Synthesis of Thiazoles Bearing Aryl Enamine/Aza-enamine Side Chains: Effect of the π-Conjugated Spacer Structure and Hydrogen Bonding on Photophysical Properties

Article abstract of DOI:10.1002/ejoc.201700518

An efficient synthesis of a new series of di- and trisubstituted thiazoles (TZs) bearing aryl enamine side-chains (ETZs) has been developed and the optical properties of these compounds compared with structural analogues containing the isoelectronic aza-enamine group (ATZs). Spectral characterization demonstrated the difference in the absorption and fluorescence of the ETZs and ATZs in solution and the emergence of fluorescent ETZs in the solid state. The optimized structural geometries and weak intramolecular interactions, electronic characteristics of the ground and excited states, HOMO and LUMO analyses, changes in electron density after S₀ → S_1v excitation and maps of electrostatic potential (MEPs) calculated by means of DFT have allowed us to estimate the particularities of the geometric and electronic structures of the ETZs and ATZs in the ground and excited states. The availability, synthetic simplicity, stability, large Stokes shifts and high sensitivity to the microenvironment (fluorosolvatochromic behaviour) make the obtained TZs a useful platform for the further design and synthesis of new effective compounds for applications in the field of fluorescence imaging.

Full text of DOI:10.1002/ejoc.201700518

A Journal of
Accepted Article
Title: Synthesis of Thiazoles Bearing Aryl Enamine/Aza-enamine
Side Chains. Effect of the π-Conjugated Spacer Structure and
Hydrogen Bonding on Photophysical Properties
Authors: Kseniya I. Lugovik, Aleksandra V. Popova, Alexander K.
Eltyshev, Enrico Benassi, and Nataliya Belskaya
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201700518
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10.1002/ejoc.201700518
European Journal of Organic Chemistry
FULL PAPER
Synthesis of Thiazoles Bearing Aryl Enamine/Aza-enamine Side Chains.
Effect of the π-Conjugated Spacer Structure and Hydrogen Bonding on
Photophysical Properties
Kseniya I. Lugovik,[a] Aleksandra V. Popova,[a] Alexander K. Eltyshev,[a] Enrico Benassi,*[b]
Nataliya P. Belskaya*[a]
of the derivatives of this heterocycle, the thiazole moiety
continues to be a key pharmacophore for medicinal chemistry and
drug discovery research.[4] Thus, the various applications of
thiazoles allow them to remain a focus in heterocyclic chemistry.
A remarkable advantage for the development of new synthetic
thiazole is the numerous convenient methods for their
construction, which give different possibilities for peripheral
derivatization [5] and allow the tuning of the optical properties of
these compounds by varying their electronic nature with electron-
donor and electron-acceptor groups and the length and nature of
their conjugated systems. The most well-known approach for
forming the thiazole ring is the Hantzsch synthesis, where primary
thioamides or thioureas react with α-halocarbonyl compounds to
afford various TZs in a single step.[5,6] This is an excellent method
for functionalizing thiazole rings with primary, secondary and
tertiary amine groups and different electron-donating and
electron-accepting alkyl, aryl, and heteroaryl substituents.[3]
An eloquent example of the excellent fluorescence of this
heterocycle derivatives depending on the attached substituents
structure is represented by recently published results of the
synthesis and investigation of photophysical properties for a
series of 5-arylaminothiazoles, with wide tuned emission ranged
from 460 to 610 nm and fluorescence quantum yield between
0.01-0.86.[3d] A family of asymmetrical D-π-A and symmetrical D-
π-D types of thiazole-based fluorescent compounds were
prepared also and their photophysical and electrochemical
characteristics exhibit high electrochemical activity with a green
Abstract: An efficient synthesis of
a new series of di- and
trisubstituted thiazoles (TZs) bearing aryl enamine side chains (ETZs)
was developed, and the optical properties of these compounds were
compared with structural analogues containing the isoelectronic aza-
enamine group (ATZs). Spectral characterization has demonstrated
the difference in the absorption and fluorescence of the ETZs and
ATZs in solution and emergence of fluorescence ETZs in a solid state.
The optimized structural geometries and weak intramolecular
interactions, electronic characteristics of the ground and excited
states, HOMO and LUMO analysis, changes in electron density after
the S0 → S1v excitation, and map of the electrostatic potential (MEP)
calculated at DFT level allowed us to estimate the particularities in the
geometric and electronic structures of the ETZs and ATZs in the
ground and excited states. The availability, synthetic simplicity,
stability, large Stokes shift, and high sensitivity to the
microenvironment (fluorosolvatochromic behaviour) make the
obtained TZs a useful platform for the further design and synthesis of
new effective compounds for applications in the field of fluorescence
imaging.
Introduction
fluorescence
emission.[3e]
4-Hydroxy-1,3-thiazoles
were
Thiazoles and their derivatives are abundant in natural products,
biologically active compounds and some pharmaceuticals.[1] This
structural element is also found in commercial products, such as
thiazole orange, which is a commonly used cyanine dye for
binding to nucleic acids. In this compound, the thiazole ring is part
of a benzothiazole, which is especially suitable for biosensors and
imaging applications.[2] Substituted monocyclic thiazoles (TZs),
which are typically linked to aryl or heteroaryl groups, are
privileged structural motifs applied in different fields, such as
materials science, for the preparation of liquid crystals, molecular
switches, and sensors.[3] Furthermore, because of the low toxicity
suggested as a new class of promising functional fluorophores
and therefore they are extensively studied for various
application.[3c] The azide-modified thiazole-based reporter
molecule with better properties for fluorescence and UV detection
compare to the commercially available fluorophores were also
synthesized and characterised.[3f]
On the other hand, introducing flexible bridge within the
molecule increases the ability of these compounds to adopt
various
structural
conformations
and
form
weak
intra/intermolecular interactions that may affect the chemical,
photophysical and biological properties and may be used to
control them.[7] Thus, estimating the relationships between the
structural features and the ratios of conformers/rotamers and
intra/intermolecular hydrogen bonding is essential for different
applications. To understand the fluorescence of a molecule, it is
important to know its conformational properties, which may help
to predict the energy irradiation during vibrational relaxation.
Hence, weak interactions are notable and may play a central role,
because they affect the energy of the oscillations of a molecule’s
excited states and probability of its vibrational transitions.
The most commonly employed and widely studied flexible
bridging structures linking the donor and acceptor moieties of the
photoactive molecule are polymethine chain, ethylene, azo or
azomethine bonds.[8] We propose to study structural features and
photophysical properties of compounds 1 and 2 (Figure 1), which
[a]
[b]
Kseniya, I. Lugovik, Aleksandra V. Popova, Alexander K. Eltyshev,
Prof. Nataliya P. Belskaya
Ural Federal University
19 Mira Str., Yekaterinburg 620002 (Russian Federation)
E-mail: n.p.belskaya@urfu.ru
Dr. Enrico Benassi
Scuola Normale Superiore,
Piazza dei Cavalieri 7 56126, Pisa (Italy)
E-mail: enrico.benassi@sns.it
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201700518
European Journal of Organic Chemistry
FULL PAPER
bear a conjugated π-spacer, including -NH-X=C< link, and differ
from each other only by a CH unit (in compound 1) replaced by a
N atom (in compound 2). Moreover, compounds 1 and 2 are
suitable for formation of possible intramolecular hydrogen bonds
due to the presence of the NH-fragment and thiazole nitrogen
atom as donor of electrons.
The dependency of the electronics, location and strength on the
substituents on opposite sides of the molecules allows us to
evaluate the effect of the enamine/aza-enamine chains on
intramolecular charge transfer (ICT), photophysical properties
and weak intramolecular interactions.
Results and Discussion
Synthesis and characterization
The required starting materials for the synthesis of thiazoles 1 are
arylaminothioacrylamides 6 with unsubstituted thioamide group.
For their synthesis, we apply a recently developed protocol based
Figure 1. Design of the new thiazole derivatives with aryl enamine and aryl aza-
enamine side groups.
on the condensation of cyanothioacetamide
3
with
dimethylformamide dimethyl acetal (DMFDMA), followed by the
nucleophilic substitution of the dimethylamine moiety with the
desired arylamines 5a-f,h and 9-ethyl-aminocarbazole (5g)
A convenient method for the synthesis of azaenaminethiazoles
(ATZs) was described in the literature and is based on the
reaction
of
arylhydrazonothioacetamides
with
(Scheme 1, Table 1).[10]
bromoacetophenones.[6] However, at the best of our knowledge,
there are no reported examples of synthesis of thiazoles using
thioamides bearing enamine functional groups. This may be
explained by the unique reactivity of enamino group, which
usually produces thiophenes by reacting with haloketones.[9] The
development of a simple protocol for thiazole synthesis based on
broad pool of potential starting reagents provides prospects for
the synthesis of a set desired compounds with different types of
the push-pull systems (Figure 1).
A variety of substituents was introduced to the 4- and 2-
positions of the arylamino moiety in enamines 6a-h using
arylamines 5a-h. The reactions of 3-amino-9-ethylcarbazole (5g)
and N-methyl-N-phenylamine (5h) also afforded compounds 6g,h
with good yields.
The main goal of our investigation is, therefore, to design and
synthesize thiazoles 1 with an aryl enamine side group (X=C) and
compare their electronic characteristics, fine structures, weak
intramolecular interactions and photophysical properties to those
of their structural analogous – aza-enamines 2 (X=N) – using
experimental and theoretical methods (Figure 1). The structures
of compounds 1 and 2 involve an aryl(B)/diaryl(B,C)-substituted
heterocyclic ring and an additional aromatic/heteroaromatic cycle
(A) with electron-donating and electron-accepting groups, which
are interlinked by a conjugated system.
Scheme 1. Reagents and conditions: (a) Dimethylformamide dimethylacetale,
EtOH, 50 °C, 5h; (b) R1R2NH (5a-h) EtOH, HCl, 60 °C.
