Design, synthesis, and photophysics of bi- And tricyclic fused pyrazolines

Article abstract of DOI:10.1039/d0nj06287a

Three series of bi- and tricyclic functionalized new pyrazoline fluorophores have been synthesized for investigation of their photophysical properties. Spectral studies indicated significant absorption and emission properties. The quantum yields reached 9

Full text of DOI:10.1039/d0nj06287a

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Design, synthesis, and photophysics of bi- and
tricyclic fused pyrazolines†
Cite this: New J. Chem., 2021,
45, 6315
a
Alexandra V. Popova,a Ali Kanaa,
Vladislava S. Vavilova,a Maria A. Mironova,a
ab
ab
Pavel A. Slepukhin,
Enrico Benassi*c and Nataliya P. Belskaya
*
Three series of bi- and tricyclic functionalized new pyrazoline fluorophores have been synthesized for
investigation of their photophysical properties. Spectral studies indicated significant absorption and
emission properties. The quantum yields reached 93% and Stokes shifts increased up to 148 nm. The
compounds exhibited positive solvato(fluoro)chromism. Fluorescence was sensitive to both structural
changes and the microenvironment, especially to protic solvents, such as EtOH, n-BuOH, and DMSO/
H2O mixture, and ethylene glycol. The experimental findings were supported by quantum mechanical
calculations. Modification of the electronic nature of the substituents and their spatial effects can change
the nature and direction of intramolecular charge transfer (ICT). These findings provide valuable insights
for the development of new fused pyrazolines with tunable photophysical properties. The pyrazolines
exhibited high intensity solid-state emissions, making them suitable for applications in photonics. Active
functional groups may be used to bind pyrazolines and natural compounds, drugs, and diagnostic
molecules, for possible use in biological systems and medicine.
Received 28th December 2020,
Accepted 22nd February 2021
DOI: 10.1039/d0nj06287a
rsc.li/njc
The commonly used method for the synthesis of pyrazolines
is based on the Claisen–Schmidt condensation of aromatic
Introduction
Pyrazolines are generally known as blue, fluorescent dyes with chalcones with aryl/hetaryl hydrazines.6 However, this reaction
high fluorescence quantum yields.1 Moreover, numerous pyrazo- usually leads to aryl- or hetaryl-substituted pyrazolines, which
line materials have been investigated for electronic applications rarely contain additional functional groups. Other disadvan-
in device technology,2 such as dye solar cells, and hole trans- tages of this method include the lack and limited volume of
porting materials or emitting materials in organic light-emitting suitable starting materials, especially hydrazines, and the forma-
diodes.3
tion of two regioisomeric pyrazolines when using asymmetric
In addition, pyrazolines are known to exhibit a wide range of substrates. Triaryl/hetarylpyrazolines are weakly soluble in
biological activities and this motif is ubiquitous in drugs.1a,4 organic solvents and insoluble in water, which limits their use
Outstanding optical properties and the absence of cytotoxicity in aqueous media and in biological and medical research. A new
have allowed the application of pyrazolines in biological investiga- method for dihydropyrazoline synthesis has recently been devel-
tions and in medical research pertaining to diagnostics, thera- oped, entailing the CuCl-catalyzed oxidative coupling of aldehyde
nostics, drug delivery, and treatment response monitoring.1a,5 hydrazones with maleimides. However, its scope is limited by the
However to obtain hybrid structures comprising a pyrazoline availability of the starting aldehydes and hydrazones.7
fluorophore and a biomolecule (natural compound or drug), the
presence of certain functional groups should be included.
Pyrazolines can be built via the 1,3-dipolar cycloaddition of 1,3-
diaryl(hetaryl)nitrile imines to dipolarophiles.8 This approach to
pyrazoline ring construction is based on the fundamental princi-
ples underlying the cycloaddition mechanism.9 Cycloaddition
reaction pathways are characterized by a large negative entropy
of activation and stereospecificity, which indicates the formation
of a highly organized transition state during the reaction and high
regioselectivity. The nitrile imine source may be a tetrazole, which
can generate active moieties by photoirradiation and form the
pyrazoline core with dipolarophiles (NITEC – nitrile imine-
mediated tetrazole–ene cycloaddition).10 However, tetrazoles are
very hazardous and their availability is scarce; hence this route is
not suitable for practical applications.
a Ural Federal University, 19 Mira Str., Yekaterinburg 620002, Russian Federation.
E-mail: n.p.belskaya@urfu.ru
b Postovsky Institute of Organic Synthesis, Ural Branch of Russian Academy of
Science, 22 S. Kovalevskaya Str., Yekaterinburg, 620219, Russian Federation
c Shihezi University, 280 N 4th Rd, Shihezi, Xinjiang 832000, China.
E-mail: ebenassi3@gmail.com
† Electronic supplementary information (ESI) available: Copies of NMR spectra
for new compounds; XRD crystal data; details of photophysical investigations,
quantum-mechanical calculations, and the coordinates of compounds optimized
at B3LYP/6-31G**level. CCDC 2044826 and 2044827. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/d0nj06287a
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compounds containing electron-donating and electron-with-
drawing substituents on the N1-bonded aromatic fragment,
different carbonyl functionalities at the C3 position of the pyrazo-
line ring, and different structures of the fused heterocyclic cores.
