Triflic acid-catalyzed metal-free synthesis of (: E)-2-cyanoacrylamides and 3-substituted azetidine-2,4-diones

Article abstract of DOI:10.1039/c7nj05169g

A TfOH-catalyzed highly efficient synthesis of biologically active (E)-2-cyanoacrylamides and 3-substituted azetidine-2,4-diones has been reported with 64-94% yields under metal-free conditions. The reaction proceeds through sequential Knoevenagel condens

Full text of DOI:10.1039/c7nj05169g

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PAPER
Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
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Triflic Acid Catalyzed Metal-Free Synthesis of (E)-2-
Cyanoacrylamides and 3-Substituted Azetidine-2,4-diones
Received 00th January 20xx,
Accepted 00th January 20xx
Bapurao D. Rupanwar, Santosh S. Chavan, Anil M. Shelke and Gurunath M. Suryavanshi *
A TfOH-catalyzed highly efficient synthesis of biologically active (E)-2-cyanoacrylamides and 3-substituted azetidine-2,4-
diones has been reported in 64-94% yields under metal-free condition. The reaction proceeds through sequential
knoevenagel condensation/stereoselective in-situ monohydration of nitrile or C-N cyclization protocol in one-pot. The
attractive features of this tandem process are moderate reaction conditions, high atom economy, broad substrate scope,
gram scale reaction and easy operation.
DOI: 10.1039/x0xx00000x
www.rsc.org/
documented over base catalysis.8 The main challenge
associated in the hydrolysis of nitrile to amide is that it’s very
difficult to stop the reaction at the amide stage because it
Introduction
Highly substituted 2-cyanoacrylamides and its derivatives are
not only the distinctive structural frameworks but also shows
significant biological activities such as protein kinase
inhibitors,1a GTPase inhibitory activity,1b Galactokinase
inhibitors,1c and diverse pre-functionalized cyanoacrylamides
has shown promising inhibitor activities in MSK/RSK-family
kinase.1d However, multi functionalized azetidines and its
derivatives serves as a markedly active drugs against influenza
A H2N2 virus,1 anti-HIV-1, anti-HSV-1 and HSV-2 potential.2
Amides and nitriles are not only the synthetically important
moietys but also productive functional groups in chemistry for
the key chemical transformations such as amines, carboxylic
acids, esters, aldehydes and alcohols etc.3 In general, the
conventional methods for the synthesis of 2-cyanoacrylamides
are well-known knoevenagel condensation of aromatic
aldehydes or ketones with 2-cyanoacetamide (Scheme 1, eq.
1)3a,3b and other methods include use of strong acid or base
catalysis,2 microwave assisted condensation,4 Titanium
tetrachloride and MgO,5 heterogeneous catalysis,6 and use of
ionic liquids.7 However, the reported methods known in the
literature for the synthesis of 2-cyanoacrylamides have some
drawbacks such as they are limited to condensation of only
active methylene compounds and having readily available NH2,
CONH2 and CN functional groups in the starting material. In
the past decades, worldwide researchers have attracted
considerable attention towards hydration of nitriles to amides
and the traditional methods for hydration of nitriles is well
undergoes further hydrolysis to give acid. Both homogenous
metal catalysts9 and heterogeneous catalysts such as
(Au/TiO2),10a (Ru(OH)x /Al2O3),10b (Ag/HAP),10c KF/Al2O3,10d
10f
KF/phosphate,10e MnO2/SiO2 Ru-substituted hydroxyapatite
((RuCl)2Ca8(PO4)6(OH)2)10 have been reported for the selective
conversion of nitriles to amides. However, these reactions
often require inert atmosphere and harsh reaction conditions
such as the use of high temperature and expensive metal salts.
Scheme 1. Strategies for the synthesis of 2-cyanoacrylamides
Dong and co-workers described an alternative route for the
homogeneous and stereoselective monohydration of 2-
methylenemalononitriles to 2-cyanoacrylamides by using Cu
(II) in acetic acid (Scheme 1, eq. 2)11a and more recently rode et
al reported
a direct method for the synthesis of 2-
cyanoacrylamides by the condensation and selective
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monohydration of nitriles starting from aldehyde and acetal catalysts were screened, such as FeCl3, AlCl3, MgCl2, TiCl4, and
with malononitrile in the presence of solid acid ferrite AgCOCF3 but unfortunately the reaction failed to give the
catalyst.11b To the best of our knowledge, there is no direct desired product 3a (Table 1, entries 2-6). Next, we examined a
metal-free method for the synthesis of (E)-2-cyanoacrylamides series of Brønsted acid catalyst (Table 1, entries 7-12). Only the
as well as for 3-substituted azetidine-2,4-diones. Considering TFAA, TfOH and TsOH catalysts were provided the desired
the importance of 2-cyanoacrylamides along with 3- product 3a in 53 to 86% yield. Next, we performed various
substituted azetidine-2,4-diones and as a part of our ongoing solvents study (Table 1, entries 13-20). After careful
research in the development of new synthetic methodologies evaluation, we found that toluene, DMSO, dioxane, THF and
and organic transformations over heterogeneous catalyst,12 EtOH were found to be less effective in the reaction to afford
we herein, disclose for the first time, a one pot TfOH-catalyzed the corresponding product 3a in 31 to 47% yield. However,
synthesis of (E)-2-cyanoacrylamides and 3-substituted acetonitrile as a solvent provided the high yields of desired
azetidine-2,4-diones via knoevenagel condensation of product in 70% yield and solvents such as IPA and DMF were
aromatic aldehydes with malononitrile/ethyl cyanoacetate unsuccessful to produce the corresponding required product
under moderate reaction conditions in good to excellent (Table 1, entries 18-20).
yields.
Table 2. Substrate scope of aromatic aldehydes 1a-1za for the synthesis of (E)-2-
cyanoacrylamides a
Results and discussion
Initially, we carried out the reaction between benzaldehyde 1a
with malononitrile 2a in the presence of Zinc (II) chloride as a
o
catalyst in DCE solvent at 110 C for 16 h. To our delight, the
expected product 3a was obtained in 60% yield (Table 1, entry
1).
Table 1.Optimization of the reaction conditions a
entry
catalyst
solvent
temp. oC
time (h)
yieldb (%)
1
2
ZnCl2
FeCl3
DCE
DCE
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
70
16
16
16
16
16
16
16
16
16
16
24
16
24
24
24
24
24
24
24
24
24
60
N.R
N.R
N.R
N.R
Trace
Trace
Trace
N.R
53
3
AlCl3
DCE
4
MgCl2
TiCl4
DCE
5
DCE
6
AgCOCF3
BF3.Et2O
TFA
DCE
7
DCE
8
DCE
9
(CF3SO2)2O
TFAA
DCE
10
11
12
13
14
15
16
17
18
19
20
21c
DCE
TfOH
DCE
84
TsOH
TfOH
DCE
79
PhMe
DMSO
dioxane
THF
36
TfOH
41
TfOH
47
TfOH
31
TfOH
EtOH
MeCN
IPA
80
46
TfOH
90
70
TfOH
110
110
110
N.R
N.R
78
TfOH
DMF
DCE
a Reaction conditions: 1a-1za (1 mmol), 2a (1.2 mmol), TfOH (25 mol%) in DCE (5
TfOH
mL) at 110 oC for 24 h.
a Reaction conditions: 1a (1 mmol), 2a (1.2 mmol), catalyst (25 mol%), solvent (5
o
b
mL), 70-110 C for 16-24 h. Isolated yields. c Catalyst TfOH (20 mol%). N.R = No
The catalyst loading 20 mol% was afforded less yield of the
product 3a as compare to 25 mol% of the catalyst (Table 1,
entry 21). After detailed optimization study, we were pleased
to find that reaction proceeded very well with TfOH (25 mol %)
in DCE solvent (Table 1, entry 11). After having the optimized
reaction.
