Structural elaboration of dicyanopyrazine: Towards push-pull molecules with tailored photoredox activity

Article abstract of DOI:10.1039/c9ra04731j

As an extension of the successful dicyanopyrazine photoredox catalysts, a series of X-shaped push-pull molecules with a systematically altered structure were designed and facilely synthesized; their structure-property relationship was elucidated in detail

Full text of DOI:10.1039/c9ra04731j

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Structural elaboration of dicyanopyrazine: towards
push–pull molecules with tailored photoredox
Cite this: RSC Adv., 2019, 9, 23797
activity†
a
Zuzana Hlouskova,
Milan Klikar,a Oldrich Pytela,a Numan Almonasy,a
ˇ
´
ˇ
b
a
Veronika Jandovaa and Filip Bures
*
Ales Ruzicka,
ˇ
˚ˇ ˇ
´
ˇ
As an extension of the successful dicyanopyrazine photoredox catalysts, a series of X-shaped push–pull
molecules with a systematically altered structure were designed and facilely synthesized; their structure–
property relationship was elucidated in detail via experimental as well as theoretical calculations.
Dicyanopyrazines are proven to be powerful photoredox catalysts with a push–pull arrangement that
allows facile property tuning by interchanging a particular part of the D–p–A system. Changing the
mutual position of the cyano acceptors and the methoxy, methylthio and thienyl donors as well as
modifying the linker allowed wide tuning of the fundamental properties of the catalysts. Contrary to the
currently available organic photoredox catalysts, we provided a series of catalysts based on a pyrazine
heterocyclic scaffold with easy synthesis and further modification, diverse photoredox characteristics
and wide application potential across modern photoredox transformations. The photoredox catalytic
activities of the target catalysts were examined in a benchmark cross-dehydrogenative coupling and
novel and challenging annulation reactions.
Received 24th June 2019
Accepted 15th July 2019
DOI: 10.1039/c9ra04731j
rsc.li/rsc-advances
(ref. 9), C–O (ref. 10) and C–P (ref. 11) bond formation. VL
photoredox catalysis has also been well utilized in cycloaddition
reactions.12 In the last two decades, the research on PC has
Introduction
The idea of using visible light (VL) as a stimulant to promote
organic transformations is more than a hundred years old, and
G. Ciamician was the rst researcher to utilize VL in photo-
chemical reactions.1 Nowadays, the transformation of solar
energy into energy of a chemical bond is a burgeoning area of
photochemistry.2 This process, inspired by the chlorophyll
mechanism of action, is realized by a photoredox catalyst/
catalysis (PC) under laboratory conditions. An essential
prerequisite of PCs is their ability to undergo single electron
transfer (SET) either from or to the catalyst/substrate. In the last
decade, it has been veried that photoredox catalysis is a very
efficient tool in a number of chemical transformations. They
also include new and unprecedented reactions, which provide
novel compounds both for academia and industry. The port-
folio of common VL-catalysed organic transformations includes
but is not limited to oxidations,3 reductions,4 sp2–sp2 (ref. 5)/
sp2–sp3 (ref. 6)/sp3–sp3 (ref. 7) C–C as well as C–S (ref. 8), C–N
mostly been focused on the application of transition metal
complexes. The polypyridyl complexes of ruthenium and
iridium represent the most prominent PCs with superior
properties and wide applications.13 Dual catalysis is another
signicant extension of the original PC, which utilizes
combined complexes of gold/iridium,14 gold/ruthenium15 and
nickel/iridium.16 The main advantages of these complexes
include their high photoredox activity, stability, facile synthesis
and further modication. However, they are generally expen-
sive, and the presence of toxic heavy metals is undesirable.
On the other hand, organic dyes represent a very promising
group of rising photocatalysts. They include the well-known
xanthene dyes such as uorescein,17 Eosin Y,18 Eosin B,19 rose
Bengal,20 acridinium21 and pyrilium salts,22 which are readily
available, cheap and possess good catalytic activity; neverthe-
less, the tuning of their properties is limited. Therefore, the
attention of chemists has recently been drawn to the synthesis
of organic catalysts with tunable properties.23 The positive
aspects of organic PCs include low price, accessibility, stability
and solubility, but mostly their property tuning towards a given
photoredox process.24 Organic PCs should possesses essential
properties as follows: (i) absorption of light within the UV/Vis
wavelength range, (ii) absorption maximum overlapping the
emission band of the light source and (iii) capability to undergo
SET or energy transfer. Good solubility in the reaction medium,
aInstitute of Organic Chemistry and Technology, Faculty of Chemical Technology,
´
University of Pardubice, Studentska 573, Pardubice, 53210, Czech Republic. E-mail:
lip.bures@upce.cz
bDepartment of General and Inorganic Chemistry, Faculty of Chemical Technology,
´
University of Pardubice, Studentska 573, Pardubice, 53210, Czech Republic
† Electronic supplementary information (ESI) available: Further synthetic details,
RTG data, UV/Vis spectra, electrochemical data, DFT calculations and 1H/13C NMR
spectra. CCDC 1553203, 1553204, 1897538–1897540. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/c9ra04731j
This journal is © The Royal Society of Chemistry 2019
RSC Adv., 2019, 9, 23797–23809 | 23797

View Article Online
RSC Advances
Paper
inactivity towards substrate/product of the catalysed reaction
and low catalytic loadings are also desirable.24
In 2012, push–pull molecules based on 4,5-disubstituted
pyrazine-2,3-dicarbonitrile (dicyanopyrazine, DPZ) have been
synthesized in our research group.25 These X-shaped molecules
proved superior CT-chromophores (charge-transfer, CT) with
nonlinear optical properties. Further structural tuning resulted
in DPZ derivative 1 bearing two 5-methoxythienyl donors, which
showed an excellent performance as a photoredox catalyst.
Subsequently, DPZ 1 was successfully applied in a benchmark
cross-dehydrogenative coupling (CDC) reaction,26 oxidation,
oxidative hydroxylation, reductive dehalogenation,24 chemo-
divergent radical cascade reactions between N-tetrahy-
droisoquinolines
and
N-itaconimides,27
pH-controlled
photooxygenation of indoles28 and enantioselective oxidative
C(sp3)–H olenations.29 Its catalytic activity in the aforemen-
tioned reactions was outstanding, and in many cases superior
to that of other organometallic catalysts. Hence, our further
synthetic attempts were focused on the structural modication
of 1, especially in terms of introducing an additional 2,5-thie-
nylene ring.30 In the present study, we present a thorough
structural elaboration of the DPZ family of photoredox catalysts
(Fig. 1). Considering that the original DPZ 1 is a D–p–A push–
pull molecule,31,32 the structural variation may in principle
involve the alternation of the acceptor (dicyanopyrazine), p-
linker (2,5-thienylene) and the donor (methoxy group).
Fig. 1 summarizes the structural changes carried out within
this work, which according the particular part of the DPZ D–p–A
system include:
(a) Alternation of the acceptor, especially in terms of mutual
position of the CN groups: two series of disubstituted pyrazine-
2,3/2,6-dicarbonitrile isomers.
Fig. 1 Structural tuning of the DPZ push–pull molecules.
(b) Utilization of OMe and SMe groups as electron donors
and unsubstituted derivatives (R ¼ H) as reference compounds.
(c) Introduction of an additional suldic (–S–) linker, which
separates the electron donor from the pyrazine acceptor.
(d) Removal of the 2,5-thienylene p-linker and direct
connection of electron donors to the pyrazine ring.
All the new DPZ derivatives 2–14 were spectrally character-
ized, and their fundamental properties were further investi-
gated by X-ray analysis, electrochemistry, electronic absorption
and emission spectra, which were supported by DFT calcula-
tions. DPZs 1–14 were subsequently tested as photoredox cata-
lysts in benchmark CDC and annulation reactions and their
thorough structure–catalytic activity relationships were
elucidated.
substitution using another malononitrile,35 acid-catalysed
cyclization35 and nal Sandmeyer reaction36 afforded 16 in
22% overall yield. More synthetic details are provided in the
ESI.†
The chloro atoms in both derivatives 15 and 16 could be
replaced in terms of nucleophilic substitution or Suzuki–
Miyaura cross-coupling reaction (Scheme 1). Unfortunately, the
same set of reactions carried out on the third possible isomer,
3,6-dibromopyrazine-2,5-dicarbonitrile,37 failed. All attempts to
further optimize/vary the reaction conditions were unsuccess-
ful. Target molecules 1–3 and 9–10, bearing a thiophene ring
directly attached to the pyrazine core, were synthesized by
Suzuki–Miyaura cross-coupling reactions between dichloropyr-
azine 15 or 16 and appropriate boronic acid derivative 17–19.
DPZ 10 proved to be unstable during storage. All PCs were iso-
lated by column chromatography in yields in the range of 25–
86%. Boronic acid pinacol esters 17 and 18 were synthesized as
shown in the ESI.†
Results and discussions
Synthesis
The synthesis of the original DPZ derivative 1 was published
previously.24 The synthetic strategy (Scheme 1) towards target
molecules 2–14 utilized the commercially available 5,6-
dichloropyrazine-2,3-dicarbonitrile 15, and its isomer 3,5-
dichloropyrazine-2,6-dicarbonitrile 16, which was prepared in
a ve-step reaction sequence starting from malononitrile
(Scheme 2). Its gradual nitrosation,33 tosylation,34 nucleophilic
Compounds 4–8 and 11–14 were prepared from 15 or 16 and
nucleophiles 20–24 in yields in the range of 24–72%. Derivatives
7, 8, and 13 were reported previously.38–40 Thiolates 20 and 21
were generated in situ from the corresponding thiophene
23798 | RSC Adv., 2019, 9, 23797–23809
This journal is © The Royal Society of Chemistry 2019