We have developed an efficient method for the construction
of carbonyl-bearing fused pyrazolines 2–4 (Scheme 1) via 1,3-
dipolar cycloaddition between arylhydrazonoyl halides and
N-methylmaleimide (5), N-phenylmaleimide (6), and norbornene
(7). N-Methyl- and N-phenylmaleimides are electron-deficient
dipolarophiles that readily react with various 1,3-dipoles in
cycloaddition reactions. Their inclusion into chromophore or
fluorophore molecules is potentially advantageous due to the
presence of several heteroatoms and because of their known
optical properties.12 Norbornene, or bicyclo-[2.2.1]hept-2-ene, is
a strained cyclic olefin, which is highly reactive in cycloaddition
reactions and can confer particular electronic properties on a
fused heterocyclic core post-cycloaddition.
Scheme 1 Retrosynthesis of targeted fused pyrazolines.
Results and discussion
Synthetic study
An alternative, safer procedure for nitrile imine generation
involves the base-promoted dehydrohalogenation of the corres- The 1,3-dipolar cycloaddition of nitrile imines to dipolarophiles
ponding hydrazonoyl halide.11 Moreover, this approach is a well-known reaction; it can be conducted over a wide
Q
enables the inclusion of various C O-bearing substituents temperature range, in various organic solvents (benzene, chloro-
on the pyrazoline ring (Scheme 1), which can serve as active form, methylene chloride, dioxane, ethyl acetate, and diethyl
sites for the insertion of various functionalities for further ether), and in the presence of a base (TEA, or Na2CO3).7 The
modification, or for binding with targeted biomolecules or starting hydrazonoyl chlorides were synthesized according to an
analytes. An outlined modification of pyrazoline derivatives existing method, involving the interaction of freshly prepared
would allow tuning their physicochemical properties or bio- aqueous solutions of aryldiazonium salts with 3-chloro-2,4-
logical behavior, thereby potentially expanding the scope of their pentadione or ethyl 2-chloro-3-oxobutanoate.11 Refluxing in
applicability in medicine and biology. However, functionalized chloroform in the presence of TEA is recommended for nitrile
bi- and tricyclic pyrazolines are rarely synthesized and their imine 1,3-dipolar cycloadditions;7,8 however, employing this
optical properties have not yet been investigated.
protocol for the reaction of hydrazonoyl chloride 1a with
Traditionally, chromophore or fluorophore design is based N-methylmaleimide provided pyrazoline 2a in low yield (35%).
on the creation of a conjugated system of multiple bonds, hetero- The reaction was sluggish and was accompanied by the forma-
atoms, and aromatic/heteroaromatic rings. The most well-known tion of products of the destruction, which increased with the
and largest groups of pyrazolines are the bi-aryl/hetaryl or tri-aryl/ expansion of heating.
hetaryl monocyclic pyrazolines. Several studies have been con-
Nitrile imine (A, Table 1) containing an acetyl or ethoxycar-
ducted to reveal substituent effects at the N1, C3, and C5 positions bonyl group at the C1 position is more stable than nitrile
on their electronic properties.1a The presence of the N1 atom with imines with a conventional aromatic substituent.11i This elec-
lone pair non-bonding electrons is crucial for the effectiveness of tronic effect results in lengthy and sluggish cycloadditions and
the charge transfer within pyrazolines, as it promotes electron in the necessity for more stringent conditions. To establish the
density transfer from the aromatic ring via N1–N2QC3 conjuga- optimal conditions for the cycloaddition of functionalized
tion, or via a C4–C5 s-bond to the C5 substituent.1a Charge nitrile imines to maleimides, we studied the interaction of
transfer via the N1–N2–C3 route is more effective. Moreover, it hydrazonoyl chloride 1a with N-methylmaleimide in various
has been shown that the C5 aryl/hetaryl substituent does not solvents (chloroform, benzene, toluene, and xylene) at room
participate in the molecular electronic system, as its structure temperature, under reflux, and under microwave conditions,
deviates significantly from the pyrazoline ring planarity. Neverthe- and with the addition of various amounts of TEA (Table 1).
less, this substituent can affect the photophysical characteristics,
causing a decrease in the fluorescence intensity due to energy N-methylmaleimide 5 forming the corresponding hexahydropyrrolo-
loss during the geometry relaxation in the excited state. [3,4-c]pyrazole 2a in a regioselective manner. The highest yield
The nitrile imine 1a undergoes 1,3-dipolar cycloaddition to
Herein, we present the synthesis of fused pyrazolines 2–4 and a was obtained by refluxing the reagents with 3 equiv. TEA in
detailed investigation of their optical properties. To understand chloroform, affording the corresponding product 2a in 61% yield
the influence of structural fragments and substituents on the (Table 1, entry 3). To intensify the process conditions and shorten
photophysical properties of the targeted pyrazolines, we designed the reaction time, we studied the same reaction in CHCl3, benzene,
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Table 1 Optimization of conditions for the reaction of hydrazonoyl chloride 1a with N-methylmaleimide 5
Entry
X, equiv.
