Design of High-Performance Pyridine/Quinoline Hydrazone Photoswitches

Article abstract of DOI:10.1021/acs.joc.1c01174

The design of P-type photoswitches with thermal stability of the metastable form of hundreds of years that would efficiently transform using excitation wavelengths above 350 nm remains a challenge in the field of photochromism. In this regard, we designed and synthesized an extended set of 13 pyridine/quinoline hydrazones and systematically investigated the structure-property relationships, defining their kinetic and photoswitching parameters. We show that the operational wavelengths of the pyridine hydrazone structural motif can be effectively shifted toward the visible region without simultaneous loss of their high thermal stability. Furthermore, we characterized the ground-state and excited-state potential energy surfaces with quantum-chemical calculations and ultrafast transient absorption spectroscopy, which allowed us to rationalize both the thermal and photochemical reaction mechanisms of the designed hydrazones. Whereas introducing an electron-withdrawing pyridyl moiety in benzoylpyridine hydrazones leads to thermal stabilities exceeding 200 years, extended π-conjugation in naphthoylquinoline hydrazones pushes the absorption maxima toward the visible spectral region. In either case, the compounds retain highly efficient photoswitching characteristics. Our findings open a route to the rational design of a new family of hydrazone-based P-type photoswitches with high application potential in photonics or photopharmacology.

Full text of DOI:10.1021/acs.joc.1c01174

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Article
Design of High-Performance Pyridine/Quinoline Hydrazone
Photoswitches
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Bernard Mravec, Simon Budzák,* Miroslav Medved’, Lukás F. Pasteka, Chavdar Slavov,
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̌
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Torben Saßmannshausen, Josef Wachtveitl, Jozef Kozísek, Lea Hegedusová, Juraj Filo, and Marek Cigán*
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ABSTRACT: The design of P-type photoswitches with thermal stability of the
metastable form of hundreds of years that would efficiently transform using
excitation wavelengths above 350 nm remains a challenge in the field of
photochromism. In this regard, we designed and synthesized an extended set of
13 pyridine/quinoline hydrazones and systematically investigated the
structure−property relationships, defining their kinetic and photoswitching
parameters. We show that the operational wavelengths of the pyridine
hydrazone structural motif can be effectively shifted toward the visible region
without simultaneous loss of their high thermal stability. Furthermore, we
characterized the ground-state and excited-state potential energy surfaces with
quantum-chemical calculations and ultrafast transient absorption spectroscopy,
which allowed us to rationalize both the thermal and photochemical reaction
mechanisms of the designed hydrazones. Whereas introducing an electron-
withdrawing pyridyl moiety in benzoylpyridine hydrazones leads to thermal stabilities exceeding 200 years, extended π-conjugation
in naphthoylquinoline hydrazones pushes the absorption maxima toward the visible spectral region. In either case, the compounds
retain highly efficient photoswitching characteristics. Our findings open a route to the rational design of a new family of hydrazone-
based P-type photoswitches with high application potential in photonics or photopharmacology.
motif by planarization of the structure resulted in an undesired
decrease in the photoswitch thermal stability (from hundreds
of years to approximately 20 days).21 Earlier, Hecht’s group
also prepared several P-type acylhydrazone photoswitches
containing pyridine subunit, although without quantitative
determination of the thermal half-lives.22 Although excellent
improvement in the absorption red shift of azoacenes as
configurational photoswitches to vis/NIR region has been
achieved by research groups of Herges and Woolley, their half-
lives usually do not exceed several hours or days.23−28 To the
best of our knowledge, the only exception is the DOM-azo dye
stable for months in neutral aqueous solutions.28 Very recently,
we proposed an alternative structural modification leading to
2-(benzoyl)pyridine hydrazone photochromes (including
compound 1 in Scheme 1) which mimic the photoswitching
characteristics of ketoester hydrazones exhibiting relatively
good thermal stability (up to 1.9 years) and absorption in the
UV region.29,30 We showed that introducing an electron-
INTRODUCTION
■
P-type photochromic compounds with the high thermal
stability of the thermodynamically less stable form have
received increasing attention from the scientific community as
they can be used as light-controlled molecular switches in a
wide range of applications in opto-(bio)electronics1−7 and
photopharmacology,8−12 including 3D visualization in volu-
metric displays13 and precise temporal and spatial control over
drug delivery.14 In recent years, Hecht15 and Fuchter16 showed
that the thermal isomerization half-lives of azoarenes, the most
widely used configurational photoswitches, can be increased up
to 2−3 years by functionalization of an azobenzene skeleton
with o-fluorine substituents or with an appropriate methyl
substitution pattern on arylazopyrazoles. A breakthrough in
this direction was achieved by Aprahamian and his co-workers,
who discovered that a new family of configurational P-type
photoswitches based on a hydrazone skeleton exhibits
extraordinary half-lives of hundreds up to thousands of
years.17,18 Contrary to parent photochemically locked E- and
Z-isomers of pyridine hydrazones/acylhydrazones introduced
by Aprahamian19 and Lehn,20 respectively, the replacement of
a pyridyl ring by a phenyl in Aprahamian’s ketoester
hydrazones led to excellent bistable photoswitching (Scheme
1). However, recent efforts to induce a red shift of the
absorption maxima of the core ketoester hydrazone structural
Received: May 20, 2021
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displayed in Scheme 2 instead of “rotor” and “stator” used in
previously published articles related to hydrazone photo-
switches, because the rotation of the N−N bond in the “stator”
part plays a key role in both the thermal and photochemical
isomerization of the studied hydrazones.
Scheme 1
Thermal E-to-Z Isomerization. Aprahamian’s research
group showed that EW groups (−CN, −NO2) in the para
position of the hydrazine phenyl ring of ketoester hydrazones
resulted in a 3−4 fold increase in thermal stability, whereas ED
groups (−OCH3, −NMe2) led to a rather unexpected 6 orders
of magnitude decrease in thermal half-lives.18 They hypothe-
sized that the acceleration of the E-to-Z thermal isomerization
results from the partial single-bond character of the CN
double bond due to the mesomeric (+M) effect of the ED
substituents changing the reaction mechanism from inversion
to rotation. However, only a qualitative explanation was
provided. The substitutional effect in the ketone part of the
molecule was found to be less pronounced.18,29 Although a
system with the ketone part containing an electron-donating
−NMe2 group proved to be thermally more stable compared
to that with electron-withdrawing −NO2, the difference in
thermal stability was rather small. The set of 13 hydrazones
presented in this work enables us to study the structure−
thermal stability relationships in detail.
To quantify the effect of the electronic changes induced by a
hydrazine aromatic ring in the 2-(p-nitrobenzoyl)pyridine
hydrazones 1−7, we constructed a Hammett plot31 using σp−
values32 that describe the stabilization of negative charge
through resonance (Figure 1; SI, Table S1). The rate of the
thermal back isomerization represented by the corresponding
rate constant kX decreases with the increasing σ−p value
(exception being the pentafluorophenyl substituent), in line
with the previous study.18 However, contrary to ketoester
hydrazones, the presence of a strong ED methoxy substituent
does not lead to the acceleration of the E-to-Z thermal
isomerization and thus to the hypothesized change of the
reaction mechanism from inversion to rotation of the imine
bond. The deviation of −C6F5 from the otherwise strongly
linear dependence can be explained by a decreased level of
conjugation with the hydrazine moiety caused by the partial
rotation of the aryl ring (∼20°) due to the steric repulsion
between the o-F and N lone pairs. Excluding the −C6F5
derivative from the analysis significantly improves the
correlation, thus enabling a confident prediction of the thermal
stability simply based on the σ−p values. Let us note that the
traditional Swain−Lupton analysis31−34 distinguishing between
the influence of inductive and mesomeric/resonance effects of
the hydrazine ring on the rate of the thermal isomerization is
not applicable in the present study (see discussion in the SI).
Our quantum-chemical calculations at the ωB97XD/def2-
TZVPP level35 revealed a rather complex three-step inversion-
rotation reaction mechanism of the thermal E-to-Z isomer-
ization of 2-(p-nitrobenzoyl)pyridine hydrazones. The reaction
path can be illustrated using molecule 7 as an example (Figure
2). The initial step is the CN bond inversion which is also
the rate-limiting step with the calculated activation energy
equal to 31.2 kcal/mol. The relaxation proceeds to a shallow
local minimum L1. Here, the energetically less expensive N−N
single bond rotation occurs with the barrier of 3.0 kcal/mol,
bringing the system to a fleeting local minimum L2. The last
step toward the global Z minimum requires a low-energy
rotation (barrier 0.1 kcal/mol) of the ketone pyridyl ring,
establishing an optimal configuration with a hydrogen bond.
withdrawing (EW) p-nitro group on the ketone phenyl ring of
2-(benzoyl)pyridine hydrazones leads to a significant improve-
ment of the photoswitch addressability, fatigue resistance, and
also mutual ratio of Z-to-E and E-to-Z photoisomerization
efficiency compared to an electron-donating (ED) p-
dimethylamino substituent.29
Here, we present 12 newly synthesized 2-(p-nitrobenzoyl)-
pyridine/2-(p-cyanobenzoyl)pyridine/2-(naphthoyl)qui-noline
hydrazone photoswitches (Scheme 2; SI, the Synthesis
section) designed to gain insight into the photoswitching
mechanism and reveal the underlying structure−property
relationships for this type of chromophores. To study these
relationships in detail, we employed both quantum-chemical
calculations and photochemical experiments including ultrafast
transient absorption spectroscopy. We show that extended π-
conjugation of the parent 2-(benzoyl)pyri-dine structural motif
by fused aromatic rings shifts the photoswitching to desired
longer wavelengths with sufficient thermal stability of several
years. A detailed understanding of the topology of the ground-
state (GS) and excited-state (ES) potential energy surfaces
(PES) opens a route to the design of new hydrazone-based P-
type photoswitches, with high application potential in both
optoelectronics and photopharmacology.
RESULTS AND DISCUSSION
■
We designed a group of eight 2-(p-nitrobenzoyl)pyridine
hydrazones 1−8 (Scheme 1) to investigate the substitutional
effects on the hydrazine ring on the thermal stability and the
photophysical characteristics of hydrazones. In addition, to
corroborate the role of an EW substituent in the para position
of the ketone phenyl ring, cyano derivatives 9 and 10 were also
synthesized and thoroughly characterized. Finally, three 2-
(naphthoyl)quinoline hydrazones 11−13 were designed to
pursue the possibility of shifting the photoactivity of the
photochromes to longer wavelengths.