The structures of arylaminothioacrylamides 6 were confirmed
1
by FTIR, H NMR, 13C NMR, mass spectrometry and elemental
analysis data. Details of the experimental procedures and data for
the structural characterization are disclosed in the Experimental
Section and Supporting Information (SI). Notably, the NMR
spectra show that compounds 6a-g exist as a mixture of two steric
isomers (SI, Figures S1-8).
Table 1. Conversion time of thioamide 4 in its reactions with arylamines 5a-h, yields of arylaminothioacrylamides 6a-h, and ratios of isomers.
R1
R2
R1
R2
Time [h]
Comp 5
Comp 6
Ratio of isomers 6[a]
Yield 6 [%][b]
Entry
5a
5b
5c
5d
6a
6b
6c
6d
1
2
3
4
4-MeOC6H4
Ph
H
H
H
H
4-MeOC6H4
Ph
H
H
H
H
1:2
2:5
1:4
1:4
2.0
4.0
4.0
5.0
89
56
80
99
4-ClC6H4
4-O2NC6H4
4-ClC6H4
4-O2NC6H4
5e
6e
5
2-ClC6H4
H
2-ClC6H4
H
1:9
8.0
82
5f
6f
6
7
2,6-Cl2C6H3
H
H
2,6-Cl2C6H3
H
H
1:2
2:3
8.0
2.0
60
75
5g
6g
9-Ethylcarbazol-3-yl
9-Ethylcarbazol-3-yl
[c]
5h
6h
8
Ph
Me
Ph
Me
-
4.5
70
[a] The isomeric ratio was determined from the 1H NMR spectra in DMSO-d6. [b] Isolated yield. [c] One set of signals in 1H NMR spectrum.
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For the synthesis of ETZs 1, the Hantzsch reaction was
performed according to the protocol previously used for the
interaction of arylhydrazonothioacetamides with halocarbonyl
compounds.[6] Screening the conditions for the reaction of
Products 1a-j were fully characterized using spectroscopic
analysis: FTIR, 1H NMR, 13C NMR (see the Experimental Section
and SI, Figures S9-19), and EI-MS, and their purity was
established using elemental analysis. In the IR spectra, the
arylaminothioacrylamide 6a with phenacyl bromide 7a (DMF, TEA, characteristic bands for the stretching vibrations of C≡N and N-H
80 °C and DMF, 80 °C) demonstrated that the reaction proceeds
well without any base and selectively lead to formation only one
product (1a) (Scheme 2, Table 2). Further reactions of
bromoacetophenones 7a,b and 2-chloro-1,2-diphenylethanone
7c with thioamides 6a-h under moderate heating in DMF
produced ETZs 1a-j in good yields (Table 2).
bonds were observed at 2199-2210 cm-1 and at 3101-3256 cm-1,
respectively. The mass spectra of ETZs 1a-j each exhibited a
molecular ion with high intensity (approximately 100%).
1
The H NMR spectra of thiazoles 1a-d,g exhibited two sets of
signals, while compounds 1e,f,h-j displayed one set of signals.
The most noteworthy signals were the doublet (or doublets) of the
CH-enamine moiety, and signals of the protons of the aromatic
rings (A, B and C) and proton-containing substituents in the A-
and B-cycles and for compounds 1a-h,g (R4 = H) the singlet or
two singlets of the C5H-thiazole proton at 7.7-8.5 ppm.
The advantage of this method is the possibility of introduce two
aromatic cycles on the thiazole ring simultaneously, which was
achieved in the condensation of 2-chloro-1,2-diphenylethanone
(7c). It should be mentioned that usually, transition-metal-
catalysed coupling reactions for forming new C-C bonds are
applied for this type of extension of the π–conjugated system of a
molecule.[10] This well-known and widespread strategy requires
expensive catalysts, solvents, and reagents and elongate the
process by requiring additional stages, i.e., halogenation of the
thiazole ring followed by a palladium-catalysed cross-coupling
reaction with an aryl boronate ester.
Scheme 2. Reagents and conditions: (a) DMF, 80 °C, 0.5-2h.
Table 2. Conversion time of thioamides 6a-h in their reactions with 2-bromoacethophenones 7a,b, and 2-chloro-1,2-diphenylethanone (7c), yields
of ETZs 1a-j, and the ratios of the isomers of thiazoles 1a-j.
R1
R2
R3
R4
Time [h]
Comp 1
Ratio of isomers 6[a]
Yield 6 [%][b]
Entry
1a
1b
1c
1d
1e
1f
1
2
4-MeOC6H4
Ph
H
H
Cl
Cl
H
H
9:1
10:1
6:1
1.5
2.0
1.0
1.0
3.0
1.0
0.5
1.5
4.0
1.5
65
84
80
74
83
80
67
68
70
70
3
4-ClC6H4
H
Cl
H
4
4-O2NC6H4
2-ClC6H4
H
Cl
H
4:1
[c]
5
H
Cl
H
-
[c]
6
2,6-Cl2C6H3
4-MeOC6H4
9-Ethylcarbazol-3-yl
4-MeOC6H4
Ph
H
Cl
H
-
1g
1h
1i
7
H
NO2
Cl
H
7:1
[c]
8
H
H
-
[c]
9
H
H
Ph
H
-
[c]
1j
10
Me
Cl
-
[a] The isomeric ratio was determined from the 1H NMR spectra in DMSO-d6. [b] Isolated yield. [c] One set of signals in 1H NMR spectrum.
The analogous thiazoles 2a-d, which have aza-enamine
functionalities (ATZs), were obtained following the same
procedure as was depicted in Scheme 2 for enamines 6 (Scheme
3, Table 3). The obtained results demonstrated the differences in
the reactivities of these two types of compounds. For example,
aza-enamines 8a-c reacted with halocarbonyls faster than
enamines 6a-c.
The synthesized compounds (2a-d) were characterized by
elemental analysis, MS, FTIR and NMR. These data, which are
detailed in the Experimental Section, are consistent with the
proposed structures. Similar to ETZs 1a-d,g, ATZs 2a-d exhibited
Scheme 3. Reagents and conditions: DMF, 80 °C, 0.5-3 h.
two sets of signals in their NMR spectra (Table 3, Figures S20-
23).
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10.1002/ejoc.201700518
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and 2a,c,d were subjected to the standard atoms in molecules
(AIM) theory of bonding based on electron density.[11] The BCP
(bond critical point) (3, -1)-type for the N1H∙∙∙NTZ hydrogen bond
and RCP (ring critical points) (3, +1) for the pseudo-cycle, which
is formed by the NH-enamine/aza-enamine chain and N-atom of
the TS ring (Figure 3 and additional examples in the SI, Figure
S26) confirm hydrogen bond formation in the structures of the Z,Z-
isomers.
However, the AIM theory is not ideal for investigating and
visualizing non-covalent interactions (NCIs). The absence of a
BCP should not necessarily be considered as evidence of the
absence of a chemical bond. Therefore, we additionally apply a
recently introduced type of NCI Index[12] as a more general
description of intramolecular interactions based on density
changes instead of its local values, as was done in the AIM
method. The NCI index is defined as a normalized and
dimensionless reduced density gradient (RDG),
Table 3. Yields and conversion times for the synthesis of ATZs 2a-d and
ratios of isomers.
Ratio of
isomers 2[b]
Time
[h]
Yield[a]
[%]
Entry
ATZs
R1
R3
R4
1
2
3
4
2a
2b
2c
2d
MeO
H
Cl
Cl
Cl
H
H
H
0.5
0.5
1.0
3.0
64
86
85
75
2:3
1:2
1:3
1:2
NO2
MeO
H
Ph
[a] Isolated yield. [b] The isomeric ratio was determined from the 1H NMR
spectra in DMSO-d6.
Molecular structures of ETZs and ATZs
|
|
∇휌
1
푠 =
.
1/3 4/3
휌
2
2(3휋
)
As mentioned above, most examples of compounds 1 and 2 exist
as a mixture of steric isomers (rotamers) because of the different
locations of substituents relative to the double bonds (-HC=C< for
the enamines and -N=C< for the aza-enamines) and because of
the two conjugated double bonds (C=C and endocyclic C=N
bonds) in the molecules. The isomeric ratios for compounds 1a
and 2a are evaluated by quantum mechanical calculations. The
optimized structures of the isomers of compounds 1a and 2a are
shown in Figure 2. The thermochemical results computed in
dioxane showthat 1a-Z,Z and 2a-Z,Z are unambiguously the most
stable isomers. The second most stable isomers for enamine 1a
and aza-enamine 2a are 1a-E,Z, and 2a-E,E, respectively.
The RDG value demonstrates the probability of NCI formation.
The attractive/repulsive character of this interaction can be
identified by the sign of the RDG second derivative along the
second main axis of variation λ2 (eigenvalue), which is negative
for attractive interactions and positive for repulsive ones (Figure 4
and SI, Figure S27). This approach has been developed to reveal
non-covalent interactions (e.g., hydrogen bonding) in 3D space.
Regions where the electron density ρ(r) and reduced electron
density gradient s are low correspond to regions where non-
covalent interactions occur. It follows that isosurfaces of the
reduced density gradient at low densities can be used to visualize
the position and nature of non-covalent interactions in 3D space.
NCI isosurfaces, therefore, illustrate the nature of the
intramolecular interactions. A continuous color-coding scheme
based on the second derivatives is used to provide qualitative
information about the strength of interaction, where strong
attractive interactions are represented in blue, weak interactions
in green, and strong repulsive interactions in red.
1
The H NMR spectra of the isomers of TZs 1a and 2a were
simulated in 1,4-dioxane and chloroform (SI, Table S1-4). The
experimental data and quantum mechanical calculation results
demonstrate the correlation of the chemical shifts of the proton-
containing groups with those of the most stable Z,Z-rotamer.
