Tuning the Electronic Properties of 2-Cyano-3-phenylacrylamide Derivatives

Article abstract of DOI:10.1021/acs.joc.5b02226

We are the first to report the synthesis of a new class of 2-cyanoarylacrylamide (2-CAA) derivatives and observe that the synthesized 2-CAA shows fluorescence properties due to the formation of a dimeric interaction of hydrogen bonds between carbonyl oxygens and amide hydrogens (C=O?H-N-C=O?H-N?); i.e., dimers are linked through dimeric N-H?O hydrogen bonds. The single-crystal X-ray structure shows molecules to be hydrogen-bonded dimers, which further form a parallel stacking arrangement, mediated by significant π-π interactions. The ¹H NMR and fluorescence spectral studies indicate the coexistence of amide and iminol tautomers in solution, which can be influenced by the nature of the solvent. Further, the excitation-wavelength-dependent fluorescence spectrum and the biexponential fluorescence decay profiles suggest the presence of more than one emitting species; i.e., amide and iminol tautomers coexists in solution. We have also shown that the equilibrium between the two tautomers can be tuned by the judicious choice of electron-donating or -withdrawing substituents.

Full text of DOI:10.1021/acs.joc.5b02226

Article
pubs.acs.org/joc
Tuning the Electronic Properties of 2‑Cyano-3-phenylacrylamide
Derivatives
Ramachandran Gunasekar,†,‡ Pichandi Thamaraiselvi,§ Ravindranath S. Rathore,∥
Kulathu Iyer Sathiyanarayanan,*,† and Shanmugam Easwaramoorthi*,§
†Chemistry Division, School of Advanced Sciences, VIT University, Vellore 632014, India
‡Research Center for Materials Science and the Department of Chemistry, Nagoya University, Chikusa, Nagoya 464-8602, Japan
§Chemical Laboratory, CSIR-Central Leather Research Institute, Adyar, Chennai 600020, India
∥Department of Biotechnology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India
S
* Supporting Information
ABSTRACT: We are the first to report the synthesis of a new
class of 2-cyanoarylacrylamide (2-CAA) derivatives and
observe that the synthesized 2-CAA shows fluorescence
properties due to the formation of a dimeric interaction of
hydrogen bonds between carbonyl oxygens and amide
hydrogens (CO···H−N−CO···H−N···); i.e., dimers are
linked through dimeric N−H···O hydrogen bonds. The single-
crystal X-ray structure shows molecules to be hydrogen-
bonded dimers, which further form a parallel stacking
arrangement, mediated by significant π−π interactions. The
1H NMR and fluorescence spectral studies indicate the
coexistence of amide and iminol tautomers in solution, which can be influenced by the nature of the solvent. Further, the
excitation-wavelength-dependent fluorescence spectrum and the biexponential fluorescence decay profiles suggest the presence of
more than one emitting species; i.e., amide and iminol tautomers coexists in solution. We have also shown that the equilibrium
between the two tautomers can be tuned by the judicious choice of electron-donating or -withdrawing substituents.
Particularly, aggregation-induced emission enhancement
(AIEE) of cyanostilbene derivatives in their nano- or
microaggregated state and crystalline states has been promising
in terms of their applications in light-emitting devices. The
emission enhancement is caused by the aggregation-induced
planarization, which prevents the nonradiative decay pathways
due to isomerization. Thus, considering the importance of
phenyl acrylonitrile derivatives,10 we have synthesized new
molecules based on 2-cyano-3-arylacrylamide (2-CAA) having
different electron-donating and -withdrawing substituents as
fluorescent probes. The combination of electron-donating aryl
groups and the electron-withdrawing 2-cyanoacrylamide
moieties makes these molecules excellent chromophores. For
example, 2-cyano-3-[4-aminophenyl]-2-propenamide deriva-
tives show solvatochromism in fluorescence due to intra-
molecular charge transfer interactions between the donor
(diarylamine) and acceptor (2-cyanoacrylamide) moieties;
however, systematic studies have not been reported yet.11
Bosch et al. have demonstrated that naphthalene-based 2-CAA
can be used to probe the photopolymerization reaction by
virtue of changes in fluorescence intensity in real time.12−14
Further, the (E)-2-cyano-3-(1H-indol-3-yl)acrylamide scaffold
INTRODUCTION
■
Studies on molecules having an intense color and stronger
fluorescence are always of great interest due to their
applications as dyes; fluorescent probes; sensors for anions,
cations, and neutral molecules; light emitters in organic light-
emitting diodes; sensitizers in solar cells; etc. Indeed, these are
one of the molecular level spectroscopic tools employed for the
detection and monitoring of specific properties or functions of
the medium they are incorporated in. These kinds of
applications are possible due to the sensitivity of fluorescence
properties with respect to temperature, pH, viscosity, polarity,
and rigidity of the surrounding environment.1−5 The preferred
configuration for molecules with environment-sensitive fluo-
rescent properties is the presence of electron-donating and
-withdrawing substituents connected covalently through
intervening π-conjugation. This feature offers a unique choice
of designing the new fluorophores having desired properties
with the judicious choice of available electron-donating and
-withdrawing moieties in different permutations and combina-
tions. In this regard, molecules based on the 3-phenyl-
acrylonitrile skeleton were known to show moderate to
excellent fluorescent properties depending upon the substitu-
ents. For example, the diphenylacrylonitrile (cyanostilbenes)
derivatives gained much attention owing to their unique,
tunable, highly responsive luminescent characteristics.6−9
Received: September 28, 2015
© XXXX American Chemical Society
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has also been used as a tricyclic CRTh2 receptor.15 In addition,
Zhang and co-workers have shown that the p-dimethylamino-
substituted 2-CAA derivative exhibits piezofluorochromic
properties wherein the yellow-green compound was converted
to orange-red simply by grinding with a pestle and mortar, and
the reversible conversion was possible through heating the
sample at 80 °C.16 It should also be noted that the strong,
complementary intermolecular hydrogen bonding between the
amine proton and carbonyl group of amide moiety are
susceptible to show reversible amide ↔ iminol tautomerism.
