Synthesis, electrochemical and spectroscopic characterization of selected quinolinecarbaldehydes and their Schiff base derivatives

Article abstract of DOI:10.3390/molecules25092053

A new approach to the synthesis of selected quinolinecarbaldehydes with carbonyl groups located at C5 and/or in C7 positions is presented in this paper in conjunction with spectroscopic characterization of the products. The classical Reimer-Tiemann, Vilsmeier-Haack and Duff aldehyde synthesis methods were compared due to their importance. Computational studies were carried out to explain the preferred selectivity of the presented formylation transformations. A carbene insertion reaction based on Reimer-Tiemann methodology is presented for making 7-bromo-8-hydroxyquinoline-5-carbaldehyde. Additionally, Duff and Vilsmeier-Haack reactions were used in the double formylation of quinoline derivatives and their analogues benzo[h]quinolin-10-ol, 8-hydroxy-2-methylquinoline-5,7-dicarbaldehyde, 8-(dimethylamino) quinoline-5,7-dicarbaldehyde and 10-hydroxybenzo[h]quinoline-7,9-dicarbaldehyde. Four Schiff base derivatives of 2,6-diisopropylbenzenamine were prepared from selected quinoline-5-carbaldehydes and quinoline-7-carbaldehyde by an efficient synthesis protocol. Their properties have been characterized by a combination of several techniques: MS, HRMS, GC-MS, FTIR, electronic absorption spectroscopy and multinuclear NMR. The electrochemical properties of 8-hydroxy-quinoline-5-carbaldehyde, 6-(dimethylamino)quinoline-5-carbaldehyde and its methylated derivative were investigated, and a strong correlation between the chemical structure and obtained reduction and oxidation potentials was found. The presence of a methyl group facilitates oxidation. In contrast, the reduction potential of methylated compounds was more negative comparing to non-methylated structure. Calculations of frontier molecular orbitals supported the finding. The structures of 8-hydroxy-2-methylquinoline-5,7-dicarbaldehyde and four Schiff bases were determined by single-crystal X-ray diffraction measurements.

Full text of DOI:10.3390/molecules25092053

molecules
Article
Synthesis, Electrochemical and Spectroscopic
Characterization of Selected Quinolinecarbaldehydes
and Their Schiff Base Derivatives
1
2
3,4
1,
Jakub Wantulok , Marcin Szala
, Andrea Quinto , Jacek E. Nycz * ,
Stefania Giannarelli 4 , Romana Sokolová * , Maria Ksia˛ z˙ ek and Joachim Kusz 5
3,
5
1
Institute of Chemistry, University of Silesia in Katowice, ul. Szkolna 9, PL-40007 Katowice, Poland;
jakub.wantulok1@gmail.com
Institute of Polymer and Dye Technology, Lodz University of Technology, Stefanowskiego 12/16,
2
9
0-924 Lodz, Poland; marcin.szala@p.lodz.pl
3
4
5
J. Heyrovsk Institute of Physical Chemistry of the Czech Academy of Sciences, Dolejškova 3, 18223 Prague,
Czech Republic; andrea.quinto28@libero.it
Department of Chemistry and Industrial Chemistry, University of Pisa, Via Moruzzi 13, 56124 Pisa, Italy;
stefania.giannarelli@unipi.it
Silesian Center for Education and Interdisciplinary Research, University of Silesia, Institute of Physics,
ý
7
5 Pułku Piechoty 1a, 41-500 Chorzów, Poland; maria.ksiazek@us.edu.pl (M.K.);
joachim.kusz@us.edu.pl (J.K.)
*
Correspondence: jacek.nycz@us.edu.pl (J.E.N.); sokolova@jh-inst.cas.cz (R.S.);
Tel.: +48-32-359-1446 (J.E.N.); +420-26605-3525 (R.S.)
ꢀ
ꢁꢂꢀꢃꢄꢅꢆꢇ
Academic Editors: Sven Mangelinckx and Jacek Nycz
Received: 7 April 2020; Accepted: 26 April 2020; Published: 28 April 2020
ꢀ
ꢁꢂꢃꢄꢅꢆ
Abstract: A new approach to the synthesis of selected quinolinecarbaldehydes with carbonyl
groups located at C5 and/or in C7 positions is presented in this paper in conjunction with
spectroscopic characterization of the products. The classical Reimer-Tiemann, Vilsmeier-Haack and
Duff aldehyde synthesis methods were compared due to their importance. Computational studies
were carried out to explain the preferred selectivity of the presented formylation transformations.
A carbene insertion reaction based on Reimer-Tiemann methodology is presented for making
7
-bromo-8-hydroxyquinoline-5-carbaldehyde. Additionally, Duff and Vilsmeier-Haack reactions were
used in the double formylation of quinoline derivatives and their analogues benzo[h]quinolin-10-ol,
-hydroxy-2-methylquinoline-5,7-dicarbaldehyde, 8-(dimethylamino) quinoline-5,7-dicarbaldehyde
8
and 10-hydroxybenzo[h]quinoline-7,9-dicarbaldehyde. Four Schiff base derivatives of 2,6-
diisopropylbenzenamine were prepared from selected quinoline-5-carbaldehydes and quinoline-7-
carbaldehyde by an efficient synthesis protocol. Their properties have been characterized by a
combination of several techniques: MS, HRMS, GC-MS, FTIR, electronic absorption spectroscopy
and multinuclear NMR. The electrochemical properties of 8-hydroxy-quinoline-5-carbaldehyde,
6-(dimethylamino)quinoline-5-carbaldehyde and its methylated derivative were investigated,
and a strong correlation between the chemical structure and obtained reduction and oxidation
potentials was found. The presence of a methyl group facilitates oxidation. In contrast,
the reduction potential of methylated compounds was more negative comparing to non-methylated
structure. Calculations of frontier molecular orbitals supported the finding. The structures
of 8-hydroxy-2-methylquinoline-5,7-dicarbaldehyde and four Schiff bases were determined by
single-crystal X-ray diffraction measurements.
Keywords: vilsmeier-haack; reimer-tiemann; duff; aldehyde; aldazine; heterocyclic; cyclic voltammetry
Molecules 2020, 25, 2053; doi:10.3390/molecules25092053
www.mdpi.com/journal/molecules

Molecules 2020, 25, 2053
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1
. Introduction
Aldehydes are a class of compounds of great interest from the synthetic, theoretical and application
point of view, which can be transformed into a wide range of structural frameworks through application
of a variety of reactions. Various synthetic protocols have been developed including the classical
Reimer-Tiemann, Vilsmeier-Haack and Duff reactions, which are well known as versatile synthetic
tools for the formylation of electron-rich aromatics. However, literature data has often inaccurately
reported the position of the newly formed carbonyl group(s). Formylation of 8-hydroxyquinoline
under Reimer-Tiemann condition can go to both the C5 (38%) and C7 (10%) positions [
hand Gonz lez-Vera et al. reported the formylation of 2-methylquinolin-8-ol leading exclusively to
-hydroxy-2-methylquinoline-5-carbaldehyde in 64% yield [ ] similarly to Chen et al. who formylated
-hydroxyquinoline and obtained 8-hydroxyquinoline-5-carbaldehyde in 19.3% yield [ ]. Ding. et al.
].
1]. On the other
á
8
8
2
3
only obtained 8-hydroxy-7-quinaldinecarbaldehyde, a product formylated in a different position [
4
In this study we propose the transformation of some newly formed aldehydes into sterically hindered
crystalline Schiff bases.
2
. Results and Discussion
In the current study, the formylation reactions of selected quinoline derivatives at R,
R1 and R2
positions were the focus. These type compounds have not been fully exploited and may be served as
interesting building blocks for synthetic purposes.
2
.1. Synthesis and Structural Characterization
The synthesis of certain quinolinecarbaldehydes
2 were based on closely related Reimer-Tiemann
(R-T), Vilsmeier-Haack (V-H) and Duff (D) formylation reactions (Scheme 1).
Scheme 1. Formylation of 8-hydroxyquinoline (1c).
The aim of the current study is to explore selected synthetic routes, and formylated a series of
derivatives of 8-hydroxyquinoline have been prepared as shown in Schemes 2 and 3.

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Compound
R
Method Yield (%)
1
R2
2
a
b
b
c
R
H
H
H
H
HC=O R-T V-H
D
C8-OH
C8-OH
C8-OH
C8-OH
C8-OH
C8-OH
C6-NMe
C6-NMe
C6-OH
C8-OH
C8-NMe
C8-NMe
H
C5-Cl
C5-Cl
C5-CH
C5-CH
C7-Br
H
C5
C7
C7
C7
C7
C5
C5
C5
C5
10.1
7.2
-
8.0
-
<1
-
-
-
-
-
-
-
-
-
-
70.0
3
3
c
H
-
-
75.0
-
-
-
28.1
14.9
-
d
e
f
g
h
i
CH
CH
H
H
CH
H
3
3
2
2
38.6
73.8
-
-
<1
<1
H
H
H
H
3
C5, C7
C5
C5, C7
2
2
j
H
H
-
-
Scheme 2. Synthesis of quinolinecarbaldehydes 2.
Scheme 3. Duff type formylation of benzo[h]quinolin-10-ol (1j).
A lone pair of electrons on the hydroxyl oxygen or dimethylamino nitrogen at R1 position on
phenyl ring are conjugated with the system of quinolone, which increases the electron density
at both the C5 and C7 positions on the phenyl ring in all studied quinolines [ ]. Both positions
are suitable for substitution reaction via a S Ar mechanism [ ]. The formulation mechanisms of
π
5,6
6
E
Reimer-Tiemann, Vilsmeier-Haack and Duff reactions are similar to each other and to other electrophilic
aromatic substitution reactions. However the initial electrophile reactions are different among these
methods. In the case of the Reimer-Tiemann reaction, it is in situ Fisher type electrophilic carbene
generated (in most cases dichlorocarbene), for Vilsmeier-Haack it is Vilsmeier’s reagent, and for Duff
reaction it has been proposed an initial aminoalkylation followed by dehydrogenation (generated
from HMTA) [7] (Scheme 1). It is important to notice that all these electophiles possess different
electrophilicity. The attack by an electrophile generates a Wheland intermediate cation (or arenium
ion) followed by the loss of a proton to restore the aromaticity (Scheme 1). Analogically to our recent
2
results [
carbon than at C7 (
6
] the substitution at C5 (
R
) position would have a great stabilizing effect on the adjacent
1
R
) position in quinoline constitution (Scheme 2). Several authors announced the
similar structure of 8-hydroxyquinoline with newly formed group at C5 position on phenol ring in the
same type of reactions.
The Vilsmeier’s reagent and electrophilic dichlorocarbene possess electron-withdrawing (EW)
ability. One consequence of the existence of EW groups in electrophiles is a decreased electron