Analysis of the optimized geometry of the TZs isomers shows
that the preferred formation of the Z,Z-rotamer can be ascribed to
the hydrogen bonding between the NH group of the enamine/aza-
enamine and the nitrogen atom of the thiazole ring (NTZ). To study
the weak bond formation in the structure of TZs, isomers 1a-g,i
1a-Z,Z
ΔG = 0 kcal/mol
f = 0.998
1a-Z,E
ΔG = 8.9 kcal/mol
f = 0.000
1a-E,Z
ΔG = 3.8 kcal/mol
f = 0.002
1a-E,E
ΔG = 6.3 kcal/mol
f = 0.000
2a-Z,Z
ΔG = 0 kcal/mol
f = 0.982
2a-Z,E
ΔG = 9.6 kcal/mol
f = 0.000
2a-E,Z
ΔG = 5.2 kcal/mol
f = 0.000
2a-E,E
ΔG = 2.4 kcal/mol
f = 0.018
Figure 2. Computational results for the relative stability (ΔG) of the isomers of ETZ 1a and ATZ 2a. Level of theory: DFT M06-2X (SMD) / aug-cc-pVTZ. The
Boltzmann factors (f) at 300 K are also reported.
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Table 4. UV spectra[a] of ETZs 1a,b,d and ATZs 2a-c in EtOH.
εmax [M-1∙cm-1]
Thiazoles 1,2
Entry
λabs [nm]
1
2
3
4
5
6
1a
1b
1d
2а
2b
2c
254, 298, 373
249, 292, 367
244, 291, 393
251, 291, 414
245, 286, 397
247, 282, 416
36800, 8260, 31241
31021, 7618, 25681
6880, 2980, 6600
26380, 6420, 23320
31763, 8278, 25237
11228, 6778, 13188
1a
1d
1i
2a
2c
2d
[a] UV-vis absorption wavelengths at room temperature (c = 5×10-5 mol/L).
Figure 3. Critical points GS (S0) for the Z,Z-isomers of compounds 1a,d,i, and
2a,c,d in dioxane. Colour legend of the atoms: white (H), grey (C), blue (N), red
(O), and yellow (S). Colour legend for CPs: dark-red (RCP) and pink (BCP).
1a
2a
Figure 4. Plots of the NCI isosurfaces (s = 0.5 a.u. and a blue-green-red colour
scale from -0.012 a.u. < sign(λ2) ρ(r) < +0.012 a.u.) for the Z,Z-rotamers of
compounds 1a and 2a in the ground state.
These results provide additional proof of the ability of the weak
NH∙∙∙NTZ interaction to effectively stabilize the Z,Z-isomers of
enamines 1a-i and aza-enamines 2a-c. This phenomenon results
in the folding of the flexible side chain (enamine or aza-enamine).
Figure 5. Electronic absorption spectra of ETZs 1a,b,d and ATZs 2a-c in EtOH
at room temperature (c = 5×10-5 mol/L).
The structure of enamines 1a-j substantially affects their
emission characteristics. The largest quantum yields were
obtained for compounds 1e-g (Table 5, entries 5-7). We can
assume that this is explained by the limited rotation of the
aromatic cycle (A) around the σ-bond because of the spatial effect
of the substituent or two substituents at the ortho-positions of
ETZs 1e and 1f.
The strengthening of the rigidity of ETZ 1g, which has a push-
pull system in its structure, may be the reason for the strong
conjugation in molecule as it increases the partial double
character of the σ–bonds, restricting the molecular rotation in the
ES.
The Stokes shifts of the thiazoles are relatively large (35-112
nm) and vary depending on the combination of electronic and
spatial effects of the substituents on aromatic cycles (A and B).
ETZs 1d,g, which have substituents on their aromatic rings with
the opposite electronic effect, exhibit larger Stokes shift values
(Table 5, entries 4,7). ETZ 1c with the same substituents in the
aromatic cycles (A and B), and ETZs 1e,f, which have one or two
substituents at the ortho-positions in aromatic cycle A, show
smaller Stokes shifts (Table 5, entries 5 and 6).
Electronic absorption and fluorescence
The UV–vis spectra of thiazoles 1a,b,d and 2a-c are recorded in
ethanol, and their molar absorption coefficients ε at absorption
maxima (λabs) are recorded in Table 4. The UV−vis absorption
spectra (Figure 5) show maxima in three separate regions: 245-
257 nm, 282-298 nm and 373-416 nm. ETZ 1c, which has a
strong electron-accepting group (R1 = 4-NO2) exhibits an
additional band at 535 nm, which is caused by the strengthening
of intramolecular charge transfer (ICT) due to the strong
interaction of the molecule with the highly polar solvent.[7a] The
replacement of the electron-donating substituents with electron-
accepting ones in the aromatic portion (A) of enamines 1a-c
causes a small redshift (up to 26 nm).
The fluorescence emission profiles of thiazoles 1a-j and 2a,c,d
are recorded in dioxane (Figure 6). The absorption (λabs) and
emission maxima (λem), extinction coefficient (ε), and quantum
yield (ΦF) of thiazoles 1a-j and 2a,c,d are presented in Table 5.
All compounds show a single fluorescence emission band with a
maxima between 404 and 515 nm. These bands are more
redshifted with respect to the corresponding absorption spectra,
which indicates the effect of enhanced conjugation on the singlet
state (S1).
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Theoretical calculations of the absorption and
emission
To gain further insight into the effect of different substituents and
the structure of the bridged linear chain (enamine/aza-enamine)
linking the thiazole ring and aromatic cycle
A on the
conformational properties in compounds 1 and 2, we performed
an extensive quantum mechanical investigation considering the
geometry of the ground and excited states. The optimized
geometries of the Z,Z-isomers of thiazoles 1a-g,i and 2a,c,d in
dioxane are shown in Figure S28. Selected bond lengths, bond
angles and torsion angles of 1a-g,i and 2a,c,d are provided in
Tables S6 and S7 (SI).
The optimized geometries show the planarity between the
enamine/aza-enamine chain and the cyano group and thiazole
fragment (see Table S5, Figure S29) and the twisting of aromatic
cycle B in the ground state (θ2 = 22.4 – 42.1°). The geometry of
cycle A is different in the structures of ETZs 1a-g,i and ATZs
2a,c,d. Whereas the geometries of the ETZs exhibit substantial
torsion angles (θ1 = 17.7-51.6°), the geometries of the ATZs show
very small torsion angles (approximately θ1 =2.61-2.62°). We can
conclude that this aromatic ring participates in the whole
conjugated systems of compounds 2a,c,d and is the reason for
the bathochromic shift in the absorption band compared to the
ETZs (Table 5). The largest deviation from planarity for the
aromatic ring A is observed in compounds bearing one or two
substituents in the ortho-positions (49.0 – 51.6°), i.e., 1f and 1e,
which had the most blueshifted absorption bands. ETZ 1d is one
exception from this general trend. The structure of this compound
is more planar due to strong conjugation (8.9° in dioxane and 6.8°
in ethanol).
Extensive changes occurred during excitation, particularly the
torsion angle θ1 in ETZs 1a-c,e-g,i geometry, which considerably
decreased (to 0.2°). However, one interesting exception was
observed. The same (θ1) dihedral angle of ETZ 1d in ethanol (GS)
was 6.8° in the ground state and 91.2° in the excited state (ES),
a remarkable increase (Tables S6,S7 and Figure S28). This
rotation has caused a considerable twisting of the 4-nitrophenyl
aromatic ring (R1 = 4-NO2C6H4) during excitation and loss of
emission intensity in this solvent.
The introduction of a second aromatic cycle (C) to the thiazole
ring (R4 = Ph) causes the formation of propeller-like structures for
compounds 1i and 2d in the GS and ES, although more twisting
was observed for ETZ 1i than for ATZ 2d. However, both
compounds demonstrate decreasing lengths of the bonds linking
aromatic cycles A, B, and C with the framework of the molecules
because of the enhancing of the conjugated system and the
redshifting the wavelengths in the absorption and emission
spectra.
Notably, detailed analysis of the geometries of ETZs 1 and
ATZs 2 shows the probability of the formation of different weak
intramolecular interactions. The number of these interactions may
vary depending on the structures of compounds 1 and 2. The
most substantial interaction involves the hydrogen in the central
part of the molecule, as previously discussed and shown in
Figures 3 and 7, both in the GS and ES.
a
b
Figure 6. Absorption (a) and emission (b) spectra of ETZs 1a-j in dioxane at
room temperature.
Table 5. Photophysical properties of ETSs 1a-j and ATSs 2a,c,d in
dioxane.
Stokes
[a]
[b]
[c]
λmax
εmax
λem
ФF
[%]
Entry
Comp
shift,
[nm]
374
368
371
397
366
350
374
390
383
357
414
409
423
[M-1 cm-1]
[nm]
458
424
406
509
404
405
459
421
459
416
462
480
515
[nm/cm-1]
1
2
1a
1b
1c
1d
1e
1f
25342
23688
34173
37266
22115
25533
27594
24274
26524
24162
26627
43771
27946
1.15
1.00
0.79
0.43
1.68
2.14
2.05
1.00
1.64
0.50
0.10
0.10
0.05
84/4904
56/3589
35/2324
112/5543
38/2570
55/3880
85/4951
31/1888
76/4323
59/3973
48/2510
71/3617
92/4223
3
4
5
6
7
1g
1h
1i
8
9
10
11
12
13
1j
2a
2c
2d
[a] UV-vis absorption wavelengths at room temperature and
a
concentration of c = 5×10-5 mol/L. [b] Fluorescence wavelengths at room
temperature at a concentration of 10-6 mol/L. Excitation wavelengths
correspond to absorption maximum λmax. [c] Fluorescence quantum yields
measured using a 0.1 M H2SO4 solution of quinine sulphate (ΦF = 0.54) as
a reference.[13]
The length of the N1H∙∙∙NTZ hydrogen bond is shortened in the
GS of compounds 1a-g,i (1.949-1.981 Å) but is much shorter for
2a,c,d (1.914-1.924 Å). Notably, for most of the thiazoles the
hydrogen bond is strengthened in the ES (1.784-1.936 Å). Two
exceptions are compounds 1d (both in dioxane and in EtOH) and
1f, where this bond length substantially increases from 1.949-
1.975 Å in the GS to 2.002-2.084 Å in the ES.
