Cu-catalyzed debrominative cyanation of gem-dibromoolefins: A facile access to α,β-unsaturated nitriles

Article abstract of DOI:10.1039/c5ob00394f

An efficient catalytic route for the synthesis of α,β-unsaturated nitriles from easily accessible gem-dibromoolefins has been developed. The method utilized inexpensive reagents such as Cu₂O as a catalyst, l-proline as a ligand and NaCN as a cyanide source to afford α,β-unsaturated nitriles in high yields (62-86%). A deuterium exchange study has shown that one of the bromide atoms of gem-dibromoolefins exchanges with cyanide while the other with a deuterium atom.

Full text of DOI:10.1039/c5ob00394f

Organic &
Biomolecular Chemistry
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Cu-catalyzed debrominative cyanation of
gem-dibromoolefins: a facile access to
α,β-unsaturated nitriles†
Cite this: Org. Biomol. Chem., 2015,
13, 5918
Brij Bhushan Ahuja and Arumugam Sudalai*
An efficient catalytic route for the synthesis of α,β-unsaturated nitriles from easily accessible gem-dibro-
moolefins has been developed. The method utilized inexpensive reagents such as Cu2O as a catalyst,
L-proline as a ligand and NaCN as a cyanide source to afford α,β-unsaturated nitriles in high yields
(62–86%). A deuterium exchange study has shown that one of the bromide atoms of gem-dibromoolefins
exchanges with cyanide while the other with a deuterium atom.
Received 26th February 2015,
Accepted 20th April 2015
DOI: 10.1039/c5ob00394f
www.rsc.org/obc
α,β-Unsaturated nitriles are ubiquitous structural units fre-
quently found in natural products and act as valuable syn-
thetic intermediates for pharmaceuticals, agrochemicals, dyes
and functional materials.1 They also serve as synthetic precur-
sors for the transformation of a variety of functional groups
such as amides, esters, ketones, amines and alcohols.2 The
compact nature of the nitrile moiety, as well as its hydrogen
bond accepting ability, and metabolic stability have made it an
important functional group in medicinal chemistry research.
Some of the representative examples of pharmaceutical agents
which comprise an α,β-unsaturated nitrile group include
IDX899 and rilpivirine, the potent anti-HIV nonnucleoside
reverse transcriptase inhibitors; entacapone, a drug for Parkin-
son’s disease; and CC-5079, the anticancer agent (Fig. 1).3
Therefore, the development of newer methods for their facile
access is of significant interest for organic chemists. A number
of synthetic routes to α,β-unsaturated nitriles are known such
as amide dehydrogenation reaction,4 Wittig/Horner–Wads-
worth–Emmons5 or Peterson olefination,6 carbocyanation of
alkynes,7 cyanation of alkenyl halides8 and oxidative trans-
formation of the corresponding aldehydes,9 amines,10
amides,11 alcohols,12 azides,13 and hydrazones.14 Although
some of these methods are attractive, they suffer from certain
limitations of using extreme conditions, poor yields and
expensive reagents. Therefore, the development of a con-
venient and user-friendly procedure for the synthesis of α,β-un-
saturated nitriles by using inexpensive reagents and from
easily accessible starting materials is highly desirable.
Fig. 1 Representative examples of pharmaceuticals containing the
α,β-unsaturated nitrile group.
The chemistry of gem-dibromoolefins (1a–r), was almost
confined to the synthesis of terminal alkynes through the
Corey–Fuchs reaction.15 Recently, the versatility of gem-dibromo-
olefins has been exploited in the synthesis of various carbo-
cycles and heterocycles such as indoles,16 benzofuran,17
benzothiophenes,18 isocoumarins19 and other heterocycles20
through metal catalyzed tandem coupling reactions (Suzuki,
Sonogashira, Heck or Ullmann type) or C–H activation. In
addition the versatility of gem-dibromoolefins in metal cata-
lyzed cross coupling reactions with alkynes, vinylalanes and
organoboranes, and tin, magnesium and zinc compounds to
give
a highly stereoselective synthesis of trisubstituted
alkenes21 by prudent selection of the coupling partner has
been exploited. To the best of our knowledge, a direct method
for the synthesis of α,β-unsaturated nitriles utilizing gem-
dibromoolefins as precursors remains elusive in the literature.
In continuation of our studies on the Cu-mediated/catalyzed
National Chemical Laboratory, Chemical Engineering & Process Development
Division, Pune 411008, Maharastra, India. E-mail: a.sudalai@ncl.res.in;
Fax: +91 20 25902676; Tel: +91 20 25902174
†Electronic supplementary information (ESI) available: Experimental procedure,
characterization data, and 1H and 13C NMR spectra. See DOI: 10.1039/
c5ob00394f
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12 h were the best optimized conditions for achieving 2a in
high yields (81%, entry 4), however, significant improvement
in selectivity was not observed. Replacing the solvent (dioxane,
toluene) or CN source (K4[Fe(CN)6] or TMSCN) had a deleter-
ious effect on the conversion (entries 4 and 8). Also lowering
the Cu2O concentration (5 mol%) afforded 2a in low yields
(43%). The result was also inferior when the catalyst was
changed to CuX (X = Br, Cl, I or CN) (entries 10–13).