Molecules 2020, 25, 2053
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density in the newly generated Wheland cations (Scheme 1), which deactivate the N,N-dimethylaniline
or phenol) ring for the next substitution. A dimethylamino moiety, like a hydroxyl group in the C8
(
position, increases the electron density at both the C5 and C7 sites, which makes double formylation
leading to 8-(dimethylamino)quinoline-5,7-dicarbaldehyde (2j, yield < 1%) possible in the case of
the Vilsmeier-Haack transformation (Figure 1). In contrast the Duff cyclic electrophile, after the
generation of a Wheland cation (Scheme 1), does not deactivate the phenol ring for the next substitution,
which allows the double formylation to generate 8-hydroxy-2-methylquinoline-5,7-dicarbaldehyde
(
2h) and 10-hydroxybenzo[h]quinoline-7,9-dicarbaldehyde (2j) in good yields. Zhang et al. have
claimed an 82% isolated yield of 8-hydroxyquinoline-5,7-dicarbaldehyde in a similar procedure [ ].
The absence of a methyl group in the C2 ( ) position could have a positive influence to increase the
yield of products. substituents can undergo further side reactions. Additionally, in both reaction
8
R
R
mixtures we identified monoformylated products. It is, at first sight, somewhat surprising that the
formylation of 6-hydroxyquinoline (1h) using the Duff method led exclusively to a monoaldehyde
with the newly formed carbonyl group in the C5 position (Scheme 2) [9]. The differences in reactivity
between 8-hydroxyquinoline (1c), 6-hydroxyquinoline (1h), N,N-dimethylquinolin-6-amine (1e) and
N,N-dimethylquinolin-8-amine (1i) could be explained by the differences in electrostatic potentials of
the atoms participating in the formylation transformation (Figure 1). The formal charge of atoms in
the C5-H and C7-H bonds were calculated based on electrostatic potentials, which are given in units
of electrons and are shown in Figure 1. A positive charge indicates a deficiency of electrons on an
atom and a negative charge, an excess of electrons. The electrostatic potential for a hydrogen atom
is marked in gray (positive value) and for carbon in black (negative value). The differences in their
potential are marked in blue. The higher difference in atomic charges between C5 and C7 positions
show the preference of selected monoformylations products with novel carbonyl group only in C5
position. The difference of electrostatic potential of C5-H bond 0.556 for 1e suggests the easier cleavage
of H atom from C5, compared to C7-H with electrostatic potential difference 0.318 (for 1h, similarly).
The smaller differences in the atomic charges difference of atoms in bonds C5-H and C7-H suggest the
possibility of double formylation and the presence of both regioisomers with new carbonyl group in
C5 and C7 positions (Figure 1).
Figure 1. The electrostatic potentials for the selected quinolines.

Molecules 2020, 25, 2053
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The two transition states presented in Scheme 1 would be similar in terms of structure between
intermediate and . If we accept Scheme 1 as a model for the formylation, a substitution at the C5
A
B
position would have a greater stabilizing effect on the adjacent carbon than that at the C7 position in the
quinoline scaffold. This discrepancy between the electron density and preferred position of substitution
was explained by Olah, as the weaker electrophiles (or with less nucleophilicity of aromatics) showed
higher substrate selectivity. The transition states are of a “late” nature resembling the intermediates
and the ortho/para ratio decreases, with para-substitution becoming predominant [10]. Formylation
of 2-methylquinolin-8-ol (1b) and 8-hydroxyquinoline (1c) in all the presented methodologies led
to complicated reaction mixtures. However, it was noticed that dialdehydes 2h and 2k were easy
to isolate because of their low solubility in most solvents. In this case isolation relies on filtration,
followed by washing with chloroform and methanol. In the reaction mixtures of the Reimer-Tiemann
and Vilsmeier-Haack transformations the presence of two possible regioisomers with newly formed
1
carbonyl groups at the C5 and C7 positions was detected by H-NMR and GC-MS techniques for
the first time (Schemes 1 and 2, Figure S1e in the Supplementary Data). For the Reimer-Tiemann
reaction both regioisomers were obtained in a 35:28 ratio (2a:2a’) (Figure S1e). These regioisomers
with trC5-C=O = 6.024 min. and trC7-C=O = 6.360 min. possess similar mass spectral patterns, and the
+
same m/z (Figure S1c,d, Supplementary Data) and display characteristic m/z = 173 M molecular ions,
and m/z = 144 and 116 fragment ions. All the presented quinolinecarbaldehydes
2 show a preferential
fragmentation with the initial loss of a carbonyl group, followed by the loss of C=O of the phenolic
ring and further decomposition (Supplementary Data).
1
The H-NMR spectra of molecules
2
showed distinctive H-1 signals from the HC=O proton of
carbonyl group located at the C5 and C7 positions (or C7 and C9 in the case of heterocycle 2k) with
1
chemical shifts of ca. 10.1 and 10.5 ppm, respectively. The analysis of the trends in H-NMR chemical
shifts revealed that the presence of intramolecular hydrogen bonds between neighboring carbonyl
group located at C7 position and hydroxyl or dimethylamino group at C8 position increased the
deshielding effect, resulting in the low-field signals. The chemical shifts in DMSO solution were moved
to downfield (larger
δ; 10.5 ppm), while the higher field signal (10.1 ppm) is for a carbonyl group
located at C5 position, where intramolecular hydrogen bonds were absent. In contrast, the proton of
1
3
HC=N group for molecules
3
(Scheme 5) are located at C5 (8.51 ppm) and C7 (8.38 ppm). The C-NMR
1
spectra showed an opposite effect to the H-NMR ones. The carbon atoms of the carbonyl groups
located at the C5 and C7 positions showed distinctive signals with 13C chemical shifts of ca. 192 and
1
88 ppm, respectively. The chemical shifts were moved to downfield (larger δ) for a non-protonated
carbonyl group at the C5 position with resonance signals at ca. 192 ppm. The deprotonation of the
carbonyl group makes the carbon atom more positive, which moves the chemical shift downfield
(larger δ). In the constitution of molecules 3 (Scheme 5), the carbon atoms of the HC=N group located
at C5 (163 ppm) and C7 (165 ppm) positions showed opposite effects, which can be explained in the
frame of electron density.
The IR spectra of molecules
C7 [or C7 and C9 in the case of heterocycle 2k] positions in the range 1663–1686
2
showed distinctive carbonyl signals for the groups located at C5 and
C=O. The analysis of
ν
the trends suggests that carbonyl group located at C5 possess rather smaller values than that at C7.
In the case of 2j, for the first time we were able to detect two signals from both carbonyl groups located
at C5 and C7 (Figure 2).
Comparison of the double formylated products 2h and 2j revealed that the presence of
intramolecular and intermolecular hydrogen bonds between the carbonyls and hydroxyl groups
has the impact on overlapping signals (Figure 2). This could explain why compound 2j possesses a
dimethylamino group at the C8 position instead of a hydroxyl group and has two separate signals at
1
678 νC=O and 1661 νC=O.