Solvent
T, 1C
Time, h
Yield 2a,a
%
1
2
3
4
5
6
7
8
9
10
1
2
3
3
3
3
3
3
3
3
CHCl3
CHCl3
CHCl3
CHCl3
Benzene
m-Xylene
CHCl3
Benzene
m-Xylene
m-Xylene
61
61
61
25
80
48.0
13.0
7.0
25.0
25.0
8.0
7.0
2.5
0.5
1.5
35
57
61
b
—
—
b
134
60
42
52
60
78
80 (MW)
100 (MW)
150 (MW)
150 (MW)
a
b
Isolated yield. The reaction did not proceed to completion, hence the product was not isolated.
and m-xylene under microwave heating. Hence, the optimal
conditions, in terms of yield, purity of the final product, and
the duration of the process, entailed heating in xylene at 150 1C
under microwave radiation in the presence of 3 equiv. of TEA for
1.5 h (Table 1, entry 10).
Employing the optimal conditions, hydrazonoyl chlorides 1a–k
were reacted with N-methylmaleimide 5, N-phenylmaleimide 6,
and norbornene 7 (Scheme 2 and Table 2). The products were
isolated using liquid column chromatography after solvent
removal via distillation.
As a result, 1-aryl-3a,6a-dihydropyrrolo[3,4-c]pyrazole-4,6-
(1H,5H)-diones (Me-DPPs) 2a–k, 1-aryl-3a,6a-dihydropyrrolo[3,4- Scheme 2 Scope of the reaction of hydrazonoyl chlorides with N-methyl-
and N-phenyl-maleimides, and norbornene.
c]pyrazole-4,6(1H,5H)-diones (Ph-DPPs) 3a–e, and 1-aryl-hexa-
hydro-1H-4,7-methanoindazoles (HMIs) 4a–e were obtained in
good yields. The structures of Me-DPPs 2a–k, Ph-DPPs 3a–e, and
HMIs 4a–e were confirmed by NMR spectral data and elemental
the literature.13 This indicates the occurrence of conjugation
between the aryl and pyrazoline rings. The rigidity of 2h and 4d
is supported by intramolecular interactions. Thus, 4d contained
two hydrogen bonds, while in addition to hydrogen bonds,
pyrazoline 2b formed non-covalent interactions between O1
and N2 atoms (Fig. 1a) due to the presence of ester groups in
the molecule.
and XRD structural analyses. The key characteristics of the
1H NMR spectra of pyrazolines 2–4 were signals indicating
an AB-system of two nodal CH-protons at 4.80 and 5.65 ppm
with 3J = 10.9 Hz (Fig. S4–S23, ESI†). Such an arrangement
suggests axial positioning of these protons, indicative of endo-
overlapping of the dipole and dipolarophile orbitals in the
transition state.8
Pyrazoline photophysical properties
Crystals of Me-DPP 2h and HMI 4d were grown in a mixture
of CHCl3/EtOH and AcOEt/hexane (Fig. 1, Fig. S25, S26 and The solutions of Me-DPPs 2a–k, Ph-DPPs 3a–e, and HMIs 4a–e
Table S1, ESI†). The angle between the aromatic and pyrazole in organic solvents were colorless in daylight, but exhibited
rings in Me-DPP 2h was 29.81. This is possibly due to steric yellow-green, turquoise, and blue fluorescence, respectively,
hindrance caused by the presence of an ortho-chlorine in the under UV irradiation (Fig. 2). The UV spectra of CHCl3 solutions
aromatic ring, which causes torsional tension and deviation of pyrazolines 2–4 exhibited an intense peak in the range of 320–
from coplanarity. By contrast, the aromatic and pyrazoline 385 nm, derived from p - p* transitions (Fig. 2a, e, i and m).
rings in HMI 4d were almost coplanar. The bond length HMIs 4 displayed the most significant red shift at 362–385 nm. The
between the ipso-carbon and the N1 of the pyrazoline 4d molar extinction coefficients were high, reaching 20 700 Mꢀ1 cmꢀ1
was B1.394 Å, and increased up to 1.415 Å in 2h, which is for 2a (Table S2, entry 1, ESI†). The normalized fluorescence
shorter than the length of the single C–N bond according to spectra of pyrazolines 2a–k, 3a–e and 4a–e are shown in Fig. 2b, f, j
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Table 2 Cycloaddition of hydrazonoyl chlorides 1a–k with dipolarophiles 5–7; conversion times and yields of pyrazolines 2–4
Hydrazone 1
Pyrazolines, 2–4
Entry
Compd
R1
R2
Dipolarophile
Time, min
Compd
R1
R2
Yield, %
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
4-MeO
4-AcHN
4-Me
H
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
Me
Me
Me
OEt
OEt
Me
Me
Me
OEt
OEt
Me
Me
Me
5
5
5
5
5
5
5
5
5
5
5
6
6
6
6
6
7
7
7
7
7
90
180
60
30
60
60
45
90
60
15
15
35
90
40
60
40
35
40
40
40
40
2a
2b
2c
2d
2e
2f
2g
2h
2i
4-MeO
4-AcHN
4-Me
H
OEt
OEt
OEt
OEt
OEt
OEt
OEt
OEt
Me
Me
Me
OEt
OEt
Me
Me
Me
OEt
OEt
Me
Me
Me
78
57
79
80
77
71
78
68
75
91
88
66
69
70
90
73
66
74
89
81
75
4-Cl
4-Cl
4-CF3
4-CN
2-Cl
4-Me
H
4-CN
4-Me
4-CN
4-Me
H
4-CN
4-Me
4-CN
4-Me
H
4-CF3
4-CN
2-Cl
4-Me
H
4-CN
4-Me
4-CN
4-Me
H
4-CN
4-Me
4-CN
4-Me
H
9
10
11
12
13
14
15
16
17
18
19
20
21
1j
2j
1k
1g
1i
1j
1k
1i
1c
1g
1i
1j
1k
2k
3a
3b
3c
3d
3e
4a
4b
4c
4d
4e
4-CN
4-CN
Fig. 1 Representative molecular structure of Me-DPP 2h (a and b), and HMI 4d (c and b): (a and c) front view; (b and d) side view, respectively, with
dashed short contacts and angles between the cyclic fragments.