For the sake of consistency with the mechanism (vide infra),
we will use terms “ketone” and “hydrazine” parts to refer to the
upper and lower moieties, respectively, of the skeleton
B
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Scheme 2
The experimentally determined Gibbs activation energy values
of the E-to-Z thermal isomerization (Table 1) agree well with
the calculated overall ΔG‡ values for the representative
hydrazones 1 and 7 (SI, Table S2). The negative slope
(sensitivity constant) of the Hammett plot in Figure 1
indicates that the reduced electron density on the hydrazone
NH nitrogen by the EW hydrazine aromatic ring hinders the
sp2/sp rehybridization of the neighboring hydrazone CN
nitrogen in the inversion transition state (TS) (Figure 3). The
molecular orbital (MO) analysis revealed that the activation
barrier of inversion is indeed predominantly related to an
increase of the orbital energy of the nitrogen lone pair (Figure
3B) by 42.8 and 43.5 kcal/mol for 1 and 7, respectively, which
is partially balanced by the stabilization of the highest occupied
MO (HOMO) (delocalized π-orbital) by −5.8 and −5.0 kcal/
mol, respectively (SI, Table S3 and Figure S104). Interestingly,
the EW character of the hydrazine moiety of 7 stabilizes the
lone pair orbital as well as the HOMO in both the E isomer
and the TS. However, the stabilization is more pronounced in
the E minimum, which results in a higher activation barrier for
Figure 1. Hammett plot; σ−p , Hammet constant; kX, rate constant of
E-to-Z thermal isomerization of hydrazones 1−7 with substituent X;
kH, rate constant of E-to-Z thermal isomerization of hydrazone 1. The
solid line represents a linear fit through all points; the dashed line
represents a linear fit excluding the −F5 outlier.
C
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Figure 2. Reaction path profile for thermal E-to-Z transformation of hydrazone 7 calculated at ωB97XD/def2-TZVPP level of theory (see Video
S2).
Table 1. Kinetic Data and Activation Parameters for the E-to-Z Thermal Isomerization of the Studied Hydrazone E-Isomers in
1
Toluene-d8 (T = 298.15 K; Determined from H NMR Experimental Data)
a
b
c
d
ΔH⧧
d
ΔS⧧
d
ΔG⧧
hydrazone
k
τ1/2
Ea
[s−1
]
[year]
[kcal/mol]
[kcal/mol]
[cal/(mol K)]
[kcal/mol]
(E)-1
(E)-2
(E)-3
(E)-4
(E)-5
(E)-6
(E)-7
(E)-8
(E)-9
(E)-10
(E)-11
(E)-12
(E)-13
1.09(31) × 10−7
8.21(110) × 10−8
9.95(49) × 10−9
7.73(20) × 10−9
3.26(75) × 10−9
1.33(36) × 10−9
1.09(22) × 10−10
7.78(84) × 10−10
2.48(61) × 10−8
7.97(168) × 10−11
1.18(36) × 10−7
3.38(62) × 10−9
5.95(34) × 10−8
0.20(11)
0.26(5)
27.64(15)
27.82(7)
29.07(14)
29.22(4)
29.72(12)
30.25(55)
31.73(13)
30.57(9)
28.52(21)
31.92(18)
27.70(19)
29.71(15)
28.00(23)
26.65(15)
27.12(9)
28.37(3)
28.52(9)
29.03(18)
29.56(19)
31.04(13)
30.03(16)
27.83(24)
31.23(14)
26.90(11)
29.01(12)
27.31(4)
−0.43(40)
−0.03(0)
0.23(1)
0.10(14)
−0.10(58)
−0.01(37)
−0.16(3)
0.15(8)
26.95(15)
27.12(9)
28.37(3)
28.52(9)
29.03(18)
29.56(19)
31.04(13)
29.88(7)
27.83(24)
31.23(14)
26.90(11)
29.01(12)
27.31(4)
2.21(12)
2.84(43)
6.72(39)
16.4(62)
200(50)
28.2(35)
0.89(29)
280(70)
0.17(9)
0.31(7)
−0.06(4)
−0.08(4)
0.37(5)
6.50(142)
0.37(2)
0.17(3)
a
Rate constant of E-to-Z isomerization determined by nonlinear fitting of experimental data (including back thermal Z-to-E isomerization).
b
c
Thermal stability of the thermodynamically less stable E-isomer (calculated from the experimentally determined rate constant k). Activation
d
barrier calculated using the Arrhenius equation. Thermodynamic activation parameters calculated using the Eyring equation.
the inversion and thus also higher thermal stability of 7
compared to 1.
photoswitch onto various surfaces or incorporate the photo-
switch into a biomolecule. Moreover, contrary to a more than
50-fold decrease in thermal stability of the parent hydrazone 1
in polar solvents,29 hydrazone 7 retains good thermal stability
also in a polar environment (∼35 years in acetonitrile-d3).
To demonstrate the effect of the 2-pyridyl hydrazine ring on
the thermal stability of benzoylpyridine hydrazones with p-
acceptor substituted ketone phenyl ring, we designed cyano
derivatives 9 and 10 (Scheme 2; Table 1). The incorporation
of the 2-pyridyl hydrazine ring instead of the phenyl leads to a
significant increase in the photoswitch thermal stability from
0.9 to 280 years in line with our previous findings on the
related hydrazones 1 and 7. However, in the case of the 2-
(naphthoyl)quinoline hydrazone 13, the analogous substitu-
tion unexpectedly reduces the thermal stability as compared to
the parent hydrazone 12, which exhibits a remarkable half-life
of 6.5 years, indicating that the electron distribution in the
thermally active central hydrazone skeleton of 13 linked to a
weak acceptor (quinoline), a stronger acceptor (2-pyridyl), and
The rotation as a possible pathway can be clearly ruled out
since the calculated activation energy is 12.4 and 12.3 kcal/mol
higher compared to inversion for hydrazones 1 and 7,
respectively (SI, Table S2). Note that the calculated activation
entropy for inversion and rotation has practically the same
value (SI, Table S2); therefore, the activation entropy cannot
be used to experimentally distinguish between the inversion
and rotation mechanisms of the thermal isomerization of
hydrazones.
Kinetic data (rate constants and thermal half-lives) and
other activation parameters for the studied hydrazones are
summarized in Table 1. Unambiguously, the half-life of the E-
to-Z thermal isomerization increases with increasing EW
character of the hydrazine ring (consider hydrazones 1−8).
The hydrazone photoswitch 7 with the pyridyl hydrazine ring
achieves an excellent thermal stability of 200 years. Due to the
number of commercially available 2-pyridyl hydrazines, this
skeleton could be further modified to immobilize the
D
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Figure 3. (A) The sp2/sp rehybridization of hydrazone CN nitrogen in the inversion transition state of E-to-Z thermal isomerization of studied
2-(p-nitrobenzoyl)pyridine hydrazones. (B) Change of lone pair orbital during the E-to-Z inversion reaction. The isosurface value is 0.05.
a
Table 2. Photoswitching Parameters of Hydrazones 113 Measured in Toluene (T = 298.15 K)
ϵ/λmax
/
Φ
PSS (E/Z)
hydrazone
E
Z
E → Z
Z → E
E → Z
Z → E
1
2
3
4
5
6
7
8
21200/338/
11000/351/
26400/310/
18400/332/
21300/341/
23900/388/
28400/322/
22000/384/
20400/353/
25600/338/
27100/369/
36000/370/
39000/361/
18700/406/
12000/423/
22400/367/
18500/394/
23900/400/
27500/417/
31000/387/
22100/429/
25700/391/
28400/373/
13200/427/
20600/432/
20600/407/
1.9(2)
1.2(2)
12.3(21)
8.7(11)
9.1(11)
1.6(5)
8.4(11)
0.3(1)
1.3(2)
3.6(4)
1.8(2)
6.8(4)
8.4(6)
0.3(1)
0.4(1)
0.8(3)
0.8(3)
1.4(1)
0.01(3)
1.9(4)
0.05(1)
0.4(1)
0.13(3)
2.0(2)
2.1(2)
1.1(4)
13:87
16:84
4:96
2:98
5:95
1:99
15:85
2:98
18:82
5:95
25:75
5:95
80:20
69:31
49:51
67:33
50:50
7:93
83:17
65:35
75:25
63:37
96:4
9
10
11
12
13
93:7
83:17
7:93
a
ϵ, molar absorption (extinction) coefficient (in dm3 mol−1cm−1); λmax, UV−vis absorption maximum (in nm); Φ, quantum yield of
photoisomerization (in %); PSS, photostationary state composition at the corresponding irradiation wavelength (in %; irradiation wavelength: PSS
(E → Z): 315 nm for 3, 7; 341 nm for 1, 2, 4, 5, 9, 10 and 370 nm for 6, 8, 11−13; PSS (Z → E): 370 nm for 3; 405 nm for 1, 4, 5, 7, 9, 10, 13 and
465 nm for 2, 6, 8, 11, 12).
a weak donor (2-naphthyl) differs from that of 7 which
contains three relatively strong electron acceptor groups.
The X-ray structure of the E-isomer of benzoylpyridine
hydrazone 7 (SI, Figures S105−S107 and Table S4) is
consistent with findings from quantum-chemical calculations:30
(a) the more stable rotamer of E-isomers exhibits the 180°
rotation of the ketone pyridine ring compared to the Z-isomer;
(b) the E-isomers are characterized by the approximately 60°
mutual rotation of the aromatic rings on the ketone part of the
molecule; with significant distortion of the ketone phenyl ring
compared to the rest of the molecule (details in SI, section
2.4). Furthermore, we hypothesize that the close crystal
packing due to intermolecular hydrogen bonds and slipped
stack π−π interactions (SI, Figures S106−S107) is the driving
force for rapid crystallization of the thermodynamically less
stable E-isomer from mother liquor containing both geometric
isomers under ultrasound activation (see SI, the Synthesis
section).