This initial result inspired us to investigate the optimized
reaction condition for the formation of 3a. Several Lewis acid
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reaction condition in hand, next we explored the substrate on others substrates like α,β-unsaturated aldehydes. Hence,
scope of the present reaction, by treating various substituted we screened different unsaturated aldehydes such as 6a-b
aryl aldehydes 1a-1za with 2a (Table 2, entry 3a-3za). Initially, under optimized reaction condition. The reaction was
various unsubstituted aromatic aldehydes 1a-1b were reacted successfully
afforded
the
desired
substituted
2-
with 2a under the optimized reaction condition, to provide the cyanoacrylamides in 85 and 91% yields (Scheme 2, entry 7a
desired 2-cyanoacrylamides product in good yields (Table 2, and 7b).
entries 3a-3b). This reaction was practically remarkable with
aromatic aldehydes bearing both electron-donating and
electron-withdrawing substituents on the aryl ring.
Consequently, different aryl aldehydes 1c-1za reacted
smoothly to produce the corresponding 2-cyanoacrylamides
Scheme 2. Substrate scope of the α,β-unsaturated aldehydes 6a-b
with good to excellent yields (Table 2, entries 3c-3za). A variety
of functional groups such as Me, OMe, OH, OPh, SMe present
Recently, we reported
a novel Sn(II)-catalyzed tandem
at the ortho, meta and para positions of the aromatic
aldehydes, mono and disubstituted aldehydes were well
tolerated under the optimized reaction condition giving
excellent yields of the desired substituted 2-cyanoacrylamides.
The (E)- stereoselectivity of product 2-cyanoacrylamides were
confirmed using NOESY experiment of substrate 3n (see SI).
The substrates having electron-withdrawing substituent on the
aromatic ring of aldehydes for example, NO2, Cl, Br, F and CF3
groups were efficiently reacted to produce the substituted 2-
cyanoacrylamides in slightly higher yield (Table 2, entries 3s-
za). This tandem reaction shows good compatibility with most
of the substrates and good functional group tolerance. The
success in the synthesis of various (E)-2-cyanoacrylamides 3a-
3za and key chemical transformation over Brønsted acid
catalyst under metal-free condition prompted us to further
extend the substrate scope. Also because of the great
potential applications of the nitrile and amide functionality for
redox-economy in organic synthesis, we were interested in the
synthesis of substituted 2-cyanoacrylamides.13 Thus, different
unsubstituted heterocyclic aldehydes such as 4a-b and
substituted heterocyclic aldehydes such as 4c-d were
subjected to our optimized reaction condition and the results
are shown in Table 3.
cyclization reaction of aromatic aldehydes with ethyl
cyanoacetate for the synthesis of 3-substituted azetidine-2,4-
diones.14 Therefore, we thought to use ethyl cyanoacetate 2b
as the reaction partner instead of malononitrile 2a in our
previously optimized reaction condition.
Table 4. Substrate scope of aromatic aldehydes 8a-h for the 3-substituted azetidine-
2,4-dionesa
aReaction conditions: 8a-h (1 mmol), 2b (1.2 mmol), TfOH (25 mol %), in 1,4-
dioxane (5 mL) at 110 oC for 14 h.
Table 3. Substrate scope of the heterocyclic aldehydes 4a-d for the synthesis of (E)-2-
cyanoacrylamidesa
As depicted in Table 4, the reaction proceeded smoothly with
several substituted aromatic aldehydes 8a-h giving excellent
yields of the desired 3-substituted azetidine-2,4-diones and
was not found to be much dependent upon the electronic
nature of the substituents (Table 4, entry 9a-h). In this
substrate study, both electron donating and withdrawing
functional groups on the aromatic aldehydes were found to be
very effective. To further demonstrate the significant
practicality and efficiency of the developed reaction sequence,
a gram scale reaction was performed. The synthesis of (E)-2-
cyano-3-(p-tolyl)acrylamide (3e, 4.96 g) could be achieved in
80% yield from 4-methylbenzaldehyde as the starting material
(Scheme 3). The obtained yield of gram scale reaction is similar
to the submillimolar scale reaction.
aReaction conditions: 4a-4d (1 mmol), 2a (1.2 mmol), TfOH (25 mol %), in DCE (5
mL) at 110 oC for 24 h.
To our delight, furfuraldehyde, 2-Thiophene carboxaldehyde,
5-bromothiophene-2-carbaldehyde and 3-methylthiophene-2-
carbaldehyde were reacted under the standard reaction
conditions giving excellent yields of the desired products
(Table 3, entries 5a-d). Motivated by the above results for
achieving the monohydration reaction in one-pot, next we
thought to investigate the application of present methodology
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Scheme 3. Gram scale synthesis of (E)-2-cyano-3-(p-tolyl)acrylamide 3e
Millipore, Alfa Aesar and Avra Synthesis. Aldehydes were
purified either by distillation or washing with NaHCO3 after
dissolving in ether, prior to use and all AR grade solvents were
used without further purification.
Based on the results obtained together with the literature
precedence15 and previous work on triflic acid catalysis, we
proposed a possible reaction mechanism for the formation of
Petroleum ether of boiling range 60–80 °C was used. Melting
(E)-2-cyanoacrylamides 3a via direct condensation
/
points are uncorrected. 1H NMR and 13C NMR spectra were
recorded on AC-200, 400, 500 MHz NMR spectrometers.
Deuterated solvent CDCl3+ CCl4 (70:30) were used as internal
standard and singlet at 96.1 ppm in 13C NMR corresponds to
carbon of CCl4. HRMS data for all new compounds were
recorded using Orbitrap mass analyzer associated with Accela
1250 pump. Purification was done using column
chromatography (100-200 mesh). The reactions were
monitored by TLC visualized by UV (254 nm) and/or with
iodine. Coupling constants are given in hertz (Hz) and the
classical abbreviations are used to describe the signal
multiplicities.
stereoselective in-situ monohydration of nitrile/cyclization
reaction (Scheme 4). Initially, benzaldehyde 1a and
malononitrile 2a undergoes knoevenagel condensation
reaction to generate methylenemalononitriles
hydration then commences from the coordination of
methylenemalononitriles ( ) with the triflic acid to afford the
intermediate (II). The anti-cyano group of ( ) with reference to
(I). The
I
I
aryl group is favoured to coordinate to the triflic acid due to
both electronic and steric effects.
General procedure for the optimization of reaction
conditions: In a 25 mL round bottom flask benzaldehyde 1a (1
mmol), malanonitrile 2a (1.2 mmol), catalyst (20-25 mol %)
and solvent (5 mL) were added. The round bottom flask was
equipped with condenser and the resultant reaction mixture
was refluxed at 70-110 oC for 24 h (Table 1) and the progress
of the reaction was monitored by TLC. Upon completion of the
reaction, reaction mixture was dried under vacuum. Then the
crude reaction mixture was diluted with ethyl acetate (10 mL)
and filtered through a pad of silica gel and eluted with EtOAc
(20 mL). The solvent was evaporated and the crude residue
was preadsorbed on silica gel and purified by column
chromatography to afford the corresponding compound 3a in
moderate to good yields.