View Article Online
Paper
RSC Advances
Scheme 1 General reaction scheme leading to the target push–pull pyrazines 1–14.
derivative and its gradual lithiation and reaction with sulphur, orientation of both rings is reverse and parallel with a mutual
˚
with more details presented in the Experimental section.
distance of about 4 A. The D–A interaction, in particular the
push–pull molecules, was estimated through the aromaticity
Bird index of the pyrazine and thiophene rings.41 The pyrazine
rings in 1, 2, 7 and 12 possess I6 values of 81.8, 84.4, 71.2 and
90.8. A, respectively, in comparison to the unsubstituted pyr-
azine (I6 ¼ 88.8), revealing a higher bond length alternation,
and thus higher ICT in the 2,3-isomeric DPZs 1, 2 and 7.
The 2,6-isomer 12 possesses higher aromaticity than pyr-
azine, and therefore, the extent of the intramolecular charge
transfer (ICT) is lower. This is because the additional suldic
linker: (i) is generally a weaker electron donor than the methoxy
group (such as in 7),31 (ii) separates the 5-methoxythiophene
moiety from the pyrazine acceptor and disallows their mutual
D–A interaction and (iii) also delocalizes its lone electron pairs
partially to the appended thiophene. The average Bird index of
the thiophene rings in 1, 2 and 12 are 61.6, 64.3 and 59.8,
respectively. Taking I5 ¼ 66 as a reference value for the unsub-
stituted thiophene, the thiophene rings in 12 seem to be the
most polarized, but are not directly conjugated to the DPZ
X-ray analysis
Suitable single crystals of compounds 7 and 12 were prepared
by slow evaporation and hexane diffusion of their DCM solu-
tions. X-ray analyses of parent compounds 1 and 2 were pub-
lished previously.30 Fig. 2 shows the ORTEP plots of all the
aforementioned derivatives, and the ESI† presents more details
and X-ray analysis of intermediate 27. As can be seen from the
dimethoxy derivative 7, the parent DPZ adopts an almost planar
arrangement with a torsion angle below 1.5ꢀ (see the side view).
However, both thiophene rings in 1 and 2 showed considerable
twist with a torsion angle between 15–35ꢀ. As a result, the
dicyanopyrazine moiety in 1 and 2 is curved with inner torsion
angles between 5–15ꢀ. In contrast to the DPZ 2,3-isomers (1, 2
and 7), the 2,6-isomer 12 with a suldic linker adopts
a completely different arrangement. Although the DPZ acceptor
is planar, both 5-methoxythiophenes appended at positions 3
and 5 are perpendicularly localized below the DPZ ring. The
Scheme 2 Synthesis of 3,5-dichloropyrazine-2,6-dicarbonitrile 16.
This journal is © The Royal Society of Chemistry 2019
RSC Adv., 2019, 9, 23797–23809 | 23799

View Article Online
RSC Advances
Paper
Fig. 2 ORTEP representations of the DPZ derivatives (a) 1 (CCDC 1553203), (b) 2 (CCDC 1553204), (c) 7 (CCDC 1897538) and (d) 12 (CCDC
1897539). Vibrational ellipsoids obtained at 150 K are shown at the 50% probability level, R ¼ 0.04–0.05. Top and side views are provided.
Table 1 Experimentally obtained photophysical and electrochemical parameters of DPZ derivatives 1–14
Electrochemical dataa
Photophysical dataa
lAmax [nm
Ground state
Excited state
Stokes shi
E
ele(HOMO)
Comp. eVꢁ1
]
lFmax [nm eVꢁ1] qF
[cmꢁ1 eVꢁ1] E0,0b [eV] Ep(ox1) [V] Ep(red1) [V] DEd [V] [eV]
E
ele(LUMO) [eV] Eox*f [V] Ered*f [V]
c
c
1
2
3
4
5
6
7
8
440/2.82 571/2.17
379/3.27 488/2.54
443/2.79 552/2.25g
<0.02 5200/0.65
<0.02 5900/0.73
2.50
2.91
1.32
1.75
1.32
1.82
1.31
1.25
—
—
—
1.57
1.79
1.34
—
ꢁ1.14
ꢁ1.12
ꢁ1.01
ꢁ0.97
ꢁ1.00
ꢁ0.95
ꢁ1.53
ꢁ1.23
ꢁ1.04
ꢁ1.15
ꢁ0.97
ꢁ1.00
ꢁ1.41
ꢁ1.16
2.46
2.87
2.33
2.79
2.31
2.20
—
—
—
2.72
2.76
2.34
—
ꢁ5.79
ꢁ6.22
ꢁ5.79
ꢁ6.29
ꢁ5.78
ꢁ5.72
—
—
—
ꢁ6.04
ꢁ6.26
ꢁ5.81
—
ꢁ3.33
ꢁ1.18 1.36
ꢁ1.16 1.79
ꢁ0.90g 1.21g
ꢁ3.35
ꢁ3.46
ꢁ3.50
ꢁ3.47
ꢁ3.52
ꢁ2.94
ꢁ3.24
ꢁ3.43
ꢁ3.32
ꢁ3.50
ꢁ3.47
ꢁ3.06
ꢁ3.31
<0.02g 4100/0.51g 2.22g
315/3.94
279/4.44
307/4.04
—
—
—
—
—
—
—
—
—
—
—
—
4.00
—
—
—
—
—
—
—
—
—
2.47
1.74g
2.11
278/4.46 349/3.55
323/3.84 409/3.03g
343/3.62 462/2.68
389/3.19 562/2.21
0.024 7300/0.91
—
6300/0.78g 2.97g
9
<0.02 7600/0.93
<0.02 4500/0.98
3.15
2.70
—
—
3.64
3.17
10
11
12
13
14
ꢁ1.13 1.55
363/3.42
351/3.53
—
—
—
—
—
—
—
—
—
—
2.23
2.01
—
—
322/3.85 363/3.42
371/3.34 417/3.00
0.18 3600/0.43
<0.02 3000/0.37
—
—
—
a
Measured in acetonitrile. b Excited state energy; calculated as the midpoint between the absorption and emission maxima (ref. 23). c Ep(ox1) and
d
Ep(red1) are the peak potentials of the rst oxidation and reduction, respectively; all potentials are given vs. SSCE. DE ¼ Ep(ox1) ꢁ Ep(red1)
(electrochemical gap). Eel(HOMO/LUMO) ¼ Ep(ox1/red1) + 4.429 (in AcCN vs. SCE) + 0.036 (difference between SCE (0.241 vs. SHE) and SSCE
e
f
(0.205 vs. SHE)). Excited-state redox potentials in acetonitrile calculated as follows: Eox* ¼ Ep(ox1) ꢁ E0,0 and Ered* ¼ Ered + E0,0 (ref. 23).
g
Measured/calculated using emission maxima obtained in DCM.
23800 | RSC Adv., 2019, 9, 23797–23809
This journal is © The Royal Society of Chemistry 2019

View Article Online
Paper
RSC Advances
Fig. 3 UV/Vis absorption spectra of selected DPZ derivatives.
acceptor. The methoxy groups appended at the thiophene as in and distinguishes the quadrupolar and linear nature of 1 and 10
1 also cause signicant polarization compared to the unsub- (similarly to the pair 2 and 9), respectively. Thus, the mutual
stituted derivative 2.
position of the donors and acceptors appended at the pyrazine
core affects the shape and position of the bands signicantly.
This structural variation also dramatically affects the molar
extinction coefficient, which dropped by two times.
Photophysical properties
The colour of the DPZ derivatives 1–14 ranges from yellow to
red. Their fundamental photophysical properties were
measured in acetonitrile (Table 1) and the less polar dichloro-
methane and 1,4-dioxane (Table S1 in the ESI†). However, only
slight solvatochromism of the absorption spectra was observed
with DlAmax ¼ 0–21 nm. The emission spectra of 1, 2, 9 and 10
with an enlarged p-system showed positive solvatochromism
with DlFmax ¼ 0–46 nm, but no solvatochromism was observed
for 7–8 and 13–4 with a truncated p-system.
The electronic absorption spectra of the representative
derivatives are shown in Fig. 3. The longest-wavelength
absorption maxima appear within a wide range of 278 to
443 nm and is clearly a function of the chromophore structure.
Although the spectrum of the parent DPZ 1 contains two well-
developed CT-bands, isomer 10 showed a single peak located
between the two peaks of 1 (Fig. 3a). This observation obeys the
Frenkel exciton model of multipodal push–pull chromophores42
Fig. 3b demonstrates the effect of the peripheral donor
groups on the representative DPZ derivatives 9 and 10, both
with a single narrow absorption peak. Upon going from 9 to 10,
and thus two methoxy groups attached, the longest-wavelength
absorption maximum shis bathochromically by almost 50 nm.
Further replacement of OMe with SMe groups, for instance in
13/14 or 7/8, is accompanied by a similar red shi. The same
trend was also observed in the well-developed series 2/1/3 (H/
OMe/SMe). However, the increasing donating ability of the R-
substituents in subseries 4–6 or 11–12 has the opposite effect,
which reects a non-conjugated arrangement due to the suldic
bridge. Its impact can further be demonstrated by comparing
representative chromophores 3 and 6, both with SMe peripheral
donors (Fig. 3c). The latter showed a substantially blue shied
spectrum by 136 nm. Truncation of the p-system has very
similar effect, as shown for chromophores 1 and 7 in Fig. 3d.
Table 2 DFT-calculated parameters of DPZ derivatives 1–14a
Radical anion
Radical cation
Ground state
Triplet state
Ec+(aHOMO)
[eV]
EG(LUMO)
[eV]
ET(bHOMO)
[eV]
ET(aHOMO)
[eV]
Ecꢁ(aHOMO)
[eV]
Comp.
lDmFaTx [nm eVꢁ1
]
EG(HOMO) [eV]
DEG [eV]
1
2
3
4
5
6
7
8
ꢁ6.55
ꢁ7.24
ꢁ6.45
ꢁ6.94
ꢁ6.50
ꢁ6.42
ꢁ8.51
ꢁ7.91
ꢁ7.77
ꢁ7.07
ꢁ7.13
ꢁ7.09
ꢁ8.84
ꢁ8.18
454/2.73
402/3.08
472/2.63
337/3.68
335/3.70
363/3.42
279/4.44
340/3.65
380/3.26
420/2.95
345/3.60
342/3.63
297/4.18
350/3.55
ꢁ5.86
ꢁ6.44
ꢁ5.81
ꢁ6.96
ꢁ6.31
ꢁ6.70
ꢁ7.21
ꢁ6.75
ꢁ6.76
ꢁ6.19
ꢁ6.98
ꢁ6.23
ꢁ7.22
ꢁ6.79
ꢁ2.94
ꢁ3.13
ꢁ2.99
ꢁ2.90
ꢁ2.88
ꢁ2.93
ꢁ2.65
ꢁ2.79
ꢁ3.06
ꢁ2.84
ꢁ2.92
ꢁ2.88
ꢁ2.65
ꢁ2.78
2.92
3.33
2.81
4.05
3.44
3.77
4.56
3.95
3.70
3.36
4.07
3.36
4.57
4.01
ꢁ6.45
ꢁ7.18
ꢁ6.11
ꢁ6.49
ꢁ5.86
ꢁ5.65
ꢁ8.35
ꢁ7.40
ꢁ6.62
ꢁ5.97
ꢁ6.04
ꢁ5.51
ꢁ8.15
ꢁ7.18
ꢁ4.22
ꢁ4.55
ꢁ4.16
ꢁ4.40
ꢁ4.21
ꢁ4.18
ꢁ4.77
ꢁ4.61
ꢁ4.41
ꢁ4.15
ꢁ4.40
ꢁ4.20
ꢁ4.57
ꢁ4.46
ꢁ3.47
ꢁ3.60
ꢁ3.55
ꢁ3.56
ꢁ3.53
ꢁ3.59
ꢁ3.28
ꢁ3.42
ꢁ3.64
ꢁ3.50
ꢁ3.79
ꢁ3.71
ꢁ3.38
ꢁ3.52
9
10
11
12
13
14
a
Calculated using the DFT B3LYP/6-311++g(3df,2p) method.
This journal is © The Royal Society of Chemistry 2019
RSC Adv., 2019, 9, 23797–23809 | 23801