Both the extreme strengthening of the bridge NH-X=C- linker
conjugation in ETZ 1d and the replacement of the NH hydrogen
atom with methyl groups in ETZ 1j decrease the emission
intensity (Table 5, entries 4 and 10). Incorporating the fluorescent
carbazole moiety into the structure of TZ 1h results in a
bathochromic shift in the absorption spectrum up to 390 nm
(Table 5, entry 8) but substantially decreases the Stokes shift.
.
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10.1002/ejoc.201700518
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S1v
S1r
S1v
S1r
S1v
S1r
1a
1d
1i
1e
1f
2a
Figure 7. The critical points ESs (S1v, S1r) for ETZs 1e,f,i and ATZ 2a in dioxane. Colour legend for the atoms: white (H), grey (C), blue (N), red (O), and yellow (S);
colour legend for CP: dark-red (RCP), pink (BCP).
exception of this trend is ETZ 1g both in dioxane and in DMSO
(Table 6, entry 9-12). The main electronic transition from the
HOMO to the LUMO for this compound with the push-pull
structure is accompanied by an additional transition from the
HOMO to the LUMO + 1 (Table 6, Figure S32).
The calculated data show that (1) the S0→S1v electron transition
occurs more easily for compounds 1a, 2d and particularly 2a with
the push-pull conjugated system and highest oscillator strength;
and (2) large changes occur in electronic distribution during
excitation.
The formation of the hydrogen bond is confirmed by applying
the AIM theory[11] to analyse the intramolecular interactions in the
structures of ETZs 1 and ATZs 2 in the GS and ESs (Figures 3
and 7 and additional examples in the SI, Figure S26). The BCP
(bond critical point) (3, -1)-type for the N1H∙∙∙N2 hydrogen bond
and RCP (3, +1) for the pseudo-cycle, which was formed from the
N2-C2-C1-X-N1-H chain of atoms in the GS, Franck-Condon ES
(S1v) and relaxed ES (S1r), were found (Figure 7 and SI, S26). The
AIM approach also confirms the formation of a C9H∙∙ HC6 bond
and a new additional ring: a pseudo-macrocycle constructed from
the HC9-C7-N1-X-C1-C2-N2-C4-C5-C6H atom sequence,
particularly for the relaxed ES (S1r) of ETZs 1a-c,d-h and ATZs
2a,c.
Further analysis of the intramolecular interactions, which was
performed according to the RDG index (SI, S27 and S29),
supported most of the AIM theory predictions, including the
additional strong hydrogen bond formation between the Cl atom
at the ortho-position of the aromatic ring and C-proton of the
enamine group in compound 1e, which is an additional reason for
the restricted rotation in this molecule.
The combined effects of the intramolecular interactions lead to
strengthening of the rigidity in the TZs in the ES, which can be
evaluated by the decrease in their bond length. For instance, most
of the σ-bonds in the structure of TZs 1 and 2 have decreased
their lengths during the S0→S1 transition to, on average, 94% of
the original value. This conjugation is particularly reflected in the
variations in the length of C-NH bond linking the aromatic ring A
and the enamine chain. This bond length in ETZs 1a-c,e-g,i is
shorter in the ES than in GS. However, the opposite trend is
observed for the ATZs; i.e., this bond length increases during
excitation. These findings are very important for absorption and
emission and help explain the differences in the optic
characteristics of the ETZs and ATZs. Thus, we can conclude that
photon absorption causes strengthening of the ICT character for
ETZs. Whereas ATZs, on the contrary, demonstrated weakening
ICT upon excitation.
The theoretically optimized energy and absorption and emission
maxima, along with the oscillator strength, ground/excited state
dipole moment modulus and angles formed by the dipole moment
vectors, are provided in Table 6 and Table S8 (SI). The simulated
absorption and emission maxima for all of the investigated
compounds are consistent with the experimental values (Figures
5, 6, S24, S25, S30 and S31). The S0→S1 transitions, which are
responsible for the largest absorption band, are mainly ascribed
to the electronic transitions from the HOMO to LUMO for the
derivatives, as confirmed by the orbital coefficients (c). One
This difference emerges in the value of the dipole moments of
the investigated compounds, which remarkably increases in the
ES, particularly for enamines 1a,d,g. Moreover, for ETZs 1e,f,
and ATZs 2a,d it was accompanied by a substantial change in the
angle of the dipole moment vector (Table 6). The substantial
change in electronic distribution after the S0 → S1v excitation
supports the plots showing the difference in electronic density
between the GS and the first electronic ES of 1a-g,i and 2a,c,d in
dioxane (SI, Figure S33).
To investigate the reactive sites of the ETZs and ATZs, their
molecular electrostatic potential (MEP) was evaluated. The MEP
surfaces in Figure 8 for several examples (additional examples
are presented in the SI, Figure S34) show the sites of electrophilic
and nucleophilic attack and hydrogen bonding interactions and
the size, shape, and electrostatic potential distribution of the
molecules. The MEP surface is a useful tool for investigating the
GS and ES, especially regarding the effect of intermolecular
interactions on absorption and emission. Consequently, the most
active sites in the title compounds are used to rationalize their
interactions with solvents or bioanalytes. Figures 8 and S34 (SI)
show that in the GS, the CN and NO2 groups gather negative
charge, indicating that they are potential sites for electrophilic
attack. Positive charge covers the MeO group in most
compounds, except thiazole 1d, where the positive charge is
concentrated around the enamine NH group, and ATZ 2c, where
the positive charge is localized on the thiazole and R3-aromatic
ring. Thus, these parts of the compounds are potential sites for
nucleophilic attack.
A large difference is observed between the molecular surfaces
in the GS and ES. Compounds 1d,g and 2a,c,d exhibit strong
enlargement of and increase in the negative and positive active
site areas, particularly TZs 1d,g, and 2a,d. These observations
enable us to select compounds 1a, 1d and 1g as representative
examples to investigate (fluoro-)solvatochromic behaviour.
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10.1002/ejoc.201700518
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Table 6. Calculated absorption and emission properties[a] for (Z,Z)-ETSs 1a-g,i and ATSs 2a,c,d in dioxane.
Entry
Comp
n
c
λ0n [nm]
f0n
μ0 [D]
μnv [D]
c’
λ10 [nm]
f10
μ1r [D]
θ0,nv [°]
θ0,1r [°]
1
2
1a
1a[b]
1b
1
1
1
1
1
1
1
1
1
2
1
2
1
1
1
1
0.69655
0.69882
0.69593
0.69685
0.70399
0.70511
0.68870
0.68682
0.70519
0.63073
0.70633
0.63884
0.69572
0.70278
0.68992
0.70399
374.9
380.0
367.8
369.8
398.7
396.9
364.3
350.1
488.8
375.2
567.0
377.6
384.2
415.4
409.9
423.8
0.8338
0.8702
0.5919
0.6579
0.4710
0.4805
0.5093
0.4313
0.0496
0.5422
0.0734
0.2724
0.5769
0.9144
0.6700
0.8026
4.2
7.3
3.6
2.3
4.7
6.0
4.9
4.6
4.5
4.5
5.3
7.8
13.1
4.5
9.9
42.6
13.5
5.4
-0.70254
0.70220
0.69740
-0.69848
0.70443
0.70477
-0.69587
0.69274
0.70668c
-
458.6
469.2
422.1
414.5
503.7
838.7-
405.4
406.3
458.7
-
0.5650
0.0417
0.5424
0.6100
0.3502
0.0000
0.4901
0.3785
0.4111
-
9.1
18.2
4.8
4.3
20.7
35.8
6.2
6.9
27.1
-
16.1
60.7
26.1
11.3
5.9
3
3.8
4
1с
1d
19.1
26.5
5.4
6.8
5
1d[c]
2.1
8.2
6
35.4
67.5
26.9
3.7
36.3
77.3
26.3
-
7
1e
1f
5.6
8
26.9
11.1
30.3
26.8
8.3
9
1g
1g
1g[b]
1g[b]
1i
10
11
12
13
14
15
16
15.3
17.6
17.4
39.5
3.2
0.70978
-
453.4
-
0.0591
-
33.8
-
21.7
-
5.6
3.3
7.5
5.4
0.70362
0.70577
0.69501
-0.70724
458.7
463.2
480.6
514.1
0.8396
0.2598
0.4678
0.6820
9.1
7.9
18.3
9.0
30.5
37.6
6.6
8.8
2a
14.7
9.3
2c
48.1
51.2
2d
[a] Computed orbital’s coefficient (c and c’), absorption wavelength (λ0n, nm), fluorescence wavelength (λ10, nm), oscillator strength (f0n and f10), modulus
of the electric dipole moments of the ground state (μ0, D) and of the vertical FC excited state (μnv, D), angles formed by the dipole moment vectors (θ0,nv
and θ0,1r (°)). [b] in DMSO (IEF-PCM). [c] in MeCN (IEF-PCM).
S0
S1v
S2v
Comp
1a
(Fluoro-)Solvatochromism
The photophysical data for ETZs 1a,1d and 1g in various solvents
are shown in Table 7. The absorption and emission spectra of
thiazoles 1a, 1d and 1g are presented in Figure 9. The
absorbance spectra in most solvents did not depend on the
solvent properties, as shown in Table 7 and Figure 9, except
compound 1d in DMF. In this solvent, thiazole 1d exhibits two long
wavelength bands at 404 and 527 nm because of its stronger
interaction with the polar solvent (Table 7, entry 16; Figure 9c).
By contrast, the fluorescence did strong depend on the nature
of the solvents. The fluorescence band shows an upward shift of
39-89 nm for 1a, and 69-139 nm for 1g and 41-85 for 1g with
increasing solvent polarity. The greater stabilization of the excited
singlet state ocсures in polar solvents and confirming their high
polarity and ICT character in that state, in accordance with the
calculation results (Table 7 and Table S8).
1d
1d[a]
1g
2a
The quantum yields also respond to the variation in solvent
properties. The emission intensity of thiazole 1a, which shows a
moderate change in its dipole moment modulus during excitation
is highest in nonpolar, aprotic dioxane (Table 7, entry 2), but is
completely quenched in dichloromethane (Table 7, entry 5).