and n. Quantum yields (QY) were widely distributed (1.7–93.1%), (CN) on the aromatic ring. Stokes shifts were relatively large
depending on the aromatic substituent, and reached a maximum (up to 151 nm); therefore, self-absorption was not observed.
for HMI 4b. High QYs were registered for Me-DPP 2g, Ph-DPP 3b,
Further analyses of the pyrazoline optical properties eloquently
and HMI 4b, bearing an electron-withdrawing CN group on the supported its sensitivity to changes in the heterocyclic core
aromatic ring (Fig. 2 and Table S2, ESI†). Thus, QYs increased structure and electronic nature of the substituents. The fluore-
B46-fold from that of 2a with an electron-donating MeO-group, scence maximum ranged from 443 to 512 nm and was red
to that of Me-DPP 2g, bearing an electron-withdrawing group shifted for pyrazolines bearing an electron-donating substituent
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Fig. 2 (a, e, i and m) Absorption and (b, f, j and n) emission spectra of pyrazolines 2a–k, 3a–e, and 4a–e, respectively, in CHCl3 at room temperature,
c = 1 ꢁ 10ꢀ6 M). Photographs of the CHCl3 solutions of Me-DPPs 2a–k, Ph-DPPs 3a–e, and HMI 4a–e under (c, g, k and o) daylight and (d, h, l and p) with
UV radiation (l = 365 nm), respectively.
(MeO or Me) in the para-position of the N1-aromatic ring. For subsequently confirmed by quantum mechanical calculations
example, the maximal emission was redshifted by 41–64 nm for (vide infra). The optical properties of 1-(2-chlorophenyl)pyrrolo-
the pyrazolines 2a, 2i, 3a, 3c, 4a, and 4c in comparison with the pyrazoline 2i (R1 = 2-Cl) were also dependent on the location of
compounds 2g, 2k, 3b, 3e, 4b, and 4e with an electron-with- the substituent. The presence of the Cl substituent in the ortho-
drawing CN-group. 3-Ethoxycarbonyl derivatives Me-DPPs 2g, position in 2i leads to considerable steric hindrance, resulting in a
Ph-DPPs 3b, and HMIs 4b demonstrated higher QYs (72.3% to hypsochromic shift of the long-wavelength maximum by 30 nm
93.1%), than pyrazolines 2i, 3b, and 4b with an acetyl fragment and a 2-fold decrease in QY with respect to that of the 4-substituted
at C3 (Fig. 2 and Table S2, ESI†). This behavior is likely related congener 2e (R1 = 4-Cl).
to an increase in the rigidity of these intramolecular systems,
Investigating the influence of compound concentration on
the formation of which was observed by XRD analysis and the optical characteristics indicated a 1.2–4.3-fold decrease in
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sensitivity to the environment (Fig. 4 and Table S5, ESI†). The
absorption and emission maxima were red shifted in polar
solvents by 3–8 nm and 23–46 nm, respectively. The unequal
sensitivities of the pyrazolines in their excited states (ES) is a result
of the higher polarity of the ES compared with the GS (see later in
Table 5). Positive solvatochromism is generally observed for 2g,
3b, 4b, and 4d. Absorption molarities exhibited high values (the
highest for HMI 4d in most solvents used), with highly polar
(DMF) and protic solvents (EtOH and n-BuOH) giving the best
results. QYs showed high values both in low polar EtOAc (57.6–
92.4%) and CHCl3 (33.2–93.1%), as well as in high polar DMF
(23.4–82.0%) for all the investigated compounds (Table S5, ESI†).
However, in protic solvents, especially in ethylene glycol, the QY
decreased considerably, except for that of 4b. A large red shift in
the long-wavelength emission maximum was observed along with
an increase in the Stokes shift of up to 116 nm, suggesting ICT.