View Article Online
RSC Advances
Paper
The CT-band of 7 is positioned hypsochromically by 162 nm in of the 2,6-isomers were affected, e.g. when going from 10 to 12.
comparison to DPZ 1. Overall, the insertion of the suldic linker reduces the electro-
As can be seen from the emission data in Table 1, DPZ chemical HOMO–LUMO gap. Truncation of the p-system by
derivatives 1–14 are generally not or only weakly emissive, with removing the thiophene linker is less electrochemically obvious
uorescence maxima lFmax in the range of 363 to 571 nm. Only 7 as oxidations of the chromophores 7–8 and 13–14 are out of the
and mainly 13 showed slight uorescence with quantum yields potential window. The redox potentials of the excited states Eox*
exceeding 2%. All the derivatives bearing a suldic linker (4–6 and Ered* were calculated by combining the electrochemical
and 11–12) proved to be not emissive.
peak potentials and the excited state energies E0,0 (Table 1), and
The Stokes shis are generally large, which implies high these values are also visualized in Fig. S19 in the ESI.† Although
geometry reorganization upon excitation. The excited state the excited state oxidation potentials are almost unaltered, the
energies E0,0 were derived from the position of the longest- principal changes are seen on the reduction potentials. Despite
wavelength absorption/emission maximum. These values refer the limited data available, DPZs 1–14 seem to be strong oxidants
to the transition between the lowest vibrational states of the with an Ered* of up to 2.47 V.
rst excited and ground levels.
DFT calculations
Electrochemistry
Quantum chemical calculations were run with the DFT soware
package Gaussian, versions 09 (ref. 43) and 16 (ref. 44). The total
energies of all the possible conformers of DPZ derivatives 1–14
were calculated using the DFT B3LYP/6-311g(2d,p) method and,
based on the lowest total energy, the most stable conformers
were chosen. The DFT B3LYP/6-311++g(3df,2p) method
involving symmetry constrains was applied to optimize their
ground state geometries and to calculate the corresponding
radical cations, radical anions, dications, dianions and triplets
in acetonitrile. The same method was used to calculate the total
energy, energy of the frontier orbitals and further quantum-
chemical characteristics in acetonitrile (Tables 2 and S2 in the
The rst oxidation and reduction processes of chromophores 1–
14 were studied by cyclic voltammetry (CV). The most important
data is gathered in Table 1, and the ESI† presents the experi-
mental set-up, conditions and measured CV diagrams. The rst
oxidations of 1–6 and 10–12 are all irreversible, and the rst
oxidations of the DPZs without a thiophene p-linker 7–9 and
13–14 are localized out of the potential window of the used
solvent/electrolyte (MeCN/Bu4NBF4). On the other hand, the
rst reductions are irreversible, quasi- and reversible processes
for DPZs 4–8/11–12, 13–14 and 1–3/9–10, respectively. The
reversible reductions possess a cathodic/anodic peak separa-
tion of about 60 mV, which indicates one-electron processes. To
make all the electrochemical data uniform, only the peak
potentials Ep(ox1) and Ep(red1) are further considered. Inspection
of the limiting currents revealed three times higher currents for
the oxidations than for the reductions. This indicates that more
electrons are being exchanged within the oxidation step.
Although the rst reduction takes place at the DPZ moiety, the
rst oxidation most likely involves the MeO/MeS-substituted
thiophene moieties (see Fig. S20 in the ESI† for representative
HOMO(ꢁ2/ꢁ1)/LUMO(+1/+2) localizations). The peak potential
Ep(ox1) and Ep(red1) were found to be within the range of 1.25 to
1.82 V and ꢁ1.53 to ꢁ0.95 V, respectively. Since the half-wave
potentials are not available for all the studied compounds, the
Ep(ox1) and Ep(red1) values were recalculated as the HOMO/LUMO
energies. The HOMO/LUMO levels and their differences (DE)
are also visualized in the energy level diagram (Fig. S18 in the
ESI†). When comparing the electrochemical behavior of the 2,3-
and 2,6-isomers, e.g. 1 vs. 10, the latter showed a deepened
HOMO, unaltered LUMO and thus larger HOMO–LUMO gap.
This electrochemical observation also corresponds to the
aforementioned blue-shied absorption spectrum of 10. The
attachment and variation of the electron donors (H/OMe/
SMe) signicantly alters the HOMO energy. For instance, the
well-developed series of DPZs 2/1/3 (H/OMe/SMe) showed
a gradually reduced electrochemical HOMO–LUMO gap of 2.87/
2.46/2.33 eV, which also correspond to red-shied absorption
spectra (see above). In the 2,3-DPZ isomers (e.g. pairs 1/5, 2/4
and 3/6), the extension with an additional suldic linker low-
ESI†). The electronic absorption spectra (see the ESI†), longest-
DFT
max
wavelength absorption maxima l
(Table 2) and correspond-
ing electron transitions between the molecular orbitals were
calculated using the TD-DFT method with the B3LYP/6-
311++g(3df,2p) basis set (n states ¼ 10).
Fig. 4 shows the frontier molecular orbital levels of the
ground state (black) and spin orbitals of the species formed
upon one electron transfer (blue, green and yellow). The
comparison of the DFT and electrochemically obtained (red)
HOMO/LUMO levels shows good agreement. Fig. 4 can be
considered fundamental for interpreting the photoredox cata-
lytic properties of DPZ 1. Compared to the non-ionized mole-
cule, the radical cation possesses a lower highest occupied
Fig. 4 Energy level diagram of the frontier molecular orbitals and spin
ered only the LUMO, whereas both the HOMO and LUMO levels orbitals of DPZ 1.
23802 | RSC Adv., 2019, 9, 23797–23809
This journal is © The Royal Society of Chemistry 2019