Scheme 1 Cu2O catalyzed synthesis of α,β-unsaturated nitriles from
gem-dibromoolefins.
With the optimized conditions in hand [Cu2O (10 mol%),
L-proline (10 mol%), NaCN (1.2 equiv., DMF, 110 °C], we then
investigated the generality of this copper(I) oxide catalyzed de-
brominative cyanation of gem-dibromoolefins 1a–r (Table 2).
The starting materials 1a–r are readily prepared from the
corresponding commercially available aldehydes via the
Ramirez procedure.24 The substrates bearing different substi-
tutions like halogen, alkyl, alkoxy, nitro, thio etc. group on the
aromatic nucleus were well tolerated under the reaction con-
ditions and the E and Z substituted α,β-unsaturated nitriles
(2a–r) were isolated in good yields. In the case of p-chlorocin-
namonitrile 2d we obtained a single E isomer. In addition
to the aryl group, the reaction also proceeded equally well with
different gem-dibromoolefins including heteroaryl- and alkenyl
substituted alkenes. Interestingly, when 4-(3,3-dibromoallyl)-
1,2-dimethoxybenzene 1m was subjected to the standarized
conditions we obtained the isomerized product i.e. β,γ-unsatu-
rated nitrile as a single E isomer. Intriguingly, (2,2-dibromo-
vinyl)ferrocene (1n) performed well, under the optimized
development of newer synthetic methodologies,22 herein we
report a novel Cu2O catalyzed synthesis of α,β-unsaturated
nitriles from gem-dibromoolefins (Scheme 1).
In our initial study, (2,2-dibromovinyl)benzene (1a) was
treated with CuCN (3 equiv.) in DMF at 150 °C, which gave the
corresponding cinnamonitrile (2a) in 21% yield with an E/Z
ratio of 4.5/1 (Table 1, entry 1). The yield of 2a was, however,
significantly improved to 57% when L-proline (L1) was used as
a promoter in combination with CuCN in DMF at 120 °C
(entry 2).23 In order to provide a catalytic process, we have
carried out the cyanation reaction with copper(I) oxide as a
catalyst, and NaCN as a CN source. Thus, by using Cu2O
(10 mol%) along with NaCN (1.1 equiv.), 2a was obtained in
low yields (24%, entry 3). In order to improve the yield and
selectivity, a series of N-based ligands [L-proline (L1), 1,10-phe-
nanthroline (L2), N,N-dimethylethylenediamine (L3) and 1,2-
ethylenediamine (L4)] were screened along with Cu2O (entries
4–7). After several experimentations, it was found that a combi-
nation of (2,2-dibromovinyl)benzene, NaCN, copper(I) oxide
(10 mol%), and L-proline (L1, 10 mol%) in DMF at 110 °C for
Table 2 Cu2O catalyzed synthesis of substituted α,β-unsaturated
nitriles (2a–r): substrate scopea
Table 1 Cu2O-catalyzed synthesis of cinnamonitrile 2a: optimization
studiesa
No.
Substrates (1a–r) (R)
Yieldb (%)
E/Zc
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
Phenyl
4-OMe-phenyl
4-F-phenyl
84
86
80
82
89
82
79
84
86
79
84
76
74
71
74
62
72
74
4.5 : 1
1.2 : 1
1.2 : 1
E only
2 : 1
1.2 : 1
4 : 1
3 : 1
2 : 1
2 : 1
2 : 1
Ligand/additive
(10 mol%)
CN source
(equiv.)
No.
Catalyst
Yieldb (%)
4-Cl-phenyl
4-MeS-phenyl
4-CF3-phenyl
4-NO2-phenyl
2-NO2-phenyl
4-Me-phenyl
2-Thienyl
2-Furyl
Cinnamyl
3,4-(OMe)2-benzyl
Ferrocenyl
2-Br-5-OMe-phenyl
2-Br-4,5-(OMe)2-phenyl
2-Br-3,4,5-(OMe)3-phenyl
2-Br-3,5-(OMe)2-phenyl
1
2
3
4
5
6
7
8
—
—
—
CuCN (3)
CuCN (2.2)
NaCN
21c
L1 (1 equiv.)
57d
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
CuI
—
L1
L2
L3
L4
KI
L1
L1
L1
L1
L1
24
NaCN (1.1)
NaCN (1.1)
NaCN (1.1)
NaCN (1.1)
K4[Fe(CN)6] (0.5)
TMSCN
NaCN (1.1)
NaCN (1.1)
NaCN (1.1)
NaCN (1.1)
81 (43e tracef)
68
41
26
1.2 : 1
E onlyd
3 : 1
Traceg
Trace
76
9
3 : 1e
4 : 1e
3 : 1e
4 : 1e
10
11
12
13
CuBr
CuCl
CuCN
68
66
54
a (2,2-Dibromovinyl)benzene (3 mmol), catalyst (10 mol%), ligand
(10 mol%), solvent 10 mL, 12 h. b Isolated yield after column
chromatographic purification. c Temp. 150 °C. d Temp. 120 °C. e 5 mol%
Cu2O was used. f Toluene and dioxane were used separately. g DMF : H2O
was used (1 : 1).
a Reaction conditions: gem-dibromoolefin (3 mmol), NaCN (3.3 mmol),
Cu2O (10 mol%), L-proline (10 mol%), DMF, 110 °C, 12 h. b Isolated
yield after column chromatographic purification. c Determined from
1H NMR. d CvC isomerized to the β,γ-(benzylic) position. e Br on the
aromatic nucleus was also exchanged with CN.