Figure 8. MEP plots of ETZs 1a,d,g and ATZs 2a in dioxane ([a] - in ethanol) in
the GS and ESs. Negatively charged surfaces highlighted red and yellow colour
and positively charged surfaces highlighted blue colour.
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Table 7. Photophysical characteristics of ETZs 1a, 1d and 1g in selected solvents with different polarity.
Entry
Comp
Solvent
λmax [a] [nm]
εmax [M-1 cm-1]
λem [b][nm]
Stokes shift [nm/cm-1]
ФF [%][c]
1
1a
Toluene
Dioxane
AcOEt
THF
377
374
373
374
375
379
377
374
372
372
397
397
395
397
397
404, 527
397
397
393
376
374
372
376
372
375
378
373
26256
25342
28612
22749
24452
44354
31280
28169
31146
27986
36077
33425
54628
42460
40110
15574, 6318
27536
34380
4966
433
458
412
424
56/3431
84/4904
39/2538
50/3153
-
0.26
1.15
0.40
0.18
-
2
3
4
[d]
5
CH2Cl2
DMSO
DMF
-
6
468
430
414
423
412
466
509
501
498
536
89/5018
53/3269
40/2583
51/3241
40/2610
69/ 112/5543
112/ 3730
106/5356
101/5109
139/6532
-
0.15
0.36
0.14
0.09
0.34
0.88
0.43
0.18
0.24
0.18
-
7
8
Acetone
MeCN
EtOH
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
1d
Toluene
Dioxane
AcOEt
THF
CH2Cl2
DMF
[d]
-
[d]
Acetone
MeCN
EtOH
-
-
-
[d]
-
-
-
[d]
-
-
-
1g
Toluene
Dioxane
AcOEt
THF
34465
28823
40635
26775
27169
47020
27102
24731
439
459
426
417
63/3816
85/4952
54/3408
41/2615
-
1.61
2.05
0.24
1.43
-
[d]
CHCl3
DMF
-
439
452
64/3888
74/4331
-
1.09
0.55
-
DMSO
Acetone
[d]
-
[a] UV-vis absorption wavelengths at room temperature and a concentration of c = 5×10-5 mol/L. [b] Fluorescence wavelengths at room temperature at a
concentration of 10-6 mol/L. Excitation wavelengths correspond to absorption maximum λmax. [c] Fluorescence quantum yields measured using a 0.1 M H2SO4.
For the emission intensity of ETZs 1d and 1g which have the
highest dipole moment modulus in the ES (Table 6 and Table S8),
the best quantum yield is in low-polarity toluene and dioxane,
ethanol can be caused by specific and non-specific solvent-solute
interactions, which is strongest for the thiazole 1d and induced
rotation of the aromatic ring A in the Frank-Codon excited state,
whereas in polar solvents, such as DMF, acetonitrile, and acetone, as shown in Figure S28.
they are non-fluorescent. The low emission intensity of TZs 1 in
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a
b
c
d
e
f
Figure 9. Absorption and emission spectra of thiazoles 1a (a,b), 1d (c,d) and 1g (e,f) in different solvents at room temperature.
(Fluoro-)Solvatochromism is often interpreted in terms of simple
analytical models, which consider the molecule as a point dipole
placed at the centre of a spherical cavity.[7a] When the applicability
conditions of these models are matched, it is possible to obtain
regressions between the shift of the absorption (or emission) band
(or the Stokes shift) and some function, expressing the solvent
polarity, and from these regressions. If models are properly
applied, useful information about the electric dipole moment of the
molecule in the excited state may be extracted. Unfortunately our
systems do not match the conditions requested for the
applicability of those simple models, and any attempt to regress
the fluorosolvatochromic data with any polarity function (e.g.,
Lippert-Mataga, Bakhshiev, Kawsky-Chamma-Vallet, McRae,
etc.) was unsuccessful. Simple continuum models do not offer a
realistic surrounding and emission properties may be close to the
a
b
c
Figure 10. a - Emission spectra for ETZs 1a-f,h,i in the solid state at 25 °C. b
- Photographs of powders of ETZs 1a-g,i in daylight and under irradiation. c -
with a hand-held UV lamp at an emission wavelength of 380 nm.
experimental data and were able to accurately describe the ICT
nature of representation, especially for complex systems or
absorption and emission phenomena.[15] It was therefore
necessary to make usage of the state-of-the-art quantum
mechanical methods to obtain information about the nature of the
excited state. The computational findings were extremely close to
the experimental data (Tables 6,7 and Table S8) and were able
to reveal and accurately describe the ICT nature of the transitions.
It is evident, from spectral and calculation data, that compounds
reported in this study exhibit strong dependence from the solvent
polarity due to the ICT nature of the transition. Moreover, the
strength of ICT character is easily tuned by varying type of
electron withdrawing and electron donating substituents placed
on the opposite moieties of the molecule. The strongest ICT is
attributed to compounds 1d and 1g; this is confirmed by the
experimental data.
Solvent viscosity may also affect the fluorescence of TZs. This
assumption is confirmed by the emission of ETZs 1a-h in the solid
state (Figure 10). As shown in Figure 10, fluorescence at a
maximum of approximately 479-490 nm was observed for
powdered ETZs 1a-h. Because of intermolecular interactions in
the solid state, the emission band of ETZs 1 slightly shifts to
longer wavelengths.
Conclusion
In summary, we synthesised newTZ derivatives (ETZs and ATZs)
with conjugated -NH-CH=C< and -NH-N=C< linker that differ from
each other by one atom and with the structure capable to form
NH∙∙∙NThiaz intramolecular hydrogen bond. The synthesis of these
compounds does not require severe conditions or expensive
catalysts or reagents. Moreover, this method allowed us to obtain
various compounds whose electronic structure may be controlled
and tuned by varying the electronics and spatial parameters of the
substituents. The fine structures and photophysical
characteristics of ETZs and ATZs were investigated in detail using
experimental (spectral) and theoretical (calculation) data. It
should be emphasized that the theoretical and experimental data
for the position and shape of the absorption and emission bands
are consistent. Experimental and computational results based on
analysis of the HOMO-LUMO distribution, the modulus of the
dipole moment and its direction upon excitation of the investigated
compounds highlight the presence of ICT state, which is
especially polar for the excited state of compounds 1d and 1g.
The formation of a series of weak intramolecular interactions in
the GS and ES are confirmed by mean of the AIM theory and the
NCI analysis.
The difference in the geometries of the ETZs and ATZs are
essential and lead to differences in electronic contribution and, as
a result, in their absorption and emission behaviour. For example,
the fluorescence of the ETZs is more intensive than that of the
ATZs. As a result, we can conclude that the small differences in
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10.1002/ejoc.201700518
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General procedure for the synthesis of thiazoles 1a-j, 2a-d.
Halocarbonyl compound 7a-c (0.26 g, 1.15 mmol) is added to the solution
of thioamide 6a-h or 8a-c (0.25 g, 1.10 mmol) in DMF (2.0 ml). The mixture
is kept at 80 °C for 0.5-4.0 h, then diluted with ethanol (12.5 ml) and kept
at 10-12 °C for 30 min. The precipitate is collected by filtration.
structure between the investigated compounds (i.e., replacing the
carbon in the linear chain with a nitrogen atom and changing the
nature or position of the substituents in the aromatic rings) lead to
considerable changes in the photophysical properties of the
investigated TZs (λabs, λem, quantum yield, Stokes shift, solid-state
fluorescence, and environmental sensitivity) because of the
variation in their conjugated systems and polarity, as well as the
value, number and strength of their weak intramolecular
interactions. The weakened hydrogen bonding in the ES (for the
compounds 1d, 2a-d) or the impossibility of their formation (for
compound 1h) substantially decreases the emission intensity.
The computational results (polarity, MEP and HOMO-LUMO
distribution) are encouraging about the perspective to create ETZ-
based compounds whose absorption and emission properties
2-(4-(4-Chlorophenyl)thiazol-2-yl)-3-((4-methoxyphenyl)amino)-
acrylonitrile (1a): Bright yellow powder (0.263 g, 65%); mp 249-250 С;
°
̃
IR (NPVO, ZnSe): 휈 = 3101 (NH), 3012, 2987, 2958, 2936, 2905, 2830
(СН), 2199 cm-1 (CN); 1Н NMR (400 MHz, DMSO-d6, TMS): δH = 11.63*
and 10.51 (both d, J = 13.1Hz, 1Н, NHСН), 8.38* and 8.33 (both d, J =
13.1 Hz, 1Н, СНNH), 8.00-7.98 (m, 2H, HAr), 8.05* and 7.91 (both s, 1Н,
СН), 7.55* and 7.50 (both d, J = 8.5 Hz, 2H, HAr), 7.39-7.34 (m, 2H, HAr),
7.01-6.95 (m, 2H, HAr), 3.77* and 3.76 ppm (both s, 3H, ОMe); 9:1 mixture
of isomers; 13С NMR (100 MHz, DMSO-d6) δC = 164.9, 156.7, 152.9, 144.5,
133.0, 132.6, 128.9 (2C), 127.7 (2C), 119.5, 118.6 (2C), 115.2 (2C), 111.5,
76.6, 55.6 ppm; MS (EI) m/z (%): 367 (M+, 100); elemental analysis calcd
(%) for C19H14ClN3OS: C 62.04, H 3.84, N 11.42; found: C 61.8, H 4.0, N
11.2.
may
be
extremely
sensitive
to
their
surrounding
microenvironment. This feature was confirmed both by calculation
(MEP) data and (fluoro-)solvatochromic investigations for the
several examples. Moreover, the structures of the ETZs and ATZs
include a convenient combination of functionalities and thus may
be used both as useful building blocks in heterocyclic chemistry
and as multidonor ligands for constructing different types of
complexes, particularly valuable organometallic frameworks and
functional materials.