Photochemistry. The experimentally determined photo-
switching parameters (Table 2) allow us to further investigate
the structure−property trends of hydrazones 1−13. Interest-
ingly, the hydrazine pyridyl ring not only improves the thermal
stability but also increases the quantum yields (QYs) of both
photochemical isomerizations (cf. hydrazones 1 and 7; SI,
Figure S114). The observed moderate to good photo-
isomerization QYs depend on the solvent polarity, as discussed
later. Hydrazone 7 exhibited 50 photochemical cycles with
only a slight sign of photodegradation, or a competing
photochemical reaction pathway (Figure 4; SI, Figure S115),
thus demonstrating good photoswitching and high photosta-
E
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Z-to-E photoisomerizations (the nitro hydrazone 6 remains
locked in the Z isomer structure). However, the incorporation
of the nitro substituent to the chromophore structure often has
a dramatic effect on the overall photophysics of a molecule,
particularly due to the significant enhancement of the
intersystem crossing rate.36,37 Moreover, in calculations, we
also observed a low barrier (4 kcal/mol) for the excited-state
intramolecular proton transfer, which may be another factor
hindering the Z-to-E transformation of 6. Substitution of the
hydrazine phenyl ring with an 8-quinolinyl aromatic ring in
hydrazone 8 leads to a reduction of its Z-to-E photo-
isomerization efficiency, in contrast to analogous ketoester
hydrazones bearing a pyridyl ketone ring.17 Overall, the
observed E-to-Z QYs are comparable to those of ketoester
hydrazones17,18 and lower than those reported for pyridineacyl
hydrazones.22 Concerning the Z-to-E photoisomerization, our
QYs are lower than those of the ketoester hydrazones
possessing weaker intramolecular hydrogen bonding.18
Considering the absorption maxima λmax (Table 2), we
observed that naphthoylquinoline hydrazones 11−13 with
enhanced π-conjugation showed the desired shift toward
longer wavelengths while retaining a good isomer address-
ability. Moreover, these hydrazones exhibited higher Z-to-E
photoisomerization QYs compared to parent pyridine
hydrazone 1 and good to excellent PSS photoconversion.
The bathochromic shift of the absorption maxima is
particularly important for potential biological applications,
and also laser/LED sources are more potent in the UVA/Vis
region. Only recently, Aprahamian’s group achieved a similar
red shift of their core ketoester hydrazone structural motif by
coplanarization of the ketone phenyl ring; however, the
planarization in their isochromanone-like hydrazones resulted
in the undesired reduction of thermal stability from hundreds
Figure 4. Photoswitching cycles of the 2-(p-nitrobenzoyl)pyridine
hydrazone 7 in toluene during altered 315 and 405 nm LED
irradiation to photostationary states (starting from pure E-isomer).
tionary state (PSS) photoconversion (>80%) in both polar and
nonpolar solvents (Table 2; SI, Figures S122−S123).
Analogous phenyl/2-pyridyl substitution in hydrazones 9/10
and 12/13 has also a positive albeit less pronounced effect on
the E-to-Z photoisomerization QYs, while simultaneously
lowering the Z-to-E photoisomerization QYs.
Our results show that increasing the EW character of the
substituents on the hydrazine ring only leads to a slight
increase in the efficiency of the Z-to-E photoisomerization
(Table 2), whereas a steep increase of QYs can be observed in
the case of the back E-to-Z photoisomerization (SI, Figure
S114). One exception is the nitro hydrazone 6 with
significantly lower efficiency of both E-to-Z and particularly
Figure 5. Transient absorption data and corresponding evolution-associated difference spectra (EADS) of the E (A−D)- and the Z (E−H)-isomers
of hydrazone 7 measured in n-hexane (A, B, E, F) and acetonitrile (C, D, G, H) after ππ* excitation (320 and 387 nm for E and Z, respectively).
Negative absorption difference signals (light to dark blue) correspond to ground-state bleach (GSB) and stimulated emission (SE). Positive
absorption difference signals (yellow through red to black) correspond to excited-state (ESA), hot ground-state (GS), and product absorption. For
details on the pump−probe setup, see SI (section 3.5.1) and ref 38. For details on global target analysis, see the SI (section 3.5.2) and refs 39 and
40. See Figures S131−S134 for a comparison of the dynamics of 4 and 7.
F
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of years to days (∼20 days).21 In our case, the thermal stability
of naphthoylquinoline-based hydrazones ranges from 62 days
(in a sterically hindered E-isomer of 1-naphthyl derivative 11)
to 6.5 years in the case of 2-naphthyl derivative 12 (Table 1).
Particularly the 2-(naphthoyl)quinoline structural motif thus
opens the way to the important subgroup of hydrazone
photoswitches.
While a similar red shift can be observed for the nitro
hydrazone 6, the isomer addressability suffers significantly.
Interestingly, the cyano derivatives 9 and 10 also feature a
decrease in both the addressability and QYs compared to the
parent hydrazones 1 and 7.
To investigate the photochemistry of the presented 2-(p-
nitrobenzoyl)pyridine hydrazones and explain the differences
in the obtained quantum yields of both photochemical
isomerizations, we combined ultrafast transient absorption
spectroscopy and quantum-chemical calculations on the most
promising hydrazone photoswitch 7.
Ultrafast Photoconversion Dynamics. The kinetics of the
ultrafast E-to-Z and Z-to-E photoisomerizations of 7 after
excitation into the bright S1 (ππ*) state are remarkably
different in nonpolar (n-hexane) and polar (acetonitrile)
solvents (Figure 5) despite the fact that the corresponding
stationary absorption spectra are very similar (Figure S130).
The detailed analysis of the transient absorption data is
provided in the SI (section 3.5), while here we discuss our key
findings.
In the case of E-to-Z photoisomerization of 7 in n-hexane,
the transient absorption data below 1 ps is dominated by two
ESA signatures (ESA1 and ESA2) belonging to the same
initially excited S1 state and the instantaneous ground state
bleach (GSB) (Figure 5A). After ultrafast departure from the
Franck−Condon (FC) region (200 fs), the S1 state decays to
the GS with a lifetime of about 600 fs (Figure 5B, EADS S1,
S2, S3, see SI for a detailed discussion). The decay of the ES
leads to the formation of a very broad GS absorption signature
(350−475 nm) extending beyond the steady-state Z-isomer
absorption band on both the lower and the higher energy side
(Figure 5B, EADS S4). We assign this broad absorption to a
population of metastable GS Z conformers such as L1 and L2
shown in Figure 2. The pool of Z conformers cools down with
about 20 ps lifetime, as illustrated by the blue shift of the
absorption (Figure 5B, EADS S4 → S5), and finally relaxes
with a lifetime of about 700 ps to the dominant most stable Z
conformer (Figure 5B, EADS S5 → S6). The strong
nondecaying absorption difference signal composed of the E-
isomer GSB and the Z-isomer absorption is in line with the
high E-to-Z QY in n-hexane (16%; see Table S5).
The E-to-Z photoisomerization kinetics of 7 in acetonitrile
(Figure 5C) clearly differs from that in n-hexane. We observe a
single spectrally very broad ESA signature (labeled ESA3),
which undergoes a blue shift on the sub-ps time scale (Figure
5D, EADS S1 → S2). This is followed by a strongly distributed
ES decay, as indicated by the relatively broad lifetime
distribution centered at ∼10 ps (Figure S132H) and the two
similar EADS S1 and S2 (Figure 5D). The ES decay is
accompanied by a strong recovery of the GSB signal (<350
nm) and formation of a relatively weak, broad absorption band
in the 350−475 nm range (Figure 5D, EADS S5). The broad
absorption spectrum resembles the one observed in n-hexane,
which we assigned to a pool of Z conformers (Figure S135).
The decay of this pool to the thermodynamically stable Z-
isomer occurs with a 900 ps lifetime in acetonitrile (Figure 5D,
EADS S5 → S6). The significantly weaker Z-isomer product
absorption in acetonitrile is in agreement with the reduced E-
to-Z QY as compared to n-hexane (1.4%; see Table S5).
The transient absorption data from the Z-to-E photo-
isomerization in n-hexane bears some similarity to that of the
E-to-Z direction. At early times (<1 ps), we again observe two
ESA signatures (ESA1 and ESA2) in addition to the GSB
signal of the Z-isomer (385 nm). The ESA extends further to
the higher energy spectral range and is clearly visible below
350 nm. Similar spectral signatures were observed in the
ultrafast dynamics of ketoester hydrazones,41 albeit the ES
decay kinetics in those compounds was significantly slower
than what we observe here. The decay of the ES of (Z)-7
occurs with a 400 fs lifetime (Figure 5F, EADS S1) and is
associated with accumulation of hot GS signal (400−450 nm)
and significant recovery of the GSB signal (350−450 nm). The
cooling of the hot GS molecules continues on the ps time
scale. Further, we detect additional GS dynamics (∼500 ps,
>400 nm), which, based on our spectral analysis [see SI
(section 3.5 and Figure S135)], we assign to the relaxation of a
population of Z-isomer conformers (Figure 5F, EADS S5). At
the end of our detection time scale, we observe the
nondecaying GSB signal (<400 nm) corroborating the high
Z-to-E photoisomerization QY in n-hexane (9.4%; see Table
S5).
In acetonitrile, the Z-to-E photoisomerization is markedly
different (Figure 5G). After excitation, we observe the same
ESA1 and ESA2 signatures as in n-hexane (∼440 nm and ∼580
nm). However, these ESAs are very short-lived and decay with
a lifetime of about 100 fs (Figure 5H, EADS S1). Their decay
is accompanied by similarly ultrafast rise of a strongly red-
shifted stimulated emission (SE) signal (>580 nm) and a new
strong ESA signal (ESA3 at 500 nm) (Figure 5H, EADS S2).