Scheme 4. Plausible reaction mechanism
The nucleophilic attack of H2O on the carbon atom of the
nitrile of (II) afforded intermediate (III). The intermediate (III
)
an iminol then undergoes tautomerization to give the
corresponding (E)-2-cyanoacrylamide (3a).
General procedure for the synthesis of compound 3a-3za and
5a-d: In a 25 mL round bottom flask aldehydes 1a-1za (1
mmol) or 4a-d (1 mmol), malononitrile 2a (1.2 mmol), catalyst
TfOH (25 mol%) and DCE (5 mL) were taken. The round bottom
flask was equipped with condenser and the resultant reaction
mixture was refluxed at 110 oC for 24 h and progress of the
reaction was monitored by TLC. Upon completion of the
reaction, the reaction mixture was dried under vacuum. Then
the crude reaction mixture was diluted with ethyl acetate (10
mL) and filtered through a pad of silica gel and eluted with
EtOAc (20 mL). The solvent was evaporated and the crude
residue was preadsorbed on silica gel and purified by column
chromatography to afford the corresponding (E)-2-
cyanoacrylamides 3a-3za and 5a-d in good to excellent yields.
Conclusions
In summary, we have developed for the first time, a novel one-
pot metal free method for the synthesis of substituted (E)-2-
cyanoacrylamides and 3-substituted azetidine-2,4-diones via
TfOH-catalyzed knoevenagel condensation/stereoselective
monohydration and in-situ cyclization of aromatic aldehydes
and malononitrile/ethyl cyanoacetate. The attractive features
of this protocol includes metal-free reaction, good atom
economy, broad substrate scope, good functional group
tolerance, and practically remarkable in terms of yields and
scalability. Further applications of the present methodology
are currently ongoing in our laboratory.
General procedure for the synthesis of compounds 7a and 7b:
Experimental Section
Compound 7a and 7b was prepared by using similar reaction
procedure as above used for the synthesis of 3a-3za and 5a-d
.
General information:
General procedure for the synthesis of 3-substituted
azetidine-2,4-diones 9a-h: In a 10 mL round bottom flask
equipped with a magnetic stir bar was added the aldehyde 8a-
Unless otherwise specified, all reactions were carried out
under an open atmosphere in solvent at reflux condition and
reaction temperatures are reported as the temperature of the
bath surrounding the reaction vessel. All reagents and solvents
were obtained from commercial suppliers and Aldrich, Merck
h
(1 mmol), ethyl cyanoacetate 2b (1.2 mmol), TfOH (25 mol
%) and 1,4-dioxane (5 mL). Then the resultant reaction mixture
was kept in stirring at 110 oC for 14 h. Upon completion of the
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reaction, the reaction mixture was dried under vacuum. Then
ARTICLE
the crude reaction mixture was diluted with ethyl acetate (10 (E)-2-cyano-3-(p-tolyl)acrylamide (3e): Rf : 0.41 (Pet. ether /
°
mL) and washed with water. The solvent was evaporated and EtOAc = 70/30); Yield: 129 mg, 83%; White solid; mp: 136 C;
the crude residue was preadsorbed on silica gel and purified by 1H NMR (200 MHz, CDCl3)
δ
ppm: 2.4 (s, 3H), 6.4 (br.s., 2H), 7.3
column chromatography to afford the corresponding 3- (d, J = 8.2 Hz, 2H), 7.9 (d, J = 8.2 Hz, 2H), 8.3(s, 1H); 13C NMR
substituted azetidine-2,4-diones 9a-h in 75-89% yields. (50 MHz, CDCl3) ppm: 21.2, 105.3, 116.7, 129.2, 129.9, 130.1,
143.0, 150.5, 162.9; HRMS (ESI) calculated [M + H]+ for
δ
General procedure for the gram scale synthesis of 3e: C11H11ON2: 187.0866; found: 187.0862.
Following the general procedure as described above for the
synthesis of (E)-2-cyanoacrylamides, a flame-dried flask was (E)-2-cyano-3-(4-(methylthio)phenyl)acrylamide (3f): Rf : 0.32
charged with 4-methylbenzaldehyde (4 g, 33.3 mmol), (Pet. ether / EtOAc = 60/40); Yield: 108 mg, 75%; White solid;
malononitrile 2a (2.6 g, 39.6 mmol), catalyst TfOH (1.25 g, mp: 153 C; 1H NMR (200 MHz, CDCl3)
°
δ ppm: 2.55 (s, 3H), 6.17
0.0083 mmol) and 1,4-dioxane (35 mL). The round bottom (br. s., 1H), 6.33 (br. s., 1H), 7.31 (d, J = 8.6 Hz, 2H), 7.88 (d, J =
flask was equipped with condenser and the resultant reaction 8.6 Hz, 2H), 8.27 (s, 1H); 13C NMR (50 MHz, DMSO-d6)
ppm:
δ
mixture was refluxed at 110 oC for 24 h. The progress of the 13.4, 102.2, 116.0, 124.3, 126.9, 129.7, 144.6, 150.2, 161.6;
reaction was monitored by TLC. Upon completion of the HRMS (ESI) calculated [M+H]+ for C11H11ON2S: 219.0587; found:
reaction, the reaction mixture was dried under vacuum. Then 219.0581.
the crude reaction mixture was diluted with ethyl acetate (50
mL) and filtered through a pad of silica gel and eluted with (E)-2-cyano-3-(4-isopropylphenyl)acrylamide (3g): Rf : 0.41
EtOAc (600 mL). The solvent was evaporated and the crude (Pet. ether / EtOAc = 65/35); Yield: 126 mg, 87%; Yellow solid;
residue was preadsorbed on silica gel and purified by column mp: 136-138 C; 1H NMR (500 MHz, CDCl3)
°
δ ppm : 0.81 (d, J =
chromatography with eluted solvent (pet.ether + ethyl aceate 6.71 Hz, 7H) 5.67 (br. s., 1H) 5.88 (br. s., 1H) 6.88 (m, J = 8.24
65:35) to afford the corresponding (E)-2-cyano-3-(p- Hz, 2H) 7.41 (m, J = 8.24 Hz, 2H) 7.81 (s, 1H); 13C NMR (125
tolyl)acrylamide derivate 3e in (4.96 g, 80%) yield.
MHz, CDCl3) δ ppm: 23.7, 34.5, 101.8, 117.3, 127.5, 129.4,
131.2, 153.9, 154.9, 162.2; HRMS (ESI) calculated [M+H]+ for
(E)-2-cyano-3-phenylacrylamide (3a): Rf : 0.42 (Pet. Ether / C13H15ON2: 215.1179; found: 215.1177.