Molecules 2020, 25, 2053
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Figure 2. IR spectra of 2j (left) and 2i (right).
Comparing the yields of heterocycles 2 presented in Scheme 2, the Duff methodology appeared
superior to the Reimer-Tiemann and Vilsmeier-Haack reactions for formylation of phenol derivatives,
and gave a lower yield for N,N-dimethylaniline derivatives. More attention has been paid to
the Reimer-Tiemann reaction and the generation of Fisher type electrophilic carbenes to show its
potentially rich chemistry. One of the characteristic reactions of the carbene moiety is insertion reactions.
DeAngelis et al. reacted an initially generated dichlorocarbene with indoles to form a ring expansion or
a dichloromethyl-substituted product [11]. We applied the Reimer-Tiemann methodology the first time
to show carbene insertion into a C-Br bond to produce 7-bromo-8-hydroxyquinoline-5-carbaldehyde
(
7
2d). Under standard Reimer-Tiemann conditions, molecule 1a and other reagents were irradiated by a
5 W lamp to initiate the reactions in the presence of carbenes. Although relatively higher yields was
observed during irradiation, unfortunately, the yield of this preliminary reaction is not satisfactory yet
Scheme 1).
The Reimer-Tiemann and Vilsmeier-Haack reactions occur at a basic environment in contrast
to the Duff protocol which occurs in an acidic medium. A negative impact on the synthesis of
quinolinecarbaldehydes was noticed during final stage when a basic environment was applied in
(
2
hydrolysis reactions. This is not surprising, because aromatic aldehydes can disproportionate in strongly
basic solutions according to well-known Cannizzaro reaction mechanism, especially during long time
exposure. To avoid this possible reactivity in a basic environment the reaction time was reduced to three
hours for the Reimer-Tiemann protocol. The next limitation or potentially a further development for both
Reimer-Tiemann and Vilsmeier-Haack reactivity could be linked to the presence of a methyl group at the
R
position in the quinoline skeleton. The newly formed aldehydes can be reacted under base-catalyzed
condensation reactions, such as the Perkin transformation, leading to styryl type compounds.
Like Nandhakumar et al. we isolated the product from the reaction between the electrophilic Vilsmeier’s
reagent generated in situ and the methyl group located at the
R position in the quinoline ring [12].
After hydrolysis a moderate yield of (Z)-8-hydroxy-2-(2-hydroxyvinyl)quinoline-5-carbaldehyde (2l
)
was isolated (Scheme 4). This product adopts a Z conformation due to the presence of a pseudo-ring
which is stabilized by intramolecular hydrogen bonding (Scheme 4). The small JH,H coupling constants
proved the presence of Z conformer over E, due to the Karplus equation. The molecule 2l is similarly to
other quinolinecarbaldehydes
group (Figure S6d).
2 which had preferential fragmentation with the initial loss of carbonyl

Molecules 2020, 25, 2053
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Scheme 4. Synthesis of (Z)-8-hydroxy-2-(2-hydroxyvinyl)quinoline-5-carbaldehyde (2l). Intramolecular
hydrogen-bonding interactions influencing the conformation of molecule 2l.
As presented above, the reactivity between the electrophilic Vilsmeier’s reagent and the methyl
group located at the C2 position in the quinoline moiety could be explained by the electron density
at the C2 ( 0.714 1b) position. It is important to pay attention to the hazards of the Vilsmeier-Haack
−
reaction due to its thermal instability of the Vilsmeier intermediate, especially for multigram scale
reactions [13]. A further limitation of the Vilsmeier-Haack reaction was described by Morimura et al.
Derivatives of 8-hydroxyquinoline like other phenol-type reagents possess hydroxyl nucleophilic
substituents that can react with POCl and the Vilsmeier’s reagent leading to aryl formates [14].
3
The Duff reaction occurring in acidic environments also has some limitations. The low yield
obtained in the formylation of amine derivatives is a result of the acidic environment used during
the procedure. The nitrogen atoms of molecule 1e are protonated in an acidic environment and
consequently form a dimethylaminium group in situ at the C6 position which does not activate the
benzene ring to facilitate aromatic electrophilic substitution, and consequently does not undergo the
Duff reaction. In this case the starting material was recovered (Scheme 1).
Some selected quinolinecarbaldehydes
example of a primary amine giving four crystalline Schiff bases with yields up to 80% (Scheme 5).
The addition of a 2,6-diisopropylbenzenamine nucleophile to heterocycles 2a 2c 2e or 2f is a nucleophilic
2 were reacted with 2,6-diisopropylbenzenamine as an
,
,
addition–elimination reaction. The final products are an imine-Schiff base and water. As a reversible
reaction, in acidic aqueous solutions, the products are hydrolyzed back to the aldehydes and amine.
The equilibrium favors the nitrogen-protonated tetrahedral intermediate because nitrogen is more
basic than oxygen. The equilibrium can be forced toward the imine species by removing water as it is
formed. MgSO was used as dehydrating agent. The choice of 2,6-diisopropylbenzenamine is because
4
it easily forms high quality crystals [15].
3
Yield
%
R
H
CH
H
R’
HC=N
C5
C5
a
b
c
C8-OH
C6-NMe
C6-NMe
71.1
74.3
80.3
3
2
2
C5
d
H
C8-OH
C7
78.0
0
Scheme 5. Synthesis of Schiff bases 3. R = H, CH , R = Me, C8-OH, C6-NMe .
3
2

Molecules 2020, 25, 2053
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2
.2. Crystal Structure Determination and Refinement
Data for the molecules 2h 3a 3b and 3d were collected on a SuperNova diffractometer using
an Atlas CCD detector, while the measurement of compound 3c was performed on an Xcalibur
diffractometer with a Sapphire 3 CCD detector. Graphite-monochromated Mo-K radiation was used
for all measurements. The crystals of compounds 2h 3a 3b and 3d were cooled down by a cold
dry nitrogen gas stream (Oxford Cryosystems equipment), while the crystal of compound 3c was
,
,
α
,
,
measured at room temperature. The temperature stability was
±
1 K. The structures were solved by
2
direct methods using SHELXS-2013 program and refined by full-matrix least-squares on F (all data)
using the SHELXL-2014/7 program [16]. All non-hydrogen atoms were refined anisotropically. All H
atoms bound to C atoms were refined using a riding model with C–H distances of 0.95 Å (aromatic),
0
.98 Å (methyl) or 1Å (methine) and Uiso(H) values of 1.2 Ueq(C) or 1.5 Ueq(C). Hydroxyl H atoms
were refined with distances of 0.84 Å and Uiso(H) values of 1.5 Ueq(O). Details concerning crystal data
and refinement are gathered in Tables 1 and 2.
Table 1. Crystal data and structure refinement details of compounds 2h, 3a, 3b, 3c and 3d.
2
h
3a
O)
100(1)
3b
3c
3d
Empirical formula
Temperature (K)
Wavelength (Å)
Crystal system
Space group
C12H9NO3,CHCl3
100(1)
3(C22
H
24
N
2
·
CH
3
CN
C25H31N3
100(1)
C24H29N3
293(1)
C23H26N2O
80(1)
0.71073 (Mo Kα)
Orthorhombic
Pnma
Trigonal
Orthorhombic
Monoclinic
Monoclinic
P31c
Pbca
P21/c
P21/c
Unit cell dimensions
a (Å)
b (Å)
c (Å)
α (o)
β (o)
γ (o)
26.1040(14)
6.4668(4)
8.2056(4)
90
29.4970(4)
29.4970(4)
12.0258(3)
90
90
120
18.8459(8)
11.0427(3)
20.8067(6)
90
9.0651(3)
11.2850(3)
20.8767(7)
90
93.873(3)
90
24.0519(9)
16.2882(7)
9.7079(3)
90
99.189(3)
90
90
90
90
90
Volume (Å3)
1385.18(13)
4
9061.5(3)
6
4330.1(3)
8
2130.80(12)
4
3754.4(2)
8
Z
Calculated density
3
1
.604
.666
1.142
1.146
1.121
1.226
(
Mg/m )
Absorption
0
0.070
3336
0.068
1616
0.066
776
0.075
1488
coefficient (mm 1)
−
F (000)
680
Crystal dimensions
0.12 × 0.10 × 0.02
0.18 × 0.13 × 0.03
0.25 × 0.02 × 0.02
0.56 × 0.22 × 0.09
0.30 × 0.05 × 0.02
(mm)
θ range for data
collection ( )
2.932 to 26.371
2.875 to 24.710
3.452 to 26.370
3.401 to 26.367
3.033 to 26.371
o
−
32 ≤ h ≤ 32;
−34 ≤ h ≤ 34;
−34 ≤ k ≤ 31;
−14 ≤ l ≤ 14
−21 ≤ h ≤ 23;
−13 ≤ k ≤ 9;
−26 ≤ l ≤ 26
−11 ≤ h ≤ 11;
−14 ≤ k ≤ 9;
−26 ≤ l ≤ 26
−30 ≤ h ≤ 30;
−20 ≤k ≤ 20;
−9 ≤ l ≤ 12
Index ranges
−6 ≤ k ≤ 8;
−
10 ≤ l ≤ 10
13863
Reflections collected
69751
25986
25693
30149
Independent
reflections
1543 [R(int) = 0.0162] 10284 [R(int) = 0.0713] 4420 [R(int) = 0.0680] 4343 [R(int) = 0.0509] 7669 [R(int) = 0.0599]
Data/restraints/
parameters
1543/0/120
10284/1/721
4420/0/260
4343/0/251
7669/0/493
Goodness-of-fit on F2
1.223
1.070
1.072
1.026
1.032
Final R indices
R1 = 0.0547;
wR2 = 0.1379
R1 = 0.0581;
wR2 = 0.1287
R1 = 0.0488;
wR2 = 0.1082
R1 = 0.0494;
wR2 = 0.1180
R1 = 0.0521;
wR2 = 0.1228
(I > 2σ(I))
R1 = 0.0556;
wR2 = 0.1385
R1 = 0.0811;
wR2 = 0.1436
R1 = 0.0776;
wR2 = 0.1262
R1 = 0.0763;
wR2 = 0.1329
R1 = 0.0884;
wR2 = 0.1499
R indices (all data)
Largest diff. Peak
0.696 and −0.377
0.159 and −0.257
0.203 and −0.191
0.158 and −0.154
0.325 and −0.297
and hole
CCDC-Number
1890715
1501807
1501808
1829344
1829345

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Table 2. Selected bond lengths and angles of compounds 2h, 3a, 3b, 3c and 3d (Å and o).
Bond Lengths (Å)
3b
2
h
3a
3c
3d
C(10)–N(2)
C(33)–N(4)
C(5)–C(10)
C(5)–C(11)
C(7)–C(12)
C(8)–O(1)
C(6)–N(3)
-
-
-
1.269(6)
1.421(6)
1.459(7)
1.2741
1.417(2)
1.465(2)
1.265(2)
1.426(2)
1.4631
1.2816
1.4263
1.4488
1.448
1.452
1.243
-
-
-
-
-
-
-
-
-
-
-
1.341
-
1.350(5)
-
1.415(2)
1.403(2)
Angles (o)
C(10)–N(2)–C(11)
C(5)–C(10)–N(2)
116.8(4)
127.2(5)
120.5(1)
124.0(1)
117.5(1)
126.1(1)
121.18
121.52
2
.3. X-ray Studies
-Hydroxy-2-methylquinoline-5,7-dicarbaldehyde (2h) crystallizes with chloroform in the Pnma
space group (Figure 3). The molecular ring systems are both essentially planar. The packing of
the compound 2h in the structure is stabilised by parallelly-displaced stacking interactions,
forming a -stacking interaction as illustrated in Figure 4. The centroid–centroid distances is 3.544 Å
8
π-π
π
and the shift distances is 1.451 Å. Compound co-crystallised with chloroform is associated through
strong C8-O1H···Cl2C13 hydrogen bonds. In the crystal structure of compound 2h several intra- and
intermolecular hydrogen bonds are observed. To the best of our knowledge, this is first time that the
X-ray structure of quinolinecarbaldehyde has been reported.
Figure 3. ORTEPs drawing of compound 2h with 50% probability displacement ellipsoids.