Hence, to evaluate the electronic properties and explore the
feasibility of amide ↔ iminol tautomerism and their
consequences on the photophysical properties, we have
synthesized a series of 2-CAA derivatives substituted with
electron-donating and -withdrawing groups. We are the first to
observe that the synthesized 2-CAA shows fluorescence
properties due to the formation of a hydrogen-bonded dimeric
interaction between carbonyl oxygens and amide hydrogens
(CO···H−N−CO···H−N···); i.e., dimers are linked
through dimeric N−H···O hydrogen bonds. We found that
some of the 2-CAA derivatives exhibit excitation-wavelength-
dependent fluorescence that could possibly originate from the
coexistence of both tautomers in solution. The time-resolved
fluorescence study also reveals the presence of two different
light-emitting species in solution.
hydroxide was found to give relatively higher yields. Further,
better yields were obtained when a protic solvent, such as
ethanol, methanol, or isopropyl alcohol, was used. Importantly,
the product obtained using solvents like acetonitrile, dichloro-
methane, benzene, and hexane was a nonfluorescent com-
pound, whereas the one obtained by using ethanol, methanol,
and isopropyl alcohol was found to be fluorescent in nature.
1
Nevertheless, H and 13C NMR spectra confirm the formation
of (E)-2-cyano-3-phenylacrylamide irrespective of the solvent
used for the synthesis. It is really intriguing that the solvent
used for synthesis has a major role in determining the
fluorescent properties of the resultant product, even when the
structures are the same. To our surprise, an identical compound
reported in the literature was known to be a nonfluorescent
molecule.17 It is also to be noted that the melting point of 3a
was found to be slightly higher, ca. 10 °C, than the reported
one.17 Though this behavior is not clearly understood, we
believe that the presence of intermolecular hydrogen bonding
in 3a might have influenced the fluorescence properties. We
have also synthesized the series of compounds possessing 2-
cyano-3-arylacrylamide (2-CAA) substituted with electron-
withdrawing or -donating groups, as shown in the Chart 1.
The single-crystal X-ray structure of one of the derivatives,
i.e., 3j, for which data collection from a quality crystal could be
obtained, was determined. The structure of 3j shown in Figure
1 reveals planar molecules forming an (amide)N−H···O-
RESULTS AND DISCUSSION
(amide)-bonded R2 (8) molecular dimer, for which the
■
2
intermolecular N2−H2···O1i [symmetry code: (i) 2 − x, 2 −
y, −z] hydrogen bond, the H···O, N···O distances, and angle
N−H···O are respectively measured to be 2.03 Å, 2.887(3)Å,
and 174°. Crystal packing is further characterized by molecular
dimers associated into a parallel-stacking arrangement, with a
Cg1···Cg1ii [symmetry code: (ii) x, 1 + y, z] centroid-to-
centroid distance of 3.8750(13) Å, parallel distance of
3.4634(9)Å, and a slippage of 1.739 Å, where Cg1 denotes
the centroid of the (C1−C6) aryl ring.
The intensely green fluorescent target compound (E)-2-cyano-
3-phenylacrylamide (3a) shown in Chart 1 has been
synthesized, in quantitative yields, by using Knoevenagel
condensation between the cyanoacetamide and benzaldehyde
in the presence of a catalyst.
Chart 1. Phenylacrylamide Derivatives
The presence of intermolecular H-bonded amide dimers and
possible π-electron delocalization in amide is expected to
1
facilitate the amide ↔ iminol tautomerism. Indeed, H NMR
studies, as shown in Figure 2, reveal the two broad singlets for
the amide protons at 7.83 and 7.96 ppm in DMSO-d6, instead
of one broad singlet generally observed for the amide proton at
7.96 ppm,12 and also the chemical shift values of these protons
further shifted to 5.90 and 6.33 ppm in CDCl3.