View Article Online
Paper
RSC Advances
orbital (aHOMO) energy, which implies the more difficult n ¼ 13, s ¼ 3.425 10ꢁ2, r ¼ 0.972, F(2,10) ¼ 84.14.
removal of an additional electron from the positively charged
According to eqn (2), it was found that Ep(red1) depends on
species. On the contrary, the aHOMO level of the radical anion the Ecꢁ(aHOMO) of the radical anion and E2ꢁ(HOMO) of the
is higher, which facilitates the abstraction of the electron from dianion. DPZ 7 with a limiting Ep(red1) was excluded as an
the negatively charged species. Physical interpretation can be outlier. The correlations are again very tight and independent of
carried out based on the ionization energy/potential of the EG(LUMO). This implies that the electron transfer from the
electron in the orbital, which is given by the negative value of electrode to the molecule does not depend on the lowest
the energy of the particular orbital (Koopman's theorem).45 unoccupied molecular orbital in the ground state, to which the
Hence, the ionization potential of the radical cation is higher electron is being transferred, but solely on the new orbitals
and radical anion lower than that of the non-ionized molecule. generated during the electron transfer. Eqn (2) also reveals that
In the triplet, the ground state HOMO is split into two spin both one- and two-electron processes are possible and the
orbitals, a and b, with higher and lower energy, respectively. reduction is facilitated by the lowered energies Ecꢁ(aHOMO)
The unpaired electron from the aHOMO can be transferred to and E2ꢁ(HOMO).
another molecule to generate a radical cation. On the contrary,
From the aforementioned analysis, we can conclude that the
the partially occupied bHOMO may easily accept an electron electrochemical potentials can be quantum-chemically quanti-
from a molecule and form a radical anion. Both electron ed very well. Especially considering that radical cation and
transfers from/to the triplet are energetically very close to the anions are open shell systems and DFT calculations were
levels of the radical cation/anion (Fig. 4). The aforementioned carried out just for the most stable conformer.
mechanism is most likely responsible for the visible light-
induced photoredox activity of 1 and potentially also all the
other DPZ derivatives (see also Fig. S21–S33 in the ESI†).
Visible light-induced photoredox activity
According to the rst application of DPZ 1,24 the catalytic activity
The CT-band of compounds 1, 2 and 12 is solely generated by
of all the synthesized PCs 1–14 was rstly examined in
a benchmark cross-dehydrogenative coupling (CDC) reaction26
between N-phenyltetrahydroisoquinoline and nitromethane, as
shown in Table 3.
To compare the catalytic performance of all catalysts, the
CDC reactions were carried out under standard conditions
(1 mol% of the catalyst, Royal Blue LED source, 25 ꢀC and 24 h
reaction time). All reactions were repeated at least two times,
and the average isolated yields ranged from 75% to 96%. Thus,
all the PCs were capable, upon photoexcitation, to undergo SET
and induce the one-electron oxidation of THIQ 29 to a radical
cation. Although only limited excite state reduction potentials
the HOMO / LUMO excitation. For the remaining molecules,
close orbitals such as HOMOꢁ2/ꢁ1 and LUMO+1/+2 are also
involved, with the typical conguration interaction of two or
exceptionally three (for 4 and 11) electron transitions.
Multilinear regression implemented in the OPstat program
(ref. 46) was applied to explore the dependence of the electro-
chemically obtained Ep(ox1) values on a maximum of three
explanatory variables from the set of the orbital energies given
in Table S2 (see the ESI).† The rst oxidation potentials corre-
lates tightly with Ec+(aHOMO) and Ec+(bHOMO) of the radical
cation as well as with E2+ (HOMO) of the dication, excluding 4
and 11 as outliers (eqn (1)).
E
red* are available (Table 1, Fig. S19 in the ESI†), the measured
Ep(ox1) ¼ ꢁ(1.219 ꢂ 0.144) ꢁ (0.481 ꢂ 0.034)Ec+(aHOMO)
+ (0.426 ꢂ 0.049)Ec+(bHOMO)
values are generally higher than the oxidation potential of the
starting THIQ (0.79 V). As can be seen, the highest conversion
and yields were achieved with original DPZ 1 and with new the
DPZs 6, 9 and 12. On the other hand, DPZ 5 provided
ꢁ (0.297 ꢂ 0.029)E2+(HOMO),
(1)
n ¼ 7, s ¼ 1.697 10ꢁ2, r ¼ 0.996, F(3,3) ¼ 118.0.
As can be seen, the rst oxidation potential does not corre-
late with the EG(HOMO) of the ground state, which implies that
electron transfer from DPZ to the electrode is independent of
the HOMO level. This further indicates that the common, widely
applied and simplied correlations of the electrochemically and
DFT-derived HOMO levels for push–pull molecules are incor-
rect. Eqn (1) also conrms the transfer of one/two electrons and
formation of a radical cation/dication during the electro-
chemical oxidation of DPZs. The signs of the regression coeffi-
cients show that the rst oxidation becomes difficult with more
negative Ec+(aHOMO) and E2+(HOMO) values and more positive
Ec+(bHOMO).
Table 3 Benchmark photoredox CDC reaction catalysed by DPZ
catalysts 1–14
Catalyst
Isolated yield [%]
Catalyst
Isolated yield [%]
1
2
3
4
5
6
7
96
86
90
85
75
93
88
8
9
11
12
13
14
88
93
83
95
85
89
The rst reduction peak potentials Ep(red1) were examined in
the same way as Ep(ox1)
.
Ep(red1) ¼ ꢁ(3.929 ꢂ 0.312) ꢁ (0.612 ꢂ 0.092)Ecꢁ(aHOMO)
ꢁ (0.270 ꢂ 0.032)E2ꢁ(HOMO),
(2)
This journal is © The Royal Society of Chemistry 2019
RSC Adv., 2019, 9, 23797–23809 | 23803

View Article Online
RSC Advances
Paper
Table 4 Optimization of the annulation reaction
respectively. Both catalysts showed very similar and the most
bathochromically shied absorption maxima (440 and 443 nm,
respectively, Table 1), which most likely ensure the efficient
absorption of light and facilitate one-electron oxidation of the
starting aniline 31. The plausible mechanism further involves
the formation of an a-aminoalkyl radical, its reaction with
maleimide and nal cyclization/rearomatization.48e,f The calcu-
lated optical and electrochemical HOMO–LUMO gaps of the
successful catalysts 1 and 3 are the lowest within the entire DPZ
series (2.73/2.63 and 2.92/2.81 eV, respectively). Removal of the
OMe or SMe peripheral groups, as in 2, resulted in a hyp-
sochromic shi of the CT-band, enlarged HOMO–LUMO gaps
and, on the contrary, deepened ET(bHOMO). However, the
catalytic performance of 2 was worse than that of 1 and 3. It
should also be noted that the excited state reduction potentials,
DPZ loading
[mol%]
Irradiation with
Time [h] blue LED
Solvent
Isolated yield [%]
AcCN
Acetone
DCM
2
2
2
24
24
24
24
24
24
2.2
2.2
2.2
Yes
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
66
80
59
55
0
1,4-Dioxane 2
Acetone
Acetone
Acetone
Acetone
Acetone
2
0
3
1
E
red*, of 1 and 3 are very similar and closest to the oxidation
0
potential of N,N-dimethylaniline (Fig. S19 in the ESI†). The 2,6-
isomeric DPZ derivatives proved much less efficient than the
2,3-isomers. A noticeable yield of 33 was only achieved with
DPZs 9 and 11. When comparing the catalytic performance of
the most active DPZs 1 and 3 with the formerly applied PCs (see
above), they proved superior especially in terms of much shorter
reaction time (generally 18–36 h) and low catalyst loading
(generally 1–20 mol%) (Table 5).
The recent reports48 focused mostly on the variation of the
maleimide N-substituents (phenyl, substituted aryls, alkyls, etc.)
and partially also on (4-)substituted N,N-dialkylaniline. Only
Wu et al.48e examined different acceptors such as maleic anhy-
dride and acyclic olens and found them unsuitable. Hence, we
turned our attention towards expanding the original maleimide
to the six-membered 1,2-dimethyl-1,2-dihydropyridazine-3,6-
dione 34 (Table 6), which is easily accessible from maleic
anhydride and dimethylhydrazine (see the ESI†). However,
under the conditions optimized for the annulation of N-phe-
nylmaleimide 32, no cyclization product was observed.
Although acetonitrile also proved to be unsuitable solvent,
the reaction in 1,4-dioxane afforded an inseparable mixture
80
83
95
0.5
functionalized THIQ 30 in a diminished yield of75%. In
contrast to DPZ 1 with a CT-band (lAmax ¼ 440 nm) almost
perfectly centered to the emission band of the Royal Blue LED
(ꢃ430 nm), the absorption maximum of 5 is signicantly blue-
shied to 279 nm with a diminished overlap. The absorption
spectra of 6, 9 and 12 (lAmax ¼ 307, 343 and 351 nm) showed
better overlap with the emission peak of the light source. DPZ 5
also possesses one of the most positive ET(bHOMO), which
further hindered efficient SET from the substrate. Considering
the structure of the most active catalysts, it seems that the
presence of peripheral OMe/SMe groups (1, 12, and 6), thio-
phene moiety (9) or suldic linker (6 are 12) is the most crucial
factor affecting their performance in the CDC reaction. This is
consistent with the aforementioned structure–property
relationships.
Secondly, the catalytic activity of DPZs 1–14 was further
screened in a more challenging annulation reaction between
N,N-dimethylaniline 31 and N-phenylmaleimide 32. This reac-
tion was rst reported by Murata et al.;47 however, its photo-
redox version was recently reinvestigated.48 Besides common
PCs such as N-hydroxyphthalimide and Ru(bpy)3Cl2, we were
also curious whether it could be catalysed by DPZs.
Table 5 Visible light-induced annulation reaction catalysed by DPZ
catalysts 1–14
The optimization of the reaction conditions using DPZ 1 is
summarized in Table 4. The starting aniline 31 and maleimide
32 were reacted in a 2 : 1 molar ratio. The solvent screening
revealed acetone was the best solvent, and irradiation and the
presence of PCs are also essential for the reaction. Carrying out
the annulation with the optimized catalyst loading of 0.5 mol%
and the reaction time of 2.2 h (as monitored by GC/MS) afforded
the desired product 33 in 95% isolated yield. Further extension
of the reaction time led to the undesired oxidation of unreacted
31 to N-methyl-N-phenylformamide.
Catalyst
Isolated yield [%]
Catalyst
Isolated yield [%]
1
2
3
4
5
6
7
95
73
94
7
14
7
8
9
11
12
13
14
10
36
32
13
11
7
In contrast to the CDC reaction, the catalytic performance of
DPZs 1–14 in the annulation reaction differed considerably. The
best conversion and isolated yields of product 33 were achieved
14
with 2,3-isomers
1 and 3 with OMe and SMe donors,
23804 | RSC Adv., 2019, 9, 23797–23809
This journal is © The Royal Society of Chemistry 2019