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Figure 4. The π-stacking interactions in cell packing of compound 2h.
3b, 3c and 3d were crystallized in the trigonal, orthorhombic, monoclinic and
The molecules 3a
,
monoclinic space groups, respectively, which are displayed as ORTEP representations in Figure 5.
Details concerning crystal data and refinement are gathered in Tables 1 and 2.
3
a
3b
3
c
3d
Figure 5. ORTEPs drawing of Schiff bases (3a), (3b), (3c) and (3d) with 50% probability
displacement ellipsoids.

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The phenyl and quinoline rings in the compounds adopt an E configuration along the imino
functional group. In the Schiff base compounds both the planes of the quinoline and the phenyl
◦
◦
◦
◦
moieties are aligned almost perpendicularly at angles of 89.64 (3a), 87.51 (3b), 78.65 (3c) and 79.98
3d), respectively. The –C=N– bond lengths of 1.27 Å are typical E Schiff base compounds 3a 3b and
, the –C=N– bond length of 1.28 Å for compound 3d is longer due to participation in pseudo-ring.
(
3
,
c
The substituents located on the phenol ring in molecule 3d and on the imino group show their ability
to form a pseudo-ring, which is stabilized by intramolecular hydrogen bond indicated on Scheme 5.
The consequence of the formation of pseudo-ring in compound 3d constitution is the presence of
strongest hydrogen bond (O1–H1
presented compounds are stabilized by hydrogen bonds.
−
N2) among all presented Schiff bases 3. The structures of the
2
.4. Electrochemical Measurements
Electrochemical measurements were performed on a glassy carbon electrode in acetonitrile.
Compound 2a yields three reduction waves in a range of potentials from 0.1 V to 2.2 V (Figure 6A).
The first reduction wave at 1.300 V is followed by reduction wave 2 at a peak potential
1.400 V. The charge consumed during the exhaustive electrolysis behind the second reduction
−
−
−
wave corresponded to one electron.
Figure 6. Cyclic voltammograms of 0.2 mM 2a (A), 2e (B) and 2f (C) in acetonitrile and 0.1 M TBAPF6
on glassy carbon electrode.
The third one-electron reduction wave occurred at
2.1 V resulted in the consumed charge corresponding to two electrons. Such a discrepancy in number
−
2.133 V, the potentiostatic electrolysis at
−
of electrons suggests that the first two reduction waves correspond to different dissociation forms of
compound 2a, which are present in solution under experimental conditions; the consumed charge
corresponds to the sum of their concentrations. The spatial distribution of LUMO orbitals suggests that
carboxyl group accepts the first electron (Figure 7C). The reduction of aldehyde is usually two-electron
and two-proton process according to literature [17] We suggest that hydroxyl group present in the
chemical structure of compound 2a (Figure 7A) can serve as a proton donor, which participate in
reduction process. Such effects were found in literature in the case of reduction of hydroxylated

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benzonitriles, where half molecules present in solution served as proton donors and the charge after
the exhaustive electrolysis corresponded to the reduction of half molecules present in solution [18 19].
The study of this effect is not the aim of this manuscript and will be investigated in further study.
,
Figure 7. Chemical structures of compounds 2a, 2e and 2f (A), the spatial distribution of the HOMO
orbitals (B) and LUMO orbitals (C).
Cyclic voltammogram obtained for compound 2e yields four reduction waves up to
Figure 6B). All reduction waves increase linearly with concentration. The first reduction wave at
−
2.2 V
(
−
1.233 V is irreversible, the second one-electron wave at
−
1.510 V is quasi-reversible. The peak-to-peak
c
a
separation of the wave
2
is |Ep −
E
p
| = 68 mV. This behavior is similar to that of compound 2f,
which yields five reduction waves in the same range of potentials. The first irreversible reduction wave
of 2f occurs at
separation of |Ep −
reduction wave, it is delocalized over the whole
−
1.087 V and the second reversible one-electron reduction wave with peak-to-peak
c
a
E
p
| = 59 mV occurs at
−
1.346 V. Most likely, a radical anion is formed at the first
-conjugated molecule as shown by LUMO spatial
π
distribution (Figure 7C) and a fast protonation follows. The formed radical can undergo a dimerization
process or is further reduced to form corresponding alcohol. The latter can be preferential under used
experimental conditions, because the exhaustive electrolysis at the potential behind the second reduction
wave resulted in charge consuming corresponding to two electron process. We tend to investigate the
reduction mechanism in details in further study. Importantly, the peak potential of the first reduction
1
peak of compound 2e occurs at more negative potential than Ep of compound 2f. The difference is
caused by induction effect of methyl group. This agrees with calculated energies of LUMO orbitals for
both compounds, which increase in order ELUMO(2e) = −1.89 eV < E
(2f) = −1.97 eV.
LUMO
Oxidation properties were studied by means of cyclic voltammetry (Figure S1, Supplementary
material). Cyclic voltammetry of 2a yields two oxidation waves at potentials 1.349 V and 1.637 V.
The charge consumed during the exhaustive electrolysis of compound 2a at the potential behind the

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first oxidation wave corresponded to two electrons. According to Figure 7B, the electroactive site
for oxidation is most likely hydroxyl group in para position to the aldehyde. Compound 2e yields
better defined oxidation waves at E = 1.276 V and E = 1.662 V and oxidation waves at E = 1.385 V
1
2
1
and E = 1.765 V were registered for compound 2f. According to the spatial distribution of HOMO
2
orbitals (Figure 7B) the amine can be oxidized. According to the literature, oxidation can yield a
dealkylated product [20], and tail to tail coupling is also known in the literature for dialkylanilines [17].
The energies of HOMO orbitals calculated for the molecule in a vacuum suggest that compound 2e is
more easily oxidized than compound 2f; EHOMO
agreement with the experimental results.
(2e) =
−
5.67 eV > EHOMO
(
2f) = 5.77 eV, which is in
−
3
. Materials and Methods
3
.1. Materials
All experiments were carried out in an atmosphere of dry argon and flasks were flame dried.
Solvents were dried by usual methods (diethyl ether and THF over benzophenone ketyl, CHCl3
and CH Cl over P O , hexane over sodium-potassium alloy and DMF over molecular sieves) and
2
2
4
10
distilled. Chromatography was carried out on Silica Gel 60 (0.15–0.3 mm, Macherey-Nagel GmbH
Co. KG, Düren, Germany). 2,2,2-Trifluoroacetic acid (Caution! TFA is a known nigrostriatal
&
neurotoxin, and therefore compounds of this class should be handled using disposable gloves
in a properly ventilated hood), 5,7-dibromo-2-methylquinolin-8-ol (1a), hexamethylenetetramine
(HMTA), 2,6-diisopropylbenzenamine, 2-methylquinolin-8-ol (1b), 8-hydroxyquinoline (1c) and
benzo[h]quinolin-10-ol (1j) were purchased from Sigma–Aldrich (Poznan, Poland), and were
used without further purification. 5-Chloroquinolin-8-ol (1d), N,N-dimethylquinolin-6-amine
(1e), 5-methylquinolin-8-ol (1f), N,N,2-trimethylquinolin-6-amine (1g), quinolin-6-ol (1h) and
N,N-dimethylquinolin-8-amine (1i) were synthesized according to our procedures described in
the literature [21–24].
3
.2. Instrumentation
NMR spectra were obtained with Avance 400, 500 and 600 spectrometers (Bruker, Billerica,
1
13
◦
MA, USA) operating at 600.2, 500.2 or 400.1 MHz ( H) and 150, 125.78 or 100.5 MHz ( C) at 21 C.
1
13
Chemical shifts referenced to ext. TMS ( H, C) or using the residual CHCl signal (
CDCl3 (δC 77.1 ppm) as internal references for H and C-NMR, respectively. Coupling constants are
δ 7.26 ppm) and
3
H
1
13
given in Hz. For GC-MS a 7890A gas chromatograph (Agilent Technologies, Wilmington, DE, USA)
equipped with a MS (70 eV) 5975 EI/CI MSD, and a 7693 autosampler with an Agilent HP-5MS capillary
column (30 m
×
250
µ
m
×
0.25
µ
m)—press. 127.5 kPa, total flow 19 mL/min, col. flow 2 mL/min,
◦
◦
◦
◦
split—7:1, temp. prog. (70 C—hold 0.5 min, 70–290 C/25 C/min, 290 C—hold 6 min) was used.
The LCMS-IT-TOF analysis was performed on an Agilent 1200 Series binary LC system coupled to
a micrOTOF-Q system mass spectrometer (Bruker Daltonics, Bremen, Germany). High-resolution
mass spectrometry (HRMS) measurements were performed using a Synapt G2-Si mass spectrometer
(Waters, New Castle, DE, USA) equipped with an ESI source and quadrupole-time-of-flight mass
analyser. To ensure accurate mass measurements, data were collected in centroid mode and mass was
TM
corrected during acquisition using leucine enkephalin solution as an external reference (Lock-Spray ).
The results of the measurements were processed using the MassLynx 4.1 software (Waters, Milford, CT,
USA) incorporated within the instrument. A iS50 FTIR spectrometer (Nicolet, Waltham, MA, USA)
−
1
was used for recording spectra in the IR range 4000–400 cm . FTIR spectra were recorded on a Perkin
Elmer (Schwerzenbach, Switzerland) spectrophotometer in the spectral range 4000–450 cm 1 with the
−
samples in the form of KBr pellets. Elementary analysis was performed using Vario EL III apparatus
(
Elementar, Langenselbold, Germany). Melting points were determined on MPA100 OptiMelt melting
point apparatus (Stanford Research Systems, Sunnyvale, CA USA) and are uncorrected.

