 4.76 (d, J = 5.2 Hz, 1H),
4.39 (q, J = 7.2 Hz, 2H), 4.01 (d, J = 5.2 Hz, 1H), 1.37 (t, J = 7.2 Hz, 3H)
13C NMR (CDCl3), δ: 162.0, 148.6, 133.9, 132.4, 130.9, 124.8, 123.0, 115.3, 112.3, 64.6, 43.1, 37.0, 13.8
IIm
IIn
IIo
IR, (KBr) ν˜/cm−1: 2258 (C—N), 1749 (C O)
—
—
—
—
1H NMR (CDCl3), δ: 7.45–7.47 (m, 1H), 6.62 (d, J = 3.2 Hz, 1H), 6.42–6.44 (m, 1H), 4.73 (d, J = 4.8 Hz, 1H),
4.36 (q, J = 7.2 Hz, 2H), 4.14 (d, J = 4.8 Hz, 1H), 1.36 (t, J = 7.2, 3H)
13C NMR (CDCl3), δ: 162.3, 144.5, 142.6, 130.1, 128.4, 114.5, 111.3, 64.3, 40.7, 32.0, 13.8
IR, (KBr) ν˜/cm−1: 2249 (C—N), 1750 (C O)
—
—
—
—
1H NMR (CDCl3), δ: 4.36 (q, J = 7.2 Hz, 2H), 3.81 (d, J = 5.6 Hz, 1H), 3.08 (d, J = 5.6 Hz, 1H), 2.06–2.15 (m,
1H), 1.38 (t, J = 7.2 Hz, 3H), 1.11–1.24 (m, 6H)
13C NMR (CDCl3), δ: 163.3, 116.5, 113.1, 64.0, 39.5, 38.5, 29.3, 20.2, 13.8
IR, (KBr) ν˜/cm−1: 2247 (C—N), 1747 (C O)
—
—
—
—
1H NMR (CDCl3), δ: 4.36 (q, J = 7.2 Hz, 2H), 3.69 (d, J = 4.8 Hz, 1H), 3.33 (d, J = 4.8 Hz, 1H), 1.85–1.93 (m,
2H), 1.35–1.49 (m, 4H), 1.03 (t, J = 7.2 Hz, 3H), 0.99 (t, J = 5.6 Hz, 3H)
13C NMR (CDCl3), δ: 163.0, 117.7, 113.0, 64.0, 40.3, 39.0, 30.5, 25.9, 22.5, 21.2, 13.9
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599
Table 2. (continued)
Compound
Spectral data
IIp
IIq
IIr
IR, (KBr) ν˜/cm−1: 2272 (C—N), 1749 (C O)
—
—
—
—
1H NMR (CDCl3), δ: 7.56 (d, J = 7.2 Hz, 2H), 7.40–7.46 (m, 8H), 4.62 (s, 1H), 4.14 (q, J = 7.2 Hz, 2H), 1.12 (t, J
= 7.2 Hz, 3H)
13C NMR (CDCl3), δ: 161.9, 136.0, 135.5, 129.3, 129.2, 127.0, 126.8, 118.8, 113.3, 63.6, 52.5, 46.4, 13.5
IR, (KBr) ν˜/cm−1: 2249 (C—N), 1747 (C O)
—
—
—
—
1H NMR (CDCl3), δ: 7.56 (d, J = 7.6 Hz, 1H), 7.52 (d, J = 7.6 Hz, 1H), 7.41–7.46 (m, 3H), 4.19 (q, J = 7.2 Hz,
2H), 4.01 (s, 1H), 2.04 (s, 3H), 1.18 (t, J = 7.2 Hz, 3H)
13C NMR (CDCl3), δ: 162.1, 135.3, 129.4, 129.3, 125.8, 119.6, 113.1, 63.5, 48.2, 43.2, 24.9, 13.6
IR, (KBr) ν˜/cm−1: 2250 (C—N), 1747 (C O)
—
—
—
—
1H NMR (CDCl3), δ: 7.42–7.53 (m, 4H), 4.22 (q, J = 7.2 Hz, 2H), 3.93 (s, 1H), 2.03 (s, 3H), 1.24 (d, J = 7.2 Hz,
3H)
13C NMR (CDCl3), δ: 161.9, 135.7, 133.9, 129.5, 129.4, 127.5, 127.4, 119.3, 112.8, 63.8, 48.1, 42.7, 24.3, 13.7
IIs
IIt
IR, (KBr) ν˜/cm−1: 2248 (C—N), 1741 (C O)
—
—
—
—
1H NMR (CDCl3), δ: 4.34 (q, J = 7.2 Hz, 2H), 3.69 (s, 1H), 1.61 (s, 6H), 1.36 (t, J = 7.2 Hz, 3H)