We have recorded NMR for 3j in the range from 25 to 60 °C
and found that the peak at 7.85 ppm remains a singlet at 50−60
°C, whereas at 25−45 °C the peak at 7.85 ppm shifts toward an
upfield region and splits from a broad singlet in to a doublet at
Several reaction conditions were adopted to optimize the
catalyst, catalyst concentration, and solvent, and the details are
summarized in Table S1 of the Supporting Information (SI). It
can be understood from Table S1 that the reaction did not
preceded without the catalyst, and 1 mol % of sodium
Figure 1. (a) Dimeric association of 3j linked through (amide)N−H···O(amide) hydrogen bonds. (b) Molecular stacking, shown in a crystal-packing
view projected onto the bc-axis, highlighting molecular aggregation via π···π interactions also in addition to dimeric association.
B
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Figure 2. Chemical shift of 2-cyano-3-(4-chlorophenyl)acrylamide (3j) in DMSO-d6 and CDCl3.
7.9 ppm (Figure 3). This clearly supports the evidence for the
formation of intermolecular hydrogen bonding between the
protons attached to the amino nitrogen can be asscribed to the
coexistence of amide ↔ iminol tautomers in solution. The
electronic properties of 2-CAA derivatives were studied by
UV−visible absorption as well as steady-state and time-resolved
fluorescence spectroscopic techniques. UV−visible absorption
spectra of the all the samples were recorded in chloroform, and
the data are summarized in Table 1.
The representative absorption and fluorescence spectra of
compounds (E)-2-cyano-3-phenylacrylamide (3a) and (E)-2-
cyano-3-(naphthalen-2-yl)acrylamide (3n) dissolved in chloro-
form solvent are depicted in Figure 4. Both the compounds
Figure 3. 1H NMR spectrum of 2-cyano-3-(4-chlorophenyl)-
acrylamide (3j) in DMSO at high temperature from 7 to 8 ppm.
amide hydrogen and carbonyl oxygen. In our previous report,18
we described the synthesis of triazatricyclo[6.2.2.01,6]dodecane-
9,12-dione (TATCD) derivatives. In the previous report, the
synthesized TATCD derivatives possess a fluorescence
property due to the formation of the 2-CAA intermediate;
thus, the fluorescence property of this 2-CAA molecule is
retained in order for the TATCD derivatives to exhibit
fluorescence. The presence of two different peaks for the
Figure 4. UV−visible absorption (solid line) and fluorescence (dotted
line) spectra of 3a (black) and 3n (red) in chloroform solvent. The
samples were excited at 357 nm.
Table 1. Photophysical Properties of Phenylacrylamide Derivatives in Chloroform Solvent
entry
substituent
λabs, nm (ε104 M−1 cm−1
)
λfl, nm
424
Stokes shift, cm−1
τ1, ns
relative amplitude
τ2, ns
relative amplitude
τavg, ns
3a
3b
3c
3d
3e
3f
H
280 (0.459), 357 (0.069)
270 (0.689), 391 (0.065)
270 (0.496), 392 (0.116)
270 (2.32), 390 (0.24)
269 (0.643), 400 (0.097)
274 (0.134), 394 (0.008)
268 (0.424), 350 (0.17)
360 (0.48)
4482
3836
3771
3711
3165
3210
4475
4950
4999
6798
4656
6491
4931
4482
1.16
2.48
1.97
2.55
2.53
1.74
0.38
0.62
1.58
1.03
1.04
1.05
1.08
1.60
60.4
4.72
−
−
−
−
39.6
−
-
2.63
−
-
p-OCH3
o-OCH3
p-CH3
m-CH3
o-CH3
p-F
437, 460
437, 460
430, 456
433, 458
435, 455
415
100
100
100
−
−
−
−
−
−
100
100
−
3g
3h
3i
47.67
29.71
51.93
57.90
23.41
27.25
22.24
44.09
1.42
2.16
3.72
4.46
5.59
3.61
3.99
3.86
52.33
70.23
48.07
42.10
76.56
72.75
77.76
55.91
0.92
1.70
2.10
2.47
4.52
2.85
3.34
2.86
m-F
414, 444
442
o-F
280 (1.86), 357 (0.64)
351 (1.19)
3j
p-Cl
434, 461
421
3k
3l
o-Cl
282 (1.08), 352 (0.36)
278 (0.657), 356 (0.53)
275 (0.585), 350 (0.167)
276 (0.317), 357 (0.023)
p-Br
424, 463
423
3m
3n
p-CN
−
424
C
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show the lowest energy absorption band at 357 nm and the
highest energy peak around 280 nm. The extended π electron
conjugation for 3n compared to 3a does not alter the S0 → S1
transtion energy, but the molar extinction coefficient values and
relative intensities are found to be characteristic of the aryl
groups. The lowest energy peak has been attributed to the
transition from singlet ground (S0) to the first excited state
(S1), S0 → S1.