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3
.3. Electrochemical Measurements
Electrochemical measurements were carried out in 0.1 M TBAPF in acetonitrile. Cyclic
6
voltammetry as well as exhaustive electrolysis were performed using a PGSTAT 12 AUTOLAB
potentiostat (Metrohm Autolab, Utrecht, The Netherlands). A glassy carbon electrode (diameter 1 mm),
a platinum net and an Ag|AgCl|1M LiCl electrode were used as the working, the auxiliary and reference
electrode, respectively. Oxygen was removed from the solution by passing a stream of argon (99.998%,
Messer, Graz, Austria).
3
.4. Theoretical Calculations
Calculations of molecular orbital energies were performed using the density functional theory
(DFT) calculations employing the B3LYP functional and 6-31G* basis set with Spartan ’14, v.1.1.8
software (Wavefunction, Inc. Irvine, CA, USA).
3
.5. General Procedures for Synthesis of Selected Quinolinecarbaldehydes Based on the Reimer-
Tiemann Protocol
Potassium hydroxide (14.0 g; 250.0 mmol) in water (15 mL) was added into the solution of 1c
,
1
d or 1f (34.5 mmol) in ethanol (20 mL) and the resulting reaction mixture was brought to a gentle
reflux. Chloroform (8.3 mL; 103.5 mmol) was then added dropwise to the reaction mixture over the
course of 1 h. The resulting red mixture was refluxed for another 3 h, and then was cool down to
room temperature. The obtained suspension was acidified by an aqueous solution of hydrochloric
acid (1%) to pH ca. 7, and then volatiles were evaporated under reduced pressure. The resulting solid
was dried over P O and extracted at Soxhlet apparatus (chloroform). From the resulting solution
4
10
the volatiles were evaporated under reduced pressure, and finally the crude product was purified on
a silica gel chromatography with CH Cl/MeOH (3:1) as eluent, and purified by crystallization from
3
CH Cl/hexane to yield precipitates as follows:
3
◦
8
-Hydroxyquinoline-5-carbaldehyde (2a) beige 0.6 g (3.5 mmol, 10.1%) [25]; m.p. = 171.3–171.8 C;
1
3
3
H-NMR (DMSO–d ; 400.2 MHz)
δ
= 7.26 (d, J
= 8.0 Hz, 1H, aromatic), 7.78 (dd, J
= 8.6 Hz,
6
H,H
H,H
4J
=
3
3
4
= 4.1 Hz, 1H, aromatic), 8.17 (d, J
= 8.1 Hz, 1H, aromatic), 8.97 (dd, J
= 4.1 Hz, J
H,H
H,H
H,H
H,H
3
4
1.6 Hz, 1H, aromatic), 9.56 (dd, J
= 8.6 Hz, J
= 1.6 Hz, 1H, aromatic), 10.14 (s, 1H, HC=O);
H,H
δ = 110.8, 122.4, 124.6, 126.8, 133.0, 138.0, 140.2, 149.0, 159.6,
H,H
13
1
C{ H}-NMR (DMSO–d ; 100.6 MHz)
6
+
+
1
(
2
92.2; GC-MS: t
methanol; [nm] (log
845 νCH; 1663 νC=O; 1474 νC-H
r
= 6.024 min, (EI) m/z (rel. int.) M = 173 (100%); (M
−
HCO) = 144 (17%); UV-Vis
OH;
λ
ε
)): 395 (3.04), 322 (3.89), 263 (3.96), 239 (4.40), 210 (4.13); IR (KBr): 3177 ν
.
1
= 7.24 (d, 3JH,H = 7.9 Hz
8
-Hydroxyquinoline-7-carbaldehyde (2a’) [
4
] H-NMR (DMSO–d ; 400.2 MHz)
δ
,
6
3
4
3
1
1
H, aromatic), 7.57 (dd, J
= 8.1 Hz, J
H, aromatic), 8.78 (dd, JH,H = 4.4 Hz, J
= 4.3 Hz, 1H, aromatic), 7.99 (d, J
= 1.5 Hz, 1H, aromatic), 9.07 (dd, J
= 8.0 Hz,
H,H
H,H
H,H
3
4
3
= 8.0 Hz,
H,H
H,H
4J
= 1.6 Hz, 1H, aromatic), 10.41 (s, 1H, HC=O); GC-MS: t
= 6.360 min, (EI) m/z (rel. int.) M = 173
+
H,H
r
+
(12%); (M − CO + H) = 146 (100%).
◦
5
-Chloro-8-hydroxyquinoline-7-carbaldehyde (2b) yellow 0.5 g (2.5 mmol, 7.2%) [26]; m.p. = 170.0–170.6 C;
1
3
4
H-NMR (CDCl ; 500.18 MHz)
δ
= 7.71 (dd, J
= 8.5 Hz, 4JH,H = 1.5 Hz, 1H, aromatic), 8.97 (dd, J
= 1.5 Hz, 1H, aromatic), 10.39 (s, 1H, HC=O); H-NMR (DMSO–d ; 500.18 MHz)
= 8.5 Hz, J
= 4.2 Hz, 1H, aromatic), 7.86
3
H,H
H,H
3
3
(
s, 1H, aromatic), 8.56 (dd, J
= 4.2 Hz,
H,H
H,H
4J
1
δ
= 7.74
H,H
6
3
4
3
(
s, 1H, aromatic), 7.88 (dd, J
= 8.5 Hz, J
= 4.2 Hz, 1H, aromatic), 8.51 (dd, J
= 8.5 Hz,
H,H
H,H
H,H
4J
= 1.4 Hz, 1H, aromatic), 9.05 (dd, J
3
= 4.2 Hz, J
4
= 1.4 Hz, 1H, aromatic), 10.49 (s, 1H,
H,H
H,H
H,H
13
1
HC=O); C{ H}-NMR (DMSO–d ; 125.78 MHz)
δ
= 118.7, 119.8, 122.7, 125.7, 129.3, 133.1, 140.2, 149.9,
= 117.8, 121.8, 124.7, 125.4, 130.2, 133.7, 139.9, 149.9,
6
58.4, 188.0; 13C{ H}-NMR (CDCl ; 125.78 MHz)
1
δ
1
1
3
+
+
57.6, 190.6; GC-MS: t
r
= 6.917 min.; (EI) m/z (rel. int.) M = 207 (15%); (M
−
CO) = 179 (100%); UV-Vis