Concomitantly, the newly formed SE signal undergoes a very
fast (500 fs) red shift (Figure 5H, EADS S2 → S3), while the
red edge of ESA3 undergoes a blue shift. The rise of a red-
shifted emitting state for the Z-isomer in acetonitrile (as
opposed to n-hexane) is also evident in the stationary
fluorescence spectra (Figure S136). A comparison of EADS
S1 for the experiments in n-hexane and acetonitrile (Figure
5F,H) reveals that in both solvents the initially excited S1
(ππ*) states have a similar character. This is also supported by
the relatively small difference in the stationary absorption
spectra in the two solvents (Figure S130). However, the rise of
a strongly red-shifted SE in acetonitrile is indicative of an
ultrafast charge redistribution leading to the formation of an
ES with charge-transfer (CT) character. The charge redis-
tribution occurs simultaneously with the onset of the
conformational changes that guide the molecule toward the
conical intersection with the GS. The CT state in acetonitrile is
further stabilized by solvent reorganization, which lowers the
energy of the ES (SE red shift with 600 fs lifetime). Similar to
the E-to-Z photoisomerization direction, the Z-isomer ES
decay in acetonitrile is significantly slowed down as compared
to n-hexane and occurs with a lifetime of ∼2.5 ps (Figure 5H,
EADS S3). Analogous to the experiments above, the ES decay
is followed by cooling of the hot GS molecules (Figure 5H,
EADS S4). The dynamics in acetonitrile ends with a nearly
complete recovery of the GSB signal (at ∼385 nm), which is in
agreement with the strongly reduced Z-to-E QY in this solvent
(2.2%; see Table S5).
Computational Insights into the Photochemistry. Focus-
ing on low-lying excited states and comparing different levels
G
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Figure 6. (A) Ground state and excited-state potential energy surfaces near the Z-isomer of the hydrazone 1. Calculated as relaxed scan in the S1
state at the ωB97XD/def2-SVPP level of theory in toluene. (B) Rigid scan of the potential energy surface in the vicinity of the MECI point.
Calculated at the SF-TD-BHHLYP/def2-SVPP level of theory.44,45
of theory, an overall agreement between TD-ωB97X-D, wave
function-based methods, and experiment was found, justifying
the choice of the TD-DFT method for the analysis of ES
potential energy surfaces far from the CI region. In particular,
the theoretical S0 → S1 excitation energy of the Z-isomer was
consistently red-shifted with respect to that of the E-isomer,
although both values tend to be blue-shifted compared to the
experiment by about 0.5 and 0.1 eV, respectively (SI, Tables
S6−S7). Importantly, the S1 and S2 (nπ*, dark) states in the Z-
isomer were found to be more separated (∼0.4−0.5 eV)
compared to the E-isomer (∼0.1−0.3 eV) (SI, Table S8 and
Figure S137).
The photoisomerization in both directions proceeds via an
excitation to the S1 (bright, ππ*) state followed by a rotation
around the NC bond through a minimal energy conical
intersection (MECI) point and further on the GS potential
energy surface toward the product (see Video S3). In all
benzoylpyridine hydrazones 1−10, the E-to-Z photoisomeriza-
tion is more efficient compared to the Z-to-E process. This can
be rationalized in terms of different topologies of the S1
potential energy surface of the E- and Z-isomers. While the
E-to-Z isomerization via NC rotation toward the MECI
point is barrierless, for the Z-to-E isomerization, the relaxation
via N−N rotation leads to a local minimum on the S1 surface
(metastable Z-I*) still being stabilized by a weak hydrogen
bond (Figure 6A). In this geometry, the energy separation
between S1 and GS is less than 1.2 eV (∼1000 nm), enabling
the radiationless deactivation to the GS in the Z arrangement.
This deactivation process constitutes a competitive non-
productive pathway lowering the Z-to-E quantum yield.
Recently, Wang et al.42 found the same torsional motion
responsible for the nonemissive behavior of different Z-
phenylhydrazone.
hydrazones 11−13 (Scheme 2). The replacement of the
ketone pyridyl with a less basic quinoline moiety was expected
to facilitate the Z-to-E photoisomerization, and indeed, both
the QYs and the PSS composition were improved (Table 2).
However, it should be noted that the basicity of quinoline
significantly increases upon the excitation, as was also
previously shown experimentally,43 and thus, the increase of
QYs should not be simply attributed to the lower GS basicity
of quinoline. In fact, unlike for pyridine acceptors, for (Z)-13,
we theoretically observed spontaneous excited-state intra-
molecular proton transfer (ESIPT) from the NH group to the
quinoline nitrogen. ESIPT leads to rehybridization of NNH
to NN followed by a rotation around NN and subsequent
barrierless deactivation of the ES. By the involvement of the
competitive nonradiative ESIPT pathway, the Z-to-E photo-
isomerization mechanism for naphthoylquinoline hydrazones
qualitatively differs from that for pyridyl-based derivatives.
Another aspect of the differences in the observed QYs is
hidden in the topology around the MECI point (Figure 6B).
Going from the excited-state E* through MECI, the trans-
formation back to the E-isomer in the GS is favored by the
slopes of the potential energy surface equally for both 1 and 7.
The potential energy slopes toward the Z-isomer, however,
show that the E-to-Z isomerization should be more favorable
for the photochrome 7 compared to 1 (Figure 6B, blue arrow).
This is again consistent with the observed QYs (Table 2; SI,
Figure S114). For the Z-to-E photoisomerization, the slopes of
the potential energy surfaces are virtually identical for 1 and 7,
and as mentioned before, the QYs are predominantly
influenced by the hydrogen bond strength in the metastable
Z-I* ES intermediate.
In the ultrafast experiments, a broad strongly red-shifted SE
signal was only observed for (Z)-7 in acetonitrile (Figure 5).
As a plausible SE source, we localized a very shallow minimum
on the S1 pathway between the FC region and Z-I*. The
barrier protecting the minimum is less than 1 kcal/mol but has
a clear physical explanation. The S1 dipole moment in the FC
geometry has a large value of 10.9 D and is further increased to
14.2 D in the minimum denoted as Z-SE. The subsequent
disruption of the H-bond and distortion of the hydrazine part
of the molecule is accompanied by a decrease of the dipole
moment to 11.6 D in Z-I*. Whereas these changes do not
The observed differences in Z-to-E QYs between 1 and 7
can be mainly attributed to different hydrogen bond strengths
in the ES. The hydrogen bond in (Z)-7-I* is longer (2.68 Å)
and thus weaker, compared to the shorter contact (2.62 Å)
found in (Z)-1-I*. In line with higher experimental QYs, the
weaker (Z)-7-I* hydrogen bond presents a smaller barrier for
Z-to-E photoisomerization.
The role of the intramolecular hydrogen bond was further
examined by introducing quinoline in naphthoylquinoline
H
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light. Infrared spectra were recorded on a Nicolet 6700 FT-IR
spectrometer (ATR technique). Commercially available reagents were
used without further purification. The synthesis of starting materials
was performed according to literature procedures or as specified
below. HRMS spectra of compounds 2, 4−6, 8, 10−13, 15−17, and
19−21 were measured on a Thermo Scientific Orbitrap Fusion
Tribrid mass spectrometer (Thermo Fisher Scientific, Waltham, MA,
USA) (orbital trap); equipped with a Dionex Ultimate 3000RS HPLC
pump and Dionex Ultimate 3000RS autosampler. HRMS of
compounds 3 and 9 was carried out on an Orbitrap Velos Pro
Thermo Scientific, in instrument method FTMS (Fourier trans-
formation) (orbital trap). Schemes of all prepared compounds,
reaction schemes, full characterization of known compounds, and
NMR spectra are shown in the Supporting Information.
Synthesis of Alcohols. (4-Nitrophenyl)(pyridin-2-yl)methanol
(14), 4-(hydroxy(pyridin-2-yl)methyl)benzonitrile (15), naphthalen-
1-yl(quinolin-2-yl)methanol (16), and naphthalen-2-yl(quinolin-2-
yl)methanol (17) were synthesized according to the previously
published method described in ref 29. A detailed description is shown
in the Supporting Information.
affect the formation of Z-I* in nonpolar solvents (toluene, n-
hexane), they become important in polar acetonitrile, slowing
down the relaxation of Z-FC to Z-I* and giving rise to the
observed SE signal (Figure S138).
The involvement of the S2 state in the E-to-Z isomerization
cannot be fully excluded, in particular for 7, in which the
separation between S1 and S2 is less than 0.2 eV (SI, Table S7).
In the trial ES molecular dynamics simulations, we observed
the state switching between S1 and S2. In addition, the MECI
between S1 and S2 was located in the vicinity of the GS
geometry. We calculated oscillator strengths between S1, S2,
and the next 30 excited states. Although such a calculation has
limitations, one clear result emerged: there were no transitions
with significant oscillator strength between S2 and the higher
excited states. This means that, even if S2 is involved in the
photochemical transformations, it cannot be directly observed
in the transient spectra (Figure 5). The modeled S1 transient
spectrum qualitatively follows the changes observed in the
ultrafast experiments, e.g., the observed double-peak feature
(SI, Figure S139) consistent with the ESA1/ESA2 signatures in
Figure 5. The impact of the S2 state population on QYs
remains debatable, but given that (i) the separation of S1 and
S2 increases with solvent polarity and a smaller QY was
experimentally observed in MeCN compared to toluene, and
(ii) the S1 and S2 separation in 1, which has smaller QY, is
larger than in 7, the S2 state could indeed act as a trap state
affecting the photoisomerization QYs.
Synthesis of Ketones. (4-Nitrophenyl)(pyridin-2-yl)methanone
(18), 4-picolinoylbenzonitrile (19), naphthalen-1-yl(quinolin-2-yl)-
methanone (20), and naphthalen-2-yl(quinolin-2-yl)methanone (21)
were synthesized according to the previously published method
described in ref 29. A detailed description is shown in the Supporting
Information.
Synthesis of Hydrazones. General Approach. Hydrazine (0,81
mml) was added to a stirred solution of ketone (0.81 mmol) and
AcOH (0.2 mL) in EtOH (8 mL) in one portion. The reaction
mixture was refluxed 5−18 h (depends on reactivity of ketone). The
reaction progress was monitored by TLC. After a specified time, the
reaction mixture was cooled to room temperature. Precipitate crystals
of hydrazones 1, 3, 4, 6, 7, 8, 9, and 10 (excluding hydrazones 11, 12,
13, and 14, which do not precipitate from the reaction mixture) were
filtered off from the reaction mixture. The filtrate (reaction mixture)
was then concentrated under reduced pressure and dissolved in
CHCl3 (25 mL). This organic phase was washed by distilled water (2
× 10 mL), and the organic layer was dried over anhydrous Na2SO4.