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In conclusion, we have developed an efficient catalytic
process for the synthesis of α,β-unsaturated nitriles from gem-
dibromoolefins using Cu(I) oxide as a catalyst, L-proline as a
ligand, and NaCN as a cyanide source. The easily accessible
starting materials, broad reaction scope and use of cheap com-
mercially available reagents make this method of high signifi-
cance in organic synthesis.
Scheme 2 Deuterium exchange experiment.
Experimental section
General
conditions to generate the expected product in 71% yield. In
all cases we obtained thermodynamically stable E as the major
product with the ratio varying from 1.2 : 1 to 100 : 0. However,
in the case of aliphatic gem-dibromoolefins we obtained a
complex reaction mixture, which may be a limitation of this
catalytic process.
In order to gain insight into the mechanistic details of the
reaction, p-nitrodibromoalkene 1g was treated with Cu2O
(10 mol%), L-proline (10 mol%), NaCN (1.2 equiv.), and D2O (2
equiv.) in DMF at 110 °C for 12 h which resulted in α-deuter-
ated p-nitrocinnamonitrile 3 (Scheme 2). Based on this deuter-
ated study, a probable mechanism for the debrominative
coupling reaction has been proposed. First L-proline interacts
with Cu2O to generate a proline-Cu(I) complex A.25 The oxi-
dative addition of dibromoolefins to Cu(I) species then pro-
The solvents were purified and dried by standard procedures
before use; petroleum ether with a boiling range of 60–80 °C
was used. Melting points are uncorrected. Infrared spectra
were recorded on a Shimadzu FTIR-8400 spectrometer. The
wave numbers (n) of recorded IR-signals are quoted in cm−1
.
1H and 13C NMR were recorded on Bruker AV-200, AV-400 and
AV-500 NMR spectrometers, respectively. Purification was done
using column chromatography (230–400 mesh).
Note: sodium cyanide is “highly toxic” and must be handled
with care.
General experimental procedure for the preparation of
α,β-unsaturated nitriles (2a–r)
duces intermediate
B
which subsequently undergoes
To a stirred solution of gem-dibromoolefins 1a–r (3 mmol) in
dry DMF (15 mL) were added NaCN (3.3 mmol), Cu2O
(0.3 mmol) and L-proline (0.3 mmol). The entire reaction
mixture was heated to 110 °C while being stirred under N2 for
12 h (monitored by TLC). The reaction mixture was then
cooled to room temperature and excess cyanide was quenched
with aq. NaClO2, diluted with water (10 mL) and EtOAc
(15 mL). The organic layer was separated and the aqueous
layer was extracted with EtOAc (3 × 20 mL). The aqueous layer
after extraction was poured into aq. KMnO4 solution to quench
excess NaCN and then disposed off. The combined organic
extracts were washed with brine, dried over anhyd. Na2SO4 and
concentrated under reduced pressure to give crude products
which were purified by column chromatography [silica gel
(230–400 mesh) and petroleum ether : EtOAc (7 : 3) as an
eluent] to afford the corresponding α,β-unsaturated nitriles
(2a–r) in 62–89% yield.
nucleophilic displacement with NaCN to generate intermedi-
ate C. Reductive elimination of intermediate C produces
bromo cyano olefin D with the liberation of catalytic complex
A. Bromo cyano olefin D again undergoes subsequent oxidative
addition with Cu(I) complex A to generate intermediate E
which on protonation facilitates the formation of α,β-unsatu-
rated nitriles (Fig. 2).
General experimental procedure for the preparation of
α-deuterated p-nitro cinnamonitrile 3
To a stirred solution of 1-(2,2-dibromovinyl)-4-nitrobenzene
(1 mmol) in dry DMF (5 mL) were added NaCN (1.1 mmol),
Cu2O (0.1 mmol), L-proline (0.1 mmol) and D2O (1 mmol). The
entire reaction mixture was heated to 120 °C while being
stirred under N2 for 12 h (monitored by TLC). The reaction
mixture was then cooled to room temperature and excess
cyanide was quenched with aq. NaClO2, diluted with water
(10 mL) and EtOAc (15 mL). The organic layer was separated
and the aqueous layer was extracted with EtOAc (3 × 20 mL).
The aqueous layer after extraction was poured into aq. KMnO4
solution to quench excess NaCN and then disposed off. The
Fig. 2 Proposed catalytic cycle for debrominative cyanation of gem-
dibromoolefins.