Molecules 2020, 25, 2053
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(metanol;
λ
[nm] (log
ε
)): 429 (2.86), 350 (3.27),286 (3.65), 267 (4.03), 248 (3.83), 207 (4.09); IR (KBr):
3
344 νOH; 2859 νCH; 1667 νC=O; 1425 νC-H
.
◦
5
-Methyl-8-hydroxyquinoline-7-carbaldehyde (2c) greenish 0.5 g; (2.8 mmol, 8.0%) [27]; m.p. = 172.7–173.5 C
;
1
3
H-NMR (CDCl ; 400.2 MHz)
4J
1
δ
= 2.56 (s, 3H, CH ), 7.53 (s, 1H, aromatic), 7.58 (dd, J
= 8.2 Hz,
H,H
3
3
3
3
= 3.5 Hz, 1H, aromatic), 8.26 (d, J
= 8.3 Hz, 1H, aromatic), 8.90 (d, JH,H = 2.7 Hz, 1H, aromatic),
H,H
0.36 (s, 1H, HC=O); C{ H}-NMR (CDCl ; 100.6 MHz) δ= 17.9, 117.2, 124.3, 124.7, 124.9, 131.8, 133.0,
3
H,H
13
1
+
+
1
39.5, 148.9, 157.4, 192.3; GC-MS: t
[nm] (log
07 (4.35); IR (KBr): 3063 νOH; 2852 νCH; 1686 νC=O; 1426 νC-H
r
= 7.186 min.; (EI) m/z (rel. int.) M = 187 (19%); (M
ε
−
CO) = 159
(100%); UV-Vis (metanol;
λ
)): 452 (2.88), 426 (3.04), 358 (3.51), 291 (3.88), 270 (4.37), 246 (4.05),
2
.
3
.6. Synthesis of 7-Bromo-8-hydroxy-2-methylquinoline-5-carbaldehyde through a Carbene Insertion Reaction
Potassium hydroxide (40.0 g; 714.3 mmol) in water (15 mL) was added into the solution of 1a
(5.6 g; 18.0 mmol) in ethanol (20 mL). The resulting solution was irradiated (75 W) and stirred under
reflux. Next, chloroform (30 mL, 372.0 mmol) was slowly added dropwise over an hour. The resulting
red mixture was refluxed for another 16 h, and then cooled down to room temperature. Subsequently
the obtained suspension was acidified by an aqueous solution of hydrochloric acid (1%) to pH ca. 7
and then volatiles were evaporated under reduced pressure. The resulting solid was dried over
P4O10 and extracted at Soxhlet apparatus with chloroform. From the resulting solution the volatiles
were evaporated under reduced pressure, and finally the crude product was purified on a silica gel
,
chromatography with CH Cl/MeOH (3:1) as eluent, and purified by crystallization from CH Cl/hexane
3
3
to yield precipitates as follows:
1
7
δ
-Bromo-8-hydroxy-2-methylquinoline-5-carbaldehyde (2d) < 1% [26]; H-NMR (DMSO–d ; 400.2 MHz)
6
3
3
= 2.77 (s, 3H, CH ), 7.73 (d, J
= 8.7 Hz, 1H, aromatic), 8.32 (s, 1H, aromatic), 9.45 (d, J
Hz, 1H, aromatic), 10.05 (s, 1H, HC=O); GC-MS: t = 7.617 min.; (EI) m/z (rel. int.) M = 267 (15%);
r
= 8.7
H,H
3
H,H
+
+
(M − CO + H) = 238 (20%).
3
.7. General Procedures for Synthesis of Selected Quinoline-5-carbaldehydes Based on Vilsmeier-Haack Protocol
To the solution of dry chloroform (6.5 mL) and dry DMF (0.8 mL, 32.0 mmol) POCl (3.2 mL,
3
◦
4
.0 mmol) was added at 0 C and the mixture was stirred for an hour. Next 1b
,
1e
,
1g or 1i (8.0 mmol),
respectively was added, and the resulting reaction mixture was brought to a gentle reflux for 16 h.
The reaction was quenched by the addition of crushed ice and was neutralized by aqueous solution
of Na CO (10%) to pH 6–7 and then the layers were separated. The aqueous layer was extracted
2
3
by chloroform (3
the solvent was evaporated on a rotary evaporator and the obtained residue was purified by column
chromatography on silica gel with CH Cl/THF/hexane (2:1:1) as eluent.
×
30 mL), collected, and was dried over anhydrous MgSO . After filtration,
4
3
◦
-(Dimethylamino)-2-methylquinoline-5-carbaldehyde (2e) yellow 0.7 g (3.1 mmol, 38.6%); m.p. = 75.2–75.8 C;
6
1
3
H-NMR (DMSO–d ; 400.2 MHz)
δ
= 2.58 (s, 3H, CH ), 3.11 (s, 6H, 2NCH ), 7.43 (d, J
= 8.8 Hz, 1H,
H,H
6
3
3
3
3
3
aromatic), 7.64 (d, J
= 9.4 Hz, 1H, aromatic), 7.98 (d, J
= 9.4 Hz, 1H, aromatic), 9.18 (d, J
= 8.8 Hz,
H,H
H,H
H,H
1
1
1
(
H, aromatic), 10.20 (s, 1H, HC=O); 13C{ H}-NMR (DMSO–d ; 100.6 MHz)
δ= 24.2, 45.7, 114.8, 121.9, 124.1,
6
+
25.2, 131.4, 135.2, 142.4, 155.6, 157.1, 190.4; GC-MS: t
r
= 7.683 min, (EI) m/z (rel. int.) M = 214 (85%);
+
M − HCO) = 185 (55%); UV-Vis (methanol;
λ
[nm] (logε)): 416 (3.55), 365 (3.12), 304 (3.60), 289 (3.68),
260 (4.35), 214 (4.21); IR (KBr): 3386 νOH; 2878 νCH; 1671 νC=O; 1498 νC-H
.
◦
6
-(Dimethylamino)quinoline-5-carbaldehyde (2f) yellow 1.2 g (5.9 mmol, 73.8%); m.p. = 56.1–56.8 C;
1
3
4
H-NMR (DMSO–d ; 400.2 MHz)
Hz, 1H, aromatic), 7.70 (d, J
δ
= 3.16 (s, 6H, 2NCH ), 7.54 (dd, J
= 8.7 Hz, J
= 4.2
H,H
= 9.4 Hz, 1H, aromatic),
H,H
= 1.5 Hz, 1H,
H,H
δ = 45.5, 113.4, 122.7, 123.6,
6
3
H,H
3
3
= 9.5 Hz, 1H, aromatic), 8.05 (d, J
= 1.6 Hz, 1H, aromatic), 9.30 (dd, J
H,H
3
4
3
= 8.7 Hz, 4J
8.69 (dd, J
= 4.2 Hz, J
H,H
H,H
H,H
1
3
1
aromatic), 10.19 (s, 1H, HC=O); C{ H}-NMR (DMSO–d ; 125.8 MHz)
1
6
+
r
27.5, 132.0, 134.7, 141.6, 146.6, 157.5, 190.0; GC-MS: t = 7.259 min, (EI) m/z (rel. int.) M = 200 (76%);

Molecules 2020, 25, 2053
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+
(
2
M
−
HCO) = 171 (20%); UV-Vis (methanol;
λ
[nm] (log
ε
)): 423 (3.61), 373 (3.18), 307 (3.60), 268 (4.33),
22 (4.17), 204 (3.96); IR (KBr): 3421 νOH; 2895 νCH; 1636 νC=O; 1458 νC-H.
◦
8
-(Dimethylamino)quinoline-5-carbaldehyde (2i) yellow 0.01 g (0.05 mmol, 0.6%); m.p. = 100.8–101.0 C;
1
3
H-NMR (CDCl ; 400.2 MHz)
7
8
δ
= 3.36 (s, 6H, 2NCH ), 6.97 (d, J
= 8.2 Hz, 1H, aromatic),
= 8.3 Hz, 1H, aromatic),
3
3
H,H
3
4
3
.53 (dd, J
= 8.6 Hz, J
= 4.0 Hz, J
= 4.1 Hz, 1H, aromatic), 7.84 (d, J
H,H
H,H
H,H
= 8.6 Hz, 4J
3
4
3
.87 (dd, J
= 1.7 Hz, 1H, aromatic), 9.72 (dd, J
= 1.7 Hz, 1H,
H,H
H,H
H,H
H,H
13
1
aromatic), 10.06 (s, 1H, HC=O); C{ H}-NMR (CDCl ; 125.8 MHz) δ = 44.1, 111.2, 122.2, 123.3, 128.3,
3
+
133.9, 139.5, 141.0, 146.9, 155.0, 191.3; GC-MS: t
r
= 7.156 min, (EI) m/z (rel. int.) M = 200.1 (24%),
HCO) = 171.1 (38%); UV-Vis (methanol; [nm] (log )): 390 (4.07),
89 (3.91), 263 (4.20), 234 (3.99), 206 (4.36); IR (KBr): 2840 CH; 1665 C=O; 1555; 1509
+
+
(M
−
Me) = 185.1 (100%), (M
−
λ
ε
2
ν
ν
ν
C-H; 1352; 1251;
1
080; 760.
◦
8
-(Dimethylamino)quinoline-5,7-dicarbaldehyde (2j) yellow 0.006 g (0.002 mmol, 0.3%); m.p. = 100.0–100.1 C;
1
3
= 8.6 Hz, 4JH,H = 4.1 Hz, 1H, aromatic),
H-NMR (CDCl ; 400.2 MHz)
δ
= 3.61 (s, 6H, 2NCH ), 7.57 (dd, J
3
3
H,H
3
4
3
8
.26 (s, 1H, aromatic), 8.88 (d, J
= 4.1 Hz, J
= 1.7 Hz, 1H, aromatic), 9.70 (dd, J
= 8.6 Hz,
H,H
H,H
H,H
4
13
1
JH,H = 1.7 Hz, 1H, aromatic), 10.06 (s, 1H, HC=O), 10.17 (s, 1H, HC=O); C{ H}-NMR (CDCl ; 125.8 MHz)
3
δ= 48.3, 122.1, 122.6, 124.7, 130.2, 134.0, 141.9, 144.4, 147.5, 157.0, 188.5, 191.3; GC-MS: tr = 7.952 min, (EI) m/z
+
+
+
(
(
(
rel. int.) M = 227.9 (100%), (M
−
Me) = 213.0 (3%), (M + 2H
−
CO) = 202 (10%); LCMS-IT-TOF: m/z
+
+
rel. int.) (M + H) = 229 (100%), (M + H
M + H) = 229.0977, Found 229.0970; UV-Vis (methanol;
−
CO) = 201 (100%); HRMS (IT-TOF): m/z Calcd for C H N O
13
13
2
2
+
λ
[nm] (log
ε)): 400 (4.33), 355 (4.04), 287 (4.38),
234 (4.33), 210 (4.33); IR (KBr): 2872 νCH; 1678 νC=O; 1661 νC=O; 1515 νC-H; 1381, 1265, 1103, 765.
(
Z)-8-Hydroxy-2-(2-hydroxyvinyl)quinoline-5-carbaldehyde (2l) yellow 0.6 g (2.6 mmol, 32.1%);
◦
1
3
4
m.p. = 153.1–153.8 C; H-NMR (DMSO–d ; 400.2 MHz)
δ
= 7.28 (dd, J
= 5.7 Hz, J
= 3.2 Hz,
H,H
6
H,H
3
3
1
1
1
H, aromatic), 7.45–7.48 (m, 2H, aromatic), 8.58 (d, J
= 9.3 Hz, 1H, aromatic), 8.86 (d, JH,H = 9.2 Hz
H, aromatic), 9.43 (s, 2H, HC=O), 11.42 (s, 1H, OH), 16.14 (s, 1H, OH); C{ H}-NMR (DMSO–d ;
,
H,H
13
1
6
25.8 MHz) δ = 106.4, 115.1, 118.0, 118.1, 125.4, 125.9, 126.9, 142.1, 146.4, 150.7, 189.6, 191.8; LCMS-IT-TOF:
+
+
m/z (rel. int.) (M + H) = 216 (100%); HRMS (IT-TOF): m/z Calcd for C H NO (M + H) = 216.0660,
12
10
3
Found 216.0665; UV-Vis (methanol;
λ
[nm] (log
ε)): 402 (3.91), 382 (3.99), 297 (4.28), 262 (4.07), 241 (4.21),
2
14 (4.39); IR (KBr): 3102 νOH; 2906 νCH; 1594 νC=O; 1353 νC-H
.
3
.8. General Procedures for the Synthesis of Selected Quinolinecarbaldehydes Based on the Duff Protocol
These were based on a procedure described in the literature [28]. To a solution of 1b 1d 1e 1f, 1h
,
,
,
or 1j (5.0 mmol) in a minimum amount of TFA (7–8 mL) hexamethylenetetramine (1.4 g, 10.0 mmol)
◦
was gently added under an argon atmosphere. The solution was stirred at 70 C for 70 h and then at
1
◦
00 C for another 4 h. Subsequently, the obtained suspension was acidified by an aqueous solution
◦
of hydrochloric acid (10%, ~10 mL) and the reaction mixture was kept at 100 C for 1 h. The whole
suspension was cooled down to r.t. Next, the obtained reaction mixture was alkalified by aqueous
solution of NaOH (10%), and the resulting precipitate was collected in a Buchner funnel, followed by
washing with water (3
×
50 mL) and dried to afford a solid. Next, the crude product was purified by
chromatography to yield 2c precipitates as follows, or the crude product was extracted with CH Cl at
2
2
Soxhlet apparatus to yield 2h solid as follows:
5
-Chloro-8-hydroxyquinoline-7-carbaldehyde (2b) 0.7 g (3.5 mmol, 70%).
-Methyl-8-hydroxyquinoline-7-carbaldehyde (2c) 0.7 g (3.7 mmol; 75.0%).
5
◦
6
-Hydroxyquinoline-5-carbaldehyde (2g) beige 0.6 g (3.5 mmol, 28.1%) [29]; m.p. = 138.6–138.9 C;
1
3
3
H-NMR (CDCl ; 400.2 MHz)
4J
aromatic), 8.85 (d, J
δ
= 7.39 (d, J
= 9.3 Hz, 1H, aromatic), 7.53 (dd, J
= 8.6 Hz,
H,H
= 8.6 Hz, 1H,
H,H
3
H,H
3
3
= 4.2 Hz, 1H, aromatic), 8.26 (d, J
= 9.3 Hz, 1H, aromatic), 8.67 (d, J
H,H
H,H
3
13
1
= 3.1 Hz, 1H, aromatic), 10.76 (s, 1H, HC=O), 13.06 (s, 1H, OH); C{ H}-NMR
= 110.7, 123.1, 123.5, 127.0, 128.2, 140.7, 143.4, 148.7, 164.9, 192.4; GC-MS:
H,H
(CDCl ; 100.6 MHz)
δ
3