The fluorescence spectra of 3a and 3n were observed at 424
nm having a mirror image relationship with their respective
lowest energy absorption band. The Stokes shift value was
calculated to be ∼4480 cm−1 for both 3a and 3n. The higher
Stokes shift value suggests that significant structural changes
occur during the transition from ground to an excited state.
Further, the presence of the cyanoacrylamide moiety, a strong
acceptor group, connected to the aromatic ring through
intervening π-conjugation probably induces the intramolecular
charge transfer (ICT) character, which would also be
responsible for the observed larger Stokes shift values. To get
further insight on the ICT interactions, we have calculated
frontier molecular orbitals using the Gaussian 03 program.19
The crystal structure of 3j was used as an input file for the
TD-DFT calculations. The highest occupied molecular orbitals
(HOMO) and lowest unoccupied molecular orbital (LUMO)
were calculated at the B3LYP/6-31G level using the optimized
geometries at the same level of theory. As can be seen from the
Figure S1 (SI), most of the electron density was found to be
localized on the aryl ring in the HOMO, whereas in the LUMO
it was localized on the cyanoacrylamide moiety. The electron
density redistribution during the transition from HOMO to
LUMO suggests the existence of intramolecular charge transfer
interactions, which in fact can be influenced by the nature of
the substituent and its substitution position (Table S3, SI). In
addition, the HOMO and LUMO energy levels were perturbed
to a smaller than significant extent by the substituents. Further,
a qualitative correlation with respect to electron-withdrawing/
donating behavior, a plot of energies of the frontier orbital
versus the Hammett parameter (σ+)20,21 is shown in Figure 5.
While the theoretically calculated HOMO and LUMO energy
levels show a linear relationship with the Hammett parameter,
no correlation has been observed for the experimental lowest
energy absorption maximum (in wavenumbers) versus the
Hammett parameter.
Attempts have been made to tune the electronic properties of
2-CAA by introducing the different electron-withdrawing and
-donating groups at o/m/p-phenylene positions. The UV−
visible absorption spectrum of 2-CAA was found to show
significant changes in the spectral pattern with respect to the
electron-donating or -withdrawing nature of the substituent.
As can be seen from the UV−visible absorption spectra
shown in Figure 6, for the 2-CAA derivatives substituted with
an electron-donating group, the lowest energy absorption peak
becomes intensified, broadened, and red-shifted by 35−42 nm,
characteristic of the substituent. On the other hand, the
electron-donating substituents do not show any significant
spectral shifts due to substituent position. This feature suggests
that the lowest energy absorption band might have originated
due to intramolecular charge transfer transition (S0 → CT).
Further, careful examination of Table 1 reveals that the molar
extinction coefficient for the CT band was sensitive to the
substituent position; the presence of bulky group, such as
methyl and chlorine, in the ortho position resulted in a decrease
of molar extinction coefficient by at least a factor of 3 when
Figure 5. Plots of (a) HOMO energy and (b) LUMO energy
calculated using Gaussian 03 and (c) experimental absorption
maximum (in wavenumber) versus Hammett constant for phenyl-
acrylamides derivatives.
compared to the respective para-isomers. Similar to the
absorption spectra, fluorescence spectra of the substituted 2-
CAA show significant changes characteristic of the nature of the
substituent as well as to its position in the aromatic ring (Figure
S2, SI). Nonetheless, the emission maxima were found to show
only marginal changes, ca. 10 nm, with substitution. The
electron-donating methyl and methoxy substituents show two
emission peaks around 430 and 460 nm, irrespective of the
substituent position. In contrast, the electron-withdrawing
group fluorine shows substituent-position-dependent fluores-
cence spectra wherein the meta-isomer show two peaks at 414
and 444 nm, and the ortho- and para-isomers respectively emit
at 442 and 415 nm.
Further information about the excited state can be gleaned
from the fluorescence lifetime decay profiles shown in Figure 7
obtained using the time-correlated single-photon-counting
technique. The decay profiles were fitted with a single or
biexponential function, and the data are summarized in Table 1.
For 3a, two lifetimes with the time constants of 1.16 and 4.72
ns with the relative amplitudes of 60.40 and 39.60, respectively,
were obtained. The two different lifetimes might have
originated from the amide and iminol forms of 3a at the
excited state. Intriguingly, the decay profiles of the compound
substituted with electron-donating substituents, such as methyl
and methoxy group, was fitted with a single exponential
function with the lifetimes ranging from 1.74 to 2.55 ns.
Further, the ortho-substituted 2-CAA derivative show com-
paratively shorter lifetime, ca. ∼0.5 ns, than their corresponding
para congener, probably due to the steric interaction with the
cyanoacrylamide moiety, which would enhance the non-
radiative decay. In contrast, the electron-withdrawing sub-
stituents shows two fluorescence lifetimes, similar to the parent
compound 3a, but with different time constants and relative
amplitude values. The influence of substituent position on
fluorescence lifetime can be understood from the longer
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Figure 6. UV−visible absorption spectra of phenylacrylamide derivatives dissolved in chloroform solvent.