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1
combined organic extracts were washed with brine, dried over isomers; E distinct signals: H NMR (200 MHz, CDCl3) δ 2.50
anhyd. Na2SO4 and concentrated under reduced pressure to (s, 3H), 5.80 (d, J = 16.6 Hz, 1H), 7.23 (d, J = 16.6 Hz, 1H), 7.25
give crude products which were purified by column chromato- (d, J = 6.8 Hz, 2H), 7.34 (d, J = 8.2 Hz, 2H); 13C NMR (50 MHz,
graphy [silica gel (230–400 mesh) and petroleum ether : EtOAc CDCl3) δ 14.7, 94.7, 118.1, 125.5, 127.4, 129.6, 143.1, 149.4;
(7 : 3) as an eluent] to afford the corresponding α-deuterated Z distinct signals: 1H NMR (200 MHz, CDCl3) δ 2.50 (s, 3H),
p-nitro cinnamonitrile 3 in 20% yield.
5.36 (d, J = 12 Hz, 1H), 7.03 (d, J = 12 Hz, 1H), 7.25 (d, J =
8.2 Hz, 2H), 7.72 (d, J = 8.6 Hz, 2H); 13C NMR (50 MHz, CDCl3)
δ 14.6, 93.3, 117.3, 125.3, 129.1, 129.7, 142.9, 147.6; Analysis:
Spectroscopic data
Cinnamonitrile (2a). Yield: 84% (0.325 g, 2.52 mmol); Col- C10H9NS requires C, 68.53; H, 5.18; N, 7.99; S, 18.30; found:
ourless liquid; IR (CHCl3, cm−1): νmax 856, 1247, 1560, 1591, C, 68.39; H, 5.04; N, 7.72%.
2211; unseparable mixture of E/Z (4.5/1) isomers; E distinct
3-(4-(Trifluoromethyl)phenyl)acrylonitrile (2f). Yield: 82%
1
signals: H NMR (200 MHz, CDCl3) δ 5.88 (d, J = 16.7 Hz, 1H), (0.484 g, 2.46 mmol); White solid; mp. 83–84 °C;26 IR (CHCl3,
7.40 (d, J = 16.7 Hz, 1H), 7.42–7.45 (m, 5H); 13C NMR (50 MHz, cm−1): νmax 1220, 1299, 1514, 1589, 2218; unseparable mixture
CDCl3) δ 96.0, 117.8, 127.2, 128.9, 131.0, 133.4, 150.2; Z dis- of E/Z (1.2/1) isomers; E distinct signals: 1H NMR (200 MHz,
1
tinct signals: H NMR (200 MHz, CDCl3) δ 5.44 (d, J = 12.1 Hz, CDCl3) δ 5.98 (d, J = 16.6 Hz, 1H), 7.44 (d, J = 16.6 Hz, 1H),
1H), 7.11 (d, J = 12.1 Hz, 1H), 7.41–7.49 (m, 3H), 7.78–7.82 7.57 (d, J = 8.3 Hz, 2H), 7.78 (d, J = 6.5 Hz, 2H); 13C NMR
(m, 2H); 13C NMR (50 MHz, CDCl3) δ 94.9, 117.8, 128.1, 128.7, (50 MHz, CDCl3) δ 99.2, 117.2, 126 (q, J = 3.6 Hz), 127.5, 129.1,
1
128.8, 129.2, 130.7, 133.4, 148.3; Analysis: C9H7N requires C, 132 (q, J = 14.6 Hz), 136.6, 148.5; Z distinct signals: H NMR
83.69; H, 5.46; N, 10.84; found: C, 83.56; H, 5.34; N, 10.31%.
(200 MHz, CDCl3) δ 5.60 (d, J = 12.1 Hz, 1H), 7.18 (d, J =
3-(4-Methoxyphenyl)acrylonitrile (2b). Yield: 86% (0.410 g, 12.1 Hz, 1H), 7.72 (d, J = 6.6 Hz, 2H), 7.91 (d, J = 8.3 Hz, 2H);
2.58 mmol); White solid; mp. 53–54 °C;26 IR (CHCl3, cm−1): 13C NMR (50 MHz, CDCl3) δ 97.9, 116.4, 120.8, 125.7 (q, J =
νmax 1089, 1299, 1514, 1589, 2218; unseparable mixture of E/Z 3.6 Hz), 129.1, 132.3 (q, J = 15 Hz), 136.6, 146.8; Analysis:
1
(1.2/1) isomers; E distinct signals: H NMR (200 MHz, CDCl3) C10H6F3N requires C, 60.92; H, 3.07; F, 28.91; N, 7.10; found:
δ 3.85 (s, 3H), 5.70 (d, J = 16.5 Hz, 1H), 6.93 (d, J = 8.8 Hz, 2H), C, 60.52; H, 3.03; N, 7.01%.