Then the solvent was removed by distillation under reduced pressure,
and the crude reaction mixture was analyzed by TLC. If TLC analysis
showed marks for products, the concentrated organic phase was
purified by flash chromatography (for chromatography conditions, see
the characterization of hydrazones below).
General Method for the Synthesis of Hydrazones 2 and 5.
Na2CO3 (0.81 mml) was added to a stirred solution of hydrazine
hydrochloride (0.81 mmol) in EtOH (8 mL), and the mixture was
stirred for 5 min. After that, ketone (0.81 mmol) and AcOH (0.2 mL)
were added, and the reaction mixture was refluxed 18 h (depends on
the reactivity of the ketone). The reaction mixture was next
concentrated by distillation under reduced pressure and dissolved in
CHCl3 (30 mL). The organic phase was washed by distilled water (2
× 15 mL), and the organic layer was dried over anhydrous Na2SO4.
Then the solvent was removed by distillation under reduced pressure,
and the crude reaction mixture was purified by flash chromatography
(for chromatography conditions, see the characterization of
hydrazones below).
CONCLUSIONS
■
We designed and synthesized an extended series of substitu-
tional derivatives of benzoylpyridine hydrazone photoswitches
exhibiting extremely high thermal stability of the thermody-
namically metastable isomer. The large variability of
substituents enabled us to draw structure−property relation-
ships for the kinetics of thermal back-isomerization as well as
for the photoswitching parameters of this type of chromo-
phores. Combining the quantum-chemical calculations and
ultrafast transient absorption spectroscopy measurements, the
photoswitching mechanism was elucidated, and the exper-
imentally observed structure−property relationships were
rationalized at the molecular level. The lead molecular skeleton
based on the commercially available pyridyl hydrazine ring
achieves an excellent thermal stability of 200 years and efficient
photochemistry. Such a photoswitch may easily be anchored
onto various surfaces or incorporated into biomolecules. The
newly designed 2-(naphthoyl)quinoline analogs of 2-
(benzoyl)pyridine hydrazones containing an extended π-
conjugated moiety were shown to operate at the desired
longer wavelengths, preserving the thermal stability of several
years of the parent systems, which makes this family of
photoswitches attractive for various applications including
opto(bio)electronics and photopharmacology.
Alternative Synthetic Procedure of (E)-Isomers for Hydrazones 1
and 7. Phenylhydrazine (0.1 mL) was added in one portion to a
solution of ketone (0.81 mmol) and AcOH (0.5 mL) in EtOH in an
active ultrasonic bath (25 W; 50 Hz) at room temperature. The
reaction mixture was then exposed to ultrasound waves for 20 min.
The temperature of the bath was maintained not to exceed 25 °C.
Sonification at room temperature thus leads to the precipitation of the
thermodynamically less stable E-isomer for hydrazone 1. The
precipitate was then filtered and washed with cold EtOH. Hydrazone
7 did not precipitate during the action of ultrasound waves, so the
crude reaction mixture was allowed to stand at room temperature for
3 h; precipitated crystals were filtered ((E)-7, 38% yield).
EXPERIMENTAL SECTION
■
1
General Methods. H and 13C NMR spectra were recorded at
1
600 or 300 MHz for H nuclei and 151 or 75 MHz for 13C nuclei.
Chemical shifts are reported in δ units, parts per million (ppm);
signals are referenced to TMS as an internal standard. Coupling
constants (J) are given in hertz (Hz), and the multiplicity is
abbreviated as s (singlet), d (doublet), dd (doublet of doublets), t
(triplet), qd (quartet of doublets), and m (multiplet). Reactions were
monitored by thin-layer chromatography (TLC) carried out on silica
plates (Merck silica gel 60 F-254), visualized by irradiation with UV
(E)-2-((4-Nitrophenyl)(2-phenylhydrazono)methyl)pyridine (1).29
(Z)-2-((4-Nitrophenyl)(2-phenylhydrazono)methyl)pyridine (1): iso-
I
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lated by gradient flash chromatography on silica (SiO2, hexanes/
EtOAc (2:1) to pure EtOAc), (Z)-1; red solid; mp = 150−152 °C;
1H NMR (600 MHz, DMSO-d6) δ 11.89 (s, 1H), 8.87 (ddd, J = 5.1
Hz, 1.7 Hz, 0.9 Hz, 1H), 8.25 (d, J = 8.8 Hz, 2H), 8.01 (ddd, J = 7.8
Hz, 7.8 Hz, 1.4 Hz, 1H), 7.76 (d, J = 8.8 Hz, 2H), 7.56 (ddd, J = 7.6
Hz, 4,9 Hz, 1.0 Hz, 1H), 7.46 (d, J = 7.9 Hz, 1H), 7.36−7.24 (m,
1H), 6.89 (ddd, J = 6.4 Hz, 6.4 Hz, 1.9 Hz, 1H) ppm; 13C{H} NMR
(151 MHz, DMSO-d6) δ 152.0, 149.9, 146.7, 145.4, 141.0, 138.3,
Hz, 2H), 7.65−7.53 (m, 5H), 7.47−7.42 (m, 4H), 7.30 (dd, J = 7.4
Hz, 4.9 Hz, 0.5H) ppm.
(Z)-2-((4-Nitrophenyl)(2-(4-(trifluoromethyl)phenyl)-
hydrazineylidene)methyl)pyridine (4): isolated by gradient flash
chromatography on silica (SiO2, hexanes:EtOAc (2:1) to pure
EtOAc); overall yield = 110 mg (35%); orange solid; 60 mg of
(Z)-4 mp = 140−142 °C; 1H NMR (600 MHz, CDCl3) δ 13.58 (bs,
1H); 8.82 (ddd, J = 5.0 Hz, 1.8 Hz, 0.9 Hz, 1H); 8.29 (d, J = 8.8 Hz,
2H); 7.82 (ddd; J = 7.98 Hz, 7,89 Hz, 1.8 Hz, 1H); 7.79 (d, J = 8.8
Hz, 2H); 7.55 (d, J = 8.5 Hz, 1H); 7.39 (ddd, J = 7.6 Hz, 4.9 Hz, 1.1
Hz; 1H); 7.35 (ddd, J = 8.12 Hz, 1.02 Hz, 1.02 Hz, 1H), 7.31 (d, J =
8.5 Hz, 1H) ppm; 13C{H} NMR (151 MHz, DMSO-d6) δ 151.8,
150.2, 147.9, 147.1, 144.8, 143.7, 140.0, 138.4, 131.7, 128.7, 126.9 (q,
137.2, 129.6, 128.5, 124.3, 124.1, 121.3, 120.2, 114.0 ppm; IR νmax
̃
3100 (w, NH), 3024 (w, CH), 2820 (w, CH), 1586 (m, C
N), 1564 (m, CC), 1506 (s, CC) 1336 (s, CC), 1240 (m,
CN), 1147 (s), 1107 (m), 855 (s, CH), 713 (s, CH) cm−1.
(E)-2-((2-(4-Methoxyphenyl)hydrazineylidene)(4-nitrophenyl)-
methyl)pyridine (2): isolated by filtration from the reaction mixture;
overall yield = 149 mg (43%); orange solid; (E)-2 mp = 171−173 °C;
1H NMR (600 MHz, CDCl3) δ 8.43 (d, J = 8.7 Hz, 2H), 8.44−842
J = 3.9 Hz), 125.5, 124.2, 120.9 (q, J = 31.7 Hz) 113.9 ppm; IR νmax
̃
2917 (w, NH), 2635 (w, CH), 1613 (m, CN), 1528 (m),
1503 (s), 1314 (s), 1101 (s), 1060 (s), 832 (s), 793 (s), 614 (s)
cm−1; HRMS (ESI) m/z for C19H13F3N4O+2 ([M + H]+) found
387.1063, calcd C19H13F3N4O+2 ([M + H]+) 387.1063.
(m, 1H), 8.22 (ddd, J = 8.1 Hz, 1.1 Hz, 1,1 Hz, 1H), 7.73 (ddd, J =
8.1 Hz, 8.0 Hz, 1.1 Hz, 1H), 7.59 (d, J = 8.7 Hz, 2H), 7.55 (bs, 1H),
7.16 (ddd, J = 8.1 Hz, 7.5 Hz, 1.1 Hz, 0H), 7.07 (d, J = 8.9 Hz, 2H),
6.87 (d, J = 8.9 Hz, 2H), 3.79 (s, 3H) ppm; 13C{H} NMR (151 MHz,
CDCl3) δ 153.1, 151.8, 146.2, 145.3, 136.6, 134.8, 133.7, 128.2, 122.3,
(E)-4-(2-((4-Nitrophenyl)(pyridin-2-yl)methylene)hydrazineyl)-
benzonitrile (5): isolated by flash chromatography on silica (SiO2,
hexanes/EtOAc (2:1); overall yield = 150 mg (54%); pale yellow
1
solid; (E)-5 mp = 239−241 °C; H NMR (300 MHz, DMSO-d6) δ
122.2, 119.9, 117.7, 112.0, 111.8, 53.1 ppm; IR νmax
̃
2959 (w, NH),
9.94 (s, 1H), 8.44−8.34 (m, 3H), 8.25 (d, J = 8.1 Hz, 1H), 7.89 (ddd,
J = 8.0 Hz, 7.9 Hz, 1.6 Hz, 1H), 7.67 (d, J = 5.3 Hz, 2H), 7.64 (d, J =
5.3 Hz, 2H), 7.42 (d, J = 8.8 Hz, 2H), 7.33 (ddd, J = 7.5 Hz, 4.8 Hz,
1.1 Hz, 1H) ppm;1H NMR (600 MHz, CDCl3) δ 8.46 (d, J = 8.6 Hz,
2H), 8.23 (d, J = 8.1 Hz, 1H), 7.86−7.74 (m, 2H), 7.58 (d, J = 8.6
Hz, 1H), 7.56 (d, J = 8.7 Hz, 1H), 7.25−7.23 (m, 1H), 7.16 (d, J =
8.7 Hz, 1H) ppm; 13C{H} NMR (151 MHz, CDCl3) δ 153.8, 148.0,
147.4, 145.7, 143.9, 137.2, 135.4, 132.8, 129.5, 123.7, 122.3, 119.7,
2903 (w, CH), 1590 (w, CH), 1556 (m, CN), 1508 (s), 1465
(s, CC) 1426 (s, CC), 1224 (m, CN), 1030 (s), 997 (m), 831
(s, CH), 782 (s, CH), 703 (m) cm−1; HRMS (ESI) m/z calcd
for C19H16N4O+3 ([M + H]+) found 349.1294, calcd C19H16N4O+3 ([M
+ H]+) 349.1295. Elemental analysis calcd for C17H13N5O2: C, 74.43;
H, 5.14; N, 20.42%. Found: C, 74.52; H, 5.29; N, 20.33%.