°
EtOAc = 60/40); Yield: 136 mg, 84%; White solid; mp: 130 C;
1H NMR (200 MHz, DMSO-d6)
δ
ppm: 7.46 (br. s., 3H) 7.78 - (E)-2-cyano-3-(4-methoxyphenyl)acrylamide (3h): Rf : 0.35
7.95 (m, 2H) 8.06-8.22 (m, 1H); 13C NMR (50 MHz, DMSO-d6)
(Pet. ether / EtOAc = 60/40); Yield: 114 mg, 77%; Yellow solid;
ppm: 103.1 117.0, 129.2, 130.8, 131.6, 133.1, 154.0, 162.1; mp: 207-209 C; 1H NMR (400 MHz, DMSO-d6)
HRMS (ESI) calculated [M + H]+ for C10H9ON2: 173.0709; found: (br. s., 3H) 7.13 (d, J = 7.32 Hz, 2H) 7.67 (br. s., 1H) 7.80 (br. s.,
173.0706.
1H) 7.96 (d, J = 7.32 Hz, 2H) 8.11 (br. s., 1H);13C NMR (101
MHz, DMSO-d6) ppm: 55.6, 102.9, 114.83,117.09, 124,
(E)-2-cyano-3-(naphthalen-1-yl)acrylamide (3b): Rf : 0.38 (Pet. 132.47,150.1,162.59, 163.13
HRMS (ESI) calculated [M+H]+ for
ether / EtOAc = 65/35); Yield: 125 mg, 88%; White solid; mp: C11H11O2N2: 203.0815; found: 203.0814.
δ
°
δ
ppm: 3.85
δ
;
°
168 C; 1H NMR (500 MHz, DMSO-d6)
7.86 (br. s., 1H), 8.05 (br. s., 2H), 8.15 (br. s., 2H), 8.20 (br. s., (E)-2-cyano-3-(4-hydroxyphenyl)acrylamide (3i): Rf : 0.50 (Pet.
1H), 8.87 (br. s., 1H); 13C NMR (101 MHz, DMSO-d6)
ppm: ether / EtOAc = 70/30); Yield: 99 mg, 64%; White solid; mp:
111.4, 116.4,123.9, 125.6, 127.1,127.4, 127.7, 129.1,129.6, 242-243 C; H NMR (200 MHz, DMSO-d6)
131, 132.1, 133.2, 148.7, 162.9; HRMS (ESI) calculated [M+H]+ 8.7 Hz, 2H) 7.37 (br. s., 2 H) 7.79 (m, J = 8.7 Hz, 2H) 8.00 (s, 1H)
for C14H11ON2: 223.0866; found: 223.0860. ppm : 100.5, 116.0,
10.26 (s, 1H); 13C NMR (50 MHz, CDCl3)
δ ppm: 7.66 (br. s., 3H),
δ
°
1
δ
ppm : 6.85 (m, J =
δ
117.2, 122.8, 132.7, 150.9, 161.8, 163.1; HRMS (ESI) calculated
(E)-2-cyano-3-(2,4-dichlorophenyl)acrylamide (3c): Rf : 0.43 [M+H]+ for C10H9O2N2: 189.0659; found: 189.0658.
(Pet. ether / EtOAc = 60/40); Yield: 113 mg, 90%; White solid;
°
1
mp: 125 C; H NMR (200 MHz, DMSO-d6)
8.5, 2.0 Hz, 1H), 7.6 (d, J = 2.1 Hz, 1H), 7.8 (br. s., 2H), 8.0 (d, J = (Pet. ether / EtOAc = 60/40); Yield: 108 mg, 76%; Yellow; mp:
8.7 Hz, 1H), 8.3 (s, 1H); 13C NMR (50 MHz, DMSO-d6) ppm : 165 °C; 1H NMR (200 MHz, DMSO-d6)
ppm : 3.7 (s, 3H), 3.7 (s,
δ ppm : 7.5 (dd, J = (E)-2-cyano-3-(2,5-dimethoxyphenyl)acrylamide (3j): Rf : 0.41
δ
δ
110.4, 115.2, 127.7 , 129.1, 129.5 , 130.3, 135.5, 137.2, 145.7, 3H), 6.5-6.7 (m, 2H), 6.8 (d, J = 9.1 Hz, 1H), 7.0 (dd, J = 9.1, 3.0
161.2; HRMS (ESI) calculated [M+H]+ for C10H7ON2Cl2: Hz, 1H), 7.6 (d, J = 2.9 Hz, 1H), 8.6 (s, 1H); 13C NMR (50 MHz,
240.9930; found: 204.9928 DMSO-d6) δ ppm : 55.5, 56.3, 106.6, 112.8, 113.1, 116.6, 119.8,
(E)-2-cyano-3-(2,6-dichlorophenyl)acrylamide (3d): Rf : 0.42 120.8, 145.4, 152.7, 152.8, 162.6; HRMS (ESI) calculated
(Pet. ether / EtOAc = 55/45); Yield: 122 mg, 83%; White solid; [M+H]+ for C12H13O3N2: 233.0921; found: 233.0915.
1
mp : 125-128 °C; H NMR (200 MHz, DMSO-d6)
δ ppm : 7.4-7.5
(m, 4H), 7.8 (br. s., 1H), 7.9 (br. s., 1H), 8.1 (s, 1H); 13C NMR (50 (E)-2-cyano-3-(3,4-dimethoxyphenyl)acrylamide (3k): Rf : 0.38
MHz, CDCl3) ppm : 163.1, 161.8, 150.9, 132.7, 122.8, 117.2, (Pet. ether / EtOAc = 65/35); Yield: 103 mg, 74%; White solid;
116.0, 100.5, 95.6; HRMS (ESI) calculated [M+H]+ for mp: 195-196 C; 1H NMR (200 MHz, DMSO-d6
δ
°
)
δ ppm 3.81 (3
C10H7ON2Cl2: 240.9930; found: 204.9928.
H, s), 3.86 (3 H, s), 7.14 (1 H, d,
J=8.6 Hz), 7.56 (1 H, dd,
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ARTICLE
=8.5, 1.9 Hz), 7.66 (1 H, s), 7.68 - 7.89 (2 H, m), 8.06 - 8.19 8.16 (s, 1H); 13C NMR (50 MHz, DMSO-d6)
Journal Name
J
δ
ppm : 54.8, 105.7,
(1 H, m); 13C NMR (50 MHz, DMSO-d6
) δ ppm : 55.4, 55.80, 114.1, 116.2, 118.1, 122.7, 129.7, 132.8, 150.9, 159.3, 162.0;
102.8, 111.8, 112.2, 117.2, 124.4, 125.5, 148.7, 150.6, 152.5, HRMS (ESI) calculated [M+H]+ for C11H11O2N2: 203.0815; found:
163.1 HRMS (ESI) calculated [M+H]+ for C12H13O3N2: 233.0921; 203.0814.
found: 233.0915.