The possibility of intramolecular charge transfer interactions in
2-CAA derivatives can be understood from the solvent-polarity-
dependent photophysical studies using selected compounds.
Though a solvent-induced spectral change has been witnessed
for 3a, 3h, and 3j, as shown in Figure 8, the observed spectral
shift has not been characteristic of that generally observed for
the system that shows intramolecular charge transfer
interactions. For instance, 3a in toluene shows two well-
resolved emission peaks at 410 and 434 nm along with a
shoulder at 460 nm.
Notably, a similar pattern is observed for 3a in acetonitrile
and THF, a broad peak with single maximum, as was observed
in chloroform. The molecules with donor−acceptor config-
uration showing intramolecular charge transfer interactions
generally show solvent-polarity-induced red-shifted fluores-
cence, which has been quantified using a Lippert−Mataga
plot. Considering the absence of correlation between the
Lippert−Mataga plot and solvent-polarity-induced red-shifted
fluorescence, it can be understood that the difference in the
spectral pattern would have been due to the coexistence of at
least two isomers in solution, and their presence is strongly
influenced by the nature of the solvent. This hypothesis is
Figure 7. Fluorescence decay profiles of phenylacrylamide derivatives
dissolved in chloroform solvent. The decay was monitored at their
respective emission maximum wavelength.
lifetime for o-fluoro and o-chloro substituents by nearly a factor
of 2 with respect to the corresponding para-isomers.
The shorter lifetime of the para-isomer is probably due to the
fact that the para-isomer favors amide ↔ iminol tautomerism
compared to the respective ortho-isomer, which would
deactivate the excited state by a nonradiative decay pathway.
Figure 8. Fluorescence spectra of (a) 3a, (b) 3h, and (c) 3j and fluorescence decay profiles of (d) 3a dissolved in solvents of different polarity.
E
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Scheme 1
confirmed further by the fluorescence lifetime; the decay profile
analysis of 3a in different solvents given in Figure 8.
disappeared when the sample was excited beyond 320 nm. This
feature again ascertains that 2-CAA derivatives exist as
acrylamide and iminol isomers and that the isomerism is
facilitated by the intramolecular hydrogen bonding between the
carbonyl and amide moieties.
The fluorescence lifetime of the long-lived component of 3a
was measured to be 4.72, 9.84, and 11.18 ns, respectively, in
chloroform, tetrahydrofuran, and dimethyl sulfoxide. Similarly,
the short-lived component also show increased fluorescence
lifetime from 1.16 to 2.84 ns while going from chloroform to
DMSO along with the decreased relative amplitude. This
feature is not clear now; however, we believe that it can be
directly related to the hydrogen-bonding dissociation ability of
the solvent.
CONCLUSIONS
■
We are the first to report the synthesis of substituted 2-cyano-3-
phenylacrylamide fluorophore derivatives showing fluorescence
due to the presence of intermolecular hydrogen bonding
between the carbonyl oxygen and amide hydrogen. The single-
crystal X-ray structures and 1H NMR studies show the presence
of intermolecular hydrogen bonding between the carbonyl
group and amide protons. The spectral properties were found
to be strongly influenced by the electron-donating/withdrawing
nature of the substituents and their substitution position. The
phenyl group bearing an electron-donating substituent induces
the intramolecular charge transfer character, which has been
witnessed by the enhanced intensity of charge transfer
absorption. Interestingly, the fluorescence and NMR studies
suggest the presence of two isomeric forms, i.e., acrylamide and
iminol, having two different emission energies. We have shown
on the basis of the fluorescence studies that the equilibrium
between the acrylamide and iminol can be tuned by the
surrounding environment, the substituent, and its position,
which would be an ideal behavior for a molecule to be used as a
fluorescent probe for biological environments. We believe that
our preliminary studies revealed the interesting photophysical
properties of 2-cyano-3-phenylacrylamide derivatives, which
have potential applications as a new class of dyes and
fluorescent probes.
It has been known from the single-crystal X-ray structures
shown in Figure 122−24 that there exists intermolecular
hydrogen-bonding interactions that would favor the isomerism
between the acrylamide and iminol form, as shown in Scheme
1. Indeed, the isomerism between the acrylamide and iminol
1
form can be evident from the two broad singlets in the H
NMR spectra, corresponding to the two protons in a different
environment (Figures 2 and 3). Further, 3h and 3j also show a
similar pattern in solvent-dependent fluorescence studies,
indicating that acryalmide ↔ iminol isomerism occurs
irrespective of the substituent present in it.
The coexistence of isomers was further demonstrated by the
excitation-wavelength-dependent fluorescence emission of the
selected compounds 3a, 3m, and 3n in chloroform solvent,
shown in Figure 9. All the compounds show two/three
emission peaks at higher excitation wavelengths, i.e., at 270 nm.