(Z)-2-((4-Nitrophenyl)-(2-(perfluorophenyl)hydrazineylidene)-
methyl)pyridine (3): isolated by filtration; overall yield = 200 mg
118.5, 112.5, 102.7 ppm; IR νmax
̃
3080 (w, NH), 2213 (m, CN),
1
(61%); yellow solid (Z)-3 mp = 200−202 °C; H NMR (600 MHz,
1569 (m, CN), 1508 (s), 1349 (s), 1243 (m), 1132 (s) 1104 (s),
857 (s), 792 (s), 542 (s) cm−1; HRMS (ESI) m/z for C19H13N5O2+
([M + H]+) found 344.1141, calcd C19H13N5O+2 ([M + H]+)
344.1142.
DMSO-d6) δ 13.03 (bs, 1H); 8.85 (ddd, J = 4.9 Hz, 1.7 Hz, 0.8 Hz,
1H); 8.28 (d, J = 8.9 Hz, 2H); 8.03 (ddd; J = 7.9 Hz, 7.84 Hz, 1.8 Hz,
1H); 7.75 (d, J = 8.9 Hz, 2H); 7.59 (ddd, J = 7.6 Hz, 4.9 Hz, 1.0 Hz,
1H); 7.42 (d, J = 8.0 Hz; 1H) ppm; 1H NMR (600 MHz, CDCl3) δ
13.55 (s, 1H), 8.80 (d, J = 4.6 Hz, 1H), 8.27 (d, J = 8.8 Hz, 2H), 7.85
(ddd, J = 7.9 Hz, 7.8 Hz, 1.6 Hz, 1H), 7.77 (d, J = 8.8 Hz, 2H), 7.42
(dd, J = 7.2 Hz, 5.2 Hz, 1H), 7.36 (d, J = 8.1 Hz, 1H) ppm; 13C{H}
NMR (151 MHz, CDCl3) δ 152.2, 148.0, 147.5, 144.4, 139.6, 138.3
(ddd, J = 248 Hz, 14.1, 3.7 Hz), 137.4, 135.7 (ddd, J = 248, 14, 3.7
Hz), 129.4, 124.7, 123.9, 123.7, 120.4 (dd, J= 9.4, 2.9, 1.7,) ppm; 19F
NMR (564 MHz, CDCl3) δ −156.42 (dddd, J = 20.7 Hz, 4.2 Hz, 4.2
Hz, 2.3 Hz, 2F), − 163.41 (ddd, J = 21.2 Hz, 21.2 Hz, 5 Hz, 2F)
−166.72 (dddd, J = 21.84 HZ, 21.84 Hz, 4.18 Hz, 4.18 Hz, 1F) ppm;
2-((4-Nitrophenyl)-(2-phenylhydrazono)methyl)pyridine (6): iso-
lated by filtration of precipitated crystals from the reaction mixture;
1
overall yield = 60%, mixture of isomers H NMR, mixture of isomers
([E/Z]/[3:1] ratio) (600 MHz, DMSO-d6) δ 11.98 (s, 1H, Z-
isomer), 10.18 (s, 1H, E-isomer), 8.87 (ddd; J = 4.9 Hz, 1.8 Hz, 1 Hz;
1H, Z-isomer), 8.40−8.36 (m, 3H for E-isomer), 8.25−8.24 (m, 2H,
Z-isomer, overlap with 8.25 signal), 8.25 (d, J = 7.6 Hz, 1H, E-
isomer), 8.18−8.12 (m, 2H, Z-isomer); 8.14 (d, J = 9.2 Hz, 2H, E-
isomer), 8.03 (ddd, J = 7.81 Hz, 7.77 Hz, 1.8 Hz, 1H, Z-isomer), 7.89
(ddd, J = 9.4 Hz, 7.9 Hz, 1.7 Hz, 1H, E-isomer); 7.76 (d, J = 8.9 Hz,
2H, Z-isomer), 7.64 (d, J = 8.7 Hz, 2H, E-isomer), 7,62−7.58 (m, 1H,
Z-isomer), 7,50−7,42 (m, 2H for E-isomer, 3H for Z-isomer), 8.34
(ddd, J = 7.5, 4.9, 1.2 Hz, 1H, E-isomer) ppm; 13C{H} NMR (151
MHz, DMSO-d6) δ 155.5, 151.5, 150.9, 150.4, 149.0, 148.2, 147.4,
146.2, 144.3, 142.5, 140.4, 140.3, 140.1, 138.5, 137.2, 131.7, 128.9,
126.2, 126.1, 125.7, 125.0, 124.3, 124.2, 123.8, 121.0, 113.6, 113.4
ppm.
(E)-2-((4-Nitrophenyl)(2-(4-nitrophenyl)hydrazineylidene)-
methyl)pyridine (6): isolated by flash chromatography on silica
(eluent = hexanes/EtOAc (3:1)), (E)-6; pale yellow solid; mp =
243−245 °C; 1H NMR (600 MHz, DMSO-d6) δ 10.19 (s, 1H),
8.50−8.33 (m, 3H), 8.28 (ddd, J = 8.1 Hz, 1.0 Hz, 1.0 Hz, 1H), 8.16
(d, J = 9.2 Hz, 2H), 7.91 (ddd, J = 8.1 Hz, 7.5 Hz, 1.9 Hz, 1H), 7.67
(d, J = 8.7 Hz, 2H), 7.46 (d, J = 9.2 Hz, 2H), 7.36 (ddd, J = 7.5 Hz,
4.7 Hz, 1.0 Hz, 1H) ppm; 13C{H} NMR (151 MHz, DMSO-d6) δ
155.6, 150.9, 149.1, 148.2, 146.2, 140.3, 140.1, 137.2, 131.7, 126.2,
IR νmax 1739 (w), 1574 (w), 1508 (m), 1342 (m), 1216 (m), 1138
̃
(m), 974 (s), 861 (s), 796 (s), 697 (s), 566 (m) cm−1; HRMS (ESI)
m/z for C18H9F5N4O2+ ([M + H]+) found 409.0717, calcd
C18H9F5N4O+2 ([M + H]+) 409.0718.
(E)-2-((4-Nitrophenyl)(2-(4-(trifluoromethyl)phenyl)-
hydrazineylidene)methyl)pyridine (4): isolated by gradient flash
chromatography on silica (SiO2, hexanes/EtOAc (2:1) to pure
EtOAc); overall yield = 110 mg (35%); 50 mg of orange solid; (E)-4
1
mp = 166−169 °C; H NMR (600 MHz, CDCl3) δ 8.47−8.44 (m,
3H); 8.24 (ddd, J = 8.1 Hz, 1.1 Hz, 1.1 Hz, 2H); 7.82 (ddd; J = 7.92
Hz, 7.91 Hz, 1.7 Hz, 1H); 7.74 (bs, 1H); 7.23 (ddd, J = 7.4 Hz, 4.9
Hz, 1.2 Hz, 2H); 7.18 (d, J = 8.5 Hz, 1H); 7.39 (ddd, J = 7.6 Hz, 4.9
Hz, 1.1 Hz; 1H); 7.35 (ddd, J = 8.12 Hz, 1.02 Hz, 1.02 Hz, 1H), 7.31
(d, J = 8.5 Hz, 1H) ppm; 13C{H} NMR (151 MHz, DMSO-d6) δ
155.9, 148.9, 148.4, 147.9, 148.1, 143.6, 140.7, 137.1, 126.7 (q, J = 3.9
Hz), 124.7, 124.3, 123.4, 120.6, 120.4 (q, J = 31.7 Hz), 113.7 ppm; IR
νmax
̃
3309 (w, NH), 2955 (w, CH), 2920 (w, CH), 1613 (m,
124.3, 123.9, 121.0, 113.5 ppm; IR νmax
̃
2920 (w, NH), 2851 (w),
CN), 1597 (m, CC), 1512 (m, CC) 1317 (s, CC), 1257
(s,), 1099 (s), 1061 (s), 835 (s), 780 (s), 701 (s) cm−1; HRMS (ESI)
m/z for C19H13F3N4O2+ ([M + H]+) found 387.1063, calcd
C19H13F3N4O2+ ([M + H]+) 387.1063. 1H NMR (600 MHz,
DMSO-d6) mixture of isomers Z/E (2:1) δ 11.85 (s, 1H), 9.80 (s,
0.5H), 8.86 (d, J = 4.3 Hz, 1H), 8.36 (d, J = 8.3 Hz, 1.5H), 8.24 (d, J
= 8.7 Hz, 2H), 8.22 (d, J = 8.1 Hz, 0.5H), 8.01 (ddd, J = 7.8, 7.8 Hz,
1.8 Hz, 1H), 7.86 (ddd, J = 7.9, 7.9 Hz, 1.7 Hz, 0.5H), 7.75 (d, J = 8.6
1735 (w, NC), 1591 (m), 1560 (m) 1257 (s, CC), 1089 (s),
1013 (s), 789 (s), 748 (m), 695 (m), 490 (m) cm−1; HRMS (ESI)
m/z for C18H13N5O4+ ([M + H]+) found 364.1039, calcd C18H13N5O4+
([M + H]+) 364.1040.