Molecules 2020, 25, 2053
17 of 20
+
+
tr = 6.168 min, (EI) m/z (rel. int.) M = 173 (100%); (M
log )): 400 (2.46), 346 (3.16), 300 (3.43), 290 (3.37), 226 (4.04), 203 (0.98); IR (KBr): 3050
632 νC=O; 1480 νC-H
−
HCO) = 144 (20%); UV-Vis (methanol;
λ
[nm]
CH;
(
1
ε
ν
OH; 2733
ν
.
◦
1
8
-Hydroxy-2-methylquinoline-5,7-dicarbaldehyde (2h) red 0.2 g (0.7 mmol, 14.9%); m.p. > 360 C; H-NMR
3
(DMSO–d ; 400.2 MHz)
δ
= 2.85 (s, 3H, CH ), 7.92 (d, J
= 8.7 Hz, 1H, aromatic), 8.29 (s, 1H,
H,H
6
3
3
13
1
aromatic), 9.71 (d, J
= 8.7 Hz, 1H, aromatic), 9.95 (s, 1H, HC=O), 10.42 (s, 1H, HC=O); C{ H}-NMR
H,H
(
DMSO–d ; 125.8 MHz)
δ
= 21.6, 115.6, 119.5, 128.0, 128.6, 137.8, 138.5, 139.0, 155.7, 167.2, 188.2, 191.5;
6
−
−
−
LCMS-IT-TOF: m/z (rel. int.) (M
(
2
2
−
H) = 214 (100%), M = 215 (10%); (M
−
HCO) = 186 (10%);
H) = 214.0504, Found
−
−
M − 2HCO) = 157 (<1%); HRMS (IT-TOF): m/z Calcd for C H NO (M
−
12
8
3
14.0496; UV-Vis (methanol;
λ
[nm] (log
ε
)): 359 (3.65), 282 (3.91), 237 (3.59); IR (KBr): 3423
ν
OH;
965 νCH; 2847 νCH; 2835 νCH; 1657 νC=O; 1458 νC-H; CCDC 1890715.
◦
1
0-hydroxybenzo[h]quinoline-7,9-dicarbaldehyde (2k) red 0.9 g (3.5 mmol, 70.6%); m.p.
> 360 C;
dec.
1
3
4
H-NMR (DMSO–d /KOD/D O; 400.2 MHz)
7
δ
= 7.51 (dd, J
= 8.0 Hz, J
= 4.2 Hz, 1H, aromatic),
6
2
H,H
H,H
3
3
4
.96 (d, J
= 9.0 Hz, 1H, aromatic), 8.10 (s, 1H, aromatic), 8.26 (dd, J
= 8.1 Hz, J
= 2.0 Hz,
H,H
= 9.0 Hz, 1H,
H,H
H,H
H,H
3
4
3
1H, aromatic), 8.89 (dd, J
= 4.2 Hz, J
= 2.0 Hz, 1H, aromatic), 9.20 (d, J
H,H
H,H
13
1
aromatic), 9.65 (s, 1H, HC=O), 10.08 (s, 1H, HC=O); C{ H}-NMR (DMSO–d /KOD/D O; 125.8 MHz)
6
2
δ
= 115.1, 122.2, 123.8, 124.8, 126.1, 126.9, 132.3, 137.4, 140.0, 144.6, 148.1, 151.1, 182.0, 192.6, 192.7;
−
HRMS (ESI): m/z Calcd for C H NO M = 251.05826, Found 251.07750; UV-Vis (methanol;
λ [nm]
15
9
3
(logε)): 453 (2.41), 405 (3.22), 364 (3.38), 329 (3.46), 315 (3.48), 274 (3.96), 260 (4.03), 241 (4.02), 223 (4.01),
2
11 (4.04); IR (KBr): 3424 νOH; 3062 νCH; 2877 νCH; 1673 νC=O; 1483 νC-H
.
1
0-Hydroxybenzo[h]quinoline-7-carbaldehyde [30] < 1%.
0-Hydroxybenzo[h]quinoline-9-carbaldehyde [31] < 1%.
1
3
.9. General Procedure the for Synthesis of Selected Schiff Base Derivatives of 2,6-Diisopropylbenzenamine
Compounds 2a 2c 2e or 2f (2.0 mmol) and 2,6-diisopropylaniline (0.5 g; 0.565 mL; 3.0 mmol)
,
,
were dissolved in dry chloroform (70 mL) and then the resulting reaction mixture was brought to a
gentle reflux for 40 h. The reaction mixture was connected with a Soxhlet apparatus in which MgSO4
were placed as dehydrating agent. Next the solvent was evaporated under reduced pressure and the
obtained red residue was purified by chromatography and crystallization from acetonitrile to yield
precipitates as follows:
5
-[(E)-{[2,6-Di(propan-2-yl)phenyl]imino}methyl]quinolin-8-ol (3a) orange 0.5 g (1.4 mmol, 71.1%);
◦
1
3
m.p. = 126.1–126.9 C
;
H-NMR (CDCl ; 400.2 MHz)
δ
= 1.20 (d, J
= 6.9 Hz, 12H, 4CH ),
3
H,H
3
3
3
3.06 (hept, J
= 6.9 Hz, 2H, 2CH), 7.10–7.24 (m, 3H, aromatic), 7.35 (d, J
= 8.0 Hz, 1H,
H,H
H,H
3
4
3
aromatic), 7.66 (dd, J
= 8.7 Hz, J
= 4.3 Hz, 1H, aromatic), 7.84 (d, J
= 8.0 Hz, 1H, aromatic),
H,H
H,H
H,H
3
4
3
8
.51 (s, 1H, HC=N), 8.91 (dd, J
= 4.3 Hz, J
= 1.5 Hz, 1H, aromatic), 10.04 (d, J
= 8.7 Hz,
H,H
H,H
H,H
H, aromatic); 13C{ H}-NMR (CDCl ; 100.6 MHz)
1
δ
= 23.7, 28.3, 109.5, 122.7, 123.2, 123.7, 124.2, 127.3,
1
1
3
+
35.1, 135.6, 137.9, 138.3, 148.1, 149.9, 155.2, 162.7; LCMS-IT-TOF: m/z (rel. int.) (M + H) = 333 (100%);
+
HRMS (IT-TOF): m/z Calcd for C H N O (M + H) = 333.1961, Found 333.1965; UV-Vis (methanol;
22
25
2
λ
[nm] (log
ε)): 327 (3.88), 271 (3.94), 239 (4.38), 206 (4.43); IR (KBr): 3381 νOH; 2858 νCH; 2958 νOH;
1
613 νHC=N. CCDC 1501807.
5
-[(E)-{[2,6-Di(propan-2-yl)phenyl]imino}methyl]-N,N,2-trimethylquinolin-6-amine (3b) yellow 0.6 g
◦
1
= 1.20 (d, 3JH,H = 6.9 Hz
(1.5 mmol, 74.3%); m.p. = 130.1–130.5 C; H-NMR (CDCl ; 400.2 MHz)
δ
,
3
3
3
1
2H, 4CH ), 2.77 (s, 3H, CH ), 2.90 (s, 6H, 2NCH ), 3.11 (hept, J
= 6.9 Hz, 2H, 2CH), 7.14 (dd, J
= 6.6 Hz, 1H, aromatic), 7.19–7.23 (m, 2H, aromatic), 7.38 (d, J
= 9.2 Hz, 1H, aromatic), 8.80 (s, 1H, HC=N),
H,H
= 8.9, 1H, aromatic); C{ H}-NMR (CDCl ; 100.6 MHz) δ = 23.9, 24.7, 28.1, 46.2, 121.3,
H,H 3
3
3
3
H,H
H,H
3
3
=
8.6 Hz, J
= 8.9 Hz, 1H,
H,H
H,H
3
3
aromatic), 7.64 (d, J
= 9.2, 1H, aromatic), 8.18 (d, J
H,H
3
13
1
1
1
0.00 (d, J
22.7, 123.3, 123.7, 124.2, 126.1, 132.5, 135.4, 137.9, 144.1, 150.17, 155.1, 157.1, 162.5; LCMS-IT-TOF: m/z