View Article Online
Paper
RSC Advances
Table 6 Optimization of the annulation reaction with pyridazine-3,6-
dione
the amount of Lewis acid, elevated temperature and increase
in the amount of catalyst (0.5–10 mol%) did not signicantly
change the isolated yield (36–40%). The photoredox activity
of DPZ 1 was further compared with common PCs such as
Rose Bengal, Eosin Y, Ru(bpy)3Cl2 and acridinium perchlo-
rate (Table 6). Although there was limited available data for
the commercial catalyst, we can reasonably assume that the
diminished catalytic activity of Ru(bpy)3Cl2 is due to the low
oxidation capability RuII+. On the other hand, the excited
state reduction potential of acridinium perchlorate (E0,0
¼
2.67 eV)49 is too far from the oxidation potential of the aniline
3. Eosin Y possesses E0,0 ¼ 2.31 eV,50 which is close to that of
DPZ, provides 35 in diminished 20% yield. However, Rose
Bengal with similar redox properties was inactive in the
formation of 35. Table 7 summarizes the catalytic activity of
all the DPZ catalysts under the optimized conditions and 72 h
reaction time. Similarly to previous observations, catalysts 1
and 3 proved to be the most efficient and afforded 35 in the
highest yields. Moreover, these two catalysts directed the
reaction solely towards 35 with diminished side reactions,
such as oxidation and dimerization of the starting aniline 31.
Using 1 and 3, the reaction could be completed within 10
days with the isolated yields of 93% and 90%, respectively.
Quinoline polycyclic systems represent structural motifs
oen found in medicinal chemistry, drugs, alkaloids and
DNA-binders. For instance, Catto et al. demonstrated the
cytotoxic activity of pyridazino[4,3-c]quinoline derivatives
against HeLa and MCF-7 human cancer cell lines.51
Pyridazino-quinoline derivatives have also been proven to be
useful in the treatment of neurological disorders.52 Hence, we
believe that the developed photoredox strategy will open
Catalyst
loading [mol%] Solvent
Catalyst
Additivea Yield [%]
DPZ 1
DPZ 1
DPZ 1
DPZ 1
DPZ 1
DPZ 1
DPZ 1
DPZ 1
DPZ 1
0.5
0.5
0.5
0.5
0.5
0.5
2
Acetone
AcCN
1,4-Dioxane
—
—
—
—
—
20b
40
Dioxane : H2O LiPF6
Dioxane : H2O ZnCl2
Dioxane : H2O SmOTf
Dioxane : H2O LiPF6
Dioxane : H2O LiPF6
Dioxane : H2O LiPF6
Dioxane : H2O LiPF6
Dioxane : H2O LiPF6
Dioxane : H2O LiPF6
Dioxane : H2O LiPF6
34
35
36
38
39
—
20
Traces
Traces
5
10
Rose Bengalc 0.5
Eosin Y
0.5
0.5
0.5
Ru(bpy)3Cl2
Acridinium
perchlorated
0.1 eq. b According to GC/MS, accompanied by noncyclic intermediate.
Irradiated by the green LED (530 nm).
methylacridinium perchlorate.
a
c
d
9-Mesityl-10-
of the desired product 35 and the noncyclic intermediate.
Upon further solvent optimization and testing various Lewis
acids (ZnCl2, SmOTf, and LiPF6), we successfully isolated the
target pyridazino[4,5-c]quinoline derivative 35 in 40% yield.
Utilizing a dioxane : H2O (1 : 2) mixture and 0.1 eq. of LiPF6
allowed the reaction of a-aminoalkyl radical generated from
31 with 34 and subsequent cyclization to 35. An increase in
a
new synthetic pathway towards pyridazino-quinoline
derivatives.
Conclusion
A series of dicyanopyrazine-derived X-shaped push–pull mole-
cules was designed and prepared. The target D–p–A molecules
possess a systematically altered structure with varying positions
of the CN groups and different donors and linkers. The X-ray
analysis showed signicant changes in the spatial arrange-
ments of the target dicyanopyrazines depending on the
substituents. The structural changes were also reected in the
optical and electrochemical properties of all the PCs. Their
optical and electrochemical gaps could be tuned within the
wide range of 1.64 eV and 0.67 V, respectively, and the excited
state reduction/oxidation potentials were found to be up to 2.47/
ꢁ1.18 V. The DFT calculations, especially the frontier molecular
Table 7 Visible light-induced annulation reaction catalysed by DPZ
catalysts 1–14
Catalyst
Isolated yield [%]
Catalyst
Isolated yield [%] orbital and spin orbital diagrams, allowed interpretation of the
photoredox fundamental properties of all the PCs. A close
1
2
3
4
5
6
7
40/93a
8
9
11
12
13
14
20
correlation between the electrochemically measured and DFT-
5
25
37/90a
28
35
10
5
calculated data with novel physico-chemical interpretation
was provided. Finally, the photoredox activities of the target PCs
were examined in a benchmark cross-dehydrogenative coupling
and novel annulation reactions. We demonstrated the superior
photoredox activity of the DPZ catalysts and rst VL-induced
formation of pyridazino[4,5-c]quinoline derivatives.
5
5
5
5
a
Reaction times of 72/240 h.
This journal is © The Royal Society of Chemistry 2019
RSC Adv., 2019, 9, 23797–23809 | 23805

View Article Online
RSC Advances
Paper
ꢀ
continued at ꢁ45 C for 1 h. Thereaer, 5,6-dichloropyrazine-
2,3-dicarbonitrile 15 (358 mg, 1.8 mmol) or 3,5-
dichloropyrazine-2,6-dicarbonitrile 16 (358 mg, 1.8 mmol) was
added and the resulting solution was stirred overnight. The
reaction mixture was diluted with water (20 mL) and extracted
with CH2Cl2 (3 ꢄ 20 mL). The combined organic extracts were
dried over anhydrous Na2SO4, the solvents were evaporated in
vacuo and the crude product was puried by ash
chromatography.
Experimental
All reagents and solvents were reagent grade and were
purchased from Penta, Aldrich, and TCI and used as received.
The starting 4,5-dichloropyrazine-3,6-dicarbonitrile
15,
thiophen-2-yl boronic acid 19, 2-thiophenethiol 22, and sodium
thiomethoxide 24 were commercially available. All cross-
coupling reactions were carried out in ame-dried asks
under an argon atmosphere. Thin layer chromatography (TLC)
was conducted on aluminium sheets coated with silica gel 60
F254 with visualization by a UV lamp (254 or 360 nm). Column
chromatography was carried out with silica gel 60 (particle size
0.040–0.063 mm, 230–400 mesh) and commercially available
General procedure for the synthesis of compounds 4 and 11
Thiophene-2-thiol 22 (100 mg, 0.5 mmol) and 5,6-
dichloropyrazine-2,3-dicarbonitrile 15 (199 mg, 1 mmol) or 3,5-
dichloropyrazine-2,6-dicarbonitrile 16 (199 mg, 1 mmol) were
dissolved in acetone (10 mL) and pyridine (0.1 mL, 1.5 mmol)
was added. The resulting mixture was stirred for the indicated
time. The reaction mixture was diluted with water (10 mL) and
extracted with CH2Cl2 (3 ꢄ 10 mL). The combined organic
extracts were dried over anhydrous Na2SO4, the solvents were
evaporated in vacuo and the crude product was puried by ash
chromatography.
1
solvents. H and 13C NMR spectra were recorded on a Bruker
AVANCE II/III 400/500 spectrometer (400/500 MHz or 100/125
MHz, respectively). Chemical shis are reported in ppm rela-
tive to the signal of Me4Si (0.00 ppm). The residual solvent
signal was used as an internal reference (CDCl3 7.25 and 77.23
ppm). Apparent resonance multiplicities are described as s
(singlet), d (doublet), dd (doublet of doublet), and m (multiplet).
1H NMR signals of thiophene are denoted as Th. The coupling
constants, J, are reported in Hertz (Hz). High-resolution MALDI
mass spectroscopy data were collected on an LTQ Orbitrap XL.
Absorption spectra were measured on a UV/Vis PerkinElmer
Lambda 35 spectrophotometer at room temperature. Fluores-
cence spectra were measured on a PTI Quantamaster 40 steady
state spectrouorimeter, and dilute solutions with absorption
bands were used for these uorescence measurements. The
uorescence kinetics were measured on Horiba Jobin Yvon
Fluorolog TCSPC spectrouorimeter with excitation using an
IBH NanoLED 405 nm of about 250 ps FWHM pulse duration.
The uorescence lifetimes were obtained using the iterative
reconvolution procedure.
General procedure for the synthesis of compounds 7 and 13
A solution of triethylamine (0.15 mL, 1.1 mmol) in methanol (1
mL) was added dropwise to a solution of 5,6-dichloropyrazine-
2,3-dicarbonitrile 15 (100 mg, 0.5 mmol) or 3,5-
dichloropyrazine-2,6-dicarbonitrile 16 (100 mg, 0.5 mmol) in
methanol 23 (2.5 mL). The resulting mixture was stirred for the
indicated time. The reaction was diluted with water and the
crude product was extracted with Et2O (3 ꢄ 5 mL). The
combined organic extracts were dried over anhydrous Na2SO4,
the solvents were evaporated in vacuo and the crude product was
puried by ash chromatography.
General procedure for the Suzuki–Miyaura cross-coupling
In a Schlenk ask, 5,6-dichloropyrazine-2,3-dicarbonitrile 15
(199 mg, 1.0 mmol) or 3,5-dichloropyrazine-2,6-dicarbonitrile
16 (199 mg, 1.0 mmol) and a suitable amount of boronic acid
or boronic acid pinacol ester (2.2 eq.) were dissolved in
a mixture of THF/H2O (50 mL, 4 : 1). Argon was bubbled
through the solution for 10 min, whereupon Pd2(dba)3 (46 mg,
0.05 mmol, 5%), SPhos (20.5 mg, 0.05 mmol, 5%), and Cs2CO3
(684 mg, 2.1 mmol) were added and the resulting reaction
mixture was stirred at 65 ꢀC for the indicated time. The reaction
mixture was diluted with water (40 mL) and extracted with
CH2Cl2 (3 ꢄ 40 mL). The combined organic extracts were dried
over anhydrous Na2SO4, the solvents were evaporated in vacuo
and the crude product was puried by column chromatography.
General procedure for the synthesis of compounds 8 and 14
A
solution of 5,6-dichloropyrazine-2,3-dicarbonitrile 15
(100 mg, 0.5 mmol) or 3,5-dichloropyrazine-2,6-dicarbonitrile
16 (100 mg, 0.5 mmol) was dissolved in acetone (1.5 mL) at
ꢀ
0 C, and sodium thiomethoxide 24 (0.35 g, 21% aq. sol.) was
added dropwise. The resulting reaction mixture was stirred at
ꢀ
0 C for 1 h. Then the solvent was evaporated in vacuo and the
crude product was washed with water, followed by crystalliza-
tion from ethanol.
5,6-Bis(5-methoxythiophen-2-yl)pyrazine-2,3-dicarbonitrile
(1).24 The title compound was prepared from 15 (199 mg, 1.0
mmol) and pinacol ester 17 (528 mg, 2.2 mmol) following the
general method for the Suzuki–Miyaura reaction (reaction time
¼ 6 h). Compound 1 was an orange solid (304 mg, 86%); mp ¼
178 ꢀC. Rf ¼ 0.20 (SiO2, CH2Cl2 : Hex ¼ 2 : 1). Spectral data
General procedure for the synthesis of compounds 5, 6 and 12
In a Schlenk ask, 2-methoxythiophene (400 mg, 3.5 mmol) or according to the literature.24
2-methylthiothiophene (458 mg, 3.5 mmol) was dissolved in dry
5,6-Di(thiophen-2-yl)pyrazine-2,3-dicarbonitrile (2).24 The
THF (20 mL) at ꢁ78 ꢀC. nBuLi (1.62 mL, 2.5 M sol. in hexane, 4 title compound was prepared from 15 (199 mg, 1.0 mmol) and 2-
mmol) was added dropwise and the mixture was stirred 1 hour thienylboronic acid 19 (281 mg, 2.2 mmol) following the general
at ꢁ78 ꢀC. 1,2-Bis(dimethylamino)ethane (41 mg, 0.35 mmol) method for the Suzuki–Miyaura reaction (reaction time ¼ 3 h).
and sulphur (112 mg, 3.5 mmol) were added and stirring was Compound 2 was a yellow solid (72 mg, 28%); mp ¼ 178 ꢀC. Rf ¼
23806 | RSC Adv., 2019, 9, 23797–23809
This journal is © The Royal Society of Chemistry 2019