(E)-2-((4-Nitrophenyl)(2-(pyridin-2-yl)hydrazineylidene)methyl)-
pyridine (7): isolated by filtration of reaction mixture (ultrasound
condition); overall yield = 100 mg (38%); pale yellow solid (E)-7 mp
= 199−203 °C; 1H NMR (600 MHz, DMSO-d6) δ 9.47 (s, 1H), 8.39
J
https://doi.org/10.1021/acs.joc.1c01174
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(ddd, J = 4.8 Hz, 1.8 Hz, 0.9 Hz, 1H), 8.35 (d, J = 8.8 Hz, 2H), 8.24
(d, J = 8.2 Hz, 1H), 8.10 (ddd, J = 4.9 Hz, 1.8 Hz, 0.8 Hz, 1H), 7.87
(ddd, J = 8.0 Hz, 7.5 Hz, 1.8 Hz, 1H), 7.72 (ddd, J = 8.2 Hz, 7.3 Hz,
1.9 Hz, 1H), 7.62 (d, J = 8.8 Hz, 2H), 7.47 (d, J = 8.2 Hz, 1H), 7.31
(ddd, J = 7.4 Hz, 4.8 Hz, 1.1 Hz, 1H), 6.86 (ddd, J = 7.2 Hz, 4.9 Hz,
1.0 Hz, 1H) ppm; 13C{H} NMR (151 MHz, DMSO-d6) δ 156.8,
155.8, 148.9, 148.1, 148.1, 143.9, 140.3, 138.7, 137.1, 131.5, 124.4,
(E)-4-(Pyridin-2-yl(2-(pyridin-2-yl)hydrazineylidene)methyl)-
benzonitrile (10): isolated by filtration from reaction mixture; overall
1
yield = 71%; colorless solid; (E)-10 mp = 200−203 °C; H NMR
(600 MHz, CDCl3) δ 8.40 (ddd, J = 4.9 Hz, 1.8 Hz, 0.9 Hz, 1H), 8.13
(d, J = 8.1 Hz, 2H), 8.04 (ddd, J = 5.7 Hz, 1.7 Hz, 0.8 Hz, 1H), 7.69
(ddd, J = 8.1 Hz, 7.5 Hz, 1.8 Hz, 1H), 7.63−7.58 (m, 1H), 7.44 (d, J
= 8.2 Hz, 3H), 7.17−7.12 (m, 1H), 6.78 (ddd, J = 7.2 Hz, 4.9 Hz, 1.0
Hz, 1H) ppm; 13C{H} NMR (151 MHz, CDCl3) δ 155.8, 155.3,
147.8, 143.8, 138.3, 136.8, 136.3, 133.2, 133.3, 123.0, 120.6, 118.3,
123.5, 120.6, 117.0, 107.9 ppm; IR νmax
̃
2999 (w, NH), 2930 (w,
CH), 2088 (w, CH), 1594 (m, CN), 1566 (s, CC), 1508
(s, CC) 1421 (s, CC), 1295 (m, CN), 1128 (s), 1084 (m),
847 (m, CH), 771 (s, CH), 704 (s), 679 (s) cm−1. Elemental
analysis calcd for C17H13N5O2: C, 74.43; H, 5.14; N 20.42%. Found:
C, 74.48; H, 5.18; N, 20.32%.
117.0, 113.3, 107.7 ppm; IR νmax 3158 (w), 2228 (w), 1595 (m),
̃
1561 (m), 1502 (m) 1422 (s), 1295 (s), 1130 (s), 988 (s), 843 (s),
769 (s), 516 (m); HRMS (ESI) m/z for C18H13N+5 ([M + H]+) found
300.1244, calcd C18H13N+5 ([M + H]+) 300.1244.
(Z)-2-((4-Nitrophenyl)(2-(pyridin-2-yl)hydrazineylidene)methyl)-
pyridine (7): isolated by flash chromatography on silica (eluent:
EtOAc); overall yield = 178 mg (66%); orange solid, (Z)-7 mp 133−
136 °C; 1H NMR (600 MHz, DMSO-d6) δ 12.86 (bs, 1H), 8.91(ddd,
J = 4.9 Hz, 1.8 Hz, 0.8 Hz, 1H), 8.29 (d, J = 8.7 Hz, 2H), 8.20 (ddd; J
= 4.9 Hz, 1.8 Hz, 0.8 Hz, 1H), 8.02 (ddd, J = 7.9 Hz, 7.8 Hz, 1.8 Hz,
1H), 7.86 (d, J = 8.7 Hz, 2H), 7.76 (ddd, J = 8.8 Hz, 7.3 Hz, 1.8 Hz,
1H), 7.59 (ddd, J = 7.5 Hz, 4.9 Hz, 0.8 Hz, 1H), 7.47−7.41 (m, 2H);
6.94 (ddd, J = 7.4 Hz, 4.9 Hz, 0.9 Hz, 1H) ppm; 13C{H} NMR (151
MHz, DMSO-d6) δ 156.5, 151.9, 149.3, 148.4, 147.3, 145.0, 138.9,
(Z)-4-(Pyridin-2-yl(2-(pyridin-2-yl)hydrazineylidene)methyl)-
benzonitrile (10): isolated by flash chromatography on silica (SiO2,
eluent: EtOAc); overall yield = 71%; yellow solid; (Z)-10 mp = 123−
126 °C; 1H NMR (600 MHz, CDCl3) δ 12.93 (s, 1H), 8.78 (ddd, J =
4.9 Hz, 1.8 Hz, 0.9 Hz, 1H), 8.15 (ddd, J = 4.9 Hz, 1.8 Hz, 0.8 Hz,
1H), 7.74−7.71 (m, 1H), 7.68−7.61 (m, 4H), 7.59−7.54 (m, 1H),
7.41 (d, J = 8.4 Hz, 1H), 7.30 (ddd, J = 7.6 Hz, 4.9 Hz, 1.1 Hz, 1H),
7.24 (d, J = 8.0 Hz, 1H), 6.77 (ddd, J = 7.2 Hz, 4.9 Hz, 1.0 Hz, 1H)
ppm; 13C{H} NMR (151 MHz, CDCl3) δ 156.7, 148.8, 148.0, 143.3,
138.1, 137.7, 137.8, 132.1, 129.2, 124.6, 123.4, 118.9, 116.8, 111.4,
138.5, 138.4, 129.7, 125.5, 124.7, 124.1, 117.5, 107.5 ppm; IR νmax
̃
107.7 ppm; IR νmax 3100 (w), 2225 (m), 1586 (m), 1566 (m), 1491
̃
2922 (w, NH), 2294 (w), 1591 (w), 1566 (m), 1506 (s), 1486 (s)
1422 (s), 1298 (s), 1086 (s), 1 (m), 847 (s, CH), 733 (s, CH),
577 (s) cm−1. Elemental analysis calcd for C17H13N5O2: C, 74.43; H,
5.14; N, 20.42%. Found: C, 74.52; H, 5.29; N, 20.33%.
(s), 1432 (s), 1301 (s) 1245 (m), 1134 (s), 848 (s), 792 (s), 729 (s),
592 (s) cm−1; HRMS (ESI) m/z for C18H13N5+ ([M + H]+) found
300.1244, calcd C18H13N+5 ([M + H]+) 300.1244.
(E)-2-(Naphthalen-1-yl(2-phenylhydrazineylidene)methyl)-
quinoline (11): isolated by flash chromatography on silica (SiO2,
eluent = hexanes/EtOAc (5:1)); overall yield = 65% (260 mg);
yellow solid; (E)-11 mp = 140−143 °C; 1H NMR (300 MHz,
DMSO-d6) δ 9.19 (s, 1H), 8.56 (d, J = 8.8 Hz, 1H), 8.35 (d, J = 8.8
Hz, 1H), 8.07 (dd, J = 12.5 Hz, 8.3 Hz, 2H), 7.91 (d, J = 8.2 Hz, 1H),
7.70 (dd, J = 8.1 Hz, 7.1 Hz, 1H), 7.57−7.42 (m, 6H), 7.36 (ddd, J =
8.2 Hz, 6.6 Hz, 1.3 Hz, 1H), 7.31 (dd, J = 8.7 Hz, 1.2 Hz, 2H), 7.21
(dd, J = 7.9 Hz, 7.9 Hz, 2H), 6.81 (dd, J = 7.2 Hz, 7.2 Hz, 1H) ppm;
13C{H} NMR (151 MHz, DMSO-d6) δ 157.5, 147.4, 145.2, 142.4,
(E)-8-(2-((4-Nitrophenyl)(pyridin-2-yl)methylene)hydrazineyl)-
quinoline (8): isolated by filtration; overall yield = 180 mg (50%);
yellow solid; (E)-8 mp = 178−181 °C; 1H NMR (300 MHz, DMSO-
d6) δ 9.73 (bs, 1H); 8.62 (dd, J = 4.1 Hz, 1.3 Hz, 1H); 8.47 (d, J = 8.6
Hz, 2H); 8.42 (ddd; J = 5.2 Hz, 1.3 Hz, 0.5 Hz, 1H); 8.36 (d, J = 8.2
Hz, 1H); 8.31 (dd, J = 8.4 Hz, 1.7 Hz, 1H); 7.91 (ddd, J = 7.67 Hz,
7.53 Hz, 1.82 Hz; 1H); 7.85−7.77 (m, 1H), 7.78 (d, J = 8.6 Hz, 2H);
7.59 (dd, J = 7.9 Hz, 7.9 Hz, 1H); 7.50 (dd, J = 8.4 Hz, 4.2 Hz, 1H);
7.44 (d, J = 8.0 Hz, 1H); 7.34 (ddd, J = 7.3 Hz, 4.5 Hz, 0.9 Hz, 1H)
ppm; 13C{H} NMR (151 MHz, DMSO-d6) δ 155.6, 149.0, 148.9,
148.2, 144.4, 139.8, 139.0, 137.2, 136.7, 136.4, 131.5, 128.5, 128.0,
136.2, 134.1, 131.3, 131.2, 129.8, 129.4, 129.4, 129.2, 129.1, 128.6,
128.1, 127.4, 126.9, 126.6, 126.4, 125.4, 120.7, 118.9, 114.0 ppm; IR
124.8, 123.5, 122.6, 120.7, 118.9, 109.0 ppm; IR νmax
̃
3100 (w, N
νmax 3287 (w), 3069 (w), 1738 (w), 1598 (m), 1550 (s,), 1504 (s),
̃
H), 1739 (w, CH), 1577 (w, CC), 1557 (m, CN), 1517 (s,
CC), 1428 (s, CC) 1316 (s, CC), 1204 (m, CN), 1134
(m), 1107 (m), 994 (m, CH), 858 (m), 757 (s, CH), 792 (m),
702 (m) cm−1; HRMS (ESI) m/z for C21H15N5O+2 ([M + H]+) found
370.1297, calcd C21H15N5O+2 ([M + H]+) 370.1299.