7.31 (d, J = 16.5 Hz, 1H), 7.38 (d, J = 8.8 Hz, 2H); 13C NMR
3-(4-Nitrophenyl)acrylonitrile (2g). Yield: 79% (0.484 g,
(50 MHz, CDCl3) δ 55.1, 93.2, 114.3, 118.3, 128.8, 130.7, 149.6, 2.46 mmol); Separable E/Z (4/1) isomers; E isomer: Yellow
161.8; Z distinct signals: 1H NMR (200 MHz, CDCl3) δ 3.84 solid; mp. 203–204 °C; IR (CHCl3, cm−1): νmax 889, 1344, 1524,
1
(s, 3H), 5.28 (d, J = 12.1 Hz, 1H), 6.89 (d, J = 7.3 Hz, 2H), 7.02 1621, 2225; H NMR (200 MHz, CDCl3) δ 6.05 (d, J = 16.6 Hz,
(d, J = 12.1 Hz, 1H), 7.78 (d, J = 8.8 Hz, 2H); 13C NMR (50 MHz, 1H), 7.47 (d, J = 16.6 Hz, 1H), 7.63 (d, J = 8.8 Hz, 2H), 8.28
CDCl3) δ 55.1, 91.6, 114.1, 117.6, 126.1, 126.3, 130.7, 147.7, (d, J = 8.8 Hz, 2H); 13C NMR (50 MHz, CDCl3) δ 101.6,
161.4; Analysis: C10H9NO requires C, 75.45; H, 5.70; N, 8.8; 116.7, 124.4, 128.1, 139.2, 147.6; Z isomer: Yellow solid;
O, 10.05; found: C, 83.56; H, 5.34; N, 8.03%.
mp. 200–201 °C; IR (CHCl3, cm−1): νmax 883, 1374, 1531, 1591,
1
3-(4-Fluorophenyl)acrylonitrile (2c). Yield: 80% (0.353 g, 2217; H NMR (200 MHz, CDCl3) δ 5.75 (d, J = 11.6 Hz, 1H),
2.4 mmol); White solid; mp. 40–42 °C;26 IR (CHCl3, cm−1): 7.32 (d, J = 11.6 Hz, 1H), 7.56 (d, J = 8.1 Hz, 1H), 8.14 (d, J =
νmax 690, 1080, 1260, 1505, 1621, 2225; unseparable mixture of 8.1 Hz, 1H); 13C NMR (50 MHz, CDCl3) δ 99.2, 117.0, 122.2,
E/Z (1.2/1) isomers; E distinct signals: 1H NMR (200 MHz, 127.3, 141.3, 146.1, 147.6, 134.2, 146.3, 147.2; Analysis:
CDCl3) δ 5.80 (d, J = 16.6 Hz, 1H), 7.05–7.11 (m, 2H), 7.36 (d, C9H6N2O2 requires C, 62.07; H, 3.47; N, 16.09; O, 18.37; found:
J = 16.6 Hz, 1H), 7.41–7.44 (m, 2H); 13C NMR (50 MHz, CDCl3) C, 61.92; H, 3.16; N, 16.16%.
δ 96.2, 115.5, 115.9, 127.3, 127.8, (d, J = 8.1 Hz), 133.9 (d, J =
3-(2-Nitrophenyl)acrylonitrile (2h). Yield: 84% (0.438 g,
3.3 Hz), 162 (d, J, 247.7); Z distinct signals: 1H NMR (200 MHz, 2.52 mmol); Separable E/Z (3/1) isomers; E isomer: Yellow
CDCl3) δ 5.43 (d, J = 12.3 Hz, 1H), 7.08 (d, J = 12.3 Hz, 1H), solid; mp. 91–92 °C; IR (CHCl3, cm−1): νmax 891, 1201, 1366,
7.13–7.17 (m, 2H), 7.79–7.86 (m, 2H); 13C NMR (50 MHz, 1567, 1605, 2216; 1H NMR (200 MHz, CDCl3) δ 5.73 (d, J =
CDCl3) δ 96.2, 115.5, 115.9, 127.3, 127.8, (d, J = 8.1 Hz), 133.9 16.4 Hz, 1H), 7.56–7.76 (m, 3H), 7.96 (d, J = 16.4 Hz, 1H), 8.14
(d, J = 3.3 Hz), 162 (d, J, 247.7) Analysis: C9H6FN requires C, (dd, J = 7.7, 1.5 Hz, 1H); 13C NMR (50 MHz, CDCl3) δ 101.7,
73.46; H, 4.11; F, 12.91; N, 9.52; found: C, 73.35; H, 4.01; 116.7, 125.3, 128.7, 129.7, 131.2, 133.9, 146.4, 147.6; Z isomer:
N, 9.13%.