(E)-2-cyano-3-(4-phenoxyphenyl)acrylamide (3r): Rf
: 0.44
(E)-2-cyano-3-(2,4-dimethoxyphenyl)acrylamide (3l): Rf : 0.39 (Pet. ether / EtOAc = 60/40); Yield: 110 mg, 76%; White solid;
(Pet. ether / EtOAc = 60/40); Yield: 110 mg, 79%; White solid; mp : 112-114 °C ; 1H NMR (200 MHz, CDCl3)
δ
ppm : 6.40 (br. s.,
°
mp : 168-169 C ; 1H NMR (200 MHz, DMSO-d6)
δ ppm : 3.9 (s, 1H) 6.56 (br. s., 1H) 7.01-7.09 (m, 2H) 7.13-7.26 (m, 2H) 7.34 -
3H) 3.8 (s, 3H) 7.0 (d, J = 8.34 Hz, 1H) 7.2-7.5 (m, 3H) 7.6 (d, J = 7.52 (m, 4H) 7.69 (d, J = 7.83 Hz, 1H) 8.26 (s, 1H): 13C NMR (50
2.02 Hz, 1H) 8.0 (s, 1 H); 13C NMR (50 MHz, DMSO-d6)
ppm : MHz, DMSO-d6) ppm : 161.6, 150.6, 133.1, 132.3, 131.2,
δ
δ
55.3, 55.5, 95.5, 101.9, 111.0, 111.4, 117.0, 124.4, 126.0, 128.6, 127.2, 127.1, 126.4, 124.9, 122.8, 118.5, 116.4, 107.2;
148.6, 150.9, 152.4, 162.6; HRMS (ESI) calculated [M +H]+ for HRMS (ESI) calculated [M+H]+ for C16H13O2N2: 265.0972; found:
C12H13O3N2: 233.0921; found: 233.0915.
265.0969.
(E)-2-cyano-3-(3,4,5-trimethoxyphenyl)acrylamide (3m): Rf
:
(E)-3-(3-bromophenyl)-2-cyanoacrylamide (3s): Rf : 0.4 (Pet.
0.35 (Pet. ether / EtOAc = 70/30); Yield: 113 mg, 85%; White ether / EtOAc = 60/40); Yield: 122 mg, 90%; White solid; mp:
°
1
°
solid; mp : 113-114 C ; H NMR (400 MHz, DMSO-d6)
3.77 (s, 3H) 3.88 (s, 3H) 3.89 (s, 3H) 7.03 (d, J = 9.05 Hz, 1H) 1H), 7.6-7.8 (m, 3H), 7.9 (d, J = 7.8 Hz, 1H), 8.0 (s, 1H), 8.1 (s,
7.69 (br. s., 1H) 7.85 (br. s., 1H) 7.91 (d, J = 9.05 Hz, 1H) 8.25 (s, 1H); 13C NMR (50 MHz, DMSO-d6)
ppm : 107.9, 115.8, 122.2,
1H); 13C NMR (101 MHz, CDCl3)
ppm : 56.3, 60.6, 62.0, 104.4, 128.6, 130.8, 132.2, 134.0, 134.4, 148.8, 162.0; HRMS (ESI)
δ δ ppm : 7.4-7.5 (m,
ppm : 131-134 C; 1H NMR (200 MHz, DMSO-d6)
δ
δ
108.4, 117.0 , 118.3, 123.7, 141.5, 144.9, 153.6, 157.4, 163.0; calculated [M+H]+ for C10H8ON2Br: 250.9815; found: 250.9808.
HRMS (ESI) calculated [M+H]+ for C13H15O4N2: 263.1026; found:
263.1024.
(E)-2-cyano-3-(3-nitrophenyl)acrylamide (3t): Rf : 0.34 (Pet.
ether / EtOAc = 65/35); Yield: 137 mg, 84%; Brown solid; mp:
210-211 C ; 1H NMR (200 MHz, DMSO-d6)
°
(E)-3-(2-bromo-3,4,5-trimethoxyphenyl)-2-cyanoacrylamide
δ
ppm : 8.2 (s, 1H),
(3n): Rf : 0.39 (Pet. ether / EtOAc =60/40); Yield: 111 mg, 89%; 7.7-7.9 (m, 4H), 7.2 (t, J = 8.0 Hz, 1H), 6.8 (s, 1H), 6.9 (s, 1H);
°
Pale Yellow; mp: 221 C; 1H NMR(500 MHz, DMSO-d6
3.82 (br. s., 3H) 3.86 (br. s., 3H) 3.88 (br. s., 3H) 7.55 (br. s., 134.7, 132.6, 129.6, 125.3, 123.7, 114.9, 107.8; HRMS (ESI)
1H) 7.87 (br. s., 1H) 8.00 (br. s., 1 H) 8.29 (br. s., 1H);13 calculated [M+H]+ for C10H8O3N3: 218.0560; found: 218.0555.
NMR(126 MHz, DMSO-d6 ppm 56.2, 60.9, 109.1,109.6,
) δ δ ppm : 160.8, 148.2, 147.4,
ppm: 13C NMR (50 MHz, DMSO-d6)
C
)
δ
111.8, 115.8,127.1, 145.3, 149.3,150.5, 152.3,161.8; HRMS (E)-3-(4-bromophenyl)-2-cyanoacrylamide (3u): Rf : 0.41 (Pet.
(ESI) calculated [M +H]+ for C13H14O4N2Br: 341.0131; found: ether / EtOAc = 65/35); Yield: 121 mg, 89%; White Solid; mp:
°
341.0124.
198 C ; 1H NMR (500 MHz, DMSO-d6)
δ
ppm : 7.72 (d, J=8.01
Hz, 2 H) 7.77 (br. s., 1 H) 7.82 (d, J=8.01 Hz, 2 H) 7.93 (br. s., 1
H) 8.11 (s, 1 H); 13C NMR (126 MHz, DMSO-d6)
ppm : 107.51,
(E)-3-(benzo[d][1,3]dioxol-5-yl)-2-cyanoacrylamide (3o): Rf
:
δ
0.38 (Pet. ether / EtOAc = 65/35); Yield: 130 mg, 90%; white 116.4, 126.2, 131.2, 131.9, 132.5, 149.7, 162.8; HRMS (ESI)
°
1
solid; mp: 204-206 C; H NMR (200 MHz, DMSO-d6)
6.1 (s, 2H), 6.9 (d, J = 8.2 Hz, 1H), 7.2-7.5 (m, 3H), 7.6 (s, 1H),
8.0 (s, 1H); 13C NMR (50 MHz, DMSO-d6)
ppm : 101.8, 102.4, (E)-2-cyano-3-(4-cyanophenyl)acrylamide (3v): Rf : 0.35 (Pet.
107.7, 108.4, 116.6, 125.8, 128.1, 148.0, 150.4 , 150.9 , 162.4; ether / EtOAc = 60/40); Yield: 126 mg, 86%; White solid; mp:
δ
ppm : calculated [M+H]+ for C10H8ON2Br: 250.9815; found: 250.9808
δ
°
HRMS (ESI) calculated [M+H]+ for C11H9O3N2: 217.0608; found: 146-148 C; 1H NMR (200 MHz, DMSO-d6)
217.0606. 7.36 (s, 1H), 7.68-7.85 (m, 2H), 7.96 (d, J = 8.5 Hz, 2H), 8.19 (s,
1H); 13C NMR (50 MHz, CDCl3)
ppm : 110.0, 113.8, 115.8,
δ ppm : 7.44 (s, 1H),
δ
(E)-2-cyano-3-(o-tolyl)acrylamide (3p): Rf : 0.42 (Pet. ether / 118.2, 130.3, 133.0, 136.3, 148.7, 162; HRMS (ESI) calculated
EtOAc = 65/35); Yield: 125 mg, 81%; White solid; mp: 125-127 [M +H]+ for C11H8ON3: 198.0662; found: 198.0658.