This was better stabilized in the ES by the formation of intra-
molecular hydrogen bonds and electrostatic interactions between
the pyrazoline molecules and the solvent. Considering that this
trend increases in viscous ethylene glycol, we can conclude that
viscosity is also a contributing factor. The highest quantum yield
was recorded for HMI 4b in CHCl3 (Table S5, entry 23, ESI†), and
the lowest (3.20%) was observed for HMI 4d in toluene (Table S5,
entry 31, ESI†).
Water is a more suitable solvent for biological and medical
investigations. Therefore, the optical properties of Me-DPP 2a
were also explored in DMSO/water mixtures of varying ratios.
(Fig. 5 and Table S6, ESI†). The spectral pattern remains
unchanged in shape and the emission intensity decreases, which
can be attributed to the aggregation caused quenching (ACQ)
effect. Pyrazoline 2a displays decreasing emission (5.9-fold) with
an increasing water fraction ( fw) from 0% to 90%. A 23 nm
bathochromic shift was observed in emission, while the absorp-
tion maximum change was insignificant (1–2 nm).
Fig. 3 Relationship between the concentration and photophysical properties
of Ph-DPPs 3a–c and HMI 4e.
QY and a redshift of the long-wavelength maximal emission (from
4 to 36 nm) with increasing fluorophore concentration (Fig. 3).
Thus, the formation of exciplexes is hypothesized to accelerate the
rate of non-radiative energy dissipation, due to solute–solute and
solute–solvent energy transitions, and to gradually decrease the
QY of pyrazolines 3a–c and 4e. Meanwhile, the long-wavelength
maxima of Ph-DPPs 3a and 3e (R1 = Me) were red shifted from 9
to 36 nm.
The time-resolved fluorescence spectra of Me-DPPs 2i,k,
Ph-DPPs 3a–e,j, and HIMs 4b–d in CHCl3 were collected, and
the fluorescence lifetime data are summarized in Table 3 and
Table S4 (ESI†). Fluorescence decay behavior is found to be tri-
exponential in general. The singlet excited states (S1) of Me-DPPs
2j and Ph-DPPs 3c,d were investigated in CHCl3. The short-
lifetime component was chiefly attributed to ICT processes.14
The long-lifetime component may be assigned to the less or
unpolarized molecule. To verify the fluorescence dynamics, we
calculated the radiative transition rate constant (kr) and non-
radiative transition rate constant (knr) by employing the fluore-
scence lifetime and QY (Table 3). Non-radiative decay was dominant
for most compounds, with the exceptions being Ph-DPP 3b and
HMI 4b with high QYs.
Solid state fluorescence
Pyrazoline powders exhibited light-green and blue fluorescence
under UV irradiation. Their solid-state emission was investigated
(Table 4 and Fig. 6). The fluorescence wavelengths covered a
Solvato(fluoro)chromism
Analysis of the UV and fluorescence spectra of Me-DPP 2g, Ph-DPP significant range (453–533 nm) and were 3–24 nm blue-shifted
3b, and HMIs 4b and 4d in various solvents demonstrated the for compounds 2i, 2j, 3a, and 3d in comparison with their
solution emissions in CHCl3. On the other hand, pyrazolines
2k, 3b, and 3e with the 4-CNC6H4 fragment at N1 and HMIs 4b–d
displayed a redshift in the solid-state emission. The highest
fluorescence intensity was observed for Ph-DPP 3c which con-
tains an electron-donating group on the N1-bonded aromatic
cycle (R1 = 4-Me) and an acetyl fragment at C3 of the heterocycle.
Furthermore, increasing intensity was observed for 2i, 3a, and
3d. Hence, an opposite trend was observed compared with that
in the solvated phase (Table S2, ESI†). Therefore, depending on
the pyrazoline structure (the architecture of the heterocyclic core
and the nature and position of the substituent), fluorescence can
be tuned in the solid and solvated phases.
Table 3 Fluorescence lifetime (htif), radiative (kr) and non-radiative (knr
)
decay parameters of Me-DPPs 2i–k, Ph-DPPs 3a–e, and HIMs 4b–d in
CHCl3
Entry Compound QY htif (ns) kr ꢁ 10ꢀ6 (sꢀ1) knr ꢁ 10ꢀ6 (sꢀ1) kr/knr
1
2
3
4
5
6
7
8
2i
0.185 0.9097 0.203
0.139 0.4336 0.320
0.092 1.2674 0.073
0.719 4.7271 0.152
0.164 0.8673 0.189
0.128 1.3635 0.094
0.140 0.4594 0.305
0.159 1.3818 0.115
0.931 3.3694 0.276
0.389 3.4952 0.111
0.327 0.5294 0.618
0.895
1.984
0.717
0.059
0.964
0.639
1.874
0.609
0.020
0.175
1.271
0.23
0.16
0.10
2.58
0.20
0.15
0.16
0.19
13.8
0.63
0.49
2k
3a
3b
3c
3d
3e
3j
4b
4c
4d
Thus, pyrazolines exhibited strong fluorescence in the solid
state, with QYs of up to 62.6%. Moreover, QYs of solid pyrazo-
lines 2i, 3a, and 3d increased 2.5-, 67-, and 1.6-fold, respectively,
9
10
11
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Fig. 4 (a, e, i and m) Absorption spectra and (b, f, j and n) emission spectra of Me-DPP 2g, Ph-DPP 3b, HIM 4b and 4e, respectively, in different solvents.