Yellow solid; mp. 86–87 °C; IR (CHCl3, cm−1): νmax 824, 1199,
1
(E)-3-(4-Chlorophenyl)acrylonitrile (2d). Yield: 82% (0.410 g, 1354, 1561, 1643, 2217; H NMR (200 MHz, CDCl3) δ 5.73 (d,
2.58 mmol); White solid; mp. 83–84 °C; IR (CHCl3, cm−1): J = 11.7 Hz, 1H), 7.61–7.90 (m, 3H), 7.73 (d, J = 11.7 Hz, 1H),
νmax 956, 1107, 1601, 1624, 2217; E isomer 1H NMR (200 MHz, 8.22 (d, J = 8.1 Hz, 1H); 13C NMR (50 MHz, CDCl3) δ 100.2,
CDCl3) δ 5.86 (d, J = 16.6 Hz, 1H), 7.34 (d, J = 16.6 Hz, 1H), 115.7, 125.2, 129.5, 130.6, 130.9, 134.2, 146.3, 147.2; Analysis:
7.38 (s, 5H); 13C NMR (50 MHz, CDCl3) δ 97.1, 117.6, 128.4, C9H6N2O2 requires C, 62.07; H, 3.47; N, 16.09; O, 18.37; found:
129.3, 131.9, 137.2, 148.8; Analysis: C9H6ClN requires C, 66.06; C, 62.15; H, 3.29; N, 16.05%.
H, 3.70; Cl, 21.67; N, 8.56; found: C, 66.42; H, 3.31; N, 8.25%.
3-(4-(Methylthio)phenyl)acrylonitrile (2e). Yield:
3-( p-Tolyl)acrylonitrile (2i). Yield: 86% (0.369 g,
89% 2.58 mmol); gum; IR (CHCl3, cm−1): νmax 1090, 1215, 1297,
(0.467 g, 2.67 mmol); gum; IR (CHCl3, cm−1): νmax 856, 1023, 1455, 1517, 2219; unseparable mixture of E/Z (2/1) isomers;
1247, 1560, 1591, 2211; unseparable mixture of E/Z (2/1) E distinct signals: 1H NMR (200 MHz, CDCl3) δ 2.38 (s, 3H),
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5.80 (d, J = 16.7 Hz, 1H), 7.22 (d, J = 16.7 Hz, 1H), 7.31–7.39
3-(Ferrocenyl)acrylonitrile (2n). Yield: 71% (0.504 g,
(m, 4H); 13C NMR (50 MHz, CDCl3) δ 21.4, 95.0, 118.3, 127.3, 2.13 mmol); Brownish liquid; IR (CHCl3, cm−1): νmax 1142,
129.7, 130.8, 141.7, 150.3;
Z
distinct signals: 1H NMR 1334, 1514, 1621, 2223; unseparable mixture of E/Z (1.2/1)
1
(200 MHz, CDCl3) δ 2.38 (s, 3H), 5.36 (d, J = 12.1 Hz, 1H), isomers; E distinct signals: H NMR (200 MHz, CDCl3) δ 4.17
7.05 (d, J = 12.1 Hz, 1H), 7.19 (d, J = 8.1 Hz, 2H), 7.70 (d, J = (s, 5H), 4.43 (s, 4H), 5.42 (d, J = 16.4 Hz, 1H), 7.25 (d, J =
8.1 Hz, 2H); 13C NMR (50 MHz, CDCl3) δ 21.4, 93.6, 118.3, 16.4 Hz); 13C NMR (50 MHz, CDCl3) δ 68.1, 69.8, 71.3, 78.0,
128.9, 127.3, 129.7, 130.8, 141.7, 148.4; Analysis: C10H9N 91.9, 118.8, 151.6; Z distinct signals: 1H NMR (200 MHz,
requires C, 83.88; H, 6.34; N, 9.78; found: C, 83.16; H, 6.42; CDCl3) δ 4.19 (s, 5H), 4.46 (s, 4H), 5.17 (d, J = 11.6 Hz, 1H),
N, 9.66%.
6.95 (d, 11.6 Hz, 1H); 13C NMR (50 MHz, CDCl3) δ 68.1, 69.9,
3-(Thiophen-2-yl)acrylonitrile (2j). Yield: 79% (0.320 g, 71.2, 77.9, 90.4, 118.4, 144.8; Analysis: C13H11FeN requires
2.37 mmol); gum; IR (CHCl3, cm−1): νmax 886, 927, 1037, 1290, C, 65.86; H, 4.68; Fe, 23.56; N, 5.91; found: C, 65.56; H, 4.43;
1488, 1503, 2218; unseparable mixture of E/Z (2/1) isomers; N, 5.85%.
E distinct signals: 1H NMR (200 MHz, CDCl3) δ 5.64 (d, J =
2-(2-Cyanovinyl)-4-methoxybenzonitrile (2o). Yield: 74%
16.4 Hz, 1H), 7.04–7.07 (m, 1H), 7.24–7.26 (m, 1H), 7.39–7.42 (0.408 g, 2.22 mmol); Separable E/Z (3/1) isomers; E isomer:
(m, 2H); 13C NMR (50 MHz, CDCl3) δ 94.4, 117.7, 128.3, 129.1, White solid; mp. 128–129 °C; IR (CHCl3, cm−1): νmax 547, 709,
131.1, 138.3, 142.5; Z distinct signals: 1H NMR (200 MHz, 767, 833, 856, 1023, 1247, 1597, 2211; 1H NMR (200 MHz,
CDCl3) δ 5.26 (d, J = 11.7 Hz, 1H), 7.09–7.13 (m, 1H), 7.23 CDCl3) δ 3.91 (s, 3H), 6.07 (d, J = 16.5 Hz, 1H), 7.00 (dd, J = 8.5,
(d, J = 11.7 Hz, 1H), 7.50–7.57 (m, 2H); 13C NMR (50 MHz, 2.53 Hz, 1H), 7.09 (d, J = 2.5 Hz, 1H), 7.62 (d, J = 16.5 Hz, 1H),
CDCl3) δ 91.7, 117.3, 127.6, 130.1, 132.2, 137.6, 140.5; Analysis: 7.64 (d, 8.6 Hz, 1H); 13C NMR (50 MHz, CDCl3) δ 55.8, 99.9,
C7H5NS requires C, 62.19; H, 3.73; N, 10.36; S, 23.72; found: 104.9, 112.2, 116.1, 116.8, 117.8, 134.5, 137.7, 144.0, 162.9;
C, 62.05; H, 3.63; N, 10.16%.