1422 (s), 1308 (s), 1244 (s), 1147 (m), 836 (s), 788 (s), 754 (s), 697
(s) cm−1; HRMS (ESI) m/z for C26H19N+3 ([M + H]+) found
374.1651, calcd C26H19N+3 ([M + H]+) 374.1652.
(Z)-2-(Naphthalen-2-yl(2-phenylhydrazineylidene)methyl)-
quinoline (12): isolated by flash chromatography on silica (SiO2,
eluent = hexanes/EtOAc (5:1)); overall yield = 70% (280 mg);
yellow solid; (Z)-12 mp = 156−158 °C; 1H NMR (300 MHz,
CDCl3) δ 12.71 (s, 1H), 8.50 (d, J = 8.6 Hz, 1H), 8.28 (d, J = 8.4 Hz,
1H), 8.07 (d, J = 7.8 Hz, 1H), 8.03−7.81 (m, 6H), 7.71 (dd, J = 7.4
Hz, 7.4 Hz, 1H), 7.58−7.44 (m, 4H), 7.31 (m, 4H), 6.87 (dd, J = 7.0
Hz, 7.0 Hz, 1H) ppm; 13C{H} NMR (151 MHz, CDCl3) δ 153.7,
147.1, 144.9, 144.9, 138.8, 138.0, 136.5, 133.3, 133.0, 130.8, 129.7,
129.4, 128.6, 128.4, 128.4, 128.0, 127.9, 127.5, 127.2, 126.9, 126.7,
(E)-4-((2-Phenylhydrazineylidene)(pyridin-2-yl)methyl)-
benzonitrile (9): isolated by filtration from reaction mixture; overall
1
yield = 76%; yellow solid (E)-9 mp = 180−183 °C; H NMR (600
MHz, CDCl3) δ 8.37 (d, J = 4.9 Hz, 1H), 8.16 (d, J = 8.1 Hz, 1H),
7.81 (d, J = 8.2 Hz, 1H), 7.67 (ddd, J = 8.0 Hz, 8.0 Hz, 1.7 Hz, 1H),
7.56 (s, 1H), 7.45 (d, J = 8.2 Hz, 1H), 7.22 (dd, J = 7.9 Hz, 7.9 Hz,
2H), 7.11 (dd, 7.5 Hz, 4.9 1H), 7.05 (d, J = 7.9 Hz, 2H), 6.86 (dd, J =
7.3 Hz, 7.3, 1H) ppm; 13C{H} NMR (151 MHz, CDCl3) δ 155.7,
148.7, 143.7, 141.8, 137.0, 136.2, 133.1, 130.4, 129.4, 122.5, 121.3,
126.1, 122.9, 120.9, 113.8 ppm; IR νmax 3053 (w), 1744 (w), 1594 (w,
̃
120.4, 118.4, 113.3, 113.1 ppm; IR νmax 3053 (w), 2226 (w), 1599
̃
m, CN), 1497 (m), 1343 (s), 1343 (m), 1303 (m), 1232 (s), 1104
(m), 1068 (m), 872 (s), 830 (s), 796 (m), 759 (s), 688 (s); HRMS
(ESI) m/z for C26H19N+3 ([M + H]+) found 374.1652, calcd
C26H19N+3 ([M + H]+) 374.1652.
(m), 1561 (m), 1428 (s) 1241 (s), 1129 (m), 996 (m), 898 (m), 761
(s) cm−1; HRMS (ESI) m/z for C19H14N+4 ([M + H]+) found
299.1291, calcd C19H14N+4 ([M + H]+) 299.1291.
(Z)-4-((2-Phenylhydrazineylidene)(pyridin-2-yl)methyl)-
benzonitrile (9): isolated by flash chromatography on silica (SiO2,
eluent: CH2Cl2); overall yield = 76%; orange solid, (Z)-9 mp = 110−
(Z)-2-(Naphthale-2-yl(2-(pyridin-2-yl)hydrazineylidene)methyl)-
quinoline (13): isolated by flash chromatography on silica (SiO2,
eluent = hexanes/EtOAc (3:1)); overall yield = 70% (280 mg);
yellow solid; (Z)-13 mp = 145−148 °C; 1H NMR (300 MHz,
CDCl3) δ 13.23 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.14 (dd, J = 9.6
Hz, 7.1 Hz, 2H), 7.93−7.68 (m, 7H), 7.63−7.49 (m, 3H), 7.48−7.34
(m, 3H), 6.75 (dd, J = 7.8 Hz, 3.0 Hz, 1H) ppm; 13C{H} NMR (151
MHz, CDCl3) δ 157.3, 153.4, 148.1, 147.1, 140.2, 138.1, 137.0, 136.5,
133.4, 133.4, 130.5, 129.9, 128.5, 128.2, 127.9, 127.8, 127.7, 127.3,
1
112 °C; H NMR (600 MHz, CDCl3) δ 13.19 (s, 1H), 8.71 (d, J =
4.5 Hz, 1H), 7.71 (ddd, J = 7.8 Hz, 7.8 Hz, 1.6 1H), 7.66 (d, J = 8.2
Hz, 2H), 7.62 (d, J = 8.2 Hz, 2H), 7.30−7.21 (m, 4H), 7.19−7.18 (m,
2H), 6.87 (dd, J = 7.1 Hz, 7.1 Hz, 1H) ppm; 13C{H} NMR (151
MHz, CDCl3) δ 152.9, 148.0, 144.1, 143.8, 137.0, 135.0, 132.1, 129.3,
129.2, 124.3, 122.8, 121.3, 119.1, 113.7, 110.8 ppm; IR νmax 3000 (w),
̃
2222 (w), 1597 (m), 1521 (m), 11497 (m), 1238 (m), 1134 (s), 852
(m), 791 (m), 753 (m) cm−1; HRMS (ESI) m/z for C19H14N+4 ([M +
H]+) found 299.1291, calcd C19H14N4+ ([M + H]+) 299.1291.
126.6, 126.5, 122.8, 116.5, 108.1 ppm; IR νmax
1492 (s), 1301 (m), 1137 (s), 1108 (s), 1085 (s), 826 (s), 770 (s),
̃
2912 (w), 1589 (m),
K
https://doi.org/10.1021/acs.joc.1c01174
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
726 (s), 657 (s) cm−1; HRMS (ESI) m/z for C25H18N+4 ([M + H]+)
̌
̌
Jozef Kozísek − Department of Physical Chemistry, Faculty of
Chemical and Food Technology, Slovak University of
Technology, 81237 Bratislava, Slovakia
found 375.1608, calcd C25H18N+4 ([M + H]+) 375.1604.
ASSOCIATED CONTENT
* Supporting Information
Lea Hegedusová − Department of Organic Chemistry, Faculty
̈
■
sı
of Natural Sciences, Comenius University, 84215 Bratislava,
Slovakia
The following files are available free of charge. The Supporting
Information is available free of charge at https://pubs.acs.org/
doi/10.1021/acs.joc.1c01174.
Juraj Filo − Department of Organic Chemistry, Faculty of
Natural Sciences, Comenius University, 84215 Bratislava,
Slovakia; orcid.org/0000-0002-3995-2565
Synthesis, NMR spectra, thermal kinetics study, and
photochemical study (PDF)
Video S1 (MP4)
Video S2 (MP4)
Video S3 (MP4)
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c01174
Notes
The authors declare no competing financial interest.
Archive containing XYZ coordinates of all calculated
structures (ZIP)
FAIR data, including the primary NMR FID files, for
compounds 1−21 (ZIP)
ACKNOWLEDGMENTS
■
Financial support of the Slovak Research and Development
Agency (APVV-20-0098 and APVV-19-0087) and the
Scientific Grant Agency of the Slovak Republic (VEGA 1/
0562/20, 1/0777/19, and 1/0718/19) is acknowledged. C.S.
and J.W. acknowledge Deutsche Forschungsgemeinschaft (WA
1850/4-3). This project has received funding from the
European Union’s Horizon 2020 research and innovation
program under grant agreement no. 810701 (LAMatCU).
B.M., J.F., L.H., and M.C. acknowledge the support from the
Operation Program of Integrated Infrastructure for the project:
Advancing University Capacity and Competence in Research,
Development and Innovation, ITMS2014+: 313021 × 329,
cofinanced by the European Regional Development Fund. This
research used resources of a High-Performance Computing
Center of the Matej Bel University in Banska Bystrica using the
HPC infrastructure acquired in projects ITMS 26230120002
and 26210120002 (Slovak infrastructure for high-performance
computing) supported by the Research and Development
Operational Program funded by the ERDF.
Accession Codes
CCDC 2070765 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Authors
■
̌
Simon Budzák − Department of Chemistry, Faculty of Natural
Sciences, Matej Bel University, 97400 Banská Bystrica,
Slovakia; orcid.org/0000-0003-4811-8342;
Email: simon.budzak@umb.sk
̌
Marek Cigán − Department of Organic Chemistry, Faculty of
Natural Sciences, Comenius University, 84215 Bratislava,
Slovakia; orcid.org/0000-0001-7734-626X;
Email: marek.cigan@uniba.sk
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Authors
Bernard Mravec − Department of Organic Chemistry, Faculty
of Natural Sciences, Comenius University, 84215 Bratislava,
Slovakia
Miroslav Medved’ − Department of Chemistry, Faculty of
Natural Sciences, Matej Bel University, 97400 Banská
Bystrica, Slovakia; Regional Centre of Advanced Technologies
and Materials, Czech Advanced Technology and Research
́
Institute (CATRIN), Palacky University Olomouc, 77900
Olomouc, Czech Republic
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Lukás F. Pasteka − Department of Physical and Theoretical
Chemistry, Faculty of Natural Sciences, Comenius University,
84215 Bratislava, Slovakia; orcid.org/0000-0002-0617-
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Chavdar Slavov − Institute of Physical and Theoretical
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Goethe University, 60438 Frankfurt am Main, Germany
Torben Saßmannshausen − Institute of Physical and
Theoretical Chemistry, Faculty of Biochemistry, Chemistry,
Pharmacy, Goethe University, 60438 Frankfurt am Main,
Germany
Josef Wachtveitl − Institute of Physical and Theoretical
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