1
°C; H NMR (400 MHz, CDCl3)
δ ppm : 2.48 (s, 3H) 6.35 (br. s.,
1H) 6.41 (br. s., 1H) 7.27-7.47 (m, 4H) 8.07 (d, J = 7.78 Hz, 1H) (E)-2-cyano-3-(4-nitrophenyl)acrylamide (3w): Rf : 0.41 (Pet.
8.63 (s, 1H); 13C NMR (101 MHz, CDCl3)
ppm : 20.0, 104.8, ether / EtOAc = 60/40); Yield: 131 mg, 91%; Yellow solid; mp:
116.8, 126.7, 128.3, 130.9, 131.1, 132.6, 139.8, 152.1, 161.9; 198-200 C ; 1H NMR (400 MHz, DMSO-d6)
HRMS (ESI) calculated [M+H]+ for C11H11ON2: 187.0866; found: 1H) 8.06 (br. s., 1H) 8.12 (m, J = 8.80 Hz, 2H) 8.29 (s, 1H) 8.38
187.0862. ppm : 110.7,
(m, J = 8.80 Hz, 2H); 13C NMR (101 MHz, CDCl3)
δ
°
δ
ppm : 7.91 (br. s.,
δ
115.8, 124.2, 131.0, 138.1, 148.3, 148.8, 162.1; HRMS (ESI)
(E)-2-cyano-3-(2-methoxyphenyl)acrylamide (3q): Rf : 0.35 calculated [M+H]+ for C10H8O3N3: 218.0560; found: 218.0556.
(Pet. ether / EtOAc = 60/40); Yield: 111 mg, 75%; White solid;
mp : 146-148 °C; 1H NMR (200 MHz, DMSO-d6)
δ ppm : 3.85 (s, (E)-2-cyano-3-(4-(trifluoromethyl)phenyl)acrylamide (3x): Rf :
3H), 6.97-7.22 (m, 1H), 7.32- 7.50 (m, 3H), 7.53 (br. s., 2H), 0.39 (Pet. ether / EtOAc = 70/30); Yield: 127, 92%; Light Brown;
6 | J. Name., 2012, 00, 1-3
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mp: 172 °C; 1H NMR (200 MHz, CDCl3)
δ
ppm : 6.53 (br. s., 2H), (ESI) calculated [M + H]+ for C8H6ON2BrS: 258.9358; found:
258.9349.
7.76 (d, J = 8.3 Hz, 3H), 8.04 (d, J = 8.2 Hz, 2H), 8.38 (s, 1H); 13
C
NMR (50 MHz, CDCl3)
126.3 (q, J =3.66 and 7.32 Hz), 130.7, 134.3, 134.6, 152.1, (E)-2-cyano-3-(3-methylthiophen-2-yl)acrylamide (5d): Rf
161.5; HRMS (ESI) calculated [M+H]+ for C11H8ON2F3: 241.0583; 0.36 (Pet. ether / EtOAc = 60/40); Yield: 128 mg, 84%; Dark
found: 241.0577. ppm : 2.47 (s,
Brown; mp: 155 °C ; 1H NMR (200 MHz, CDCl3)
3H), 5.91-6.46 (m, 2H), 7.02 (d, J = 5.2 Hz, 1H), 7.66 (d, J = 4.8
(E)-3-(2-chlorophenyl)-2-cyanoacrylamide (3y): Rf : 0.41 (Pet. Hz, 1H), 8.53 (d, J = 0.9 Hz, 1H); 13C NMR (50 MHz, CDCl3)
ether / EtOAc = 65/35); Yield: 133 mg, 91%; off white solid; ppm : 102.6, 116.6, 121.2, 131.9, 137.5, 138.7, 142.9, 162.2;
δ ppm : 106.0, 116.2 , 120.6 , 126.1 -
:
δ
δ
°
mp: 143 C ; 1H NMR (500 MHz, METHANOL-d4
(1 H, br. s.), 7.5 - 7.6 (3 H, m), 7.8 (1 H, d, =7.2 Hz), 8.1 (1 H, 193.0426.
=7.6 Hz), 8.5 (1 H, s); 13C NMR (126 MHz, METHANOL-
ppm; 100.8, 106.9, 119.08, 121.27, 121.8, 124.9, 127.1, (2E,4E)-2-cyano-5-phenylpenta-2,4-dienamide (7a): Rf : 0.30
HRMS (ESI) calculated [M+H]+ for (Pet. ether / EtOAc = 50/50); Yield: 136 mg, 91%; Orange solid;
) δ
ppm 7.4 HRMS (ESI) calculated [M+H]+ for C9H9ON2S: 193.0430; found:
J
d,
d4
J
) δ
140.07, 154.8, 159.5
;
°
1
C11H8ON3: 198.0662; found: 198.0658.
mp: 150-152 C; H NMR (400 MHz, DMSO-d6)
8.03 (m, 1H) 7.60-7.62 (m, 2H) 7.40-7.50 (m, 5H) 7.30-7.34 (m,
(E)-2-cyano-3-(2-nitrophenyl)acrylamide (3z): Rf : 0.43 (Pet. 1H) 7.15-7.21 (m, 1H); 13C NMR (101 MHz, CDCl3)
ppm :
ether / EtOAc = 60/40); Yield: 135 mg, 94%; White solid; mp: 167.4, 156.5, 151.6, 150.9, 139.9, 135.4, 135.1, 133.9, 133.0,
δ ppm : 7.96-
δ
°
168-169 C; 1H NMR (200 MHz, DMSO-d6
H, m), 7.9 - 7.9 (2 H, m), 8.0 (1 H, br. s.), 8.3 (1 H, d,
Hz), 8.7 (1 H, s) 13C NMR (50 MHz, DMSO-d6
ppm: 108.7,
114.7, 125.1, 128.4, 130.6, 132.3, 134.7, 147.2, 154.1, 162.4
HRMS (ESI) calculated [M+H]+ for C10H8O3N3: 218.0560; found: Rf : 0.32 (Pet. ether / EtOAc = 60/40); Yield: 116 mg, 85%;
)
δ
ppm 7.5 - 7.9 (2 128.1, 120.4, 112.7, 100.8; HRMS (ESI) calculated [M+H]+ for
J=8.0 C12H11ON2: 199.0866; found: 199.0865.
)
δ
;
(2E,4E)-2-cyano-5-(2-nitrophenyl)penta-2,4-dienamide (7b):
°
1
218.0555.
White solid; mp: 207-209 C; H NMR (200 MHz, DMSO-d6)
ppm : 7.1 (dd, J = 15.1, 11.3 Hz, 1H), 7.2-7.8 (m, 5H), 7.9 (d, J =
(E)-3-(2-bromophenyl)-2-cyanoacrylamide (3za): Rf : 0.4 (Pet. 6.7 Hz, 1H), 8.0 (d, J = 8.7 Hz, 2H);13C NMR (50 MHz, DMSO-d6)
ether / EtOAc = 65/35); Yield: 126 mg, 93%; White solid; mp: ppm : 110.3,114.7, 124.5,127.2, 128.7, 129.9, 130.4, 133.5,
178 °C ; 1H NMR (200 MHz, CDCl3) ppm : 6.17 (br. s., 1H), 6.37 140.2, 147.9, 149.8, 162.0; HRMS (ESI) calculated [M+H]+ for
(br. s., 1H), 7.36 - 7.52 (m, 3H), 7.67-7.75 (m, 1H), 8.09 (dd, J = C12H10O3N3: 244.0717; found: 244.0717.