Z isomer: White solid; mp. 111–112 °C; IR (CHCl3, cm−1):
3-(Furan-2-yl)acrylonitrile (2k). Yield: 84% (0.300 g, νmax 657, 711, 840, 872, 1027, 1317, 1547, 2215; 1H NMR
2.52 mmol); Pale yellow oil; IR (CHCl3, cm−1): νmax 975, 1117, (200 MHz, CDCl3) δ 3.94 (s, 3H), 5.70 (d, J = 12.1 Hz, 1H), 7.01
1234, 1601, 1623, 2217; unseparable mixture of E/Z (2/1) (dd, J = 8.7, 2.5 Hz, 1H), 7.49 (d, J = 12.1 Hz, 1H), 7.63 (d, J =
1
isomers; E distinct signals: H NMR (200 MHz, CDCl3) δ 5.76 8.7 Hz, 1H), 7.86 (d, J = 2.5 Hz, 1H); 13C NMR (50 MHz, CDCl3)
(d, J = 16.2 Hz, 1H), 6.48–6.50 (m, 1H), 6.60 (d, J = 3.4 Hz, 1H), δ 55.7, 101.6, 104.1, 111.9, 116.6, 116.8, 135.2, 137.7, 145.5,
7.10 (d, J = 16.2 Hz, 1H), 7.49 (d, J = 1.5 Hz, 1H); 13C NMR 162.9; Analysis: C11H8N2O requires C, 71.73; H, 4.38; N, 15.21;
(50 MHz, CDCl3) δ 93.9, 112.6, 115.2, 117.2, 135.9, 145.3, O, 8.69; found: C, 71.52; H, 4.16; N, 15.09%.
150.1; Z distinct signals: 1H NMR (200 MHz, CDCl3) δ 5.23
2-(2-Cyanovinyl)-4,5-dimethoxybenzonitrile (2p). Yield: 62%
(d, J = 12.0 Hz, 1H), 6.53–6.55 (m, 1H), 6.94 (d, J = 12.0 Hz, (0.398 g, 1.86 mmol); Separable E/Z (4/1) isomers; E isomer:
1H), 7.03–7.07 (m, 1H), 7.57 (d, J = 2 Hz, 1H); 13C NMR White solid; mp. 135–136 °C; IR (CHCl3, cm−1): νmax 886, 927,
1
(50 MHz, CDCl3) δ 91.5, 112.5, 115.4, 126.7, 134.8, 144.9, 960, 1037, 1290, 1488, 1503, 2223; H NMR (200 MHz, CDCl3)
150.0; Analysis: C7H5NO requires C, 70.58; H, 4.23; N, 11.76; O, δ 3.95 (s, 3H), 3.98 (s, 3H), 5.98 (d, J = 16.5 Hz, 1H), 7.01
13.43; found: C, 70.35; H, 4.11; N, 11.48%.
(s, 1H), 7.09 (s, 1H), 7.65 (d, J = 16.5 Hz, 1H); 13C NMR
(4E)-5-Phenylpenta-2,4-dienenitrile (2l). Yield: 76% (0.353 g, (50 MHz, CDCl3) δ 54.3, 93.7, 102.2, 106.7, 112.6, 115.1,
2.27 mmol); Colourless liquid; IR (CHCl3, cm−1): νmax 767, 116.1, 128.2, 142.9, 149.2, 150.8; Z isomer: White solid;
856, 1237, 1555, 2211; unseparable mixture of E/Z (1.2/1) mp. 123–124 °C; IR (CHCl3, cm−1): νmax 829, 931, 957, 1034,
1
isomers; E distinct signals: H NMR (200 MHz, CDCl3) δ 5.42 1251, 1472, 1523, 2219; 1H NMR (200 MHz, CDCl3) δ 3.96
(d, J = 15.8 Hz, 1H), 6.80–6.87 (m, 2H), 7.07–7.15 (m, 1H), (s, 3H), 4.02 (s, 3H), 5.60 (d, J = 12.1 Hz, 1H), 7.10 (s, 1H), 7.46
7.34–7.40 (m, 3H), 7.46–7.48 (m, 2H); 13C NMR (50 MHz, (d, J = 12.1 Hz, 1H), 7.99 (s, 1H); 13C NMR (50 MHz, CDCl3)
CDCl3) δ 98.4, 118.1, 125.4, 127.6, 129.6, 129.7, 135.3, 141.6,
δ 56.3, 96.9, 106.0, 109.6, 114.1, 116.8, 130.3, 143.6,
150.1; Z distinct signals: 1H NMR (200 MHz, CDCl3) δ 5.24 150.9, 152.6; Analysis: C12H10N2O2 requires C, 67.28; H, 4.71;
(d, J = 10.5 Hz, 1H), 6.90–7.01 (m, 2H), 7.19–7.29 (m, 1H), N, 13.08; found: C, 67.79; H, 4.12; N, 13.46%.