View Article Online
Paper
RSC Advances
0.20 (SiO2, CH2Cl2 : Hex ¼ 2 : 1). Spectral data according to the thiomethoxide 24 (0.35 g, 21% aq. sol.) following the general
literature.24
method (reaction time ¼ 1 h). Compound 8 was a pale green
solid (52 mg, 47%); mp ¼ 157–160 ꢀC. Rf ¼ 0.9 (SiO2, CH2-
5,6-Bis(5-(methylthio)thiophen-2-yl)pyrazine-2,3-dicarbonitrile
(3). The title compound was prepared from 15 (199 mg, 1.0 mmol) Cl2).$1H-NMR (400 MHz, CDCl3): d(1H) ¼ 2.66 (s, 6H, SCH3)-
and
4,4,5,5-tetramethyl-2-(5-(methylthio)thiophen-2-yl)-1,3,2- ppm. 13C-NMR (125 MHz, CDCl3): d(13C) ¼ 160.77, 126.50,
dioxaborolane 18 (563 mg, 2.2 mmol) following the general 113.93, 14.10 ppm. HR-FT-MALDI-MS (none): m/z calcd. for
method for the Suzuki–Miyaura reaction (reaction time ¼ 1 h). C8H6N4S2 ([M+]), 222.00284; found: 222.00287.
+
Compound 3 was a red solid (97 mg, 25%); mp ¼ 168–171 ꢀC. Rf ¼
3,5-Di(thiophen-2-yl)pyrazine-2,6-dicarbonitrile (9). The title
0.25 (SiO2, CH2Cl2 : Hex ¼ 1 : 1). 1H-NMR (500 MHz, CDCl3): d(1H) compound was prepared from 16 (199 mg, 1.0 mmol) and 2-
¼ 7.62 (d, J ¼ 4 Hz, 2H, Th), 6.86 (d, J ¼ 4 Hz, 2H, Th), 2.63 (s, 6H, thienylboronic acid 19 (281 mg, 2.2 mmol) following the general
OCH3) ppm. 13C-NMR (125 MHz, CDCl3): d(13C) ¼ 149.87, 146.31, method for the Suzuki–Miyaura reaction (reaction time ¼ 14 h).
137.33, 131.94, 127.43, 113.32, 19.88 ppm. HR-FT-MALDI-MS Compound 8 was a yellow solid (132 mg, 45%); mp ¼ 237–
(DHB): m/z calcd. for C16H10N4S4 ([M+]), 385.97828; found: 238 ꢀC. Rf ¼ 0.63 (SiO2, CH2Cl2 : Hex ¼ 1 : 1). 1H-NMR (400
+
385.97878.
MHz, CDCl3): d(1H) ¼ 8.48 (dd, J ¼ 1 and 4 Hz, 2H, Th), 7.88 (dd,
5,6-Bis(thiophen-2-ylthio)pyrazine-2,3-dicarbonitrile (4). The J ¼ 0.4 and 4.8 Hz, 2H, Th), 7.29 (dd, J ¼ 4 and 4.8 Hz, 2H,
title compound was prepared from 15 (199 mg, 1.0 mmol) and Th) ppm. 13C-NMR (125 MHz, CDCl3): d(13C) ¼ 150.45, 138.10,
thiophene-2-thiol 22 (100 mg, 0.5 mmol) following the general 135.51, 132.50, 130.10, 120.36, 115.72 ppm. HR-FT-MALDI-MS
method (reaction time ¼ 5 h). Compound 4 was a yellow solid (DHB): m/z calcd. for C14H7N4S2 ([M + H+]), 295.01066; found:
+
ꢀ
(215 mg, 60%); mp > 220 C (decomp.). Rf ¼ 0.40 (SiO2, CH2- 295.01054.
Cl2 : Hex ¼ 1 : 1). 1H-NMR (400 MHz, CDCl3): d(1H) ¼ 7.44 (dd, J
3,5-Bis(5-methoxythiophen-2-yl)pyrazine-2,6-dicarbonitrile
¼ 1.2 and 5.6 Hz, 2H, Th), 7.35 (dd, J ¼ 1.2 and 3.6 Hz, 2H, Th), (10). The title compound was prepared from 16 (199 mg, 1.0
7.19 (dd, J ¼ 3.6 and 9.2 Hz, 2H, Th) ppm. 13C-NMR (125 MHz, mmol) and pinacol ester 17 (528 mg, 2.2 mmol) following the
CDCl3): d(13C) ¼ 159.01, 138.45, 134.50, 128.68, 120.31, general method for the Suzuki–Miyaura reaction (reaction time
113.30 ppm. HR-FT-MALDI-MS (DHB): m/z calcd. for ¼ 5 h). Compound 10 was an orange solid (106 mg, 30%) which
14H7N4S4+ ([M + H+]), 358.95481; found: 358.95496.
gradually decomposed during storage; mp ¼ 183–186 C. Rf ¼
ꢀ
C
5,6-Bis((5-methoxythiophen-2yl)thio)pyrazine-2,3-dicarbonitrile 0.39 (SiO2, CH2Cl2 : Hex ¼ 1 : 1). 1H-NMR (400 MHz, CDCl3):
(5). The title compound was prepared from 15 (358 mg, 1.8 mmol) d(1H) ¼ 8.23 (d, J ¼ 4.8 Hz, 2H, Th), 6.37 (d, J ¼ 4.8 Hz, 2H, Th),
and 2-methoxythiophene (400 mg, 3.5 mmol) following the general 4.03 (s, 6H, OCH3) ppm. 13C-NMR (125 MHz, CDCl3): d(13C) ¼
method (reaction time ¼ 14 h). Compound 5 was a yellow solid 175.74, 150.01, 133.17, 124.29, 117.28, 116.36, 107.96,
(300 mg, 40%); mp ¼ 209–212 ꢀC. Rf ¼ 0.15 (SiO2, CH2Cl2 : Hex ¼ 60.80 ppm. HR-FT-MALDI-MS (DHB): m/z calcd. for
1 : 1). H-NMR (500 MHz, CDCl3): d(1H) ¼ 7.02 (d, J ¼ 4 Hz, 2H,
Th), 6.26 (d, J ¼ 4 Hz, 2H, Th), 3.96 (s, 6H, OCH3) ppm. 13C-NMR
C
16H12N4O2S2+ ([M + 2H+]), 356.03962; found: 356.04000.
1
3,5-Bis(thiophen-2-ylthio)pyrazine-2,6-dicarbonitrile
(11).
(125 MHz, CDCl3): d(13C) ¼ 173.00, 159.96, 138.31, 128.56, 116.65, The title compound was prepared from thiophene-2-thiol 22
105.90, 105.05, 60.56 ppm. HR-FT-MALDI-MS (DHB): m/z calcd. for (100 mg, 0.5 mmol) and 16 (199 mg, 1 mmol) following the
C16H10O2N4S4+ ([M+]), 419.96811; found: 419.96794.
general method (reaction time ¼ 14 h). Compound 11 was
5,6-Bis((5-(methylthio)thiophen-2yl)thio)pyrazine-2,3-di- a yellow solid (86 mg, 24%); mp ¼ 183–186 ꢀC. Rf ¼ 0.49 (SiO2,
carbonitrile (6). The title compound was prepared from 15 CH2Cl2 : Hex ¼ 1 : 1). H-NMR (500 MHz, CDCl3): d(1H) ¼ 7.49
1
(358 mg, 1.8 mmol) and thiophene-2-thiol 22 (458 mg, 3.5 (dd, J ¼ 1 and 5.5 Hz, 2H, Th), 7.06 (dd, J ¼ 1 and 3.5 Hz, 2H,
mmol) following the general method (reaction time ¼ 14 h). Th), 6.98 (dd, J ¼ 4 and 5.5 Hz, 2H, Th) ppm. 13C-NMR (125
Compound 6 was a yellow solid (267 mg, 33%); mp ¼ 145– MHz, CDCl3): d(13C) ¼ 164.17, 138.20, 134.54, 128.34, 121.89,
1
ꢀ
148 C. Rf ¼ 0.85 (SiO2, CH2Cl2 : Hex ¼ 2 : 1). H-NMR (500 120.06, 113.11 ppm. HR-FT-MALDI-MS (DHB): m/z calcd. for
MHz, CDCl3): d(1H) ¼ 7.19 (d, J ¼ 4 Hz, 2H, Th), 7.06 (d, J ¼
C
14H6N4S4+ ([M + H+]), 358.95481; found: 358.95486.
4 Hz, 2H, Th), 2.58 (s, 6H, SCH3) ppm. 13C-NMR (125 MHz,
3,5-Bis((5-methoxythiophen-2-yl)thio)pyrazine-2,6-dicarbonitrile
CDCl3): d(13C) ¼ 158.89, 148.12, 138.97, 129.82, 128.48, (12). The title compound was prepared from 2-methoxythiophene
119.75, 113.34, 21.04 ppm. HR-FT-MALDI-MS (DCTB): m/z (400 mg, 3.5 mmol) and 16 (358 mg, 1.8 mmol) following the
calcd. for C16H10N4S6 ([M+]), 449.92242; found: 449.92258. general method (reaction time ¼ 24 h). Compound 12 was a yellow
+
ꢀ
5,6-Dimethoxypyrazine-2,3-dicarbonitrile (7). The title solid (308 mg, 41%); mp ¼ 168–172 C. Rf ¼ 0.36 (SiO2, CH2Cl2-
compound was prepared from 15 (100 mg, 0.5 mmol) and
: Hex ¼ 1 : 1). 1H-NMR (400 MHz, CDCl3): d(1H) ¼ 6.84 (d, J ¼ 4 Hz,
methanol 23 (2.5 mL) following the general method (reaction 2H, Th), 6.10 (d, J ¼ 4 Hz, 2H, Th), 3.92 (s, 6H, OCH3) ppm. 13C-NMR
time ¼ 4 h). Compound 6 was a pale yellow solid (80 mg, 85%); (125 MHz, CDCl3): d(13C) ¼ 172.71, 165.39, 138.13, 121.63, 113.23,
mp ¼ 162–165 ꢀC. Rf ¼ 0.80 (SiO2, Et2O : Hex ¼ 2 : 1). 1H-NMR 105.78, 104.88, 60.35 ppm. HR-FT-MALDI-MS (DCTB): m/z calcd. for
(400 MHz, CDCl3): d(1H) ¼ 4.12 (s, 6H, OCH3) ppm. 13C-NMR C16H8N4O2S4+ ([M ꢁ H+]),416.96028; found: 416.96046.
(125 MHz, CDCl3): d(13C) ¼ 152.12, 123.02, 113.30, 56.13 ppm.
3,5-Dimethoxypyrazine-2,6-dicarbonitrile (13). The title
compound was prepared from 16 (100 mg, 0.5 mmol) and
Spectral data according to the literature.36
5,6-Bis(methylthio)pyrazine-2,3-dicarbonitrile (8). The title methanol 23 (2.5 mL) following the general method (reaction
compound was prepared from 5,6-dichloropyrazine-2,3- time ¼ 12 h). Compound 12 was a yellow solid (68 mg, 72%); mp
dicarbonitrile 15 (100 mg, 0.5 mmol) and sodium ¼ 142–146 ꢀC. Rf ¼ 0.75 (SiO2, Et2O : Hex ¼ 2 : 1). 1H-NMR (400
This journal is © The Royal Society of Chemistry 2019
RSC Adv., 2019, 9, 23797–23809 | 23807