7.6, 1.8 Hz, 1H); 13C NMR (50 MHz, DMSO-d6)
ppm : 108.2,
δ
δ
δ
δ
114.5, 124.2, 126.7, 128.5, 131.0, 131.8, 132.1, 149.4, 160.4; 3-(3-phenoxybenzylidene)azetidine-2,4-dione (9a): Rf : 0.32
HRMS (ESI) calculated [M+H]+ for C10H8ON2Br: 250.9815; (Pet. ether / EtOAc = 60/40); Yield: 119 mg, 89%; White solid;
1
mp: 207-209 °C; H NMR (500 MHz, CHLOROFORM-d)
found: 250.9808.
δ
ppm:
6.94 - 7.02 (m, 2H), 7.07 - 7.17 (m, 2H), 7.29 - 7.36 (m, 2H),
(E)-2-cyano-3-(furan-2-yl)acrylamide (5a): Rf : 0.35 (Pet. ether 7.40 (t, J= 8.12 Hz, 1H), 7.46 (s, 1H), 7.68 (d, J= 7.70 Hz, 1H),
/ EtOAc = 60/40); Yield: 150 mg, 89%; Yellow solid; mp: 148- 8.10 (s, 1 H), 9.41 (br. s., 1 H); 13C NMR (125 MHz, CDCl3)
δ
ppm : 6.49-6.55 (m, 1H), ppm : 163.8, 158.0, 156.0, 153.6, 133.2, 130.5, 130.0, 125.0,
°
150 C; H NMR (500 MHz, CDCl3)
1
δ
6.60 (br. s., 1H), 6.70 (br. s., 1H), 7.13 (d, J = 3.4 Hz, 1H), 7.63 124.1, 122.7, 120.2, 119.4, 115.5, 104.9; HRMS (ESI) calculated
(s, 1H), 7.93 (s, 1H); 13C NMR (126 MHz, CDCl3)
ppm : 99.8 , [M+H]+ for C16H12NO3: 266.0812, found: 266.0810.
δ
113.2 , 116.4 , 120.5 , 137.4 , 147.3 , 148.8 , 161.8; HRMS (ESI)
calculated [M+H]+ for C8H7O2N2: 163.0502; found: 163.0501.
3-((2,4-dioxoazetidin-3-ylidene)methyl)benzonitrile (9b): Rf :
0.4 (Pet. ether / EtOAc = 50/50); Yield: 122 mg, 81%; White
(E)-2-cyano-3-(thiophen-2-yl)acrylamide (5b): Rf : 0.39 (Pet. solid; mp: 170 °C; 1H NMR (500 MHz, CHLOROFORM-d)
δ ppm :
ether / EtOAc = 70/30); Yield: 138 mg, 87%; Dark Brown; mp: 7.58 (t, J=8.01 Hz, 1H), 7.74 (d, J=7.63 Hz, 1H), 8.08 (s, 1H),
°
1
221 C ; H NMR (200 MHz, DMSO-d6)
1H), 7.59 (br. s., 2H), 7.78 (br. s., 1H), 7.83-8.00 (m, 1H), 8.33
(s, 1H); 13C NMR (50 MHz, DMSO-d6) ppm : 102.1, 116.7, 115.0, 113.7, 107.2; HRMS (ESI) calculated [M+H]+ for
δ
ppm : 7.10-7.32 (m, 8.12 (s, 1H), 8.16 (d, J=8.01 Hz, 1H); 13C NMR (125 MHz, CDCl3)
ppm: 163.0, 151.3, 135.3, 133.9, 133.8, 132.8, 130.2, 117.4,
δ
δ
128.6, 134.9, 135.8, 137.8, 143.6, 162.6; HRMS (ESI) calculated C11H7N2O2: 198.1820, found: 198.1818.
[M+H]+ for C8H7ON2S: 179.0274; found:179.0270.
3-(furan-2-ylmethylene)azetidine-2,4-dione (9c): Rf : 0.34 (Pet.
ether / EtOAc = 60/40); Yield: 145 mg, 86%; White solid; mp:
0.35 (Pet. ether / EtOAc = 65/35); Yield: 117 mg, 94%; Pale 146-148 °C; 1H NMR (500 MHz, DMSO-d6)
ppm: 6.62 (br. s.,
Yellow; mp: 168 °C; 1H NMR (200 MHz, CDCl3) ppm : 6.01 (br. 1H), 7.29 (br. s., 1H), 7.77 (br. s., 1H), 7.90 (br. s., 1H); 13C NMR
s., 1H), 6.24 (br. s., 1H), 7.19 (d, J = 4.0 Hz, 1H), 7.41-7.60 (m, (125 MHz, DMSO-d6) ppm : 162.6, 147.1, 137.7, 120.4, 114.5,
1H), 8.31 (s, 1H); 13C NMR (50 MHz, CDCl3) ppm : 103.02, 112.6, 98.3; HRMS (ESI) calculated [M+H]+ for C8H6NO3:
(E)-3-(5-bromothiophen-2-yl)-2-cyanoacrylamide (5c): Rf
:
δ
δ
δ
δ
117.7, 121.7, 132.34, 137.93, 139.16, 143.45, 162.67; HRMS 163.1310, found: 163.1312.
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ARTICLE
Journal Name
3-(4-fluorobenzylidene)azetidine-2,4-dione (9d): Rf : 0.32 (Pet.
Notes and references
ether / EtOAc = 60/40); Yield: 121 mg, 79%; White solid; mp:
160-164 C; 1H NMR (500 MHz, DMSO-d6)
1
(a) Q. Liu, Y. Sabnis, Z. Zhao, T. Zhang, S. J. Buhrlage, L. H.
Jones and N. S. Gray, Chem. Biol., 2013, 20, 146; (b) T. Hill, A.
Quan, L. R. Odell, R. Abagyan, J. K. Adwards, J. L. Scott, M. E.
Graham, P. J. Robinson, A. B. McGeachie, A. McCluskey and J.
Rusak, J. Med. Chem., 2005, 48, 7781; (c) S. I. Odejinmi, R. G.
Rascon, M. Tang, H. Vankayalapati and K. Lai, ACS. Med.
°
δ ppm: 7.09 (t,
J=8.58 Hz, 2H), 7.85 - 7.95 (m, 2H), 8.08 (s, 1H), 8.48 (br. s.,
1H);13C NMR (125 MHz, CDCl3)
ppm : 165.7, 163.6, 152.2,
δ
132.9, 132.9, 127.8, 116.2, 116.0, 115.6, 103.7; HRMS (ESI)
calculated [M+H]+ for C10H7NO2F: 192.0455, found: 192.0456.
Chem. Lett., 2011, 2, 667; (d) R. M. Miller, V. O. Paavilainen,
S. Krishanan, I. M. Serafimova and J. Taunton, J. Am. Chem.
Soc., 2013, 135, 5298.
3-(2-methoxybenzylidene)azetidine-2,4-dione (9e): Rf : 0.31
2
3
(a) S. Fioravanti, L. Pellacani, P. A. Tardella and M. C. Vergari,
Org. Lett., 2008, 10, 1449; (b) A. R. Mohite and R. G. Bhat,
Org. Lett., 2013, 15, 4564.