7.34–7.42 (m, 3H), 7.44–7.52 (m, 2H); 13C NMR (50 MHz,
6-(2-Cyanovinyl)-2,3,4-trimethoxybenzonitrile
(2q). Yield:
CDCl3) δ 96.7, 116.4, 124.2, 127.4, 128.9, 129.6, 129.7, 135.2, 72% (0.527 g, 2.16 mmol); Separable E/Z (3/1) isomers;
141.3, 149.1; Analysis: C11H9N requires C, 85.13; H, 5.85; E isomer: White solid; mp. 151–152 °C; IR (CHCl3, cm−1):
N, 9.03; found: C, 85.06; H, 5.73; N, 8.96%.
(E)-4-(3,4-Dimethoxyphenyl)but-3-enenitrile
νmax 791, 845, 964, 1052, 1239, 1412, 1472, 1533, 1664, 2217;
(2m). Yield: 1H NMR (200 MHz, CDCl3) δ 3.91 (s, 3H), 3.96 (s, 3H), 4.06,
74% (0.451 g, 2.22 mmol); Colourless liquid IR (CHCl3, cm−1): (s, 3H), 6.03 (d, J = 16.5, 1H), 7.81 (s, 1H), 7.59 (d, J = 16.5, 1H);
νmax 1089, 1210, 1289, 1504, 1579, 2218; E isomer 1H NMR 13C NMR (50 MHz, CDCl3) δ 56.3, 61.1, 61.7, 100.3, 104.6,
(200 MHz, CDCl3) δ 3.19 (td, J = 5.7, 1.3 Hz, 2H), 3.81 (s, 3H), 114.1, 116.9, 132.2, 143.6, 145.3, 155.8, 157.4; Z isomer: White
3.82 (s, 3H), 5.76–5.90 (m, 1H), 6.56 (d, J = 15.8 Hz, 1H), solid; mp. 138–139 °C; IR (CHCl3, cm−1): νmax 783, 941, 1056,
6.71–6.84 (m, 3H); 13C NMR (50 MHz, CDCl3) δ 20.4, 55.6, 1241, 1416, 1534, 1605, 2211; 1H NMR (200 MHz, CDCl3)
108.8, 111.0, 114.5, 117.1, 119.5, 128.5, 134.1, 148.9; Analysis: δ 3.93 (s, 3H), 4.00 (s, 3H), 4.07, (s, 3H), 5.64 (d, J = 12.2, 1H),
C12H13NO2 requires C, 70.92; H, 6.45; N, 6.89; O, 15.74; found: 7.44 (d, J = 12.2, 1H), 7.71 (s, 1H); 13C NMR (50 MHz, CDCl3)
C, 70.56; H, 6.31; N, 6.25%.
δ 56.4, 61.5, 61.8, 98.4, 101.1, 106.5, 114.1, 116.6, 132.0, 143.5,
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143.7, 155.9, 157.3; Analysis: C13H12N2O3 requires C, 63.93;
H, 4.95; N, 11.47; found: requires C, 63.71; H, 4.51; N, 11.22.
2-(2-Cyanovinyl)-4,6-dimethoxybenzonitrile (2r). Yield: 74%
(0.475 g, 2.22 mmol); Separable E/Z (4/1) isomers; E isomer:
Yellow solid; mp. 135–136 °C; IR (CHCl3, cm−1): νmax 964,
1107, 1244, 1301, 1624, 2217; 1H NMR (200 MHz, CDCl3)
δ 3.90 (s, 3H), 3.94 (s, 3H), 6.09 (d, J = 16.5, 1H), 6.52 (s, 1H),
6.64 (s, 1H), 7.61, (d, J = 16.5, 1H); 13C NMR (50 MHz, CDCl3)
δ 55.9, 56.3, 94.6, 100.1, 101.9, 103.2, 114.4, 116.7, 138.7,
145.8, 163.6, 164.2; Z isomer: Yellow solid; mp. 121–122 °C;
IR (CHCl3, cm−1): νmax 941, 1105, 1213, 1654, 2219; 1H NMR
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BBA thanks CSIR, New Delhi for the award of Senior Research
Fellowship and DST (no. SR/S1/OC-67/2010), New Delhi for
financial support. The authors thank Dr V. V. Ranade, Chair
and Head, Chemical Engineering and Process Development
Division for his constant encouragement.
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