Thus, we have demonstrated the accessibility of small thiazole
derivatives with aryl enamine and aryl aza-enamine side groups
and elucidated methods to design and synthesize new effective
molecular fluorophore candidates for further application as
analytes/bioanalytes because of their emission in solution and in
the solid state.
2-(4-(4-Chlorophenyl)thiazol-2-yl)-3-(phenylamino)acrylonitrile (1b):
°
̃
Beige powder (0.312 g, 84%); mp 254-255 С; IR (NPVO, ZnSe): 휈 = 3050,
3026, 2955, 2917 (CH), 2200 cm-1 (CN); 1Н NMR (400 MHz, DMSO-d6,
TMS): δH = 12.12 and 11.81* (both d, J = 12.9 Hz, 1Н, NHСН), 9.31 and
8.44* (both d, J = 12.9 Hz, 1Н, СНNH), 7.98-7.93 (m, 3Н, HAr+СН), 7.60-
7.50 (m, 2Н, HAr), 7.46-7.37 (m, 4Н, HAr), 7.16-7.12 ppm (m, 1Н, HAr); 10:1
mixture of isomers; 13С NMR (100 MHz, DMSO-d6) δC = 165.0 (+), 152.7
(+), 144.1 (-), 143.5 (+), 140.6 (+), 132.9 (+), 129.0 (2C) (-), 127.7 (2C) (-),
119.8 (+), 119.7 (-), 118.2 (2C) (-), 116.6 (2C) (-), 111.5 (-), 76.0 (+) ppm;
MS (EI) m/z (%): 337 (M+, 100); elemental analysis calcd (%) for
C19H12ClN3S: C 64.00, H 3.58, N 12.44; found: C 63.7, H 3.7, N 12.1.
3-((4-Chlorophenyl)amino)-2-(4-(4-chlorophenyl)thiazol-2-yl)acrylo-
°
nitrile (1c): Beige powder (0.328 g, 80%); mp 256-257 С; IR (NPVO,
Experimental Section
-1
ZnSe): 휈 = 3112, 3059, 2999 (CH), 2199 cm (CN); 1Н NMR (400 MHz,
̃
DMSO-d6, TMS): δH = 11.78* and 10.47 (both d, J = 12.8Hz, 1Н, NHСН),
8.47-8.39 (m, 1Н, СНNH), 8.00-7.95 (m, 3Н, HAr+СH), 7.51-7.49 (m, 2Н,
HAr), 7.44-7.35 ppm (m, 4Н, HAr); 6:1 mixture of isomers; 13С NMR (100
MHz, DMSO-d6) δC = 164.3, 152.9, 144.0, 138.0, 132.9, 132.1, 129.5 (2C),
129.0 (2C), 127.8 (2C), 118.7 (2C), 112.2, 78.0 ppm; MS (EI) m/z (%): 371
(M+, 100); elemental analysis calcd (%) for C18H11Cl2N3S: C 58.08, H 2.98,
N 11.29; found: C 57.8, H 3.1, N 11.1.
General: All reactants were obtained from Acros Organics and used
without further purification. 1Н NMR and 13C NMR spectra were recorded
with a Bruker Avance II (Karlsruhe, Germany) (400 MHz for 1H, 100 MHz
for 13C) spectrometer. The chemical shifts are reported in parts per million
(ppm) relative to TMS in 1H NMR and to the residual solvent signals in 13
C
NMR. The coupling constant (J) values are given in hertz (Hz). The signal
splitting patterns are described as a singlet (s), doublet (d), triplet (t),
quartet (q), sextet (sext), quintet (quin), multiplet (m), broad (br), doublet
of doublets (dd), doublet of triplets (dt) or AA'XX' - spin system of para-
substituted benzene with two different substituents. The major isomer
signal is highlighted with an asterisk (*). The 13C NMR signal patterns for
several compounds were by APT (attached proton test) and are described
as follows: + for secondary or quaternary carbon atoms (positive signal)
and - for primary or tertiary carbon atoms (negative signal). Mass spectra
were recorded on a Shimadzu GCMS-QP 2010 “Ultra” (Kyoto, Japan)
mass spectrometer using the electron impact (EI) ionization technique (40-
200 °C, 70 eV). The abbreviation [M]+ refers to the molecular ion. IR
spectra were obtained on an FTIR-ATR (attenuated total reflection, ZnSe)
spectrometer (neat) in the 4000-400 cm-1 region (Ettlingen, Germany).
Elemental analysis was conducted on a CHNS/O Perkin-Elmer 2400
Series II analyzer instrument (Shelton, CT USA). The melting points were
determined on a Stuart SMP3 apparatus (Staffordshire, ST15 OSA, UK).
The reactions were monitored by analytical thin-layer chromatography
(TLC) on aluminium-backed silica-gel plates (Sorbfil UV–254). The
components were visualized by short wavelength UV light (254 nm). The
solvents were dried and distilled according to common procedures. All
solvents were of spectroscopic grade.
2-(4-(4-Chlorophenyl)thiazol-2-yl)-3-((4-nitrophenyl)amino)-acrylo-
°
nitrile (1d): Yellow powder (0.312 g, 74%); mp 278-279 С; IR (NPVO,
ZnSe): 휈 = 3115 (NH), 3071, 3031, 3001, 2961 (СН), 2204 cm-1 (CN); 1Н
̃
NMR (400 MHz, DMSO-d6, TMS): δH = 11.98* and 10.85 (both d, J =13.0
Hz, 1Н, СНNН), 8.64* and 8.55 (both d, J = 13.0Hz, 1Н, СНNН), 8.27* and
8.22 (both d, J = 8.5 Hz, 2Н, HAr), 8.05-7.99 (m, 2Н, HAr), 8.10* and 7.94
(both s, 1Н, СН), 7.66-7.59 (m, 2Н, HAr), 7.55* and 7.45 ppm (both d, J =
8.6 Hz, 2Н, HAr); 1:4 mixture of isomers; 13С NMR (100 MHz, DMSO-d6)
δC = 164.1 (+), 153.8 (+), 143.6 (-), 145.2 (+), 143.3 (+), 133.6 (+), 132.5
(+), 129.6 (2C) (-), 128.4 (2C) (-), 126.2 (2C) (-), 119.2 (+), 117.5 (2C) (-),
113.8 (-), 81.1 (+) ppm; MS (EI) m/z (%): 382 (M+, 100); elemental analysis
calcd (%) for C18H11ClN4O2S: C 56.47, H 2.90, N 14.64; found: C 56.2, H
3.1, N 14.3.
3-((2-Chlorophenyl)amino)-2-(4-(4-chlorophenyl)thiazol-2-yl)acrylo-
nitrile (1e): Pale yellow crystal (0.339 g, 83%); mp 231-232 °С; IR (NPVO,
ZnSe): 휈 = 3164, 3113, 3076, 2921, 2852 (CH), 2204 cm-1 (CN); 1Н NMR
̃
(400 MHz, DMSO-d6, TMS): δH = 11.86 (d, J = 12.6Hz, 1H, NН), 8.53 (d, J
= 12.6Hz, 1H, СН), 8.04-8.07 (m, 3Н, CH+HAr), 7.84 (d, J = 7.9 Hz, 1H,
HAr), 7.54 (dd, J = 1.2, 8.0 Hz, 1H, HAr), 7.49 (d, J = 8.5 Hz, 2H, HAr), 7.42
(t, J = 7.4 Hz, 1H, HAr), 7.17 ppm (dt, J = 1.2, 8.0 Hz, 1H, HAr); 13С NMR
(100 MHz, DMSO-d6) δC = 164.2, 153.6, 143.2, 136.2, 133.2, 132.3, 129.8,
128.6 (2C), 128.0 (2C), 125.1, 121.4, 118.9, 117.0, 112.8, 79.8 ppm; MS
(EI) m/z (%): 371 (M+, 100); elemental analysis calcd (%) for C18H11Cl2N3S:
C 58.08, H 2.98, N 11.29; found: C 57.8, H 3.2, N 11.0.
The title products were purified by column chromatography on silica gel
(0.035–0.070, 60 Å) and recrystallized from ethanol.
Thioacetamide
(3),
dimethylaminopropenethioamide
(4)
and
arylhydrazonethioacetamides 8 were prepared using procedures reported
in the literature.[6,9b,10] Full experimental details for synthesis of
arylaminothioacrylamides 6a-h, 1H NMR and 13C NMR spectra of new
compounds (6a-h, 1a-j and 2a-d), photophysical characterization,
quantum mechanical calculation data are reported in the Supporting
Information.
2-(4-(4-Chlorophenyl)thiazol-2-yl)-3-((2,6-dichlorophenyl)amino)-
acrylonitrile (1f): Pale yellow powder (0.357 g, 80%); mp 256-257 °С; IR
(NPVO, ZnSe): 휈 =3106 (CH), 2214 cm-1 (CN); 1Н NMR (400 MHz, DMSO-
̃
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700518
European Journal of Organic Chemistry
FULL PAPER
d6, TMS): δH = 11.36 (d, J = 12.4 Hz, 1H, NН), 8.13-8.11 (m, 2H, 2СН),
8.05 (d, J = 8.5 Hz, 1H, HAr), 7.63 (d, J = 8.2 Hz, 1H, HAr), 7.50 (d, J = 8.6
Hz, 2H, HAr), 7.36 ppm (t, J = 8.2 Hz, 1H, HAr); 13С NMR (100 MHz, DMSO-
d6) δC = 164.7, 153.9, 149.6, 135.0, 133.6, 132.6, 129.9 (2C), 129.3 (2C),
129.2 (2C), 128.6, 128.4 (2C), 119.2, 112.9, 78.5 ppm; MS (EI) m/z (%):
404 (M+, 100); elemental analysis calcd (%) for C18H10Cl3N3S: C 53.16, H
2.48, N 10.33; found: C 52.9, H 2.6, N 10.1.