View Article Online
RSC Advances
Paper
MHz, CDCl3): d(1H) ¼ 4.18 (s, 6H, OCH3) ppm. 13C-NMR (125 energetics of traditional and renewable resources (ORGBAT)”
MHz, CDCl3): d(13C) ¼ 162.32, 112.78, 110.90, 56.03 ppm. No. CZ.02.1.01/0.0/0.0/16_025/0007445 and by the Technology
Spectral data according to the literature.40
Agency of the Czech Republic (TG02010058, GAMA02/002).
3,5-Bis(methylthio)pyrazine-2,6-dicarbonitrile (14). The title
compound
was
prepared
5,6-dichloropyrazine-2,3-
Notes and references
dicarbonitrile 16 (100 mg, 0.5 mmol) and sodium thiometh-
oxide 24 (0.35 g, 21% aq. sol.) following the general method
(reaction time ¼ 1 h). Compound 14 was a pale yellow solid
1 G. Ciamician, Science, 1912, 36, 385.
2 (a) D. A. Nicewicz and D. W. C. MacMillan, Science, 2008, 322,
77; (b) C. Stephenson and T. Yoon, Acc. Chem. Res., 2016, 49,
2059.
1
ꢀ
(44 mg, 40%); mp ¼ 219–220 C. Rf ¼ 0.86 (SiO2, CH2Cl2).$ H-
NMR (500 MHz, CDCl3): d(1H) ¼ 2.70 (s, 6H, SCH3) ppm. 13C-
NMR (125 MHz, CDCl3): d(13C) ¼ 164.42, 121.64, 113.51,
¨
3 B. Lechner and B. Konig, Synthesis, 2010, 1712.
+
¨
13.55 ppm. HR-FT-MALDI-MS (none): m/z calcd. for C8H6N4S2
4 T. Ghosh, T. Slanina and B. Konig, Chem. Sci., 2015, 6, 2027.
([M+]), 222.00284; found: 222.00302.
5 I. Ghosh, L. Marzo, A. Da, E. Shaikh and B. Konig, Acc. Chem.
¨
Res., 2016, 49, 1566.
6 J. C. Tellis, D. N. Primer and G. A. Molander, Science, 2014,
345, 433.
General method for the CDC reaction
In a 10 mL snap vial equipped with a magnetic stirring bar,
THIQ 29 (31 mg, 0.15 mmol) was dissolved in nitromethane (1.5
mL) and then photocatalyst 1–14 (1.5 mmol) was added. The
reaction mixture was stirred under irradiation with a Royal Blue
LED at 25 ꢀC from a distance of 5 cm. The temperature was
maintained using a Peltier cooler. Aer 24 h, the solvent was
removed in vacuo and the residue was puried by ash chro-
matography (SiO2; petroleum ether (PE) : ethyl acetate (EA)
10 : 1) to obtain pure product 30.
7 C. P. Johnston, R.
T Smith, S. Allmendinger and
D. W. C. MacMillan, Nature, 2016, 536, 322.
8 M. Majek and A. Von Wangelin, Chem. Commun., 2013, 49,
5507.
9 E. B. Corcoran, M. T. Pirnot, S. Lin, S. D. Dreher,
D. A. DiRocco, I. W. Davies, S. L. Buchwald and
D. W. C. MacMillan, Science, 2016, 353, 279.
10 J. A. Terrett, J. D. Cuthbertson, V. W. Shurtleff and
D. W. C. MacMillan, Science, 2015, 524, 330.
¨
¨
11 R. S. Shaikh, S. Dusel and B. Konig, ACS Catal., 2016, 6, 8410.
12 T. P. Yoon, Acc. Chem. Res., 2016, 6, 8410.
13 C. K. Prier, D. A. Rankic and D. W. C. MacMillan, Chem. Rev.,
2013, 113, 5322.
General method for the annulation reaction
Method A. In a 5 mL snap vial equipped with a magnetic
stirring bar, N,N-dimethylaniline 31 (63 mL, 0.5 mmol) and N-
phenylmaleimide 32 (43 mg, 0.25 mmol) were dissolved in
acetone (3 mL) and then photocatalyst 1–14 (0.5 mol%) was
added. The reaction mixture was stirred for 2 h and 20 min at
25 ꢀC (Peltier cooler) under irradiation by a Royal Blue LED from
a distance of 5 cm. The solvent was removed in vacuo and the
crude product was puried by column chromatography (Al2O3,
PE : EA 3 : 1) to obtain pure product 33.
Method B. In a 5 mL snap vial equipped with a magnetic
stirring bar, N,N-dimethylaniline 31 (63 mL, 0.5 mmol) and 1,2-
dimethyl-1,2-dihydropyridazine-3,6-dione 34 (35 mg, 0.25
mmol) were dissolved in a mixture of 1,4-dioxane : H2O (1
mL : 2 mL), and thereaer photocatalyst 1–14 (0.5 mol%) and
LiPF6 (4 mg, 0.025 mmol) were added. The reaction mixture was
stirred 72 h at 30 ꢀC (Peltier cooler) under irradiation by a Royal
Blue LED from a distance of 5 cm. The solvent was removed in
vacuo and the crude product was puried by ash chromatog-
raphy (SiO2, EA) to obtain pure product 35.
14 Y. He, H. Wu and F. D. Toste, Chem. Sci., 2015, 6, 1194.
15 D. V. Patil, H. Yun and S. Shin, Adv. Synth. Catal., 2015, 357,
2622.
16 A. Noble, S. J. McCarver and D. W. C. MacMillan, J. Am.
Chem. Soc., 2015, 137, 624.
17 W. Guo, L. Q. Lu, Y. Wang, Y. N. Wang, J. R. Chen and
W. J. Xiao, Angew. Chem., Int. Ed., 2015, 54, 2265.
18 M. Majek and A. J. Von Wangelin, Angew. Chem., Int. Ed.,
2015, 54, 2270.
19 M. Majek, F. Filace and A. J. Von Wangelin, Chem.–Eur. J.,
2015, 21, 4518.
20 H. Liu, W. Feng, C. W. Kee, Y. Zhao, D. Leow, Y. Pan and
C. H. Tan, Green Chem., 2010, 12, 953.
21 (a) D. R. Heitz, K. Rizwan and G. A. Molander, J. Org. Chem.,
2016, 81, 7308; (b) H. T. Qin, S. W. Wu, J. L. Liu and F. Liu,
Chem. Commun., 2017, 53, 1696; (c) J. B. McManus and
D. A. Nicewicz, J. Am. Chem. Soc., 2017, 139, 2880.
22 (a) N. J. Gesmundo and D. A. Nicewicz, Beilstein J. Org. Chem.,
2014, 10, 1272; (b) P. Becker, T. Duhamel, C. J. Stein,
Conflicts of interest
˜
M. Reiher and K. Muniz, Angew. Chem., Int. Ed., 2017, 56,
There are no conicts to declare.
8004.
23 N. A. Romero and D. A. Nicewicz, Chem. Rev., 2016, 116,
10075.
24 Y. Zhao, C. Zhang, K. F. Chin, O. Pytela, G. Wei, H. Liu,
Acknowledgements
ˇ
Dr N. Sato is gratefully acknowledged for providing us gener-
F. Bures and Z. Jiang, RSC Adv., 2014, 4, 30062.
ˇ
´
´
´
ously with 3,6-dibromopyrazine-2,5-dicarbonitrile. The work 25 (a) H. Cermakova, J. Kulhanek, M. Ludwig, W. Kuznik,
ˇ
ˇ
˚ˇ
I. V. Kityk, T. Mikysek, A. Ruzicka and F. Bures, Eur. J. Org.
has partially been supported from European Regional devel-
´
´
ˇ
opment Fund-Project “Organic redox couple based batteries for
Chem., 2012, 529; (b) L. Dokladalova, F. Bures, W. Kuznik,
23808 | RSC Adv., 2019, 9, 23797–23809
This journal is © The Royal Society of Chemistry 2019