The increase in the excitation wavelength leads to the
diminishment of the longer wavelength peak, and it completely
EXPERIMENTAL SECTION
■
Materials and Methods. FT-IR spectra were recorded in the
range of 4000−400 cm−1. 1H NMR and 13C NMR spectra were
recorded in CDCl3 and DMSO-d6 solvents. Chemical shifts are given
in parts per million (δ-scale), and the coupling constants are given in
hertz. For HRMS, the ionization method was electron impact
ionization (EI) and the analyzer type was magnetic field deflection
double focusing (electrostatic field and magnetic field, high
resolution). The steady-state fluorescence measurements were
determined using a fluorescence spectrophotometer. Fluorescence
lifetimes were measured by the time-correlated single-photon-counting
method (IBH). The molecules were excited at 375 nm for <200 ps
using Nano LED light, and the decay profiles are monitored at the
respective emission maximum wavelengths. Thin layer chromatog-
raphy was performed on precoated silica gel on alumina plates.
Single crystals of 3j were grown from methanol. The structure was
solved by applying the direct phase-determination technique using
SHELXS-97 and refined by full-matrix least-squares on F2 using
SHLEXL-97.17−19 Hydrogens were stereochemically fixed and refined
with the riding options. The distances with the hydrogen atoms are
aromatic/sp2 C−H = 0.93 Å, amide N−H = 0.86 Å, and Uiso =
1.2Ueq(parent). Essential crystal data are listed in Table S2 (SI).
Crystallographic data have been deposited at the Cambridge
Crystallographic Data Center with entry number CCDC 1018088.
Figure 9. Excitation-wavelength-dependent fluorescence spectra of the
compounds (a) 3a, (b) 3m, and (c) 3n in chloroform. The peak
within the rectangle in panel a is due to second-order scattering.
F
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1
General Procedure for the Synthesis of Phenylacrylamide
(3a−3n). A dry 100 mL Erlenmeyer flask was charged with
cyanoacetamide (1.0 mmol), aromatic aldehydes (1.0 mmol), sodium
hydroxide (1 mol %), and methanol (15 mL). The reaction mixture
was stirred at 40 °C for 1−2 h. The reaction was monitored by TLC
and after the completion of reaction, the reaction mixture was
neutralized by adding a few drops of 0.1 N HCl. Thus, the reaction
mixture was extracted with DCM (3 × 20 mL) and the crude reaction
mixture was recrystallized using a mixture of ethanol:THF (1:1).
2-Cyano-3-phenylacrylamide (3a). Colorless crystal; mp 143−144
°C; Rf 0.73 (50% ethyl acetate:hexane); FTIR (KBr) ν 3452, 3061,
ν 3450, 3093, 2930, 2339, 1671 cm−1; H NMR (400 MHz, CDCl3)
6.93−6.97 (t, 2H), 7.18 (s, 1H), 7.26−7.31 (m, 1H), 7.28 (s, 1H),
7.46 (s, 1H), 7.61−7.63 (d, 1H) ppm; 13C NMR (100 MHz, CDCl3)
114.5, 114.9, 122.9, 128.0, 128.6, 128.8, 128.9, 135.6, 136.7, 167.9
ppm; HRMS calcd for C10H7FN2O ([M]+) 190.0542, found 190.0543.
2-Cyano-3-(4-cholorophenyl)acrylamide (3j). Light yellow crystal;
mp 238−240 °C; Rf 0.52 (50% ethyl acetate:hexane); FTIR (KBr) ν
3473, 3094, 2952, 2373, 1642 cm−1; H NMR (400 MHz, DMSO)
1
7.63−7.65 (d, 2H), 7.83 (s, 1H), 7.94−7.96 (d, 2H), 7.96 (s, 1H), 8.18
(s, 1H) ppm; 13C NMR (100 MHz, DMSO) 110.5, 121.3, 124.6,
127.6, 127.7, 164.6 ppm; HRMS calcd for C10H7ClN2O ([M]+)
206.0247, found 206.0245.
1
2900, 2309, 1697 cm−1; H NMR (400 MHz, CDCl3) 5.50 (s, 1H),
6.15 (s, 1H), 6.82−6.84 (d, 2H), 6.89 (s, 1H), 7.18−7.12 (d, 2H),
7.36−7.39 (t, 1H) ppm; 13C NMR (100 MHz, CDCl3) 104.3, 119.5,
121.1, 121.1, 124.3, 127.9, 128.0, 165.9 ppm; HRMS calcd for
C10H8N2O ([M]+) 172.0637, found 172.0639.
2-Cyano-3-(2-cholorophenyl)acrylamide (3k). White powder; mp
208−209 °C; Rf 0.26 (50% ethyl acetate:hexane); FTIR (KBr) ν 3485,
1
3103, 2894, 2356, 1742 cm−1; H NMR (400 MHz, DMSO) 7.32 (s,
1H), 7.89 (s, 1H), 7.38−7.51 (d, 2H), 7.89−7.92 (d, 2H), 8.20 (s, 1H)
ppm; 13C NMR (100 MHz, DMSO) 114.6, 125.2, 129.4, 129.5, 136.9,
167.4 ppm; HRMS calcd for C10H7ClN2O ([M]+) 206.0247, found
206.0246.