Photographs of solutions of Me-DPP 2g, Ph-DPP 3b, HIM 4b, and 4e under (c, g, k and o) daylight, and (d, h, l and p) under UV irradiation (l = 365 nm),
respectively, in different solvents: (1) 1,4-dioxane, (2) toluene, (3) CHCl3, (4) EtOH, (5) EtOAc, (6) n-BuOH, (7) ethylene glycol, (8) DMF, (9) DMSO,
(10) MeCN. Absorption (c = 5 ꢁ 10ꢀ5 M) and emission (c = 1 ꢁ 10ꢀ6 M).
in comparison with their solutions in CHCl3. This phenomenon that the investigated compounds can show different rotamers,
is rarely observed for fluorescent compounds, as numerous thermodynamic properties for all of them were computed to
fluorophores, which are emissive in dilute solutions, demon- identify the most stable ones (Table S7, ESI†) for use in further
strate a quenching effect in the solid, due to excimer formation analysis of the spatial structures, charge distribution, HOMO–
and strengthening of ICT.14 Advances in the design and synthesis LUMO, and molecular electrostatic potential, in both the excited
of solid-state light-emitting organic materials with high fluore- and ground states. The accuracy of the geometry calculations
scence quantum yields can be applied in the fields of optical was verified by matching the computed electronic spectra with
sensors and organic light-emitting diodes (OLEDs).2,3
the experimental data. The predicted absorption and fluore-
scence maxima simulated in chloroform were in good agreement
with the experimental values (Table 5).
Quantum mechanical calculations
The geometries and electronic structures of Me-DPPs 2a,e–g,k,
Fig. S27 (ESI†) shows the optimized geometries of these
Ph-DPP 3b, and HMI 4b in CHCl3 implicit solvation were compounds, while Tables S8–S10 (ESI†) list several selected
investigated by quantum mechanical calculations. Considering geometrical parameters. It should be mentioned that in the GS,
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Fig. 5 (a) Absorption and (b) emission spectra of Me-DPP 2a in DMSO (c = 5 ꢁ 10ꢀ6 M) with varying amounts of water. (c) Plot of emission intensity (QY)
of Me-DPP 2a versus water fraction from 0% to 90% in the DMSO/H2O mixture. Inset: Fluorescence intensity changes of solutions of pyrazoline 2a: in (a) DMSO,
(b) DMSO–water (v/v 1 : 1), (c) DMSO–water (v/v 1 : 9).
Table 4 Photophysical properties of Me-DPPs 2i–k, Ph-DPPs 3a–e, and
HMIs 4b,e,d in the solid state
Entry
Compound
lex,max (nm)
lem,max (nm)
QY,a
%
1
2
3
4
5
6
7
8
2i
2j
372
369
284
373
286
365
373
284
372
259
268
479
477
468
468
457
479
466
455
453
520
533
46.0
12.5
11.2
41.4
3.3
62.6
20.1
8.9
2k
3a
3b
3c
3d
3e
4b
4e
4d
9
10
11
32.1
2.1
0.5
a
Absolute quantum yield.
the bond lengths in Me-DPP 2a,e–g,k, and Ph-DPP 3b are
comparable and vary only slightly depending on the electronic
nature of the substituent at the 4-position of the aromatic ring
and the C3-functionality. The principal difference between
pyrazolines 2 and 3 is the spatial location of the twisted
Fig. 6 (a) Normalized emission spectra of Me-DPPs 2i–k, Ph-DPPs 3a–d
N1-aromatic ring. This fragment deviates from the pyrazoline and HMIs 4b,e in the solid state. Photographs of the solid samples under
(b) visible light, (c) UV irradiation and (d) number of compounds.
ring at 25.6–27.81 in Me-DPPs 2a,e–g,k. However, the N1-bonded
aromatic ring and the pyrazoline ring in Ph-DPP 3b are coplanar,
but the N-phenyl fragment in the pyrrol-2,5-dione is twisted with
a significant deviation from planarity (57.51). Large differences the C3 atom bearing an electron withdrawing COOEt or COMe
were observed between the structures of Me-DPPs 2a,e–g,k, group. Thus, electron-donating substituents lead to a decrease
Ph-DPP 3b, and HMI 4b. The values of the lengths of ring and in the C–N and NQN bond lengths and a slight increase in the
side bonds and angles suggested that Me- and Ph-DPPs are more CQN bond length. This implies that the electronic nature of
spatially disordered. All these observations accord with the XRD the para-substituents influences the pyrazoline properties in
data (Table S1, ESI†).
the GS and this effect is enhanced in the ES, as corroborated by
The geometry of the compounds changed significantly upon experimental spectral data (Table S2, ESI†).
light absorption, i.e., transition to a vertically excited state, and
Several non-covalent intramolecular interactions were observed.
then relaxation. Most of the bonds became shorter. The aryl Hydrogen and N–O specific bonding occurs via the overlapping of
moieties at the N4 pyrazoline atom adopt a nearly planar non-bonded and occupied orbitals of neighboring heteroatoms.15
orientation with the pyrazoline ring, as can be inferred from Moreover, the combination of these factors results in the
the dihedral angles in Tables S8–S10 (ESI†). The effect of the strengthening of pyrazoline planarity and conjugation between
substituent on the lone pair of electrons at N1 results in ICT the molecular termini, thereby lowering energy dissipation during
being further widespread around the pyrazoline NQC bond to relaxation and enhancing the emission intensity.