1Н, СН), 8.05-7.99 (m, 2H, HAr), 7.55* and 7.16 (both d, J = 8.6Hz, 2H,
HAr), 7.46-7.41 (m, 4H, HAr), 7.34* and 7.06 ppm (both t, J = 8.4 Hz, 1H,
HAr); 2:1 mixture of isomers; 13С NMR (100 MHz, DMSO-d6) δC
=
163.4*/159.3, 153.9/153.2*, 142.3*/141.2, 133.5/132.8*, 132.4*/131.3,
129.6/129.4* (2C), 129.1/128.8* (2C), 128.0/127.6* (2C), 124.7/123.6*,
116.5*/116.4, 115.3*/115.1 (2C), 108.4*/106.8, 110.5* ppm; mixture of
isomers; MS (EI) m/z (%): 338 (M+, 49); elemental analysis calcd (%) for
C17H11ClN4S: C 60.27, H 3.27, N 16.54; found: C 60.0, H 3.4, N 16.3.
3-((4-Methoxyphenyl)amino)-2-(4-(4-nitrophenyl)thiazol-2-yl)-
acrylonitrile (1g): Orange powder (0.279 g, 67%); mp 276-277 С; IR
°
4-(4-Chlorophenyl)-N-(4-nitrophenyl)thiazole-2-carbohydrazonoyl
-1
°
(NPVO, ZnSe): 휈 = 3106 (NH), 2988, 2940, 2913, 2831 (СН), 2200 cm
cyanide (2c): Bright yellow powder (0.359 g, 85%); mp 288-290 С; 1Н
̃
(CN); 1Н NMR (400 MHz, DMSO-d6, TMS): δH = 11.63* and 10.43 (both d,
J = 13.1 Hz, 1Н, NHСН), 8.82* and 8.12 (both s, 1H, СН), 8.41-8.35 (m,
3H, HAr+CH), 8.25-8.22 (m, 2H, HAr), 7.40* и 7.32 (both d, J = 8.9 Hz, 2Н,
HAr), 6.97* and 6.93 (both d, J = 8.9 Hz, 2Н, HAr), 3.80* and 3.79 ppm (both
s, 3H, ОMe); 9:1 mixture of isomers; 13С NMR (100 MHz, DMSO-d6) δC =
165.5 (+), 156.8 (+), 151.9 (+), 147.1 (+), 144.8 (-), 139.3 (+), 132.5 (+),
127.1 (2С) (-), 124.2 (2C) (-), 119.5 (+), 118.7 (2C) (-), 115.2 (2C) (-), 114.9
(-), 76.3 (+), 55.5 (-) ppm; MS (EI) m/z (%): 378 (M+, 100); elemental
analysis calcd (%) for C19H14N4O3S: C 60.31, H 3.73, N 14.81; found: C
60.1, H 3.9, N 14.5.
NMR (400 MHz, DMSO-d6, TMS): δH = 14.00 and 12.33* (both s, 1Н, NН),
8.28 and 8.23* (both d, J = 9.2 Hz, 2H, HAr), 8.17* and 7.93 (both s, 1Н,
СН), 8.08 and 8.01* (both d, J = 8.6 Hz, 2H, HAr), 7.64 and 7.60* (both d,
J = 9.2 Hz, 2H, HAr), 7.55 and 7.46* ppm (both d, J = 8.6 Hz, 2H, HAr); 3:1
mixture of isomers; 13С NMR (100 MHz, DMSO-d6) δC = 162.4, 153.7,
147.8, 142.4, 133.0, 132.2, 128.9 (2C), 127.7, 125.6 (2C), 116.4(2C),
115.0 (2C), 112.6, 109.9 ppm; MS (EI) m/z (%): 383 (M+, 64); elemental
analysis calcd (%) for C17H10ClN5O2S: C 53.20, H 2.63, N 18.25; found: C
52.9, H 2.8, N 17.9.
N-(4-methoxyphenyl)-4,5-diphenylthiazole-2-carbohydrazonoyl
°
cyanide (2d): Brown powder (0.338 g, 75%); mp 167-169 С; 1Н NMR
2-(4-(4-Chlorophenyl)thiazol-2-yl)-3-((9-ethyl-9H-carbazol-3-yl)-
amino)acrylonitrile (1h): Brown powder (0.340 g, 68%); mp 290-291 °С;
1Н NMR (400 MHz, DMSO-d6, TMS): δH = 11.97 (d, J = 13.1 Hz, 1Н,
NHСН), 8.50 (d, J = 13.0 Hz, 1Н, NHСН), 8.25 (d, J = 2.1 Hz, 1Н, HAr),
8.14 (dd, J = 2.1, 7.7 Hz, 1Н, HAr), 8.02 (d, J = 8.6 Hz, 1Н, HAr), 7.89 (s,
1H, CH), 7.57-7.42 (m, 6H, HAr), 7.20 (t, J = 7.1Hz, 1Н, HAr), 4.45 (q, J =
7.1Hz, 2Н, CH2), 1.42 ppm (t, J = 7.1Hz, 3Н, Me); 13С NMR (100 MHz,
DMSO-d6) δC = 165.0, 152.8, 144.7, 140.3, 137.1, 132.9, 132.3, 131.5,
129.0 (2C), 127.8 (2C), 126.2, 123.0, 121.9, 120.7, 119.9, 118.8, 116.7,
111.4, 110.1, 109.3, 108.4, 76.1, 37.1, 13.6 ppm; MS (EI) m/z (%): 454
(M+, 100); elemental analysis calcd (%) for C26H19ClN4S: C 68.64, H 4.21,
N 12.31; found: C 68.7, H 4.1, N 12.0.
(400 MHz, DMSO-d6, TMS): δH = 11.11 and 11.79* (both s, 1Н, NH), 7.56-
7.50 (m, 2H, HAr), 7.41-7.28 (m, 10H, HAr), 6.97 and 6.89* (both d, J =
9.0Hz, 2H, HAr), 3.80 and 3.78 ppm (both s, 3H, Me); 2:1 mixture of
isomers; 13С NMR (100 MHz, DMSO-d6) δC
= 161.3*/157.2 (+),
156.7/156.0* (+), 149.7/149.4* (+), 136.0*/134.8 (+), 134.1*/133.0,
132.9/132.0* (+), 130.9*/129.8, 129.5/129.2* (2C) (-), 129.0* (2C) (-),
128.7*/128.6 (2C) (-), 128.6*/128.5 (2C) (-), 128.4*/128.1 (2C) (-),
116.8/110.7* (+), 116.5* (2C) (-), 115.0*/114.7 (2C) (-), 106.8*/105.5 (+),
55.3/55.2* (-) ppm; mixture of isomers; MS (EI) m/z (%): 410 (M+, 71);
elemental analysis calcd (%) for C24H18N4OS: C 70.22, H 4.42, N 13.65;
found: C 69.9, H 4.6, N 13.4.
2-(4,5-Diphenylthiazol-2-yl)-3-((4-methoxyphenyl)amino)acrylonitrile
Electronic absorption and emission spectroscopy
°
̃
(1i): Yellow powder (0.450 g, 70%); mp 270-271 С; IR (NPVO, ZnSe): 휈
UV-vis absorption spectra were recorded on a Perkin-Elmer Lambda 35
UV-vis spectrophotometer (Shelton, CT, USA). The fluorescence of the
sample solutions was measured on a Hitachi F-7000 spectrophotometer
(Tokyo, Japan). The absorption and emission spectra were recorded in
1,4-dioxane, toluene, acetone, MeCN, THF, DCM, DMF, DMSO, EtOH and
AcOEt using 10.00 mm quartz cells. The excitation wavelength was the
absorption maxima. The atmospheric oxygen contained in solutions was
= 3058, 3029, 2952, 2937, 2902, 2805 (CH), 2201 cm-1 (CN); 1Н NMR (400
MHz, DMSO-d6, TMS): δH = 11.90 (d, J = 12.9Hz, 1Н, NHСН), 8.34 (d, J
=13.0Hz, 1Н, NHСН), 7.53-7.51 (m, 2H, HAr), 7.38-7.34 (m, 8H, HAr), 7.23
and 6.93 (AA′XX′, J = 8.9Hz, 4H, HAr), 3.78 ppm (s, 3H, ОMe). 13С NMR
(100 MHz, DMSO-d6) δC = 163.0, 157.1, 149.2, 145.2, 134.5, 132.4, 131.3,
129.9 (2C), 129.5 (2C), 129.3, 129.1, 129.0 (2C), 128.9 (2C), 128.7, 120.0,
118.8 (2C), 115.7 (2C), 76.4, 56.0 ppm; MS (EI) m/z (%): 409 (M+, 100);
elemental analysis calcd (%) for C25H19N3OS: C 73.33, H 4.68, N 10.26;
found: C 73.1, H 4.8, N 10.0.
not removed. The concentrations of the compounds in solution were 5×10-
5
M
and 10-6
M for absorption and fluorescence measurements,
respectively. The relative fluorescence quantum yields (ΦF) were
determined using quinine sulfate (10-5 M) in 0.1 M H2SO4 as a standard
]
(ΦF = 0.546).[13
2-(4-(4-Chlorophenyl)thiazol-2-yl)-3-(methyl(phenyl)amino)acrylo-
°
nitrile (1j): Beige powder (0.271 g, 70%); mp 165-167 С; 1Н NMR (400
MHz, DMSO-d6, TMS): δH = 8.24 (s, 1Н, СН), 7.92 (d, J = 8.6 Hz, 2H, HAr),
7.73 (s, 1Н, СН), 7.50-7.46 (m, 2H, HAr), 7.39 (t, J = 7.3 Hz, 4H, HAr), 7.32
(t, J = 7.3 Hz, 1H, HAr), 3.82 ppm (s, 3H, Me); 13С NMR (100 MHz, DMSO-
d6) δC = 166.1, 153.2, 149.1, 145.8, 133.3, 133.0, 130.1 (3C), 129.2 (2C),
128.2 (2C),127.4, 123.5, 118.5, 112.0, 76.5, 41.6 ppm; MS (EI) m/z (%):
351 (M+, 100); elemental analysis calcd (%) for C19H14ClN3S: C 64.86, H
4.01, N 11.94; found: C 64.6, H 4.3, N 11.6.