View Article Online
Paper
I. V. Kityk, A. Wojciechowski, T. Mikysek, N. Almonasy,
RSC Advances
O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli,
J. W. Ochterski, R. L. Martin, K. Morokuma,
V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg,
S. Dapprich, A. D. Daniels, O. Farkas, J. B. Foresman,
J. V. Ortiz, J. Cioslowski, and D. J. Fox, Gaussian 09,
Revision D.01, Gaussian, Inc., Wallingford CT, 2013.
ˇ
´
´
M. Ramaiyan, Z. Padelkova, J. Kulhanek and M. Ludwig,
Org. Biomol. Chem., 2014, 12, 5517.
´
´
26 A. G. Condie, J. C. Gonzales-Gomez and C. R. J. Stephenson,
J. Am. Chem. Soc., 2010, 132, 1464.
ˇ
27 X. Liu, X. Ye, F. Bures, H. Liu and Z. Jiang, Angew. Chem., Int.
Ed., 2015, 54, 11443.
28 C. Zhang, S. Li, F. Bures, R. Lee, X. Ye and Z. Jiang, ACS
Catal., 2016, 6, 6853.
29 G. Wei, C. Zhang, F. Bures, X. Ye, C. H. Tan and Z. Jiang, ACS
44 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone,
G. A. Petersson, H. Nakatsuji, X. Li, M. Caricato,
A. V. Marenich, J. Bloino, B. G. Janesko, R. Gomperts,
B. Mennucci, H. P. Hratchian, J. V. Ortiz, A. F. Izmaylov,
J. L. Sonnenberg, D. Williams-Young, F. Ding, F. Lipparini,
F. Egidi, J. Goings, B. Peng, A. Petrone, T. Henderson,
D. Ranasinghe, V. G. Zakrzewski, J. Gao, N. Rega,
G. Zheng, W. Liang, M. Hada, M. Ehara, K. Toyota,
R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda,
O. Kitao, H. Nakai, T. Vreven, K. Throssell,
J. A. Montgomery Jr, J. E. Peralta, F. Ogliaro,
M. J. Bearpark, J. J. Heyd, E. N. Brothers, K. N. Kudin,
V. N. Staroverov, T. A. Keith, R. Kobayashi, J. Normand,
K. Raghavachari, A. P. Rendell, J. C. Burant, S. S. Iyengar,
J. Tomasi, M. Cossi, J. M. Millam, M. Klene, C. Adamo,
R. Cammi, J. W. Ochterski, R. L. Martin, K. Morokuma,
O. Farkas, J. B. Foresman, and D. J. Fox, Gaussian 16,
Revision A.03, Gaussian, Inc., Wallingford CT, 2016.
ˇ
ˇ
Catal., 2016, 6, 3708.
ˇ
´
´
30 Z. Hlouskova, J. Tydlitat, M. Kong, O. Pytela, T. Mikysek,
ˇ´
ˇ
˚ˇ
M. Klikar, N. Almonasy, M. Dvorak, Z. Jiang, A. Ruzicka
ˇ
and F. Bures, ChemistrySelect, 2018, 3, 4262.
ˇ
31 F. Bures, RSC Adv., 2014, 4, 58826.
´
ˇ
32 M. Klikar, P. Solanke, J. Tydlitat and F. Bures, Chem. Rec.,
2016, 16, 1886.
33 M. F. Fathalla and S. H. Khattab, J. Chem. Soc. Pak., 2011, 33, 324.
34 G. Kinast, Liebigs Ann. Chem., 1981, 1561.
35 J. Perchais and J. P. Fleury, Tetrahedron, 1974, 30, 999.
´
36 D. Vazquez Vilarelle, C. Peinador Veira and J. M. Quintela
´
Lopez, Tetrahedron, 2004, 60, 275.
37 (a) N. Sato and S. Fukuya, J. Heterocycl. Chem., 2012, 49, 675;
(b) K. Shirai, A. Yanagisawa, H. Takahashi, K. Fukunishi and
M. Matsuoka, Dyes Pigm., 1998, 39, 49.
38 E. H. Morkved, H. Ossletten and H. Kjosen, Acta Chem. 45 T. Koopmans, Physica, 1934, 1, 104.
Scand., 1999, 53, 1117.
46 O. Pytela, OPStat, version 6.10, 2019, http://bures.upce.cz/OPgm.
39 Kyowa gas chem ind. Co. ltd., 2,3-Dicyanopyrazines, US Pat. 47 S. Murata, K. Teramoto, M. Miura and M. Nomura,
US4259489, 31.3.1981.
40 DuPont de Nemours and Co., Pyrazinderivative und 48 (a) Z. J. Wang, S. Ghasimi, K. Landfester and K. I. Zhang, Adv.
Heterocycles, 1993, 36, 2147.
Verfahren zu ihrer Herstellung, Deutches Pat., DE2216925,
6.3.1972.
Synth. Catal., 2016, 358, 2576; (b) K. Sharma, B. Das and
P. Gogoi, New J. Chem., 2018, 42, 18894; (c) M. Hosseini-
Sarvari, M. Koohgard, S. Firoozi, A. Mohajeri and
H. Tavakolian, New J. Chem., 2018, 42, 6880; (d) S. Firoozi,
M. Hosseini-Sarvari and M. Koohgard, Green Chem., 2018,
20, 5540; (e) X. L. Yang, J. D. Guo, T. Lei, B. Chen,
C. H. Tung and L. Z. Wu, Org. Lett., 2018, 20, 2916; (f)
41 (a) C. W. Bird, Tetrahedron, 1986, 42, 89; (b) C. W. Bird,
Tetrahedron, 1985, 41, 1409; (c) S. I. Kotelevskii and
O. V. Prezhdo, Tetrahedron, 2001, 57, 5715; (d)
T. M. Krygowski, H. Szatylowicz, O. A. Stasyuk,
J. Dominikowska and M. Palusiak, Chem. Rev., 2014, 114,
6383.
´
C. W. Hsu and H. Sunden, Org. Lett., 2018, 20, 2051; (g)
42 D. Cvejn, E. Michail, K. Seintis, M. Klikar, O. Pytela,
T. Mikysek, N. Almonasy, M. Ludwig, V. Giannetas,
J. T. Guo, D. C. Yang, Z. Guan and Y. H. He, J. Org. Chem.,
2017, 82, 1888; (h) A. K. Yadav and L. D. S. Yadav,
Tetrahedron Lett., 2017, 58, 552; (i) A. K. Yadav and
L. D. S. Yadav, Tetrahedron Lett., 2016, 57, 1489.
ˇ
M. Fakis and F. Bures, RSC Adv., 2016, 6, 12819.
43 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, 49 A. C. Benniston, A. Harriman, P. Li, P. Rostron, H. J. van
B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato,
X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng,
Ramesdonk, M. M. Groeneveld, H. Zhang and
J. W. Verhoeven, J. Am. Chem. Soc., 2005, 127, 16054.
J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, 50 X. F. Zhang, I. Zhang and L. Liu, Photochem. Photobiol., 2010,
R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, 86, 492.
O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery Jr, 51 F. Palluotto, A. Sosic, O. Pinato, G. Zoidis, M. Catto, C. Sissi,
J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, B. Gatto and A. Carotti, Eur. J. Med. Chem., 2016, 123, 704.
E. Brothers, K. N. Kudin, V. N. Staroverov, T. Keith, 52 T. M. Bare, M. J. Chapdelaine, T. W. Davenport,
R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell,
J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega,
J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken,
C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann,
J. R. Empeld, L. E. Garcia-Davenport, P. F. Jackson,
J. A. McKinney, C. D. McLaren, R. B. Sparks, US Pat.,
US6214826, 8.2.1999.
This journal is © The Royal Society of Chemistry 2019
RSC Adv., 2019, 9, 23797–23809 | 23809