(a) H. Moison, F. Coise, T. Boullct and A. Foucaud,
Tetrahedron, 1987, 43, 537; (b) R. Kumbhare and M. Sridhar,
(Pet. ether / EtOAc = 60/40); Yield: 120 mg, 87%; White solid;
°
1
mp: 176-178 C; H NMR (400 MHz, DMSO-d6)
(1H, s), 8.17 (1H, d, J = 7.3 Hz), 7.42 (1H, t, J = 7.6 Hz), 6.83-
7.04 (2H, m), 3.81 (3H, s); 13C NMR (101 MHz, CDCl3)
ppm :
δ ppm : 8.62
δ
163.9, 158.5, 148.7, 134.2, 128.6, 120.3, 115.8, 110.7, 102.8,
55.2; HRMS (ESI) calculated [M+H]+ for C11H9NO3Na: 226.0475,
found: 226.0478.
Catal. Commun., 2008,
Chen, X. Zeng, G. Zhong, RSC Adv., 2017,
J. S. Yadav, B. S. S. Reddy, A. K. Basak, B. Visali, A. V. Narsaiah
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K. Bartley, D. I. Enache, D. W. Knight, and G. J. Hutchings,
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Chem. Int. Ed. Engl., 1977, 36, 2661; (b) M. L. Kantam, B. M.
Choudary, C. V. Reddy, K. K. Rao and F. Figueras, Chem.
Commun., 1998, 1033; (c) K. R. Kloetstra, H. V. Bekkum, J.
Chem. Soc. Chem. Commun., 1995, 1005.
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C. Su, Z.-C. Chen and Q.-G. Zhen, Synthesis, 2003, 555; (c) J.
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2000.
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9
, 403. (c) L. Zhu, P.i Yan, L. Zhang, Z.
, 51352.
7
4
5
3-(3,4,5-trimethoxybenzylidene)azetidine-2,4-dione (9f): Rf :
0.35 (Pet. ether / EtOAc = 70/30); Yield: 107 mg, 80%; White
solid; mp: 210 °C; H NMR (500 MHz, CHLOROFORM-d)
1
6
7
δ ppm:
3.77 - 3.87 (m, 9H), 7.14 - 7.27 (m, 2H), 8.02 (br. s., 1H);13C
NMR (125 MHz, CDCl3) ppm 164.0, 153.9, 152.9, 142.1,
δ
126.5, 116.1, 108.2, 102.1, 60.7, 55.9, 40.0; HRMS (ESI)
calculated [M+H]+ for C13H13NO5Na: 286.0686, found:
286.0690.
3-(4-isopropylbenzylidene)azetidine-2,4-dione (9g): Rf : 0.37
8
9
(Pet. ether / EtOAc = 60/40); Yield: 108 mg, 75%; White solid;
mp: 246 °C; 1H NMR (400 MHz, CDCl3)
δ
ppm : 8.30 (1H, s), 7.99
(2H, m, J = 7.9 Hz), 7.40 (2H, m, J = 7.9 Hz), 2.94-3.07 (1H, m),
1.26-1.31 (7H, m); 13C NMR (50 MHz, CDCl3)
ppm : 163.5,
δ
154.5, 154.3, 131.0, 129.3, 127.4, 116.3, 102.6, 33.7, 23.4;
HRMS (ESI) calculated [M+H]+ for C13H14NO2: 216.1019, found:
216.1022.
10 (a) Y.-M. Liu, L. He, M.-M. Wang, Y. Cao, H.-Y. He and K.-N.
Fan, ChemSusChem, 2012, , 1392; (b) K. Yamaguchi, M.
Matsushita and N. Mizuno, Angew. Chem, Int. Ed., 2004, 116
5
,
1602; (c) T. Mitsudom, Y. Mikami, H. Mori, S. Arita, T.
Mizugaki, K. Jitsukawa and K. Kaneda, Chem. Commun.,
2009, 3258; (d) C. G. Rao, Synth. Commun., 1982, 12, 177; (e)
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1996, 37, 6555; (f) K. T. Li, M. H. Shih, H. W. Huang and C. J.
Hu, Synthesis, 1988, 715; (g) K. Mori, K. Yamaguchi, T.
Mizugaki, K. Ebitani and K. Kaneda, Chem. Commun., 2001,
461.
3-(2,4-dimethoxybenzylidene)azetidine-2,4-dione (9h): Rf : 0.3
(Pet. ether / EtOAc = 60/40); Yield: 117 mg, 84%; White solid;
°
1
mp: 216 C; H NMR (200 MHz, CDCl3)
8.28 (1H, d, J = 8.8 Hz), 6.39 (1H, d, J = 2.3 Hz), 3.77-3.84 (7H,
m); 13C NMR (50 MHz, CDCl3)
ppm : 164.99, 164.49, 160.7,
δ ppm : 8.57 (1H, s),
δ
147.6, 130.22, 116.65, 113.37, 105.67, 98.52, 97.43, 56.31,
55.17; HRMS (ESI) calculated [M+H]+ for C12H12NO4: 234.0761,
found: 234.0766.
11 (a) X. Xin, D. Xiang, J. Yang, Q. Zhang, F. Zhou and D. Dong, J.
Org. Chem., 2013, 78, 11956; (b) S. B. Kamble, C. V. Rode,
ChemCatChem, 2016,
12 (a) S. A. R. Mulla, M. Y. Pathan, and S. S. Chavan, RSC Adv.,
2013, , 20281; (b) S. A. R. Mulla, M. Y. Pathan, S. S. Chavan,
S. P. Gample and D. Sarkar, RSC Adv., 2014, , 7666; (c) A. M.
Shelke and G. Suryavanshi, Org. Biomol. Chem., 2015, 13
8669; (d) A. M. Shelke, V. Rawat, A. Sudalai and G.
Suryavanshi, RSC Adv., 2014, , 49770; (e) A. M. Shelke and
8, 2678.
3
4
Conflicts of interest
,
There are no conflicts to declare.
4
G. Suryavanshi, Org. Lett., 2016, 18, 3968.
13 N. Z. Burns, P. S. Baran and R. W. Hoffmann, Angew. Chem.
Int. Ed., 2009, 48, 2854.
Acknowledgements
14 S. S. Chavan, M. V. Supekar, P. A. Burate, B. D. Rupanwar, A.
,
M. Shelke and G. Suryavanshi, Org. Biomol. Chem., 2017, 15
2385.
Authors are highly thankful to CSIR & UGC-New Delhi for the
award of fellowship. We also thank to Dr S. S. Tambe, chair of
the Chemical Engineering and Process Development Division
(CSIR-NCL) for their constant support.
15 X. Xin, D. Xiang, J. Yang, Q. Zhang, F. Zhou and D. Dong, J.
Org. Chem., 2013, 78, 11956.
8 | J. Name., 2012, 00, 1-3
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New Journal of Chemistry
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DOI: 10.1039/C7NJ05169G
Triflic Acid Catalyzed Metal-Free Synthesis of (E)-2-Cyanoacrylamides
and 3-Substituted Azetidine-2,4-diones
Bapurao D. Rupanwar, Santosh S. Chavan, Anil M. Shelke and Gurunath M.
Suryavanshi *
Chemical Engineering & Process Development Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune,
Maharashtra, India- 411008.
*Corresponding author: Tel.: +91 20 25902547; Fax: +91 20 25902676; e-mail: gm.suryavanshi@ncl.res.in