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Table 5 Absorption and emission propertiesa of Me-DPPs 2a–k, Ph-DPPs 3b and HMI 4b, in implicit (IEF-PCM) solvated phase (CHCl3) obtained from
quantum chemical calculations
Entry
Compd
cH–L
la
f01
m0
m1v
y0,1v
cL–H
le
f10
m1r
y0,1r
1
2
3
4
5
6
7
2a
2e
2f
2g
2k
3b
4b
0.59480
0.49850
0.56130
0.54595
0.49858
0.59017
0.69048
367
352
343
348
359
346
362
0.2913
0.4602
0.4917
0.7096
0.6896
0.7282
0.9807
4.6
3.0
4.2
5.7
0.2
6.2
7.1
10.2
1.5
3.9
5.6
4.0
11.1
5.9
58.9
21.2
5.4
5.2
5.3
14.3
4.4
0.67838
0.32902
0.54553
0.46461
0.48737
0.66591
0.69234
519
478
455
452
450
455
443
0.5085
0.1045
0.1007
0.2017
0.0013
0.2083
0.8475
11.8
2.8
4.7
6.7
0.9
13.3
5.3
66.0
13.8
8.2
3.6
4.2
18.2
0.9
a
Absorption wavelength (la, nm) and oscillator strength ( f01), emission wavelength (le, nm) and oscillator strength ( f10), modulus of the electric
dipole moments of the ground state (m0, D), of the vertical FC excited state (m1v, D), and of the relaxed excited state (m1r, D), and angles formed by the
dipole moment vectors (y0,1v,((deg.) and y0,1r (deg.)).
The characteristics of excitation and emission, dipole moment N-phenyl-pyrrolidine fragment only partly cover the pyrazoline
magnitudes and orientation, in the GS and the ES, were computed ring. The Ph-DPP 3e LUMO shifted to the electron-accepting
and are listed in Table 5.
CN–C6H4-fragment and was completely absent at the N-phenyl
HOMO–LUMO and LUMO–HOMO coefficients (cH–L and cL–H
)
site but localized to a large extent on the pyrrol-2,5-dione
demonstrated that absorption and emission mainly involved the cycle. The HOMOs of HMI 4b were widespread over the
HOMO and LUMO. The largest oscillator strength was found for aromatic cycle, pyrazoline, and cyclopentane, and even pene-
HMI 4b, which also had the highest QY (93.1%), decreasing trated the cyclohexyl fragment of norbornane. The LUMO
significantly for 2k, 2e, and 2f with less effective emissions. The distribution of 4b differed by the shift of the electronic clouds
electric dipole moment changes were dependent on the pyrazo- from norbornane through the pyrrolizine C5 atom to the
line structure. Thus, the polarity increased for pyrazolines 2a, 2k, aromatic ring substituted with electron-withdrawing CN. The
and 3b and decreased for 2e, 2f, 2g, and 4b upon excitation. electronic distribution was widespread from the C3 pyrroli-
Compounds 2a and 3b exhibited the largest dipole moment; zine atom to the oxygen atom of the COOEt functionality. The
however, the dipole moment direction for Me-DPP 2a shifted to a oxygen atoms of the COOEt or COMe groups in Me-DPPs 2a–k
greater extent in the ES compared with that of the other provide a small contribution to the HOMOs, while the oxygen
pyrazolines. The energy gaps between the HOMOs and LUMOs atoms of the COOEt groups in Me-DPPs 2a–k and Ph-DPPs 3e
of pyrazolines 2–4 were calculated to be 5.93–6.79 eV.
do not take part in both the HOMOs and LUMOs. By contrast,
The FMO isosurfaces (Fig. 7) exhibited considerable dissim- the oxygen atoms of the COOEt group in HMI 4b significantly
ilarities depending on the substituents on the N1-bonded aro- contribute to both the HOMO and LUMO.