13C NMR (CDCl3), δ: 162.5, 120.6, 112.9, 63.7, 46.2, 33.9, 25.7, 24.2, 13.8
IR, (KBr) ν˜/cm−1: 2241 (C—N), 1749 (C O)
—
—
—
—
1H NMR (CDCl3), δ: 4.35 (q, J = 7.2 Hz, 2H), 3.73 (s, 1H), 2.33–2.40 (m, 2H), 1.88–1.99 (m, 6H), 1.36 (t, J =
7.2 Hz, 3H)
13C NMR (CDCl3), δ: 162.8, 120.8, 113.4, 63.7, 44.4, 43.7, 37.4, 36.9, 24.1, 23.9, 13.8
IIu
IR, (KBr) ν˜/cm−1: 2242 (C—N), 1748 (C O)
—
—
—
—
1H NMR (CDCl3), δ: 4.35 (q, J = 7.2 Hz, 2H), 3.64 (s, 1H), 1.52–2.23 (m, 10H), 1.35 (t, J = 7.2 Hz, 3H)
13C NMR (CDCl3), δ: 162.4, 119.0, 113.1, 63.6, 46.5, 40.5, 34.1, 33.0, 24.4, 22.6, 22.5, 13.9
Table 3. Conjugate hydrocyanation of α-cyanoacrylates with K4[Fe(CN)6]a
Entry Compound
Name
R1
R2
H
Product
Time/h Yieldb/%
1
2
3
IIa
IIb
IIc
ethyl 2,3-dicyano-3-phenylpropanoate C6H5
4
4
4
90
87
89
ethyl 2,3-dicyano-3-(o-tolyl)propanoate 2-Me-C6H4
ethyl 2,3-dicyano-3-(p-tolyl)propanoate 4-Me-C6H4
H
H
4
IId
ethyl 2,3-dicyano-3-(2-methoxyphenyl) 2-MeO-C6H4
propanoate
H
4
86
5
6
7
IIe
IIf
IIg
ethyl 2,3-dicyano-3-(4-methoxyphenyl) 4-MeO-C6H4
propanoate
H
H
H
4
4
5
85
88
84
ethyl 3-(benzo[d][1,3]dioxol-5-yl)-2,3-
dicyanopropanoate
ethyl 2,3-dicyano-3-(4-fluorophenyl)
propanoate
4-F-C6H4
2-Cl-C6H4
8
9
IIh
IIi
ethyl 3-(2-chlorophenyl)-2,3-
dicyanopropanoate
H
H
5
5
84
83
ethyl 3-(4-chlorophenyl)-2,3-
dicyanopropanoate
4-Cl-C6H4
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Table 3. (continued)
10
11
IIj
ethyl 2,3-dicyano-3-(4-(trifluoro-
methyl)phenyl)propanoate
4-CF3-C6H4
2-NO2-C6H4
H
H
5
5
85
86
IIk
ethyl 2,3-dicyano-3-(2-nitrophenyl)
propanoate
12
IIl
ethyl 2,3-dicyano-3-(3-nitrophenyl)
propanoate
3-NO2-C6H4
H
5
89
13
14
15
IIm
IIn
IIo
ethyl 2,3-dicyano-3-(furan-2-
yl)propanoate
H
H
H
5
4
4
82
89
91
ethyl 2,3-dicyano-4-methylpentanoate
ethyl 2,3-dicyanoheptanoate
(CH3)2CH
CH3(CH2)3
16
IIp
ethyl 2,3-dicyano-3,3-diphenyl-
propanoate
C6H5
C6H5
6
77
17
18
19
IIq
IIr
IIs
ethyl 2,3-dicyano-3-phenylbutanoate
C6H5
Me
Me
Me
6
6
4
87
85
90
ethyl 3-(4-chlorophenyl)-2,3-
dicyanobutanoate
4-Cl-C6H4
ethyl 2,3-dicyano-3-methylbutanoate
Me
20
21
IIt
ethyl 2-cyano-2-(1-cyanocyclopentyl)
acetate
-(CH2)4-
5
5
89
88
IIu
ethyl 2-cyano-2-(1-cyanocyclohexyl)
acetate
-(CH2)5-
a) Reaction conditions: K4[Fe(CN)6] (0.4 mmol), benzoyl chloride (2 mmol), α-cyanoacrylate (2 mmol) and potassium carbonate
(0.2 mmol) in 5 mL of EtOH, 160◦C and r.t.; b) isolated yields.