2-Cyano-3-(4-methoxyphenyl)acrylamide (3b). Light yellow
powder; mp 253−255 °C; Rf 0.62 (50% ethyl acetate:hexane); FTIR
1
(KBr) ν 3476, 3095, 2961, 2364, 1727 cm−1; H NMR (400 MHz,
CDCl3) 3.86 (s, 3H), 5.76 (s, 1H), 6.31 (s, 1H), 6.81−6.90 (m, 2H),
7.14−7.18 (m, 2H), 7.15 (s, 1H) ppm; 13C NMR (100 MHz, CDCl3)
42.5, 111.0, 114.4, 120.1, 123.3, 124.7, 129.0, 129.8, 136.1, 169.7 ppm;
HRMS calcd for C11H10N2O2 ([M]+) 202.0742, found 202.0740.
2-Cyano-3-(2-methoxyphenyl)acrylamide (3c). Yellow powder;
mp 261−263 °C; Rf 0.47 (50% ethyl acetate:hexane); FTIR (KBr) ν
2-Cyano-3-(4-bromophenyl)acrylamide (3l). Light brown powder;
mp 257−258 °C; Rf 0.64 (50% ethyl acetate:hexane); FTIR (KBr) ν
1
3459, 3041, 2978, 2329, 1681 cm−1; H NMR (400 MHz, CDCl3)
5.68 (s, 1H), 6.23 (s, 1H), 6.83 (s, 1H), 7.33−7.35 (d, 2H), 7.40−7.42
(d, 2H) ppm; 13C NMR (100 MHz, CDCl3) 122.0, 127.5, 128.7,
128.8, 131.9, 132.1, 133.7, 135.9, 168.2 ppm; HRMS calcd for
C10H7BrN2O ([M]+) 249.9742, found 249.9743.
1
3462, 3084, 2882, 2379, 1703 cm−1; H NMR (400 MHz, CDCl3)
2-Cyano-3-(4-cyanophenyl)acrylamide (3m). Light yellow pow-
3.88 (s, 3H), 5.98 (s, 1H), 6.42 (s, 1H), 6.83−6.92 (m, 2H), 7.15−
7.20 (t, 1H), 7.25 (s, 1H), 7.51−7.53 (d, 1H) ppm; 13C NMR (100
MHz, CDCl3) 49.9, 114.5, 125.8, 127.8, 128.5, 130.9, 134.6, 136.2,
169.6 ppm; HRMS calcd for C11H10N2O2 ([M]+) 202.0742, found
202.0743.
der; mp 281−282 °C; Rf 0.42 (50% ethyl acetate:hexane); FTIR (KBr)
1
ν 3474, 3051, 2892, 2346, 1701 cm−1; H NMR (400 MHz, CDCl3)
5.62 (s, 1H), 5.89 (s, 1H), 6.73 (s, 1H), 6.82−6.84 (d, 2H), 6.94−6.96
(d, 2H) ppm; 13C NMR (100 MHz, CDCl3) 123.1, 125.3, 129.6,
130.5, 131.5, 135.7, 137.6, 169.9 ppm; HRMS calcd for C11H7N3O
([M]+) 197.0589, found 197.0591.
2-Cyano-3-(p-tolyl)acrylamide (3d). Light white powder; mp 205−
206 °C; Rf 0.53 (50% ethyl acetate:hexane); FTIR (KBr) ν 3447,
1
3003, 2946, 2373, 1661 cm−1; H NMR (400 MHz, CDCl3) 2.42 (s,
2-Cyano-3-(naphthalen-1-yl)acrylamide (3n). Colorless crystal;
mp 245−246 °C; Rf 0.88 (50% ethyl acetate:hexane); FTIR (KBr) ν
3H), 5.72 (s, 1H), 6.15 (s, 1H), 6.76 (s, 1H), 7.34−7.36 (d, 2H),
7.42−7.44 (d, 2H) ppm; 13C NMR (100 MHz, CDCl3) 27.7, 122.2,
128.9, 129.0, 131.5, 132.2, 133.7, 134.5, 134.6, 167.8 ppm; HRMS
calcd for C11H10N2O ([M]+) 186.0793, found 186.0796.
1
3471, 3068, 2953, 2329, 1681 cm−1; H NMR (400 MHz, CDCl3)
6.51 (s, 1H), 6.85 (s, 1H), 6.84−6.86 (d, 1H), 7.44−7.54 (m, 4H),
7.82−7.84 (d, 1H), 7.89−7.90 (d, 1H), 8.22−8.24 (d, 1H) ppm; 13C
NMR (100 MHz, CDCl3) 114.5, 122.6, 123.7, 124.8, 125.9, 126.1,
127.1, 128.6, 129.4, 131.0, 132.3, 133.8, 136.6, 167.8 ppm; HRMS
calcd for C14H10N2O ([M]+) 222.0793, found 222.0792.