matic ring and the specific structure of the central heterocyclic
The ICT within these compounds therefore occurs at vary-
core. The FMO electron density in the GS and ES was mainly ing magnitudes and directions and is governed by the type of
closed for individual compounds, excluding the HOMOs of heterocyclic core and the electronic nature of the N1-bonded
Me-DPPs. Thus, the HOMOs of Me-DPPs 2a–k in the GS extend aromatic substituent. In addition, these results explain the
over the pyrazoline ring and N1-bonded aromatic ring, while the blue shifts in the emission maxima of Me-DPPs, Ph-DPPs, and
Q
C
O groups, the N-atom of the N–Me groups of the pyrrol-2,5- HMI comprising a 4-CN–C6H4 fragment at the N1 atom, and
dione moiety, and the C3-bonded carbonyl functionality were the red shift of the maxima in the fluorescent spectra of
rather poor in terms of electronic density. The same trend HMIs 4. The electronic channel directed to the C3 function-
was observed for the HOMOs of 2a–e in the ES. However, the ality is weaker whereas that of the unsaturated cycle fused
electronic density of these groups, and even of the N–Me to the pyrazoline ring at C4–C5 is stronger, altering the ICT
fragment in 2e–k, significantly increased with an increase in direction in comparison with traditional and classic pyrazo-
the electron-withdrawing properties of the substituents at the line fluorophores with N1 and C3 aryl/hetaryl substituents
N1-bonded aromatic ring. Upon excitation, Me-DPPs 2a and 2d, (Scheme 3).
bearing electron-donating substituents, exhibited significant
Molecular Electrostatic Potential maps (MEP; Fig. S28, ESI†),
shifts in electron density from the aromatic and pyrazoline which reveal information regarding the dispersal of charges,16
Q
rings to the C O group and the N-atom of the pyrrol-2,5-dione show that the negative potential regions (red and yellow colors)
Q
ring. Hence, the aromatic rings of Me-DPPs 2a and 2d experienced are related to electronegative atoms (the oxygen atom of C
O
a significant reduction in their electron density, while the groups of ester and maleimide, and the nitrogen atom of the
electron density of the aromatic rings in 2e, 2f, and 2k was large. CN substituent in the GS), whereas the positive potential
Q
Thus, these two molecular electronic channels compete in terms regions (intense blue) are localized at the C atom of the C
O
of electron density. group, the C atoms of the pyrazoline ring, and the hydrogen
Ph-DPP 3e exhibited a different HOMO and LUMO distri- atoms of the N–CH3 or N–Ph groups of the pyrrol-2,5-dione.
bution trend in the GS and ES. The HOMOs located at the These positive and negative centers became more ponounced
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Fig. 7 Frontier molecular orbitals (FMOs) HOMO and LUMO in the ground and excited states for 2a, 2d–f, 2k, 3e, and 4b in CHCl3 (|isovalue(MO)| =
0.02 a.u.; |isovalue(r)| = 0.0004 a.u.).
upon photoexcitation and subsequent ES relaxation. Thus, the active sites, which was evidenced by an increase in the
these maps confirmed the strengthening of the reactivity of sensitivity of pyrazolines in the ES.
Scheme 3 Two competing electronic channels in bicyclic and tricyclic pyrazolines 2–4.
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Conclusions and outlook
A series of new pyrazolines were designed and synthesized via
1,3-dipolar cycloaddition of nitrile imines, generated from hydra-
zonoyl chlorides, with N-methyl- and N-phenylmaleimides and
norbornene. The reaction conditions were optimized, and micro-
wave irradiation was included to achieve an effective procedure
for the preparation of pyrazolines fused with N-phenylpyrroldione,
N-methylpyrroldione, and norbornane, bearing the desired sub-
stituents. The obtained compounds demonstrated significant
optical properties. Heterocyclic cores are not aromatic and have
a few unsaturated elements, which should cause a break in
conjugation; nevertheless, Me-DPPs, Ph-DPPs, and HMIs demon-
strated blue or green fluorescence with high QYs (up to 93%).
A large Stokes shift excludes energy loss due to reabsorption. The
obtained pyrazolines exhibited positive solvato(fluoro)chromism,
a specific behavior in protic solvents (alcohols and water), and
sensitivity to the environment. Thus, the optical properties of new
fluorescent pyrazolines are comparable to or exceed those of
widespread bi- and tri-aromatic pyrazolines.1 Moreover, the valuable
properties of these compounds are their intense green solid-state
emissions rendering them potential candidates for the design
and synthesis of novel solid-state light-emitting organic materials.
The simultaneous manifestation of high fluorescence in solutions
and in solid form is a rare phenomenon both for pyrazolines and
for other classes of organic fluorophores.1
The remarkable photophysical properties of Me-DPPs, Ph-DPPs,
and HMIs are the result of their specific electronic properties and
spatial structure, which depends on the structure of the central
non-saturated cycle. N-Methylpyrrol-2,5-dione, N-phenylpyrrol-
2,5-dione, and the norbornane ring are very active in the intra-
molecular charge transfer process and formed a new electronic
channel in comparison with the traditional bi- and tri-aromatic
fluorescent pyrazolines. The opportunity of carrying out various
chemical modifications of the obtained fluorophores opens a
route to the expansion of their applicability in various fields.
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Conflicts of interest
The authors declare no conflicts of interest.
7 J.-N. Zhu, W.-K. Wang, Z.-H. Jin, Q.-K. Wang and S.-Y. Zhao,
Org. Lett., 2019, 21, 5046.
Acknowledgements
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We thank RFBR for financially supporting this work through
the project no. 19-03-00720A. EB thanks Bingtuan Oasis Foreign
Expert fund. The Siberian Branch of the Russian Academy of
Sciences (SB RAS) Siberian Supercomputer Centre is gratefully
acknowledged for providing supercomputer facilities.
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