General procedure for conjugate hydrocyana-
tion of α-cyanoacrylates
filtered to remove the solids, then the liquor was con-
centrated and the residue was separated by column
chromatography using petroleum ether and ethyl ac-
etate (ϕr = 10 : 1) as eluent to obtain the pure prod-
uct.
The mixture of K4[Fe(CN)6] (0.4 mmol) and ben-
zoyl chloride (2 mmol) was heated at 160◦C for 3 h,
then the reaction system was cooled to ambient tem-
perature, α-cyanoacrylate (2 mmol), potassium car-
bonate (0.2 mmol) and ethanol (5 mL) were added.
The mixture was stirred at ambient temperature for
the appropriate time as indicated in Table 3. After
completion of the reaction monitored by TLC, the re-
sulting mixture was diluted using ethanol (5 mL) and
Results and discussion
Previously, our groups explored a highly efficient
promoter to abstract cyanide ions from K4[Fe(CN)6]
without using any transition metals as catalysts. It
was found that benzoyl chloride could efficiently pro-
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Table 4. Effect of catalysts on yield of conjugate hydrocyanation of Ia with K4[Fe(CN)6]a
Entry
Catalyst
Reaction time/h
Yieldb/%
1
2
3
4
5
6
7
8
9
K2CO3
Na2CO3
NaHCO3
Et3N
DMAP
DABCO
piperidine
HOAc
3
3
3
3
3
3
3
24
24
90
86
55
76
41
30
68
0
HCl
0
a) Reaction conditions: K4[Fe(CN)6] (0.4 mmol), benzoyl chloride (2 mmol), Ia (2 mmol) and catalyst (0.2 mmol) in 5 mL of
ethanol at 160◦C and r.t.; b) isolated yields.
Table 5. Effect of solvents on yield of conjugate hydrocyanation of Ia with K4[Fe(CN)6]a
Entry
Solvent
Reaction time/h
Yieldb/%
1
2
3
4
5
6
7
8
CH2Cl2
PhMe
DMF
EtOH
MeOH
i-PrOH
MeCN
THF
24
24
3
3
3
3
3
3
0
0
0c
90
50
87
85
30
a) Reaction conditions: K4[Fe(CN)6] (0.4 mmol), benzoyl chloride (2 mmol), Ia (2 mmol) and potassium carbonate (0.2 mmol) in
5 mL of solvent, 160◦C and r.t.; b) isolated yields; c) unidentified by-products were observed.
mote a release of cyanide ions from K4[Fe(CN)6] to
obtain an intermediate benzoyl cyanide (Li et al.,
2010). Accordingly, in the present work, ethyl 2-
cyano-3-phenylacrylate (Ia) was selected as a sub-
strate for testing the feasibility of hydrocyanation of
α-cyanoacrylates by using K4[Fe(CN)6] as an eco-
friendly cyanide source and benzoyl chloride as a
promoter. It was demonstrated that benzoyl chloride
could efficiently promote the reaction to produce 1,4-
adduct, 2,3-dicyano-3-phenylpropanoate (IIa) under
the appropriate conditions. In addition, no 1,2-adduct
and other by-products were observed in this reaction,
which indicated the high chemoselectivity of the reac-
tion.
NaHCO3, 4-dimethylaminopyridine (DMAP), triethyl-
amine (Et3N), 1,4-diazabicyclo[2.2.2]octane (DABCO)
and piperidine (Table 4, Entries 1–7). Amongst
these, K2CO3 could afford the best yield in the short-
est time. However, some acids (HOAc and HCl) had
no catalytic effect on the reaction (Table 4, Entries 8
and 9).