Acknowledgements
The research was supported by the Government of the Russian
Federation (Act 211, contract # 02.A03.21.0006). K. L. Thanks
RFBR for funding № 16-33-00327 mol_a. E. B. thanks the Italian
“Ministero per l’Università e la Ricerca Scientifica e Tecnologica”
for fundings [FIRB 2013, RBFR13PSB6].
4-(4-Chlorophenyl)-N-(4-methoxyphenyl)thiazole-2-carbohydrazo-
noyl cyanide (2a): Bright orange powder (0.260 g, 64%); mp 177-178 °С;
1Н NMR (400 MHz, DMSO-d6, TMS): δH = 13.93 and 11.84* (both s, 1Н,
NН), 8.37* and 8.06 (both s, 1Н, СН), 8.04-7.98 (m, 2H, HAr), 7.55 and
7.47* (both d, J = 8.3 Hz, 2H, HAr), 7.40-7.38 (m, 2H, HAr), 6.99 and 6.94
(both d, J = 8.8 Hz, 2H, HAr), 3.80 and 3.77* ppm (both s, 3H, Me); 3:2
mixture of isomers; 13С NMR (100 MHz, DMSO-d6) δC = 163.7*/159.6,
156.8/156.1*, 153.9/153.2*, 136.0*/134.9, 133.5/132.8*, 132.5*/131.0,
129.1/128.8* (2C), 128.0/127.7* (2C), 116.9*/116.8 (2C), 115.0/114.8 (2C),
114.7*, 110.7*, 107.1*/105.6, 55.4* ppm; mixture of isomers. MS (EI) m/z
(%): 368 (M+, 58); elemental analysis calcd (%) for C18H13ClN3OS: C 58.62,
H 3.55, N 15.19; found: C 58.4, H 3.7, N 14.9.
Keywords:
Thiazoles;
Fluorescence;
Solvatochromism;
Hydrogen bond; Density functional theory
References:
[1]
a) M. T. Chhabria, Sh. Patel, P. Modi, P. S. Brahmkshatriya, Curr. Top.
Med. Chem. 2016; 26, 2841-2862; b) C. B. Mishra, S. Kumari, M. Tiwari,
Eur. J. Med. Chem. 2015, 92, 1-34; c) A. M. Matos, A. P. Francisco,
ChemMedChem 2013, 8, 1751-1765.
[2]
a) O. Seitz, F. Bergmann, D. A. Heindl, Angew. Chem. Int. Ed. 1999, 38,
2203-2206; b) O. Köhler, O. Seitz, Chem. Commun. 2003, 23, 2938-
4-(4-Chlorophenyl)-N-phenylthiazole-2-carbohydrazonoyl
cyanide
(2b): Bright yellow powder (0.320 g, 86%); mp 184-185 °С; 1Н NMR (400
MHz, DMSO-d6, TMS): δH = 13.98* and 11.85 (both s, 1Н, NН), 8.39* (s,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700518
European Journal of Organic Chemistry
FULL PAPER
2939; c) O. Köhler, D. V. Jarikote, O. Seitz, ChemBioChem 2005, 6, 69–
77.
[9]
a) H. B. Jalani, A. N. Pandya, D. H. Pandaya, J. A. Sharma, V.
Sudarsanam, K. K. Vasu, Tetrahedron Lett. 2012, 53, 6927-6930; b) N.
P. Belskaya, K. I. Lugovik, A. D. Ivina, V. A. Bakulev, Z. J. Fan, Chem.
Het. Comp. 2014, 50, 888-900.
[3]
a) F. Bellina, C. Manzini, G. Marianetti, C. Pezzetta, E. Fanizza, M. Lessi,
P. Minei, V. Barone, A. Pucci, Dyes and Pigm. 2016, 134, 118-128; b) R.
P. Tayade, N. Sekar, J. Fluoresc. 2016, 26, 1-14; c) R. Kammel, O.
Tarabova, O. Machalický, M. Nepraš, B. Flumarová, J. Hanusek, Dyes
and Pigm. 2016, 128, 101-110; d) K. Yamaguchi, T. Murai, S. Hasegawa,
Y. Miwa, S. Kutsumizu, T. Maruyama,T. Sasamori, N. Tokitoh, J. Org.
Chem. 2015, 80, 10742-10756; e) T. Tao, B.-B. Ma, Y.-X. Peng, X.-X.
Wang, W. Huang, X.-Z. You, J. Org. Chem. 2013, 78, 8669–8679; f) S.
Wolfram, H. Würfel, S. H. Habenicht, C. Lembke, P. Richter, E. Birckner,
R. Beckert, G. Pohnert, Beilstein J. Org. Chem. 2014, 10, 2470-2479.
a) P. Arora, R. Narang, S. K. Nayak, S. K. Singh, V. Judge, Med. Chem.
Res. 2016, 25, 1717-1743; b) A. Ayati, S. Emami, A. Asadipour, A.
Shafiee, A. Foroumadi, Eur. J. Med. Chem. 2015, 97, 699-718.
N. K. Downer-Riley, Y. A. Jackson, Curr. Top. Med. Chem. 2016, 16,
3617-3626.
I. V. Paramonov, N. P. Belskaia, V. A. Bakulev, Chem. Het. Comp. 2003,
39, 1385-1395.
a) B. Valeur, M. N. Berberan-Santos, Molecular Fluorescence: Principles
and Applications, 2nd Edition, Wiley-VCH, Weinheim, 2013, p. 592; b) T.
Chu, J. Xu, J. Mol. Model. 2016, 22, 200; c) V. S. Padalkar, S. Seki,
Chem. Soc. Rev. 2016, 45, 169-202.
[10] a) S. Tanaka, K. Ashida, G. Tatsuta, A. Mori, Synlett 2015, 26, 1496-
1500; b) Y. Wang, M.-Y. Yang, M.-H. Zheng, X.-L. Zhao, Y.-Z. Xie, J.-Y.
Jin, Tetrahedron Lett. 2016, 57, 2399-2402.
[11] a) R. F. W. Bader, H. Essen, J. Chem. Phys. 1983, 80, 1943-1960; b) R.
F. W. Bader, Atoms in molecules. A quantum theory. Oxford: Oxford
University Press; 1990. c) R. F. W. Bader, Chem. Rev. 1991, 91, 893-
892.
[12] a) H. J. Bohórquez, C. F. Matta, R. J. Boyd, Int. J. Quant. Chem. 2010,
110, 2418-2425; b) E. R. Johnson, S. Keinan, P. Mori-Sánchez, J.
Contreras-Garcia, A. J. Cohen, W. Yang, J. Am. Chem. Soc. 2010, 132,
6498-6506; c) J. Lane, J. Contreras-García, J.-P. Piquemal, B. J. Miller,
H. G. Kjaergaard, J. Chem. Theory Comput. 2013, 9, 3263–3266; d) R. A.
Boto, J. Contreras-Garcia, J. Tierny, J.-P. Piquemal, Mol. Phys. 2015,
DOI: 10.1080/00268976.2015.1123777; e) J. Andres, S. Berski, J.
Contreras-Garcia, P. Gonzalez-Navarrete, J. Phys. Chem. 2014, 118,
1663-1672; f) J. González, I. Baños, I. León, J. Contreras-García, E. J.
Cocinero, A. Lesarri, J. A. Fernández, J. Millán J. Chem. Theory Comput.
2016, 12, 523–534; g) Y. Zhang, H. He, K. Dong, S. Zhang, RSC Adv.,
2017, 7, 12670-12682.
[4]
[5]
[6]
[7]
[8]
a) Y. Ge, D. F. O’Shea, Chem. Soc. Rev., 2016, 45, 3846-3864; b) R. P.
Tayade, N. Sekar, J. Fluoresc. 2017, 27, 167–180; c) B. Carlotti, E.
Benassi, V. Barone, A. Spalletti. F. Elisei, ChemPhysChem. 2015, 16,
1440-1450; d) B. Carlotti, E. Benassi, C. G. Fortuno, V. Barone, A.
Cesaretti, C. G. Fortuna, A. Spaletti, V. Barone, F. Elisei,
ChemPhysChem. 2016, 17, 136-1446; e) E. Benassi, B. Carlotti, M.
Segado, A. Cesaretti, A. Spalletti, F. Elisei, V. Barone, J. Phis. Chem. B.
2015, 119, 6035-6040; f) E. Benassi, F. Edigi, V. Barone, J Phys. Chem.
2015, 119, 3155-3173; g) K. Chen, H-Y. Tsai, Int. J. Mol. Sci. 2014, 15,
18706-18724; h) S. S. Razi, P. Srivastava, R. Ali, R. C. Gupta, S. K.
Dwivedi, A. Mistra, Sensor and Activators B: Chemical. 2015, 209, 162-
171.
[13] W. H. Melhuish, J. Phys. Chem. 1961, 65, 229-235.
[14] U. Schmidt, H. Kubitzek, Chem. Ber. 1960, 93, 1559-1564.
[15] M. Ruiz-Lopez in Quantum Modeling of Complex Molecular Systems
(Ed.: J.-L. Rivail), Springer, Berlin, 2015, pp. 343-365.
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10.1002/ejoc.201700518
European Journal of Organic Chemistry
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Absorption
FL (dioxane)
FL (solid)
Fluorescence, Intramolecular Charge
Transfer*
Kseniya I. Lugovik, Aleksandra V.
Popova, Alexander K. Eltyshev, Enrico
Benassi,* Nataliya P. Belskaya*
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Two series of di- and trisubstituted thiazoles bearing pendant aryl enamine/aza-
enamine groups (X = C, N) were synthesized, and their structural features,
geometries and photophysical properties in solution and in the solid state were
evaluated by spectroscopic methods and quantum mechanical calculations. The
effect of weak intramolecular interactions on their photophysical properties was
elucidated.
Synthesis of Thiazoles Bearing Aryl
Enamine/Aza-enamine Side Chains.
Effect of the π-Conjugated Spacer
Structure and Hydrogen Bonding on
Photophysical Properties
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