2-Cyano-3-(m-tolyl)acrylamide (3e). Creamy powder; mp 254−
256 °C; Rf 0.69 (50% ethyl acetate:hexane); FTIR (KBr) ν 3482,
1
3019, 2971, 2356, 1636 cm−1; H NMR (400 MHz, CDCl3) 2.24 (s,
3H), 6.01 (s, 1H), 6.42 (s, 1H), 7.00 (s, 1H), 7.03−7.08 (t, 1H),
7.13−7.17 (t, 1H), 7.27−7.34 (q, 1H), 7.43−7.46 (d, 1H) ppm; 13C
NMR (100 MHz, CDCl3) 26.3, 114.6, 122.4, 128.8, 129.0, 134.3,
135.0, 135.6, 167.8 ppm; HRMS calcd for C11H10N2O ([M]+)
186.0793, found 186.0792.
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.5b02226.
2-Cyano-3-(o-tolyl)acrylamide (3f). White powder; mp 225−227
°C; Rf 0.37 (50% ethyl acetate:hexane); FTIR (KBr) ν 3483, 3094,
1
2953, 2328, 1643 cm−1; H NMR (400 MHz, CDCl3) 2.21 (s, 3H),
Table summarizing synthetic conditions, spectroscopic
characterization of all compounds, HOMO and LUMO
of 2-CAA derivatives, crystal data for 3j, and Cartesian
coordinates for 3a−i,k−m (PDF)
6.08 (s, 1H), 6.45 (s, 1H), 6.91−6.95 (t, 1H), 7.09 (s, 1H), 7.24−7.28
(t, 1H), 7.44−7.46 (d, 1H), 7.58−7.61 (d, 1H) ppm; 13C NMR (100
MHz, CDCl3) 21.0, 114.5, 122.9, 129.3, 133.4, 135.5, 166.9 ppm;
HRMS calcd for C11H10N2O ([M]+) 186.0793, found 186.0792.
2-Cyano-3-(4-fluorophenyl)acrylamide (3g). Light yellowish
powder; mp 211−212 °C; Rf 0.82 (50% ethyl acetate:hexane); FTIR
Crystallographic data in CIF format for 3j (CIF)
1
(KBr) ν 3423, 3121, 2983, 2375, 1684 cm−1; H NMR (400 MHz,
AUTHOR INFORMATION
CDCl3) 6.73 (s, 1H), 6.82−6.85 (d, 1H), 7.11 (s, 1H), 7.32 (s, 1H),
7.31−7.34 (d, 1H), 7.39−7.42 (d, 2H) ppm; 13C NMR (100 MHz,
CDCl3) 112.0, 114.3, 120.0, 123.4, 125.1, 129.0, 129.6, 135.9, 168.9
ppm; HRMS calcd for C10H7FN2O ([M]+) 190.0542, found 190.0544.
2-Cyano-3-(3-fluorophenyl)acrylamide (3h). Greenish powder;
mp 203−205 °C; Rf 0.41 (50% ethyl acetate:hexane); FTIR (KBr) ν
■
Corresponding Authors
*K.I.S. E-mail: sathiya_kuna@hotmail.com.
*S.E. E-mail: moorthi@clri.res.in.
Present Address
(R.S.R.) Department of Biotechnology, DSCE, Dayanandasagar
Institute, Bangalore 560 078, India.
1
3412, 3133, 2921, 2345, 1666 cm−1; H NMR (400 MHz, CDCl3)
5.93 (s, 1H), 6.34 (s, 1H), 6.71−6.73 (d, 1H), 7.12−7.14 (d, 1H),
7.23−7.27 (t, 1H), 7.31 (s, 1H), 7.39−7.47 (m, 1H) ppm; 13C NMR
(100 MHz, CDCl3) 114.5, 115.9, 116.1, 122.4, 123.8, 124.0, 129.4,
130.3, 136.1, 166.8 ppm; HRMS calcd for C10H7FN2O ([M]+)
190.0542, found 190.0540.
Author Contributions
R.G. and P.T. contributed equally to this work.
Notes
2-Cyano-3-(2-fluorophenyl)acrylamide (3i). Light greenish pow-
der; mp 227−229 °C; Rf 0.63 (50% ethyl acetate:hexane); FTIR (KBr)
The authors declare no competing financial interest.
G
DOI: 10.1021/acs.joc.5b02226
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
ACKNOWLEDGMENTS
■
The work is supported by the suprainstitutional project
“STRAIT” of CSIR-CLRI. P.T. acknowledges the Department
of Science and Technology for the INSPIRE fellowship. The
DST-FIST NMR facility at VIT University is greatly acknowl-
edged. We also thank Prof. P. Ramamurthy and Dr. C.
Selvaraju, NCUFP, University of Madras, for their help with
fluorescence lifetime measurements. This work is CSIR-CLRI
contribution no. 1094.
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J. Org. Chem. XXXX, XXX, XXX−XXX