The solvents also have significant effects on the re-
action (Table 5). It was found that the reaction in
PhMe, CH2Cl2 could not afford any of the desired
products (Table 5, Entries 1 and 2) while the reaction
in N,N-dimethylformamide (DMF) only afforded the
unidentified by-products (Table 5, Entry 3). However,
the reaction in MeOH, EtOH, i-PrOH, MeCN and
tetrahydrofurane (THF) was able to proceed smoothly
to afford the desired product with mid to high yields
(Table 5, Entries 4–8). Amongst these, EtOH was the
best solvent for the reaction (Table 5, Entry 4).
Under the optimal conditions, a series of 3-
Catalysts played a key role in the reaction. Some
catalysts were examined for the reaction of Ia with
K4[Fe(CN)6] using benzoyl chloride as a promoter (Ta-
ble 4). It was found that the reaction could take place
by using bases as catalysts, such as K2CO3, Na2CO3,
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602
Y. P. Zhang et al./Chemical Papers 69 (4) 596–603 (2015)
Fig. 1. Conjugate hydrocyanation of α-cyanoacrylates. For substituents R1 and R2, see Table 3.
Fig. 2. Proposed mechanism for conjugate hydrocyanation of α-cyanoacrylates with K4[Fe(CN)6].
position mono- or di-substituted α-cyanoacrylates
were investigated for the conjugate hydrocyanation
using K4[Fe(CN)6] as a cyanide source, benzoyl chlo-
ride as a promoter and potassium carbonate as a cata-
lyst in ethanol (Fig. 1). The results are summarised in
Table 3. In general, α-cyanoacrylates with 3-position
mono-aromatic substituents all afforded the corre-
sponding 3-aryl-2,3-dicyanopropanoates with a high
yield (Table 3, Entries 1–12). The electron-donating
(Me, MeO) and electron-withdrawing (F, Cl, CF3,
NO2) groups on the aromatic rings had no obvi-
ous effect on the reactions. Heteroaryl-substituted α-
cyanoacrylate was also efficient in the reaction (Ta-
ble 3, Entry 13). The aliphatic mono-substituted α-
cyanoacrylates could also afford the desired prod-
ucts with a satisfactory yield (Table 3, Entries
14 and 15). By contrast, 3-position di-substituted
α-cyanoacrylates exhibited different situations. α-
Cyanoacrylates bearing 3-position diaryl groups gave
a slightly lower yield for the corresponding products
because of the large sterical hindrance (Table 3, Entry
16) although dialkyl α-cyanoacrylates remained highly
efficient in the reactions (Table 3, Entries 19–21).
A plausible mechanism for the conjugate hydro-
cyanation of α-cyanoacrylates using K4[Fe(CN)6] as
a cyanide source is given in Fig. 2. K4[Fe(CN)6] first
reacts with benzoyl chloride to form benzoyl cyanide
as an intermediate. Next, benzoyl cyanide is attacked
by water from the undried solvent in the presence of
potassium carbonate to produce cyanide ion in situ,
which subsequently reacts with α-cyanoacrylates I by
1,4-addition to form intermediates III. Intermediates
III combine with hydrogen ion from water to produce
the final products, α,β-dicyanopropanoates II.
Conclusions
In summary, an eco-friendly method for the con-
jugate hydrocyanation of α-cyanoacrylates through
chemoselective 1,4-addition to synthesise α,β-dicyano-
propanoates by a one-pot two-step procedure has
been developed, using K4[Fe(CN)6] as an eco-friendly
cyanide source, benzoyl chloride as a promoter and
potassium carbonate as a catalyst. The advantageous
features of this protocol include the use of a non-toxic,
non-volatile and inexpensive cyanating reagent, high
yield, broad substrate scope and simple working pro-
cedure.
Acknowledgements. The authors wish to thank the National
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Y. P. Zhang et al./Chemical Papers 69 (4) 596–603 (2015)
603
Natural Science Foundation of China (21162024, 21462038)
for the financial support provided for this work.
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Supplementary data
Supplementary data associated with this article
can be found in the online version of this paper (DOI:
10.1515/chempap-2015-0055).
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