Molecules 2020, 25, 2053
18 of 20
+
+
(
rel. int.) (M + H) = 374 (100%); HRMS (IT-TOF): m/z Calcd for C H N (M + H) = 374.2590,
25 32 3
Found 374.2588; UV-Vis (methanol;
λ
[nm] (log
ε)): 377 (3.87), 306 (4.06), 260 (4.59), 214 (4.71); IR (KBr):
2
959 νCH; 1629 νHC=N. CCDC 1501808.
5
-[(E)-{[2,6-Di(propan-2-yl)phenyl]imino}methyl]-N,N-dimethylquinolin-6-amine (3c) dark yellow 0.6 g
◦
1
3
(1.6 mmol, 80.3%); m.p. = 116.9–117.2 C; H-NMR (CDCl ; 400.2 MHz)
δ
= 1.25 (d, J
= 6.9 Hz,
H,H
3
3
12H, 4CH ), 2.97 (s, 6H, 2NCH ), 3.14 (hept, J
= 6.9 Hz, 2H, 2CH), 7.16–7.32 (m, 3H, aromatic),
3
3
H,H
3
4
3
3
7
.53 (dd, J
= 8.8 Hz, J
= 4.1 Hz, 1H, aromatic), 7.72 (d, J
= 9.2 Hz, 1H, aromatic), 8.27 (d, J
H,H
H,H
H,H
H,H
3
4
=
9.2 Hz, 1H, aromatic), 8.84 (s, 1H, HC=N), 8.89 (dd, J
= 4.0 Hz, J
= 1.4 Hz, 1H, aromatic),
H,H
H,H
3
13
1
10.15 (d, J
= 8.7 Hz, 1H, aromatic); C{ H}-NMR (CDCl ; 100.6 MHz)
δ
= 23.9, 28.1, 46.2, 120.8,
H,H
3
1
22.6, 122.7, 123.2, 124.2, 128.0, 133.5, 134.9, 137.9, 144.8, 148.4, 150.1, 155.7, 162.3; LCMS-IT-TOF: m/z
+
+
(rel. int.) (M + H) = 360 (100%); HRMS (IT-TOF): m/z Calcd for C H N (M + H) = 360.2434,
24 30 3
Found 360.2432; UV-Vis (methanol;
λ [nm] (logε)): 379 (3.62), 305 (3.80), 263 (4.29), 213 (4.42); IR (KBr):
2
959 νCH; 1619 νHC=N. CCDC 1829344.
(
E)-7-(((2,6-Diisopropylphenyl)imino)methyl)-5-methylquinolin-8-ol (3d) yellow 0.5 g (1.6 mmol, 78.0%);
◦
1
3
m.p. = 175.1–176.1 C; H-NMR (CDCl ; 500.18 MHz)
2
7
aromatic), 8.38 (s, 1H, HC=N), 9.03 (dd, J
OH); 13C{ H}-NMR (CDCl ; 125.78 MHz)
δ
= 1.25 (d, J
= 6.9 Hz, 12H, 4CH3),
H,H
3
4
3
.63 (d, J
= 0.9 Hz, 3H, CH ), 3.09 (hept, J
= 6.8 Hz, 2H, 2CH), 7.23–7.24 (m, 4H, aromatic),
H,H
= 4.2 Hz, 1H, aromatic), 8.28 (dd, J
H,H
3
3
4
3
4
.58 (dd, J
= 8.5 Hz, J
= 8.5 Hz, J
= 1.6 Hz, 1H,
H,H
H,H
H,H
H,H
3
4
= 4.2 Hz, J
= 1.6 Hz, 1H, aromatic), 14.46 (s, 1H,
H,H
H,H
1
δ
= 18.1, 23.7, 28.3, 113.9, 123.1, 123.3, 123.5, 126.1, 127.5,
30.9, 132.5, 139.7, 141.3, 144.5, 149.1, 161.2, 165.3; LCMS-IT-TOF: m/z (rel. int.) (M
3
−
1
−
H) = 345 (100%);
−
HRMS (IT-TOF): m/z Calcd for C H N O (M
λ
−
H) = 345.1967, Found 345.1969; UV-Vis (methanol;
23
25
2
[nm] (log
ε
)): 446 (2.98), 361 (3.17), 277 (3.93), 226 (3.71), 208 (4.02); IR (KBr): 3062
ν
OH; 2962
ν
CH;
1
617 νHC=N. CCDC 1829345.
3
.10. Crystallization
Crystals suitable for X-ray analysis were obtained from a hot acetonitrile solution for 3a
and 3d, and from a hot CHCl solution for 2h.
,
3b
,
3c
3
4
. Conclusions
The research has been focused on the synthesis of quinolinecarbaldehydes
2
and Schiff bases 3 as
their derivatives. The presented synthesis protocols allowed the synthesis of the target compounds
more efficiently with yields up to 75% for molecule 2c and 80.3% for compound 3c. The structures of
the obtained molecules were proved by a combination of various techniques, such as NMR, IR, GC-MS,
MS, HRMS, UV-Vis and X-ray crystallography. The chemistry was mostly based on inexpensive
and commercially available reagents. A variety of substituents (halogens Cl and Br and hydroxyl,
methyl and NMe groups) were chosen in order to represent different electronic features. Formylation
2
reactions of electron-rich aromatics in our studies mainly led to quinoline-5-carbaldehyde structures
with newly formed carbonyl groups at the C5 position. In the case of a C5 position blocked by bromine
or chlorine atoms or methyl groups, formylation reactions produced quinoline-7-carbaldehydes with
the carbonyl group in C7 position. We presented a very simple, chromatography-free procedure for
the double formylation of 2-methylquinolin-8-ol and benzo[h]quinolin-10-ol using very convenient
Duff reaction protocols. For the first time we showed a carbene insertion reaction into C-Br bonds
to produce 7-bromo-8-hydroxyquinoline-5-carbaldehyde by applying the Reimer-Tiemann method.
The electrochemical properties of compounds 2a, 2e and 2f were investigated. Oxidation and reduction
potentials of these compounds in acetonitrile showed the influence of the various functional groups in
the structure.
Supplementary Materials: The following are available online, CCDC 1890715, 1501807, 1501808, 1829344 and
1
829345 for 2h, 3a, 3b, 3c and 3d, respectively contains the supplementary crystallographic data for the compounds.
These data can be obtained free of charge from http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the

Molecules 2020, 25, 2053
19 of 20
Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-033;
or e-mail: deposit@ccdc.cam.ac.uk. Calculations have been carried out in Wroclaw Centre for Networking and
Supercomputing (http://www.wcss.wroc.pl).
Author Contributions: J.W., M.S., J.E.N. performed the experiments; M.K. and J.K. X-ray measurements and
diffraction data analysis; A.Q. and J.W. performed the electrochemical experiments; R.S. and S.G. electrochemistry
data analysis; J.W. and R.S. theoretical calculations (DFT); M.S. and J.W. IR and UV-Vis measurements; J.E.N.
designed and analyzed the data; J.E.N., J.W. and R.S. wrote and edited manuscript. All authors have read and
agreed to the published version of the manuscript.
Funding: Romana Sokolova greatly acknowledges the Czech Academy of Sciences (RVO:61388955).
Acknowledgments: We thank the Erasmus Plus for the 3 months award to stay at J. Heyrovský Institute of
Physical Chemistry of the Czech Academy of Sciences, Dolejskova 3, 18223, Prague, Czech Republic to J. Wantulok.
Conflicts of Interest: The authors declare no conflict of interest.
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Sample Availability: Samples of the compounds 2e, 2f, 2j, 2h, 2k, 3a, 3b, 3c, 3d are available from the authors.
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